1999 NASA High-Speed Research Program Aerodynamic Performance Workshop. Volume 1; Configuration Aerodynamics

NASA Technical Reports Server (NTRS)

Hahne, David E. (Editor)

1999-01-01

NASA's High-Speed Research Program sponsored the 1999 Aerodynamic Performance Technical Review on February 8-12, 1999 in Anaheim, California. The review was designed to bring together NASA and industry High-Speed Civil Transport (HSCT) Aerodynamic Performance technology development participants in the areas of Configuration Aerodynamics (transonic and supersonic cruise drag prediction and minimization), High Lift, and Flight Controls. The review objectives were to (1) report the progress and status of HSCT aerodynamic performance technology development; (2) disseminate this technology within the appropriate technical communities; and (3) promote synergy among the scientists and engineers working on HSCT aerodynamics. In particular, single and midpoint optimized HSCT configurations, HSCT high-lift system performance predictions, and HSCT simulation results were presented, along with executive summaries for all the Aerodynamic Performance technology areas. The HSR Aerodynamic Performance Technical Review was held simultaneously with the annual review of the following airframe technology areas: Materials and Structures, Environmental Impact, Flight Deck, and Technology Integration. Thus, a fourth objective of the Review was to promote synergy between the Aerodynamic Performance technology area and the other technology areas of the HSR Program. This Volume 1/Part 2 publication covers the design optimization and testing sessions.

A critical review of which children with acute myeloid leukaemia need stem cell procedures.

PubMed

Hasle, Henrik

2014-07-01

The last decades have seen parallel improvements in chemotherapy-based and haematopoietic stem cell transplantation (HSCT) regimens for acute myeloid leukaemia (AML) in children. There has been no consensus on indication for HSCT. Reserving HSCT for high-risk and relapsed patients spare many patients from the long-term toxicity of this treatment. The results of matched unrelated donor HSCT equal family donor transplantation and the presence of a matched sibling should no longer be a transplant indication. Minimal residual disease measured by flow cytometry may identify poor responders benefitting from HSCT in first complete remission (CR1) and those with a favourable response to induction therapy who do not need HSCT even with adverse cytogenetic aberrations. FLT3-internal tandem duplication without NPM1 mutation has a very high relapse rate despite favourable response and HSCT is indicated in CR1 in these cases. Finding the optimal indications for HSCT is a delicate balance between risk of relapse and late effects. © 2014 John Wiley & Sons Ltd.

Optimization of fixed-range trajectories for supersonic transport aircraft

NASA Astrophysics Data System (ADS)

Windhorst, Robert Dennis

1999-11-01

This thesis develops near-optimal guidance laws that generate minimum fuel, time, or direct operating cost fixed-range trajectories for supersonic transport aircraft. The approach uses singular perturbation techniques to time-scale de-couple the equations of motion into three sets of dynamics, two of which are analyzed in the main body of this thesis and one of which is analyzed in the Appendix. The two-point-boundary-value-problems obtained by application of the maximum principle to the dynamic systems are solved using the method of matched asymptotic expansions. Finally, the two solutions are combined using the matching principle and an additive composition rule to form a uniformly valid approximation of the full fixed-range trajectory. The approach is used on two different time-scale formulations. The first holds weight constant, and the second allows weight and range dynamics to propagate on the same time-scale. Solutions for the first formulation are only carried out to zero order in the small parameter, while solutions for the second formulation are carried out to first order. Calculations for a HSCT design were made to illustrate the method. Results show that the minimum fuel trajectory consists of three segments: a minimum fuel energy-climb, a cruise-climb, and a minimum drag glide. The minimum time trajectory also has three segments: a maximum dynamic pressure ascent, a constant altitude cruise, and a maximum dynamic pressure glide. The minimum direct operating cost trajectory is an optimal combination of the two. For realistic costs of fuel and flight time, the minimum direct operating cost trajectory is very similar to the minimum fuel trajectory. Moreover, the HSCT has three local optimum cruise speeds, with the globally optimum cruise point at the highest allowable speed, if range is sufficiently long. The final range of the trajectory determines which locally optimal speed is best. Ranges of 500 to 6,000 nautical miles, subsonic and supersonic mixed flight, and varying fuel efficiency cases are analyzed. Finally, the payload-range curve of the HSCT design is determined.

Engraftment Efficiency after Intra-Bone Marrow versus Intravenous Transplantation of Bone Marrow Cells in a Canine Nonmyeloablative Dog Leukocyte Antigen-Identical Transplantation Model.

PubMed

Lange, Sandra; Steder, Anne; Killian, Doreen; Knuebel, Gudrun; Sekora, Anett; Vogel, Heike; Lindner, Iris; Dunkelmann, Simone; Prall, Friedrich; Murua Escobar, Hugo; Freund, Mathias; Junghanss, Christian

2017-02-01

An intra-bone marrow (IBM) hematopoietic stem cell transplantation (HSCT) is assumed to optimize the homing process and therefore to improve engraftment as well as hematopoietic recovery compared with conventional i.v. HSCT. This study investigated the feasibility and efficacy of IBM HSCT after nonmyeloablative conditioning in an allogeneic canine HSCT model. Two study cohorts received IBM HSCT of either density gradient (IBM-I, n = 7) or buffy coat (IBM-II, n = 6) enriched bone marrow cells. An historical i.v. HSCT cohort served as control. Before allogeneic HSCT experiments were performed, we investigated the feasibility of IBM HSCT by using technetium-99m marked autologous grafts. Scintigraphic analyses confirmed that most IBM-injected autologous cells remained at the injection sites, independent of the applied volume. In addition, cell migration to other bones occurred. The enrichment process led to different allogeneic graft volumes (IBM-I, 2 × 5 mL; IBM-II, 2 × 25 mL) and significantly lower counts of total nucleated cells in IBM-I grafts compared with IBM-II grafts (1.6 × 10 8 /kg versus 3.8 × 10 8 /kg). After allogeneic HSCT, dogs of the IBM-I group showed a delayed engraftment with lower levels of donor chimerism when compared with IBM-II or to i.v. HSCT. Dogs of the IBM-II group tended to reveal slightly faster early leukocyte engraftment kinetics than intravenously transplanted animals. However, thrombocytopenia was significantly prolonged in both IBM groups when compared with i.v. HSCT. In conclusion, IBM HSCT is feasible in a nonmyeloablative HSCT setting but failed to significantly improve engraftment kinetics and hematopoietic recovery in comparison with conventional i.v. HSCT. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Early application of related SCT might improve clinical outcome in adult T-cell leukemia/lymphoma.

PubMed

Fuji, S; Fujiwara, H; Nakano, N; Wake, A; Inoue, Y; Fukuda, T; Hidaka, M; Moriuchi, Y; Miyamoto, T; Uike, N; Taguchi, J; Eto, T; Tomoyose, T; Kondo, T; Yamanoha, A; Ichinohe, T; Atsuta, Y; Utsunomiya, A

2016-02-01

Allogeneic hematopoietic SCT (allo-HSCT) is a curative treatment for aggressive adult T-cell leukemia/lymphoma (ATLL). Considering the dismal prognosis associated with conventional chemotherapies, early application of allo-HSCT might be beneficial for patients with ATLL. However, no previous study has addressed the optimal timing of allo-HSCT from related donors. Hence, to evaluate the impact of timing of allo-HSCT for patients with ATLL, we retrospectively analyzed data from patients with ATLL who received an allo-HSCT from a related donor. The median age was 52 years. Patients were grouped according to the interval from diagnosis to allo-HSCT: early transplant group, <100 days, n=72; late transplant group, ⩾100 days, n=428. The corresponding constituents of disease status were not statistically different between the two groups (P=0.11). The probability of OS in the early transplant group was significantly higher than that in the late transplant group (4-year OS, 49.3% vs 31.2%). Multivariate analysis revealed that late allo-HSCT was an unfavorable prognostic factor for OS (hazard ratio, 1.46; 95% confidence interval (CI), 1.01-2.11; P=0.04). Despite the limitations of a retrospective study, it might be acceptable to consider early application of allo-HSCT for ATLL.

Sonic Boom Minimization Efforts on Boeing HSCT Baseline

NASA Technical Reports Server (NTRS)

Cheung, Samson H.; Fouladi, Kamran; Haglund, George; Tu, Eugene

1999-01-01

A team was formed to tackle the sonic boom softening issues of the current Boeing HSCT design. The team consisted of personnel from NASA Ames, NASA Langley, and Boeing company. The work described in this paper was done when the first author was at NASA Ames Research Center. This paper presents the sonic boom softening work on two Boeing High Speed Civil Transport (HSCT) baseline configurations, Reference-H and Boeing-1122. This presentation can be divided into two parts: parametric studies and sonic boom minimization by CFD optimization routines.

HSCT4.0 Application: Software Requirements Specification

NASA Technical Reports Server (NTRS)

Salas, A. O.; Walsh, J. L.; Mason, B. H.; Weston, R. P.; Townsend, J. C.; Samareh, J. A.; Green, L. L.

2001-01-01

The software requirements for the High Performance Computing and Communication Program High Speed Civil Transport application project, referred to as HSCT4.0, are described. The objective of the HSCT4.0 application project is to demonstrate the application of high-performance computing techniques to the problem of multidisciplinary design optimization of a supersonic transport configuration, using high-fidelity analysis simulations. Descriptions of the various functions (and the relationships among them) that make up the multidisciplinary application as well as the constraints on the software design arc provided. This document serves to establish an agreement between the suppliers and the customer as to what the HSCT4.0 application should do and provides to the software developers the information necessary to design and implement the system.

Minimum Climb to Cruise Noise Trajectories Modeled for the High Speed Civil Transport

NASA Technical Reports Server (NTRS)

Berton, Jeffrey J.

1998-01-01

The proposed U.S. High Speed Civil Transport (HSCT) will revolutionize commercial air travel by providing economical supersonic passenger service to destinations worldwide. Unlike the high-bypass turbofan engines that propel today's subsonic airliners, HSCT engines will have much higher jet exhaust speeds. Jet noise, caused by the turbulent mixing of high-speed exhaust with the surrounding air, poses a significant challenge for HSCT engine designers. To resolve this challenge, engineers have designed advanced mixer rejector nozzles that reduce HSCT jet noise to airport noise certification levels by entraining and mixing large quantities of ambient air with the engines' jet streams. Although this works well during the first several minutes of flight, far away from the airport, as the HSCT gains speed and climbs, poor ejector inlet recovery and ejector ram drag contribute to poor thrust, making it advantageous to turn off the ejector. Doing so prematurely, however, can cause unacceptable noise levels to propagate to the ground, even when the aircraft is many miles from the airport. This situation lends itself ideally to optimization, where the aircraft trajectory, throttle setting, and ejector setting can be varied (subject to practical aircraft constraints) to minimize the noise propagated to the ground. A method was developed at the NASA Lewis Research Center that employs a variation of the classic energy state approximation: a trajectory analysis technique historically used to minimize climb time or fuel burned in many aircraft problems. To minimize the noise on the ground at any given throttle setting, high aircraft altitudes are desirable; but the HSCT may either climb quickly to high altitudes using a high, noisy throttle setting or climb more slowly at a lower, quieter throttle setting. An optimizer has been programmed into NASA's existing aircraft and noise analysis codes to balance these options by dynamically choosing the best altitude-velocity path and throttle setting history. The noise level standard, or metric, used in the optimizer should be one that accurately reflects the subjective annoyance levels of ground-based observers under the flight path. A variety of noise metrics are available, many of which are practical for airport-vicinity noise certification. Unlike airport noise, however, the HSCT's climb noise will be characterized by relatively low noise levels, long durations, and low-frequency spectra. The noise metrics used in these calculations are based on the recommendations of researchers at the NASA Langley Research Center, who have correlated the flyover noise annoyance levels of actual laboratory subjects with a variety of measurements. Analysis of data from this optimizer has shown that significant reductions in noise may be obtained with trajectory optimization. And since throttling operations are performed in the subsonic portion of the climb path (where thrust is plentiful), only small penalties in HSCT range or fuel performance occur.

Traumeel S in preventing and treating mucositis in young patients undergoing SCT: a report of the Children’s Oncology Group

PubMed Central

Sencer, SF; Zhou, T; Freedman, LS; Ives, JA; Chen, Z; Wall, D; Nieder, ML; Grupp, SA; Yu, LC; Sahdev, I; Jonas, WB; Wallace, JD; Oberbaum, M

2012-01-01

Mucositis can be a serious complication of hematopoietic SCT (HSCT). A previous phase II trial in 32 children undergoing HSCT reported a beneficial effect of the homeopathic remedy Traumeel S. The Children’s Oncology Group sought to replicate the results in a multi-institutional trial. The study was an international multi-center, double-blind, randomized trial comparing Traumeel with placebo in patients aged 3–25 years undergoing myeloablative HSCT. Traumeel/placebo was started on Day −1 as a five-time daily mouth rinse. Efficacy of the treatment was assessed using the modified Walsh scale for mucositis, scored daily from Day −1 to 20 days after HCST. The main outcome was the sum of Walsh scale scores (area-under-the-curve (AUC)) over this period. Other outcomes included narcotic use, days of total parenteral feeding, days of nasogastric feeding and adverse events. In 181 evaluable patients, there was no statistical difference in mucositis (AUC) in the Traumeel group (76.7) compared with placebo (67.3) (P = 0.13). There was a trend towards less narcotic usage in the Traumeel patients. No statistically beneficial effect from Traumeel was demonstrated for mucositis. We could not confirm that Traumeel is an effective treatment for mucositis in children undergoing HSCT. PMID:22504933

Bone Marrow Mesenchymal Stromal Cells to Treat Complications Following Allogeneic Stem Cell Transplantation

PubMed Central

Battiwalla, Minoo

2014-01-01

Allogeneic hematopoietic stem cell transplantation (HSCT) is a technologically complicated procedure that represents the only cure for many hematologic malignancies. However, HSCT is often complicated by life-threatening toxicities related to the chemo-radiation conditioning regimen, poor engraftment of donor HSCs, the hyperinflammatory syndrome of graft-versus-host disease (GVHD), infection risks from immunosuppression, and end-organ damage. Bone marrow stromal cells (MSCs), also known as “mesenchymal stromal cells,” not only play a nurturing role in the hematopoietic microenvironment but also can differentiate into other cell types of mesenchymal origin. MSCs are poorly immunogenic, and they can modulate immunological responses through interactions with a wide range of innate and adaptive immune cells to reduce inflammation. They are easily expanded ex vivo and after infusion, home to sites of injury and inflammation to promote tissue repair. Despite promising early trial results in HSCT with significant responses that have translated into survival benefits, there have been significant barriers to successful commercialization as an off-the-shelf therapy. Current efforts with MSCs in the HSCT setting are geared toward determining the factors determining potency, understanding the precise mechanisms of action in human HSCT, knowing their kinetics and fate, optimizing dose and schedule, incorporating biomarkers as response surrogates, addressing concerns about safety, optimizing clinical trial design, and negotiating the uncharted regulatory landscape for licensable cellular therapy. PMID:24410434

Adaptive surrogate model based multi-objective transfer trajectory optimization between different libration points

NASA Astrophysics Data System (ADS)

Peng, Haijun; Wang, Wei

2016-10-01

An adaptive surrogate model-based multi-objective optimization strategy that combines the benefits of invariant manifolds and low-thrust control toward developing a low-computational-cost transfer trajectory between libration orbits around the L1 and L2 libration points in the Sun-Earth system has been proposed in this paper. A new structure for a multi-objective transfer trajectory optimization model that divides the transfer trajectory into several segments and gives the dominations for invariant manifolds and low-thrust control in different segments has been established. To reduce the computational cost of multi-objective transfer trajectory optimization, a mixed sampling strategy-based adaptive surrogate model has been proposed. Numerical simulations show that the results obtained from the adaptive surrogate-based multi-objective optimization are in agreement with the results obtained using direct multi-objective optimization methods, and the computational workload of the adaptive surrogate-based multi-objective optimization is only approximately 10% of that of direct multi-objective optimization. Furthermore, the generating efficiency of the Pareto points of the adaptive surrogate-based multi-objective optimization is approximately 8 times that of the direct multi-objective optimization. Therefore, the proposed adaptive surrogate-based multi-objective optimization provides obvious advantages over direct multi-objective optimization methods.

High BAALC copy numbers in peripheral blood prior to allogeneic transplantation predict early relapse in acute myeloid leukemia patients.

PubMed

Jentzsch, Madlen; Bill, Marius; Grimm, Juliane; Schulz, Julia; Goldmann, Karoline; Beinicke, Stefanie; Häntschel, Janine; Pönisch, Wolfram; Franke, Georg-Nikolaus; Vucinic, Vladan; Behre, Gerhard; Lange, Thoralf; Niederwieser, Dietger; Schwind, Sebastian

2017-10-20

High BAALC expression levels at acute myeloid leukemia diagnosis have been linked to adverse outcomes. Recent data indicate that high BAALC expression levels may also be used as marker for residual disease following acute myeloid leukemia treatment. Allogeneic hematopoietic stem cell transplantation (HSCT) offers a curative treatment for acute myeloid leukemia patients. However, disease recurrence remains a major clinical challenge and identification of high-risk patients prior to HSCT is crucial to improve outcomes. We performed absolute quantification of BAALC copy numbers in peripheral blood prior (median 7 days) to HSCT in complete remission (CR) or CR with incomplete peripheral recovery in 82 acute myeloid leukemia patients using digital droplet PCR (ddPCR) technology. An optimal cut-off of 0.14 BAALC / ABL1 copy numbers was determined and applied to define patients with high or low BAALC / ABL1 copy numbers. High pre-HSCT BAALC / ABL1 copy numbers significantly associated with higher cumulative incidence of relapse and shorter overall survival in univariable and multivariable models. Patients with high pre-HSCT BAALC / ABL1 copy numbers were more likely to experience relapse within 100 days after HSCT. Evaluation of pre-HSCT BAALC / ABL1 copy numbers in peripheral blood by ddPCR represents a feasible and rapid way to identify acute myeloid leukemia patients at high risk of early relapse after HSCT. The prognostic impact was also observed independently of other known clinical, genetic, and molecular prognosticators. In the future, prospective studies should evaluate whether acute myeloid leukemia patients with high pre-HSCT BAALC / ABL1 copy numbers benefit from additional treatment before or early intervention after HSCT.

High BAALC copy numbers in peripheral blood prior to allogeneic transplantation predict early relapse in acute myeloid leukemia patients

PubMed Central

Jentzsch, Madlen; Bill, Marius; Grimm, Juliane; Schulz, Julia; Goldmann, Karoline; Beinicke, Stefanie; Häntschel, Janine; Pönisch, Wolfram; Franke, Georg-Nikolaus; Vucinic, Vladan; Behre, Gerhard; Lange, Thoralf; Niederwieser, Dietger; Schwind, Sebastian

2017-01-01

High BAALC expression levels at acute myeloid leukemia diagnosis have been linked to adverse outcomes. Recent data indicate that high BAALC expression levels may also be used as marker for residual disease following acute myeloid leukemia treatment. Allogeneic hematopoietic stem cell transplantation (HSCT) offers a curative treatment for acute myeloid leukemia patients. However, disease recurrence remains a major clinical challenge and identification of high-risk patients prior to HSCT is crucial to improve outcomes. We performed absolute quantification of BAALC copy numbers in peripheral blood prior (median 7 days) to HSCT in complete remission (CR) or CR with incomplete peripheral recovery in 82 acute myeloid leukemia patients using digital droplet PCR (ddPCR) technology. An optimal cut-off of 0.14 BAALC/ABL1 copy numbers was determined and applied to define patients with high or low BAALC/ABL1 copy numbers. High pre-HSCT BAALC/ABL1 copy numbers significantly associated with higher cumulative incidence of relapse and shorter overall survival in univariable and multivariable models. Patients with high pre-HSCT BAALC/ABL1 copy numbers were more likely to experience relapse within 100 days after HSCT. Evaluation of pre-HSCT BAALC/ABL1 copy numbers in peripheral blood by ddPCR represents a feasible and rapid way to identify acute myeloid leukemia patients at high risk of early relapse after HSCT. The prognostic impact was also observed independently of other known clinical, genetic, and molecular prognosticators. In the future, prospective studies should evaluate whether acute myeloid leukemia patients with high pre-HSCT BAALC/ABL1 copy numbers benefit from additional treatment before or early intervention after HSCT. PMID:29152132

Population Pharmacokinetics of Vancomycin in Patients Undergoing Allogeneic Hematopoietic Stem-Cell Transplantation.

PubMed

Okada, Akira; Kariya, Misato; Irie, Kei; Okada, Yutaka; Hiramoto, Nobuhiro; Hashimoto, Hisako; Kajioka, Ryosuke; Maruyama, Chika; Kasai, Hidefumi; Hamori, Mami; Nishimura, Asako; Shibata, Nobuhito; Fukushima, Keizo; Sugioka, Nobuyuki

2018-05-15

Vancomycin is a commonly used antimicrobial agent for patients undergoing allogeneic hematopoietic stem-cell transplantation (allo-HSCT). Vancomycin has large inter- and intraindividual pharmacokinetic variability, which is mainly described by renal function; various studies have indicated that vancomycin pharmacokinetics are altered in special populations. However, little is known regarding vancomycin pharmacokinetics in patients undergoing allo-HSCT. Therefore, we aimed to develop a population pharmacokinetic (PopPK) model of vancomycin in patients undergoing allo-HSCT for effective and safe antimicrobial therapy and to develop a vancomycin dosing nomogram for a vancomycin optimal-dosing strategy. In total, 285 observations from 95 patients undergoing allo-HSCT were available. The final PopPK parameter estimates were central volume of distribution (V1, L), 39.2; clearance (L/h), 4.25; peripheral volume of distribution (V2, L), 56.1; and intercompartmental clearance (L/h), 1.95. The developed vancomycin model revealed an increase in V1 and V2 compared with those in the general population that consisted of patients with methicillin-resistant Staphylococcus aureus. Moreover, serum creatinine was reduced because of an increase in the plasma fraction because of destruction of hematopoietic stem cells accompanying allo-HSCT pretreatment, suggesting that the Cockcroft-Gault equation-based creatinine clearance value was overestimated. To our knowledge, this is the first PopPK study to develop a dosing nomogram for vancomycin in patients undergoing allo-HSCT and was proven to be useful in optimizing the dosage and dosing interval of vancomycin in these patients. This strategy will provide more useful information for vancomycin therapy with an evidence-based dose adjustment. © 2018, The American College of Clinical Pharmacology.

1999 NASA High-Speed Research Program Aerodynamic Performance Workshop. Volume 1; Configuration Aerodynamics

NASA Technical Reports Server (NTRS)

Hahne, David E. (Editor)

1999-01-01

NASA's High-Speed Research Program sponsored the 1999 Aerodynamic Performance Technical Review on February 8-12, 1999 in Anaheim, California. The review was designed to bring together NASA and industry High-Speed Civil Transport (HSCT) Aerodynamic Performance technology development participants in the areas of Configuration Aerodynamics (transonic and supersonic cruise drag prediction and minimization), High Lift, and Flight Controls. The review objectives were to: (1) report the progress and status of HSCT aerodynamic performance technology development; (2) disseminate this technology within the appropriate technical communities; and (3) promote synergy among the scientists and engineers working on HSCT aerodynamics. In particular, single and midpoint optimized HSCT configurations, HSCT high-lift system performance predictions, and HSCT simulation results were presented, along with executive summaries for all the Aerodynamic Performance technology areas. The HSR Aerodynamic Performance Technical Review was held simultaneously with the annual review of the following airframe technology areas: Materials and Structures, Environmental Impact, Flight Deck, and Technology Integration. Thus, a fourth objective of the Review was to promote synergy between the Aerodynamic Performance technology area and the other technology areas of the HSR Program. This Volume 1/Part 1 publication covers configuration aerodynamics.

1999 NASA High-Speed Research Program Aerodynamic Performance Workshop. Volume 2; High Lift

NASA Technical Reports Server (NTRS)

Hahne, David E. (Editor)

1999-01-01

NASA's High-Speed Research Program sponsored the 1999 Aerodynamic Performance Technical Review on February 8-12, 1999 in Anaheim, California. The review was designed to bring together NASA and industry High-Speed Civil Transport (HSCT) Aerodynamic Performance technology development participants in the areas of Configuration Aerodynamics (transonic and supersonic cruise drag prediction and minimization), High Lift, and Flight Controls. The review objectives were to (1) report the progress and status of HSCT aerodynamic performance technology development; (2) disseminate this technology within the appropriate technical communities; and (3) promote synergy among die scientists and engineers working on HSCT aerodynamics. In particular, single and midpoint optimized HSCT configurations, HSCT high-lift system performance predictions, and HSCT simulation results were presented, along with executive summaries for all the Aerodynamic Performance technology areas. The HSR Aerodynamic Performance Technical Review was held simultaneously with the annual review of the following airframe technology areas: Materials and Structures, Environmental Impact, Flight Deck, and Technology Integration. Thus, a fourth objective of the Review was to promote synergy between the Aerodynamic Performance technology area and the other technology areas of the HSR Program. This Volume 2/Part 2 publication covers the tools and methods development session.

Defibrotide sodium for the treatment of hepatic veno-occlusive disease/sinusoidal obstruction syndrome.

PubMed

Richardson, Paul G; Triplett, Brandon M; Ho, Vincent T; Chao, Nelson; Dignan, Fiona L; Maglio, Michelle; Mohty, Mohamad

2018-02-01

Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is an unpredictable condition associated with endothelial-cell damage due to conditioning for hematopoietic stem-cell transplantation (HSCT) or chemotherapy without HSCT. Mortality in patients with VOD/SOS and multi-organ dysfunction (MOD) may be >80%. Areas covered: Defibrotide is the only approved drug for the treatment of severe hepatic VOD/SOS after HSCT in the European Union and hepatic VOD/SOS with renal or pulmonary dysfunction in the United States. Its efficacy in patients with VOD/SOS with MOD post-HSCT was demonstrated in a clinical-trial program that included a historically controlled treatment study, a phase 2 trial, and a large T-IND expanded-access program that also included patients without MOD and who received chemotherapy without HSCT. Expert commentary: Defibrotide appears to protect endothelial cells and restore the thrombolytic-fibrinolytic balance. It addresses a significant clinical need and has demonstrated favorable Day +100 survival and overall adverse-event rates that seem similar to control groups receiving supportive care alone. Currently, defibrotide is under investigation for the prevention of VOD/SOS in high-risk pediatric and adult patients.

Excellent outcome of allogeneic hematopoietic SCT with reduced-intensity conditioning for the treatment of chronic active EBV infection.

PubMed

Kawa, K; Sawada, A; Sato, M; Okamura, T; Sakata, N; Kondo, O; Kimoto, T; Yamada, K; Tokimasa, S; Yasui, M; Inoue, M

2011-01-01

Since we reported the first successful case of allogeneic hematopoietic SCT (allo-HSCT), we have performed allo-HSCT for 29 patients with chronic active EBV infection (CAEBV), using either myeloablative conditioning (MAC) allo-HSCT (MAST) or reduced-intensity conditioning (RIC) allo-HSCT (RIST). In this retrospective analysis we compared the outcomes after MAST and RIST to identify the optimal conditioning for patients with CAEBV. Of 29 patients, 11 underwent allo-HSCT with MAC, consisting of TBI (12 Gy), etoposide (900 mg/m²) and CY (120 mg/kg) or melphalan (210 mg/m²), and the remaining 18 patients received allo-HSCT after RIC, consisting of fludarabine (∼ 180 mg/m²) and melphalan (140 mg/m²) or CY (120 mg/kg), with/without antithymocyte globulin and low-dose irradiation. Donor sources were 8 related BM, 2 related peripheral blood, 5 CD34 selected cells from HLA-haploidentical donors, 8 unrelated BM and 8 unrelated cord blood. The 3-year-EFS rate was 54.5 ± 15.0% for MAST group and 85.0 ± 8.0% for RIST group, and the 3-year OS rate was 54.5 ± 15.0% for MAST group and 95.0 ± 4.9% for RIST group (P = 0.016). Allo-HSCT after RIC seems to be a promising approach for the treatment of CAEBV.

Pilot Study of Parent Psychophysiologic Outcomes in Pediatric Hematopoietic Stem Cell Transplantation

PubMed Central

Ward, Jessica; Swanson, Barbara; Fogg, Louis; Rodgers, Cheryl

2016-01-01

Background Parents of children undergoing hematopoietic stem cell transplantation (HSCT) are at risk for psychological distress. This distress may result in aberrant immune, inflammatory or endocrine effects. These physiologic outcomes have not been reported previously. Main Objective To examine the feasibility of longitudinal testing of psychophysiological parameters of stress in parents of children undergoing HSCT. Methods This pilot study was conducted at a large children's hospital in the Midwest, and included parents of children who received autologous or allogeneic HSCT. Time points included: prior to start of HSCT conditioning, day +30, +60, and +100. Outcome variables included parent perceived stress, lymphocyte subsets, c-reactive protein (CRP), pro-inflammatory cytokines, salivary cortisol, and salivary amylase. Effect sizes were calculated for each outcome. Results Twelve parent-child dyads were enrolled (10 mothers, 2 fathers). Missing data was minimal. Parent perceived stress significantly increased from pre-HSCT through day +100, and parent CD3+ T lymphocyte counts decreased from pre-HSCT through day +100. No significant effects were observed for salivary studies, CRP, or pro-inflammatory cytokines. Effect sizes ranged from 1.23 (perceived stress) to 0.07 (CRP). Conclusion Results of this study suggest that it is feasible longitudinally measure parent psychophysiologic outcomes in the pediatric HSCT setting. Additionally, parent perceived stress increased linearly from start of conditioning through day +100, while parent T lymphocytes decreased concurrently. Implications for practice Routine psychological and physical health screening of parents of children undergoing HSCT are needed. Multidisciplinary psychosocial support services should be offered to parents at regular intervals during their child's HSCT. PMID:27257801

Allogeneic Hematopoietic Stem Cell Transplantation Is an Effective Salvage Therapy for Patients with Chronic Myeloid Leukemia Presenting with Advanced Disease or Failing Treatment with Tyrosine Kinase Inhibitors.

PubMed

Nair, Anish P; Barnett, Michael J; Broady, Raewyn C; Hogge, Donna E; Song, Kevin W; Toze, Cynthia L; Nantel, Stephen H; Power, Maryse M; Sutherland, Heather J; Nevill, Thomas J; Abou Mourad, Yasser; Narayanan, Sujaatha; Gerrie, Alina S; Forrest, Donna L

2015-08-01

Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only known curative therapy for chronic myeloid leukemia (CML); however, it is rarely utilized given the excellent long-term results with tyrosine kinase inhibitor (TKI) treatment. The purpose of this study is to examine HSCT outcomes for patients with CML who failed TKI therapy or presented in advanced phase and to identify predictors of survival, relapse, and nonrelapse mortality (NRM). Fifty-one patients with CML underwent HSCT for advanced disease at diagnosis (n = 15), TKI resistance as defined by the European LeukemiaNet guidelines (n = 30), TKI intolerance (n = 2), or physician preference (n = 4). At a median follow-up of 71.9 months, the 8-year overall survival (OS), event-free survival (EFS), relapse, and NRM were 68%, 46%, 41%, and 23%, respectively. In univariate analysis, predictors of OS included first chronic phase (CP1) disease status at HSCT (P = .0005), European Society for Blood and Marrow Transplantation score 1 to 4 (P = .04), and complete molecular response (CMR) to HSCT (P < .0001). Donor (female) to patient (male) gender combination (P = .02) and CMR to HSCT (P < .0001) predicted lower relapse. In multivariate analysis, CMR to HSCT remained an independent predictor of OS (odds ratio [OR], 43), EFS (OR, 56) and relapse (OR, 29). This report indicates that the outlook is excellent for those patients who remain in CP1 at the time of HSCT and achieve a CMR after HSCT. However, only approximately 50% of those in advanced phase at HSCT are long-term survivors. This highlights the ongoing need to try to identify patients earlier, before disease progression, who are destined to fail this treatment to optimize transplantation outcomes. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Configuration Management of an Optimization Application in a Research Environment

NASA Technical Reports Server (NTRS)

Townsend, James C.; Salas, Andrea O.; Schuler, M. Patricia

1999-01-01

Multidisciplinary design optimization (MDO) research aims to increase interdisciplinary communication and reduce design cycle time by combining system analyses (simulations) with design space search and decision making. The High Performance Computing and Communication Program's current High Speed Civil Transport application, HSCT4.0, at NASA Langley Research Center involves a highly complex analysis process with high-fidelity analyses that are more realistic than previous efforts at the Center. The multidisciplinary processes have been integrated to form a distributed application by using the Java language and Common Object Request Broker Architecture (CORBA) software techniques. HSCT4.0 is a research project in which both the application problem and the implementation strategy have evolved as the MDO and integration issues became better understood. Whereas earlier versions of the application and integrated system were developed with a simple, manual software configuration management (SCM) process, it was evident that this larger project required a more formal SCM procedure. This report briefly describes the HSCT4.0 analysis and its CORBA implementation and then discusses some SCM concepts and their application to this project. In anticipation that SCM will prove beneficial for other large research projects, the report concludes with some lessons learned in overcoming SCM implementation problems for HSCT4.0.

Eliminating SCID row: new approaches to SCID.

PubMed

Kohn, Donald B

2014-12-05

Treatments for patients with SCID by hematopoietic stem cell transplantation (HSCT) have changed this otherwise lethal primary immune deficiency disorder into one with an increasingly good prognosis. SCID has been the paradigm disorder supporting many key advances in the field of HSCT, with first-in-human successes with matched sibling, haploidentical, and matched unrelated donor allogeneic transplantations. Nevertheless, the optimal approaches for HSCT are still being defined, including determining the optimal stem cell sources, the use and types of pretransplantation conditioning, and applications for SCID subtypes associated with radiosensitivity, for patients with active viral infections and for neonates. Alternatively, autologous transplantation after ex vivo gene correction (gene therapy) has been applied successfully to the treatment of adenosine deaminase-deficient SCID and X-linked SCID by vector-mediated gene addition. Gene therapy holds the prospect of avoiding risks of GVHD and would allow each patient to be their own donor. New approaches to gene therapy by gene correction in autologous HSCs using site-specific endonuclease-mediated homology-driven gene repair are under development. With newborn screening becoming more widely adopted to detect SCID patients before they develop complications, the prognosis for SCID is expected to improve further. This chapter reviews recent advances and ongoing controversies in allogeneic and autologous HSCT for SCID. © 2014 by The American Society of Hematology. All rights reserved.

Hematopoietic stem cell transplantation for isolated extramedullary relapse of acute lymphoblastic leukemia in children.

PubMed

Gabelli, Maria; Zecca, Marco; Messina, Chiara; Carraro, Elisa; Buldini, Barbara; Rovelli, Attilio Maria; Fagioli, Franca; Bertaina, Alice; Lanino, Edoardo; Favre, Claudio; Rabusin, Marco; Prete, Arcangelo; Ripaldi, Mimmo; Barberi, Walter; Porta, Fulvio; Caniglia, Maurizio; Santarone, Stella; D'Angelo, Paolo; Basso, Giuseppe; Locatelli, Franco

2018-06-13

Relapse of acute lymphoblastic leukemia (ALL) may occur in extramedullary sites, mainly central nervous system (CNS) and testis. Optimal post-remissional treatment for isolated extramedullary relapse (IEMR) is still controversial. We collected data of children treated with hematopoietic stem cell transplantation (HSCT) for ALL IEMR from 1990 to 2015 in Italy. Among 281 patients, 167 had a relapse confined to CNS, 73 to testis, 14 to mediastinum, and 27 to other organs. Ninety-seven patients underwent autologous HSCT, 79 received allogeneic HSCT from a matched family donor, 75 from a matched unrelated donor, and 30 from an HLA-haploidentical donor. The 10-year overall survival was 56% and was not influenced by gender, ALL blast immune-phenotype, age, site of relapse, duration of first remission, and type of HSCT. In multivariable analysis, the only prognostic factors were disease status at HSCT and year of transplantation. Patients transplanted in third or subsequent complete remission (CR) had a risk of death 2.3 times greater than those in CR2. Children treated after 2000 had half the risk of death than those treated before that year. Our results suggest that both autologous and allogeneic HSCT may be considered for the treatment of pediatric ALL IEMR after the achievement of CR2.

Children's psychological distress during pediatric HSCT: parent and child perspectives.

PubMed

Chang, Grace; Ratichek, Sara J; Recklitis, Christopher; Syrjala, Karen; Patel, Sunita K; Harris, Lynnette; Rodday, Angie Mae; Tighiouart, Hocine; Parsons, Susan K

2012-02-01

Hematopoietic stem cell transplantation (HSCT) can be challenging to pediatric recipients and their families. Little is known about the recipients' psychological status as they initiate treatment and in the year afterwards. The purpose of this study is to describe the psychological status of 107 pediatric HSCT recipients from their parents' perspective, and to compare reports from parents and children in a subset of 55 children. We hypothesized that there would be discrepancies between parent and child report of child distress. Multi-site, prospective study of eligible child participants and their parents who completed selected modules from the Structured Clinical Interview for DSM-IV-TR, Childhood Version (KID-SCID) the month before and one year after HSCT. Diagnoses were threshold or subthreshold. According to parents, nearly 30% of children had anxiety disorder both before and after HSCT; approximately half of these met threshold criteria. Agreement between parents and children for anxiety disorders was poor at baseline (κ = -0.18, 95%CI = -0.33, -0.02) and fair at 12 months (κ  = 0.31, 95%CI  = -0.04, 0.66). Agreement about mood disorders was fair at baseline (10% prevalence, κ =  0.39, 95%CI = -0.02, 0.79) and moderate at 12 months (14% prevalence, κ = 0.41, 95%CI =  0.02, 0.80). Anxiety (30%) and mood (10-14%) symptoms are common in children both before and after HSCT; parent and child reports of these symptoms do not agree. Input from parents and children is recommended to identify more accurately children who may need additional intervention during and following HSCT. Copyright © 2011 Wiley Periodicals, Inc.

Potentially life-threatening coagulopathy associated with simultaneous reduction in coagulation and fibrinolytic function in pediatric acute leukemia after hematopoietic stem-cell transplantation.

PubMed

Ishihara, Takashi; Nogami, Keiji; Matsumoto, Tomoko; Nomura, Akitaka; Takeshita, Yasufumi; Ochi, Satoshi; Shima, Midori

2017-07-01

The pathogenesis of sinusoidal obstruction syndrome (SOS) and thrombotic microangiopathy (TMA) after hematopoietic stem cell transplantation (HSCT) is poorly understood, and limited information is available on global hemostatic function in HSCT. We assessed changes in coagulation and fibrinolysis using a simultaneous thrombin and plasmin generation assay (T/P-GA) during HSCT. Measurements of endogenous thrombin potential (T-EP) and plasmin peak height (P-Peak) using T/P-GA in six pediatric acute leukemia patients treated with HSCT were compared to normal plasma. In the SOS case, the ratios of T-EP and P-Peak to normal were simultaneously decreased at four weeks post-HSCT (Pre; ~1.1/1.1-1.4, Week+4; 0.14/0.0084, respectively). Similarly, in the TMA patient, both ratios were decreased at 3 weeks and recovered after 8 weeks (Pre; 1.2/~0.95, Week+3; 0.59/0.22, Week+8; 1.2/0.64-0.85). In the other patients, when SOS/TMA was not evident, the T/P-GA data remained within normal limits. These findings suggest that the simultaneous reduction of coagulation and fibrinolytic function in patients developing SOS/TMA can lead to a life-threatening coagulopathy. Further research is warranted to clarify global hemostatic function after HSCT to establish optimal supportive therapy for these critical clinical disorders of hemostasis.

Low-dose interleukin-2 as a modulator of Treg homeostasis after HSCT: current understanding and future perspectives.

PubMed

Matsuoka, Ken-Ichi

2018-02-01

CD4 + CD25 + Foxp3 + Treg is a functionally distinct subset of mature T cells with broad suppressive activity and has been shown to play an important role in the establishment of immune tolerance after HSCT. Altered cytokine environment in post-HSCT lymphopenia with a relative functional deficiency of IL-2 could hamper the reconstitution of Treg, leading to refractory GVHD. Based on the theory of low-dose IL-2 in which Treg can be selectively stimulated through the high-affinity IL-2 receptor, clinical studies have been conducted and demonstrated that low-dose IL-2 administration can restore Treg homeostasis and promote the expansion of this subset on the polymorphic processes of Treg reconstitution after HSCT. The new therapeutic indication of IL-2 for immune tolerance has launched in the field of HSCT and is spreading to the other fields including the treatment for autoimmune diseases. To further extend the indication of low-dose IL-2 to more patients with various immunological problems, the optimization of the timing and dosing of IL-2 intervention and the concomitant immune suppressive therapy according to each patient-based assessment are to be desired in the near future. Further prospective studies may facilitate the development of novel therapeutic algorithms for the effective and safe induction of immune tolerance after HSCT.

Hematopoietic Stem Cell Therapy as a Counter-Measure for Human Exploration of Deep Space

NASA Technical Reports Server (NTRS)

Ohi, S.; Roach, A.-N.; Ramsahai, S.; Kim, B. C.; Fitzgerald, W.; Riley, D. A.; Gonda, S. R.

2004-01-01

Human exploration of deep space depends, in part, on our ability to counter severe/invasive disorders that astronauts experience in space environments. The known symptoms include hematological/cardiac abnormalities,bone and muscle losses, immunodeficiency, neurological disorders, and cancer. Exploiting the extraordinary plasticity of hematopoietic stem cells (HSCs), which differentiate not only to all types of blood cells, but also to various tissues, we have advanced a hypothesis that ome of the space-caused disorders maybe amenable to hematopoietis stem cell therapy(HSCT) so as to maintain promote human exploration of deep space. Using mouse models of human anemia beta-thaiassemia) as well as spaceflight (hindlimb unloading system), we have obtained feasibility results of HSCT for space anemia, muscle loss, and immunodeficiency. For example, in the case of HSCT for muscle loss, the beta-galactosidese marked HSCs were detected in the hindlimbs of unloaded mouse following transplantation by -X-gal wholemaunt staining procedure. Histochemicaland physical analyses indicated structural contribution of HSCs to the muscle. HSCT for immunodeficiency was investigated ising beta-galactosidese gene-tagged Escherichia coli as the infectious agent. Results of the X-gal staining procedure indicated the rapeutic role of the HSCT. To facilitate the HSCT in space, growth of HSCs were optimized in the NASA Rotating Wall Vessel (RWV) culture systems, including Hydrodynamic Focusing Bioreactor (HFB).

An approach for aerodynamic optimization of transonic fan blades

NASA Astrophysics Data System (ADS)

Khelghatibana, Maryam

Aerodynamic design optimization of transonic fan blades is a highly challenging problem due to the complexity of flow field inside the fan, the conflicting design requirements and the high-dimensional design space. In order to address all these challenges, an aerodynamic design optimization method is developed in this study. This method automates the design process by integrating a geometrical parameterization method, a CFD solver and numerical optimization methods that can be applied to both single and multi-point optimization design problems. A multi-level blade parameterization is employed to modify the blade geometry. Numerical analyses are performed by solving 3D RANS equations combined with SST turbulence model. Genetic algorithms and hybrid optimization methods are applied to solve the optimization problem. In order to verify the effectiveness and feasibility of the optimization method, a singlepoint optimization problem aiming to maximize design efficiency is formulated and applied to redesign a test case. However, transonic fan blade design is inherently a multi-faceted problem that deals with several objectives such as efficiency, stall margin, and choke margin. The proposed multi-point optimization method in the current study is formulated as a bi-objective problem to maximize design and near-stall efficiencies while maintaining the required design pressure ratio. Enhancing these objectives significantly deteriorate the choke margin, specifically at high rotational speeds. Therefore, another constraint is embedded in the optimization problem in order to prevent the reduction of choke margin at high speeds. Since capturing stall inception is numerically very expensive, stall margin has not been considered as an objective in the problem statement. However, improving near-stall efficiency results in a better performance at stall condition, which could enhance the stall margin. An investigation is therefore performed on the Pareto-optimal solutions to demonstrate the relation between near-stall efficiency and stall margin. The proposed method is applied to redesign NASA rotor 67 for single and multiple operating conditions. The single-point design optimization showed +0.28 points improvement of isentropic efficiency at design point, while the design pressure ratio and mass flow are, respectively, within 0.12% and 0.11% of the reference blade. Two cases of multi-point optimization are performed: First, the proposed multi-point optimization problem is relaxed by removing the choke margin constraint in order to demonstrate the relation between near-stall efficiency and stall margin. An investigation on the Pareto-optimal solutions of this optimization shows that the stall margin has been increased with improving near-stall efficiency. The second multi-point optimization case is performed with considering all the objectives and constraints. One selected optimized design on the Pareto front presents +0.41, +0.56 and +0.9 points improvement in near-peak efficiency, near-stall efficiency and stall margin, respectively. The design pressure ratio and mass flow are, respectively, within 0.3% and 0.26% of the reference blade. Moreover the optimized design maintains the required choking margin. Detailed aerodynamic analyses are performed to investigate the effect of shape optimization on shock occurrence, secondary flows, tip leakage and shock/tip-leakage interactions in both single and multi-point optimizations.

The Hematopoietic Stem Cell Therapy for Exploration of Deep Space

NASA Astrophysics Data System (ADS)

Ohi, Seigo; Roach, Allana-Nicole; Ramsahai, Shweta; Kim, Bak C.; Fitzgerald, Wendy; Riley, Danny A.; Gonda, Steven R.

2004-02-01

Astronauts experience severe/invasive disorders caused by space environments. These include hematological and cardiac abnormalities, bone and muscle losses, immunodeficiency, neurological disorders and cancer. Exploiting the extraordinary plasticity of hematopoietic stem cells (HSCs), which differentiate not only to all types of blood cells, but also to various tissues, including muscle, bone, skin, liver, and neuronal cells, we advanced a hypothesis that some of the space-caused disorders might be amenable to hematopoietic stem cell therapy (HSCT) so as to maintain astronauts' homeostasis. If this were achievable, the HSCT could promote human exploration of deep space. Using mouse models of human anemia (β-thalassemia) and spaceflight (hindlimb suspension unloading system), we have obtained feasibility results of HSCT for space anemia, muscle loss, and immunodeficiency. For example, the β-thalassemic mice were successfully transplanted with isologous HSCs, resulting in chimerism of hemoglobin species and alleviation of the hemoglobinopathy. In the case of HSCT for muscle loss, β-galactosidase-marked HSCs, which were prepared from β-galactosidase-transgenic mice, were detected by the X-gal wholemount staining procedure in the hindlimbs of unloaded mice following transplantation. Histochemical and physical analyses indicated structural contribution of HSCs to the muscle. To investigate HSCT for immunodeficiency, β-galactosidase-transformed Escherichia coli was used as the reporter bacteria, and infected to control and the hindlimb suspended mice. Results of the X-gal stained tissues indicated that the HSCT could help eliminate the E. coli infection. In an effort to facilitate the HSCT in space, growth of HSCs has been optimized in the NASA Rotating Wall Vessel (RWV) culture systems, including Hydrodynamic Focusing Bioreactor (HFB).

Humoral Immune Reconstitution Kinetics after Allogeneic Hematopoietic Stem Cell Transplantation in Children: A Maturation Block of IgM Memory B Cells May Lead to Impaired Antibody Immune Reconstitution.

PubMed

Abdel-Azim, Hisham; Elshoury, Amro; Mahadeo, Kris M; Parkman, Robertson; Kapoor, Neena

2017-09-01

Although T cell immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been well studied, long-term B cell immune reconstitution remains less characterized. We evaluated humoral immune reconstitution among 71 pediatric allo-HSCT recipients. Although tetanus toxoid antibody levels were normal at 1 year after allo-HSCT, antipolysaccharide carbohydrate antibodies remained persistently low for up to 5 years. While naive B cell counts normalized by 6 months, IgM memory B cell deficiency persisted for up to 2 years (P = .01); switched memory B cell deficiency normalized by 1 year after allo-HSCT. CD4 + T cell immune reconstitution correlated with that of switched memory B cells as early as 6 months after allo-HSCT (r = .55, P = .002) but did not correlate with IgM memory B cells at any time point after allo-HSCT. Taken together, this suggests that allo-HSCT recipients have impaired antibody immune reconstitution, mainly due to IgM memory B cell maturation block, compared with more prompt T cell-dependent switched memory cell immune reconstitution. We further explored other factors that might affect humoral immune reconstitution. The use of total body irradiation was associated with lower naive B cells counts at 6 months after HSCT (P = .04) and lower IgM (P = .008) and switched (P = .003) memory B cells up to 2 years. Allo-HSCT recipients with extensive chronic graft-versus-host disease had lower IgM memory B cell counts (P = .03) up to 2 years after allo-HSCT. The use of cord blood was associated with better naive (P = .01), IgM (P = .0005), and switched memory (P = .006) B cells immune reconstitution. These findings may inform future prophylaxis and treatment strategies regarding risk of overwhelming infection, graft-versus-host disease, and post-allogeneic HSCT revaccination. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

A multi-center, randomized, controlled trial of parenteral nutrition titrated to resting energy expenditure in children undergoing hematopoietic stem cell transplantation (“PNTREE”): Rationale and design

PubMed Central

Bechard, Lori J.; Feldman, Henry A.; Gordon, Catherine; Gura, Kathleen; Sonis, Andrew; Leung, Kathryn; Venick, Robert; Guinan, Eva C.; Duggan, Christopher

2013-01-01

Background Children undergoing hematopoietic stem cell transplantation (HSCT) frequently require prolonged courses of parenteral nutrition (PN) as a consequence of gastrointestinal dysfunction related to preparative chemotherapy and radiation. PN has been associated with shorter engraftment time and decreased mortality during HSCT, however, it is also linked with complications, including infections, liver disease, and metabolic disturbances. Some of these complications may be a result of providing PN in excess of nutrient requirements. We previously described significant reductions in resting energy expenditure (REE), as measured by indirect calorimetry, over the course of HSCT. We also documented a decline in mid-arm muscle area, suggesting depletion of muscle mass, while triceps skinfold, a marker of fat stores, was unchanged. These results suggested the need for further study of energy expenditure, body composition and nutritional intake in this group of high risk patients. Design and hypothesis We hypothesize that changes in body composition affect REE during HSCT, and that standard nutritional support may lead to overfeeding. We are performing a randomized controlled trial of parenteral nutrition among children undergoing allogeneic HSCT. Subjects are randomized to receive PN designed to provide 100% of measured REE, or standard PN, i.e., 140% of estimated energy expenditure. The primary outcome variable is change in percent body fat. Secondary outcomes include glycemic control and frequency of infections, changes in REE and body composition. Conclusion This study will provide unique and comprehensive nutritional data and its results will guide nutritional therapy for children undergoing HSCT and possibly other catabolic patients. PMID:20004739

Aerodynamic shape optimization of a HSCT type configuration with improved surface definition

NASA Technical Reports Server (NTRS)

Thomas, Almuttil M.; Tiwari, Surendra N.

1994-01-01

Two distinct parametrization procedures of generating free-form surfaces to represent aerospace vehicles are presented. The first procedure is the representation using spline functions such as nonuniform rational b-splines (NURBS) and the second is a novel (geometrical) parametrization using solutions to a suitably chosen partial differential equation. The main idea is to develop a surface which is more versatile and can be used in an optimization process. Unstructured volume grid is generated by an advancing front algorithm and solutions obtained using an Euler solver. Grid sensitivity with respect to surface design parameters and aerodynamic sensitivity coefficients based on potential flow is obtained using an automatic differentiator precompiler software tool. Aerodynamic shape optimization of a complete aircraft with twenty four design variables is performed. High speed civil transport aircraft (HSCT) configurations are targeted to demonstrate the process.

Optimum Climb to Cruise Noise Trajectories for the High Speed Civil Transport

NASA Technical Reports Server (NTRS)

Berton, Jeffrey J.

2003-01-01

By entraining large quantities of ambient air into advanced ejector nozzles, the jet noise of the proposed High Speed Civil Transport (HSCT) is expected to be reduced to levels acceptable for airport-vicinity noise certification. Away from the airport, however, this entrained air is shut off and the engines are powered up from their cutback levels to provide better thrust for the climb to cruise altitude. Unsuppressed jet noise levels propagating to the ground far from the airport are expected to be high. Complicating this problem is the HSCT's relative noise level with respect to the subsonic commercial fleet of 2010, which is expected to be much quieter than it is today after the retirement of older, louder, domestic stage II aircraft by the year 2000. In this study, the classic energy state approximation theory is extended to calculate trajectories that minimize the climb to cruise noise of the HSCT. The optimizer dynamically chooses the optimal altitude velocity trajectory, the engine power setting, and whether the ejector should be stowed or deployed with respect to practical aircraft climb constraints and noise limits.

Integrated design and manufacturing for the high speed civil transport

NASA Technical Reports Server (NTRS)

1993-01-01

In June 1992, Georgia Tech's School of Aerospace Engineering was awarded a NASA University Space Research Association (USRA) Advanced Design Program (ADP) to address 'Integrated Design and Manufacturing for the High Speed Civil Transport (HSCT)' in its graduate aerospace systems design courses. This report summarizes the results of the five courses incorporated into the Georgia Tech's USRA ADP program. It covers AE8113: Introduction to Concurrent Engineering, AE4360: Introduction to CAE/CAD, AE4353: Design for Life Cycle Cost, AE6351: Aerospace Systems Design One, and AE6352: Aerospace Systems Design Two. AE8113: Introduction to Concurrent Engineering was an introductory course addressing the basic principles of concurrent engineering (CE) or integrated product development (IPD). The design of a total system was not the objective of this course. The goal was to understand and define the 'up-front' customer requirements, their decomposition, and determine the value objectives for a complex product, such as the high speed civil transport (HSCT). A generic CE methodology developed at Georgia Tech was used for this purpose. AE4353: Design for Life Cycle Cost addressed the basic economic issues for an HSCT using a robust design technique, Taguchi's parameter design optimization method (PDOM). An HSCT economic sensitivity assessment was conducted using a Taguchi PDOM approach to address the robustness of the basic HSCT design. AE4360: Introduction to CAE/CAD permitted students to develop and utilize CAE/CAD/CAM knowledge and skills using CATIA and CADAM as the basic geometric tools. AE6351: Aerospace Systems Design One focused on the conceptual design refinement of a baseline HSCT configuration as defined by Boeing, Douglas, and NASA in their system studies. It required the use of NASA's synthesis codes FLOPS and ACSYNT. A criterion called the productivity index (P.I.) was used to evaluate disciplinary sensitivities and provide refinements of the baseline HSCT configuration. AE6352: Aerospace Systems Design Two was a continuation of Aerospace Systems Design One in which wing concepts were researched and analyzed in more detail. FLOPS and ACSYNT were again used at the system level while other off-the-shelf computer codes were used for more detailed wing disciplinary analysis and optimization. The culmination of all efforts and submission of this report conclude the first year's efforts of Georgia Tech's NASA USRA ADP. It will hopefully provide the foundation for next year's efforts concerning continuous improvement of integrated design and manufacturing for the HSCT.

Epstein-Barr virus infection and related hematological diseases.

PubMed

Sawada, Akihisa

2016-01-01

Once the Epstein-Barr virus (EBV) has infected a person, it then latently infects B cells. This latent infection lasts a lifetime. However, EBV can infect T or NK cells (T/NK cells) in rare cases. Therefore, EBV causes various hematological diseases. Among these diseases, CAEBV is regarded as the most problematic because, although it is not particularly uncommon, the diagnostic tests for this disease are not covered by health insurance, a serious illness in the "non-active" periods is lacking, and the appropriate motivation for early initiation of treatment can easily be lost. However, the symptoms may suddenly change; and if the manifestations are resistant when such exacerbation occurs, CAEBC is potentially lethal. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only cure. Once the diagnosis has been made, earlier treatment initiation, safer bridging to allogeneic HSCT with multi-drug chemotherapy, and then, planned HSCT can be completed more safely and thereby achieve a better outcome.

Visfatin concentrations in children with leukemia before and after stem cell transplantation.

PubMed

Skoczen, Szymon; Tomasik, Przemyslaw J; Gozdzik, Jolanta; Fijorek, Kamil; Krasowska-Kwiecien, Aleksandra; Wiecha, Oktawiusz; Czogala, Wojciech; Dluzniewska, Agnieszka; Sztefko, Krystyna; Starzyk, Jerzy; Siedlar, Maciej

2014-04-01

Visfatin (VF) is an adipocytokine that performs many functions, including enhancing cell proliferation and biosynthesis of nicotinamide mononucleotides and dinucleotides. It also seems to be involved in the development of glucose metabolism disturbances. The goal of the study was the determination of VF concentrations in children with leukemia who are treated with stem cell transplantation. VF concentrations were measured in plasma before and after oral glucose tolerance test (OGTT; 60 and 120 minutes) in 22 children with leukemia treated with hematopoietic stem cell transplantation (HSCT) and healthy control subjects (n = 24). The HSCT group was studied twice: before HSCT (22 children) and approximately 6 months after HSCT (12 of 22 children). After fasting, concentrations of glucose, insulin, triglycerides, total cholesterol, high-density lipoprotein, and high-sensitivity C-reactive protein (hsCRP) were determined. Significantly lower (p < 0.05) median values of VF concentrations at all time points in the OGTT were found in pre- HSCT children compared with control subjects. The median VF concentration was significantly higher after HSCT compared with before HSCT. The decrease in VF in leukemic children in complete remission may be caused by myelosuppression and immunosuppression after prolong chemotherapy and is beneficial because of the decrease in its antiapoptotic activity. VF can serve as an additional biochemical marker for remission in patients with leukemia. Normalization of plasma VF concentration after HSCT might be caused by a process of immune reconstitution and prolonged inflammation (e.g., infections, graft-versus-host disease), injury to organs (e.g., lungs, gut, liver), and endocrinology deficiencies. Copyright © 2014 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

A case series of CAEBV of children and young adults treated with reduced-intensity conditioning and allogeneic bone marrow transplantation: a single-center study.

PubMed

Watanabe, Yuko; Sasahara, Yoji; Satoh, Miki; Looi, Chung Yeng; Katayama, Saori; Suzuki, Tasuku; Suzuki, Nobu; Ouchi, Meri; Horino, Satoshi; Moriya, Kunihiko; Nanjyo, Yuka; Onuma, Masaei; Kitazawa, Hiroshi; Irie, Masahiro; Niizuma, Hidetaka; Uchiyama, Toru; Rikiishi, Takeshi; Kumaki, Satoru; Minegishi, Masayoshi; Wada, Taizo; Yachie, Akihiro; Tsuchiya, Shigeru; Kure, Shigeo

2013-09-01

Epstein-Barr virus (EBV)-infected T or NK cells cause chronic active EBV infection (CAEBV). Allogeneic hematopoietic stem cell transplantation (HSCT) is curative treatment for CAEBV patients. However, chemotherapy prior to HSCT and optimal conditioning regimen for allogeneic HSCT are still controversial. We retrospectively analyzed five patients with CAEBV treated with reduced-intensity conditioning (RIC) consisted of fludarabine, cyclophosphamide, and low-dose total-body irradiation followed by allogeneic bone marrow transplantation in a single institute. Only one of five patients received chemotherapy prior to transplantation. We analyzed EBV-infected cells in a patient whose EBV load increased after HSCT by T-cell repertoire assay, separation of T-cell subpopulations, in situ hybridization and microsatellite analysis. All five patients achieved engraftment, complete chimera, and eradication of EBV load. All patients have been alive without any serious regimen-related toxicity for more than 16 months following HSCT. However, one patient transplanted from HLA-matched sibling donor developed clonal proliferation of CD4+ Vβ3+ T cells caused by monoclonal EBV infection on day 99 after transplantation. Further analysis revealed that the CD4+ Vβ3+ T cells selectively harbored EBV genome, and these infected cells were derived from donor T cells. Allogeneic HSCT with RIC is a safe and effective treatment for better overall survival and less regimen-related toxicity in patients with CAEBV. Our first pediatric case reported in the literature suggests that we should consider the possibility of persistent EBV infection in donor T cells as well as the relapse in recipient cells if EBV load increases after allogeneic HSCT. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Impact of human cytomegalovirus infection UL55-nested polymerase chain reaction method in hematopoietic stem cell transplant donors and recipients.

PubMed

Banan, A A; Yaghobi, R; Ramzi, M; Mehrabani, D

2009-09-01

Human cytomegalovirus (HCMV) is one of the most important and critical viral causes of graft rejection among hematopoietic stem cell transplant (HSCT) recipients. Monitoring of this viral infection has a critical role in the management of HSCT clinical complications. In this retrospective cohort, blood (plasma and buffy coat) and urine samples were collected from 110 HSCT patients and 95 donors pretransplantation and weekly for 100 days posttransplantation. An HCMV-optimized UL55-nested polymerase chain reaction (PCR) method was used to detect HCMV infection. Genotyping of the HCMV UL55 gene was performed for all UL55-nested, PCR-positive samples. HSCT donor and recipient laboratory and clinical data were statistically analyzed using SPSS version 15 software. UL55-nested, PCR-positive results were obtained in 3540/4950 (71.5%), 3634/4950 (73.4%), and 3292/4950 (66.5%) of these plasma, buffy coat, and urine samples, respectively. Twenty-five percent of transplant donors were infected with HCMV. An increase in HCMV infection was observed from pre- to post-HSCT conditions. Detection of the gB2 UL55 genotype in most transplant patient samples suggested the need to examine the possible impact of HCMV UL55 genotypes and HCMV infections among stem cell transplant recipients.

Integrated design and manufacturing for the high speed civil transport

NASA Technical Reports Server (NTRS)

Lee, Jae Moon; Gupta, Anurag; Mueller, Craig; Morrisette, Monica; Dec, John; Brewer, Jason; Donofrio, Kevin; Sturisky, Hilton; Smick, Doug; An, Meng Lin

1994-01-01

In June 1992, the School of Aerospace Engineering at Georgia Tech was awarded a three year NASA University Space Research Association (USRA) Advanced Design Program (ADP) grant to address issues associated with the Integrated Design and Manufacturing of High Speed Civil Transport (HSCT) configurations in its graduate Aerospace Systems Design courses. This report provides an overview of the on-going Georgia Tech initiative to address these design/manufacturing issues during the preliminary design phases of an HSCT concept. The new design methodology presented here has been incorporated in the graduate aerospace design curriculum and is based on the concept of Integrated Product and Process Development (IPPD). The selection of the HSCT as a pilot project was motivated by its potential global transportation payoffs; its technological, environmental, and economic challenges; and its impact on U.S. global competitiveness. This pilot project was the focus of each of the five design courses that form the graduate level aerospace systems design curriculum. This year's main objective was the development of a systematic approach to preliminary design and optimization and its implementation to an HSCT wing/propulsion configuration. The new methodology, based on the Taguchi Parameter Design Optimization Method (PDOM), was established and was used to carry out a parametric study where various feasible alternative configurations were evaluated. The comparison criterion selected for this evaluation was the economic impact of this aircraft, measured in terms of average yield per revenue passenger mile ($/RPM).

Successful Treatment of BK Virus Hemorrhagic Cystitis (HC) Post Allogenic Hematopoietic Stem Cell Transplantation with Low Dose Cidofovir.

PubMed

Arora, R; Jasmita; Singh, M; Garg, A; Gupta, M; Gupta, N

2017-05-01

BK virus (BKV) hemorrhagic cystitis (HC) is a serious cause of morbidity and mortality after allogeneic hematopoietic SCT (allo-HSCT) in patients with hematological malignancies. Around half of allogenic HSCT patients present with BKV viruria at some point after HSCT; about 5-40% of these patients subsequently develop active HC. Supportive care including bladder irrigation, blood transfusions and symptomatic pain management remains the mainstay of therapy; the acyclic nucleoside analogue cidofovir is currently the front-line drug for BKV-HC treatment. Here we report the first case of severe hemorrhagic cystitis from India who was successfully treated with low dose cidofovir therapy. © Journal of the Association of Physicians of India 2011.

Solving multi-objective optimization problems in conservation with the reference point method

PubMed Central

Dujardin, Yann; Chadès, Iadine

2018-01-01

Managing the biodiversity extinction crisis requires wise decision-making processes able to account for the limited resources available. In most decision problems in conservation biology, several conflicting objectives have to be taken into account. Most methods used in conservation either provide suboptimal solutions or use strong assumptions about the decision-maker’s preferences. Our paper reviews some of the existing approaches to solve multi-objective decision problems and presents new multi-objective linear programming formulations of two multi-objective optimization problems in conservation, allowing the use of a reference point approach. Reference point approaches solve multi-objective optimization problems by interactively representing the preferences of the decision-maker with a point in the criteria (objectives) space, called the reference point. We modelled and solved the following two problems in conservation: a dynamic multi-species management problem under uncertainty and a spatial allocation resource management problem. Results show that the reference point method outperforms classic methods while illustrating the use of an interactive methodology for solving combinatorial problems with multiple objectives. The method is general and can be adapted to a wide range of ecological combinatorial problems. PMID:29293650

Structural analysis for preliminary design of High Speed Civil Transport (HSCT)

NASA Technical Reports Server (NTRS)

Bhatia, Kumar G.

1992-01-01

In the preliminary design environment, there is a need for quick evaluation of configuration and material concepts. The simplified beam representations used in the subsonic, high aspect ratio wing platform are not applicable for low aspect ratio configurations typical of supersonic transports. There is a requirement to develop methods for efficient generation of structural arrangement and finite element representation to support multidisciplinary analysis and optimization. In addition, empirical data bases required to validate prediction methods need to be improved for high speed civil transport (HSCT) type configurations.

Next-Generation Sequencing-Based Detection of Circulating Tumour DNA After Allogeneic Stem Cell Transplantation for Lymphoma

PubMed Central

Herrera, Alex F.; Kim, Haesook T.; Kong, Katherine A.; Faham, Malek; Sun, Heather; Sohani, Aliyah R.; Alyea, Edwin P.; Carlton, Victoria E.; Chen, Yi-Bin; Cutler, Corey S.; Ho, Vincent T.; Koreth, John; Kotwaliwale, Chitra; Nikiforow, Sarah; Ritz, Jerome; Rodig, Scott J.; Soiffer, Robert J.; Antin, Joseph H.; Armand, Philippe

2016-01-01

Summary Next-generation sequencing (NGS)-based circulating tumour DNA (ctDNA) detection is a promising monitoring tool for lymphoid malignancies. We evaluated whether the presence of ctDNA was associated with outcome after allogeneic haematopoietic stem cell transplantation (HSCT) in lymphoma patients. We studied 88 patients drawn from a phase 3 clinical trial of reduced-intensity conditioning HSCT in lymphoma. Conventional restaging and collection of peripheral blood samples occurred at pre-specified time points before and after HSCT and were assayed for ctDNA by sequencing of the immunoglobulin or T-cell receptor genes. Tumour clonotypes were identified in 87% of patients with adequate tumour samples. Sixteen of 19 (84%) patients with disease progression after HSCT had detectable ctDNA prior to progression at a median of 3.7 months prior to relapse/progression. Patients with detectable ctDNA 3 months after HSCT had inferior progression-free survival (PFS) (2-year PFS 58% versus 84% in ctDNA-negative patients, p=0.033). In multivariate models, detectable ctDNA was associated with increased risk of progression/death (Hazard ratio 3.9, p=0.003) and increased risk of relapse/progression (Hazard ratio 10.8, p=0.0006). Detectable ctDNA is associated with an increased risk of relapse/progression, but further validation studies are necessary to confirm these findings and determine the clinical utility of NGS-based minimal residual disease monitoring in lymphoma patients after HSCT. PMID:27711974

Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial.

PubMed

van Laar, Jacob M; Farge, Dominique; Sont, Jacob K; Naraghi, Kamran; Marjanovic, Zora; Larghero, Jérôme; Schuerwegh, Annemie J; Marijt, Erik W A; Vonk, Madelon C; Schattenberg, Anton V; Matucci-Cerinic, Marco; Voskuyl, Alexandre E; van de Loosdrecht, Arjan A; Daikeler, Thomas; Kötter, Ina; Schmalzing, Marc; Martin, Thierry; Lioure, Bruno; Weiner, Stefan M; Kreuter, Alexander; Deligny, Christophe; Durand, Jean-Marc; Emery, Paul; Machold, Klaus P; Sarrot-Reynauld, Francoise; Warnatz, Klaus; Adoue, Daniel F P; Constans, Joël; Tony, Hans-Peter; Del Papa, Nicoletta; Fassas, Athanasios; Himsel, Andrea; Launay, David; Lo Monaco, Andrea; Philippe, Pierre; Quéré, Isabelle; Rich, Éric; Westhovens, Rene; Griffiths, Bridget; Saccardi, Riccardo; van den Hoogen, Frank H; Fibbe, Willem E; Socié, Gérard; Gratwohl, Alois; Tyndall, Alan

2014-06-25

High-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation (HSCT) have shown efficacy in systemic sclerosis in phase 1 and small phase 2 trials. To compare efficacy and safety of HSCT vs 12 successive monthly intravenous pulses of cyclophosphamide. The Autologous Stem Cell Transplantation International Scleroderma (ASTIS) trial, a phase 3, multicenter, randomized (1:1), open-label, parallel-group, clinical trial conducted in 10 countries at 29 centers with access to a European Group for Blood and Marrow Transplantation-registered transplant facility. From March 2001 to October 2009, 156 patients with early diffuse cutaneous systemic sclerosis were recruited and followed up until October 31, 2013. HSCT vs intravenous pulse cyclophosphamide. The primary end point was event-free survival, defined as time from randomization until the occurrence of death or persistent major organ failure. A total of 156 patients were randomly assigned to receive HSCT (n = 79) or cyclophosphamide (n = 77). During a median follow-up of 5.8 years, 53 events occurred: 22 in the HSCT group (19 deaths and 3 irreversible organ failures) and 31 in the control group (23 deaths and 8 irreversible organ failures). During the first year, there were more events in the HSCT group (13 events [16.5%], including 8 treatment-related deaths) than in the control group (8 events [10.4%], with no treatment-related deaths). At 2 years, 14 events (17.7%) had occurred cumulatively in the HSCT group vs 14 events (18.2%) in the control group; at 4 years, 15 events (19%) had occurred cumulatively in the HSCT group vs 20 events (26%) in the control group. Time-varying hazard ratios (modeled with treatment × time interaction) for event-free survival were 0.35 (95% CI, 0.16-0.74) at 2 years and 0.34 (95% CI, 0.16-0.74) at 4 years. Among patients with early diffuse cutaneous systemic sclerosis, HSCT was associated with increased treatment-related mortality in the first year after treatment. However, HCST conferred a significant long-term event-free survival benefit. isrctn.org Identifier: ISRCTN54371254.

Defibrotide for children and adults with hepatic veno-occlusive disease post hematopoietic cell transplantation.

PubMed

Corbacioglu, Selim; Richardson, Paul G

2017-10-01

Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a complication that is typically associated with conditioning for hematopoietic stem cell transplantation (HSCT). In patients with concomitant multi-organ dysfunction, mortality may be >80%. Recently, the European Society for Blood and Marrow Transplantation established separate criteria for diagnosis and severity of VOD/SOS for adults and children, to better reflect current understanding of the disease. Areas covered: This review provides an overview of post-HSCT hepatic VOD/SOS and defibrotide, including its pharmacological, clinical, and regulatory profile. In children and adults following HSCT, defibrotide is approved for the treatment of hepatic VOD/SOS with concomitant renal or pulmonary dysfunction in the United States and for the treatment of severe hepatic VOD/SOS in the European Union. Day +100 survival rates with defibrotide are superior to those of historical controls receiving best supportive care only, and safety profiles are similar. Expert commentary: Defibrotide appears to act through multiple mechanisms to restore thrombo-fibrinolytic balance and protect endothelial cells, and there are promising data on the use of defibrotide for VOD/SOS prophylaxis in high-risk children undergoing HSCT. An ongoing randomized controlled trial in children and adults will better assess the clinical value of defibrotide as a preventive medication.

Protothecosis in hematopoietic stem cell transplantation: case report and review of previous cases.

PubMed

Macesic, N; Fleming, S; Kidd, S; Madigan, V; Chean, R; Ritchie, D; Slavin, M

2014-06-01

Prototheca species are achlorophyllus algae. Prototheca wickerhamii and Prototheca zopfii cause human disease. In immunocompetent individuals, they cause soft tissue infections and olecranon bursitis, but in transplant recipients, these organisms can cause disseminated disease. We report a fatal case of disseminated P. zopfii infection in an hematopoietic stem cell transplant (HSCT) recipient with bloodstream infection and involvement of multiple soft tissue sites. We review all previous cases of protothecosis in HSCT reported in the literature. Protothecosis is uncommon after HSCT, but has a disseminated presentation that is frequently fatal. It is commonly misidentified as a yeast. Tumor necrosis factor-alpha inhibitors and contamination of central venous catheters may contribute to development of protothecosis. Optimal treatment approaches are yet to be defined. New agents such as miltefosine may be possible future therapies. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Immune Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation

PubMed Central

Ogonek, Justyna; Kralj Juric, Mateja; Ghimire, Sakhila; Varanasi, Pavankumar Reddy; Holler, Ernst; Greinix, Hildegard; Weissinger, Eva

2016-01-01

The timely reconstitution and regain of function of a donor-derived immune system is of utmost importance for the recovery and long-term survival of patients after allogeneic hematopoietic stem cell transplantation (HSCT). Of note, new developments such as umbilical cord blood or haploidentical grafts were associated with prolonged immunodeficiency due to delayed immune reconstitution, raising the need for better understanding and enhancing the process of immune reconstitution and finding strategies to further optimize these transplant procedures. Immune reconstitution post-HSCT occurs in several phases, innate immunity being the first to regain function. The slow T cell reconstitution is regarded as primarily responsible for deleterious infections with latent viruses or fungi, occurrence of graft-versus-host disease, and relapse. Here we aim to summarize the major steps of the adaptive immune reconstitution and will discuss the importance of immune balance in patients after HSCT. PMID:27909435

Optimization of bump and blowing to control the flow through a transonic compressor blade cascade

NASA Astrophysics Data System (ADS)

Mazaheri, K.; Khatibirad, S.

2018-03-01

Shock control bump (SCB) and blowing are two flow control methods, used here to improve the aerodynamic performance of transonic compressors. Both methods are applied to a NASA rotor 67 blade section and are optimized to minimize the total pressure loss. A continuous adjoint algorithm is used for multi-point optimization of a SCB to improve the aerodynamic performance of the rotor blade section, for a range of operational conditions around its design point. A multi-point and two single-point optimizations are performed in the design and off-design conditions. It is shown that the single-point optimized shapes have the best performance for their respective operating conditions, but the multi-point one has an overall better performance over the whole operating range. An analysis is given regarding how similarly both single- and multi-point optimized SCBs change the wave structure between blade sections resulting in a more favorable flow pattern. Interactions of the SCB with the boundary layer and the wave structure, and its effects on the separation regions are also studied. We have also introduced the concept of blowing for control of shock wave and boundary-layer interaction. A geometrical model is introduced, and the geometrical and physical parameters of blowing are optimized at the design point. The performance improvements of blowing are compared with the SCB. The physical interactions of SCB with the boundary layer and the shock wave are analyzed. The effects of SCB on the wave structure in the flow domain outside the boundary-layer region are investigated. It is shown that the effects of the blowing mechanism are very similar to the SCB.

miR-181b Promotes hepatic stellate cells proliferation by targeting p27 and is elevated in the serum of cirrhosis patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Baocan; Li, Wenxi; Guo, Kun

2012-04-27

Highlights: Black-Right-Pointing-Pointer miR-181a and miR-181b, especially, miR-181b could be induced by transforming growth factor-beta 1 (TGF-{beta}1) in hepatic stellate cells. Black-Right-Pointing-Pointer miR-181b could promote HSC-T6 cell proliferation by directly targeting the negative cell regulator-p27 in HSC-T6 cell. Black-Right-Pointing-Pointer miR-181b was identified as potential serum diagnostic marker for liver cirrhosis patients. -- Abstract: MicroRNAs, as a kind of negative gene regulators, were demonstrated to be involved in many types of diseases. In this study, we found that transforming growth factor-beta 1 could induce the expression of miR-181a and miR-181b, and miR-181b increased in the much higher folds than miR-181a. Because ofmore » the important role of transforming growth factor-beta 1 in HSC activation and liver cirrhosis, we investigate the effect of miR-181a and miR-181b on HSC proliferation. The results showed that miR-181b could promote HSC-T6 cell proliferation by regulating cell cycle. Further study showed p27, the cell cycle regulator, was the direct target of miR-181b in HSC-T6 cell. But miR-181a had no effects on HSC-T6 cell proliferation and cell cycle, and did not target p27. Interestingly, miR-181b is elevated significantly in serum of liver cirrhosis cases comparing to that of normal persons, whereas miR-181a expression was in the similar level with that of normal persons. These results suggested that miR-181b could be induced by TGF-{beta}1 and promote the growth of HSCs by directly targeting p27. The elevation of miR-181b in serum suggested that it may be potential diagnostic biomarkers for cirrhosis. As for miR-181a, it may work in TGF-{beta}1 pathway by a currently unknown mechanism.« less

Phase II Study of Allogeneic Transplantation for Older Patients With Acute Myeloid Leukemia in First Complete Remission Using a Reduced-Intensity Conditioning Regimen: Results From Cancer and Leukemia Group B 100103 (Alliance for Clinical Trials in Oncology)/Blood and Marrow Transplant Clinical Trial Network 0502

PubMed Central

Devine, Steven M.; Owzar, Kouros; Blum, William; Mulkey, Flora; Stone, Richard M.; Hsu, Jack W.; Champlin, Richard E.; Chen, Yi-Bin; Vij, Ravi; Slack, James; Soiffer, Robert J.; Larson, Richard A.; Shea, Thomas C.; Hars, Vera; Sibley, Alexander B.; Giralt, Sergio; Carter, Shelly; Horowitz, Mary M.; Linker, Charles; Alyea, Edwin P.

2015-01-01

Purpose Long-term survival rates for older patients with newly diagnosed acute myeloid leukemia (AML) are extremely low. Previous observational studies suggest that allogeneic hematopoietic stem-cell transplantation (HSCT) may improve overall survival (OS) because of lower rates of relapse. We sought to prospectively determine the value of HSCT for older patients with AML in first complete remission. Patients and Methods We conducted a prospective multicenter phase II study to assess the efficacy of reduced-intensity conditioning HSCT for patients between the ages of 60 and 74 years with AML in first complete remission. The primary end point was disease-free survival at 2 years after HSCT. Secondary end points included nonrelapse mortality (NRM), graft-versus-host disease (GVHD), relapse, and OS. Results In all, 114 patients with a median age of 65 years received transplantations. The majority (52%) received transplantations from unrelated donors and were given antithymocyte globulin for GVHD prophylaxis. Disease-free survival and OS at 2 years after transplantation were 42% (95% CI, 33% to 52%) and 48% (95% CI, 39% to 58%), respectively, for the entire group and 40% (95% CI, 29% to 55%) and 50% (95% CI, 38% to 64%) for the unrelated donor group. NRM at 2 years was 15% (95% CI, 8% to 21%). Grade 2 to 4 acute GVHD occurred in 9.6% (95% CI, 4% to 15%) of patients, and chronic GVHD occurred in 28% (95% CI, 19% to 36%) of patients. The cumulative incidence of relapse at 2 years was 44% (95% CI, 35% to 53%). Conclusion Reduced-intensity conditioning HSCT to maintain remission in selected older patients with AML is relatively well tolerated and appears to provide superior outcomes when compared with historical patients treated without HSCT. GVHD and NRM rates were lower than expected. Future transplantation studies in these patients should focus on further reducing the risk of relapse. PMID:26527780

Application of multi response optimization with grey relational analysis and fuzzy logic method

NASA Astrophysics Data System (ADS)

Winarni, Sri; Wahyu Indratno, Sapto

2018-01-01

Multi-response optimization is an optimization process by considering multiple responses simultaneously. The purpose of this research is to get the optimum point on multi-response optimization process using grey relational analysis and fuzzy logic method. The optimum point is determined from the Fuzzy-GRG (Grey Relational Grade) variable which is the conversion of the Signal to Noise Ratio of the responses involved. The case study used in this research are case optimization of electrical process parameters in electrical disharge machining. It was found that the combination of treatments resulting to optimum MRR and SR was a 70 V gap voltage factor, peak current 9 A and duty factor 0.8.

Next-generation sequencing-based detection of circulating tumour DNA After allogeneic stem cell transplantation for lymphoma.

PubMed

Herrera, Alex F; Kim, Haesook T; Kong, Katherine A; Faham, Malek; Sun, Heather; Sohani, Aliyah R; Alyea, Edwin P; Carlton, Victoria E; Chen, Yi-Bin; Cutler, Corey S; Ho, Vincent T; Koreth, John; Kotwaliwale, Chitra; Nikiforow, Sarah; Ritz, Jerome; Rodig, Scott J; Soiffer, Robert J; Antin, Joseph H; Armand, Philippe

2016-12-01

Next-generation sequencing (NGS)-based circulating tumour DNA (ctDNA) detection is a promising monitoring tool for lymphoid malignancies. We evaluated whether the presence of ctDNA was associated with outcome after allogeneic haematopoietic stem cell transplantation (HSCT) in lymphoma patients. We studied 88 patients drawn from a phase 3 clinical trial of reduced-intensity conditioning HSCT in lymphoma. Conventional restaging and collection of peripheral blood samples occurred at pre-specified time points before and after HSCT and were assayed for ctDNA by sequencing of the immunoglobulin or T-cell receptor genes. Tumour clonotypes were identified in 87% of patients with adequate tumour samples. Sixteen of 19 (84%) patients with disease progression after HSCT had detectable ctDNA prior to progression at a median of 3·7 months prior to relapse/progression. Patients with detectable ctDNA 3 months after HSCT had inferior progression-free survival (PFS) (2-year PFS 58% vs. 84% in ctDNA-negative patients, P = 0·033). In multivariate models, detectable ctDNA was associated with increased risk of progression/death (Hazard ratio 3·9, P = 0·003) and increased risk of relapse/progression (Hazard ratio 10·8, P = 0·0006). Detectable ctDNA is associated with an increased risk of relapse/progression, but further validation studies are necessary to confirm these findings and determine the clinical utility of NGS-based minimal residual disease monitoring in lymphoma patients after HSCT. © 2016 John Wiley & Sons Ltd.

Novel immunotherapeutic approaches for the treatment of acute leukemia (myeloid and lymphoblastic)

PubMed Central

Ishii, Kazusa; Barrett, Austin J.

2016-01-01

There have been major advances in our understanding of the multiple interactions between malignant cells and the innate and adaptive immune system. While the attention of immunologists has hitherto focused on solid tumors, the specific immunobiology of acute leukemias is now becoming defined. These discoveries have pointed the way to immune interventions building on the established graft-versus-leukemia (GVL) effect from hematopoietic stem-cell transplant (HSCT) and extending immunotherapy beyond HSCT to individuals with acute leukemia with a diversity of immune manipulations early in the course of the leukemia. At present, clinical results are in their infancy. In the coming years larger studies will better define the place of immunotherapy in the management of acute leukemias and lead to treatment approaches that combine conventional chemotherapy, immunotherapy and HSCT to achieve durable cures. PMID:26834952

Phoenix: Preliminary design of a high speed civil transport

NASA Technical Reports Server (NTRS)

Aguilar, Joseph; Davis, Steven; Jett, Brian; Ringo, Leslie; Stob, John; Wood, Bill

1992-01-01

The goal of the Phoenix Design Project was to develop a second generation high speed civil transport (HSCT) that will meet the needs of the traveler and airline industry beginning in the 21st century. The primary emphasis of the HSCT is to take advantage of the growing needs of the Pacific Basin and the passengers who are involved in that growth. A passenger load of 150 persons, a mission range of 5150 nautical miles, and a cruise speed of Mach 2.5 constitutes the primary design points of this HSCT. The design concept is made possible with the use of a well designed double delta wing and four mixed flow engines. Passenger comfort, compatibility with existing airport infrastructure, and cost competitive with current subsonic aircraft make the Phoenix a viable aircraft for the future.

Long-term outcome of patients with newly diagnosed chronic myeloid leukemia: a randomized comparison of stem cell transplantation with drug treatment.

PubMed

Gratwohl, A; Pfirrmann, M; Zander, A; Kröger, N; Beelen, D; Novotny, J; Nerl, C; Scheid, C; Spiekermann, K; Mayer, J; Sayer, H G; Falge, C; Bunjes, D; Döhner, H; Ganser, A; Schmidt-Wolf, I; Schwerdtfeger, R; Baurmann, H; Kuse, R; Schmitz, N; Wehmeier, A; Fischer, J Th; Ho, A D; Wilhelm, M; Goebeler, M-E; Lindemann, H W; Bormann, M; Hertenstein, B; Schlimok, G; Baerlocher, G M; Aul, C; Pfreundschuh, M; Fabian, M; Staib, P; Edinger, M; Schatz, M; Fauser, A; Arnold, R; Kindler, T; Wulf, G; Rosselet, A; Hellmann, A; Schäfer, E; Prümmer, O; Schenk, M; Hasford, J; Heimpel, H; Hossfeld, D K; Kolb, H-J; Büsche, G; Haferlach, C; Schnittger, S; Müller, M C; Reiter, A; Berger, U; Saußele, S; Hochhaus, A; Hehlmann, R

2016-03-01

Tyrosine kinase inhibitors represent today's treatment of choice in chronic myeloid leukemia (CML). Allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as salvage therapy. This prospective randomized CML-study IIIA recruited 669 patients with newly diagnosed CML between July 1997 and January 2004 from 143 centers. Of these, 427 patients were considered eligible for HSCT and were randomized by availability of a matched family donor between primary HSCT (group A; N=166 patients) and best available drug treatment (group B; N=261). Primary end point was long-term survival. Survival probabilities were not different between groups A and B (10-year survival: 0.76 (95% confidence interval (CI): 0.69-0.82) vs 0.69 (95% CI: 0.61-0.76)), but influenced by disease and transplant risk. Patients with a low transplant risk showed superior survival compared with patients with high- (P<0.001) and non-high-risk disease (P=0.047) in group B; after entering blast crisis, survival was not different with or without HSCT. Significantly more patients in group A were in molecular remission (56% vs 39%; P=0.005) and free of drug treatment (56% vs 6%; P<0.001). Differences in symptoms and Karnofsky score were not significant. In the era of tyrosine kinase inhibitors, HSCT remains a valid option when both disease and transplant risk are considered.

NCI 1st International Workshop on the Biology, Prevention, and Treatment of Relapse After Allogeneic Hematopoietic Stem Cell Transplantation: Summary and Recommendations from the Organizing Committee

PubMed Central

Bishop, Michael R.; Alyea, Edwin P.; Cairo, Mitchell S.; Falkenburg, J.H. Frederik; June, Carl H.; Kröger, Nicolaus; Little, Richard F.; Miller, Jeffrey S.; Pavletic, Steven Z.; Porter, David L.; Riddell, Stanley R.; van Besien, Koen; Wayne, Alan S.; Weisdorf, Daniel J.; Wu, Roy S.; Giralt, Sergio

2011-01-01

The First International Workshop on The Biology, Prevention, and Treatment of Relapse After Allogeneic Hematopoietic Stem Cell Transplantation was organized and convened to identify, prioritize, and coordinate future research activities related to relapse after allogeneic hematopoietic stem cell transplantation (alloHSCT). Each of the Workshop’s six working committees have published individual reports of ongoing basic, translational and clinical research and recommended areas for future research related to the areas of relapse biology, epidemiology, prevention and treatment. This document summarizes each of the committees’ recommendations and suggests three major initiatives for a coordinated research effort to address the problem of relapse after alloHSCT. The first is the need to establish multi-center correlative and clinical trials networks for basic/translational, epidemiological, and clinical research. Second, there is a need for a network of biorepositories for the collection of samples pre- and post-alloHSCT to aid in laboratory and clinical studies. Third, there should be further refinement, implementation, and study of the proposed Workshop disease-specific response and relapse definitions and the recommendations for monitoring of minimal residual disease. These recommendations, in coordination with ongoing research initiatives and transplant organizations, provide a research framework to rapidly and efficiently address the significant problem of relapse following alloHSCT. PMID:21224011

Autologous Hematopoetic Stem Cell Transplantation for Refractory Crohn Disease: A Randomized Clinical Trial.

PubMed

Hawkey, Christopher J; Allez, Matthieu; Clark, Miranda M; Labopin, Myriam; Lindsay, James O; Ricart, Elena; Rogler, Gerhard; Rovira, Montserrat; Satsangi, Jack; Danese, Silvio; Russell, Nigel; Gribben, John; Johnson, Peter; Larghero, Jerome; Thieblemont, Catherine; Ardizzone, Sandro; Dierickx, Daan; Ibatici, Adalberto; Littlewood, Timothy; Onida, Francesco; Schanz, Urs; Vermeire, Severine; Colombel, Jean-Frederic; Jouet, Jean-Paul; Clark, Elizabeth; Saccardi, Riccardo; Tyndall, Alan; Travis, Simon; Farge, Dominique

2015-12-15

Case reports and series suggest hematopoietic stem cell transplantation (HSCT) may benefit some patients with Crohn disease. To evaluate the effect of autologous HSCT on refractory Crohn disease. Parallel-group randomized clinical trial conducted in 11 European transplant units from July 2007 to September 2011, with follow-up through March 2013. Patients were aged 18 to 50 years with impaired quality of life from refractory Crohn disease not amenable to surgery despite treatment with 3 or more immunosuppressive or biologic agents and corticosteroids. All patients underwent stem cell mobilization before 1:1 randomization to immunoablation and HSCT (n = 23) or control treatment (HSCT deferred for 1 year [n = 22]). All were given standard Crohn disease treatment as needed. Sustained disease remission at 1 year, a composite primary end point comprising clinical remission (Crohn Disease Activity Index (CDAI) <150 [range, 0-600]), no use of corticosteroids or immunosuppressive or biologic drugs for at least the last 3 months, and no endoscopic or radiological evidence of active (erosive) disease anywhere in the gastrointestinal (GI) tract. Secondary outcomes were individual components of the primary composite outcome and other measures of disease activity, laboratory results, quality of life and functional status, and GI tract imaging. Twenty-three patients underwent HSCT and 22 received standard Crohn disease treatment (controls). Sustained disease remission was achieved in 2 patients undergoing HSCT (8.7%) vs 1 control patient (4.5%) (absolute difference, 4.2% [95% CI, -14.2% to 22.6%]; P = .60). Fourteen patients undergoing HSCT (61%) vs 5 control patients (23%) had discontinued immunosuppressive or biologic agents or corticosteroids for at least 3 months (difference, 38.1% [95% CI, 9.3% to 59.3%]; P = .01). Ten vs 2 patients had a CDAI less than 150 (remission) at the final evaluation, 8 (34.8%) vs 2 (9.1%) for 3 or more months (difference, 25.7% [95% CI, 1.1% to 47.1%]; P = .052). Eight (34.8%) vs 2 (9.1%) patients were adjudicated free of active disease on endoscopy and radiology at final assessment (difference, 25.7% [95% CI, 1.1% to 47.1%]; P = .054). There were 76 serious adverse events in patients undergoing HSCT vs 38 in controls. One patient undergoing HSCT died. Among adult patients with refractory Crohn disease not amenable to surgery who had impaired quality of life, HSCT, compared with conventional therapy, did not result in a statistically significant improvement in sustained disease remission at 1 year and was associated with significant toxicity. These findings do not support the widespread use of HSCT for patients with refractory Crohn disease. clinicaltrials.gov Identifier: NCT00297193.

Second allograft for hematologic relapse of acute leukemia after first allogeneic stem-cell transplantation from related and unrelated donors: the role of donor change.

PubMed

Christopeit, Maximilian; Kuss, Oliver; Finke, Jürgen; Bacher, Ulrike; Beelen, Dietrich Wilhelm; Bornhäuser, Martin; Schwerdtfeger, Rainer; Bethge, Wolfgang Andreas; Basara, Nadezda; Gramatzki, Martin; Tischer, Johanna; Kolb, Hans-Jochem; Uharek, Lutz; Meyer, Ralf G; Bunjes, Donald; Scheid, Christof; Martin, Hans; Niederwieser, Dietger; Kröger, Nicolaus; Bertz, Hartmut; Schrezenmeier, Hubert; Schmid, Christoph

2013-09-10

To evaluate the role of a second allogeneic hematopoietic stem-cell transplantation (HSCT2) given for relapsed acute leukemia (AL) after related or unrelated first hematopoietic stem-cell transplantation (HSCT1) and to analyze the role of donor change for HSCT2 in both settings. We performed a retrospective registry study on 179 HSCT2s given for relapse after HSCT1 from matched related donors (n = 75) or unrelated donors (n = 104), using identical or alternative donors for HSCT2. Separate analyses were performed according to donor at HSCT1. Independent of donor, 74% of patients achieved complete remission after HSCT2, and half of these patients experienced relapse again. Overall survival (OS) at 2 years was 25% ± 4% (39% ± 7% after related HSCT2; 19% ± 4% after unrelated HSCT2). Long-term survivors were observed even after two unrelated HSCT2s. Multivariate analysis for OS from HSCT2 confirmed established risk factors (remission duration after HSCT1: hazard ratio [HR], 2.37; 95% CI, 1.61 to 3.46; P < .001; stage at HSCT2: HR, 0.53; 95% CI, 0.34 to 0.83; P = .006). Outcome of HSCT2 was better after related HSCT1 than after unrelated HSCT1 (2-year OS: 37% ± 6% v 16% ± 4%, respectively; HR, 0.68; 95% CI, 0.47 to 0.98; P = .042, multivariate Cox regression). After both related and unrelated HSCT1, selecting a new donor for HSCT2 did not result in a relevant improvement in OS compared with HSCT2 from the original donor; however, donor change was not detrimental either. After relapse from allogeneic HSCT1, HSCT2 can induce 2-year OS in approximately 25% of patients. Unrelated HSCT2 is feasible after related and unrelated HSCT1. Donor change for HSCT2 is a valid option. However, a clear advantage in terms of OS could not be demonstrated.

Provisional-Ideal-Point-Based Multi-objective Optimization Method for Drone Delivery Problem

NASA Astrophysics Data System (ADS)

Omagari, Hiroki; Higashino, Shin-Ichiro

2018-04-01

In this paper, we proposed a new evolutionary multi-objective optimization method for solving drone delivery problems (DDP). It can be formulated as a constrained multi-objective optimization problem. In our previous research, we proposed the "aspiration-point-based method" to solve multi-objective optimization problems. However, this method needs to calculate the optimal values of each objective function value in advance. Moreover, it does not consider the constraint conditions except for the objective functions. Therefore, it cannot apply to DDP which has many constraint conditions. To solve these issues, we proposed "provisional-ideal-point-based method." The proposed method defines a "penalty value" to search for feasible solutions. It also defines a new reference solution named "provisional-ideal point" to search for the preferred solution for a decision maker. In this way, we can eliminate the preliminary calculations and its limited application scope. The results of the benchmark test problems show that the proposed method can generate the preferred solution efficiently. The usefulness of the proposed method is also demonstrated by applying it to DDP. As a result, the delivery path when combining one drone and one truck drastically reduces the traveling distance and the delivery time compared with the case of using only one truck.

Health-related quality of life (HRQoL): the impact of medical and demographic variables upon pediatric recipients of hematopoietic stem cell transplantation.

PubMed

Brice, Lisa; Weiss, Rebecca; Wei, Ying; Satwani, Prakash; Bhatia, Monica; George, Diane; Garvin, James; Morris, Erin; Harrison, Lauren; Cairo, Mitchell S; Sands, Stephen A

2011-12-15

The trajectory of Heath-Related Quality of Life (HRQoL) in pediatric recipients who have undergone hematopoietic stem cell transplantation (HSCT), as well as the demographic and medical factors that predict HRQoL, has lagged behind the adult research. A prospective longitudinal study of HRQoL in pediatric HSCT recipients was conducted with 95 patients at the Columbia University Medical Center between 2002 and 2009. Both children and parents completed the PedsQL 4.0 prior to HSCT and at days 100, 180, and 365-post-HSCT. The majority of patients and their parents reported linear improvements in HRQoL in the first year post-transplant; however, a portion of patients were in the at-risk group at each time point. Latent growth modeling was utilized to examine demographic and medical factors that predicted initial HRQoL and its trajectory. Older age at transplant significant predicted lowered HRQoL at baseline for self- and parent-report. Female gender significantly impacted lowered self-reported physical HRQoL over time. Ethnicity was a significant predictor of HRQoL at baseline and over time for self- and parent-report, with African-American children reporting the highest HRQoL; whereas, the worst decline in psychosocial HRQoL was often reported by parents and children of Asian descent. This research identifies the significant impact of ethnicity upon HRQoL following pediatric HSCT. It is likely that an individual's pre-morbid experiences and expectations, particularly with regard to culture, behaviors, and values, influence the parent and child's perceptions and expectations of the HSCT process. Copyright © 2011 Wiley Periodicals, Inc.

Vancomycin-resistant enterococcus infection in the hematopoietic stem cell transplant recipient: an overview of epidemiology, management, and prevention

PubMed Central

Benamu, Esther; Deresinski, Stanley

2018-01-01

Vancomycin-resistant enterococcus (VRE) is now one of the leading causes of nosocomial infections in the United States. Hematopoietic stem cell transplantation (HSCT) recipients are at increased risk of VRE colonization and infection. VRE has emerged as a major cause of bacteremia in this population, raising important clinical questions regarding the role and impact of VRE colonization and infection in HSCT outcomes as well as the optimal means of prevention and treatment. We review here the published literature and scientific advances addressing these thorny issues and provide a rational framework for their approach. PMID:29333263

Second neoplasms in adult patients submitted to haematopoietic stem cell transplantation.

PubMed

Torrent, Anna; Ferrá, Christelle; Morgades, Mireia; Jiménez, María-José; Sancho, Juan-Manuel; Vives, Susana; Batlle, Montserrat; Moreno, Miriam; Xicoy, Blanca; Oriol, Albert; Ibarra, Gladys; Ribera, Josep-Maria

2018-06-08

Patients submitted to haematopoietic stem cell transplantation (HSCT) are at increased risk of late complications, such as second neoplasm (SN). The incidence and risk factors of SN in patients receiving HSCT at a single centre were analysed. The follow-up of adult patients who received a first HSCT (autologous [auto-HSCT] or allogeneic [allo-HSCT]) between January 2000 and December 2015 was reviewed. We collected their demographic characteristics, the primary disease and type of HSCT, and analysed the cumulative incidence of SN and their risk factors. Of 699 transplanted patients (auto-HSCT, n=451; allo-HSCT, n=248), 42 (6%) developed SN (17 haematological and 25 solid), 31 post-auto-HSCT and 11 post-allo-HSCT. Haematologic SN were more frequent after auto-HSCT than after allo-HSCT. The median time between HSCT and SN was 4.09 years [range 0.07-13.15], with no differences between auto-HSCT and allo-HSCT. The cumulative incidence of SN was 5% (95% CI 3-6) at 5 years, 7% (95% CI 5-10) at 10 years and 11% (95% CI 8-15) at 15 years, without differences according to the type of HSCT. Only the age over 40 years correlated with an increased risk of SN. In this series, the incidence of post-HSCT SN was similar to that previously described. Patients submitted to an auto-HSCT showed a higher frequency of haematologic SN. A higher incidence of SN was detected in patients older than 40 at the time of HSCT. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

A single exercise bout enhances the manufacture of viral-specific T-cells from healthy donors: implications for allogeneic adoptive transfer immunotherapy

PubMed Central

Spielmann, Guillaume; Bollard, Catherine M.; Kunz, Hawley; Hanley, Patrick J.; Simpson, Richard J.

2016-01-01

Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections remain a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The adoptive transfer of donor-derived viral-specific cytotoxic T-cells (VSTs) is an effective treatment for controlling CMV and EBV infections after HSCT; however, new practical methods are required to augment the ex vivo manufacture of multi-VSTs from healthy donors. This study investigated the effects of a single exercise bout on the ex vivo manufacture of multi-VSTs. PBMCs isolated from healthy CMV/EBV seropositive participants before (PRE) and immediately after (POST) 30-minutes of cycling exercise were stimulated with CMV (pp65 and IE1) and EBV (LMP2A and BMLF1) peptides and expanded over 8 days. The number (fold difference from PRE) of T-cells specific for CMV pp65 (2.6), EBV LMP2A (2.5), and EBV BMLF1 (4.4) was greater among the VSTs expanded POST. VSTs expanded PRE and POST had similar phenotype characteristics and were equally capable of MHC-restricted killing of autologous target cells. We conclude that a single exercise bout enhances the manufacture of multi-VSTs from healthy donors without altering their phenotype or function and may serve as a simple and economical adjuvant to boost the production of multi-VSTs for allogeneic adoptive transfer immunotherapy. PMID:27181409

A single exercise bout enhances the manufacture of viral-specific T-cells from healthy donors: implications for allogeneic adoptive transfer immunotherapy.

PubMed

Spielmann, Guillaume; Bollard, Catherine M; Kunz, Hawley; Hanley, Patrick J; Simpson, Richard J

2016-05-16

Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections remain a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The adoptive transfer of donor-derived viral-specific cytotoxic T-cells (VSTs) is an effective treatment for controlling CMV and EBV infections after HSCT; however, new practical methods are required to augment the ex vivo manufacture of multi-VSTs from healthy donors. This study investigated the effects of a single exercise bout on the ex vivo manufacture of multi-VSTs. PBMCs isolated from healthy CMV/EBV seropositive participants before (PRE) and immediately after (POST) 30-minutes of cycling exercise were stimulated with CMV (pp65 and IE1) and EBV (LMP2A and BMLF1) peptides and expanded over 8 days. The number (fold difference from PRE) of T-cells specific for CMV pp65 (2.6), EBV LMP2A (2.5), and EBV BMLF1 (4.4) was greater among the VSTs expanded POST. VSTs expanded PRE and POST had similar phenotype characteristics and were equally capable of MHC-restricted killing of autologous target cells. We conclude that a single exercise bout enhances the manufacture of multi-VSTs from healthy donors without altering their phenotype or function and may serve as a simple and economical adjuvant to boost the production of multi-VSTs for allogeneic adoptive transfer immunotherapy.

Long-term outcome of patients with newly diagnosed chronic myeloid leukemia: a randomized comparison of stem cell transplantation with drug treatment

PubMed Central

Gratwohl, A; Pfirrmann, M; Zander, A; Kröger, N; Beelen, D; Novotny, J; Nerl, C; Scheid, C; Spiekermann, K; Mayer, J; Sayer, H G; Falge, C; Bunjes, D; Döhner, H; Ganser, A; Schmidt-Wolf, I; Schwerdtfeger, R; Baurmann, H; Kuse, R; Schmitz, N; Wehmeier, A; Th Fischer, J; Ho, A D; Wilhelm, M; Goebeler, M-E; Lindemann, H W; Bormann, M; Hertenstein, B; Schlimok, G; Baerlocher, G M; Aul, C; Pfreundschuh, M; Fabian, M; Staib, P; Edinger, M; Schatz, M; Fauser, A; Arnold, R; Kindler, T; Wulf, G; Rosselet, A; Hellmann, A; Schäfer, E; Prümmer, O; Schenk, M; Hasford, J; Heimpel, H; Hossfeld, D K; Kolb, H-J; Büsche, G; Haferlach, C; Schnittger, S; Müller, M C; Reiter, A; Berger, U; Saußele, S; Hochhaus, A; Hehlmann, R

2016-01-01

Tyrosine kinase inhibitors represent today's treatment of choice in chronic myeloid leukemia (CML). Allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as salvage therapy. This prospective randomized CML-study IIIA recruited 669 patients with newly diagnosed CML between July 1997 and January 2004 from 143 centers. Of these, 427 patients were considered eligible for HSCT and were randomized by availability of a matched family donor between primary HSCT (group A; N=166 patients) and best available drug treatment (group B; N=261). Primary end point was long-term survival. Survival probabilities were not different between groups A and B (10-year survival: 0.76 (95% confidence interval (CI): 0.69–0.82) vs 0.69 (95% CI: 0.61–0.76)), but influenced by disease and transplant risk. Patients with a low transplant risk showed superior survival compared with patients with high- (P<0.001) and non-high-risk disease (P=0.047) in group B; after entering blast crisis, survival was not different with or without HSCT. Significantly more patients in group A were in molecular remission (56% vs 39% P=0.005) and free of drug treatment (56% vs 6% P<0.001). Differences in symptoms and Karnofsky score were not significant. In the era of tyrosine kinase inhibitors, HSCT remains a valid option when both disease and transplant risk are considered. PMID:26464170

Douglas Aircraft HSCT status and future research needs

NASA Technical Reports Server (NTRS)

Welge, H. Robert

1992-01-01

Current activities on the High Speed Civil Transport (HSCT) at Douglas are focussed on baseline vehicle development at Mach 1.6 and 2.4. Parallel design activities incorporating the latest technologies in structures/materials, propulsion/noise, and aerodynamics are also being conducted and incorporated into the baseline to establish performance, economic viability, and environmental compliance. Studies are also being conducted to establish the feasibility of incorporating laminar flow control and minimized sonic boom concepts into the baseline. A decision point on these last two technologies is targeted prior to the start of the NASA HSR Phase 2 Program in 1993.

Evaluation of thromboelastometry parameters as predictive markers for sinusoidal obstruction syndrome in patients undergoing allogeneic stem cell transplantation for acute leukaemia

PubMed Central

Rupa-Matysek, Joanna; Gil, Lidia; Wojtasińska, Ewelina; Kanduła, Zuzanna; Nowicki, Adam; Matuszak, Magdalena; Komarnicki, Mieczysław

2017-01-01

Hepatic sinusoidal obstruction syndrome (previously named veno-occlusive disease, SOS/VOD) is a serious complication of allogeneic stem cell transplantation (HSCT). Early identification of patients at risk of SOS/VOD may possibly improve the outcome and reduce mortality. Rotation thromboelastometry (ROTEM) is global assay allowing for the precise assessment of both bleeding and thrombotic conditions, however, its usefulness in patients undergoing HSCT for acute leukaemia has not been studied. We evaluated the thromboelastometry parameters in patients undergoing allogeneic HSCT for acute leukaemia to identify candidate biomarkers of SOS/VOD occurrence. ROTEM assays (INTEM, EXTEM, FIBTEM, APTEM) were performed on day -10, on the day of stem cell infusion (day 0) and on days +12 and +28 post-HSCT. The diagnosis of SOS/VOD was based on the Baltimore criteria. Seven patients (26%) developed SOS/VOD. On day +12, the patients with SOS/VOD had statistically significant longer INTEM-CT (clotting time, 199 ± 33.41vs166 ± 23.65s, p = 0.0033), EXTEM-CT (69.5 ± 6.39vs.52 ± 3.42s, p = 0.0139) and FIBTEM-CT (69.5 ± 22.75vs. 50.8 ± 14.31s, p = 0.0124) compared to SOS/VOD (-). ROC curve on day +12 indicated a cut-off value of 179s in INTEM-CT (AUC = 0.91), 69s in EXTEM-CT (AUC = 0.90) and 102s in FIBTEM-CT (AUC = 0.82) for the prediction of SOS/VOD. This is the first study evaluating the usefulness of ROTEM assays in the early detection of haemostasis abnormalities predictive of SOS/VOD development in patients undergoing HSCT for acute leukemia. Patients with SOS/VOD had a significant delay in the initiation of thrombin formation in the analysed ROTEM assays. The utility of ROTEM assays in the optimal management of patients undergoing HSCT should be clarified in further prospective studies. PMID:28938703

Bacterial infections in pediatric hematopoietic stem cell transplantation recipients: incidence, epidemiology, and spectrum of pathogens: report of the Polish Pediatric Group for Hematopoietic Stem Cell Transplantation.

PubMed

Zając-Spychała, O; Wachowiak, J; Pieczonka, A; Siewiera, K; Frączkiewicz, J; Kałwak, K; Gorczyńska, E; Chybicka, A; Czyżewski, K; Jachna-Sawicka, K; Wysocki, M; Klepacka, J; Goździk, J; Zaucha-Prażmo, A; Kowalczyk, J R; Styczyński, J

2016-10-01

Infectious complications are a significant cause of hematopoietic stem cell transplantation (HSCT) failure, especially allogeneic HSCT (allo-HSCT) because of delayed immune reconstitution and graft-versus-host disease (GVHD) occurrence. Identifying the factors responsible for bacterial infections (BI) in patients undergoing HSCT will provide much more effective empirical antimicrobial treatment in this group of patients. The aim of this study was to evaluate the epidemiology and profile of BI in patients after HSCT in 5 centers of the Polish Pediatric Group for Hematopoietic Stem Cell Transplantation in 2012-2013. In 308 HSCT recipients, we retrospectively analyzed 273 episodes of BI in 113 (36.7%) children aged 0.02-22 years (median age: 7 years), 92 after allo-HSCT and 22 after autologous HSCT (auto-HSCT). We assessed incidence of BI in different HSCT types by calculating the Index of Bacterial Infection (IBI) as a ratio of patients with at least 1 BI to all patients who underwent this type of HSCT in the analyzed period. We assessed the profile of BI with particular emphasis on multidrug-resistant organisms, and impact of underlying disease and of graft-versus-host disease on BI episodes. In the studied group, 273 episodes of BI were diagnosed, including 237 episodes after allo-HSCT and 36 after auto-HSCT. Among allo-HSCT recipients diagnosed with at least 1 BI, the IBI was 0.4 (matched sibling donor-HSCT 0.3; matched donor-HSCT 0.4; mismatched unrelated donor [MMUD]-HSCT 0.8; P = 0.027) and after auto-HSCT 0.3 per 1 transplanted patient. In patient after allo-HSCT because of myelo- or lymphoproliferative diseases and bone marrow failures, the major cause of infections was Enterobacteriaceae, while gram-positive bacteria predominated in the group with primary immunodeficiencies. In all patients after auto-HSCT, the dominant pathogen of BI were Enterobacteriaceae (P = 0.011). Time from each type of HSCT to infection caused by different pathogens did not differ significantly. The risk of BI does not depend on the underlying disease, but only on HSCT donor type and is the highest after MMUD-HSCT procedure. The profile of BI depends on the underlying disease and HSCT donor type, but does not depend on the occurrence of acute GVHD. Gram-negative bacteria predominated in patients with myelo- and lymphoproliferative diseases, while in patients with primary immunodeficiencies gram-positive strains were predominant. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Earlier defibrotide initiation post-diagnosis of veno-occlusive disease/sinusoidal obstruction syndrome improves Day +100 survival following haematopoietic stem cell transplantation.

PubMed

Richardson, Paul G; Smith, Angela R; Triplett, Brandon M; Kernan, Nancy A; Grupp, Stephan A; Antin, Joseph H; Lehmann, Leslie; Miloslavsky, Maja; Hume, Robin; Hannah, Alison L; Nejadnik, Bijan; Soiffer, Robert J

2017-07-01

Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a progressive, potentially fatal complication of conditioning for haematopoietic stem cell transplant (HSCT). The VOD/SOS pathophysiological cascade involves endothelial-cell activation and damage, and a prothrombotic-hypofibrinolytic state. Severe VOD/SOS (typically characterized by multi-organ dysfunction) may be associated with >80% mortality. Defibrotide is approved for treating severe hepatic VOD/SOS post-HSCT in the European Union, and for hepatic VOD/SOS with renal or pulmonary dysfunction post-HSCT in the United States. Previously, defibrotide (25 mg/kg/day in 4 divided doses for a recommended ≥21 days) was available through an expanded-access treatment protocol for patients with VOD/SOS. Data from this study were examined post-hoc to determine if the timing of defibrotide initiation post-VOD/SOS diagnosis affected Day +100 survival post-HSCT. Among 573 patients, defibrotide was started on the day of VOD/SOS diagnosis in approximately 30%, and within 7 days in >90%. The relationship between Day +100 survival and treatment initiation before/after specific days post-diagnosis showed superior survival when treatment was initiated closer to VOD/SOS diagnosis with a statistically significant trend over time for better outcomes with earlier treatment initiation (P < 0·001). These results suggest that initiation of defibrotide should not be delayed after diagnosis of VOD/SOS. © 2017 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

Free-form Airfoil Shape Optimization Under Uncertainty Using Maximum Expected Value and Second-order Second-moment Strategies

NASA Technical Reports Server (NTRS)

Huyse, Luc; Bushnell, Dennis M. (Technical Monitor)

2001-01-01

Free-form shape optimization of airfoils poses unexpected difficulties. Practical experience has indicated that a deterministic optimization for discrete operating conditions can result in dramatically inferior performance when the actual operating conditions are different from the - somewhat arbitrary - design values used for the optimization. Extensions to multi-point optimization have proven unable to adequately remedy this problem of "localized optimization" near the sampled operating conditions. This paper presents an intrinsically statistical approach and demonstrates how the shortcomings of multi-point optimization with respect to "localized optimization" can be overcome. The practical examples also reveal how the relative likelihood of each of the operating conditions is automatically taken into consideration during the optimization process. This is a key advantage over the use of multipoint methods.

Sensitivity of Lumped Constraints Using the Adjoint Method

NASA Technical Reports Server (NTRS)

Akgun, Mehmet A.; Haftka, Raphael T.; Wu, K. Chauncey; Walsh, Joanne L.

1999-01-01

Adjoint sensitivity calculation of stress, buckling and displacement constraints may be much less expensive than direct sensitivity calculation when the number of load cases is large. Adjoint stress and displacement sensitivities are available in the literature. Expressions for local buckling sensitivity of isotropic plate elements are derived in this study. Computational efficiency of the adjoint method is sensitive to the number of constraints and, therefore, the method benefits from constraint lumping. A continuum version of the Kreisselmeier-Steinhauser (KS) function is chosen to lump constraints. The adjoint and direct methods are compared for three examples: a truss structure, a simple HSCT wing model, and a large HSCT model. These sensitivity derivatives are then used in optimization.

Application of Multi-Objective Human Learning Optimization Method to Solve AC/DC Multi-Objective Optimal Power Flow Problem

NASA Astrophysics Data System (ADS)

Cao, Jia; Yan, Zheng; He, Guangyu

2016-06-01

This paper introduces an efficient algorithm, multi-objective human learning optimization method (MOHLO), to solve AC/DC multi-objective optimal power flow problem (MOPF). Firstly, the model of AC/DC MOPF including wind farms is constructed, where includes three objective functions, operating cost, power loss, and pollutant emission. Combining the non-dominated sorting technique and the crowding distance index, the MOHLO method can be derived, which involves individual learning operator, social learning operator, random exploration learning operator and adaptive strategies. Both the proposed MOHLO method and non-dominated sorting genetic algorithm II (NSGAII) are tested on an improved IEEE 30-bus AC/DC hybrid system. Simulation results show that MOHLO method has excellent search efficiency and the powerful ability of searching optimal. Above all, MOHLO method can obtain more complete pareto front than that by NSGAII method. However, how to choose the optimal solution from pareto front depends mainly on the decision makers who stand from the economic point of view or from the energy saving and emission reduction point of view.

Session on High Speed Civil Transport Design Capability Using MDO and High Performance Computing

NASA Technical Reports Server (NTRS)

Rehder, Joe

2000-01-01

Since the inception of CAS in 1992, NASA Langley has been conducting research into applying multidisciplinary optimization (MDO) and high performance computing toward reducing aircraft design cycle time. The focus of this research has been the development of a series of computational frameworks and associated applications that increased in capability, complexity, and performance over time. The culmination of this effort is an automated high-fidelity analysis capability for a high speed civil transport (HSCT) vehicle installed on a network of heterogeneous computers with a computational framework built using Common Object Request Broker Architecture (CORBA) and Java. The main focus of the research in the early years was the development of the Framework for Interdisciplinary Design Optimization (FIDO) and associated HSCT applications. While the FIDO effort was eventually halted, work continued on HSCT applications of ever increasing complexity. The current application, HSCT4.0, employs high fidelity CFD and FEM analysis codes. For each analysis cycle, the vehicle geometry and computational grids are updated using new values for design variables. Processes for aeroelastic trim, loads convergence, displacement transfer, stress and buckling, and performance have been developed. In all, a total of 70 processes are integrated in the analysis framework. Many of the key processes include automatic differentiation capabilities to provide sensitivity information that can be used in optimization. A software engineering process was developed to manage this large project. Defining the interactions among 70 processes turned out to be an enormous, but essential, task. A formal requirements document was prepared that defined data flow among processes and subprocesses. A design document was then developed that translated the requirements into actual software design. A validation program was defined and implemented to ensure that codes integrated into the framework produced the same results as their standalone counterparts. Finally, a Commercial Off the Shelf (COTS) configuration management system was used to organize the software development. A computational environment, CJOPT, based on the Common Object Request Broker Architecture, CORBA, and the Java programming language has been developed as a framework for multidisciplinary analysis and Optimization. The environment exploits the parallelisms inherent in the application and distributes the constituent disciplines on machines best suited to their needs. In CJOpt, a discipline code is "wrapped" as an object. An interface to the object identifies the functionality (services) provided by the discipline, defined in Interface Definition Language (IDL) and implemented using Java. The results of using the HSCT4.0 capability are described. A summary of lessons learned is also presented. The use of some of the processes, codes, and techniques by industry are highlighted. The application of the methodology developed in this research to other aircraft are described. Finally, we show how the experience gained is being applied to entirely new vehicles, such as the Reusable Space Transportation System. Additional information is contained in the original.

Multi-objective optimization of a continuous bio-dissimilation process of glycerol to 1, 3-propanediol.

PubMed

Xu, Gongxian; Liu, Ying; Gao, Qunwang

2016-02-10

This paper deals with multi-objective optimization of continuous bio-dissimilation process of glycerol to 1, 3-propanediol. In order to maximize the production rate of 1, 3-propanediol, maximize the conversion rate of glycerol to 1, 3-propanediol, maximize the conversion rate of glycerol, and minimize the concentration of by-product ethanol, we first propose six new multi-objective optimization models that can simultaneously optimize any two of the four objectives above. Then these multi-objective optimization problems are solved by using the weighted-sum and normal-boundary intersection methods respectively. Both the Pareto filter algorithm and removal criteria are used to remove those non-Pareto optimal points obtained by the normal-boundary intersection method. The results show that the normal-boundary intersection method can successfully obtain the approximate Pareto optimal sets of all the proposed multi-objective optimization problems, while the weighted-sum approach cannot achieve the overall Pareto optimal solutions of some multi-objective problems. Copyright © 2015 Elsevier B.V. All rights reserved.

Large Engine Technology Program. Task 22: Variable Geometry Concepts for Rich-Quench-Lean Combustors

NASA Technical Reports Server (NTRS)

Tacina, Robert R. (Technical Monitor); Cohen, J. M.; Padget, F. C.; Kwoka, D.; Wang, Q.; Lohmann, R. P.

2005-01-01

The objective of the task reported herein was to define, evaluate, and optimize variable geometry concepts suitable for use with a Rich-Quench-Lean (RQL) combustor. The specific intent was to identify approaches that would satisfy High Speed Civil Transport (HSCT) cycle operational requirements with regard to fuel-air ratio turndown capability, ignition, and stability margin without compromising the stringent emissions, performance, and reliability goals that this combustor would have to achieve. Four potential configurations were identified and three of these were refined and tested in a high-pressure modular RQL combustor rig. The tools used in the evolution of these concepts included models built with rapid fabrication techniques that were tested for airflow characteristics to confirm sizing and airflow management capability, spray patternation, and atomization characterization tests of these models and studies that were supported by Computational Fluid Dynamics analyses. Combustion tests were performed with each of the concepts at supersonic cruise conditions and at other critical conditions in the flight envelope, including the transition points of the variable geometry system, to identify performance, emissions, and operability impacts. Based upon the cold flow characterization, emissions results, acoustic behavior observed during the tests and consideration of mechanical, reliability, and implementation issues, the tri-swirler configuration was selected as the best variable geometry concept for incorporation in the RQL combustor evolution efforts for the HSCT.

Evaluation of Frameworks for HSCT Design Optimization

NASA Technical Reports Server (NTRS)

Krishnan, Ramki

1998-01-01

This report is an evaluation of engineering frameworks that could be used to augment, supplement, or replace the existing FIDO 3.5 (Framework for Interdisciplinary Design and Optimization Version 3.5) framework. The report begins with the motivation for this effort, followed by a description of an "ideal" multidisciplinary design and optimization (MDO) framework. The discussion then turns to how each candidate framework stacks up against this ideal. This report ends with recommendations as to the "best" frameworks that should be down-selected for detailed review.

New Approaches to HSCT Multidisciplinary Design and Optimization

NASA Technical Reports Server (NTRS)

Schrage, Daniel P.; Craig, James I.; Fulton, Robert E.; Mistree, Farrokh

1999-01-01

New approaches to MDO have been developed and demonstrated during this project on a particularly challenging aeronautics problem- HSCT Aeroelastic Wing Design. To tackle this problem required the integration of resources and collaboration from three Georgia Tech laboratories: ASDL, SDL, and PPRL, along with close coordination and participation from industry. Its success can also be contributed to the close interaction and involvement of fellows from the NASA Multidisciplinary Analysis and Optimization (MAO) program, which was going on in parallel, and provided additional resources to work the very complex, multidisciplinary problem, along with the methods being developed. The development of the Integrated Design Engineering Simulator (IDES) and its initial demonstration is a necessary first step in transitioning the methods and tools developed to larger industrial sized problems of interest. It also provides a framework for the implementation and demonstration of the methodology. Attachment: Appendix A - List of publications. Appendix B - Year 1 report. Appendix C - Year 2 report. Appendix D - Year 3 report. Appendix E - accompanying CDROM.

Self-Regulatory Fatigue, Quality of Life, Health Behaviors, and Coping in Patients with Hematologic Malignancies

PubMed Central

Ehlers, Shawna L.; Patten, Christi A.; Gastineau, Dennis A.

2015-01-01

Background Self-regulatory fatigue may play an important role in a complex medical illness. Purpose Examine associations between self-regulatory fatigue, quality of life, and health behaviors in patients pre- (N=213) and 1-year post-hematopoietic stem cell transplantation (HSCT; N=140). Associations between self-regulatory fatigue and coping strategies pre-HSCT were also examined. Method Pre- and 1-year post-HSCT data collection. Hierarchical linear regression modeling. Results Higher self-regulatory fatigue pre-HSCT associated with lower overall, physical, social, emotional, and functional quality of life pre- (p’s<.001) and 1-year post-HSCT (p’s<.01); lower physical activity pre-HSCT (p<.02) and post-HSCT (p<.03) and less healthy nutritional intake post-HSCT (p<.01); changes (i.e., decrease) in quality of life and healthy nutrition over the follow-up year; and use of avoidance coping strategies pre-HSCT (p’s<.001). Conclusion This is the first study to show self-regulatory fatigue pre-HSCT relating to decreased quality of life and health behaviors, and predicting changes in these variables 1-year post-HSCT. PMID:24802991

Subsequent vitiligo after hematopoietic stem cell transplantation: A nationwide population-based cohort study from Korea.

PubMed

Bae, Jung Min; Choi, Kwang Hyun; Jung, Han Mi; Kim, Sook Young; Kim, Miri; Kim, Gyung Moon; Yu, Dong Soo; Lee, Young Bok

2017-03-01

Subsequent vitiligo after hematopoietic stem cell transplantation (HSCT) has been described sporadically in case series. To investigate the incidence and risk factors of subsequent vitiligo after HSCT. A nationwide, population-based cohort study was performed using the Korean National Health Insurance Claims Database from 2009 to 2013. All HSCT recipients who had undergone HSCT between 2010 and 2011 and not treatment for vitiligo in 2009 (to exclude preexisting active vitiligo) were included in the HSCT recipient group, and an age- and sex-matched control group without HSCT was also established. A total of 2747 HSCT recipients and 8241 controls were enrolled. Newly acquired vitiligo occurred in 1.06% of HSCT recipients between 2010 and 2013, and there was a significant increase (OR 3.130, 95% CI 1.859-5.271) in cases of vitiligo in HSCT recipients compared with controls (0.34%). Allogeneic HSCT (OR 5.593, 95% CI 1.628-19.213) and bone marrow-sourced stem cells (as compared with peripheral blood-sourced stem cells; OR 2.492, 95% CI 1.114-5.576) were independently associated with the development of vitiligo after HSCT. Medical record review was not available. Vitiligo developed at a significantly increased rate after HSCT compared with controls. Allogeneic HSCT and bone marrow-sourced stem cells were independent risk factors. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Allogeneic T Cells That Express an Anti-CD19 Chimeric Antigen Receptor Induce Remissions of B-Cell Malignancies That Progress After Allogeneic Hematopoietic Stem-Cell Transplantation Without Causing Graft-Versus-Host Disease.

PubMed

Brudno, Jennifer N; Somerville, Robert P T; Shi, Victoria; Rose, Jeremy J; Halverson, David C; Fowler, Daniel H; Gea-Banacloche, Juan C; Pavletic, Steven Z; Hickstein, Dennis D; Lu, Tangying L; Feldman, Steven A; Iwamoto, Alexander T; Kurlander, Roger; Maric, Irina; Goy, Andre; Hansen, Brenna G; Wilder, Jennifer S; Blacklock-Schuver, Bazetta; Hakim, Frances T; Rosenberg, Steven A; Gress, Ronald E; Kochenderfer, James N

2016-04-01

Progressive malignancy is the leading cause of death after allogeneic hematopoietic stem-cell transplantation (alloHSCT). After alloHSCT, B-cell malignancies often are treated with unmanipulated donor lymphocyte infusions (DLIs) from the transplant donor. DLIs frequently are not effective at eradicating malignancy and often cause graft-versus-host disease, a potentially lethal immune response against normal recipient tissues. We conducted a clinical trial of allogeneic T cells genetically engineered to express a chimeric antigen receptor (CAR) targeting the B-cell antigen CD19. Patients with B-cell malignancies that had progressed after alloHSCT received a single infusion of CAR T cells. No chemotherapy or other therapies were administered. The T cells were obtained from each recipient's alloHSCT donor. Eight of 20 treated patients obtained remission, which included six complete remissions (CRs) and two partial remissions. The response rate was highest for acute lymphoblastic leukemia, with four of five patients obtaining minimal residual disease-negative CR. Responses also occurred in chronic lymphocytic leukemia and lymphoma. The longest ongoing CR was more than 30 months in a patient with chronic lymphocytic leukemia. New-onset acute graft-versus-host disease after CAR T-cell infusion developed in none of the patients. Toxicities included fever, tachycardia, and hypotension. Peak blood CAR T-cell levels were higher in patients who obtained remissions than in those who did not. Programmed cell death protein-1 expression was significantly elevated on CAR T cells after infusion. Presence of blood B cells before CAR T-cell infusion was associated with higher postinfusion CAR T-cell levels. Allogeneic anti-CD19 CAR T cells can effectively treat B-cell malignancies that progress after alloHSCT. The findings point toward a future when antigen-specific T-cell therapies will play a central role in alloHSCT. © 2016 by American Society of Clinical Oncology.

High Speed Research (HSR) Multi-Year Summary Report for Calendar Years 1995-1999

NASA Technical Reports Server (NTRS)

Baker, Myles; Boyd, William

1999-01-01

The Aeroelasticity Task is intended to provide demonstrated technology readiness to predict and improve flutter characteristics of an HSCT configuration. This requires aerodynamic codes that are applicable to the wide range of flight regimes in which the HSCT will operate, and are suitable to provide the higher fidelity required for evaluation of aeroservoelastic coupling effects. Prediction of these characteristics will result in reduced airplane weight and risk associated with a highly flexible, low-aspect ratio supersonic airplane with narrow fuselage, relatively thin wings, and heavy engines. This Task is subdivided into three subtasks. The first subtask includes the design, fabrication, and testing of wind-tunnel models suitable to provide an experimental database relevant to HSCT configurations. The second subtask includes validation of candidate unsteady aerodynamic codes, applicable in the Mach and frequency ranges of interest for the HSCT, through analysis test correlation with the test data. The third subtask includes efforts to develop and enhance these codes for application to HSCT configurations. The wind tunnel models designed and constructed during this program furnished data which were useful for the analysis test correlation work but there were shortcomings. There was initial uncertainty in the proper tunnel configuration for testing, there was a need for higher quality measured model geometry, and there was a need for better measured model displacements in the test data. One of the models exhibited changes in its dynamic characteristics during testing. Model design efforts were hampered by a need for more and earlier analysis support and better knowledge of material properties. Success of the analysis test correlation work was somewhat muted by the uncertainties in the wind tunnel model data. The planned extent of the test data was not achieved, partly due to the delays in the model design and fabrication which could not be extended due to termination of the HSR program.

A variable-gain output feedback control design approach

NASA Technical Reports Server (NTRS)

Haylo, Nesim

1989-01-01

A multi-model design technique to find a variable-gain control law defined over the whole operating range is proposed. The design is formulated as an optimal control problem which minimizes a cost function weighing the performance at many operating points. The solution is obtained by embedding into the Multi-Configuration Control (MCC) problem, a multi-model robust control design technique. In contrast to conventional gain scheduling which uses a curve fit of single model designs, the optimal variable-gain control law stabilizes the plant at every operating point included in the design. An iterative algorithm to compute the optimal control gains is presented. The methodology has been successfully applied to reconfigurable aircraft flight control and to nonlinear flight control systems.

Structural damage detection-oriented multi-type sensor placement with multi-objective optimization

NASA Astrophysics Data System (ADS)

Lin, Jian-Fu; Xu, You-Lin; Law, Siu-Seong

2018-05-01

A structural damage detection-oriented multi-type sensor placement method with multi-objective optimization is developed in this study. The multi-type response covariance sensitivity-based damage detection method is first introduced. Two objective functions for optimal sensor placement are then introduced in terms of the response covariance sensitivity and the response independence. The multi-objective optimization problem is formed by using the two objective functions, and the non-dominated sorting genetic algorithm (NSGA)-II is adopted to find the solution for the optimal multi-type sensor placement to achieve the best structural damage detection. The proposed method is finally applied to a nine-bay three-dimensional frame structure. Numerical results show that the optimal multi-type sensor placement determined by the proposed method can avoid redundant sensors and provide satisfactory results for structural damage detection. The restriction on the number of each type of sensors in the optimization can reduce the searching space in the optimization to make the proposed method more effective. Moreover, how to select a most optimal sensor placement from the Pareto solutions via the utility function and the knee point method is demonstrated in the case study.

Multi-rendezvous low-thrust trajectory optimization using costate transforming and homotopic approach

NASA Astrophysics Data System (ADS)

Chen, Shiyu; Li, Haiyang; Baoyin, Hexi

2018-06-01

This paper investigates a method for optimizing multi-rendezvous low-thrust trajectories using indirect methods. An efficient technique, labeled costate transforming, is proposed to optimize multiple trajectory legs simultaneously rather than optimizing each trajectory leg individually. Complex inner-point constraints and a large number of free variables are one main challenge in optimizing multi-leg transfers via shooting algorithms. Such a difficulty is reduced by first optimizing each trajectory leg individually. The results may be, next, utilized as an initial guess in the simultaneous optimization of multiple trajectory legs. In this paper, the limitations of similar techniques in previous research is surpassed and a homotopic approach is employed to improve the convergence efficiency of the shooting process in multi-rendezvous low-thrust trajectory optimization. Numerical examples demonstrate that newly introduced techniques are valid and efficient.

Final results from a defibrotide treatment-IND study for patients with hepatic veno-occlusive disease/sinusoidal obstruction syndrome.

PubMed

Kernan, Nancy A; Grupp, Stephan; Smith, Angela R; Arai, Sally; Triplett, Brandon; Antin, Joseph H; Lehmann, Leslie; Shore, Tsiporah; Ho, Vincent T; Bunin, Nancy; Iacobelli, Massimo; Liang, Wei; Hume, Robin; Tappe, William; Soiffer, Robert; Richardson, Paul

2018-05-16

Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening complication of haematopoietic stem cell transplant (HSCT) conditioning and chemotherapy. Defibrotide is approved for treatment of hepatic VOD/SOS with pulmonary or renal dysfunction [i.e., multi-organ dysfunction (MOD)] after HSCT in the United States and severe VOD/SOS after HSCT in patients aged older than 1 month in the European Union. Defibrotide was available as an investigational drug by an expanded-access treatment programme (T-IND; NCT00628498). In the completed T-IND, the Kaplan-Meier estimated Day +100 survival for 1000 patients with documented defibrotide treatment after HSCT was 58·9% [95% confidence interval (CI), 55·7-61·9%]. Day +100 survival was also analysed by age and MOD status, and post hoc analyses were performed to determine Day +100 survival by transplant type, timing of VOD/SOS onset (≤21 or >21 days) and timing of defibrotide treatment initiation after VOD/SOS diagnosis. Day +100 survival in paediatric patients was 67·9% (95% CI, 63·8-71·6%) and 47·1% (95% CI, 42·3-51·8%) in adults. All patient subgroups without MOD had higher Day +100 survival than those with MOD; earlier defibrotide initiation was also associated with higher Day +100 survival. The safety profile of defibrotide in the completed T-IND study was similar to previous reports. © 2018 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

Phase 3 trial of defibrotide for the treatment of severe veno-occlusive disease and multi-organ failure

PubMed Central

Riches, Marcie L.; Kernan, Nancy A.; Brochstein, Joel A.; Mineishi, Shin; Termuhlen, Amanda M.; Arai, Sally; Grupp, Stephan A.; Guinan, Eva C.; Martin, Paul L.; Steinbach, Gideon; Krishnan, Amrita; Nemecek, Eneida R.; Giralt, Sergio; Rodriguez, Tulio; Duerst, Reggie; Doyle, John; Antin, Joseph H.; Smith, Angela; Lehmann, Leslie; Champlin, Richard; Gillio, Alfred; Bajwa, Rajinder; D’Agostino, Ralph B.; Massaro, Joseph; Warren, Diane; Miloslavsky, Maja; Hume, Robin L.; Iacobelli, Massimo; Nejadnik, Bijan; Hannah, Alison L.; Soiffer, Robert J.

2016-01-01

Hepatic veno-occlusive disease (VOD), also called sinusoidal obstruction syndrome (SOS), is a potentially life-threatening complication of hematopoietic stem cell transplantation (HSCT). Untreated hepatic VOD/SOS with multi-organ failure (MOF) is associated with >80% mortality. Defibrotide has shown promising efficacy treating hepatic VOD/SOS with MOF in phase 2 studies. This phase 3 study investigated safety and efficacy of defibrotide in patients with established hepatic VOD/SOS and advanced MOF. Patients (n = 102) given defibrotide 25 mg/kg per day were compared with 32 historical controls identified out of 6867 medical charts of HSCT patients by blinded independent reviewers. Baseline characteristics between groups were well balanced. The primary endpoint was survival at day +100 post-HSCT; observed rates equaled 38.2% in the defibrotide group and 25% in the controls (23% estimated difference; 95.1% confidence interval [CI], 5.2-40.8; P = .0109, using a propensity-adjusted analysis). Observed day +100 complete response (CR) rates equaled 25.5% for defibrotide and 12.5% for controls (19% difference using similar methodology; 95.1% CI, 3.5-34.6; P = .0160). Defibrotide was generally well tolerated with manageable toxicity. Related adverse events (AEs) included hemorrhage or hypotension; incidence of common hemorrhagic AEs (including pulmonary alveolar [11.8% and 15.6%] and gastrointestinal bleeding [7.8% and 9.4%]) was similar between the defibrotide and control groups, respectively. Defibrotide was associated with significant improvement in day +100 survival and CR rate. The historical-control methodology offers a novel, meaningful approach for phase 3 evaluation of orphan diseases associated with high mortality. This trial was registered at www.clinicaltrials.gov as #NCT00358501. PMID:26825712

Phase 3 trial of defibrotide for the treatment of severe veno-occlusive disease and multi-organ failure.

PubMed

Richardson, Paul G; Riches, Marcie L; Kernan, Nancy A; Brochstein, Joel A; Mineishi, Shin; Termuhlen, Amanda M; Arai, Sally; Grupp, Stephan A; Guinan, Eva C; Martin, Paul L; Steinbach, Gideon; Krishnan, Amrita; Nemecek, Eneida R; Giralt, Sergio; Rodriguez, Tulio; Duerst, Reggie; Doyle, John; Antin, Joseph H; Smith, Angela; Lehmann, Leslie; Champlin, Richard; Gillio, Alfred; Bajwa, Rajinder; D'Agostino, Ralph B; Massaro, Joseph; Warren, Diane; Miloslavsky, Maja; Hume, Robin L; Iacobelli, Massimo; Nejadnik, Bijan; Hannah, Alison L; Soiffer, Robert J

2016-03-31

Hepatic veno-occlusive disease (VOD), also called sinusoidal obstruction syndrome (SOS), is a potentially life-threatening complication of hematopoietic stem cell transplantation (HSCT). Untreated hepatic VOD/SOS with multi-organ failure (MOF) is associated with >80% mortality. Defibrotide has shown promising efficacy treating hepatic VOD/SOS with MOF in phase 2 studies. This phase 3 study investigated safety and efficacy of defibrotide in patients with established hepatic VOD/SOS and advanced MOF. Patients (n = 102) given defibrotide 25 mg/kg per day were compared with 32 historical controls identified out of 6867 medical charts of HSCT patients by blinded independent reviewers. Baseline characteristics between groups were well balanced. The primary endpoint was survival at day +100 post-HSCT; observed rates equaled 38.2% in the defibrotide group and 25% in the controls (23% estimated difference; 95.1% confidence interval [CI], 5.2-40.8;P= .0109, using a propensity-adjusted analysis). Observed day +100 complete response (CR) rates equaled 25.5% for defibrotide and 12.5% for controls (19% difference using similar methodology; 95.1% CI, 3.5-34.6;P= .0160). Defibrotide was generally well tolerated with manageable toxicity. Related adverse events (AEs) included hemorrhage or hypotension; incidence of common hemorrhagic AEs (including pulmonary alveolar [11.8% and 15.6%] and gastrointestinal bleeding [7.8% and 9.4%]) was similar between the defibrotide and control groups, respectively. Defibrotide was associated with significant improvement in day +100 survival and CR rate. The historical-control methodology offers a novel, meaningful approach for phase 3 evaluation of orphan diseases associated with high mortality. This trial was registered at www.clinicaltrials.gov as #. © 2016 by The American Society of Hematology.

Causes of mortality after haploidentical hematopoietic stem cell transplantation and the comparison with HLA-identical sibling hematopoietic stem cell transplantation.

PubMed

Yan, C H; Xu, L P; Wang, F R; Chen, H; Han, W; Wang, Yu; Wang, J Z; Liu, K Y; Huang, X J

2016-03-01

This study was performed to investigate incidence, causes and factors influencing mortality after haploidentical hematopoietic stem cell transplantation (HSCT) and to compare differences between haploidentical HSCT and HLA-identical sibling HSCT. From January 2000 to June 2011, 1411 patients with acute leukemia or myelodysplastic syndrome were included in this study. Of these patients, 571 received HLA-identical sibling HSCT and 840 received haploidentical HSCT. The cumulative incidence of overall mortality and transplant-related mortality (TRM) after haploidentical HSCT was higher than those after HLA-identical sibling HSCT (38.7% vs. 33.3%, P=0.012 and 27.5% vs. 19.9%, P=0.002), but the incidence of relapse-related mortality (RRM) did not differ between the two groups (15.6% vs. 16.7%, P=0.943). A multivariate analysis suggested that high-risk disease status and haploidentical HSCT correlated with a higher incidence of overall mortality (P<0.0001, hazard ratio=1.911 and P=0.019, hazard ratio=1.249); in addition, in haploidentical HSCT, only high-risk disease status correlated with a higher incidence of overall mortality (P<0.0001, hazard ratio=1.845). Our study suggested that haploidentical HSCT provided a higher incidence of overall mortality and TRM but the same incidence of RRM compared with HLA-identical sibling HSCT. Therefore, HLA-identical sibling HSCT remains the first choice, but haploidentical HSCT is available for patients without an HLA-identical sibling donor.

Vancomycin-Resistant Enterococcus Colonization and Bacteremia and Hematopoietic Stem Cell Transplantation Outcomes.

PubMed

Ford, Clyde D; Gazdik, Michaela A; Lopansri, Bert K; Webb, Brandon; Mitchell, Birgitta; Coombs, Jana; Hoda, Daanish; Petersen, Finn Bo

2017-02-01

The association between pre-hematopoietic stem cell transplantation (HSCT) vancomycin-resistant Enterococcus (VRE) colonization, HSCT-associated VRE bacteremia, and HSCT mortality is disputed. We studied 161 consecutive patients with acute leukemia who underwent HSCT at our hospital between 2006 and 2014, of whom 109 also received leukemia induction/consolidation on our unit. All inpatients had weekly VRE stool surveillance. Pre-HSCT colonization was not associated with increases in HSCT mortality but did identify a subgroup of HSCT recipients with a higher risk for VRE bacteremia and possibly bacteremia from other organisms. The major risk factor for pre-HSCT colonization was the number of hospital inpatient days between initial admission for leukemia and HSCT. One-third of evaluable patients colonized before HSCT were VRE-culture negative on admission for HSCT; these patients had an increased risk for subsequent VRE stool surveillance positivity but not VRE bacteremia. Molecular typing of VRE isolates obtained before and after HSCT showed that VRE strains frequently change. Postengraftment VRE bacteremia was associated with a much higher mortality than pre-engraftment VRE bacteremia. Pre-engraftment bacteremia from any organism was associated with an alternative donor and resulted in an increase in hospital length of stay and cost. Mortality was similar for pre-engraftment VRE bacteremia and pre-engraftment bacteremia due to other organisms, but mortality associated with post-engraftment VRE bacteremia was higher and largely explained by associated severe graft-versus-host disease and relapsed leukemia. These data emphasize the importance of distinguishing between VRE colonization before HSCT and at HSCT, between pre-engraftment and postengraftment VRE bacteremia, and between VRE bacteremia and bacteremia from other organisms. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

HLA Match Likelihoods for Hematopoietic Stem-Cell Grafts in the U.S. Registry

PubMed Central

Gragert, Loren; Eapen, Mary; Williams, Eric; Freeman, John; Spellman, Stephen; Baitty, Robert; Hartzman, Robert; Rizzo, J. Douglas; Horowitz, Mary; Confer, Dennis; Maiers, Martin

2018-01-01

Background Hematopoietic stem-cell transplantation (HSCT) is a potentially lifesaving therapy for several blood cancers and other diseases. For patients without a suitable related HLA-matched donor, unrelated-donor registries of adult volunteers and banked umbilical cord–blood units, such as the Be the Match Registry operated by the National Marrow Donor Program (NMDP), provide potential sources of donors. Our goal in the present study was to measure the likelihood of finding a suitable donor in the U.S. registry. Methods Using human HLA data from the NMDP donor and cord-blood-unit registry, we built population-based genetic models for 21 U.S. racial and ethnic groups to predict the likelihood of identifying a suitable donor (either an adult donor or a cord-blood unit) for patients in each group. The models incorporated the degree of HLA matching, adult-donor availability (i.e., ability to donate), and cord-blood-unit cell dose. Results Our models indicated that most candidates for HSCT will have a suitable (HLA-matched or minimally mismatched) adult donor. However, many patients will not have an optimal adult donor — that is, a donor who is matched at high resolution at HLA-A, HLA-B, HLA-C, and HLA-DRB1. The likelihood of finding an optimal donor varies among racial and ethnic groups, with the highest probability among whites of European descent, at 75%, and the lowest probability among blacks of South or Central American descent, at 16%. Likelihoods for other groups are intermediate. Few patients will have an optimal cord-blood unit — that is, one matched at the antigen level at HLA-A and HLA-B and matched at high resolution at HLA-DRB1. However, cord-blood units mismatched at one or two HLA loci are available for almost all patients younger than 20 years of age and for more than 80% of patients 20 years of age or older, regardless of racial and ethnic background. Conclusions Most patients likely to benefit from HSCT will have a donor. Public investment in donor recruitment and cord-blood banks has expanded access to HSCT. (Funded by the Office of Naval Research, Department of the Navy, and the Health Resources and Services Administration, Department of Health and Human Services.) PMID:25054717

Autologous hematopoietic stem cell transplantation in extranodal natural killer/T cell lymphoma: a multinational, multicenter, matched controlled study.

PubMed

Lee, Jeeyun; Au, Wing-Yan; Park, Min Jae; Suzumiya, Junji; Nakamura, Shigeo; Kameoka, Jun-Ichi; Sakai, Chikara; Oshimi, Kazuo; Kwong, Yok-Lam; Liang, Raymond; Yiu, Harry; Wong, Kam-Hung; Cheng, Hoi-Ching; Ryoo, Baek-Yeol; Suh, Cheolwon; Ko, Young Hyeh; Kim, Kihyun; Lee, Jae-Won; Kim, Won Seog; Suzuki, Ritsuro

2008-12-01

Extranodal natural killer (NK)/T cell lymphoma, nasal type, is a recently recognized distinct entity and the most common type of non-B cell extranodal lymphoma in Asia. This retrospective analysis studied the potential survival benefits of hematopoeitic stem cell transplantation (HSCT) compared with a historical control group. A total of 47 patients from 3 previously published series of HSCT were matched according to NK/T cell lymphoma International Prognostic Index (NKIPI) risk groups and disease status at transplantation with 107 patients from a historical control group for analysis. After a median follow-up of 116.5 months, the median survival time was not determined for the HSCT group, but it was 43.5 months for the control group (95% confidence interval [CI] = 6.7 to 80.3 months; P = .127, log-rank test). In patients who were in complete remission (CR) at the time of HSCT or at surveillance after remission, disease-specific survival rates were significantly higher in the HSCT group compared with the control group (disease-specific 5-year survival rate, 87.3% for HSCT vs 67.8% for non-HSCT; P = .027). In contrast, in subgroup analysis on non-CR patients at the time of HSCT or non-HSCT treatment, disease-specific survival rates were not significantly prolonged in the HSCT group compared with the control group (1-year survival rate, 66.7% for HSCT vs 28.6% for non-HSCT; P = .141). The impact of HSCT on the survival of all patients was significantly retained at the multivariate level with a 2.1-fold (95% CI =1.2- to 3.7-fold) reduced risk of death (P = .006). HSCT seems to confer a survival benefit in patients who attained CR on postremission consolidation therapy. These findings suggest that, in particular, patients in CR with high NKIPI risk scores at diagnosis should receive full consideration for HSCT.

T-cell-replete haploidentical HSCT with low-dose anti-T-lymphocyte globulin compared with matched sibling HSCT and unrelated HSCT.

PubMed

Luo, Yi; Xiao, Haowen; Lai, Xiaoyu; Shi, Jimin; Tan, Yamin; He, Jingsong; Xie, Wanzhuo; Zheng, Weiyan; Zhu, Yuanyuan; Ye, Xiujin; Yu, Xiaohong; Cai, Zhen; Lin, Maofang; Huang, He

2014-10-23

We developed an approach of T-cell-replete haploidentical hematopoietic stem cell transplantation (HSCT) with low-dose anti-T-lymphocyte globulin and prospectively compared outcomes of all contemporaneous T-cell-replete HSCT performed at our center using matched sibling donors (MSDs), unrelated donors (URDs), and haploidentical related donors (HRDs). From 2008 to 2013, 90 patients underwent MSD-HSCT, 116 underwent URD-HSCT, and 99 underwent HRD-HSCT. HRDs were associated with higher incidences of grades 2 to 4 (42.4%) and severe acute graft-versus-host disease (17.2%) and nonrelapse mortality (30.5%), compared with MSDs (15.6%, 5.6%, and 4.7%, respectively; P < .05), but were similar to URDs, even fully 10/10 HLA-matched URDs. For high-risk patients, a superior graft-versus-leukemia effect was observed in HRD-HSCT, with 5-year relapse rates of 15.4% in HRD-HSCT, 28.2% in URD-HSCT (P = .07), and 49.9% in MSD-HSCT (P = .002). Furthermore, 5-year disease-free survival rates were not significantly different for patients undergoing transplantation using 3 types of donors, with 63.6%, 58.4%, and 58.3% for MSD, URD, and HRD transplantation, respectively (P = .574). Our data indicate that outcomes after HSCT from suitably matched URDs and HRDs with low-dose anti-T-lymphocyte globulin are similar and that HRD improves outcomes of patients with high-risk leukemia. This trial was registered at www.chictr.org (Chinese Clinical Trial Registry) as #ChiCTR-OCH-12002490. © 2014 by The American Society of Hematology.

Parvovirus B19 in the Context of Hematopoietic Stem Cell Transplantation: Evaluating Cell Donors and Recipients

PubMed Central

Gama, Bianca E.; Emmel, Vanessa E.; Oliveira-Silva, Michelle; Gutiyama, Luciana M.; Arcuri, Leonardo; Colares, Marta; de Cássia Tavares, Rita; Bouzas, Luis F.; Abdelhay, Eliana; Hassan, Rocio

2017-01-01

Background Parvovirus B19 (B19V) is a common human pathogen, member of the family Parvoviridae. Typically, B19V has been found to infect erythroid progenitors and cause hematological disorders, such as anemia and aplastic crisis. However, the persistence of genomic deoxyribonucleic acid (DNA) has been demonstrated in tonsils, liver, skin, brain, synovial, and testicular tissues as well as bone marrow, for both symptomatic and asymptomatic subjects. Although the molecular and cellular mechanisms of persistence remain undefined, it raises questions about potential virus transmissibility and its effects in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Methods With this aim, we retrospectively screened allogeneic stem cell donors from 173 patients admitted for allo-HSCT from January 2008 to May 2013 using a seminested polymerase chain reaction approach. Results We found 8 positive donor samples, yielding a 4.6% of parvovirus prevalence (95% confidence interval, 2.36-8.85). Pre- and post-HSCT samples (n = 51) from the 8 recipients of the positive donors were also investigated, and 1 case exhibited B19V DNA in the post-HSCT follow-up (D + 60). Direct DNA sequencing was performed to determine the genotype of isolates and classification, performed by phylogenetic reconstruction, showed a predominance of genotype 1a, whereas the rare genotype 3b was detected in 2 additional patients. By molecular cloning, different B19V 1a substrains polymorphisms were evidenced in the single case in which donor and its recipient were B19V+. Conclusions Our results suggest that HSCT allografts are not a main source for B19V transmission, pointing to potential events of reinfection or endogenous viral reactivation. PMID:29184906

Parvovirus B19 in the Context of Hematopoietic Stem Cell Transplantation: Evaluating Cell Donors and Recipients.

PubMed

Gama, Bianca E; Emmel, Vanessa E; Oliveira-Silva, Michelle; Gutiyama, Luciana M; Arcuri, Leonardo; Colares, Marta; de Cássia Tavares, Rita; Bouzas, Luis F; Abdelhay, Eliana; Hassan, Rocio

2017-11-01

Parvovirus B19 (B19V) is a common human pathogen, member of the family Parvoviridae. Typically, B19V has been found to infect erythroid progenitors and cause hematological disorders, such as anemia and aplastic crisis. However, the persistence of genomic deoxyribonucleic acid (DNA) has been demonstrated in tonsils, liver, skin, brain, synovial, and testicular tissues as well as bone marrow, for both symptomatic and asymptomatic subjects. Although the molecular and cellular mechanisms of persistence remain undefined, it raises questions about potential virus transmissibility and its effects in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. With this aim, we retrospectively screened allogeneic stem cell donors from 173 patients admitted for allo-HSCT from January 2008 to May 2013 using a seminested polymerase chain reaction approach. We found 8 positive donor samples, yielding a 4.6% of parvovirus prevalence (95% confidence interval, 2.36-8.85). Pre- and post-HSCT samples (n = 51) from the 8 recipients of the positive donors were also investigated, and 1 case exhibited B19V DNA in the post-HSCT follow-up (D + 60). Direct DNA sequencing was performed to determine the genotype of isolates and classification, performed by phylogenetic reconstruction, showed a predominance of genotype 1a, whereas the rare genotype 3b was detected in 2 additional patients. By molecular cloning, different B19V 1a substrains polymorphisms were evidenced in the single case in which donor and its recipient were B19V+. Our results suggest that HSCT allografts are not a main source for B19V transmission, pointing to potential events of reinfection or endogenous viral reactivation.

HSCT noise reduction technology development at GE Aircraft Engines

NASA Technical Reports Server (NTRS)

Majjigi, Rudramuni K.

1992-01-01

The topics covered include the following: High Speed Civil Transport (HSCT) exhaust nozzle design approaches; GE aircraft engine (GEAE) HSCT acoustics research; 2DCD non-IVP suppressor ejector; key sensitivities from reference aircraft; acoustic experiments; aero-mixing experimental set-up; fluid shield nozzle; HSCT Mach 2.4 flade nozzle; noise prediction; nozzle concept for GE/Boeing joint test; scale model hot core flow path modified to prevent hub-choking CFL3-D solution; HSCT exhaust nozzle status; and key acoustic technology issues for HSCT's.

HSCT noise reduction technology development at GE Aircraft Engines

NASA Astrophysics Data System (ADS)

Majjigi, Rudramuni K.

1992-04-01

The topics covered include the following: High Speed Civil Transport (HSCT) exhaust nozzle design approaches; GE aircraft engine (GEAE) HSCT acoustics research; 2DCD non-IVP suppressor ejector; key sensitivities from reference aircraft; acoustic experiments; aero-mixing experimental set-up; fluid shield nozzle; HSCT Mach 2.4 flade nozzle; noise prediction; nozzle concept for GE/Boeing joint test; scale model hot core flow path modified to prevent hub-choking CFL3-D solution; HSCT exhaust nozzle status; and key acoustic technology issues for HSCT's.

[Social connection: a report of the SFGM-TC on the maintaining social and family connections during Hematopoietic Stem Cell Transplantation].

PubMed

Rohrlich, P S; Kerautret, K; Bancillon, N; Vauzelle, K; Bertrand-Letort, M; Ruiz, M; Schmitt, S; Samy, J-P; Guiraud, M; Yakoub-Agha, I

2013-08-01

To set up the minimal conditions necessary to ensure that the social and familial network of the patient is preserved during the hospital stay for allogeneic hematopoïetic stem cell transplantation. A national survey was conducted to increase knowledge about the conditions of hospital stay of adult and pediatric stem cell recipients. Then a multidisciplinary panel of health workers including doctors and nurses met to establish recommendations for maintaining the social and familial relationships optimally during the HSCT procedure. Practices and policies are very heterogeneous among the transplant centers. No consensus has been established and the literature data are scarce. The panel has thus established a list of recommendations to maintain optimal relationships between the patient and his relatives and friends during the hospital stay. The objective is to ensure a better acceptation of the isolation conditions and to facilitate the return home after D30. Since there is no established scientific background for drastic isolation conditions, a multi-disciplinary approach in relationship with patients associations should allow softening of the procedures without impairing the quality of care. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Disease-specific hematopoietic stem cell transplantation in children with inherited bone marrow failure syndromes.

PubMed

Li, Qian; Luo, Changying; Luo, Chengjuan; Wang, Jianmin; Li, Benshang; Ding, Lixia; Chen, Jing

2017-08-01

Hematopoietic stem cell transplantation (HSCT) using an optimized conditioning regimen is essential for the long-term survival of patients with inherited bone marrow failure syndromes (IBMFS). We report HSCT in 24 children with Fanconi anemia (FA, n = 12), Diamond-Blackfan anemia (DBA, n = 7), and dyskeratosis congenita (DC, n = 5) from a single HSCT center. The graft source was peripheral blood stem cells (n = 19) or cord blood stem cells (n = 5). FA and DC patients received reduced-intensity conditioning, while DBA patients had myeloablative conditioning. The median numbers of infused mononuclear cells and CD34+ cells were 14.20 × 10 8 /kg and 4.3 × 10 6 /kg, respectively. The median time for neutrophil and platelet recovery was 12 and 18 days, respectively. Complete donor engraftment was achieved in 23 of 24 patients. There was one primary graft failure. During a median follow-up of 27.5 months (range, 2-130 months), the overall survival in all patients was 95.8%. The incidence of grade II-III acute graft versus host disease (GvHD) and chronic GvHD was 29.2% and 16.7%, respectively. We conclude that HSCT can be a curative option for patients with IBMFS. Modification of the conditioning regimen based on the type of disease may lead to encouraging long-term outcomes.

Clinical outcomes of myeloid/lymphoid neoplasms with fibroblast growth factor receptor-1 (FGFR1) rearrangement.

PubMed

Umino, Kento; Fujiwara, Shin-Ichiro; Ikeda, Takashi; Toda, Yumiko; Ito, Shoko; Mashima, Kiyomi; Minakata, Daisuke; Nakano, Hirofumi; Yamasaki, Ryoko; Kawasaki, Yasufumi; Sugimoto, Miyuki; Yamamoto, Chihiro; Ashizawa, Masahiro; Hatano, Kaoru; Sato, Kazuya; Oh, Iekuni; Ohmine, Ken; Muroi, Kazuo; Kanda, Yoshinobu

2018-02-28

Myeloid/lymphoid neoplasms with fibroblast growth factor receptor-1 (FGFR1) rearrangement are hematopoietic stem cell disorders with a poor prognosis, but no established standard therapy. We experienced a patient with T-lymphoblastic lymphoma (LBL) associated with FGFR1 rearrangement who underwent cord blood transplantation, but died of pulmonary complication. We collected the clinical data of patients with FGFR1 rearrangement from the medical literature and analyzed 45 patients, including our patient. The primary diagnoses were myeloproliferative neoplasm (MPN) or myelodysplastic syndromes (MDS) in 14 and acute leukemia or LBL in 31. In MPN and MDS patients, the cumulative incidence of transformation to blast phase (BP) at 12 months was 46.2%. The 1-year overall survival (OS) from diagnosis in all cases was 43.1%. With regard to the impact of treatment response on survival, the achievement of complete response with a landmark at 2 months after diagnosis of BP was associated with a superior OS (40.0% vs. 26.0% P = 0.011 for 1-year OS from BP). Allogeneic hematopoietic stem cell transplantation (HSCT) was performed in 13 patients, and the 1-year OS from allogeneic HSCT was 61.5%. The hazard ratio for mortality was 0.34 (95% CI, 0.08-1.51, P = 0.15) for allogeneic HSCT treated as a time-dependent covariate, which suggests that allogeneic HSCT may confer a clinical benefit. The further accumulation of clinical data is needed to determine the optimal therapeutic approach for these neoplasms.

Having a sibling as donor: patients' experiences immediately before allogeneic hematopoietic stem cell transplantation.

PubMed

Kisch, Annika; Bolmsjö, Ingrid; Lenhoff, Stig; Bengtsson, Mariette

2014-08-01

Allogeneic hematopoietic stem cell transplantation (HSCT) offers a potential cure for a variety of diseases but is also associated with significant risks. With HSCT the donor is either a relative, most often a sibling, or an unrelated registry donor. The aim was to explore patients' experiences, immediately before transplantation, regarding having a sibling as donor. Ten adult patients with sibling donors were interviewed before admission for HSCT. The interviews were digitally recorded, transcribed verbatim and subjected to qualitative content analysis. The main theme Being in no man's land is a metaphor for the patients' complex situation with its mixture of emotions and thoughts prior to transplantation. The three subthemes Trust in the sibling donor, Concern about others and Loss of control cover the various experiences. The patient's experiences are influenced by their personal situation and the quality of the relationship with the sibling donor. While patients feel secure in having a sibling donor, they are dependent for their survival on the cell donation and feel responsible for the donor's safety during donation. These emotions intensify the patients' sense of dependency and loss of control. In caring for HSCT patients the nurses should be aware of the complexity of the patients' situation and keep in mind that having a sibling donor might imply extra pressure, including a sense of responsibility. Caring for both patients and sibling donors optimally is a challenge, which needs further improvement and exploration. Copyright © 2014 Elsevier Ltd. All rights reserved.

Performance optimization of the power user electric energy data acquire system based on MOEA/D evolutionary algorithm

NASA Astrophysics Data System (ADS)

Ding, Zhongan; Gao, Chen; Yan, Shengteng; Yang, Canrong

2017-10-01

The power user electric energy data acquire system (PUEEDAS) is an important part of smart grid. This paper builds a multi-objective optimization model for the performance of the PUEEADS from the point of view of the combination of the comprehensive benefits and cost. Meanwhile, the Chebyshev decomposition approach is used to decompose the multi-objective optimization problem. We design a MOEA/D evolutionary algorithm to solve the problem. By analyzing the Pareto optimal solution set of multi-objective optimization problem and comparing it with the monitoring value to grasp the direction of optimizing the performance of the PUEEDAS. Finally, an example is designed for specific analysis.

Outcome of aplastic anaemia in children. A study by the severe aplastic anaemia and paediatric disease working parties of the European group blood and bone marrow transplant.

PubMed

Dufour, Carlo; Pillon, Marta; Sociè, Gerard; Rovò, Alicia; Carraro, Elisa; Bacigalupo, Andrea; Oneto, Rosi; Passweg, Jakob; Risitano, Antonio; Tichelli, Andrè; Peffault de Latour, Regis; Schrezenmeier, Hubert; Hocshmann, Britta; Peters, Christina; Kulasekararaj, Austin; Van Biezen, Anja; Samarasinghe, Sujith; Hussein, Ayad Ahmed; Ayas, Mouhab; Aljurf, Mahmoud; Marsh, Judith

2015-05-01

This study analysed the outcome of 563 Aplastic Anaemia (AA) children aged 0-12 years reported to the Severe Aplastic Anaemia Working Party database of the European Society for Blood and Marrow Transplantation, according to treatment received. Overall survival (OS) after upfront human leucocyte antigen-matched family donor (MFD) haematopoietic stem cell transplantation (HSCT) or immunosuppressive treatment (IST) was 91% vs. 87% (P 0·18). Event-free survival (EFS) after upfront MFD HSCT or IST was 87% vs. 33% (P 0·001). Ninety-one of 167 patients (55%) failed front-line IST and underwent rescue HSCT. The OS of this rescue group was 83% compared with 91% for upfront MFD HSCT patients and 97% for those who did not fail IST up-front (P 0·017). Rejection was 2% for MFD HSCT and HSCT post-IST failure (P 0·73). Acute graft-versus-host disease (GVHD) grade II-IV was 8% in MFD graft vs. 25% for HSCT post-IST failure (P < 0·0001). Chronic GVHD was 6% in MFD HSCT vs. 20% in HSCT post-IST failure (P < 0·0001). MFD HSCT is an excellent therapy for children with AA. IST has a high failure rate, but remains a reasonable first-line choice if MFD HSCT is not available because high OS enables access to HSCT, which is a very good rescue option. © 2015 John Wiley & Sons Ltd.

Growth after Hematopoietic Stem Cell Transplantation in Children with Acute Myeloid Leukemia

PubMed Central

Chung, Seung Joon; Park, Seung Wan; Kim, Min Kyoung; Kang, Min Jae; Lee, Young Ah; Lee, Seong Yong; Yang, Sei Won; Kang, Hyoung Jin; Park, Kyung Duk; Shin, Hee Young; Ahn, Hyo Seop

2013-01-01

Previous studies have shown that hematopoietic stem cell transplantation (HSCT) may result in growth impairment. The purpose of this study was to evaluate the growth during 5 yr after HSCT and to determine factors that influence final adult height (FAH). We retrospectively reviewed the medical records of acute myeloid leukemia (AML) patients who received HSCT. Among a total of 37 eligible patients, we selected 24 patients who began puberty at 5 yr after HSCT (Group 1) and 19 patients who reached FAH without relapse (Group 2). In Group 1, with younger age at HSCT, sex, steroid treatment, hypogonadism and hypothyroidism were not significantly associated with growth impairment 5 yr after HSCT. History of radiotherapy (RT) significantly impaired the 5 yr growth after HSCT. Chronic graft-versus-host disease (cGVHD) only temporarily impaired growth after HSCT. In Group 2, with younger age at HSCT, steroid treatment and hypogonadism did not significantly reduce FAH. History of RT significantly reduced FAH. Growth impairment after HSCT may occur in AML patients, but in patients without a history of RT, growth impairment seemed to be temporary and was mitigated by catch-up growth. PMID:23341720

Matched sibling versus matched unrelated allogeneic hematopoietic stem cell transplantation in children with severe acquired aplastic anemia: experience of the polish pediatric group for hematopoietic stem cell transplantation.

PubMed

Szpecht, Dawid; Gorczyńska, Ewa; Kałwak, Krzysztof; Owoc-Lempach, Joanna; Choma, Marta; Styczyński, Jan; Goździk, Jolanta; Dłużniewska, Agnieszka; Wysocki, Mariusz; Kowalczyk, Jerzy R; Chybicka, Alicja; Pieczonka, Anna; Wachowiak, Jacek

2012-06-01

In the study, 48 children with severe acquired aplastic anemia (SAA) transplanted from matched sibling donor (MSD) between 1991 and 2009, and 38 children with SAA transplanted from matched unrelated donor (MUD) between 2000 and 2009 were evaluated. Engraftment was achieved in 45 (93.75 %) patients after MSD-hematopoietic stem cell transplantation (HSCT) and in 33 (86.8 %) after MUD-HSCT. Transplant-related mortality rate after MSD-HSCT was 8 %, while 37 % after MUD-HSCT. After MSD-HSCT 44 (91.7 %) patients are alive for 1-216 months (median: 85 months), while after MUD-HSCT 24 (63.2 %) patients for 1-84 months (median: 16 months). The 5-year probability of event-free survival after MSD-HSCT and MUD-HSCT was 87 and 53 %, respectively, while 5 years of overall survival was 91 and 64 %, respectively. It was concluded that MSD-HSCT as the first line treatment for children with SAA is a safe therapeutic approach with a low rate of treatment failures and excellent outcome. Results of MUD-HSCT in pediatric patients with SAA who failed to respond to immunosuppressive therapy are still inferior than those of MSD-HSCT. Treatment failures of MUD-HSCT are mainly related to infectious complications and graft failure. It seems, however, that HLA-matching of unrelated donors at allelic level along with early MUD-HSCT after FCA (FLUDA, low-dose cyclophosphamide, and anti-thymocyte globulin) conditioning, perhaps using lower Thymoglobulin dose could enable further improvement of long-term results in children with SAA who lack MSD.

Reassessing the approach to informed consent: the case of unrelated hematopoietic stem cell transplantation in adult thalassemia patients

PubMed Central

2014-01-01

Introduction The informed consent process is the legal embodiment of the fundamental right of the individual to make decisions affecting his or her health., and the patient’s permission is a crucial form of respect of freedom and dignity, it becomes extremely important to enhance the patient’s understanding and recall of the information given by the physician. This statement acquires additional weight when the medical treatment proposed can potentially be detrimental or even fatal. This is the case of thalassemia patients pertaining to class 3 of the Pesaro classification where Allogenic hematopoietic stem cell transplantation (HSCT) remains the only potentially curative treatment. Unfortunately, this kind of intervention is burdened by an elevated transplantation-related mortality risk (TRM: all deaths considered related to transplantation), equal to 30% according to published reports. In thalassemia, the role of the patient in the informed consent process leading up to HSCT has not been fully investigated. This study investigated the hypothesis that information provided by physicians in the medical scenario of HSCT is not fully understood by patients and that misunderstanding and communication biases may affect the clinical decision-making process. Methods A questionnaire was either mailed or given personally to 25 patients. A second questionnaire was administered to the 12 physicians attending the patients enrolled in this study. Descriptive statistics were used to evaluate the communication factors. Results The results pointed out the difference between the risks communicated by physicians and the risks perceived by patients. Besides the study highlighted the mortality risk considered to be acceptable by patients and that considered to be acceptable by physicians. Conclusions Several solutions have been suggested to reduce the gap between communicated and perceived data. A multi-disciplinary approach may possibly help to attenuate some aspects of communication bias. Several tools have also been proposed to fill or to attenuate the gap between communicated and perceived data. But the most important tool is the ability of the physician to comprehend the right place of conscious consent in the relationship with the patient. PMID:25115172

Optimal Ventilation Control in Complex Urban Tunnels with Multi-Point Pollutant Discharge

DOT National Transportation Integrated Search

2017-10-01

Zhen Tan (ORCID ID 0000-0003-1711-3557) H. Oliver Gao (ORCID ID 0000-0002-7861-9634) We propose an optimal ventilation control model for complex urban vehicular tunnels with distributed pollutant discharge points. The control problem is formulated as...

Reconstitution of lymphocyte subpopulations after hematopoietic stem cell transplantation: comparison of hematologic malignancies and donor types in event-free patients.

PubMed

Park, Borae G; Park, Chan-Jeoung; Jang, Seongsoo; Chi, Hyun-Sook; Kim, Dae-Young; Lee, Jung-Hee; Lee, Je-Hwan; Lee, Kyoo-Hyung

2015-12-01

The reconstitution of different immunocyte subsets after hematopoietic stem cell transplantation (HSCT), follows different timelines. We prospectively investigated changes in lymphocyte subsets after HSCT and their associations with primary diagnosis, conditioning regimen, and HSCT type in event-free patients. A total of 95 patients (48 with acute myeloid leukemia, 22 with acute lymphoid leukemia, and 25 with myelodysplastic syndrome) who underwent allogeneic HSCT (34 sibling matched, 37 unrelated matched, and 24 haploidentical HSCT) but did not experience any events such as relapse or death were enrolled in this study. Lymphocyte subpopulations (T cells, helper/inducer T cells, cytotoxic/suppressor T cells, memory T cells, regulatory T cells, natural killer (NK) cells, NK-T cells, and B cells) were quantified by flow cytometry of peripheral blood from recipients 7 days before and 1, 2, 3, 6, and 12 months after HSCT. Leukocyte counts recovered within 1 month after HSCT. However, the number of T and B lymphocytes recovered at 2 months after HSCT. NK cell counts recovered shortly after haploidentical HSCT. However, T lymphocytes and their subpopulations showed delayed recovery after haploidentical HSCT. Lymphocyte subsets showed different sequential patterns according to HSCT type but no differences were seen according to primary diagnosis or conditioning regimen. Copyright © 2015 Elsevier Ltd. All rights reserved.

Parent Outlook: How Parents View the Road Ahead as They Embark on Hematopoietic Stem Cell Transplantation for Their Child

PubMed Central

Ullrich, Christina K.; Rodday, Angie Mae; Bingen, Kristin; Kupst, Mary Jo; Patel, Sunita K.; Syrjala, Karen L.; Harris, Lynnette L.; Recklitis, Christopher J.; Schwartz, Lisa; Davies, Stella; Guinan, Eva C.; Chang, Grace; Wolfe, Joanne; Parsons, Susan K.

2015-01-01

Pediatric hematopoietic stem cell transplantation (HSCT) offers cure for high-risk malignancies and other conditions, but carries a risk of complications. Parental outlook regarding their child’s transplantation course and future health has been largely unexplored. This report presents the Parent Outlook Scale, describes its properties, and examines the outlook of parents embarking on their child’s transplantation course and the associated variables. Parents of children scheduled to undergo HSCT (n = 363) at 8 US transplantation centers completed the Parent Outlook Scale, comprising 4 items assessing frequency of the parent’s thoughts about the potential difficulty of the child’s transplantation (Transplant Diffficult subscale) and worsened health (Health Worse subscale). Item responses were rated on a 5-point Likert scale (ranging from “none” to “all of the time”) and, along with scale/subscale scores, transformed to 100-point scales, with higher scores connoting greater thought frequency. Psychometrics were explored. Multivariable models identified personal and clinical characteristics associated with scale and subscale scores. The Parent Outlook Scale (α = 0.75) and subscales were found to have sound psychometric properties. Factor loading supported the single scale with 2 subscales representing distinct aspects of overall outlook. Mean scores (Parent Outlook, 52.5 ± 21.7; Transplant Difficult, 64.4 ± 25.6; Health Worse, 40.7 ± 25.7) revealed variability within and across scale/subscales. Significantly different mean subscale scores (P < .001) indicated more frequent Transplant Difficult thoughts than Health Worse thoughts. Clinical factors (solid tumor diagnosis and unrelated donor transplant) and a parent factor (worse emotional functioning) were associated with higher scale and subscale scores. Our findings show that the outlook of parents embarking on their child’s HSCT course is varied and not solely a product of clinical factors readily apparent to clinicians. Referring and transplantation clinicians should create opportunities to explore with parents their perspectives and concerns before and during the course of HSCT. PMID:26348891

Long-term survival following autologous and allogeneic stem cell transplantation for blastic plasmacytoid dendritic cell neoplasm.

PubMed

Aoki, Tomohiro; Suzuki, Ritsuro; Kuwatsuka, Yachiyo; Kako, Shinichi; Fujimoto, Katsuya; Taguchi, Jun; Kondo, Tadakazu; Ohata, Kinya; Ito, Toshiro; Kamoda, Yoshimasa; Fukuda, Takahiro; Ichinohe, Tatsuo; Takeuchi, Kengo; Izutsu, Koji; Suzumiya, Junji

2015-06-04

We sought to clarify the role of high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) to treat blastic plasmacytoid dendritic cell neoplasm (BPDCN). We retrospectively identified 25 BPDCN patients (allo-HSCT, n = 14; auto-HSCT, n = 11) from registry data of the Japan Society for Hematopoietic Cell Transplantation and analyzed clinicopathologic data and clinical outcomes after transplantation. The median age at HSCT was 58 years (range, 17-67 years). All 11 patients who underwent auto-HSCT were in the first complete remission (CR1). With a median follow-up of 53.5 months, the overall survival rates at 4 years for patients who underwent auto-HSCT and allo-HSCT were 82% and 53% (P = .11), respectively, and progression-free survival rates were 73% and 48% (P = .14), respectively. Auto-HSCT for BPDCN in CR1 appears to provide promising results and deserves further evaluation in the setting of prospective trials. © 2015 by The American Society of Hematology.

Acute myeloid leukemia in children: Current status and future directions.

PubMed

Taga, Takashi; Tomizawa, Daisuke; Takahashi, Hiroyuki; Adachi, Souichi

2016-02-01

Acute myeloid leukemia (AML) accounts for 25% of pediatric leukemia and affects approximately 180 patients annually in Japan. The treatment outcome for pediatric AML has improved through advances in chemotherapy, hematopoietic stem cell transplantation (HSCT), supportive care, and optimal risk stratification. Currently, clinical pediatric AML studies are conducted separately according to the AML subtypes: de novo AML, acute promyelocytic leukemia (APL), and myeloid leukemia with Down syndrome (ML-DS). Children with de novo AML are treated mainly with anthracyclines and cytarabine, in some cases with HSCT, and the overall survival (OS) rate now approaches 70%. Children with APL are treated with an all-trans retinoic acid (ATRA)-combined regimen with an 80-90% OS. Children with ML-DS are treated with a less intensive regimen compared with non-DS patients, and the OS is approximately 80%. HSCT in first remission is restricted to children with high-risk de novo AML only. To further improve outcomes, it will be necessary to combine more accurate risk stratification strategies using molecular genetic analysis with assessment of minimum residual disease, and the introduction of new drugs in international collaborative clinical trials. © 2015 Japan Pediatric Society.

The Problem of Size in Robust Design

NASA Technical Reports Server (NTRS)

Koch, Patrick N.; Allen, Janet K.; Mistree, Farrokh; Mavris, Dimitri

1997-01-01

To facilitate the effective solution of multidisciplinary, multiobjective complex design problems, a departure from the traditional parametric design analysis and single objective optimization approaches is necessary in the preliminary stages of design. A necessary tradeoff becomes one of efficiency vs. accuracy as approximate models are sought to allow fast analysis and effective exploration of a preliminary design space. In this paper we apply a general robust design approach for efficient and comprehensive preliminary design to a large complex system: a high speed civil transport (HSCT) aircraft. Specifically, we investigate the HSCT wing configuration design, incorporating life cycle economic uncertainties to identify economically robust solutions. The approach is built on the foundation of statistical experimentation and modeling techniques and robust design principles, and is specialized through incorporation of the compromise Decision Support Problem for multiobjective design. For large problems however, as in the HSCT example, this robust design approach developed for efficient and comprehensive design breaks down with the problem of size - combinatorial explosion in experimentation and model building with number of variables -and both efficiency and accuracy are sacrificed. Our focus in this paper is on identifying and discussing the implications and open issues associated with the problem of size for the preliminary design of large complex systems.

[Role of long-term follow-up in management of late-onset post-hematopoietic stem cell transplant complications].

PubMed

Asano-Mori, Yuki

As the number of long-term survivors after allogeneic hematopoietic stem cell transplantation (HSCT) has increased owing to advances in transplantation and supportive care techniques, the health and welfare of these survivors have come into focus. However, they are still at risks for various complications, including chronic graft-versus-host disease, infectious diseases, and secondary cancers even in the late period, which can not only interfere with the patient's quality of life (QOL) but also lead to death. The importance of long-term follow-up (LTFU) and management have been recently recognized, and nationwide systems to promote LTFU care in patients receiving HSCT, such as medical fee revision, publication of a LTFU guideline unique to Japan, and preparation of patient pocketbook, is under consideration. The number of medical facilities at LTFU outpatient clinic is also increasing; therefore, an optimal comprehensive support system may be established sooner or later. However, self-management by patients is essential to overcome late complications as well as to improve QOL after HSCT. Healthcare professionals should collaborate and continue to make the greatest possible efforts to educate patients regarding the risks of late complications and their prevention.

Employment Status as an Indicator of Recovery and Function One Year after Hematopoietic Stem Cell Transplantation.

PubMed

Morrison, Eleshia J; Ehlers, Shawna L; Bronars, Carrie A; Patten, Christi A; Brockman, Tabetha A; Cerhan, James R; Hogan, William J; Hashmi, Shahrukh K; Gastineau, Dennis A

2016-09-01

Employment after hematopoietic stem cell transplantation (HSCT) is an indicator of post-transplantation recovery and function, with economic and social implications. As survival rates for HSCT continue to improve, greater emphasis can be placed on factors affecting the quality of post-transplantation survival, including the ability to resume employment. A sample of recipients of autologous or allogeneic HSCT was accrued (n = 1000) to complete a longitudinal lifestyle survey before transplantation and at 1 year after transplantation. The present study examines associations between employment and patient characteristics, disease variables, illness status, and quality of life among 1-year survivors (n = 702). Participants had a mean age of 55 years (range, 18 to 78) and were predominately male (59.7%), married/partnered (77.1%), and non-Hispanic Caucasian (89.5%); most (79.4%) had received autologous transplantation. Of the 690 participants reporting some form of employment before illness diagnosis, 62.4% had returned to work by 1 year after HSCT. Full-time employment at 1 year after HSCT was significantly associated with remission of illness, improved illness, fewer post-transplantation hospitalizations, less fatigue and pain, higher quality of life, and higher rating of perceived health. Those unemployed because of their health reported the highest rates of fatigue and pain and lowest quality of life, and they were most likely to report poor perceived health. These findings highlight work reintegration as an important outcome and marker of survivors' overall adjustment after transplantation. Identifying factors affecting post-transplantation employment offers opportunities for behavioral interventions to target modifiable risk factors to optimize post-transplantation survivorship, inclusive of increased rates of return to work and decreased rates of associated disability. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Pre- and post-transplant minimal residual disease predicts relapse occurrence in children with acute lymphoblastic leukaemia.

PubMed

Lovisa, Federica; Zecca, Marco; Rossi, Bartolomeo; Campeggio, Mimma; Magrin, Elisa; Giarin, Emanuela; Buldini, Barbara; Songia, Simona; Cazzaniga, Giovanni; Mina, Tommaso; Acquafredda, Gloria; Quarello, Paola; Locatelli, Franco; Fagioli, Franca; Basso, Giuseppe

2018-03-01

Relapse remains the leading cause of treatment failure in children with acute lymphoblastic leukaemia (ALL) undergoing allogeneic haematopoietic stem cell transplantation (HSCT). We retrospectively investigated the prognostic role of minimal residual disease (MRD) before and after HSCT in 119 children transplanted in complete remission (CR). MRD was measured by polymerase chain reaction in bone marrow samples collected pre-HSCT and during the first and third trimesters after HSCT (post-HSCT1 and post-HSCT3). The overall event-free survival (EFS) was 50%. The cumulative incidence of relapse and non-relapse mortality was 41% and 9%. Any degree of detectable pre-HSCT MRD was associated with poor outcome: EFS was 39% and 18% in patients with MRD positivity <1 × 10 -3 and ≥1 × 10 -3 , respectively, versus 73% in MRD-negative patients (P < 0·001). This effect was maintained in different disease remissions, but low-level MRD had a very strong negative impact only in patients transplanted in second or further CR. Also, MRD after HSCT enabled patients to be stratified, with increasing MRD between post-HSCT1 and post-HSCT3 clearly defining cohorts with a different outcome. MRD is an important prognostic factor both before and after transplantation. Given that MRD persistence after HSCT is associated with dismal outcome, these patients could benefit from early discontinuation of immunosuppression, or pre-emptive immuno-therapy. © 2018 John Wiley & Sons Ltd.

Outcomes of Hematopoietic Stem Cell Transplantation at a Limited-Resource Center in Mexico Are Comparable to Those in Developed Countries.

PubMed

Leon Rodriguez, Eucario; Rivera Franco, Monica M

2017-11-01

The first hematopoietic stem cell transplantation (HSCT) in Mexico was performed at our institution in 1980. Eighteen years later, our HSCT program was restructured to reduce transplantation-related mortality (TRM) and improve overall survival (OS). The aim of this study was to describe outcomes of HSCT at our institution despite limited resources. Consecutive patients undergoing HSCT, from November 1998 to February 2017, were retrospectively analyzed at the National Institute of Medical Sciences and Nutrition Salvador Zubiran in Mexico City. Three hundred nine HSCT (59% autologous) were performed in 275 patients. From 114 patients (41%) undergoing an allogeneic HSCT, acute and chronic graft-versus-host disease developed in 21% and 33%, respectively. From the entire cohort, 98 patients relapsed after HSCT and at the last follow-up, 183 (67%) patients were alive. The 100-day TRM rates were 1.9% and 6.1% for autologous and allogeneic HSCT, respectively. Ten-year relapse/progression-free survival were 54% and 65%, for autologous and allogeneic HSCT, respectively. Ten-year OS rates in autologous and allogeneic HSCT were 61% and 57%, respectively. We highlight that HSCT is feasible in developing countries, despite financial and infrastructure limitations, and conclude that our results are comparable to international literature and probably better in terms of TRM and cost-effectiveness. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

A dynamic multi-level optimal design method with embedded finite-element modeling for power transformers

NASA Astrophysics Data System (ADS)

Zhang, Yunpeng; Ho, Siu-lau; Fu, Weinong

2018-05-01

This paper proposes a dynamic multi-level optimal design method for power transformer design optimization (TDO) problems. A response surface generated by second-order polynomial regression analysis is updated dynamically by adding more design points, which are selected by Shifted Hammersley Method (SHM) and calculated by finite-element method (FEM). The updating stops when the accuracy requirement is satisfied, and optimized solutions of the preliminary design are derived simultaneously. The optimal design level is modulated through changing the level of error tolerance. Based on the response surface of the preliminary design, a refined optimal design is added using multi-objective genetic algorithm (MOGA). The effectiveness of the proposed optimal design method is validated through a classic three-phase power TDO problem.

Comparable results of autologous and allogeneic haematopoietic stem cell transplantation for adults with Philadelphia-positive acute lymphoblastic leukaemia in first complete molecular remission: An analysis by the Acute Leukemia Working Party of the EBMT.

PubMed

Giebel, Sebastian; Labopin, Myriam; Potter, Michael; Poiré, Xavier; Sengeloev, Henrik; Socié, Gerard; Huynh, Anne; Afanasyev, Boris V; Schanz, Urs; Ringden, Olle; Kalhs, Peter; Beelen, Dietrich W; Campos, Antonio M; Masszi, Tamás; Canaani, Jonathan; Mohty, Mohamad; Nagler, Arnon

2018-06-01

Allogeneic haematopoietic stem cell transplantation (alloHSCT) is considered a standard treatment for patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) achieving complete remission after induction containing tyrosine kinase inhibitors (TKIs). We retrospectively compared results of myeloablative alloHSCT from either matched sibling donor (MSD) or unrelated donor (URD) with autologous (auto) HSCT for adults with Ph+ ALL in molecular remission, treated between 2007 and 2014. In univariate analysis, the incidence of relapse at 2 years was 47% after autoHSCT, 28% after MSD-HSCT and 19% after URD-HSCT (P = 0.0002). Respective rates of non-relapse mortality were 2%, 18%, and 22% (P = 0.001). The probabilities of leukaemia-free survival were 52%, 55% and 60% (P = 0.69), while overall survival rates were 70%, 70% and 69% (P = 0.58), respectively. In multivariate analysis, there was a trend towards increased risk of overall mortality after MSD-HSCT (hazard ratio [HR], 1.5, P = 0.12) and URD-HSCT (HR, 1.6, P = 0.08) when referred to autoHSCT. The use of total body irradiation (TBI)-based regimens was associated with reduced risk of relapse (HR, 0.65, P = 0.02) and overall mortality (HR, 0.67, P = 0.01). In the era of TKIs, outcomes of myeloablative autoHSCT and alloHSCT for patients with Ph+ ALL in first molecular remission are comparable. Therefore, autoHSCT appears to be an attractive treatment option potentially allowing for circumvention of alloHSCT sequelae. Irrespective of the type of donor, TBI-based regimens should be considered the preferable type of conditioning for Ph+ ALL. Copyright © 2018 Elsevier Ltd. All rights reserved.

Strange Bedfellows No More: How Integrated Stem-Cell Transplantation and Palliative Care Programs Can Together Improve End-of-Life Care.

PubMed

Levine, Deena R; Baker, Justin N; Wolfe, Joanne; Lehmann, Leslie E; Ullrich, Christina

2017-09-01

In the intense, cure-oriented setting of hematopoietic stem-cell transplantation (HSCT), delivery of high-quality palliative and end-of-life care is a unique challenge. Although HSCT affords patients a chance for cure, it carries a significant risk of morbidity and mortality. During HSCT, patients usually experience high symptom burden and a significant decrease in quality of life that can persist for long periods. When morbidity is high and the chance of cure remote, the tendency after HSCT is to continue intensive medical interventions with curative intent. The nature of the complications and overall condition of some patients may render survival an unrealistic goal and, as such, continuation of artificial life-sustaining measures in these patients may prolong suffering and preclude patient and family preparation for end of life. Palliative care focuses on the well-being of patients with life-threatening conditions and their families, irrespective of the goals of care or anticipated outcome. Although not inherently at odds with HSCT, palliative care historically has been rarely offered to HSCT recipients. Recent evidence suggests that HSCT recipients would benefit from collaborative efforts between HSCT and palliative care services, particularly when initiated early in the transplantation course. We review palliative and end-of-life care in HSCT and present models for integrating palliative care into HSCT care. With open communication, respect for roles, and a spirit of collaboration, HSCT and palliative care can effectively join forces to provide high-quality, multidisciplinary care for these highly vulnerable patients and their families.

Early Improvement in Marrow Fibrosis Following Haploidentical Stem Cell Transplantation for a Patient with Myelodysplastic Syndrome with Bone Marrow Fibrosis

PubMed Central

Takahashi, Shuichiro; Tsumanuma, Riko; Aizawa, Keiko; Osakabe, Mitsumasa; Maeda, Kunihiko; Omoto, Ejiro

2016-01-01

The prognosis for myelodysplastic syndrome with bone marrow fibrosis (MDS-F) is worse than the prognosis of MDS without fibrosis. Hematopoietic stem cell transplantation (HSCT) is the only curative therapy; however, the indications and the procedures involved in HSCT remain unclear. We herein describe a 69-year-old Japanese man with MDS-F who received haploidentical HSCT and post-transplantation cyclophosphamide. Although the first HSCT resulted in secondary graft failure, the second HSCT using PTCy led to successful engraftment after early improvement in fibrosis. Since the incidence of graft failure is high in myelofibrosis patients, a secondary HSCT using PTCy may be successful if employed. PMID:27853082

Risk factor analysis of bloodstream infection in pediatric patients after hematopoietic stem cell transplantation.

PubMed

Sarashina, Takeo; Yoshida, Makoto; Iguchi, Akihiro; Okubo, Hitoshi; Toriumi, Naohisa; Suzuki, Daisuke; Sano, Hirozumi; Kobayashi, Ryoji

2013-01-01

Bloodstream infection (BSI) is a recognized cause of morbidity and mortality in children after hematopoietic stem cell transplantation (HSCT). However, there are limited reports on BSI after HSCT in pediatric patients in multiple centers. This study was a retrospective cohort analysis of consecutive patients who underwent allogeneic and autologous HSCT at the Department of Paediatrics, Hokkaido University Hospital, between 1988 and 2009; the Department of Paediatrics, Sapporo Hokuyu Hospital, between 2007 and 2009; and the Department of Paediatrics, Asahikawa Medical University, between 1989 and 2009. A total of 277 patients underwent HSCT during the study period. In this multicenter analysis, cases of BSI after HSCT were recorded in the early posttransplant period (within the first 100 d), and BSI was observed in 24 of 277 HSCT patients. Multivariate analysis showed that nonmalignant disease was an independent factor associated with BSI after HSCT (hazard ratio 6.3 for aplastic anemia or Wiskott-Aldrich syndrome patients; confidence interval, 1.4-12.8; P = 0.012). We conclude that aplastic anemia and Wiskott-Aldrich syndrome were the novel risk factors for BSI in pediatric patients after HSCT.

Multipoint to multipoint routing and wavelength assignment in multi-domain optical networks

NASA Astrophysics Data System (ADS)

Qin, Panke; Wu, Jingru; Li, Xudong; Tang, Yongli

2018-01-01

In multi-point to multi-point (MP2MP) routing and wavelength assignment (RWA) problems, researchers usually assume the optical networks to be a single domain. However, the optical networks develop toward to multi-domain and larger scale in practice. In this context, multi-core shared tree (MST)-based MP2MP RWA are introduced problems including optimal multicast domain sequence selection, core nodes belonging in which domains and so on. In this letter, we focus on MST-based MP2MP RWA problems in multi-domain optical networks, mixed integer linear programming (MILP) formulations to optimally construct MP2MP multicast trees is presented. A heuristic algorithm base on network virtualization and weighted clustering algorithm (NV-WCA) is proposed. Simulation results show that, under different traffic patterns, the proposed algorithm achieves significant improvement on network resources occupation and multicast trees setup latency in contrast with the conventional algorithms which were proposed base on a single domain network environment.

Hematopoietic Stem Cell Transplantation for Progressive Combined Immunodeficiency and Lymphoproliferation in Activated PI3K Syndrome Type 1.

PubMed

Okano, Tsubasa; Imai, Kohsuke; Tsujita, Yuki; Mitsuiki, Noriko; Yoshida, Kenichi; Kamae, Chikako; Honma, Kenichi; Mitsui-Sekinaka, Kanako; Sekinaka, Yujin; Kato, Tamaki; Hanabusa, Katsuyuki; Endo, Eri; Takashima, Takehiro; Hiroki, Haruka; Yeh, Tzu-Wen; Tanaka, Keisuke; Nagahori, Masakazu; Tsuge, Ikuya; Bando, Yuki; Iwasaki, Fuminori; Shikama, Yoshiaki; Inoue, Masami; Kimoto, Tomiko; Moriguchi, Naohiko; Yuza, Yuki; Kaneko, Takashi; Suzuki, Kyoko; Matsubara, Tomoyo; Maruo, Yoshihiro; Kunitsu, Tomoaki; Waragai, Tomoko; Sano, Hideki; Hashimoto, Yuko; Tasaki, Kazuhiro; Suzuki, Osamu; Shirakawa, Toshihiko; Kato, Motohiro; Uchiyama, Toru; Ishimura, Masataka; Tauchi, Tetsuzo; Yagasaki, Hiroshi; Jou, Shiann-Tarng; Yu, Hsin-Hui; Kanegane, Hirokazu; Kracker, Sven; Durandy, Anne; Kojima, Daiei; Muramatsu, Hideki; Wada, Taizo; Inoue, Yuzaburo; Takada, Hidetoshi; Kojima, Seiji; Ogawa, Seishi; Ohara, Osamu; Nonoyama, Shigeaki; Morio, Tomohiro

2018-05-17

Activated phosphatidylinositol-3-OH kinase-delta (PI3Kδ) syndrome type 1 (APDS1) is a recently described primary immunodeficiency syndrome characterized by recurrent respiratory infections, lymphoid hyperplasia, and herpesviridae infections due to germline gain-of-function mutations of PIK3CD. Hematopoietic stem cell transplantation (HSCT) may be considered to ameliorate progressive immunodeficiency and associated malignancy, but appropriate indications, method, and outcomes of HSCT for APDS1 remain undefined. Our objective was to analyze the clinical manifestations, laboratory findings, prognosis, and treatment of APDS1 and explore appropriate indications and methods of HSCT. We retrospectively reviewed the medical records of cohorts undergoing HSCT at collaborating facilities. Thirty-year overall survival was 86.1%, but event-free survival was 39.6%. Life-threatening events, such as severe infections or lymphoproliferation, were frequent in childhood and adolescence, and were common indications for HSCT. Nine patients underwent HSCT with fludarabine-based reduced intensity conditioning (RIC). Seven patients survived after frequent adverse complications and engraftment failure. Most symptoms improved after HSCT. Patients with APDS1 showed variable clinical manifestations. Life-threatening progressive combined immunodeficiency and massive lymphoproliferation were common indications for HSCT. Fludarabine-based RIC-HSCT ameliorated clinical symptoms, but transplant-related complications were frequent, including graft failure. Copyright © 2018. Published by Elsevier Inc.

Evaluation of the immune status against measles, mumps, and rubella in adult allogeneic hematopoietic stem cell transplantation recipients.

PubMed

Kawamura, Koji; Yamazaki, Rie; Akahoshi, Yu; Nakano, Hirofumi; Ugai, Tomotaka; Wada, Hidenori; Yamasaki, Ryoko; Ishihara, Yuko; Sakamoto, Kana; Ashizawa, Masahiro; Sato, Miki; Terasako-Saito, Kiriko; Kimura, Shun-ichi; Kikuchi, Misato; Nakasone, Hideki; Kanda, Junya; Kako, Shinichi; Tanihara, Aki; Nishida, Junji; Kanda, Yoshinobu

2015-03-01

Previous studies have shown that most patients lose immunity to measles, mumps, and rubella (MMR) during long-term follow-up after allogeneic hematopoietic stem cell transplantation (HSCT), and immunizations against them have been investigated. However, these previous studies mainly targeted pediatric patients and information in adult patients is still insufficient. We evaluated the immunity to MMR in 45 adult allogeneic HSCT patients. None of these patients received vaccination after HSCT. The seropositive rates at six years after allogeneic HSCT were estimated to be less than 44% for measles, less than 10% for mumps, and less than 36% for rubella. Thirteen of the 16 female patients who were 16-39 years old were negative or equivocal for rubella. Patients who developed grade II-IV acute graft-versus-host disease tended to become seronegative for measles and rubella at two years after HSCT, although the difference was not statistically significant. This study showed that most adult patients lost immunity to MMR after allogeneic HSCT. Although we did not evaluate the safety and efficacy of vaccination in this study, most HSCT guidelines recommend vaccination for HSCT recipients without active chronic graft-versus-host disease or ongoing immunosuppressive therapy at 24 months after HSCT. Immunization against rubella is especially important for female patients of reproductive age. Further studies will be necessary to evaluate the effect of vaccination on the antibody response in adult allogeneic HSCT recipients.

Accelerated bone mass senescence after hematopoietic stem cell transplantation.

PubMed

Serio, B; Pezzullo, L; Fontana, R; Annunziata, S; Rosamilio, R; Sessa, M; Giudice, V; Ferrara, I; Rocco, M; De Rosa, G; Ricci, P; Tauchmanovà, L; Montuori, N; Selleri, C

2013-01-01

Osteoporosis and avascular necrosis (AVN) are long-lasting and debilitating complications of hematopoietic stem cell transplantation (HSCT). We describe the magnitude of bone loss, AVN and impairment in osteogenic cell compartment following autologous (auto) and allogeneic (allo) HSCT, through the retrospective bone damage revaluation of 100 (50 auto- and 50 allo-HSCT) long-term survivors up to 15 years after transplant. Current treatment options for the management of these complications are also outlined. We found that auto- and allo-HSCT recipients show accelerated bone mineral loss and micro-architectural deterioration during the first years after transplant. Bone mass density (BMD) at the lumbar spine, but not at the femur neck, may improve in some patients after HSCT, suggesting more prolonged bone damage in cortical bone. Phalangeal BMD values remained low for even more years, suggesting persistent bone micro-architectural alterations after transplant. The incidence of AVN was higher in allo-HSCT recipients compared to auto-HSCT recipients. Steroid treatment length, but not its cumulative dose was associated with a higher incidence of bone loss. Allo-HSCT recipients affected by chronic graft versus host disease seem to be at greater risk of continuous bone loss and AVN development. Reduced BMD and higher incidence of AVN was partly related to a reduced regenerating capacity of the normal marrow osteogenic cell compartment. Our results suggest that all patients after auto-HSCT and allo-HSCT should be evaluated for their bone status and treated with anti-resorptive therapy as soon as abnormalities are detected.

Treatment of adult ALL with central nervous system involvement at diagnosis using autologous and allogeneic transplantation: a study from the Société Française de Greffe de Moelle et de Thérapie Cellulaire.

PubMed

Chantepie, S P; Mohty, M; Tabrizi, R; Robin, M; Deconinck, E; Buzyn, A; Contentin, N; Raus, N; Lhéritier, V; Reman, O

2013-05-01

To assess the role of hematopoietic SCT (HSCT) in adult ALL patients with central nervous system involvement at diagnosis, we retrospectively analyzed 90 patients who underwent autologous HSCT (auto-HSCT group; n=27) or allogeneic HSCT (allo-HSCT group; n=63) and reported to the Société Française de Greffe de Moelle et de Thérapie Cellulaire registry between 1994 and 2008. At the time of transplantation, 67 patients (74%) were in first CR, 15 (17%) in CR2 and 8 (9%) with progressive disease. The 5-year probabilities of overall survival (OS) and disease-free survival (DFS) were 52% and 46% for the allo-HSCT and 37% and 33% for the auto-HSCT groups, respectively (P=NS). The TRM at 5 years was 29.8% for the allo-HSCT group and 3.7% for the auto-HSCT group. Using univariate analysis, a time for transplantation of <12 months, the remission status at transplantation, the use of high-dose TBI and the number of the transplant were all determined to be prognostic factors for improved DFS and OS probabilities. Using multivariate analysis, we demonstrated that both the use of high-dose TBI and the remission status had a favorable impact on OS. Although the DFS and OS were better in the allo-HSCT group, the differences were not statistically significant.

Red cell alloimmunisation in oncology patients: A study from eastern India.

PubMed

Dhar, Supriya; Basu, Sabita

2015-06-01

Red cell alloimmunisation is an important complication in multi-transfused patients with haematologic and surgical malignancies. Antibody screening with identification is necessary to ensure transfusion safety. Data on the prevalence of alloimmunisation in oncology patients is limited. In this study we assessed multitransfused haematology-oncology patients for red cell alloimmunisation. This was a retrospective analysis undertaken to assess the alloantibody prevalence and determine the antibody specificity. Retrospective analysis of antibody screening data was done for haematopoietic stem cell transplant (HSCT) patients as well as surgical oncology patients, from April 2013 to May 2014. This included the antibody screening done prior to surgery, antibody screening prior to HSCT and any antibody screening performed for these patients at cross match. Antibody screening was done using the three cell panel (surgiscreen) and if positive, further identification performed using the 11 cell panel (Resolve Panel A). If the antibody screen (three cell panel) was positive, an autocontrol was performed using reverse diluent (Ortho Biovue System) card. Patients with autoantibodies were excluded from this study. Our overall red cell alloimmunisation rate was 2.5%. Alloimmunisation rate among HSCT transplant patients was 1.6% as compared to the 2.4% in patients with solid organ malignancies. Keeping in view the low alloimmunisation rate, the justification of repeating antibody screening 72 hours post transfusion in this category of patients needs to be re-assessed. Copyright © 2015. Published by Elsevier Ltd.

System Analyses of Pneumatic Technology for High Speed Civil Transport Aircraft

NASA Technical Reports Server (NTRS)

Mavris, Dimitri N.; Tai, Jimmy C.; Kirby, Michelle M.; Roth, Bryce A.

1999-01-01

The primary aspiration of this study was to objectively assess the feasibility of the application of a low speed pneumatic technology, in particular Circulation Control (CC) to an HSCT concept. Circulation Control has been chosen as an enabling technology to be applied on a generic High Speed Civil Transport (HSCT). This technology has been proven for various subsonic vehicles including flight tests on a Navy A-6 and computational application on a Boeing 737. Yet, CC has not been widely accepted for general commercial fixed-wing use but its potential has been extensively investigated for decades in wind tunnels across the globe for application to rotorcraft. More recently, an experimental investigation was performed at Georgia Tech Research Institute (GTRI) with application to an HSCT-type configuration. The data from those experiments was to be applied to a full-scale vehicle to assess the impact from a system level point of view. Hence, this study attempted to quantitatively assess the impact of this technology to an HSCT. The study objective was achieved in three primary steps: 1) Defining the need for CC technology; 2) Wind tunnel data reduction; 3) Detailed takeoff/landing performance assessment. Defining the need for the CC technology application to an HSCT encompassed a preliminary system level analysis. This was accomplished through the utilization of recent developments in modern aircraft design theory at Aerospace Systems Design Laboratory (ASDL). These developments include the creation of techniques and methods needed for the identification of technical feasibility show stoppers. These techniques and methods allow the designer to rapidly assess a design space and disciplinary metric enhancements to enlarge or improve the design space. The takeoff and landing field lengths were identified as the concept "show-stoppers". Once the need for CC was established, the actual application of data and trends was assessed. This assessment entailed a reduction of the wind tunnel data from the experiments performed by Mr. Bob Englar at the GTRI. Relevant data was identified and manipulated based on the required format of the analysis tools utilized. Propulsive, aerodynamic, duct sizing, and vehicle sizing investigations were performed and information supplied to a detailed takeoff and landing tool, From the assessments, CC was shown to improve the low speed performance metrics, which were previously not satisfied. An HSCT with CC augmentation does show potential for full-scale application. Yet, an economic assessment of an HSCT with and without CC showed that a moderate penalty was incurred from the increased RDT&E costs associated with developing the CC technology and slight increases in empty weight.

The Cost of Hematopoietic Stem-Cell Transplantation in the United States

PubMed Central

Broder, Michael S.; Quock, Tiffany P.; Chang, Eunice; Reddy, Sheila R.; Agarwal-Hashmi, Rajni; Arai, Sally; Villa, Kathleen F.

2017-01-01

Background Hematopoietic stem-cell transplantation (HSCT) requires highly specialized, resource-intensive care. Myeloablative conditioning regimens used before HSCT generally require inpatient stays and are more intensive than other preparative regimens, and may therefore be more costly. Objective To estimate the costs associated with inpatient HSCT according to the type of the conditioning regimen used and other potential contributors to the overall cost of the procedure. Method We used data from the Truven Health MarketScan insurance claims database to analyze healthcare costs for pediatric (age <18 years) and adult (age ≥18 years) patients who had autologous or allogeneic inpatient HSCT between January 1, 2010, and September 23, 2013. We developed an algorithm to determine whether conditioning regimens were myeloablative or nonmyeloablative/reduced intensity. Results We identified a sample of 1562 patients who had inpatient HSCT during the study period for whom the transplant type and the conditioning regimen were determinable: 398 patients had myeloablative allogeneic HSCT; 195 patients had nonmyeloablative/reduced-intensity allogeneic HSCT; and 969 patients had myeloablative autologous HSCT. The median total healthcare cost at 100 days was $289,283 for the myeloablative allogeneic regimen cohort compared with $253,467 for the nonmyeloablative/reduced-intensity allogeneic regimen cohort, and $140,792 for the myeloablative autologous regimen cohort. The mean hospital length of stay for the index (first claim of) HSCT was 35.6 days in the myeloablative allogeneic regimen cohort, 26.6 days in the nonmyeloablative/reduced-intensity allogeneic cohort, and 21.8 days in the myeloablative autologous regimen cohort. Conclusion Allogeneic HSCT was more expensive than autologous HSCT, regardless of the regimen used. Myeloablative conditioning regimens led to higher overall costs than nonmyeloablative/reduced-intensity regimens in the allogeneic HSCT cohort, indicating a greater cost burden associated with inpatient services for higher-intensity preparative conditioning regimens. Pediatric patients had higher costs than adult patients. Future research should involve validating the algorithm for identifying conditioning regimens using clinical data. PMID:29263771

Induction of tolerance and prolongation of islet allograft survival by syngeneic hematopoietic stem cell transplantation in mice.

PubMed

Yang, Shi-feng; Xue, Wu-jun; Lu, Wan-hong; Xie, Li-yi; Yin, Ai-ping; Zheng, Jin; Sun, Ji-ping; Li, Yang

2015-10-01

Syngeneic or autologous hematopoietic stem cells transplantation (HSCT) has been proposed to treat autoimmune diseases because of its immunosuppressive and immunomodulatory effects, which can also contribute to posttransplant antirejection therapy. In this study, we explored the tolerogenic effect of syngeneic HSCT on prolonging islet allograft survival. C57BL/6 mice received syngeneic HSCT plus preconditioning with sublethal irradiation. Then islets of BALB/c mice were transplanted into the renal subcapsular of C57BL/6 mice after chemically induced into diabetes. HSCT mice exhibited improved islet allograft survival and increased serum insulin compared to control mice. Islet allografts of HSCT mice displayed lower level lymphocyte infiltration and stronger insulin staining than control mice. T cells of HSCT mice proliferated poorly in response to allogeneic splenocytes compared to control mice. Mice appeared reversed interferon-γ (IFN-γ)/interleukin-4 (IL-4) ratio to a Th2 immune deviation after syngeneic HSCT. The percentage of CD8(+) T cells was lower, while percentage of CD4(+)CD25(+)Foxp3(+) T regulatory cells (Tregs) was higher in HSCT mice than control mice. HSCT mice showed higher percentage of CTLA-4(+) T cells and expression of CTLA-4 mRNA than control mice. Targeting of CTLA-4 by intraperitoneal injection of anti-CTLA-4 mAb abrogated the effect of syngeneic HSCT on prolonging islet allograft survival, inhibiting activity of T cells in response to alloantigen, promoting Th1 to Th2 immune deviation and up regulating CD4(+)CD25(+)Foxp3(+) Tregs. Syngeneic HSCT plus preconditioning of sublethal irradiation induces tolerance and improves islet allograft survival in fully mismatched mice model. Th1 to Th2 immune deviation, increased CD4(+)CD25(+)Foxp3(+) Tregs and up-regulation of CTLA-4 maybe contribute to the tolerogenic effect induced by syngeneic HSCT. Copyright © 2015 Elsevier B.V. All rights reserved.

[Evaluation of selected endocrine complications in patients treated with auto- and allo-haematopoietic stem cell transplantation].

PubMed

Niedzielska, Ewa; Wójcik, Dorota; Barg, Ewa; Pietras, Wojciech; Sega-Pondel, Dorota; Doroszko, Adrian; Niedzielska, Małgorzata; Skarzyńska, Małgorzata; Chybicka, Alicja

2008-01-01

The aim of this study was to evaluate the endocrine complications, in particular disorders of growth and thyroid function and glucose metabolism dysfunctions in patients treated with allo- and auto-haematopoietic stem cell transplantation (HSCT). The investigated group consisted of: I. 16 patients after auto-HSCT (6 girls, 10 boys) aged 3-20 years (average 10,8+/-) because of acute myelogenous leukaemia (n=5), non Hodgkin lymphoma (n=3), neuroblastoma (n=3), embryonal cancer (n=2), medulloblastoma (n=1), Ewing's sarcoma/PNET (n=1), hyper eosinophilic syndrome (n=1). High dose chemiotherapy (HDC/T) included: BU/MEL (busulfan/melfalan) (n=7), BEAM (carmustine, eteposide, cytosine arabinose, melfalan) (n=3). II. 30 patients after allo-HSCT (20 girls, 10 boys) aged 3-17 years (average 9,56). Indication for HSCT was acute lymphoblastic leukaemia (n=11), acute myelogenous leukaemia (n=5), chronic myeloid leukaemia-CML (n=6), myelodysplastic syndromes (n=2), non Hodgkin lymphoma (n=1), juvenile myelomonocytic leukemia (n=1), severe aplastic anaemia (n=1), Blackfan-Diamond anaemia (n=1), severe combined immune deficiency (n=1), rhabdomyosarcoma (n=1). The patients underwent the following types of transplantation: HSCT of matched sibling donor (n=13), HSCT of matched unrelated donor (n=11) and HLA-mismatched related donor (n=6). The preparative regimens consisted of HDC/T usually BU/MEL (n=3); BU/CY/VP (busulfan, cyclophosphamide, etoposide) (6); BU/CY/ATG (anti-thymocyte globulin) (n=5), VP/ATG/TBI (total body irradiation) (n=3). 19 children received CI (cranial irradiation) prior to grafting: auto-HSCT (n=6) and allo-HSCT (n=13) and 6 patients underwent TBI. 18 children received high steroid doses at least 28 days before transplant, 4 patients in the auto-HSCT group, and in the allo-HSCT group 14 patients before and 20 after HSCT procedure. The analysis of thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), hemoglobin A1c (HbA1c), prolactine (PRL), oral glucose tolerance test, growth hormone (GH test) and thyrotropin releasing hormone (TRH) test was performed in each case. Hypothyroidism was found in 5 patients (3 after allo-HSCT, 2 after auto-HSCT). Thyroid hormone substitution was applied. No case of hyperthyroidism was diagnosed. Growth deficit was found in 8 patients (6 girls, 2 boys) between 13 to 70 months after allo-transplantation (average 36 months). Three children from the above group received CI. Growth hormone substitution was applied in 1 girl (ALL, HLA MM REL, CI). An impaired excretion of GH after stimulation was diagnosed in 14 pts (10 after allo-HSCT, 4 after auto-HSCT). The growth process should still be observed in this subgroup. Glucose intolerance was found in 7 patients: in 4 treated with auto-HSCT and in 3 after allo-HSCT. Diabetes mellitus was diagnosed in none of them. An impaired glucose tolerance curve with increased excretion of insulin was diagnosed in 12 children. Early endocrinological care is necessary in patients treated both with auto-HSCT and allo-HSCT due to high risk of hormonal disorders.

Multi-point optimization of recirculation flow type casing treatment in centrifugal compressors

NASA Astrophysics Data System (ADS)

Tun, Min Thaw; Sakaguchi, Daisaku

2016-06-01

High-pressure ratio and wide operating range are highly required for a turbocharger in diesel engines. A recirculation flow type casing treatment is effective for flow range enhancement of centrifugal compressors. Two ring grooves on a suction pipe and a shroud casing wall are connected by means of an annular passage and stable recirculation flow is formed at small flow rates from the downstream groove toward the upstream groove through the annular bypass. The shape of baseline recirculation flow type casing is modified and optimized by using a multi-point optimization code with a metamodel assisted evolutionary algorithm embedding a commercial CFD code CFX from ANSYS. The numerical optimization results give the optimized design of casing with improving adiabatic efficiency in wide operating flow rate range. Sensitivity analysis of design parameters as a function of efficiency has been performed. It is found that the optimized casing design provides optimized recirculation flow rate, in which an increment of entropy rise is minimized at grooves and passages of the rotating impeller.

SiC Recession Due to SiO2 Scale Volatility Under Combustor Conditions

NASA Technical Reports Server (NTRS)

Robinson, Raymond Craig

1997-01-01

One of today's most important and challenging technological problems is the development of advanced materials and processes required to design and build a fleet of supersonic High Speed Civil Transport (HSCT) airliners, a follow-up to the Concorde SST. The innovative combustor designs required for HSCT engines will need high-temperature materials with long-term environmental stability. Higher combustor liner temperatures than today's engines and the need for lightweight materials will require the use of advanced ceramic-matrix composites (CMC's) in hot-section components. The HSCT is just one example being used to demonstrate the need for such materials. This thesis evaluates silicon carbide (SiC) as a potential base material for HSCT and other similar applications. Key issues are the environmental durability for the materials of interest. One of the leading combustor design schemes leads to an environment which will contain both oxidizing and reducing gas mixtures. The concern is that these environments may affect the stability of the silica (SiO2) scale on which SiC depends for environmental protection. A unique High Pressure Burner Rig (HPBR) was developed to simulate the combustor conditions of future gas turbine engines, and a series of tests were conducted on commercially available SiC material. These tests are intended as a feasibility study for the use of these materials in applications such as the HSCT. Linear weight loss and surface recession of the SiC is observed as a result of SiO2 volatility for both fuel-lean and fuel-rich gas mixtures. These observations are compared and agree well with thermogravimetric analysis (TGA) experiments. A strong Arrhenius-type temperature dependence exists. In addition, the secondary dependencies of pressure and gas velocity are defined. As a result, a model is developed to enable extrapolation to points outside the experimental space of the burner rig, and in particular, to potential gas turbine engine conditions.

Research on Intelligent Control System of DC SQUID Magnetometer Parameters for Multi-channel System

NASA Astrophysics Data System (ADS)

Chen, Hua; Yang, Kang; Lu, Li; Kong, Xiangyan; Wang, Hai; Wu, Jun; Wang, Yongliang

2018-07-01

In a multi-channel SQUID measurement system, adjusting device parameters to optimal condition for all channels is time-consuming. In this paper, an intelligent control system is presented to determine the optimal working point of devices which is automatic and more efficient comparing to the manual one. An optimal working point searching algorithm is introduced as the core component of the control system. In this algorithm, the bias voltage V_bias is step scanned to obtain the maximal value of the peak-to-peak current value I_pp of the SQUID magnetometer modulation curve. We choose this point as the optimal one. Using the above control system, more than 30 weakly damped SQUID magnetometers with area of 5 × 5 mm^2 or 10 × 10 mm^2 are adjusted and a 36-channel magnetocardiography system perfectly worked in a magnetically shielded room. The average white flux noise is 15 {μ Φ }_0/Hz^{1/2}.

Research on Intelligent Control System of DC SQUID Magnetometer Parameters for Multi-channel System

NASA Astrophysics Data System (ADS)

Chen, Hua; Yang, Kang; Lu, Li; Kong, Xiangyan; Wang, Hai; Wu, Jun; Wang, Yongliang

2018-03-01

In a multi-channel SQUID measurement system, adjusting device parameters to optimal condition for all channels is time-consuming. In this paper, an intelligent control system is presented to determine the optimal working point of devices which is automatic and more efficient comparing to the manual one. An optimal working point searching algorithm is introduced as the core component of the control system. In this algorithm, the bias voltage V_bias is step scanned to obtain the maximal value of the peak-to-peak current value I_pp of the SQUID magnetometer modulation curve. We choose this point as the optimal one. Using the above control system, more than 30 weakly damped SQUID magnetometers with area of 5 × 5 mm^2 or 10 × 10 mm^2 are adjusted and a 36-channel magnetocardiography system perfectly worked in a magnetically shielded room. The average white flux noise is 15 μΦ_0/Hz^{1/2}.

Application of Probabilistic Methods for the Determination of an Economically Robust HSCT Configuration

NASA Technical Reports Server (NTRS)

Mavris, Dimitri N.; Bandte, Oliver; Schrage, Daniel P.

1996-01-01

This paper outlines an approach for the determination of economically viable robust design solutions using the High Speed Civil Transport (HSCT) as a case study. Furthermore, the paper states the advantages of a probability based aircraft design over the traditional point design approach. It also proposes a new methodology called Robust Design Simulation (RDS) which treats customer satisfaction as the ultimate design objective. RDS is based on a probabilistic approach to aerospace systems design, which views the chosen objective as a distribution function introduced by so called noise or uncertainty variables. Since the designer has no control over these variables, a variability distribution is defined for each one of them. The cumulative effect of all these distributions causes the overall variability of the objective function. For cases where the selected objective function depends heavily on these noise variables, it may be desirable to obtain a design solution that minimizes this dependence. The paper outlines a step by step approach on how to achieve such a solution for the HSCT case study and introduces an evaluation criterion which guarantees the highest customer satisfaction. This customer satisfaction is expressed by the probability of achieving objective function values less than a desired target value.

The 1995 scientific assessment of the atmospheric effects of stratospheric aircraft

NASA Technical Reports Server (NTRS)

Stolarski, Richard S.; Baughcum, Steven L.; Brune, William H.; Douglass, Anne R.; Fahey, David W.; Friedl, Randall R.; Liu, Shaw C.; Plumb, R. Alan; Poole, Lamont R.; Wesoky, Howard L.

1995-01-01

This report provides a scientific assessment of our knowledge concerning the impact of proposed high-speed civil transport (HSCT) aircraft on the atmosphere. It comes at the end of Phase 1 of the Atmospheric Effects of Stratospheric Aircraft element of the NASA High-Speed Research Program. The fundamental problem with stratospheric flight is that pollutant residence times are long because the stratosphere is a region of permanent temperature inversion with stable stratification. Using improved two-dimensional assessment models and detailed fleet emissions scenarios, the assessment examines the possible impact of the range of effluents from aircraft. Emphasis is placed on the effects of NO(x) and H2O on the atmospheric ozone content. Measurements in the plume of an in-flight Concorde supersonic transport indicated a large number of small particles. These measurements, coupled with model sensitivity studies, point out the importance of obtaining a more detailed understanding of the fate of sulfur in the HSCT exhaust. Uncertainties in the current understanding of the processes important for determining the overall effects of HSCT's on the atmosphere are discussed and partially quantified. Research directions are identified to improve the quantification of uncertainties and to reduce their magnitude.

The budget impact and cost-effectiveness of defibrotide for treatment of veno-occlusive disease with multi-organ dysfunction in patients post-hematopoietic stem cell transplant.

PubMed

Veenstra, David L; Guzauskas, Gregory F; Villa, Kathleen F; Boudreau, Denise M

2017-05-01

A Phase-3 study of defibrotide compared with historical controls demonstrated a 23% improvement in 100-day survival post-hematopoietic stem cell transplantation (HSCT) among patients with veno-occlusive disease with multi-organ dysfunction (VOD with MOD). To estimate the budget impact and cost-effectiveness of introducing defibrotide to a transplant center. The authors developed a budget impact model from the perspective of a bone-marrow transplant center. It was estimated that 2.3% of adults and 4.2% of children would develop VOD with MOD following HSCT based on a retrospective hospital database analysis and the effect that treating patients with defibrotide would have on costs for adult and pediatric centers was estimated. A cost-utility analysis (CUA) was also developed to capture the long-term cost-effectiveness of defibrotide. Projected life expectancies in the two groups were estimated based on trial data, transplant registry data, studies of long-term survival among HSCT patients, and US population life-tables. There was an estimated 3% increase ($330,706) per year in total adult transplantation center costs associated with adopting defibrotide, and a <1% increase ($106,385) for pediatric transplant centers, assuming 100 transplants per year. In the CUA, the lifetime increase in cost per patient was $106,928, life expectancy increased by 3.74 years, and quality-adjusted life-years (QALYs) increased by 2.24. The incremental cost-effectiveness ratio (ICER) was $47,736 per QALY gained; 88% probability defibrotide was cost-effective at a $100,000/QALY threshold. The budget impact of defibrotide for a transplant center is relatively modest compared to the overall cost of transplantation. Defibrotide provides an important survival advantage for VOD with MOD patients, and the life years gained lead to defibrotide being highly cost-effective.

Donor and recipient chemokine receptor CCR5 genotype is associated with survival after bone marrow transplantation

PubMed Central

McDermott, David H.; Conway, Susan E.; Wang, Tao; Ricklefs, Stacy M.; Agovi, Manza A.; Porcella, Stephen F.; Tran, Huong Thi Bich; Milford, Edgar; Spellman, Stephen

2010-01-01

Despite continual improvement, morbidity and mortality after hematopoietic stem cell transplantation (HSCT) remain high. The importance of chemokines in HSCT lies in their regulation of immune responses that determine transplantation outcomes. We investigated the role of recipient and donor chemokine system gene polymorphisms by using a candidate gene approach on the incidence of graft-versus-host disease and posttransplantation outcomes in 1370 extensively human leukocyte antigen–matched, unrelated donor-recipient pairs by using multivariate Cox regression models. Our analysis identified that recipients homozygous for a common CCR5 haplotype (H1/H1) had better disease-free survival (DFS; P = .005) and overall survival (P = .021). When the same genotype of both the donor and recipient were considered in the models, a highly significant association with DFS and overall survival was noted (P < .001 and P = .007, respectively) with absolute differences in survival of up to 20% seen between the groups at 3 years after transplantation (50% DFS for pairs with recipient CCR5 H1/H1 vs 30% for pairs with donor CCR5 H1/H1). This finding suggests that donor and/or recipient CCR5 genotypes may be associated with HSCT outcome and suggests new diagnostic and therapeutic strategies for optimizing therapy. PMID:20068218

Virus reactivations after autologous hematopoietic stem cell transplantation detected by multiplex PCR assay.

PubMed

Inazawa, Natsuko; Hori, Tsukasa; Nojima, Masanori; Saito, Makoto; Igarashi, Keita; Yamamoto, Masaki; Shimizu, Norio; Yoto, Yuko; Tsutsumi, Hiroyuki

2017-02-01

Several studies have indicated that viral reactivations following allogeneic hematopoietic stem cell transplantation (allo-HSCT) are frequent, but viral reactivations after autologous HSCT (auto-HSCT) have not been investigated in detail. We performed multiplex polymerase chain reaction (PCR) assay to examine multiple viral reactivations simultaneously in 24 patients undergoing auto-HSCT between September 2010 and December 2012. Weekly whole blood samples were collected from pre- to 42 days post-HSCT, and tested for the following 13 viruses; herpes simplex virus 1 (HSV-1), HSV-2, varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), HHV-7, HHV-8, adeno virus (ADV), BK virus (BKV), JC virus (JCV), parvovirus B19 (B19V), and hepatitis B virus (HBV).  Fifteen (63%) patients had at least one type of viral reactivation. HHV6 (n = 10; 41.7%) was most frequently detected followed by EBV (n = 7; 29.2%). HHV-6 peaked on day 21 after HSCT and promptly declined. In addition, HBV, CMV, HHV7, and B19V were each detected in one patient. HHV6 reactivation was detected in almost half the auto-HSCT patients, which was similar to the incidence in allo-HSCT patients. The incidence of EBV was unexpectedly high. Viral infections in patients undergoing auto-HSCT were higher than previously reported in other studies. Although there were no particular complications of viral infection, we should pay attention to possible viral reactivations in auto-HSCT patients. J. Med. Virol. 89:358-362, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Clinical impact of sarcopenia and relevance of nutritional intake in patients before and after allogeneic hematopoietic stem cell transplantation.

PubMed

Tanaka, Shouichi; Imataki, Osamu; Kitaoka, Atsuo; Fujioka, Shuji; Hanabusa, Etsuyo; Ohbayashi, Yumiko; Uemura, Makiko; Arima, Nobuo; Yamamoto, Tetsuji

2017-06-01

We conducted a retrospective study to evaluate the effect of rehabilitation on minimizing sarcopenia during hematopoietic stem cell transplantation (HSCT) therapy. We developed a protocol to test for retention of physical function during HSCT. Muscle strength, muscle circumference, and muscle function before and after HSCT were measured. Consecutive patients with hematological malignancies who underwent HSCT treatment were recruited in this research. We included 34 patients (16 females, 18 males; median age, 51.5 years). Bodyweight significantly decreased after HSCT (p < 0.001). Nine females and three males had sarcopenia prior to allogeneic HSCT. After HSCT, bilateral hand grip strength and bilateral knee extensor strength decreased significantly. The total caloric intakes for pre-conditioning, during preparation regimen, and after transplant were 1709, 1024, and 1445 kcal, respectively, and were significantly attenuated in the post-transplant period. Serum albumin was significantly decreased in the final period. Conversely, C-reactive protein was slightly but significantly increased across the transplantation process. Multivariate regression analysis revealed that oral caloric intake after the transplantation period and sex were significantly related to muscle weakness (p = 0.033 and 0.036, respectively). Sarcopenia during HSCT was affected by oral caloric intake during the preparation regimen and after transplantation. Physical therapy in conjunction with nutritional therapy may help prevent weakness in HSCT recipients.

Epidemiology of Invasive Mold Infections in Allogeneic Stem Cell Transplant Recipients: Biological Risk Factors for Infection According to Time after Transplantation

PubMed Central

Garcia-Vidal, Carol; Upton, Arlo; Kirby, Katharine A.; Marr, Kieren A.

2009-01-01

Background Invasive mold infections (IMIs) are common in individuals who have undergone hematopoietic stem cell transplantation (HSCT). We sought to determine clinical and biological risk factors for different IMIs during each period (early and late) after allogeneic HSCT. Methods Cases of proven and probable IMI diagnosed in HSCT recipients at the Fred Hutchinson Cancer Research Center (Seattle, WA) from 1 January 1998 through 31 December 2002 were included. Survival was estimated with Kaplan-Meier curves, and Cox regression models were used for multivariable analyses. Results During the study period, 1248 patients underwent allogeneic HSCT; 163 (13.1%) received a diagnosis of probable or proven IMI. The majority of cases were caused by Aspergillus species (88%). The incidence of IMI caused by other molds remained low (<2%) over the 4-year study period. Risk factors for IMI early after HSCT and late after HSCT differed, with host variables (age) and transplant variables (human leukocyte antigen match) predominating as early risk factors and other clinical complications (graft-versus-host disease and cytomegalovirus disease) predominating later. Biological risk factors that were important during all periods included multiple cytopenias (neutropenia, lymphopenia, and monocytopenia) and iron overload. Conclusions Risk factors for invasive aspergillosis after allogeneic HSCT are multifactorial and differ according to timing after HSCT. Increased attention should be placed on understanding the immunopathogenesis of fungal disease after HSCT. PMID:18781877

High Speed Civil Transport (HSCT) Isolated Nacelle Transonic Boattail Drag Study and Results Using Computational Fluid Dynamics (CFD)

NASA Technical Reports Server (NTRS)

Midea, Anthony C.; Austin, Thomas; Pao, S. Paul; DeBonis, James R.; Mani, Mori

2005-01-01

Nozzle boattail drag is significant for the High Speed Civil Transport (HSCT) and can be as high as 25 percent of the overall propulsion system thrust at transonic conditions. Thus, nozzle boattail drag has the potential to create a thrust drag pinch and can reduce HSCT aircraft aerodynamic efficiencies at transonic operating conditions. In order to accurately predict HSCT performance, it is imperative that nozzle boattail drag be accurately predicted. Previous methods to predict HSCT nozzle boattail drag were suspect in the transonic regime. In addition, previous prediction methods were unable to account for complex nozzle geometry and were not flexible enough for engine cycle trade studies. A computational fluid dynamics (CFD) effort was conducted by NASA and McDonnell Douglas to evaluate the magnitude and characteristics of HSCT nozzle boattail drag at transonic conditions. A team of engineers used various CFD codes and provided consistent, accurate boattail drag coefficient predictions for a family of HSCT nozzle configurations. The CFD results were incorporated into a nozzle drag database that encompassed the entire HSCT flight regime and provided the basis for an accurate and flexible prediction methodology.

High Speed Civil Transport (HSCT) Isolated Nacelle Transonic Boattail Drag Study and Results Using Computational Fluid Dynamics (CFD)

NASA Technical Reports Server (NTRS)

Midea, Anthony C.; Austin, Thomas; Pao, S. Paul; DeBonis, James R.; Mani, Mori

1999-01-01

Nozzle boattail drag is significant for the High Speed Civil Transport (HSCT) and can be as high as 25% of the overall propulsion system thrust at transonic conditions. Thus, nozzle boattail drag has the potential to create a thrust-drag pinch and can reduce HSCT aircraft aerodynamic efficiencies at transonic operating conditions. In order to accurately predict HSCT performance, it is imperative that nozzle boattail drag be accurately predicted. Previous methods to predict HSCT nozzle boattail drag were suspect in the transonic regime. In addition, previous prediction methods were unable to account for complex nozzle geometry and were not flexible enough for engine cycle trade studies. A computational fluid dynamics (CFD) effort was conducted by NASA and McDonnell Douglas to evaluate the magnitude and characteristics of HSCT nozzle boattail drag at transonic conditions. A team of engineers used various CFD codes and provided consistent, accurate boattail drag coefficient predictions for a family of HSCT nozzle configurations. The CFD results were incorporated into a nozzle drag database that encompassed the entire HSCT flight regime and provided the basis for an accurate and flexible prediction methodology.

The ethics of a proposed study of hematopoietic stem cell transplant for children with "less severe" sickle cell disease.

PubMed

Nickel, Robert S; Hendrickson, Jeanne E; Haight, Ann E

2014-08-07

Hematopoietic stem cell transplant (HSCT) is the only cure for sickle cell disease (SCD). HSCT using an HLA-identical sibling donor is currently an acceptable treatment option for children with severe SCD, with expected HSCT survival >95% and event-free survival >85%. HSCT for children with less severe SCD (children who have not yet suffered overt disease complications or only had mild problems) is controversial. It is important to consider the ethical issues of a proposed study comparing HLA-identical sibling HSCT to best supportive care for children with less severe SCD. In evaluating the principles of nonmaleficence, respect for individual autonomy, and justice, we conclude that a study of HLA-identical sibling HSCT for all children with SCD, particularly hemoglobin SS and Sβ(0)-thalassemia disease, is ethically sound. Future work should explore the implementation of a large trial to help determine whether HSCT is a beneficial treatment of children with less severe SCD. © 2014 by The American Society of Hematology.

Improved outcome of children transplanted for high-risk leukemia by using a new strategy of cyclosporine-based GVHD prophylaxis.

PubMed

Bleyzac, N; Cuzzubbo, D; Rénard, C; Garnier, N; Dubois, V; Domenech, C; Goutagny, M-P; Plesa, A; Grardel, N; Goutelle, S; Janoly-Duménil, A; Bertrand, Y

2016-05-01

There is currently a major concern regarding the optimal immunosuppression therapy to be administered after hematopoietic stem cell transplantation (HSCT) to reduce both the toxicity of GvHD and the rate of relapse. We report the outcome of high-risk leukemia children transplanted with a new way of managing cyclosporine (CsA)-based GvHD prophylaxis. A total of 110 HSCT in 109 ALL or AML children who received CsA without mycophenolate or methotrexate in matched related as well as in matched or mismatched unrelated stem cell transplantation were included. CsA dosage regimens were individualized to obtain specific trough blood concentrations values. The incidences of grade I-II and III-IV acute GvHD were 69.1% and 1.8%, respectively, and 8.4% for chronic GvHD. GvHD was neither more frequent nor severe in unrelated than in related HSCT. GvHD occurred in 87% of patients with a mean CsA trough concentration ⩽120 ng/mL versus 43% with concentration >120 ng/mL (P<0.0001). Five-year disease-free survival (DFS) and overall survival were 78% and 83.6%, respectively. DFS was 76.9% for ALL and 80.4% for AML patients. There was no difference in DFS between matched siblings and matched unrelated or mismatched unrelated HSCT. DFS in patients with minimal residual disease (MRD) ⩾10(-3) and in those with MRD <10(-3) before SCT was comparable. Our results indicate that a GvHD prophylaxis regimen based on CsA without mycophenolate or methotrexate is safe and effective whatever the donor compatibility is. These results suggest that GvL effect may be enhanced by this strategy of GvHD prophylaxis.

Successful management of multilineage autoimmune cytopenia complicated with severe infection and deep vein thrombosis in a patient with Hodgkin lymphoma post-autologous hematopoietic stem cell transplantation.

PubMed

Hsu, Wan-Yi; Chiou, Shyh-Shin; Liao, Yu-Mei; Shu, Hsiu-Lan; Zeng, Yu-Sheng; Wong, Cheong-Chew; Lin, Pei-Chin

2016-02-01

Autoimmune cytopenia (AIHA, AITP or AIN) were uncommon paraneoplastic manifestations of HL and have been recognized in patients after HSCT with dismal outcome. We presented a case of 16-yr-old male with Hodgkin's lymphoma who developed severe AIC involving all three cell lineages after autologus bone marrow transplantation. No disease relapse was noted. Treatments with steroid, IVIG and immunosuppresants were in vain and the disease course was complicated with sepsis and deep vein thrombosis. Rituximab was administered along with broad-spectrum antibiotics and low-molecular weight heparin. The condition became stable and pancytopenia recovered after four doses of rituximab treatment. Severe multi-lineage AIC post HSCT is usually refractory to first-line treatment and difficult to manage. Second-line treatment, such as rituximab, and dedicated care for pancytopenia-induced or treatment-related complications may provide a better outcome. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Oral complaints and dental care of haematopoietic stem cell transplant patients: a qualitative survey of patients and their dentists.

PubMed

Bos-den Braber, Jacolien; Potting, Carin M J; Bronkhorst, Ewald M; Huysmans, Marie-Charlotte D N J M; Blijlevens, Nicole M A

2015-01-01

Little is known about the understanding of the oral and dental needs of haematopoietic stem cell transplant (HSCT) patients or about dentists' views and experiences regarding this patient group. This information is essential if we want to improve the standard of peri-HSCT dental care. The primary objective of this qualitative survey was to explore the following: (1) The understanding of dental care pre- and post-HSCT (2) The subjective oral complaints of HSCT patients both short- and long-term (3) The relationship of these oral complaints to the severity of oral mucositis during hospitalization The secondary objective was to explore the opinions of dentists regarding dental care before and after HSCT. All adult patients who survived HSCT at the Radboud University Medical Centre between 2010 and 2011 (n = 101) received a questionnaire. During hospitalization, mucositis scores were recorded daily in the patient's chart. The patients' dentist (n = 88) was also sent a questionnaire after permission of the patient. Ninety-six out of 101 patients (95%) responded. The average period since HSCT was 19 months (range 8-31 months). The overall mean maximum mucositis score was 6.6 (sd = 3.3). Only eight patients reported not having visited a dentist pre-HSCT. The majority of the patients (59%) reported short-term oral complaints, and 28% reported long-term oral complaints. Fifty-two dentists responded (59%). Nine had not performed pre-HSCT screening and eight dentists reported screening their patients but could not complete the necessary treatments. Only 44 dentists succeeded in completing the required treatments. The most important advice of the dentist was to reinforce the importance of regular dental care. Most patients report short-term and/or long-term oral complaints after HSCT. Most dentists stress the importance of regular dental care before and after HSCT but report not being familiar with the particular dental care needs of this patient group. The high response rate and the high rate of HSCT-related oral complaints emphasize the need of further research in this area.

Clinical effectiveness of hyperbaric oxygen therapy for BK-virus-associated hemorrhagic cystitis after allogeneic bone marrow transplantation.

PubMed

Savva-Bordalo, J; Pinho Vaz, C; Sousa, M; Branca, R; Campilho, F; Resende, R; Baldaque, I; Camacho, O; Campos, A

2012-08-01

Late-onset hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (HSCT) has been associated with BK virus (BKV). Antiviral drugs are of limited efficacy and the optimal treatment for HC has not yet been established. Hyperbaric oxygen (HBO) may benefit these patients. We, therefore, retrospectively evaluated the effectiveness of HBO therapy in 16 patients with HC after allogeneic HSCT. All 16 patients had macroscopic hematuria and BKV infection. Patients received 100% oxygen in a hyperbaric chamber at 2.1 atmospheres for 90 min, 5 days per week, with a median 13 treatments (range, 4-84). Fifteen patients (94%) showed complete resolution of hematuria. Median urinary DNA BKV titers declined after HBO (P<0.05). Patients started on HBO earlier after diagnosis of HC responded sooner (P<0.05). HBO was generally well tolerated and proved to be a reliable option for this difficult to manage condition.

Quality of life in Arab Muslim cancer survivors following hematopoietic stem cell transplantation: comparison with matched healthy group.

PubMed

Alaloul, Fawwaz; Brockopp, Dorothy Y; Andrykowski, Michael A; Hall, Lynne A; Al Nusairat, Taghreed S

2015-07-01

The aims of this study were to determine if quality of life (QOL) among Arab Muslim hematopoietic stem cell transplantation (HSCT) survivors differs from that of a healthy matched comparison group and to examine the relationships of demographic and medical variables and perceived social support with post-HSCT QOL. HSCT survivors (n = 63) were recruited from the King Hussein Cancer Center outpatient clinic. A matched (age, gender, education), healthy comparison group (n = 63) was recruited through public advertisements. Participants completed the EORTC-30 QOL scale and the Medical Outcomes Study Social Support Survey. Differences were found between the Arab Muslim HSCT survivor and healthy comparison groups for physical functioning (p < .0001), role functioning (p < .01), social functioning (p < .0001) QOL domains, and an overall symptom score (p = .003) with the HSCT group reporting poorer status than the healthy comparison group. Effect sizes for the three QOL domains ranged from .50 (role functioning) to 1.20 (social functioning). No significant difference was noted between the Arab Muslim HSCT and comparison groups in emotional and cognitive QOL domains. Higher overall symptom scores were significantly associated with poorer QOL across all QOL domains. Similar to prior research with HSCT survivors, results suggest that HSCT has a significant negative impact on QOL. However, despite this general similarity, results suggest that the needs and experience of Muslim Arab HSCT survivors might differ from those of Western HSCT survivors in the social and emotional QOL domains. Given growing numbers of Arab and Muslim cancer survivors in the USA and other Western countries, future research is warranted.

Clinical outcome in children with chronic granulomatous disease managed conservatively or with hematopoietic stem cell transplantation.

PubMed

Cole, Theresa; Pearce, Mark S; Cant, Andrew J; Cale, Catherine M; Goldblatt, David; Gennery, Andrew R

2013-11-01

Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by serious infections and inflammation. It can be managed conservatively with prophylactic antimicrobial agents or curatively with hematopoietic stem cell transplantation (HSCT). In the United Kingdom and Ireland there are cohorts of children managed both conservatively and curatively. This study aimed to compare clinical outcomes (mortality and morbidity) in children managed conservatively and curatively. Children were identified from specialist centers and advertising through special interest groups. Clinical data were collected from medical records regarding infections, inflammatory complications and growth, other admissions, and curative treatment. Comparisons were made for patients not undergoing HSCT and patients after HSCT. Seventy-three living children were identified, 59 (80%) of whom were recruited. Five deceased children were also identified. Clinical information was available for 62 children (4 deceased). Thirty (48%) children had undergone HSCT. Children who did not undergo transplantation had 0.71 episodes of infection/admission/surgery per CGD life year (95% CI, 0.69-0.75 events per year). Post-HSCT children had 0.15 episodes of infection/admission/surgery per transplant year (95% CI, 0.09-0.21 events per year). The mean z score for height and body mass index (BMI) for age was significantly better in post-HSCT children. Survival in the non-HSCT group was 90% at age 15 years. Survival in the post-HSCT group was 90%. Children with CGD not undergoing transplantation have more serious infections, episodes of surgery, and admissions compared with post-HSCT children. Children undergoing transplantation have better height for age. Survival is good at the end of the pediatric age range and also after HSCT. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Health related quality of life and emotional health in children with chronic granulomatous disease: a comparison of those managed conservatively with those that have undergone haematopoietic stem cell transplant.

PubMed

Cole, Theresa; McKendrick, Fiona; Titman, Penny; Cant, Andrew J; Pearce, Mark S; Cale, Catherine M; Goldblatt, David; Gennery, Andrew R

2013-01-01

Chronic Granulomatous Disease (CGD) is a rare primary immunodeficiency that predisposes to life-threatening infections and inflammation. Haematopoietic stem cell transplant (HSCT) can cure CGD. Chronic illness reduces quality of life. Children with haematological malignancies report improved quality of life post-HSCT. There are no data for children with CGD. This study evaluated quality of life and emotional well-being in CGD children treated conventionally or transplanted. Parents and children completed the Pediatric Quality of Life Inventory v4.0 (PedsQL) and Strengths and Difficulties Questionnaires (SDQ). Mean scores were compared with published UK norms. Comparisons were made for those that had or had not undergone HSCT. Forty-seven parents completed PedsQL (children aged 3-15). Twenty-one were post-HSCT. Forty-two completed SDQ (children aged 3-15). Nineteen post-HSCT. Median age for non-HSCT group 9 years. Median age for post-HSCT group 10 years. The HSCT group were median 3 years post-HSCT (range 1-9 years). HSCT survival was 90 %-two died without completing questionnaires Parent and self-reported quality of life for non-transplanted children was significantly lower than healthy children. Parents reported increased emotional difficulties compared to published norms. PedsQL and SDQ scores for transplanted children were not significantly different from healthy norms. This study demonstrates the quality of life is reduced in CGD. Transplanted patients have quality of life comparable to levels reported in healthy children. This data will help inform families and clinicians when deciding about treatment and may have relevance for other immunodeficiencies treated with transplant.

Haemopoietic stem cell transplantation for children in Australia and New Zealand, 1998-2006: a report on behalf of the Australasian Bone Marrow Transplant Recipient Registry and the Australian and New Zealand Children's Haematology Oncology Group.

PubMed

Moore, Andrew S; Shaw, Peter J; Hallahan, Andrew R; Carter, Tina L; Kilo, Tatjana; Nivison-Smith, Ian; O'Brien, Tracey A; Tapp, Heather; Teague, Lochie; Wilson, Shaun R; Tiedemann, Karin

2009-02-02

To document haemopoietic stem cell transplantation (HSCT) activity and trends among paediatric patients in Australia and New Zealand. A retrospective analysis of data reported to the Australasian Bone Marrow Transplant Recipient Registry by the seven paediatric HSCT institutions in Australia and New Zealand over the 9-year period 1998-2006, with particular focus on the most recent years (2002-2006). Types of HSCT performed; transplant-related mortality (TRM); stem cell sources; indications for HSCT; causes of death after HSCT. Over the period 1998-2006, 522 autologous HSCT procedures (41%) and 737 allogeneic procedures (59%) were performed. About 60% of allogeneic transplants involved alternative donors (donors other than a human leukocyte antigen-matched sibling). The use of umbilical cord blood as a source of haemopoietic stem cells has doubled since 1998, with 34% of allogeneic transplants in 2006 using cord blood. Over the period 2002-2006, the median age of patients receiving transplants was 7 years (range, 0-19 years). The most common indications for allogeneic HSCT were acute lymphoblastic leukaemia (33%) and acute myeloid leukaemia (24%). The most common indications for autologous HSCT were neuroblastoma (23%), medulloblastoma (21%) and Ewing sarcoma (10%). TRM at 1 year after transplant was 22% for alternative donor transplants, 7% for matched-sibling transplants and 5% for autologous transplants. Relapse or persistence of a child's underlying condition accounted for 54% of all deaths within 1 year after transplant. HSCT is an important procedure for children with a range of life-threatening illnesses. Local trends in the indications for HSCT, donor selection and TRM reflect contemporary international practice.

Parent Outlook: How Parents View the Road Ahead as They Embark on Hematopoietic Stem Cell Transplantation for Their Child.

PubMed

Ullrich, Christina K; Rodday, Angie Mae; Bingen, Kristin; Kupst, Mary Jo; Patel, Sunita K; Syrjala, Karen L; Harris, Lynnette L; Recklitis, Christopher J; Schwartz, Lisa; Davies, Stella; Guinan, Eva C; Chang, Grace; Wolfe, Joanne; Parsons, Susan K

2016-01-01

Pediatric hematopoietic stem cell transplantation (HSCT) offers cure for high-risk malignancies and other conditions, but carries a risk of complications. Parental outlook regarding their child's transplantation course and future health has been largely unexplored. This report presents the Parent Outlook Scale, describes its properties, and examines the outlook of parents embarking on their child's transplantation course and the associated variables. Parents of children scheduled to undergo HSCT (n = 363) at 8 US transplantation centers completed the Parent Outlook Scale, comprising 4 items assessing frequency of the parent's thoughts about the potential difficulty of the child's transplantation (Transplant Difficult subscale) and worsened health (Health Worse subscale). Item responses were rated on a 5-point Likert scale (ranging from "none" to "all of the time") and, along with scale/subscale scores, transformed to 100-point scales, with higher scores connoting greater thought frequency. Psychometrics were explored. Multivariable models identified personal and clinical characteristics associated with scale and subscale scores. The Parent Outlook Scale (α = 0.75) and subscales were found to have sound psychometric properties. Factor loading supported the single scale with 2 subscales representing distinct aspects of overall outlook. Mean scores (Parent Outlook, 52.5 ± 21.7; Transplant Difficult, 64.4 ± 25.6; Health Worse, 40.7 ± 25.7) revealed variability within and across scale/subscales. Significantly different mean subscale scores (P < .001) indicated more frequent Transplant Difficult thoughts than Health Worse thoughts. Clinical factors (solid tumor diagnosis and unrelated donor transplant) and a parent factor (worse emotional functioning) were associated with higher scale and subscale scores. Our findings show that the outlook of parents embarking on their child's HSCT course is varied and not solely a product of clinical factors readily apparent to clinicians. Referring and transplantation clinicians should create opportunities to explore with parents their perspectives and concerns before and during the course of HSCT. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Oral Complications in Hematopoietic Stem Cell Recipients: The Role of Inflammation

PubMed Central

Haverman, T. M.; Raber-Durlacher, J. E.; Rademacher, W. M. H.; Vokurka, S.; Epstein, J. B.; Huisman, C.; Hazenberg, M. D.; de Soet, J. J.; de Lange, J.; Rozema, F. R.

2014-01-01

Hematopoietic stem cell transplantation (HSCT) is widely used as a potentially curative treatment for patients with various hematological malignancies, bone marrow failure syndromes, and congenital immune deficiencies. The prevalence of oral complications in both autologous and allogeneic HSCT recipients remains high, despite advances in transplant medicine and in supportive care. Frequently encountered oral complications include mucositis, infections, oral dryness, taste changes, and graft versus host disease in allogeneic HSCT. Oral complications are associated with substantial morbidity and in some cases with increased mortality and may significantly affect quality of life, even many years after HSCT. Inflammatory processes are key in the pathobiology of most oral complications in HSCT recipients. This review article will discuss frequently encountered oral complications associated with HSCT focusing on the inflammatory pathways and inflammatory mediators involved in their pathogenesis. PMID:24817792

Current practices for screening, consent and care of related donors in France: Haematopoietic stem cell transplantation coordinator nurses' perceptions.

PubMed

Polomeni, A; Bompoint, C; Gomez, A; Brissot, E; Ruggeri, A; Belhocine, R; Mohty, M

2017-11-01

Haematopoietic stem cell transplantation-coordinating nurses (HSCT-CNs) play an important role in informing related donors (RDs) and in organising human leucocyte antigen (HLA) tests, pre-donation workup and stem cells collection. Our pilot study aimed to explore French HSCT-CNs' perceptions of RD care issues. Twenty-nine French HSCT adult units were sent a questionnaire on the subject of donation procedures, HSCT-CNs' data and their professional experience of related donation issues. Twenty-two HSCT-CNs returned a completed questionnaire, and 90% of HSCT units were involved to some degree in both patient and donor care. Responses indicated that the provision of information to potential donors prior to HLA tests was insufficient, while donors were given a medical consultation only during the pre-donation workup. Questions were raised about the consent and voluntary status of RDs. None of the HSCT teams organised a post-donation consultation, while 57% provided follow-up by phone or via a questionnaire. Our results draw attention to the conflict of interest experienced by HSCT-CNs when caring simultaneously for patients and donors. The specific psychosocial difficulties associated with becoming an RD are also highlighted. French HSCT-CNs' perceptions of related donation reveal many ethical and clinical problems that have yet to be fully explored. Data on this topic remain scarce, and our pilot study may contribute to the current debate on the organisation of RD care. © 2016 John Wiley & Sons Ltd.

Defibrotide for the treatment of hepatic veno-occlusive disease/sinusoidal obstruction syndrome following nontransplant-associated chemotherapy: Final results from a post hoc analysis of data from an expanded-access program.

PubMed

Kernan, Nancy A; Richardson, Paul G; Smith, Angela R; Triplett, Brandon M; Antin, Joseph H; Lehmann, Leslie; Messinger, Yoav; Liang, Wei; Hume, Robin; Tappe, William; Soiffer, Robert J; Grupp, Stephan A

2018-06-06

Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially fatal complication of conditioning for hematopoietic stem cell transplantation (HSCT) but can occur after nontransplant-associated chemotherapy. Following HSCT, VOD/SOS with multi-organ dysfunction (MOD) may be associated with >80% mortality. Defibrotide is approved to treat severe hepatic VOD/SOS post-HSCT in patients aged >1 month in the European Union and hepatic VOD/SOS with renal or pulmonary dysfunction post-HSCT in the United States. Prior to US approval, defibrotide was available to treat VOD/SOS through an expanded-access treatment (T-IND) program. A post hoc analysis of nontransplant-associated VOD/SOS patients treated with defibrotide initiated within 30 days of starting chemotherapy and followed for 70 days is presented. Patients were diagnosed by Baltimore or modified Seattle criteria or biopsy, and received defibrotide 25 mg/kg/day in four divided doses (≥21 days recommended). Of the 1,154 patients in the T-IND, 137 had nontransplant-associated VOD/SOS, 82 of whom developed VOD/SOS within 30 days of starting chemotherapy. Of them, 66 (80.5%) were aged ≤16 years. Across all the 82 patients, Kaplan-Meier estimated day +70 survival was 74.1%, 65.8% in patients with MOD (n = 38), and 81.3% in patients without MOD (n = 44). By age group, Kaplan-Meier estimated day +70 survival was 80.1% in pediatric patients (n = 66) and 50.0% in adults (n = 16). Treatment-related adverse events occurred in 26.8%. In this post hoc analysis of 82 patients initiating defibrotide within 30 days of starting chemotherapy, Kaplan-Meier estimated survival was 74.1% at 70 days after defibrotide initiation. Safety profile was consistent with prior defibrotide studies. © 2018 The Authors. Pediatric Blood & Cancer Published by Wiley Periodicals, Inc.

Automatic Clustering Using Multi-objective Particle Swarm and Simulated Annealing

PubMed Central

Abubaker, Ahmad; Baharum, Adam; Alrefaei, Mahmoud

2015-01-01

This paper puts forward a new automatic clustering algorithm based on Multi-Objective Particle Swarm Optimization and Simulated Annealing, “MOPSOSA”. The proposed algorithm is capable of automatic clustering which is appropriate for partitioning datasets to a suitable number of clusters. MOPSOSA combines the features of the multi-objective based particle swarm optimization (PSO) and the Multi-Objective Simulated Annealing (MOSA). Three cluster validity indices were optimized simultaneously to establish the suitable number of clusters and the appropriate clustering for a dataset. The first cluster validity index is centred on Euclidean distance, the second on the point symmetry distance, and the last cluster validity index is based on short distance. A number of algorithms have been compared with the MOPSOSA algorithm in resolving clustering problems by determining the actual number of clusters and optimal clustering. Computational experiments were carried out to study fourteen artificial and five real life datasets. PMID:26132309

Assessment of the Effects of High-Speed Aircraft in the Stratosphere: 1998

NASA Technical Reports Server (NTRS)

Kawa, S. Randolph; Anderson, James G.; Baughcum, Steven L.; Brock, Charles A.; Brune, William H.; Cohen, Ronald C.; Kinnison, Douglas E.; Newman, Paul A.; Rodriquez, Jose M.; Stolarski, Richard S.;

Assessment of the Effects of High-Speed Aircraft in the Stratosphere: 1998

NASA Technical Reports Server (NTRS)

Kawa, S. Randolph; Anderson, James G.; Baughcum, Steven L.; Brock, Charles A.; Brune, William H.; Cohen, Ronald C.; Kinnison, Douglas E.; Newman, Paul A.; Rodriguez, Jose M.; Stolarski, Richard S.;

Cellular therapies supplement: strategies for improving transplant efficiency in the context of cellular therapeutics.

PubMed

Jimenez, Antonio; Fung, Henry C; Christopherson, Kent W

2011-11-01

The field of hematopoietic stem cell transplantation (HSCT) has overcome many obstacles that have led to our current clinical ability to utilize cells collected from marrow, mobilized peripheral blood, or umbilical cord blood for the treatment of malignant and nonmalignant hematologic diseases. It is in this context that it becomes evident that future progress will lie in our development of an understanding of the biology by which the process of HSCT is regulated. By understanding the cellular components and the mechanisms by which HSCT is either enhanced or suppressed it will then be possible to design therapeutic strategies to improve rates of engraftment that will have a positive impact on immune reconstitution post-HSCT. In this review we focus primarily on allogeneic hematopoietic stem cell transplantation (allo-HSCT), the current challenges associated with allo-HSCT, and some developing strategies to improve engraftment in this setting. © 2011 American Association of Blood Banks.

Integrated design and manufacturing for the high speed civil transport (a combined aerodynamics/propulsion optimization study)

NASA Technical Reports Server (NTRS)

Baecher, Juergen; Bandte, Oliver; DeLaurentis, Dan; Lewis, Kemper; Sicilia, Jose; Soboleski, Craig

1995-01-01

This report documents the efforts of a Georgia Tech High Speed Civil Transport (HSCT) aerospace student design team in completing a design methodology demonstration under NASA's Advanced Design Program (ADP). Aerodynamic and propulsion analyses are integrated into the synthesis code FLOPS in order to improve its prediction accuracy. Executing the integrated product and process development (IPPD) methodology proposed at the Aerospace Systems Design Laboratory (ASDL), an improved sizing process is described followed by a combined aero-propulsion optimization, where the objective function, average yield per revenue passenger mile ($/RPM), is constrained by flight stability, noise, approach speed, and field length restrictions. Primary goals include successful demonstration of the application of the response surface methodolgy (RSM) to parameter design, introduction to higher fidelity disciplinary analysis than normally feasible at the conceptual and early preliminary level, and investigations of relationships between aerodynamic and propulsion design parameters and their effect on the objective function, $/RPM. A unique approach to aircraft synthesis is developed in which statistical methods, specifically design of experiments and the RSM, are used to more efficiently search the design space for optimum configurations. In particular, two uses of these techniques are demonstrated. First, response model equations are formed which represent complex analysis in the form of a regression polynomial. Next, a second regression equation is constructed, not for modeling purposes, but instead for the purpose of optimization at the system level. Such an optimization problem with the given tools normally would be difficult due to the need for hard connections between the various complex codes involved. The statistical methodology presents an alternative and is demonstrated via an example of aerodynamic modeling and planform optimization for a HSCT.

The Use of Intravenous Antibiotics at the Onset of Neutropenia in Patients Receiving Outpatient-Based Hematopoietic Stem Cell Transplants

PubMed Central

Hamadah, Aziz; Schreiber, Yoko; Toye, Baldwin; McDiarmid, Sheryl; Huebsch, Lothar; Bredeson, Christopher; Tay, Jason

2012-01-01

Empirical antibiotics at the onset of febrile neutropenia are one of several strategies for management of bacterial infections in patients undergoing Hematopoietic Stem Cell Transplant (HSCT) (empiric strategy). Our HSCT program aims to perform HSCT in an outpatient setting, where an empiric antibiotic strategy was employed. HSCT recipients began receiving intravenous antibiotics at the onset of neutropenia in the absence of fever as part of our institutional policy from 01 Jan 2009; intravenous Prophylactic strategy. A prospective study was conducted to compare two consecutive cohorts [Year 2008 (Empiric strategy) vs. Year 2009 (Prophylactic strategy)] of patients receiving HSCT. There were 238 HSCTs performed between 01 Jan 2008 and 31 Dec 2009 with 127 and 111 in the earlier and later cohorts respectively. Infection-related mortality pre- engraftment was similar with a prophylactic compared to an empiric strategy (3.6% vs. 7.1%; p = 0.24), but reduced among recipients of autologous HSCT (0% vs. 6.8%; p = 0.03). Microbiologically documented, blood stream infections and clinically documented infections pre-engraftment were reduced in those receiving a prophylactic compared to an empiric strategy, (11.7% vs. 28.3%; p = 0.001), (9.9% vs. 24.4%; p = 0.003) and (18.2% vs. 33.9% p = 0.007) respectively. The prophylactic use of intravenous once-daily ceftriaxone in patients receiving outpatient based HSCT is safe and may be particularly effective in patients receiving autologous HSCT. Further studies are warranted to study the impact of this Prophylactic strategy in an outpatient based HSCT program. PMID:23029441

Pre-existing anti-HLA antibodies negatively impact survival of pediatric aplastic anemia patients undergoing HSCT.

PubMed

Zhu, Hua; He, Jun; Cai, Junchao; Yuan, Xiaoni; Jiang, Hua; Luo, Changying; Wang, Jianmin; Luo, Chengjuan; Pan, Zhijuan; Terasaki, Paul I; Ding, Lixia; Chen, Jing

2014-11-01

Graft failure and survival are the major problems for patients with aplastic anemia undergoing hematopoietic stem cell transplantation (HSCT). Previous studies showed that anti-HLA antibodies negatively impact engraftment in HSCT. This retrospective study of 51 pediatric patients with acquired aplastic anemia who underwent allogeneic HSCT at a single institution between 2006 and 2012 investigated the influence of anti-HLA antibodies on the outcome of HSCT. Serum samples collected before HSCT were tested for the presence of anti-HLA antibodies. Pre-existing anti-HLA antibodies were detected in 54.9% (28/51) of patients, among whom 39.2% (20/51) had anti-HLA class I antibodies. Anti-HLA antibodies were associated with worse five-yr survival (78.6% vs. 100%, p = 0.021) and higher treatment-related mortality (21.4% vs. 0%, p = 0.028) compared with antibody-negative patients. Anti-HLA class I antibody-positive patients had poorer five-yr survival (75.0%) than anti-HLA class I&II antibody-positive and antibody-negative patients (87.5% and 100.0%, respectively, p = 0.039). Presence of anti-HLA class I antibodies (p = 0.024) and older age (10 yr or more; p = 0.027) significantly increased the risk of post-HSCT mortality. Pre-existing anti-HLA antibodies negatively affect the outcome of HSCT in pediatric patients with aplastic anemia. Routine testing for anti-HLA antibodies concurrent with efficient treatment should be conducted prior to HSCT. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Hematopoietic Reconstitution and Prognosis of HLA Matched and Haploidentical Hematopoietic Stem Cell Transplantation Using Modified FC/ATG Conditioning for Treatment of Severe Aplastic Anemia].

PubMed

Wang, Li; Wu, Ya-Mei; Cao, Yong-Bin; Li, Xiao-Hong; Xu, Li-Xin; Wang, Hai-Tao; Gao, Ya-Hui; Wu, Xiao-Xiong

2016-12-01

To analyse the feasibility and compare differences between hematopoietic reconstitution and prognosis of patients with severe aplastic anemia(SAA) after matched sibling donor (MSD) or haploidentical family donor (HFD) hematopoietic stem cell transplantation (HSCT) using the modified FC/ATG conditioning. The clinical data of 56 patients with SAA who received HSCT in First Affiliated Hospital of Chinese PLA General Hospital from January 2011 to June 2016 were analyzed retrospectively. The hematopoietic reconstitution, graft verus host disease (GVHD), transplantation related toxicity (TRT) and prognosis after transplantation were compared. Furthermore, the modifed conditioning FC/ATG included low-dose cyclophosphamide (total dose 100 mg/kg), infustion of third-party donor-derived mesenchymal stem cells. All 56 patients with MSD-HSCT or HFD-HSCT achieved hematopoietic reconstitution. Among them, not only the recovery of neutrophils and platelets, but also the incidences of III-IV aGVHD, extensive cGVHD and TRT were not significantly different (the P value were 0.58, 0.61, 0.73, 0.73 and 0.67, respectively). After following-up for 32(2-66) months, 48 patients alive well, the 1-year overall survival rates were 86% in HFD-HSCT group and 89% in MSD-HSCT group, respectively (P=0.58). After HSCT using the modifed FC/ATG conditioning, patients with SAA achieved stable engraftment, low toxicity, mild GVHD and excellent outcomes. Furthermore, the HFD-HSCT achieved comparable outcomes to MSD-HSCT and may be served as an alternate therapy for patients with SAA.

Dual-mode nested search method for categorical uncertain multi-objective optimization

NASA Astrophysics Data System (ADS)

Tang, Long; Wang, Hu

2016-10-01

Categorical multi-objective optimization is an important issue involved in many matching design problems. Non-numerical variables and their uncertainty are the major challenges of such optimizations. Therefore, this article proposes a dual-mode nested search (DMNS) method. In the outer layer, kriging metamodels are established using standard regular simplex mapping (SRSM) from categorical candidates to numerical values. Assisted by the metamodels, a k-cluster-based intelligent sampling strategy is developed to search Pareto frontier points. The inner layer uses an interval number method to model the uncertainty of categorical candidates. To improve the efficiency, a multi-feature convergent optimization via most-promising-area stochastic search (MFCOMPASS) is proposed to determine the bounds of objectives. Finally, typical numerical examples are employed to demonstrate the effectiveness of the proposed DMNS method.

Vitamin D Deficiency and Survival in Children after Hematopoietic Stem Cell Transplant.

PubMed

Wallace, Gregory; Jodele, Sonata; Howell, Jonathan; Myers, Kasiani C; Teusink, Ashley; Zhao, Xueheng; Setchell, Kenneth; Holtzapfel, Catherine; Lane, Adam; Taggart, Cynthia; Laskin, Benjamin L; Davies, Stella M

2015-09-01

Vitamin D has endocrine function as a key regulator of calcium absorption and bone homeostasis and also has intracrine function as an immunomodulator. Vitamin D deficiency before hematopoietic stem cell transplantation (HSCT) has been variably associated with higher risks of graft-versus-host disease (GVHD) and mortality. Children are at particular risk of growth impairment and bony abnormalities in the face of prolonged deficiency. There are few longitudinal studies of vitamin D deficient children receiving HSCT, and the prevalence and consequences of vitamin D deficiency 100 days after transplant has been poorly studied. Serum samples from 134 consecutive HSCT patients prospectively enrolled into an HSCT sample repository were tested for 25-hydroxy (25 OH) vitamin D levels before starting HSCT (baseline) and at 100 days after transplantation. Ninety-four of 134 patients (70%) had a vitamin D level < 30 ng/mL before HSCT, despite supplemental therapy in 16% of subjects. Post-transplant samples were available in 129 patients who survived to day 100 post-transplant. Vitamin D deficiency persisted in 66 of 87 patients (76%) who were already deficient before HSCT. Moreover, 24 patients with normal vitamin D levels before HSCT were vitamin D deficient by day 100. Overall, 68% of patients were vitamin D deficient (<30 ng/mL) at day 100, and one third of these cases had severe vitamin D deficiency (<20 ng/mL). Low vitamin D levels before HSCT were not associated with subsequent acute or chronic GVHD, contrary to some prior reports. However, severe vitamin D deficiency (<20 ng/mL) at 100 days post-HSCT was associated with decreased overall survival after transplantation (P = .044, 1-year rate of overall survival: 70% versus 84.1%). We conclude that all pediatric transplant recipients should be screened for vitamin D deficiency before HSCT and at day 100 post-transplant and that aggressive supplementation is needed to maintain sufficient levels. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

The role of telomeres and telomerase in hematologic malignancies and hematopoietic stem cell transplantation

PubMed Central

2014-01-01

Telomeres are specific nucleoprotein structures at the ends of eukaryotic chromosomes. Telomeres and telomere-associated proteins maintain genome stability by protecting the ends of chromosomes from fusion and degradation. In normal somatic cells, the length of the telomeres gradually becomes shortened with cell division. In tumor cells, the shortening of telomeres length is accelerated under the increased proliferation pressure. However, it will be maintained at an extremely short length as the result of activation of telomerase. Significantly shortened telomeres, activation of telomerase, and altered expression of telomere-associated proteins are common features of various hematologic malignancies and are related with progression or chemotherapy resistance in these diseases. In patients who have received hematopoietic stem cell transplantation (HSCT), the telomere length and the telomerase activity of the engrafted donor cells have a significant influence on HSCT outcomes. Transplantation-related factors should be taken into consideration because of their impacts on telomere homeostasis. As activation of telomerase is widespread in tumor cells, it has been employed as a target point in the treatment of neoplastic hematologic disorders. In this review, the characteristics and roles of telomeres and telomerase both in hematologic malignancies and in HSCT will be summarized. The current status of telomerase-targeted therapies utilized in the treatment of hematologic malignancies will also be reviewed. PMID:25139287

A conceptual framework for economic optimization of an animal health surveillance portfolio.

PubMed

Guo, X; Claassen, G D H; Oude Lansink, A G J M; Saatkamp, H W

2016-04-01

Decision making on hazard surveillance in livestock product chains is a multi-hazard, multi-stakeholder, and multi-criteria process that includes a variety of decision alternatives. The multi-hazard aspect means that the allocation of the scarce resource for surveillance should be optimized from the point of view of a surveillance portfolio (SP) rather than a single hazard. In this paper, we present a novel conceptual approach for economic optimization of a SP to address the resource allocation problem for a surveillance organization from a theoretical perspective. This approach uses multi-criteria techniques to evaluate the performances of different settings of a SP, taking cost-benefit aspects of surveillance and stakeholders' preferences into account. The credibility of the approach has also been checked for conceptual validity, data needs and operational validity; the application potentials of the approach are also discussed.

Distributed optimization system and method

DOEpatents

Hurtado, John E.; Dohrmann, Clark R.; Robinett, III, Rush D.

2003-06-10

A search system and method for controlling multiple agents to optimize an objective using distributed sensing and cooperative control. The search agent can be one or more physical agents, such as a robot, and can be software agents for searching cyberspace. The objective can be: chemical sources, temperature sources, radiation sources, light sources, evaders, trespassers, explosive sources, time dependent sources, time independent sources, function surfaces, maximization points, minimization points, and optimal control of a system such as a communication system, an economy, a crane, and a multi-processor computer.

Distributed Optimization System

DOEpatents

Hurtado, John E.; Dohrmann, Clark R.; Robinett, III, Rush D.

2004-11-30

A search system and method for controlling multiple agents to optimize an objective using distributed sensing and cooperative control. The search agent can be one or more physical agents, such as a robot, and can be software agents for searching cyberspace. The objective can be: chemical sources, temperature sources, radiation sources, light sources, evaders, trespassers, explosive sources, time dependent sources, time independent sources, function surfaces, maximization points, minimization points, and optimal control of a system such as a communication system, an economy, a crane, and a multi-processor computer.

Prophylactic platelet transfusions in patients with blood malignancies: cost analysis of a randomized trial.

PubMed

Campbell, Helen E; Estcourt, Lise J; Stokes, Elizabeth A; Llewelyn, Charlotte A; Murphy, Michael F; Wood, Erica M; Stanworth, Simon J

2014-10-01

This cost analysis uses data from a randomized trial comparing a no prophylaxis versus prophylactic platelet (PLT) transfusion policy (counts <10 × 10(9) /L) in adult patients with hematologic malignancies. Results are presented for all patients and separately for autologous hematopoietic stem cell transplantation (HSCT) (autoHSCT) and chemotherapy/allogeneic HSCT (chemo/alloHSCT) patients. Data were collected to 30 days on PLT and red blood cell (RBC) transfusions, major bleeds, serious adverse events, critical care, and hematology ward stay. Data were costed using 2011 to 2012 UK unit costs and converted into US$. Sensitivity analyses were performed on uncertain cost variables. Across the whole trial no prophylaxis saved costs compared to prophylaxis: -$1760 per patient (95% confidence interval [CI], -$3250 to -$249; p < 0.05). For autoHSCT patients there was no cost difference between arms: -$110 per patient (95% CI, -$1648 to $1565; p = 0.89). For chemo/alloHSCT patients no prophylaxis cost significantly less than prophylaxis: -$5686 per patient (95% CI, -$8580 to -$2853; p < 0.01). The cost impact of no prophylaxis differed significantly between subgroups. Sensitivity analyses varying daily treatment costs and ward stay for chemo/alloHSCT patients reduced cost differences to -$941 per patient (p = 0.21) across the whole trial and -$2927 per patient (p < 0.05) in chemo/alloHSCT subgroup. It is unclear whether a no-prophylaxis policy saves costs overall. In chemo/alloHSCT patients cost savings are apparent but their magnitude is sensitive to a number of variables and must be considered alongside clinical data showing increased bleeding rates. In autoHSCT patients savings generated through lower PLT use in no-prophylaxis arm were offset by cost increases elsewhere, for example, additional RBC transfusions. Cost-effectiveness analyses of alternative PLT transfusion policies simultaneously considering costs and patient-reported outcomes are warranted. © 2014 AABB.

Adoptively transferred TRAIL+ T cells suppress GVHD and augment antitumor activity

PubMed Central

Ghosh, Arnab; Dogan, Yildirim; Moroz, Maxim; Holland, Amanda M.; Yim, Nury L.; Rao, Uttam K.; Young, Lauren F.; Tannenbaum, Daniel; Masih, Durva; Velardi, Enrico; Tsai, Jennifer J.; Jenq, Robert R.; Penack, Olaf; Hanash, Alan M.; Smith, Odette M.; Piersanti, Kelly; Lezcano, Cecilia; Murphy, George F.; Liu, Chen; Palomba, M. Lia; Sauer, Martin G.; Sadelain, Michel; Ponomarev, Vladimir; van den Brink, Marcel R.M.

2013-01-01

Current strategies to suppress graft-versus-host disease (GVHD) also compromise graft-versus-tumor (GVT) responses. Furthermore, most experimental strategies to separate GVHD and GVT responses merely spare GVT function without actually enhancing it. We have previously shown that endogenously expressed TNF-related apoptosis-inducing ligand (TRAIL) is required for optimal GVT activity against certain malignancies in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). In order to model a donor-derived cellular therapy, we genetically engineered T cells to overexpress TRAIL and adoptively transferred donor-type unsorted TRAIL+ T cells into mouse models of allo-HSCT. We found that murine TRAIL+ T cells induced apoptosis of alloreactive T cells, thereby reducing GVHD in a DR5-dependent manner. Furthermore, murine TRAIL+ T cells mediated enhanced in vitro and in vivo antilymphoma GVT response. Moreover, human TRAIL+ T cells mediated enhanced in vitro cytotoxicity against both human leukemia cell lines and against freshly isolated chronic lymphocytic leukemia (CLL) cells. Finally, as a model of off-the-shelf, donor-unrestricted antitumor cellular therapy, in vitro–generated TRAIL+ precursor T cells from third-party donors also mediated enhanced GVT response in the absence of GVHD. These data indicate that TRAIL-overexpressing donor T cells could potentially enhance the curative potential of allo-HSCT by increasing GVT response and suppressing GVHD. PMID:23676461

Uniscale multi-view registration using double dog-leg method

NASA Astrophysics Data System (ADS)

Chen, Chao-I.; Sargent, Dusty; Tsai, Chang-Ming; Wang, Yuan-Fang; Koppel, Dan

2009-02-01

3D computer models of body anatomy can have many uses in medical research and clinical practices. This paper describes a robust method that uses videos of body anatomy to construct multiple, partial 3D structures and then fuse them to form a larger, more complete computer model using the structure-from-motion framework. We employ the Double Dog-Leg (DDL) method, a trust-region based nonlinear optimization method, to jointly optimize the camera motion parameters (rotation and translation) and determine a global scale that all partial 3D structures should agree upon. These optimized motion parameters are used for constructing local structures, and the global scale is essential for multi-view registration after all these partial structures are built. In order to provide a good initial guess of the camera movement parameters and outlier free 2D point correspondences for DDL, we also propose a two-stage scheme where multi-RANSAC with a normalized eight-point algorithm is first performed and then a few iterations of an over-determined five-point algorithm is used to polish the results. Our experimental results using colonoscopy video show that the proposed scheme always produces more accurate outputs than the standard RANSAC scheme. Furthermore, since we have obtained many reliable point correspondences, time-consuming and error-prone registration methods like the iterative closest points (ICP) based algorithms can be replaced by a simple rigid-body transformation solver when merging partial structures into a larger model.

Solid organ transplants following hematopoietic stem cell transplant in children.

PubMed

Bunin, Nancy; Guzikowski, Virginia; Rand, Elizabeth R; Goldfarb, Samuel; Baluarte, Jorge; Meyers, Kevin; Olthoff, Kim M

2010-12-01

SOT may be indicated for a select group of pediatric patients who experience permanent organ failure following HSCT. However, there is limited information available about outcomes. We identified eight children at our center who received an SOT following an HSCT. Patients were six months to 18 yr at HSCT. Diseases for which children underwent HSCT included thalassemia, Wiskott-Aldrich syndrome, Shwachman-Diamond/bone marrow failure, sickle cell disease (SCD), erythropoietic porphyria (EP), ALL, chronic granulomatous disease, and neuroblastoma. Time from HSCT to SOT was 13 days to seven yr (median, 27 months. Lung SOT was performed for two patients with BO, kidney transplants for three patients, and liver transplants for three patients (VOD, chronic GVHD). Seven patients are alive with functioning allografts 6-180 months from SOT. Advances in organ procurement, operative technique, immunosuppressant therapy, and infection control may allow SOT for a select group of patients post-HSCT. However, scarcity of donor organs available in a timely fashion continues to be a limiting factor. Children who have undergone HSCT and develop single organ failure should be considered for an SOT if there is a high likelihood of cure of the primary disease. © 2010 John Wiley & Sons A/S.

Incident cancers and late mortality in Australian children treated by allogeneic stem cell transplantation for non-malignant diseases.

PubMed

Nelson, Adam S; Vajdic, Claire M; Ashton, Lesley J; Le Marsney, Renate E; Nivison-Smith, Ian; Wilcox, Leonie; Dodds, Anthony J; O'Brien, Tracey A

2017-01-01

Hematopoietic stem cell transplantation (HSCT) is a life-saving procedure for children with a variety of non-malignant conditions. However, these children face an increased risk of late death and incident cancers after HSCT, which may occur many years after their initial HSCT. We examined cancer occurrence and late mortality in a population-based cohort of 318 Australian children who underwent allogeneic HSCT for non-malignant disease. Standardized incident ratios (SIRs) and standardized mortality ratios (SMRs) were calculated and compared with population controls. We identified six (1.9%) cancers at a median 9.2 years post-HSCT. Cancer occurred 15 times more frequently than in the general population (SIR 15.4, 95% CI = 6.9-34.2). Of the 198 patients who survived for at least 2 years post-HSCT, 11 (5.6%) died at a median 7.5 years post-HSCT. The mortality rate was 17 times higher than in the general population (SMR 17.5, 95% CI = 9.7-31.2). Children transplanted for non-malignant conditions require evidence-based survivorship programs to reduce excess morbidity and mortality. © 2016 Wiley Periodicals, Inc.

Special Issues Related to Hematopoietic Stem Cell Transplantation in the Eastern Mediterranean Region and the First Regional Activity Report

PubMed Central

Aljurf, Mahmoud; Zaidi, Syed Z; El Solh, Hassan; Hussain, Fazal; Ghavamzadeh, Ardeshir; Mahmoud, Hossam Kamel; Shamsi, Tahir; Othman, Tarek Ben; Sarhan, Mahmoud M.; Dennison, David; Ibrahim, Ahmad; Benchekroun, Said; Chaudhri, Naeem; Labar, Boris; Horowitz, Mary; Niederwieser, Dietger; Gratwohl, Alois

2012-01-01

Although several centers are now performing allogeneic HSCT in the Eastern Mediterranean (EM) region, the availability is still limited. Special issues including compatible donor availability and potential for alternate donor programs are discussed. In comparison to Europe & North America, differences in pattern of diseases and pre-HSCT general status particularly for patients with BM failure are described. Other differences including high seropositivity for CMV, Hepatitis B and C infection and specific observations about GVHD with its relation to genetically homogeneous community are also discussed. We report that a total of 17 HSCT programs (performing 5 or more HSCTs annually) exist in 9 countries of the EM region. Only 6 programs are currently reporting to EBMT or IBMTR. A total of 7617 HSCTs have been performed by these programs including 5701 allogeneic HSCTs. Due to low HSCT team density (1.5583 teams/10 million inhabitants vs. 14.4333 in Europe) and very low HSCT team distribution (0.2729 teams/10,000 sq km area vs. <1 to 6 teams in Europe). GNI/capita had no clear association with low HSCT activity; however improvement in infrastructure & formation of EM regional HSCT registry are needed. PMID:19043456

Grey-Theory-Based Optimization Model of Emergency Logistics Considering Time Uncertainty.

PubMed

Qiu, Bao-Jian; Zhang, Jiang-Hua; Qi, Yuan-Tao; Liu, Yang

2015-01-01

Natural disasters occur frequently in recent years, causing huge casualties and property losses. Nowadays, people pay more and more attention to the emergency logistics problems. This paper studies the emergency logistics problem with multi-center, multi-commodity, and single-affected-point. Considering that the path near the disaster point may be damaged, the information of the state of the paths is not complete, and the travel time is uncertainty, we establish the nonlinear programming model that objective function is the maximization of time-satisfaction degree. To overcome these drawbacks: the incomplete information and uncertain time, this paper firstly evaluates the multiple roads of transportation network based on grey theory and selects the reliable and optimal path. Then simplify the original model under the scenario that the vehicle only follows the optimal path from the emergency logistics center to the affected point, and use Lingo software to solve it. The numerical experiments are presented to show the feasibility and effectiveness of the proposed method.

Grey-Theory-Based Optimization Model of Emergency Logistics Considering Time Uncertainty

PubMed Central

Qiu, Bao-Jian; Zhang, Jiang-Hua; Qi, Yuan-Tao; Liu, Yang

2015-01-01

Natural disasters occur frequently in recent years, causing huge casualties and property losses. Nowadays, people pay more and more attention to the emergency logistics problems. This paper studies the emergency logistics problem with multi-center, multi-commodity, and single-affected-point. Considering that the path near the disaster point may be damaged, the information of the state of the paths is not complete, and the travel time is uncertainty, we establish the nonlinear programming model that objective function is the maximization of time-satisfaction degree. To overcome these drawbacks: the incomplete information and uncertain time, this paper firstly evaluates the multiple roads of transportation network based on grey theory and selects the reliable and optimal path. Then simplify the original model under the scenario that the vehicle only follows the optimal path from the emergency logistics center to the affected point, and use Lingo software to solve it. The numerical experiments are presented to show the feasibility and effectiveness of the proposed method. PMID:26417946

CD20 positivity and white blood cell count predict treatment outcomes in Philadelphia chromosome-negative acute lymphoblastic leukemia patients ineligible for pediatric-inspired chemotherapy.

PubMed

Isshiki, Yusuke; Ohwada, Chikako; Sakaida, Emiko; Onoda, Masahiro; Aotsuka, Nobuyuki; Tanaka, Hiroaki; Fukazawa, Motoharu; Cho, Ryuko; Sugawara, Takeaki; Kawaguchi, Takeharu; Hara, Satoru; Yokota, Akira

2017-11-01

The efficacy of conventional chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been controversial as post-remission therapies for adult Philadelphia chromosome-negative acute lymphoblastic leukemia patients. We retrospectively analyzed 96 adolescent and adult cases of Philadelphia chromosome-negative acute lymphoblastic leukemia to evaluate whether allo-HSCT should be performed after first complete remission (1CR). In total, 34 patients received chemotherapy followed by allo-HSCT (HSCT group) and 62 received chemotherapy alone (chemotherapy group). No significant differences in the event-free survival (EFS) or overall survival were observed between the two groups. In the chemotherapy group, use of pediatric regimens was significantly associated with favorable EFS, while high white blood cell (WBC) count and CD20 positivity were associated with poor outcome. In patients who received pediatric regimens, subsequent allo-HSCT did not influence EFS. In patients who received conventional chemotherapy (adult regimen), subsequent allo-HSCT did not improve EFS. High WBC count and CD20 positivity were also significantly associated with poor EFS in patients who received adult regimens. Patients with low WBC count and absence of CD20 who received adult regimens did not benefit from allo-HSCT. Allo-HSCT may not be required in the pediatric regimen-eligible patients; however, pediatric regimen-ineligible patients with either CD20 positivity or high WBC count should receive allo-HSCT after achieving 1CR. This study was registered at http://www.umin.ac.jp/ctr/ as #C000016287. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Mutations in epigenetic regulators are involved in acute lymphoblastic leukemia relapse following allogeneic hematopoietic stem cell transplantation.

PubMed

Xiao, Haowen; Wang, Li-Mengmeng; Luo, Yi; Lai, Xiaoyu; Li, Caihua; Shi, Jimin; Tan, Yamin; Fu, Shan; Wang, Yebo; Zhu, Ni; He, Jingsong; Zheng, Weiyan; Yu, Xiaohong; Cai, Zhen; Huang, He

2016-01-19

Although steady improvements to chemotherapeutic treatments has helped cure 80% of childhood acute lymphoblastic leukemia (ALL) cases, chemotherapy has proven to be less effective in treating the majority of adult patients, leaving allogeneic hematopoietic stem cell transplantation (allo-HSCT) as the primary adult treatment option. Nevertheless relapse are the leading cause of death following allo-HSCT. The genetic pathogenesis of relapse following allo-HSCT in Philadelphia chromosome- negative ALL (Ph- ALL) remains unexplored. We performed longitudinal whole-exome sequencing analysis in three adult patients with Ph- B-cell ALL (Ph- B-ALL) on samples collected from diagnosis to relapse after allo-HSCT. Based on these data, we performed target gene sequencing on 23 selected genes in 58 adult patients undergoing allo-HSCT with Ph- B-ALL. Our results revealed a significant enrichment of mutations in epigenetic regulators from relapsed samples, with recurrent somatic mutations in SETD2, CREBBP, KDM6A and NR3C1. The relapsed samples were also enriched in signaling factor mutations, including KRAS, PTPN21, MYC and USP54. Furthermore, we are the first to reveal the clonal evolution patterns during leukemia relapse after allo-HSCT. Cells present in relapsed specimens were genetically related to the diagnosed tumor, these cells therefore arose from either an existing subclone that was not eradicated by allo-HSCT therapy, or from the same progenitor that acquired new mutations. In some cases, however, it is possible that leukemia recurrence following allo-HSCT could result from a secondary malignancy with a distinct set of mutations. We identified novel genetic causes of leukemia relapse after allo-HSCT using the largest generated data set to date from adult patients with Ph- B-ALL.

Posaconazole plasma exposure correlated to intestinal mucositis in allogeneic stem cell transplant patients.

PubMed

Vanstraelen, Kim; Prattes, Juergen; Maertens, Johan; Lagrou, Katrien; Schoemans, Hélène; Peersman, Nele; Vermeersch, Pieter; Theunissen, Koen; Mols, Raf; Augustijns, Patrick; Annaert, Pieter; Hoenigl, Martin; Spriet, Isabel

2016-08-01

Low posaconazole plasma concentrations (PPCs) are frequently encountered in allogeneic hematopoietic stem cell transplant (HSCT) patients, due to variable gastrointestinal absorption. In this study, the impact of intestinal mucositis on posaconazole exposure is investigated. A prospective pharmacokinetic study was performed including allogeneic HSCT patients receiving posaconazole prophylaxis with the oral suspension or tablets. Steady state PPCs were determined using high-performance liquid chromatography-fluorescence detection at the day of transplantation (=day 0), day +7, and +14. Citrulline was measured using liquid chromatography-tandem mass spectrometry to evaluate severity of mucositis, at baseline (day -7 or -6), and at day 0, +7 and +14. Additionally, citrulline plasma concentrations and steady state trough PPCs were determined in hematological patients without HSCT or mucositis. Thirty-four HSCT patients received posaconazole oral suspension together with 25 cL of Coca Cola, 6 HSCT patients received posaconazole tablets and 33 hematological patients not receiving HSCT received posaconazole oral suspension. The median (interquartile range) average PPC was 0.26 mg/L (0.17-0.43), 0.67 mg/L (0.27-1.38), and 1.08 mg/L (0.96-1.38), with suspension in HSCT patients, suspension in hematological patients and tablets in HSCT patients, respectively. A higher trough PPC was encountered with the oral suspension when citrulline plasma concentrations were above 10 μmol/L compared to values below 10 μmol/L (p < 0.001), whereas for tablets, average PPCs remained high with citrulline plasma concentrations below or above 10 μmol/L (p = 0.64). Posaconazole tablets should be preferred to suspension in HSCT patients immediately after transplantation to prevent insufficient plasma exposure due to intestinal mucositis.

Acute cholecystitis is a common complication after allogeneic stem cell transplantation and is associated with the use of total parenteral nutrition.

PubMed

Bagley, Stephen J; Sehgal, Alison R; Gill, Saar; Frey, Noelle V; Hexner, Elizabeth O; Loren, Alison W; Mangan, James K; Porter, David L; Stadtmauer, Edward A; Reshef, Ran; Luger, Selina M

2015-04-01

The incidence and risk factors for acute cholecystitis after allogeneic hematopoietic stem cell transplantation (HSCT) are not well defined. Of 644 consecutive adult transplants performed at our institution between 2001 and 2011, acute cholecystitis occurred in the first year of transplant in 32 patients (5.0%). We conducted 2 retrospective case-control studies of this population to determine risk factors for cholecystitis after HSCT and to evaluate the performance of different methods of imaging to diagnosis cholecystitis in patients undergoing HSCT compared with non-HSCT patients. In the HSCT population, development of cholecystitis was associated with an increased 1-year overall mortality rate (62.5% versus 19.8%, P < .001). The risk of developing cholecystitis was higher in patients who received total parenteral nutrition (TPN) (adjusted odds ratio, 3.41; P = .009). There was a trend toward more equivocal abdominal ultrasound findings in HSCT recipients with acute cholecystitis compared with nontransplant patients (50.0% versus 30.6%, P = .06). However, hepatobiliary iminodiacetic acid (HIDA) scans were definitively positive for acute cholecystitis in most patients in both populations (80.0% of HSCT recipients versus 77.4% of control subjects, P = .82). In conclusion, acute cholecystitis is a common early complication of HSCT, the risk is increased in patients who receive TPN, and it is associated with high 1-year mortality. In HSCT recipients with findings suggestive of acute cholecystitis, especially those receiving TPN, early use of HIDA scan may be considered over ultrasound. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Mutations in epigenetic regulators are involved in acute lymphoblastic leukemia relapse following allogeneic hematopoietic stem cell transplantation

PubMed Central

Lai, Xiaoyu; Li, Caihua; Shi, Jimin; Tan, Yamin; Fu, Shan; Wang, Yebo; Zhu, Ni; He, Jingsong; Zheng, Weiyan; Yu, Xiaohong; Cai, Zhen; Huang, He

2016-01-01

Although steady improvements to chemotherapeutic treatments has helped cure 80% of childhood acute lymphoblastic leukemia (ALL) cases, chemotherapy has proven to be less effective in treating the majority of adult patients, leaving allogeneic hematopoietic stem cell transplantation (allo-HSCT) as the primary adult treatment option. Nevertheless relapse are the leading cause of death following allo-HSCT. The genetic pathogenesis of relapse following allo-HSCT in Philadelphia chromosome- negative ALL (Ph− ALL) remains unexplored. We performed longitudinal whole-exome sequencing analysis in three adult patients with Ph− B-cell ALL (Ph− B-ALL) on samples collected from diagnosis to relapse after allo-HSCT. Based on these data, we performed target gene sequencing on 23 selected genes in 58 adult patients undergoing allo-HSCT with Ph− B-ALL. Our results revealed a significant enrichment of mutations in epigenetic regulators from relapsed samples, with recurrent somatic mutations in SETD2, CREBBP, KDM6A and NR3C1. The relapsed samples were also enriched in signaling factor mutations, including KRAS, PTPN21, MYC and USP54. Furthermore, we are the first to reveal the clonal evolution patterns during leukemia relapse after allo-HSCT. Cells present in relapsed specimens were genetically related to the diagnosed tumor, these cells therefore arose from either an existing subclone that was not eradicated by allo-HSCT therapy, or from the same progenitor that acquired new mutations. In some cases, however, it is possible that leukemia recurrence following allo-HSCT could result from a secondary malignancy with a distinct set of mutations. We identified novel genetic causes of leukemia relapse after allo-HSCT using the largest generated data set to date from adult patients with Ph− B-ALL. PMID:26527318

Combustor materials requirements and status of ceramic matrix composites

NASA Technical Reports Server (NTRS)

Hecht, Ralph J.; Johnson, Andrew M.

1992-01-01

The HSCT combustor will be required to operate with either extremely rich or lean fuel/air ratios to reduce NO(x) emission. NASA High Speed Research (HSR) sponsored programs at Pratt & Whitney (P&W) and GE Aircraft Engines (GEAE) have been studying rich and lean burn combustor design approaches which are capable of achieving the aggressive HSCT NO(x) emission goals. In both of the combustor design approaches under study, high temperature (2400-3000 F) materials are necessary to meet the HSCT emission goals of 3-8 gm/kg. Currently available materials will not meet the projected requirements for the HSCT combustor. The development of new materials is an enabling technology for the successful introduction to service of the HSCT.

Infectious complications after hematopoietic stem cell transplantation: current status and future perspectives in Korea

PubMed Central

Cho, Sung-Yeon; Lee, Hyeon-Jeong; Lee, Dong-Gun

2018-01-01

Hematopoietic stem cell transplantation (HSCT) is a treatment for hematologic malignancies, immune deficiencies, or genetic diseases, ect. Recently, the number of HSCTs performed in Korea has increased and the outcomes have improved. However, infectious complications account for most of the morbidity and mortality after HSCT. Post-HSCT infectious complications are usually classified according to the time after HSCT: pre-engraftment, immediate post-engraftment, and late post-engraftment period. In addition, the types and risk factors of infectious complications differ according to the stem cell source, donor type, conditioning intensity, region, prophylaxis strategy, and comorbidities, such as graft-versushost disease and invasive fungal infection. In this review, we summarize infectious complications after HSCT, focusing on the Korean perspectives. PMID:29506345

Immunogenicity and Safety of Yellow Fever Vaccine in Allogeneic Hematopoietic Stem Cell Transplant Recipients After Withdrawal of Immunosuppressive Therapy.

PubMed

Sicre de Fontbrune, Flore; Arnaud, Cécile; Cheminant, Morgane; Boulay, Aude; Konopacki, Johana; Lapusan, Simona; Robin, Christine; Bernaudin, Françoise; Suarez, Felipe; Simon, François; Socié, Gérard; Colin de Verdière, Nathalie; Consigny, Paul-Henri

2018-01-17

As a live attenuated vaccine, yellow fever vaccine (YFV) is not routinely performed after allogeneic hematopoietic stem cell transplant (HSCT) despite it being the only efficient preventive therapy. We retrospectively identified 21 HSCT recipients immunized with YFV at a median of 39 months after HSCT and a median of 33 months after withdrawal of immunosuppression without any side effects. Eighteen evaluable patients had protective immunity after YFV. We also observed that a third of the recipients vaccinated with YFV before HSCT had persistent protective immunity after HSCT. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

High speed civil transport

NASA Technical Reports Server (NTRS)

Bogardus, Scott; Loper, Brent; Nauman, Chris; Page, Jeff; Parris, Rusty; Steinbach, Greg

1990-01-01

The design process of the High Speed Civil Transport (HSCT) combines existing technology with the expectation of future technology to create a Mach 3.0 transport. The HSCT was designed to have a range in excess of 6000 nautical miles and carry up to 300 passengers. This range will allow the HSCT to service the economically expanding Pacific Basin region. Effort was made in the design to enable the aircraft to use conventional airports with standard 12,000 foot runways. With a takeoff thrust of 250,000 pounds, the four supersonic through-flow engines will accelerate the HSCT to a cruise speed of Mach 3.0. The 679,000 pound (at takeoff) HSCT is designed to cruise at an altitude of 70,000 feet, flying above most atmospheric disturbances.

Gut microbiota injury in allogeneic haematopoietic stem cell transplantation.

PubMed

Shono, Yusuke; van den Brink, Marcel R M

2018-05-01

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is considered to be the strongest curative immunotherapy for various malignancies (primarily, but not limited to, haematologic malignancies). However, application of allo-HSCT is limited owing to its life-threatening major complications, such as graft-versus-host disease (GVHD), relapse and infections. Recent advances in large-scale DNA sequencing technology have facilitated rapid identification of the microorganisms that make up the microbiota and evaluation of their interactions with host immunity in various diseases, including cancer. This has resulted in renewed interest regarding the role of the intestinal flora in patients with haematopoietic malignancies who have received an allo-HSCT and in whether the microbiota affects clinical outcomes, including GVHD, relapse, infections and transplant-related mortality. In this Review, we discuss the potential role of intestinal microbiota in these major complications after allo-HSCT, summarize clinical trials evaluating the microbiota in patients who have received allo-HSCT and discuss how further studies of the microbiota could inform the development of strategies that improve outcomes of allo-HSCT.

A stepwise, multi-objective, multi-variable parameter optimization method for the APEX model

USDA-ARS?s Scientific Manuscript database

Proper parameterization enables hydrological models to make reliable estimates of non-point source pollution for effective control measures. The automatic calibration of hydrologic models requires significant computational power limiting its application. The study objective was to develop and eval...

Gauchers disease--a reappraisal of hematopoietic stem cell transplantation.

PubMed

Ito, Sawa; Barrett, A John

2013-03-01

Hematopoietic stem cell transplantation (HSCT), first performed in 1984, was the first treatment approach for Gaucher's disease (GD) which had curative intent. The early successes in HSCT were soon eclipsed by the introduction of a highly effective enzyme replacement therapy (ERT), which has remained the single most widely used treatment. Experience with HSCT is limited to about 50 reported cases, mainly performed in the last century, with an overall survival around 85%. HSCT typically achieves complete correction of visceral and bony changes and can fully stabilize neurological features in otherwise progressive type II and III GD. ERT, in contrast, is completely safe and effective, but is limited by cost, incomplete resolution of visceral, hematological, and bony features in some patients, and lack of neurological correction in type II and III disease. In this review, we summarize and compare HSCT and ERT. With 20 years of experience of ERT, its limitations as well as its advantages are now well delineated. Meanwhile progress in HSCT over the last decade suggests that transplantation would today represent a very safe curative approach for GD offering one time complete correction of the disease, contrasting with the lifelong need for ERT with its associated expense and dependence on sophisticated drug manufacture. Additionally, unlike ERT, HSCT can be beneficial for neurological forms of GD. We conclude that the time has come to re-evaluate HSCT in selected patients with GD where ERT is less likely to fully eradicate symptoms of the disease.

Health-Related Quality of Life among Children and Adolescents during Hematopoietic Stem Cell Transplant Recovery.

PubMed

Rodgers, Cheryl; Wills-Bagnato, Patricia; Sloane, Richard; Hockenberry, Marilyn

2015-01-01

Health-related quality of life (HRQoL) has been noted to fluctuate among children during hematopoietic stem cell transplant (HSCT) recovery; however, the specific timing and associations of these changes are poorly understood. This repeated-measures study aimed to describe HRQoL changes among children and adolescents during the first 6 months of HSCT recovery and estimate the associations of demographic factors, diagnosis, transplant information, and symptoms with HRQoL. Twenty-three children and adolescents who received an allogeneic HSCT were recruited from a pediatric teaching institution in the southern United States. Demographic, diagnosis, and transplant information was obtained from the medical record. The Memorial Symptom Assessment questionnaire and the Peds Quality of Life Cancer Module (PedsQL CM) were completed at 1 month post-HSCT and then once monthly for 5 additional months. Mean HRQoL scores fluctuated during the study with the lowest mean HRQoL noted at 1 month post-HSCT and the highest mean HRQoL noted at 4 months post-HSCT. No significant differences in HRQoL scores were noted among demographic, diagnosis, or transplant factors. Feeling tired, sad, or worried or having insomnia at 1 month post-HSCT was negatively correlated to HRQoL. Nurses have opportunities to explore important issues with patients and need to be aware of fluctuations with HRQoL and factors associated with lower HRQoL during HSCT recovery. © 2015 by Association of Pediatric Hematology/Oncology Nurses.

Automatic multi-organ segmentation using learning-based segmentation and level set optimization.

PubMed

Kohlberger, Timo; Sofka, Michal; Zhang, Jingdan; Birkbeck, Neil; Wetzl, Jens; Kaftan, Jens; Declerck, Jérôme; Zhou, S Kevin

2011-01-01

We present a novel generic segmentation system for the fully automatic multi-organ segmentation from CT medical images. Thereby we combine the advantages of learning-based approaches on point cloud-based shape representation, such a speed, robustness, point correspondences, with those of PDE-optimization-based level set approaches, such as high accuracy and the straightforward prevention of segment overlaps. In a benchmark on 10-100 annotated datasets for the liver, the lungs, and the kidneys we show that the proposed system yields segmentation accuracies of 1.17-2.89 mm average surface errors. Thereby the level set segmentation (which is initialized by the learning-based segmentations) contributes with an 20%-40% increase in accuracy.

A Scalable, Parallel Approach for Multi-Point, High-Fidelity Aerostructural Optimization of Aircraft Configurations

NASA Astrophysics Data System (ADS)

Kenway, Gaetan K. W.

This thesis presents new tools and techniques developed to address the challenging problem of high-fidelity aerostructural optimization with respect to large numbers of design variables. A new mesh-movement scheme is developed that is both computationally efficient and sufficiently robust to accommodate large geometric design changes and aerostructural deformations. A fully coupled Newton-Krylov method is presented that accelerates the convergence of aerostructural systems and provides a 20% performance improvement over the traditional nonlinear block Gauss-Seidel approach and can handle more exible structures. A coupled adjoint method is used that efficiently computes derivatives for a gradient-based optimization algorithm. The implementation uses only machine accurate derivative techniques and is verified to yield fully consistent derivatives by comparing against the complex step method. The fully-coupled large-scale coupled adjoint solution method is shown to have 30% better performance than the segregated approach. The parallel scalability of the coupled adjoint technique is demonstrated on an Euler Computational Fluid Dynamics (CFD) model with more than 80 million state variables coupled to a detailed structural finite-element model of the wing with more than 1 million degrees of freedom. Multi-point high-fidelity aerostructural optimizations of a long-range wide-body, transonic transport aircraft configuration are performed using the developed techniques. The aerostructural analysis employs Euler CFD with a 2 million cell mesh and a structural finite element model with 300 000 DOF. Two design optimization problems are solved: one where takeoff gross weight is minimized, and another where fuel burn is minimized. Each optimization uses a multi-point formulation with 5 cruise conditions and 2 maneuver conditions. The optimization problems have 476 design variables are optimal results are obtained within 36 hours of wall time using 435 processors. The TOGW minimization results in a 4.2% reduction in TOGW with a 6.6% fuel burn reduction, while the fuel burn optimization resulted in a 11.2% fuel burn reduction with no change to the takeoff gross weight.

An Efficacious Multi-Objective Fuzzy Linear Programming Approach for Optimal Power Flow Considering Distributed Generation.

PubMed

Warid, Warid; Hizam, Hashim; Mariun, Norman; Abdul-Wahab, Noor Izzri

2016-01-01

This paper proposes a new formulation for the multi-objective optimal power flow (MOOPF) problem for meshed power networks considering distributed generation. An efficacious multi-objective fuzzy linear programming optimization (MFLP) algorithm is proposed to solve the aforementioned problem with and without considering the distributed generation (DG) effect. A variant combination of objectives is considered for simultaneous optimization, including power loss, voltage stability, and shunt capacitors MVAR reserve. Fuzzy membership functions for these objectives are designed with extreme targets, whereas the inequality constraints are treated as hard constraints. The multi-objective fuzzy optimal power flow (OPF) formulation was converted into a crisp OPF in a successive linear programming (SLP) framework and solved using an efficient interior point method (IPM). To test the efficacy of the proposed approach, simulations are performed on the IEEE 30-busand IEEE 118-bus test systems. The MFLP optimization is solved for several optimization cases. The obtained results are compared with those presented in the literature. A unique solution with a high satisfaction for the assigned targets is gained. Results demonstrate the effectiveness of the proposed MFLP technique in terms of solution optimality and rapid convergence. Moreover, the results indicate that using the optimal DG location with the MFLP algorithm provides the solution with the highest quality.

An Efficacious Multi-Objective Fuzzy Linear Programming Approach for Optimal Power Flow Considering Distributed Generation

PubMed Central

Warid, Warid; Hizam, Hashim; Mariun, Norman; Abdul-Wahab, Noor Izzri

2016-01-01

This paper proposes a new formulation for the multi-objective optimal power flow (MOOPF) problem for meshed power networks considering distributed generation. An efficacious multi-objective fuzzy linear programming optimization (MFLP) algorithm is proposed to solve the aforementioned problem with and without considering the distributed generation (DG) effect. A variant combination of objectives is considered for simultaneous optimization, including power loss, voltage stability, and shunt capacitors MVAR reserve. Fuzzy membership functions for these objectives are designed with extreme targets, whereas the inequality constraints are treated as hard constraints. The multi-objective fuzzy optimal power flow (OPF) formulation was converted into a crisp OPF in a successive linear programming (SLP) framework and solved using an efficient interior point method (IPM). To test the efficacy of the proposed approach, simulations are performed on the IEEE 30-busand IEEE 118-bus test systems. The MFLP optimization is solved for several optimization cases. The obtained results are compared with those presented in the literature. A unique solution with a high satisfaction for the assigned targets is gained. Results demonstrate the effectiveness of the proposed MFLP technique in terms of solution optimality and rapid convergence. Moreover, the results indicate that using the optimal DG location with the MFLP algorithm provides the solution with the highest quality. PMID:26954783

An Integer Programming Model for Multi-Echelon Supply Chain Decision Problem Considering Inventories

NASA Astrophysics Data System (ADS)

Harahap, Amin; Mawengkang, Herman; Siswadi; Effendi, Syahril

2018-01-01

In this paper we address a problem that is of significance to the industry, namely the optimal decision of a multi-echelon supply chain and the associated inventory systems. By using the guaranteed service approach to model the multi-echelon inventory system, we develop a mixed integer; programming model to simultaneously optimize the transportation, inventory and network structure of a multi-echelon supply chain. To solve the model we develop a direct search approach using a strategy of releasing nonbasic variables from their bounds, combined with the “active constraint” method. This strategy is used to force the appropriate non-integer basic variables to move to their neighbourhood integer points.

Re-infection of Toxoplasma gondii after HSCT presenting lymphadenopathy resembling recurrence of lymphoma.

PubMed

Hashiguchi, Junichi; Onozawa, Masahiro; Naka, Tomoaki; Hatanaka, Kanako C; Shiratori, Souichi; Sugita, Junichi; Fujimoto, Katsuya; Matsuno, Yoshihiro; Teshima, Takanori

2018-06-01

Toxoplasma gondii (T. gondii) reactivation is one of the fatal complications after hematopoietic stem cell transplantation (HSCT); however, re-infection has not been reported. Here, we report a case of mycosis fungoides in which cervical lymphadenopathy developed after HSCT. Initially, recurrent lymphoma was suspected. However, biopsy of the lymph node showed typical histology of toxoplasmosis and serology showed re-infection of T. gondii. Toxoplasmosis needs to be differentiated for cases with lymphoadenopthy after HSCT. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Outcome of patients with relapsed/refractory adult T-cell leukemia-lymphoma after salvage therapy].

PubMed

Taniguchi, Hiroaki; Imaizumi, Yoshitaka; Makiyama, Junya; Itonaga, Hidehiro; Ando, Koji; Sawayama, Yasushi; Imanishi, Daisuke; Taguchi, Jun; Tsushima, Hideki; Hata, Tomoko; Hasegawa, Hiroo; Hayashi, Tomayoshi; Niino, Daisuke; Ohshima, Koichi; Tsukasaki, Kunihiro; Miyazaki, Yasushi

2013-12-01

We retrospectively analyzed 81 relapsed or refractory adult T-cell leukemia-lymphoma (ATL) patients who received salvage therapy in our institution between 2000 and 2010. These patients had received chemotherapy, radiation, or hematopoietic stem cell transplantation (HSCT) as an initial treatment, and were then given chemotherapy, radiation, HSCT, or donor lymphocyte infusion (DLI) as salvage therapy. Median survival time was 3.9 months. Of 5 long-term survivors, who survived more than 2 years after the first salvage therapy, 4 patients received HSCT or DLI, and the other was given mogamulizumab as the salvage therapy. For patients with relapsed or refractory ATL, HSCT/DLI is a promising treatment for achieving long-term survival. Mogamulizumab may be the good choice for those who are ineligible for HSCT.

Aircraft Emission Inventories Projected in Year 2015 for a High Speed Civil Transport (HSCT) Universal Airline Network

NASA Technical Reports Server (NTRS)

Baughcum, Steven L.; Henderson, Stephen C.

1995-01-01

This report describes the development of a three-dimensional database of aircraft fuel burn and emissions (fuel burned, NOx, CO, and hydrocarbons) from projected fleets of high speed civil transports (HSCT's) on a universal airline network.Inventories for 500 and 1000 HSCT fleets, as well as the concurrent subsonic fleets, were calculated. The objective of this work was to evaluate the changes in geographical distribution of the HSCT emissions as the fleet size grew from 500 to 1000 HSCT's. For this work, a new expanded HSCT network was used and flights projected using a market penetration analysis rather than assuming equal penetration as was done in the earlier studies. Emission inventories on this network were calculated for both Mach 2.0 and Mach 2.4 HSCT fleets with NOx cruise emission indices of approximately 5 and 15 grams NOx/kg fuel. These emissions inventories are available for use by atmospheric scientists conducting the Atmospheric Effects of Stratospheric Aircraft (AESA) modeling studies. Fuel burned and emissions of nitrogen oxides (NOx as NO2), carbon monoxide, and hydrocarbons have been calculated on a 1 degree latitude x 1 degree longitude x 1 kilometer attitude grid and delivered to NASA as electronic files.

Viral-specific T-cell transfer from HSCT donor for the treatment of viral infections or diseases after HSCT.

PubMed

Qian, C; Wang, Y; Reppel, L; D'aveni, M; Campidelli, A; Decot, V; Bensoussan, D

2018-02-01

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative option for treatment of some malignant and non-malignant hematological diseases. However, post-HSCT patients are severely immunocompromised and susceptible to viral infections, which are a major cause of morbidity and mortality. Although antiviral agents are now available for most types of viral infections, they are not devoid of side effects and their efficacy is limited when there is no concomitant antiviral immune reconstitution. In recent decades, adoptive transfer of viral-specific T cells (VSTs) became an alternative treatment for viral infection after HSCT. However, two major issues are concerned in VST transfer: the risk of GVHD and antiviral efficacy. We report an exhaustive review of the published studies that focus on prophylactic and/or curative therapy by donor VST transfer for post-HSCT common viral infections. A low incidence of GVHD and a good antiviral efficacy was observed after adoptive transfer of VSTs from HSCT donor. Viral-specific T-cell transfer is a promising approach for a broad clinical application. Nevertheless, a randomized controlled study in a large cohort of patients comparing antiviral treatment alone to antiviral treatment combined with VSTs is still needed to demonstrate efficacy and safety.

Risk of sinusoidal obstruction syndrome in allogeneic stem cell transplantation after prior gemtuzumab ozogamicin treatment: a retrospective study from the Acute Leukemia Working Party of the EBMT.

PubMed

Battipaglia, G; Labopin, M; Candoni, A; Fanin, R; El Cheikh, J; Blaise, D; Michallet, M; Ruggeri, A; Contentin, N; Ribera, J M; Stadler, M; Sierra, J; von dem Borne, P A; Bloor, A; Socié, G; Nagler, A; Mohty, M

2017-04-01

Gemtuzumab ozogamicin (GO) may increase the risk of sinusoidal obstruction syndrome (SOS) when used prior to allogeneic stem cell transplantation (HSCT). We assessed SOS incidence and outcomes after HSCT of 146 adults, with a median age of 50 years, previously receiving GO. SOS prophylaxis was used in 69 patients (heparin n=57, ursodeoxycholic acid n=8, defibrotide n=4). Cumulative incidence (CI) of SOS was 8% (n=11), with death in 3 patients. Median interval between last GO dose and HSCT was 130 days. Overall survival (OS) and SOS incidence did not differ for patients receiving GO ⩽3.5 months before HSCT and the others. CI of acute and chronic GVHD was 31% and 25%, respectively. Probability of OS and leukemia-free survival (LFS) at 5 years was 40% and 37%, respectively. Relapse incidence and non-relapse mortality were 42% and 21%, respectively. In multivariate analysis, active disease at HSCT was associated with relapse and worse LFS and OS (P<0.03). Liver abnormalities before HSCT correlated with worse OS (P<0.03). Use of low-dose GO prior to HSCT is associated with an acceptable SOS incidence. Prospective studies investigating the role and the utility of SOS prophylaxis are warranted.

Memory B lymphocytes determine repertoire oligoclonality early after haematopoietic stem cell transplantation

PubMed Central

OMAZIC, B; LUNDKVIST, I; MATTSSON, J; PERMERT, J; NÄSMAN-BJÖRK, I

2003-01-01

The objective of this study was to investigate if oligoclonality of the Ig repertoire post-haematopoietic stem cell transplantation (HSCT) is restricted to memory B lymphocytes or if it is a general property among B lymphocytes. As a measure of B lymphocyte repertoire diversity, we have analysed size distribution of polymerase chain reaction (PCR) amplified Ig H complementarity determining region 3 (CDR3) in naive and memory B lymphocytes isolated from patients before HSCT and at 3, 6 and 12 months after HSCT as well as from healthy controls. We demonstrate a limited variation of the IgH CDR3 repertoire in the memory B lymphocyte population compared to the naive B cell population. This difference was significant at 3 and 6 months post-HSCT. Compared to healthy controls there is a significant restriction of the memory B lymphocyte repertoire at 3 months after HSCT, but not of the naive B lymphocyte repertoire. Twelve months after HSCT, the IgH CDR3 repertoire in both memory and naive B lymphocytes are as diverse as in healthy controls. Thus, our findings suggest a role for memory B cells in the restriction of the oligoclonal B cell repertoire observed early after HSCT, which may be of importance when considering reimmunization of transplanted patients. PMID:12974769

Clinical Impact of Pretransplant Multidrug-Resistant Gram-Negative Colonization in Autologous and Allogeneic Hematopoietic Stem Cell Transplantation.

PubMed

Forcina, Alessandra; Lorentino, Francesca; Marasco, Vincenzo; Oltolini, Chiara; Marcatti, Magda; Greco, Raffaella; Lupo-Stanghellini, Maria Teresa; Carrabba, Matteo; Bernardi, Massimo; Peccatori, Jacopo; Corti, Consuelo; Ciceri, Fabio

2018-03-02

Multidrug-resistant Gram-negative bacteria (MDR-GNB) are an emerging cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Three-hundred forty-eight consecutive patients transplanted at our hospital from July 2012 to January 2016 were screened for a pretransplant MDR-GNB colonization and evaluated for clinical outcomes. A pretransplant MDR-GNB colonization was found in 16.9% of allo-HSCT and in 9.6% of auto-HSCT recipients. Both in auto- and in allo-HSCT, carriers of a MDR-GNB showed no significant differences in overall survival (OS), transplant-related mortality (TRM), or infection-related mortality (IRM) compared with noncarriers. OS at 2 years for carriers compared with noncarriers was 85% versus 81% (P = .262) in auto-HSCT and 50% versus 43% (P = .091) in allo-HSCT. TRM at 2 years was 14% versus 5% (P = .405) in auto-HSCT and 31% versus 25% (P = .301) in allo-HSCT. IRM at 2 years was 14% versus 2% (P = .142) in auto-HSCT and 23% versus 14% (P = .304) in allo-HSCT. In multivariate analysis, only grade III to IV acute graft-versus-host disease was an independent factor for reduced OS (P < .001) and increased TRM (P < .001) and IRM (P < .001). During the first year after transplant, we collected 73 GNB bloodstream infectious (BSI) episodes in 54 patients, 42.4% of which sustained by a MDR-GNB. Rectal swabs positivity associated with the pathogen causing subsequent MDR-GNB BSI episodes in 13 of 31 (41.9%). Overall, OS at 4 months from MDR-GNB BSI episode onset was of 67.9%, with a 14-day attributed mortality of 12.9%, not being significantly different between carriers and noncarriers (P = .207). We conclude that in this extended single-center experience, a pretransplant MDR-GNB colonization did not significantly influence OS, TRM, and IRM both in auto- and allo-HSCT settings and that MDR-GNB attributed mortality can be controlled in carriers when an early pre-emptive antimicrobial therapy is started in case of neutropenic fever. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Evaluation of a stepwise, multi-objective, multi-variable parameter optimization method for the APEX model

USDA-ARS?s Scientific Manuscript database

Hydrologic models are essential tools for environmental assessment of agricultural non-point source pollution. The automatic calibration of hydrologic models, though efficient, demands significant computational power, which can limit its application. The study objective was to investigate a cost e...

Current Concepts in Pediatric Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

PubMed Central

Bernt, Kathrin M.; Hunger, Stephen P.

2014-01-01

The t(9;22)(q34;q11) or Philadelphia chromosome creates a BCR–ABL1 fusion gene encoding for a chimeric BCR–ABL1 protein. It is present in 3–4% of pediatric acute lymphoblastic leukemia (Ph+ ALL), and about 25% of adult ALL cases. Prior to the advent of tyrosine kinase inhibitors (TKI), Ph+ ALL was associated with a very poor prognosis despite the use of intensive chemotherapy and frequently hematopoietic stem-cell transplantation (HSCT) in first remission. The development of TKIs revolutionized the therapy of Ph+ ALL. Addition of the first generation ABL1 class TKI imatinib to intensive chemotherapy dramatically increased the survival for children with Ph+ ALL and established that many patients can be cured without HSCT. In parallel, the mechanistic understanding of Ph+ ALL expanded exponentially through careful mapping of pathways downstream of BCR–ABL1, the discovery of mutations in master regulators of B-cell development such as IKZF1 (Ikaros), PAX5, and early B-cell factor (EBF), the recognition of the complex clonal architecture of Ph+ ALL, and the delineation of genomic, epigenetic, and signaling abnormalities contributing to relapse and resistance. Still, many important basic and clinical questions remain unanswered. Current clinical trials are testing second generation TKIs in patients with newly diagnosed Ph+ ALL. Neither the optimal duration of therapy nor the optimal chemotherapy backbone are currently defined. The role of HSCT in first remission and post-transplant TKI therapy also require further study. In addition, it will be crucial to continue to dig deeper into understanding Ph+ ALL at a mechanistic level, and translate findings into complementary targeted approaches. Expanding targeted therapies hold great promise to decrease toxicity and improve survival in this high-risk disease, which provides a paradigm for how targeted therapies can be incorporated into treatment of other high-risk leukemias. PMID:24724051

Hematopoietic Stem Cell Transplantation in Thalassemia and Sickle Cell Disease. Unicenter Experience in a Multi-Ethnic Population.

PubMed Central

Marziali, Marco; Isgrò, Antonella; Gaziev, Javid; Lucarelli, Guido

2009-01-01

Hematopoietic stem cell transplantation (HSCT) still remains the only definitive cure currently available for patients with thalassemia and sickle cell anemia. Results of transplant in thalassemia and in sickle cell anemia have steadily improved over the last two decades due to improvements in preventive strategies, and effective control of transplant-related complications. From 2004 through 2009, 145 consecutive patients with thalassemia and sickle cell anemia, ethnically heterogeneous from Mediterranean and Middle East countries, were given HSCT in the International Center for Transplantation in Thalassemia and Sickle Cella Anemia in Rome. This experience is characterized by two peculiarities: patients were ethnically very heterogeneous and the vast majority of these patients were not regularly transfesed/chelated and therefore were highly sensitized due to RBC transfusions without leukodepletion filters. Consequently, they could have a high risk of graft rejection as a result of sensitization to HLA antigens. The Rome experience of SCT in patients with thalassemia and sickle cell anemia confirmed the results obtained in Pesaro, and most importantly showed the reproducibility of these results in other centers. PMID:21415995

Optimal Information Extraction of Laser Scanning Dataset by Scale-Adaptive Reduction

NASA Astrophysics Data System (ADS)

Zang, Y.; Yang, B.

2018-04-01

3D laser technology is widely used to collocate the surface information of object. For various applications, we need to extract a good perceptual quality point cloud from the scanned points. To solve the problem, most of existing methods extract important points based on a fixed scale. However, geometric features of 3D object come from various geometric scales. We propose a multi-scale construction method based on radial basis function. For each scale, important points are extracted from the point cloud based on their importance. We apply a perception metric Just-Noticeable-Difference to measure degradation of each geometric scale. Finally, scale-adaptive optimal information extraction is realized. Experiments are undertaken to evaluate the effective of the proposed method, suggesting a reliable solution for optimal information extraction of object.

Feasibility of allogeneic stem-cell transplantation after azacitidine bridge in higher-risk myelodysplastic syndromes and low blast count acute myeloid leukemia: results of the BMT-AZA prospective study.

PubMed

Voso, M T; Leone, G; Piciocchi, A; Fianchi, L; Santarone, S; Candoni, A; Criscuolo, M; Masciulli, A; Cerqui, E; Molteni, A; Finelli, C; Parma, M; Poloni, A; Carella, A M; Spina, F; Cortelezzi, A; Salvi, F; Alessandrino, E P; Rambaldi, A; Sica, S

2017-07-01

Allogeneic stem-cell transplantation (HSCT) is the only curative treatment in myelodysplastic syndromes (MDS). Azacitidine (AZA) is increasingly used prior to HSCT, however in Europe it is only approved for patients who are not eligible for HSCT. We conducted a phase II multicenter study to prospectively evaluate the feasibility of HSCT after treatment with AZA in 70 patients with a myelodysplastic syndrome (MDS), 19 with acute myeloid leukemia (AML), and 8 with chronic myelomonocytic leukemia (CMML). After a median of four cycles (range 1-11): 24% of patients achieved complete remission, 14% partial remission, 8% hematologic improvement, 32% had stable and 22% progressive disease. Ten patients discontinued treatment before the planned four cycles, due to an adverse event in nine cases. A HSC donor was identified in 73 patients, and HSCT was performed in 54 patients (74% of patients with a donor). Main reasons for turning down HSCT were lack of a donor, an adverse event, or progressive disease (9, 12, and 16 patients, respectively). At a median follow-up of 20.5 months from enrolment, response to AZA was the only independent prognostic factor for survival. Compared to baseline assessment, AZA treatment did not affect patients' comorbidities at HSCT: the HCT-CI remained stable in 62% patients, and worsened or improved in 23% and 15% of patients, respectively. Our study shows that HSCT is feasible in the majority of patients with HR-MDS/AML/CMML-2 after AZA treatment. As matched unrelated donor was the most frequent source of donor cells, the time between diagnosis and HSCT needed for donor search could be 'bridged' using azacitidine. These data show that AZA prior to HSCT could be a better option than intensive chemotherapy in higher-risk MDS. The trial has been registered with the EudraCT number 2010-019673-1. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

[Effects of blueberry on apoptosis and expression of Bcl-2 and Bax in HSC-T6].

PubMed

Lu, Shuang; Cheng, Mingliang; Yang, Demeng; Liu, Yang; Guan, Li; Wu, Jun

2015-08-18

To investigate the effects of blueberry on the apoptosis, expression of Bcl-2 and Bax in rat hepatic stellate cell (HSC-T6). 10% blueberry serum at low, middle and high dose, 10% Fu-Fang-Bie-Jia-Ruan-Gan tablet serum and 10% saline serum were prepared by method of serum pharmacology. Subcultured HSC-T6 was divided into saline serum control group, blueberry serum at low, middle, high dose and Fu-Fang-Bie-Jia-Ruan-Gan tablet serum group, and then was respectively incubated at different dose of 10% blueberry serum, 10% Fu-Fang-Bie-Jia-Ruan-Gan tablet serum and 10% saline serum for 72 hours.Apoptosis of HSC-T6 was detected using flow cytometry with annexin V FITC/PI double staining. The expression of Bcl-2 and Bax in HSC-T6 were examined using immunocytochemistry and Western blotting, respectively. There was no significant difference for HSC-T6 Bax protein expression in the low, middle and high dose blueberry serum groups, compared with saline serum control group, respectively.In the high-dose blueberry serum group HSC-T6 early and total apoptosis rate increased significantly compared with the saline serum control group (5.55% ± 0.98% vs 2.53% ± 0.46%, 7.01% ± 1.05% vs 2.96% ± 0.81%, both P<0.05); Bcl-2 protein expression was significantly decreased (A value, 82 ± 35 vs 51 ± 13, P<0.05); Bcl-2/Bax ratio was significantly decreased (0.26 ± 0.02 vs 0.46 ± 0.03, P<0.05); HSC-T6 early and total apoptosis rate, Bcl-2 expression and Bcl-2/Bax ratio in the low and the middle dose blueberry serum group showed no significant difference with the saline serum control group. Blueberry can induce HSC-T6 apoptosis by down-regulating Bcl-2 expression and decreasing the ratio of Bcl-2/Bax in HSC-T6 cells, so it may have potential interference effects on hepatic fibrosis.

Psychopathological Aspects in Childhood Hematopoietic Stem Cell Transplantation (HSCT): The Perception of Parents and Adolescents.

PubMed

Zanato, Silvia; Traverso, Annalisa; Tremolada, Marta; Sinatora, Francesco; Porreca, Alessio; Pozziani, Giorgio; Di Florio, Nicoletta; Capello, Fabia; Marzollo, Antonio; Tumino, Manuela; Cattelan, Chiara; Basso, Giuseppe; Messina, Chiara

2017-01-01

Background: Data about psychosocial sequelae of childhood Hematopoietic Stem Cell Transplantation (HSCT) are limited and the association with a specific donor type or other medical factors is largely unknown (Chang et al., 2012). The aim of the present study was to compare the psychological aspects of pediatric HSCT survivors with healthy peers. A secondary aim was to detect whether parents and children differed in the perception of mental health status. The influence of medical factors on psychological status was also examined. Method: Thirty seven HSCT survivors (23 males) with a mean age of 14.4 years ( SD = 3.03; range 8.16-18.33) were recruited. Twenty-six patients underwent an allogenic HSCT (matched unrelated donor, n = 20; matched sibling donor, n = 6) and 11 patients received an autologous HSCT. The children psychological aspects were assessed using the Youth Self Report (YSR) (Achenbach and Rescorla, 2001) and compared to a group of matched healthy peers. At the same time, parents were requested to complete the Child Behavior Checklist 6-18 (Achenbach and Rescorla, 2001). Medical and socio-demographic data were also collected. Results: HSCT survivors reported significantly higher levels of somatic complains ( t 27 = 3.14; p = 0.004; mean = 3.1) when compared to healthy peers (mean = 1.5). The parent CBCL scores on "child total competence" exceeded the normative clinical cutoff in 48.6% cases. Inter-rater agreement between parent and patient reports was present only in three scales: total competence score ( K = 0.06, p = 0.002), somatic complaints ( K = 0.21, p = 0.003) and attention problems ( k = 0.13; p = 0.02). According to Ancova models, internalizing problems were more frequent in HSCT from family donors ( F 2 = 3.13; p = 0.06) or in the presence of acute complications ( F 1 = 11.95; p = 0.003). Conclusion: In contrast to the perception of parents, pediatric HSCT survivors reported good psychological health. However, they complained about more somatic problems as compared with healthy peers. Medical aspects such as donor source and the presence of acute complications should be taken into consideration for the psychological approach in order to improve pediatric HSCT survivor care.

Persistent MRD before and after allogeneic BMT predicts relapse in children with acute lymphoblastic leukaemia.

PubMed

Sutton, Rosemary; Shaw, Peter J; Venn, Nicola C; Law, Tamara; Dissanayake, Anuruddhika; Kilo, Tatjana; Haber, Michelle; Norris, Murray D; Fraser, Chris; Alvaro, Frank; Revesz, Tamas; Trahair, Toby N; Dalla-Pozza, Luciano; Marshall, Glenn M; O'Brien, Tracey A

2015-02-01

Minimal residual disease (MRD) during early chemotherapy is a powerful predictor of relapse in acute lymphoblastic leukaemia (ALL) and is used in children to determine eligibility for allogeneic haematopoietic stem cell transplantation (HSCT) in first (CR1) or later complete remission (CR2/CR3). Variables affecting HSCT outcome were analysed in 81 children from the ANZCHOG ALL8 trial. The major cause of treatment failure was relapse, with a cumulative incidence of relapse at 5 years (CIR) of 32% and treatment-related mortality of 8%. Leukaemia-free survival (LFS) and overall survival (OS) were similar for HSCT in CR1 (LFS 62%, OS 83%, n = 41) or CR2/CR3 (LFS 60%, OS 72%, n = 40). Patients achieving bone marrow MRD negativity pre-HSCT had better outcomes (LFS 83%, OS 92%) than those with persistent MRD pre-HSCT (LFS 41%, OS 64%, P < 0·0001) or post-HSCT (LFS 35%, OS 55%, P < 0·0001). Patients with B-other ALL had more relapses (CIR 50%, LFS 41%) than T-ALL and the main precursor-B subtypes including BCR-ABL1, KMT2A (MLL), ETV6-RUNX1 (TEL-AML1) and hyperdiploidy >50. A Cox multivariate regression model for LFS retained both B-other ALL subtype (hazard ratio 4·1, P = 0·0062) and MRD persistence post-HSCT (hazard ratio 3·9, P = 0·0070) as independent adverse prognostic variables. Persistent MRD could be used to direct post-HSCT therapy. © 2014 John Wiley & Sons Ltd.

Hematopoietic stem cell transplantation for Morquio A syndrome.

PubMed

Yabe, Hiromasa; Tanaka, Akemi; Chinen, Yasutsugu; Kato, Shunichi; Sawamoto, Kazuki; Yasuda, Eriko; Shintaku, Haruo; Suzuki, Yasuyuki; Orii, Tadao; Tomatsu, Shunji

2016-02-01

Morquio A syndrome features systemic skeletal dysplasia. To date, there has been no curative therapy for this skeletal dysplasia. No systemic report on a long-term effect of hematopoietic stem cell transplantation (HSCT) for Morquio A has been described. We conducted HSCT for 4 cases with Morquio A (age at HSCT: 4-15years, mean 10.5years) and followed them at least 10years (range 11-28years; mean 19years). Current age ranged between 25 and 36years of age (mean 29.5years). All cases had a successful full engraftment of allogeneic bone marrow transplantation without serious GVHD. Transplanted bone marrow derived from HLA-identical siblings (three cases) or HLA-identical unrelated donor. The levels of the enzyme activity in the recipient's lymphocytes reached the levels of donors' enzyme activities within two years after HSCT. For the successive over 10years post-BMT, GALNS activity in lymphocytes was maintained at the same level as the donors. Except one case who had osteotomy in both legs one year later post BMT, other three cases had no orthopedic surgical intervention. All cases remained ambulatory, and three of them could walk over 400m. Activity of daily living (ADL) in patients with HSCT was better than untreated patients. The patient who underwent HSCT at four years of age showed the best ADL score. In conclusion, the long-term study of HSCT has demonstrated therapeutic effect in amelioration of progression of the disease in respiratory function, ADL, and biochemical findings, suggesting that HSCT is a therapeutic option for patients with Morquio A. Copyright © 2015 Elsevier Inc. All rights reserved.

Hematopoietic Stem Cell Transplantation for Morquio A Syndrome

PubMed Central

Yabe, Hiromasa; Tanaka, Akemi; Chinen, Yasutsugu; Kato, Shunichi; Sawamoto, Kazuki; Yasuda, Eriko; Shintaku, Haruo; Suzuki, Yasuyuki; Orii, Tadao; Tomatsu, Shunji

2016-01-01

Morquio A syndrome features systemic skeletal dysplasia. To date, there has been no curative therapy for this skeletal dysplasia. No systemic report on a long-term effect of hematopoietic stem cell transplantation (HSCT) for Morquio A has been described. We conducted HSCT for 4 cases with Morquio A (age at HSCT: 4–15 years, mean 10.5 years) and followed them at least 10 years (range 11–28 years; mean 19 years). Current age ranged between 25 and 36 years of age (mean 29.5 years). All cases had a successful full engraftment of allogeneic bone marrow transplantation without serious GVHD. Transplanted bone marrow derived from HLA-identical siblings (three cases) or HLA-identical unrelated donor. The levels of the enzyme activity in the recipient’s lymphocytes reached the levels of donors’ enzyme activities within two years after HSCT. For the successive over 10 years post-BMT, GALNS activity in lymphocytes was maintained at the same level as the donors. Except one case who had osteotomy in both legs one year later post BMT, other three cases had no orthopedic surgical intervention. All cases remained ambulatory, and three of them could walk over 400 m. Activity of daily living (ADL) in patients with HSCT was better than untreated patients. The patient who underwent HSCT at four years of age showed the best ADL score. In conclusion, the long-term study of HSCT has demonstrated therapeutic effect in amelioration of progression of the disease in respiratory function, ADL, and biochemical findings, suggesting that HSCT is a therapeutic option for patients with Morquio A. PMID:26452513

Prospective assessment of bone turnover and clinical bone diseases after allogeneic hematopoietic stem-cell transplantation.

PubMed

Petropoulou, Anna D; Porcher, Raphael; Herr, Andrée-Laure; Devergie, Agnès; Brentano, Thomas Funck; Ribaud, Patricia; Pinto, Fernando O; Rocha, Vanderson; Peffault de Latour, Régis; Orcel, Philippe; Socié, Gérard; Robin, Marie

2010-06-15

Bone complications after hematopoietic stem-cell transplantation (HSCT) are relatively frequent. Evaluation of biomarkers of bone turnover and dual energy x-ray absorptiometry (DEXA) are not known in this context. We prospectively evaluated bone mineral density, biomarkers of bone turnover, and the cumulative incidence of bone complications after allogeneic HSCT. One hundred forty-six patients were included. Bone mineral density was measured by DEXA 2-month and 1-year post-HSCT. The markers of bone turnover were serum C-telopeptide (C-TP), 5 tartrate-resistant acid phosphatase (bone resorption), and osteocalcin (bone formation) determined pre-HSCT and 2 months and 1 year thereafter. Potential association between osteoporosis at 2 months, osteoporotic fracture or avascular necrosis and, individual patient's characteristics and biologic markers were tested. C-TP was high before and 2 months after transplant. At 2 months, DEXA detected osteoporosis in more than half the patients tested. Male sex, median age less than or equal to 15 years, and abnormal C-TP before HSCT were risk factors significantly associated with osteoporosis. Three-year cumulative incidences of fractures and avascular necrosis were 8% and 11%, respectively. Children were at higher risk of fracture, whereas corticosteroid treatment duration was a significant risk factor for developing a clinical bone complication post-HSCT. Bone complications and osteoporosis are frequent after HSCT. Bone biologic markers and DEXA showed that subclinical bone abnormalities appeared early post-HSCT. The risk factors, age, gender, and C-TP easily available at the time of transplantation were identified. Biphosphonates should probably be given to patients with those risk factors.

Risk Factors and Outcomes Related to Pediatric Intensive Care Unit Admission after Hematopoietic Stem Cell Transplantation: A Single-Center Experience.

PubMed

Pillon, Marta; Amigoni, Angela; Contin, Annaelena; Cattelan, Manuela; Carraro, Elisa; Campagnano, Emiliana; Tumino, Manuela; Calore, Elisabetta; Marzollo, Antonio; Mainardi, Chiara; Boaro, Maria Paola; Nizzero, Marta; Pettenazzo, Andrea; Basso, Giuseppe; Messina, Chiara

2017-08-01

To describe incidence, causes, and outcomes related to pediatric intensive care unit (PICU) admission for patients undergoing hematopoietic stem cell transplantation (HSCT), we investigated the risk factors predisposing to PICU admission and prognostic factors in terms of patient survival. From October 1998 to April 2015, 496 children and young adults (0 to 23 years) underwent transplantation in the HSCT unit. Among them, 70 (14.1%) were admitted to PICU. The 3-year cumulative incidence of PICU admission was 14.3%. The main causes of PICU admission were respiratory failure (36%), multiple organ failure (16%), and septic shock (13%). The overall 90-day cumulative probability of survival after PICU admission was 34.3% (95% confidence interval, 24.8% to 47.4%). In multivariate analysis, risk factors predisposing to PICU admission were allogeneic HSCT (versus autologous HSCT, P = .030) and second or third HSCT (P = .018). Characteristics significantly associated with mortality were mismatched HSCT (P = .011), relapse of underlying disease before PICU admission (P < .001), acute respiratory distress syndrome at admission (P = .012), hepatic failure at admission (P = .021), and need for invasive ventilation during PICU course (P < .001). Our data indicate which patients have a high risk for PICU admission after HSCT and for dismal outcomes after PICU stay. These findings may provide support for the clinical decision-making process on the opportunity of PICU admission for severely compromised patients after HSCT. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Evolution, trends, outcomes, and economics of hematopoietic stem cell transplantation in severe autoimmune diseases.

PubMed

Snowden, John A; Badoglio, Manuela; Labopin, Myriam; Giebel, Sebastian; McGrath, Eoin; Marjanovic, Zora; Burman, Joachim; Moore, John; Rovira, Montserrat; Wulffraat, Nico M; Kazmi, Majid; Greco, Raffaella; Snarski, Emilian; Kozak, Tomas; Kirgizov, Kirill; Alexander, Tobias; Bader, Peter; Saccardi, Riccardo; Farge, Dominique

2017-12-26

Hematopoietic stem cell transplantation (HSCT) has evolved for >20 years as a specific treatment of patients with autoimmune disease (AD). Using European Society for Blood and Marrow Transplantation registry data, we summarized trends and identified factors influencing activity and outcomes in patients with AD undergoing first autologous HSCT (n = 1951; median age, 37 years [3-76]) and allogeneic HSCT (n = 105; median age, 12 years [<1-62]) in 247 centers in 40 countries from 1994 to 2015. Predominant countries of activity were Italy, Germany, Sweden, the United Kingdom, The Netherlands, Spain, France, and Australia. National activity correlated with the Human Development Index ( P = .006). For autologous HSCT, outcomes varied significantly between diseases. There was chronological improvement in progression-free survival (PFS, P < 10 -5 ), relapse/progression ( P < 10 -5 ), and nonrelapse mortality ( P = .01). Health care expenditure was associated with improved outcomes in systemic sclerosis and multiple sclerosis (MS). On multivariate analysis selecting adults for MS, systemic sclerosis, and Crohn disease, better PFS was associated with experience (≥23 transplants for AD, P = .001), learning (time from first HSCT for AD ≥6 years, P = .01), and Joint Accreditation Committee of the International Society for Cellular Therapy and European Society for Blood and Marrow Transplantation accreditation status ( P = .02). Despite improved survival over time ( P = .02), allogeneic HSCT use remained low and largely restricted to pediatric practice. Autologous HSCT has evolved into a treatment modality to be considered alongside other modern therapies in severe AD. Center experience, accreditation, interspecialty networking, and national socioeconomic factors are relevant for health service delivery of HSCT in AD.

Multi-Criterion Preliminary Design of a Tetrahedral Truss Platform

NASA Technical Reports Server (NTRS)

Wu, K. Chauncey

1995-01-01

An efficient method is presented for multi-criterion preliminary design and demonstrated for a tetrahedral truss platform. The present method requires minimal analysis effort and permits rapid estimation of optimized truss behavior for preliminary design. A 14-m-diameter, 3-ring truss platform represents a candidate reflector support structure for space-based science spacecraft. The truss members are divided into 9 groups by truss ring and position. Design variables are the cross-sectional area of all members in a group, and are either 1, 3 or 5 times the minimum member area. Non-structural mass represents the node and joint hardware used to assemble the truss structure. Taguchi methods are used to efficiently identify key points in the set of Pareto-optimal truss designs. Key points identified using Taguchi methods are the maximum frequency, minimum mass, and maximum frequency-to-mass ratio truss designs. Low-order polynomial curve fits through these points are used to approximate the behavior of the full set of Pareto-optimal designs. The resulting Pareto-optimal design curve is used to predict frequency and mass for optimized trusses. Performance improvements are plotted in frequency-mass (criterion) space and compared to results for uniform trusses. Application of constraints to frequency and mass and sensitivity to constraint variation are demonstrated.

Functionally Active HIV-Specific T Cells that Target Gag and Nef Can Be Expanded from Virus-Naïve Donors and Target a Range of Viral Epitopes: Implications for a Cure Strategy after Allogeneic Hematopoietic Stem Cell Transplantation.

PubMed

Patel, Shabnum; Lam, Sharon; Cruz, Conrad Russell; Wright, Kaylor; Cochran, Christina; Ambinder, Richard F; Bollard, Catherine M

2016-03-01

Allogeneic hematopoietic stem cell transplantation (HSCT) can potentially cure human immunodeficiency virus (HIV) by eliminating infected recipient cells, particularly in the context of technologies that may confer HIV resistance to these stem cells. But, to date, the Berlin patient remains the only case of HIV cure despite multiple attempts to eradicate infection with HSCT. One approach to improve this is to administer virus-specific T cells, a strategy that has proven success in preventing other infections after transplantation. Although we have reported that broadly HIV-specific T cells can be expanded from HIV+ patients, allogeneic transplantations only contain virus-naïve T cells. Modifying this approach for the allogeneic setting requires a robust, reproducible platform that can expand HIV-specific cells from the naïve pool. Hence, we hypothesized that HIV-specific T cells could be primed ex vivo from seronegative individuals to effectively target HIV. Here, we show that ex vivo-primed and expanded HIV-specific T cells released IFNγ in response to HIV antigens and that these cells have enhanced ability to suppress replication in vitro. This is the first demonstration of ex vivo priming and expansion of functional, multi-HIV antigen-specific T cells from HIV-negative donors, which has implications for use of allogeneic HSCT as a functional HIV cure. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Cytomegalovirus retinitis in a patient with secondary acute lymphosarcoma leukemia undergoing allogeneic hematopoietic stem-cell transplantation

PubMed Central

Zhao, Ning; Liu, Lei; Xu, Junjie

2017-01-01

Abstract Rationale: Cytomegalovirus (CMV) retinitis is a common opportunistic infection in immunocompromised patients, which may lead to blindness. CMV retinitis is not an uncommon infectious disease in patients with immune regulatory abnormalities, for example, human immunodeficiency virus (HIV) patients. However, CMV retinitis in a patient with acute lymphosarcoma leukemia (ALL) undergoing allogeneic hematopoietic stem-cell transplantation (HSCT) phase is very rare. Patient concerns: A case of CMV retinitis in a patient receiving immunosuppressive therapy as a part of ALL allogeneic HSCT is described including the pathogenesis, clinical signs, and therapy. Diagnoses: CMV retinitis. Interventions: Ganciclovir intravitreal injection at weekly intervals for 4 weeks. Outcomes: Patient's vision had improved and the load of CMV deoxyribonucleic acid (DNA) in the aqueous humor declined. The CMV retinitis and perivascular of retina infiltration regressed. Lessons: We propose that the concentration of CMV DNA load in the aqueous humor could be useful in making the diagnosis and in selecting the optimal treatment in this kind of CMV retinitis. PMID:28489788

Cytomegalovirus retinitis in a patient with secondary acute lymphosarcoma leukemia undergoing allogeneic hematopoietic stem-cell transplantation: A rare case report: a care-compliant article.

PubMed

Zhao, Ning; Liu, Lei; Xu, Junjie

2017-05-01

Cytomegalovirus (CMV) retinitis is a common opportunistic infection in immunocompromised patients, which may lead to blindness. CMV retinitis is not an uncommon infectious disease in patients with immune regulatory abnormalities, for example, human immunodeficiency virus (HIV) patients. However, CMV retinitis in a patient with acute lymphosarcoma leukemia (ALL) undergoing allogeneic hematopoietic stem-cell transplantation (HSCT) phase is very rare. A case of CMV retinitis in a patient receiving immunosuppressive therapy as a part of ALL allogeneic HSCT is described including the pathogenesis, clinical signs, and therapy. CMV retinitis. Ganciclovir intravitreal injection at weekly intervals for 4 weeks. Patient's vision had improved and the load of CMV deoxyribonucleic acid (DNA) in the aqueous humor declined. The CMV retinitis and perivascular of retina infiltration regressed. We propose that the concentration of CMV DNA load in the aqueous humor could be useful in making the diagnosis and in selecting the optimal treatment in this kind of CMV retinitis.

Additional Development and Systems Analyses of Pneumatic Technology for High Speed Civil Transport Aircraft

NASA Technical Reports Server (NTRS)

Englar, Robert J.; Willie, F. Scott; Lee, Warren J.

1999-01-01

In the Task I portion of this NASA research grant, configuration development and experimental investigations have been conducted on a series of pneumatic high-lift and control surface devices applied to a generic High Speed Civil Transport (HSCT) model configuration to determine their potential for improved aerodynamic performance, plus stability and control of higher performance aircraft. These investigations were intended to optimize pneumatic lift and drag performance; provide adequate control and longitudinal stability; reduce separation flowfields at high angle of attack; increase takeoff/climbout lift-to-drag ratios; and reduce system complexity and weight. Experimental aerodynamic evaluations were performed on a semi-span HSCT generic model with improved fuselage fineness ratio and with interchangeable plain flaps, blown flaps, pneumatic Circulation Control Wing (CCW) high-lift configurations, plain and blown canards, a novel Circulation Control (CC) cylinder blown canard, and a clean cruise wing for reference. Conventional tail power was also investigated for longitudinal trim capability. Also evaluated was unsteady pulsed blowing of the wing high-lift system to determine if reduced pulsed mass flow rates and blowing requirements could be made to yield the same lift as that resulting from steady-state blowing. Depending on the pulsing frequency applied, reduced mass flow rates were indeed found able to provide lift augmentation at lesser blowing values than for the steady conditions. Significant improvements in the aerodynamic characteristics leading to improved performance and stability/control were identified, and the various components were compared to evaluate the pneumatic potential of each. Aerodynamic results were provided to the Georgia Tech Aerospace System Design Lab. to conduct the companion system analyses and feasibility study (Task 2) of theses concepts applied to an operational advanced HSCT aircraft. Results and conclusions from these experimental evaluations are presented herein, as are recommendations for further development and follow-on investigations. Also provided as an Appendix for reference are the basic results from the previous pneumatic HSCT investigations.

Hematopoietic stem cell transplantation in Europe 2014: more than 40 000 transplants annually.

PubMed

Passweg, J R; Baldomero, H; Bader, P; Bonini, C; Cesaro, S; Dreger, P; Duarte, R F; Dufour, C; Kuball, J; Farge-Bancel, D; Gennery, A; Kröger, N; Lanza, F; Nagler, A; Sureda, A; Mohty, M

2016-06-01

A record number of 40 829 hematopoietic stem cell transplantation (HSCT) in 36 469 patients (15 765 allogeneic (43%), 20 704 autologous (57%)) were reported by 656 centers in 47 countries to the 2014 survey. Trends include: continued growth in transplant activity, more so in Eastern European countries than in the west; a continued increase in the use of haploidentical family donors (by 25%) and slower growth for unrelated donor HSCT. The use of cord blood as a stem cell source has decreased again in 2014. Main indications for HSCT were leukemias: 11 853 (33%; 96% allogeneic); lymphoid neoplasias; 20 802 (57%; 11% allogeneic); solid tumors; 1458 (4%; 3% allogeneic) and non-malignant disorders; 2203 (6%; 88% allogeneic). Changes in transplant activity include more allogeneic HSCT for AML in CR1, myeloproliferative neoplasm (MPN) and aplastic anemia and decreasing use in CLL; and more autologous HSCT for plasma cell disorders and in particular for amyloidosis. In addition, data on numbers of teams doing alternative donor transplants, allogeneic after autologous HSCT, autologous cord blood transplants are presented.

Safety and effects of prophylactic defibrotide for sinusoidal obstruction syndrome in hematopoietic stem cell transplantation.

PubMed

Park, Meerim; Park, Hyeon Jin; Eom, Hyeon-Seok; Kwon, Young Joo; Park, Jeong A; Lim, Yeon Jung; Yoon, Jong Hyung; Kong, Sun-Young; Ghim, Thad T; Lee, Hye Won; Yun, Tak; Park, Byung-Kiu

2013-01-28

Sinusoidal obstruction syndrome (SOS) is a serious complication of hematopoietic stem cell transplantation (HSCT), with a mortality rate of up to 90%. We report our experience on the use of defibrotide for SOS prophylaxis in HSCT. We retrospectively reviewed data of 49 patients who received defibrotide as SOS prophylaxis during the course of HSCT at the National Cancer Center, Goyang, Korea, between August 2005 and July 2008. Thirty-four patients (69.4%) were classified as a high-risk group for developing SOS. Defibrotide was well-tolerated, without any grade 3 or 4 toxicity. The median value of maximum total bilirubin within 100 days after HSCT was within the normal range. SOS was diagnosed in only 1 patient, who underwent autologous HSCT due to relapsed medulloblastoma. There was no day 100 treatment-related mortality in our study. Defibrotide appears to be a safe prophylaxis for SOS. This study suggests that it could be effective to use prophylactic defibrotide in advance to improve HSCT outcomes in patients at risk of SOS.

High non-relapse mortality and low relapse incidence in gender-mismatched allogeneic hematopoietic stem cell transplantation from a parous female donor with a male child.

PubMed

Shinohara, Akihito; Inamoto, Yoshihiro; Kurosawa, Saiko; Hiramoto, Nobuhiro; Ueda, Ryosuke; Tanaka, Takashi; Tada, Kohei; Kobayashi, Yujin; Morikawa, Noriyuki; Okinaka, Keiji; Kim, Sung-Won; Tajima, Kinuko; Fukuda, Takahiro

2017-03-01

To clarify the influence of exposure to a male fetus during a female donor's (FD) pregnancy in allogeneic hematopoietic stem cell transplantation (HSCT), we retrospectively examined 292 HSCT patients. The 5-year non-relapse mortality (NRM) was 33.5% among 31 male recipients who had HSCT from FD with a male child (MC), 23.0% among 40 male recipients who had HSCT from FD without MC and 19.6% among 221 other recipients. The 5-year relapse incidence (RI) was 22.6%, 42.0%, and 43.1% for the respective group. In multivariate analysis, male recipients who had HSCT from FD with MC had an increased risk of NRM (hazard ratio [HR] 1.92, 95% CI 1.08-3.42, p = .03), a reduced risk of RI (HR 0.42, 95% CI 0.18-0.96, p = .04), resulting in no significant difference regarding overall survival. Male child of FD is suggested to influence NRM and RI in gender-mismatched HSCT.

A multi-objective simulation-optimization model for in situ bioremediation of groundwater contamination: Application of bargaining theory

NASA Astrophysics Data System (ADS)

Raei, Ehsan; Nikoo, Mohammad Reza; Pourshahabi, Shokoufeh

2017-08-01

In the present study, a BIOPLUME III simulation model is coupled with a non-dominating sorting genetic algorithm (NSGA-II)-based model for optimal design of in situ groundwater bioremediation system, considering preferences of stakeholders. Ministry of Energy (MOE), Department of Environment (DOE), and National Disaster Management Organization (NDMO) are three stakeholders in the groundwater bioremediation problem in Iran. Based on the preferences of these stakeholders, the multi-objective optimization model tries to minimize: (1) cost; (2) sum of contaminant concentrations that violate standard; (3) contaminant plume fragmentation. The NSGA-II multi-objective optimization method gives Pareto-optimal solutions. A compromised solution is determined using fallback bargaining with impasse to achieve a consensus among the stakeholders. In this study, two different approaches are investigated and compared based on two different domains for locations of injection and extraction wells. At the first approach, a limited number of predefined locations is considered according to previous similar studies. At the second approach, all possible points in study area are investigated to find optimal locations, arrangement, and flow rate of injection and extraction wells. Involvement of the stakeholders, investigating all possible points instead of a limited number of locations for wells, and minimizing the contaminant plume fragmentation during bioremediation are new innovations in this research. Besides, the simulation period is divided into smaller time intervals for more efficient optimization. Image processing toolbox in MATLAB® software is utilized for calculation of the third objective function. In comparison with previous studies, cost is reduced using the proposed methodology. Dispersion of the contaminant plume is reduced in both presented approaches using the third objective function. Considering all possible points in the study area for determining the optimal locations of the wells in the second approach leads to more desirable results, i.e. decreasing the contaminant concentrations to a standard level and 20% to 40% cost reduction.

Similar outcome of upfront-unrelated and matched sibling stem cell transplantation in idiopathic paediatric aplastic anaemia. A study on behalf of the UK Paediatric BMT Working Party, Paediatric Diseases Working Party and Severe Aplastic Anaemia Working Party of EBMT.

PubMed

Dufour, Carlo; Veys, Paul; Carraro, Elisa; Bhatnagar, Neha; Pillon, Marta; Wynn, Rob; Gibson, Brenda; Vora, Ajay J; Steward, Colin G; Ewins, Anna M; Hough, Rachael E; de la Fuente, Josu; Velangi, Mark; Amrolia, Persis J; Skinner, Roderick; Bacigalupo, Andrea; Risitano, Antonio M; Socie, Gerard; Peffault de Latour, Regis; Passweg, Jakob; Rovo, Alicia; Tichelli, André; Schrezenmeier, Hubert; Hochsmann, Britta; Bader, Peter; van Biezen, Anja; Aljurf, Mahmoud D; Kulasekararaj, Austin; Marsh, Judith C; Samarasinghe, Sujith

2015-11-01

We explored the feasibility of unrelated donor haematopoietic stem cell transplant (HSCT) upfront without prior immunosuppressive therapy (IST) in paediatric idiopathic severe aplastic anaemia (SAA). This cohort was then compared to matched historical controls who had undergone first-line therapy with a matched sibling/family donor (MSD) HSCT (n = 87) or IST with horse antithymocyte globulin and ciclosporin (n = 58) or second-line therapy with unrelated donor HSCT post-failed IST (n = 24). The 2-year overall survival in the upfront cohort was 96 ± 4% compared to 91 ± 3% in the MSD controls (P = 0·30) and 94 ± 3% in the IST controls (P = 0·68) and 74 ± 9% in the unrelated donor HSCT post-IST failure controls (P = 0·02).The 2-year event-free survival in the upfront cohort was 92 ± 5% compared to 87 ± 4% in MSD controls (P = 0·37), 40 ± 7% in IST controls (P = 0·0001) and 74 ± 9% in the unrelated donor HSCT post-IST failure controls (n = 24) (P = 0·02). Outcomes for upfront-unrelated donor HSCT in paediatric idiopathic SAA were similar to MSD HSCT and superior to IST and unrelated donor HSCT post-IST failure. Front-line therapy with matched unrelated donor HSCT is a novel treatment approach and could be considered as first-line therapy in selected paediatric patients who lack a MSD. © 2015 John Wiley & Sons Ltd.

Post-Transplantation Natural Killer Cell Count: A Predictor of Acute Graft-Versus-Host Disease and Survival Outcomes After Allogeneic Hematopoietic Stem Cell Transplantation.

PubMed

Kim, Seo Yeon; Lee, Hyewon; Han, Mi-Soon; Shim, Hyoeun; Eom, Hyeon-Seok; Park, Boram; Kong, Sun-Young

2016-09-01

Reconstitution of the immune system after allogeneic hematopoietic stem cell transplantation (allo-HSCT) plays an important role in post-transplant outcomes. However, the clinical relevance of the lymphocyte subset (LST) counts to transplant-related complications and survival outcomes after allo-HSCT has not been fully elucidated. A total of 70 patients who had undergone allo-HSCT from 2007 to 2013, with LST results both 7 days before conditioning and 30 or 90 days after allo-HSCT were included. The LST counts in the peripheral blood were determined using 6-color flow cytometry. Clinical information, including transplant-related events during the first 100 days after allo-HSCT, was reviewed, and any association between these events and LST was analyzed. At 30 days after allo-HSCT, the CD4 + T-cell (P = .009) and B-cell (P = .035) counts were lower and the natural killer (NK) cell count was greater (P < .001) than before conditioning. The CD8 + T-cell (P = .001) and NK cell (P < .001) counts were high 90 days after transplantation. The hazard ratios for a low NK cell count on days 30 and 90 for acute graft-versus-host disease were 6.22 and 14.67, respectively. Patients with low NK cell counts at 30 and 90 days after allo-HSCT had poorer overall survival (P = .043 and P = .028, respectively) and greater nonrelapse mortality (P = .036 and P = .033, respectively). A low NK cell count on day 30 was still prognostic for overall survival (P = .039) on multivariable analysis. NK cell counts after allo-HSCT, especially on day 30, were predictive of acute graft-versus-host disease, nonrelapse mortality, and survival. Serial lymphocyte subset analysis can be used to identify and treat patients at risk during the early period after allo-HSCT. Copyright © 2016 Elsevier Inc. All rights reserved.

[Outcome of haploidentical hematopoietic stem cell transplantation for non-Hodgkin lymphoma].

PubMed

Xu, T; Chen, J; Jin, Z M; Miao, M; Fu, C C; Qiu, H Y; Tang, X W; Han, Y; Sun, A N; Wu, D P

2016-08-14

To explore the efficacy and safety of haploidentical hematopoietic stem cell transplantation (Haplo- HSCT) for refractory, relapsed or highly aggressive non- Hodgkin lymphoma (NHL) patients. A total of 26 patients with refractory, relapsed or highly aggressive NHL who received Haplo- HSCT from Jan. 2004 to Mar. 2015 were analyzed retrospectively. Of them, 4 patients had diffuse large B-cell lymphoma (DLBCL), 1 had follicular lymphoma, 5 had B-lymphoblastic lymphoma/leukemia, 9 had T- lymphoblastic lymphoma/leukemia, 1 patient anaplastic large cell lymphoma (ALK-negative), 5 had peripheral T-cell lymphoma (NOS), and 1 had NK/T-cell lymphoma. At the time of initial diagnosis, 6 patients had Ann Arbor stage Ⅲ disease, 20 patients showed stage Ⅳ. At the time of Haplo- HSCT, 7 patients were in the first complete remission (CR1), 4 in the second complete remission (CR2), 7 in partial remission, 1 in stable disease, 7 in progressive disease, and 19 of 26 patients were refractory or relapsed. The neutrophil and platelet counts recovered at 12 (11-17) d and 14 (11-31) d after Haplo- HSCT, respectively. All patients achieved full donor chimerism at 30d after Haplo- HSCT. With a median follow- up of 14 (4- 136) months, 20 cases (76.92%) survived, 15 (57.69%) survived without lymphoma, and 7 (26.92%) relapsed. Conditioning regimen related adverse reactions were all disappeared after treatment. The estimated 2-year recurrence rate after Haplo-HSCT was 42.20%. The estimated 2-year overall survival (OS) and disease-free survival (DFS) rate was 71.60% and 48.90%, respectively. Patients in CR before Haplo- HSCT experienced better 2- year OS (100.0% vs 52.4%, P=0.023) and 2- year DFS (88.9% vs 27.0%, P=0.013). Haplo- HSCT may effective and safe for those relapsed, refractory or highly aggressive NHL patients who did not have matched donor nor suitable for autologous HSCT.

Vertical Field of View Reference Point Study for Flight Path Control and Hazard Avoidance

NASA Technical Reports Server (NTRS)

Comstock, J. Raymond, Jr.; Rudisill, Marianne; Kramer, Lynda J.; Busquets, Anthony M.

2002-01-01

Researchers within the eXternal Visibility System (XVS) element of the High-Speed Research (HSR) program developed and evaluated display concepts that will provide the flight crew of the proposed High-Speed Civil Transport (HSCT) with integrated imagery and symbology to permit path control and hazard avoidance functions while maintaining required situation awareness. The challenge of the XVS program is to develop concepts that would permit a no-nose-droop configuration of an HSCT and expanded low visibility HSCT operational capabilities. This study was one of a series of experiments exploring the 'design space' restrictions for physical placement of an XVS display. The primary experimental issues here was 'conformality' of the forward display vertical position with respect to the side window in simulated flight. 'Conformality' refers to the case such that the horizon and objects appear in the same relative positions when viewed through the forward windows or display and the side windows. This study quantified the effects of visual conformality on pilot flight path control and hazard avoidance performance. Here, conformality related to the positioning and relationship of the artificial horizon line and associated symbology presented on the forward display and the horizon and associated ground, horizon, and sky textures as they would appear in the real view through a window presented in the side window display. No significant performance consequences were found for the non-conformal conditions.

Poor CMV-specific CD8+ T central memory subset recovery at early stage post-HSCT associates with refractory and recurrent CMV reactivation.

PubMed

Liu, Jing; Chang, Ying-Jun; Yan, Chen-Hua; Xu, Lan-Ping; Jiang, Zheng-Fan; Zhang, Xiao-Hui; Liu, Kai-Yan; Huang, Xiao-Jun

2016-09-01

Refractory and recurrent cytomegalovirus (CMV) reactivation were independent risk factors of CMV disease and transplant-related mortality post allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our aims were to identify the recovery of CMV-specific CD8+ T cells with a central memory phenotype (TCM) associated with refractory and recurrent CMV reactivation. We analyzed findings in a prospective study comprising (n = 107) post allo-HSCT. CMV-specific CD8+ T cells were determined using HLA class I pentamers together with extended phenotypic analyses. The patients with lower level of CMV-specific CD8+ TCM at day 30 post-HSCT had an increased risk of refractory and recurrent CMV (68.5%) comparing with the higher one (13.2%) (p < 0.001) and poorer long term CMV-specific CD8+ T cell reconstitution post-HSCT (p = 0.026). Multivariate analysis revealed that CMV-specific CD8+ TCM at day 30 was an independent prognostic factor for refractory and recurrent reactivation (p = 0.002). The CMV-specific CD8+ TCM subset at day 30 post-HSCT is associated with CMV-specific T cell immunity recovery as well as the refractory and recurrent CMV reactivation post-HSCT. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Haematopoietic stem cell transplantation survivorship and quality of life: is it a small world after all?

PubMed

Brice, Lisa; Gilroy, Nicole; Dyer, Gemma; Kabir, Masura; Greenwood, Matt; Larsen, Stephen; Moore, John; Kwan, John; Hertzberg, Mark; Brown, Louisa; Hogg, Megan; Huang, Gillian; Tan, Jeff; Ward, Christopher; Gottlieb, David; Kerridge, Ian

2017-02-01

The aim of this qualitative study was to gain a rich understanding of the impact that haematopoietic stem cell transplantation (HSCT) has on long-term survivor's quality of life (QoL). Participants included 441 survivors who had undergone HSCT for a malignant or non-malignant disease. Data were obtained by a questionnaire positing a single open-ended question asking respondents to list the three issues of greatest importance to their QoL in survivorship. Responses were analysed and organised into QoL themes and subthemes. Major themes identified included the following: the failing body and diminished physical effectiveness, the changed mind, the loss of social connectedness, the loss of the functional self and the patient for life. Each of these themes manifests different ways in which HSCT survivor's world and opportunities had diminished compared to the unhindered and expansive life that they enjoyed prior to the onset of disease and subsequent HSCT. HSCT has a profound and pervasive impact on the life of survivors-reducing their horizons and shrinking various parts of their worlds. While HSCT survivors can describe the ways in which their life has changed, many of their fears, anxieties, regrets and concerns are existential in nature and are ill-defined-making it exceeding unlikely that they would be adequately captured by standard psychometric measures of QoL post HSCT.

A population-based cohort study of late mortality in adult autologous hematopoietic stem cell transplant recipients in Australia.

PubMed

Ashton, Lesley J; Le Marsney, Renate E; Dodds, Anthony J; Nivison-Smith, Ian; Wilcox, Leonie; O'Brien, Tracey A; Vajdic, Claire M

2014-07-01

We assessed overall and cause-specific mortality and risk factors for late mortality in a nation-wide population-based cohort of 4547 adult cancer patients who survived 2 or more years after receiving an autologous hematopoietic stem cell transplantation (HSCT) in Australia between 1992 and 2005. Deaths after HSCT were identified from the Australasian Bone Marrow Transplant Recipient Registry and through data linkage with the National Death Index. Overall, the survival probability was 56% at 10 years from HSCT, ranging from 34% for patients with multiple myeloma to 90% for patients with testicular cancer. Mortality rates moved closer to rates observed in the age- and sex-matched Australian general population over time but remained significantly increased 11 or more years from HSCT (standardized mortality ratio, 5.9). Although the proportion of deaths from nonrelapse causes increased over time, relapse remained the most frequent cause of death for all diagnoses, 10 or more years after autologous HSCT. Our findings show that prevention of disease recurrence remains 1 of the greatest challenges for autologous HSCT recipients, while the increasing rates of nonrelapse deaths due to the emergence of second cancers, circulatory diseases, and respiratory diseases highlight the long-term health issues faced by adult survivors of autologous HSCT. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Bacterial meningitis in hematopoietic stem cell transplant recipients: a population-based prospective study.

PubMed

van Veen, K E B; Brouwer, M C; van der Ende, A; van de Beek, D

2016-11-01

We performed a nationwide prospective cohort study on the epidemiology and clinical features of community-acquired bacterial meningitis. Patients with a medical history of autologous or allogeneic hematopoietic stem cell transplantation (HSCT) were identified from the cohort performed from March 2006 to October 2014. Fourteen of 1449 episodes (1.0%) of bacterial meningitis occurred in patients with a history of HSCT. The incidence of bacterial meningitis in HSCT recipients was 40.4 per 100 000 patients per year (95% confidence interval (CI) 23.9-62.2), which is 30-fold (95% CI 18-51; P<0.001) higher compared with persons without HSCT. Incidence was higher in allogeneic HSCT compared with autologous HSCT (70.0 vs 15.8 per 100 000 patients per year). Causative organisms were Streptococcus pneumoniae in 11 patients, Neisseria meningitidis in two and Streptococcus mitis in one patient. Mortality was 3 of 14 (21%) and 6 of 11 (55%) survivors had sequelae. Nine of 11 patients (82%) with pneumococcal meningitis were infected with a serotype included in the 23-valent pneumococcal polysaccharide vaccine, of whom four developed meningitis despite vaccination. In conclusion, HSCT recipients have a substantially increased risk compared with the general population of acquiring bacterial meningitis, which is mostly due to S. pneumoniae, and disease is associated with high mortality and morbidity. Vaccination is important to prevent disease although vaccine failures did occur.

Transient responses' optimization by means of set-based multi-objective evolution

NASA Astrophysics Data System (ADS)

Avigad, Gideon; Eisenstadt, Erella; Goldvard, Alex; Salomon, Shaul

2012-04-01

In this article, a novel solution to multi-objective problems involving the optimization of transient responses is suggested. It is claimed that the common approach of treating such problems by introducing auxiliary objectives overlooks tradeoffs that should be presented to the decision makers. This means that, if at some time during the responses, one of the responses is optimal, it should not be overlooked. An evolutionary multi-objective algorithm is suggested in order to search for these optimal solutions. For this purpose, state-wise domination is utilized with a new crowding measure for ordered sets being suggested. The approach is tested on both artificial as well as on real life problems in order to explain the methodology and demonstrate its applicability and importance. The results indicate that, from an engineering point of view, the approach possesses several advantages over existing approaches. Moreover, the applications highlight the importance of set-based evolution.

Favorable outcome in non-infant children with MLL-AF4-positive acute lymphoblastic leukemia: a report from the Tokyo Children's Cancer Study Group.

PubMed

Tomizawa, Daisuke; Kato, Motohiro; Takahashi, Hiroyuki; Fujimura, Junya; Inukai, Takeshi; Fukushima, Takashi; Kiyokawa, Nobutaka; Koh, Katsuyoshi; Manabe, Atsushi; Ohara, Akira

2015-11-01

Unlike acute lymphoblastic leukemia (ALL) in infants, MLL gene rearrangement (MLL-r) is rare in ALL children (≥1 year old). The outcome and optimal treatment options for MLL-r ALL remain controversial. Among the 1827 children enrolled in the Tokyo Children's Cancer Study Group ALL studies L95-14, L99-15, L99-1502, L04-16, and L07-1602 (1995-2009), 25 MLL-r ALL patients (1.3 %) were identified. Their median age and leukocyte count at diagnosis was 2 years old (range 1-15 years) and 27,690/μL (range 1800-1,113,000/μL), respectively. All but one patient achieved complete remission (CR) after induction therapy, and 19 underwent allogeneic hematopoietic stem cell transplantation (HSCT) in first CR according to the protocol. The 5-year event-free survival (EFS) and overall survival (OS) rate were 60.0 % [standard error (SE), 9.7 %] and 64.0 % (SE 9.6 %), respectively. Notably, 9/12 cases with MLL-AF4-positive ALL are alive in continuous CR with a 75.0 % (SE 12.5 %) EFS rate. The causes of treatment failure were as follows: one induction failure, five relapses, and five transplant-related deaths. With intensive chemotherapy and allogeneic HSCT, favorable outcome of children (≥1 year old) with MLL-AF4-positive ALL was observed. However, considering the risk of acute and late toxicities associated with HSCT, its indication should be restricted.

Comparison of Donor Sources in Hematopoietic Stem Cell Transplantation for Childhood Acute Leukemia: A Nationwide Retrospective Study.

PubMed

Sakaguchi, Hirotoshi; Watanabe, Nobuhiro; Matsumoto, Kimikazu; Yabe, Hiromasa; Kato, Shunichi; Ogawa, Atsushi; Inagaki, Jiro; Goto, Hiroaki; Koh, Katsuyoshi; Yoshida, Nao; Kato, Keisuke; Cho, Yuko; Kosaka, Yoshiyuki; Takahashi, Yoshiyuki; Inoue, Masami; Kato, Koji; Atsuta, Yoshiko; Miyamura, Koichi

2016-12-01

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the best therapeutic option for childhood high-risk acute leukemia. However, which donor source is optimal for children lacking an identical sibling remains unclear. To evaluate the clinical impact of donor source on allo-HSCT in childhood acute leukemia, we analyzed data from 577 children who underwent allo-HSCT after a myeloablative regimen during first or second complete remission from 2005 to 2012, using registry data of the Japan Society for Hematopoietic Cell Transplantation, and we compared outcomes of 7/8 to 8/8 HLA allelic-matched unrelated bone marrow transplantation (UR-BMT, n = 218) and 4/6 to 6/6 HLA allelic-matched unrelated cord blood transplantation (UR-CBT, n = 200) to those of HLA-identical related bone marrow transplantation (ID-BMT, n = 159). The median follow-up of survivors was 40.0 months. Three-year overall survival (OS) and leukemia-free survival (LFS) rates for ID-BMT, UR-BMT, and UR-CBT were 74.8% and 69.0%, 75.0% and 69.6%, and 71.8% and 63.8%, respectively. The multivariate analysis demonstrated that OS and LFS for the 3 groups are comparable, although UR-CBT carries a greater risk of nonrelapse mortality (hazard ratio, 2.20; P = .03, compared to ID-BMT) in the myeloablative setting for childhood high-risk acute leukemia. Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Psychosocial Changes Associated with Participation in Art Therapy Interventions for Siblings of Pediatric Hematopoietic Stem Cell Transplant Patients

ERIC Educational Resources Information Center

Wallace, Jo; Packman, Wendy; Huffman, Lynne C.; Horn, Biljana; Cowan, Morton; Amylon, Michael D.; Kahn, Colleen; Cordova, Matt; Moses, Jim

2014-01-01

Hematopoietic stem cell transplantation (HSCT) is an accepted medical treatment for many serious childhood diseases. HSCT is a demanding procedure that creates both physical and emotional challenges for patients and their family members. Research has demonstrated that siblings of children undergoing HSCT are at risk for developing psychosocial…

Development of a health-related website for parents of children receiving hematopoietic stem cell transplant: HSCT-CHESS.

PubMed

Mayer, Deborah K; Ratichek, S; Berhe, H; Stewart, S; McTavish, F; Gustafson, D; Parsons, S K

2010-03-01

Parents of pediatric hematopoietic stem cell transplant (HSCT) play a pivotal role in the care of their child during and after transplant. In addition to the child's comforter, parents also serve as care coordinators and conduits of communication between various health care providers, family and community members. The stress on the parent and family is enormous during this process, which for many is compounded by geographic dislocation to accompany their child during the rigorous treatment and recovery process. For many parents, their own recovery spans months to years. Parental activation, a process of becoming informed to participate in decisions, collaborate with health care providers, and manage care provided the conceptual framework to develop an eHealth approach for this population. HSCT-CHESS was developed, based on previous success with an existing eHealth system of integrated services, the Comprehensive Health Enhancement Support System (CHESS). CHESS(TM) is designed to help individuals and families cope with a health crisis or medical concern. The iterative user-centered development process for HSCT-CHESS included parents of HSCT recipients, representatives from an HSCT Advocacy Group, and members of the clinical, research, development and design teams. This rigorous process, including online focus groups and surveys, utilization of a parental user group, and an editorial and development process are described. As the population of cancer survivors and caregivers increase and as the oncology workforce becomes more stretched; developing eHealth applications may be an approach to address many of caregivers unmet needs. The purpose in describing this process is to help others when considering such an endeavor. HSCT-CHESS is now being tested in a randomized controlled trial versus standard care to evaluate its impact on the quality of life of both the parent and child HSCT recipient.

Incidence and Outcomes of Central Nervous System Hemophagocytic Lymphohistiocytosis Relapse after Reduced-Intensity Conditioning Hematopoietic Stem Cell Transplantation.

PubMed

Lounder, Dana T; Khandelwal, Pooja; Chandra, Sharat; Jordan, Michael B; Kumar, Ashish R; Grimley, Michael S; Davies, Stella M; Bleesing, Jack J; Marsh, Rebecca A

2017-05-01

Hemophagocytic lymphohistiocytosis (HLH) is an immune regulatory disorder that commonly presents with central nervous system (CNS) involvement. The only cure for genetic HLH is hematopoietic stem cell transplantation (HSCT), typically treated with reduced-intensity conditioning (RIC) regimens. We sought to estimate the incidence of CNS relapse after RIC HSCT, determine risk factors, and evaluate outcomes. We performed a retrospective chart review of 94 consecutive children and young adults with primary HLH who received RIC HSCT. CNS relapse within 1 year after transplantation was diagnosed by review of clinical symptoms, cerebral spinal fluid (CSF), and radiologic findings. Four (4.25%) patients developed symptoms of possible CNS HLH after HSCT and 3 patients were diagnosed. Eight patients underwent screening lumbar puncture because of history of active CNS disease at the onset of the conditioning regimen and 4 had evidence of continued disease. The overall incidence of CNS relapse and continued CNS disease after RIC HSCT was 8%. All patients with CNS disease after HSCT responded to CNS-directed therapy. Whole blood donor chimerism at the time of CNS relapse was low at 1% to 34%, but it remained high at 88% to 100% for patients with continued CNS disease. Overall survival for patients with CNS relapse was 50%, compared with 75% for patients without CNS disease (P = .079). Our data suggest that a low level of donor chimerism or active CNS disease at the time of transplantation increase the risk of CNS HLH after HSCT. Surveillance CSF evaluation after allogeneic RIC HSCT should be considered in patients with risk factors and CNS-directed treatment should be initiated if appropriate. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Clinical Observation of Factors in the Efficacy of Blood Component Transfusion in Patients following Hematopoietic Stem Cell Transplantation

PubMed Central

Zhang, Xi; Xiao, Yanni; Ran, Qian; Liu, Yao; Duan, Qianbi; Duan, Huiling; Ye, Xingde; Li, Zhongjun

2012-01-01

Background Factors affecting the efficacy of platelet and red blood cell (RBC) transfusion in patients undergoing hematopoietic stem cell transplantation (HSCT) have not been studied extensively. We aimed to evaluate platelet and RBC transfusion efficacy by measuring the platelet corrected count increment and the hemoglobin increment, respectively, 24 h after transfusion in 105 patients who received HSCT. Methodology/Principal Findings Using retrospective analysis, we studied whether factors, including gender, time of transplantation, the compatibility of ABO group between HSC donors and recipients, and autologous or allogenic transplantation, influence the efficacy of blood component transfusion. We found that the infection rate of HSCT patients positively correlated with the transfusion amount, and the length of stay in the laminar flow room was associated with transfusion. We found that platelet transfusion performed during HSCT showed significantly better efficacy than that performed before HSCT. The effect of platelet transfusion in auto-transplantation was significantly better than that in allo-transplantation. The efficacy of RBC transfusion during HSCT was significantly lower than that performed before HSCT. The efficacy of RBC transfusion in auto-transplantation was significantly higher than that in allo-transplantation. Allo-transplantation patients who received HSCs from compatible ABO groups showed significantly higher efficacy during both platelet and RBC transfusion. Conclusions We conclude that the efficacy of platelet and RBC transfusions does not correlate with the gender of patients, while it significantly correlates with the time of transplantation, type of transplantation, and ABO compatibility between HSC donors and recipients. During HSCT, the infection rate of patients positively correlates with the transfusion amount of RBCs and platelets. The total volume of RBC units transfused positively correlates with the length of the patients’ stay in the laminar flow room. PMID:22701516

Imatinib use immediately before stem cell transplantation in children with Philadelphia chromosome-positive acute lymphoblastic leukemia: Results from Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) Study Ph(+) ALL04.

PubMed

Manabe, Atsushi; Kawasaki, Hirohide; Shimada, Hiroyuki; Kato, Itaru; Kodama, Yuichi; Sato, Atsushi; Matsumoto, Kimikazu; Kato, Keisuke; Yabe, Hiromasa; Kudo, Kazuko; Kato, Motohiro; Saito, Tomohiro; Saito, Akiko M; Tsurusawa, Masahito; Horibe, Keizo

2015-05-01

Incorporation of imatinib into chemotherapeutic regimens has improved the prognosis of children with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL). We investigated a role of imatinib immediately before hematopoietic stem cell transplantation (HSCT). Children with Ph(+) ALL were enrolled on JPLSG Ph(+) ALL 04 Study within 1 week of initiation of treatment for ALL. Treatment regimen consisted of Induction phase, Consolidation phase, Reinduction phase, 2 weeks of imatinib monotherapy phase, and HSCT phase (Etoposide+CY+TBI conditioning). Minimal residual disease (MRD), the amount of BCR-ABL transcripts, was measured with the real-time PCR method. The study was registered in UMIN-CTR: UMIN ID C000000290. Forty-two patients were registered and 36 patients (86%) achieved complete remission (CR). Eight of 17 patients (47%) who had detectable MRD at the beginning of imatinib monotherapy phase showed disappearance or decrease in MRD after imatinib treatment. Consequently, 26 patients received HSCT in the first CR and all the patients had engraftment and no patients died because of complications of HSCT. The 4-year event-free survival rates and overall survival rates among all the 42 patients were 54.1 ± 7.8% and 78.1 ± 6.5%, respectively. Four of six patients who did achieve CR and three of six who relapsed before HSCT were salvaged with imatinib-containing chemotherapy and subsequently treated with HSCT. The survival rate was excellent in this study although all patients received HSCT. A longer use of imatinib concurrently with chemotherapy should eliminate HSCT in a subset of patients with a rapid clearance of the disease. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Transplant-related mortality following allogeneic hematopoeitic stem cell transplantation for pediatric acute lymphoblastic leukemia: 25-year retrospective review.

PubMed

Mateos, Marion K; O'Brien, Tracey A; Oswald, Cecilia; Gabriel, Melissa; Ziegler, David S; Cohn, Richard J; Russell, Susan J; Barbaric, Draga; Marshall, Glenn M; Trahair, Toby N

2013-09-01

Over the last 25 years, donor source, conditioning, graft-versus-host disease prevention and supportive care for children undergoing hematopoeitic stem cell transplantation (HSCT) have changed dramatically. HSCT indications for acute lymphoblastic leukemia (ALL) now include high-risk patients in first and subsequent remission. There is a large burden of infectious and pre-HSCT morbidities, due to myelosuppressive therapy required for remission induction. We hypothesized that, despite these trends, overall survival (OS) had increased. A retrospective audit of allogeneic pediatric HSCT for ALL was performed in our institution over 25 years. Outcomes for 136 HSCTs were analyzed in three consecutive 8-year periods (Period 1: 1/1/1984-31/8/1992, Period 2: 1/9/1992-30/4/2001, Period 3: 1/5/2001-31/12/2009). Despite a significant increase in unrelated donor HSCT, event-free and OS over 25 years improved significantly. (EFS 31.6-64.8%, P = 0.0027; OS 41.8-78.9%, P < 0.0001) Concurrently, TRM dropped from 33% to 5% (P = 0.0004) whilst relapse rate was static (P = 0.07). TRM reduced significantly for matched sibling and unrelated cord blood transplantation (UCT) in Period 3 compared with earlier periods (P = 0.036, P = 0.0098, respectively). Factors leading to improved survival in patients undergoing UCT include better matching, higher total nucleated cell doses, and significantly faster neutrophil engraftment. Length of initial HSCT admission was similar over time. EFS and OS have increased significantly despite heightened HSCT complexity. This survival gain was due to TRM reduction. Contemporary patients have benefited from refined donor selection and improved supportive care. Overall rates of leukemic relapse post-HSCT are unchanged, and remain the focus for improvement. Copyright © 2013 Wiley Periodicals, Inc.

Evolution, trends, outcomes, and economics of hematopoietic stem cell transplantation in severe autoimmune diseases

PubMed Central

Badoglio, Manuela; Labopin, Myriam; Giebel, Sebastian; McGrath, Eoin; Marjanovic, Zora; Burman, Joachim; Moore, John; Rovira, Montserrat; Wulffraat, Nico M.; Kazmi, Majid; Greco, Raffaella; Snarski, Emilian; Kozak, Tomas; Kirgizov, Kirill; Alexander, Tobias; Bader, Peter; Saccardi, Riccardo; Farge, Dominique

2017-01-01

Hematopoietic stem cell transplantation (HSCT) has evolved for >20 years as a specific treatment of patients with autoimmune disease (AD). Using European Society for Blood and Marrow Transplantation registry data, we summarized trends and identified factors influencing activity and outcomes in patients with AD undergoing first autologous HSCT (n = 1951; median age, 37 years [3-76]) and allogeneic HSCT (n = 105; median age, 12 years [<1-62]) in 247 centers in 40 countries from 1994 to 2015. Predominant countries of activity were Italy, Germany, Sweden, the United Kingdom, The Netherlands, Spain, France, and Australia. National activity correlated with the Human Development Index (P = .006). For autologous HSCT, outcomes varied significantly between diseases. There was chronological improvement in progression-free survival (PFS, P < 10−5), relapse/progression (P < 10−5), and nonrelapse mortality (P = .01). Health care expenditure was associated with improved outcomes in systemic sclerosis and multiple sclerosis (MS). On multivariate analysis selecting adults for MS, systemic sclerosis, and Crohn disease, better PFS was associated with experience (≥23 transplants for AD, P = .001), learning (time from first HSCT for AD ≥6 years, P = .01), and Joint Accreditation Committee of the International Society for Cellular Therapy and European Society for Blood and Marrow Transplantation accreditation status (P = .02). Despite improved survival over time (P = .02), allogeneic HSCT use remained low and largely restricted to pediatric practice. Autologous HSCT has evolved into a treatment modality to be considered alongside other modern therapies in severe AD. Center experience, accreditation, interspecialty networking, and national socioeconomic factors are relevant for health service delivery of HSCT in AD. PMID:29296926

The 1990 high-speed civil transport studies

NASA Technical Reports Server (NTRS)

1992-01-01

This summary report contains the results of the Douglas Aircraft Company system studies related to High-Speed Civil Transports (HSCT's). The tasks were performed under an 18-month extension of NASA Langley Research Center Contract NAS1-18378. The system studies were conducted to assess the emission impact of HSCT's at design Mach numbers ranging from 1.6 to 3.2. The tasks specifically addressed an HSCT market and economic assessment, development of supersonic route networks, and an atmospheric emissions scenario. The general results indicated: (1) market projections predict sufficient passenger traffic for the 2000 to 2025 time period to support a fleet of economically viable and environmentally compatible HSCT's; (2) the HSCT route structure to minimize supersonic overland traffic can be increased by innovative routing to avoid land masses; and (3) the atmospheric emission impact on ozone would be significantly lower for Mach 1.6 operations than for Mach 3.2 operations.

Fungemia due to Rhodotorula mucilaginosa after allogeneic hematopoietic stem cell transplantation.

PubMed

Mori, T; Nakamura, Y; Kato, J; Sugita, K; Murata, M; Kamei, K; Okamoto, S

2012-02-01

Rhodotorula species have been increasingly recognized as emerging pathogens, particularly in immunocompromised patients. We herein report on a patient with myelodysplastic syndrome who developed fungemia due to Rhodotorula mucilaginosa after allogeneic hematopoietic stem cell transplantation (HSCT) from an unrelated donor. He developed severe acute graft-versus-host disease requiring high-dose steroids, and had serially been administered fluconazole and micafungin for the prophylaxis of fungal infection. Although several cases of Rhodotorula infection after HSCT have been reported, all of them were recipients of autologous HSCT, not allogeneic HSCT. A review of all the reported cases of Rhodotorula infection after HSCT revealed that all patients had received fluconazole or echinocandins before the onset of infection. The findings suggest that Rhodotorula species could be causative yeasts, particularly in patients receiving fluconazole or echinocandins, both of which are inactive against the species. © 2011 John Wiley & Sons A/S.

Recent Results from NASA's Morphing Project

NASA Technical Reports Server (NTRS)

McGowan, Anna-Maria R.; Washburn, Anthony E.; Horta, Lucas G.; Bryant, Robert G.; Cox, David E.; Siochi, Emilie J.; Padula, Sharon L.; Holloway, Nancy M.

2002-01-01

The NASA Morphing Project seeks to develop and assess advanced technologies and integrated component concepts to enable efficient, multi-point adaptability in air and space vehicles. In the context of the project, the word "morphing" is defined as "efficient, multi-point adaptability" and may include macro, micro, structural and/or fluidic approaches. The project includes research on smart materials, adaptive structures, micro flow control, biomimetic concepts, optimization and controls. This paper presents an updated overview of the content of the Morphing Project including highlights of recent research results.

Treosulfan-based conditioning regimens for allogeneic HSCT in children with acute lymphoblastic leukaemia.

PubMed

Boztug, Heidrun; Zecca, Marco; Sykora, Karl-Walter; Veys, Paul; Lankester, Arjan; Slatter, Mary; Skinner, Roderick; Wachowiak, Jacek; Pötschger, Ulrike; Glogova, Evgenia; Peters, Christina

2015-02-01

Standard myeloablative conditioning regimens for children with acute lymphoblastic leukaemia are based on total body irradiation (TBI). However, TBI causes profound short-term and long-term side effects, provoking the necessity for alternative regimens. Treosulfan combines a potent immunosuppressive and antileukaemic effect with myeloablative activity and low toxicity profile. We retrospectively studied toxicity and outcome of 71 paediatric patients with acute lymphoblastic leukaemia (ALL) undergoing haematopoietic stem cell transplantation (HSCT) following treosulfan-based conditioning aiming to identify risk factors for treatment failure and dose-depending outcome differences. Early regimen-related toxicity was low. No case of veno-occlusive disease was reported. There was no association of toxicity with age or number of HSCT. Event-free survival (EFS) of infants was significantly better compared to older children. Overall survival (OS) at 3 years was 51 % and not significantly influenced by number of HSCT (first HSCT 54 %, ≥second HSCT 44 %, p = 0.71). In multivariate analysis, OS and EFS were significantly worse for patients transplanted without complete remission (p = 0.04 and 0.004). Treatment-related mortality was low at 14 %. We conclude that treosulfan-based conditioning is a safe and efficacious approach for paediatric ALL.

EBMT activity survey 2004 and changes in disease indication over the past 15 years.

PubMed

Gratwohl, A; Baldomero, H; Frauendorfer, K; Urbano-Ispizua, A

2006-06-01

This fifteenth annual European Group for Blood and Marrow Transplantation activity report lists the transplant activity in Europe in 2004 and documents the changes in indication over the past 15 years. In 2004, there were 22 216 first hematopoetic stem cells (HSCT), 7407 allogeneic (33%), 14 809 autologous (67%) and 4378 additional re- or multiple transplants reported from 592 centres in 38 European and five affiliated countries. Main indications were leukemias (7045 (32%; 78% allogeneic)); lymphomas (12 310 (55%; 94% autologous)); solid tumors (1759 (8%; 93% autologous)) and nonmalignant disorders (1015 (5%; 92% allogeneic)). In comparison, 145 teams from 20 countries performed 4234 HSCT (2137 allogeneic, 50%; 2097 autologous, 50%) in 1990. The overall increase was accompanied by major changes. Stem cell source changed from bone marrow to peripheral blood. More than one-third of allogeneic HSCT are now from unrelated donors. Reduced intensity conditioning is employed for one-third of allogeneic HSCT. Leukemias for allogeneic and lymphoproliferative disorders for autologous HSCT continue to increase. The decline in HSCT for chronic myeloid leukemia appears to level off for the first time since 1999. These data are informative for patient counselling and decision making for health care professionals.

Ovarian tissue cryopreservation in girls undergoing haematopoietic stem cell transplant: experience of a single centre.

PubMed

Biasin, E; Salvagno, F; Berger, M; Nesi, F; Quarello, P; Vassallo, E; Evangelista, F; Marchino, G L; Revelli, A; Benedetto, C; Fagioli, F

2015-09-01

Fertility after childhood haemopoietic stem cell transplant (HSCT) is a major concern. Conditioning regimens before HSCT present a high risk (>80%) of ovarian failure. Since 2000, we have proposed cryopreservation of ovarian tissue to female patients undergoing HSCT at our centre, to preserve future fertility. After clinical and haematological evaluation, the patients underwent ovarian tissue collection by laparoscopy. The tissue was analysed by histologic examination to detect any tumour contamination and then frozen following the slow freezing procedure and cryopreserved in liquid nitrogen. From August 2000 to September 2013, 47 patients planned to receive HSCT, underwent ovarian tissue cryopreservation. The median age at diagnosis was 11.1 years and at the time of procedure it was 13 years, respectively. Twenty-four patients were not pubertal at the time of storage, whereas 23 patients had already experienced menarche. The median time between laparoscopy and HSCT was 25 days. Twenty-six out of 28 evaluable patients (93%) developed hypergonadotropic hypogonadism at a median time of 23.3 months after HSCT. One patient required autologous orthotopic transplantation that resulted in one live birth. Results show a very high rate of iatrogenic hypergonadotropic hypogonadism, highlighting the need for fertility preservation in these patients.

Symptom prevalence and physiologic biomarkers among adolescents using a mobile phone intervention following hematopoietic stem cell transplantation.

PubMed

Rodgers, Cheryl C; Krance, Robert; Street, Richard L; Hockenberry, Marilyn J

2014-05-01

To examine symptom reports and physiologic parameters in adolescents using the Eating After Transplant (EAT!) intervention during recovery after hematopoietic stem cell transplantation (HSCT). Repeated measures design. HSCT service at a pediatric teaching institution in the southern United States. 16 adolescents recovering from a first-time allogeneic HSCT. Use of EAT! was monitored electronically, symptom reports were obtained from a questionnaire, and physiologic parameters were obtained from the medical record at HSCT hospital discharge and 20, 40, and 60 days postdischarge. EAT! use, symptom prevalence, symptom-related distress, and physiologic parameters including weight, body mass index (BMI), pre-albumin, and albumin. Symptom prevalence was highest at hospital discharge and steadily declined; however, mean symptom distress scores remained stable. Mean weight and BMI significantly declined during the first 60 days postdischarge; pre-albumin and albumin markers were unchanged. No correlation was noted among use of EAT! and any research variables. The most frequent symptoms were not always the most distressing symptoms. Weight and BMI significantly declined during HSCT recovery. Nurses should assess symptom frequency and distress to fully understand patients' symptom experiences. Nurses should monitor weight and BMI throughout HSCT recovery.

Toward dual hematopoietic stem-cell transplantation and solid-organ transplantation for sickle-cell disease

PubMed Central

Levine, Jeffrey; Abt, Peter; Henry, David; Porter, David L.

2018-01-01

Sickle-cell disease (SCD) leads to recurrent vaso-occlusive crises, chronic end-organ damage, and resultant physical, psychological, and social disabilities. Although hematopoietic stem-cell transplantation (HSCT) is potentially curative for SCD, this procedure is associated with well-recognized morbidity and mortality and thus is ideally offered only to patients at high risk of significant complications. However, it is difficult to identify patients at high risk before significant complications have occurred, and once patients experience significant organ damage, they are considered poor candidates for HSCT. In turn, patients who have experienced long-term organ toxicity from SCD such as renal or liver failure may be candidates for solid-organ transplantation (SOT); however, the transplanted organs are at risk of damage by the original disease. Thus, dual HSCT and organ transplantation could simultaneously replace the failing organ and eliminate the underlying disease process. Advances in HSCT conditioning such as reduced-intensity regimens and alternative donor selection may expand both the feasibility of and potential donor pool for transplantation. This review summarizes the current state of HSCT and organ transplantation in SCD and discusses future directions and the clinical feasibility of dual HSCT/SOT. PMID:29535106

Demands and challenges for patients with sickle-cell disease requiring hematopoietic stem cell transplantation in Saudi Arabia.

PubMed

Alsultan, Abdulrahman; Jastaniah, Wasil; Al Afghani, Sameera; Al Bagshi, Muneer H; Nasserullah, Zaki; Al-Suliman, Ahmed M; Alabdulaali, Mohammed K

2016-09-01

Allogeneic HSCT is the only curative treatment for SCD. In this study, we estimated the number of Saudi patients with SCD who are candidates for HSCT. We used the presence of overt stroke, recurrent ACS, and frequent severe pain crisis as indications for HSCT. We calculated the frequencies of these complications among a Saudi SCD cohort of 376 patients with SCD, 250 from SW and 126 from Eastern (E) provinces. We found that 59 (23.6%) of SW patients were transplant candidates compared to 22 (17.4%) from E province. It is estimated that about 61 000 patients with SCD live in Saudi Arabia. Thus, the projected number of Saudi patients with SCD who are candidates for HSCT is 10 536 patients. Of those, 2148 are children. The burden of SCD on HSCT centers in Saudi Arabia is substantial and is difficult currently to meet the demand. We recommend recruiting/training more transplant physicians and nurses, expand current capacity of centers if feasible, and open new transplant centers to make HSCT a practical therapeutic option for patients with severe SCD in Saudi Arabia. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Psychopathological Aspects in Childhood Hematopoietic Stem Cell Transplantation (HSCT): The Perception of Parents and Adolescents

PubMed Central

Zanato, Silvia; Traverso, Annalisa; Tremolada, Marta; Sinatora, Francesco; Porreca, Alessio; Pozziani, Giorgio; Di Florio, Nicoletta; Capello, Fabia; Marzollo, Antonio; Tumino, Manuela; Cattelan, Chiara; Basso, Giuseppe; Messina, Chiara

2017-01-01

Background: Data about psychosocial sequelae of childhood Hematopoietic Stem Cell Transplantation (HSCT) are limited and the association with a specific donor type or other medical factors is largely unknown (Chang et al., 2012). The aim of the present study was to compare the psychological aspects of pediatric HSCT survivors with healthy peers. A secondary aim was to detect whether parents and children differed in the perception of mental health status. The influence of medical factors on psychological status was also examined. Method: Thirty seven HSCT survivors (23 males) with a mean age of 14.4 years (SD = 3.03; range 8.16–18.33) were recruited. Twenty-six patients underwent an allogenic HSCT (matched unrelated donor, n = 20; matched sibling donor, n = 6) and 11 patients received an autologous HSCT. The children psychological aspects were assessed using the Youth Self Report (YSR) (Achenbach and Rescorla, 2001) and compared to a group of matched healthy peers. At the same time, parents were requested to complete the Child Behavior Checklist 6–18 (Achenbach and Rescorla, 2001). Medical and socio-demographic data were also collected. Results: HSCT survivors reported significantly higher levels of somatic complains (t27 = 3.14; p = 0.004; mean = 3.1) when compared to healthy peers (mean = 1.5). The parent CBCL scores on “child total competence” exceeded the normative clinical cutoff in 48.6% cases. Inter-rater agreement between parent and patient reports was present only in three scales: total competence score (K = 0.06, p = 0.002), somatic complaints (K = 0.21, p = 0.003) and attention problems (k = 0.13; p = 0.02). According to Ancova models, internalizing problems were more frequent in HSCT from family donors (F2 = 3.13; p = 0.06) or in the presence of acute complications (F1 = 11.95; p = 0.003). Conclusion: In contrast to the perception of parents, pediatric HSCT survivors reported good psychological health. However, they complained about more somatic problems as compared with healthy peers. Medical aspects such as donor source and the presence of acute complications should be taken into consideration for the psychological approach in order to improve pediatric HSCT survivor care. PMID:28424633

Nash equilibrium and multi criterion aerodynamic optimization

NASA Astrophysics Data System (ADS)

Tang, Zhili; Zhang, Lianhe

2016-06-01

Game theory and its particular Nash Equilibrium (NE) are gaining importance in solving Multi Criterion Optimization (MCO) in engineering problems over the past decade. The solution of a MCO problem can be viewed as a NE under the concept of competitive games. This paper surveyed/proposed four efficient algorithms for calculating a NE of a MCO problem. Existence and equivalence of the solution are analyzed and proved in the paper based on fixed point theorem. Specific virtual symmetric Nash game is also presented to set up an optimization strategy for single objective optimization problems. Two numerical examples are presented to verify proposed algorithms. One is mathematical functions' optimization to illustrate detailed numerical procedures of algorithms, the other is aerodynamic drag reduction of civil transport wing fuselage configuration by using virtual game. The successful application validates efficiency of algorithms in solving complex aerodynamic optimization problem.

Artificial Bee Colony Optimization for Short-Term Hydrothermal Scheduling

NASA Astrophysics Data System (ADS)

Basu, M.

2014-12-01

Artificial bee colony optimization is applied to determine the optimal hourly schedule of power generation in a hydrothermal system. Artificial bee colony optimization is a swarm-based algorithm inspired by the food foraging behavior of honey bees. The algorithm is tested on a multi-reservoir cascaded hydroelectric system having prohibited operating zones and thermal units with valve point loading. The ramp-rate limits of thermal generators are taken into consideration. The transmission losses are also accounted for through the use of loss coefficients. The algorithm is tested on two hydrothermal multi-reservoir cascaded hydroelectric test systems. The results of the proposed approach are compared with those of differential evolution, evolutionary programming and particle swarm optimization. From numerical results, it is found that the proposed artificial bee colony optimization based approach is able to provide better solution.

Development of Methodologies for the Estimation of Thermal Properties Associated with Aerospace Vehicles

NASA Technical Reports Server (NTRS)

Scott, Elaine P.

1996-01-01

A thermal stress analysis is an important aspect in the design of aerospace structures and vehicles such as the High Speed Civil Transport (HSCT) at the National Aeronautics and Space Administration Langley Research Center (NASA-LaRC). These structures are complex and are often composed of numerous components fabricated from a variety of different materials. The thermal loads on these structures induce temperature variations within the structure, which in turn result in the development of thermal stresses. Therefore, a thermal stress analysis requires knowledge of the temperature distributions within the structures which consequently necessitates the need for accurate knowledge of the thermal properties, boundary conditions and thermal interface conditions associated with the structural materials. The goal of this proposed multi-year research effort was to develop estimation methodologies for the determination of the thermal properties and interface conditions associated with aerospace vehicles. Specific objectives focused on the development and implementation of optimal experimental design strategies and methodologies for the estimation of thermal properties associated with simple composite and honeycomb structures. The strategy used in this multi-year research effort was to first develop methodologies for relatively simple systems and then systematically modify these methodologies to analyze complex structures. This can be thought of as a building block approach. This strategy was intended to promote maximum usability of the resulting estimation procedure by NASA-LARC researchers through the design of in-house experimentation procedures and through the use of an existing general purpose finite element software.

Whole CMV Proteome Pattern Recognition Analysis after HSCT Identifies Unique Epitope Targets Associated with the CMV Status

PubMed Central

Pérez-Bercoff, Lena; Valentini, Davide; Gaseitsiwe, Simani; Mahdavifar, Shahnaz; Schutkowski, Mike; Poiret, Thomas; Pérez-Bercoff, Åsa; Ljungman, Per; Maeurer, Markus J.

2014-01-01

Cytomegalovirus (CMV) infection represents a vital complication after Hematopoietic Stem Cell Transplantation (HSCT). We screened the entire CMV proteome to visualize the humoral target epitope-focus profile in serum after HSCT. IgG profiling from four patient groups (donor and/or recipient +/− for CMV) was performed at 6, 12 and 24 months after HSCT using microarray slides containing 17174 of 15mer-peptides overlapping by 4 aa covering 214 proteins from CMV. Data were analyzed using maSigPro, PAM and the ‘exclusive recognition analysis (ERA)’ to identify unique CMV epitope responses for each patient group. The ‘exclusive recognition analysis’ of serum epitope patterns segregated best 12 months after HSCT for the D+/R+ group (versus D−/R−). Epitopes were derived from UL123 (IE1), UL99 (pp28), UL32 (pp150), this changed at 24 months to 2 strongly recognized peptides provided from UL123 and UL100. Strongly (IgG) recognized CMV targets elicited also robust cytokine production in T-cells from patients after HSCT defined by intracellular cytokine staining (IL-2, TNF, IFN and IL-17). High-content peptide microarrays allow epitope profiling of entire viral proteomes; this approach can be useful to map relevant targets for diagnostics and therapy in patients with well defined clinical endpoints. Peptide microarray analysis visualizes the breadth of B-cell immune reconstitution after HSCT and provides a useful tool to gauge immune reconstitution. PMID:24740411

Reproductive issues in patients undergoing Hematopoietic Stem Cell Transplantation: an update.

PubMed

Guida, Maurizio; Castaldi, Maria Antonietta; Rosamilio, Rosa; Giudice, Valentina; Orio, Francesco; Selleri, Carmine

2016-11-01

In 1963 George Mathé announced to the world that he had cured a patient of leukaemia by means of a bone-marrow transplant. Since than much progress has been made and nowadays Hematopoietic Stem Cell Transplantation (HSCT) is considered the most effective treatment of numerous severe haematological diseases. Gynaecological complications in HSCT women represent a serious concern for these patients, but often underestimated by clinicians in the view of Overall Survival. The main gynaecological complications of HSCT are represented by: premature ovarian failure (POF), thrombocytopenia-associated menorrhagia, genital symptoms or sexual problems in course of chronic GVHD (cGVHD), osteoporosis, secondary solid tumours due to immunosuppressive drugs to treat cGVHD and severity of cGVHD, and fertility and pregnancy issues. In particular fertility-related issues are always more relevant for patients, whose life expectation is constantly growing up after HSCT.Thus, taking care of a patient undergoing HSCT should primarily include gynaecological evaluation, even before conditioning regimen or chemotherapy for the underlying malignancy, as, in our opinion, it is of great importance to ensure a complete diagnostic work-up and intervention options to guarantee maximum reproductive health and a better quality of life in HSCT women.The present review aims at describing principal features of the aforementioned gynaecological complications of HSCT, and to define, on the basis of current international literature, a specific protocol for the prevention, diagnosis, management and follow-up of gynaecological complications of both autologous and heterologous transplantation, before and after the procedure.

Antifungal prophylaxis with fluconazole in allogeneic stem cell transplantation recipients who had prior invasive aspergillosis with subsequent complete resolution by computed tomography.

PubMed

Akahoshi, Yu; Kimura, Shun-Ichi; Gomyo, Ayumi; Hayakawa, Jin; Tamaki, Masaharu; Harada, Naonori; Kusuda, Machiko; Kameda, Kazuaki; Ugai, Tomotaka; Wada, Hidenori; Ishihara, Yuko; Kawamura, Koji; Sakamoto, Kana; Sato, Miki; Terasako-Saito, Kiriko; Kikuchi, Misato; Nakasone, Hideki; Kako, Shinichi; Kanda, Yoshinobu

2018-04-01

Consensus has yet to be reached regarding secondary prophylaxis in allogeneic hematopoietic stem cell transplantation (HSCT) with a complete resolution of invasive aspergillosis (IA) confirmed by chest computed tomography (CT). We retrospectively evaluated the feasibility of antifungal prophylaxis with fluconazole in allogeneic HSCT recipients who had previously developed IA which showed complete resolution as confirmed by chest CT before HSCT. Consecutive adult patients who underwent allogeneic HSCT at our institution and who had received fluconazole as systemic antifungal prophylaxis from June 2007 to January 2015 were included. We compared the clinical outcomes between patients with a past history of IA who showed a complete resolution of chest CT abnormalities (n = 13) and those without a previous history of IA (n = 137). The cumulative incidence of proven or probable IA was 8.8% in the group without a past history of IA and 0.0% in the group with a past history of IA (p = .268). The cumulative incidence of proven or probable invasive fungal disease (IFD) within 100 days after allogeneic HSCT was 10.9% in the group without a past history of IA and 15.4% in the group with a past history of IA (p = .647). Fluconazole was switched to anti-mould agents in two-thirds of the patients in each group by day 100 after HSCT. Fluconazole was confirmed to be an acceptable prophylactic agent early after allogeneic HSCT in appropriately selected patients.

Successful Combination of Sequential Gene Therapy and Rescue Allo-HSCT in Two Children with X-CGD - Importance of Timing.

PubMed

Siler, Ulrich; Paruzynski, Anna; Holtgreve-Grez, Heidi; Kuzmenko, Elena; Koehl, Ulrike; Renner, Eleonore D; Alhan, Canan; de Loosdrecht, Arjan A van; Schwäble, Joachim; Pfluger, Thomas; Tchinda, Joelle; Schmugge, Markus; Jauch, Anna; Naundorf, Sonja; Kühlcke, Klaus; Notheis, Gundula; Güngor, Tayfun; Kalle, Christof V; Schmidt, Manfred; Grez, Manuel; Seger, Reinhard; Reichenbach, Janine

2015-01-01

We report on a series of sequential events leading to long-term survival and cure of pediatric X-linked chronic granulomatous disease (X-CGD) patients after gamma-retroviral gene therapy (GT) and rescue HSCT. Due to therapyrefractory life-threatening infections requiring hematopoietic stem cell transplantation (HSCT) but absence of HLAidentical donors, we treated 2 boys with X-CGD by GT. Following GT both children completely resolved invasive Aspergillus nidulans infections. However, one child developed dual insertional activation of ecotropic viral integration site 1 (EVI1) and signal transducer and activator of transcription 3 (STAT3) genes, leading to myelodysplastic syndrome (MDS) with monosomy 7. Despite resistance to mismatched allo-HSCT with standard myeloablative conditioning, secondary intensified rescue allo-HSCT resulted in 100 % donor chimerism and disappearance of MDS. The other child did not develop MDS despite expansion of a clone with a single insertion in the myelodysplasia syndrome 1 (MDS1) gene and was cured by early standard allo-HSCT. The slowly developing dominance of clones harboring integrations in MDS1-EVI1 may guide clinical intervention strategies, i.e. early rescue allo-HSCT, prior to malignant transformation. GT was essential for both children to survive and to clear therapy-refractory infections, and future GT with safer lentiviral self-inactivated (SIN) vectors may offer a therapeutic alternative for X-CGD patients suffering from life-threatening infections and lacking HLA-identical HSC donors.

Prevalence of sarcopenia and relevance of body composition, physiological function, fatigue, and health-related quality of life in patients before allogeneic hematopoietic stem cell transplantation.

PubMed

Morishita, Shinichiro; Kaida, Katsuji; Tanaka, Takashi; Itani, Yusuke; Ikegame, Kazuhiro; Okada, Masaya; Ishii, Shinichi; Kodama, Norihiko; Ogawa, Hiroyasu; Domen, Kazuhisa

2012-12-01

Cachexia in patients with hematological malignancies is often related to sarcopenia. We believe that allogeneic hematopoietic stem cell transplant (allo-HSCT) patients often exhibit sarcopenia prior to transplantation. Here, we aimed to investigate the prevalence of sarcopenia and its relationship with body composition, physiological function, nutrition, fatigue, and health-related quality of life (QOL) in patients before allo-HSCT. We further investigated the confounding factors associated with sarcopenia. We included 164 patients with allo-HSCT in this study. Body composition, handgrip, knee extensor strength, and 6-min walk test were evaluated. Furthermore, fatigue, nutritional status, and health-related QOL were also evaluated. Eighty-three patients (50.6 %) enrolled in our study had sarcopenia prior to allo-HSCT. Patients with sarcopenia experienced decreased muscular strength and increased fatigue compared with patients without sarcopenia (p < 0.05). Patients with sarcopenia showed significantly lower scores in physical functioning, bodily pain, and vitality in health-related QOL than those without sarcopenia. Multivariate regression analysis revealed that only gender and body mass index were significantly related to sarcopenia (gender, odds ratio, 3.09; body mass index, odds ratio, 0.70; p < 0.01). Sarcopenia is common in patients before allo-HSCT and related to low muscle strength, fatigue, and health-related QOL. Male patients may be more susceptible to sarcopenia than female patients before allo-HSCT. Further study of rehabilitation with gender insight is warranted for patients receiving allo-HSCT.

Heat shock protein vaccination and directed IL-2 therapy amplify tumor immunity rapidly following bone marrow transplantation in mice

PubMed Central

Newman, Robert G.; Dee, Michael J.; Malek, Thomas R.; Podack, Eckhard R.; Levy, Robert B.

2014-01-01

Tumor relapse is the primary cause of mortality in patients with hematologic cancers following autologous hematopoietic stem cell transplantation (HSCT). Vaccination early after HSCT can exploit both the state of lymphopenia and minimal residual disease for generating antitumor immunity. Here, multiple vaccinations using lymphoma cells engineered to secrete heat shock protein fusion gp96-Ig within 2 weeks of T cell-replete syngeneic HSCT led to cross-presentation and increased survival of lymphoma-bearing mice. To enhance vaccine efficacy, interleukin (IL)-2 was directed to predominantly memory phenotype CD8+ T lymphocytes and natural killer (NK) cells via administration bound to anti-IL-2 monoclonal antibody clone S4B6 (IL-2S4B6). Combination therapy with gp96-Ig vaccination and coordinated infusions of IL-2S4B6 resulted in marked prolongation of survival, which directly correlated with ∼500% increase in effector CD8+ T-cell numbers. Notably, this dual regimen elicited large increases in both donor CD8+ T and NK cells, but not CD4+ T lymphocytes; the former 2 populations are essential for both vaccine efficacy and protection against opportunistic infections after HSCT. Indeed, IL-2S4B6-treated HSCT recipients infected with Listeria monocytogenes exhibited decreased bacterial levels. These preclinical studies validate a new strategy particularly well suited to the post-HSCT environment, which may augment adaptive and innate immune function in patients with malignant disease receiving autologous HSCT. PMID:24687086

Late-onset Epstein-Barr virus-related disease in acute leukemia patients after haploidentical hematopoietic stem cell transplantation is associated with impaired early recovery of T and B lymphocytes.

PubMed

Liu, Jiangying; Yan, Chenhua; Zhang, Chunli; Xu, Lanping; Liu, Yanrong; Huang, Xiaojun

2015-10-01

Epstein-Barr virus-related disease (EBVD) is a serious clinical complication in patients who have undergone haploidentical hematopoietic stem cell transplantation (haploHSCT). Some recipients develop EBVD relatively late after haploHSCT, and most of these patients suffer a poor outcome. This retrospective cohort study characterized the early adaptive immune recovery of patients with acute leukemia presenting with EBVD more than 100 d after haploHSCT. Patients with acute leukemia who received haploHSCT and developed EBVD 100 d later (n = 8) were compared with a matched control group without EBVD (n = 24) with regard to peripheral WBC, lymphocytes, and neutrophils (at 30, 60, and 90 d) and recoveries of B and T lymphocytes (at 30 and 90 d, via immunophenotyping/flow cytometry). Ninety days after haploHSCT, the median values of WBCs and lymphocytes, and the recoveries of CD19(+) B cells and CD4(+) , CD8(+) , and CD4(+) CD45RO(+) T cells, were significantly lower in patients who developed EBVD, relative to the control group. These results suggest a significant association between deficient early recovery of B and T lymphocytes and the development of late-onset EBVD after haploHSCT. Our observation could facilitate clinical intervention and the improvement of overall survival of patients undergoing haploHSCT. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Strength Training Following Hematopoietic Stem Cell Transplantation

PubMed Central

Hacker, Eileen Danaher; Larson, Janet; Kujath, Amber; Peace, David; Rondelli, Damiano; Gaston, Lisa

2010-01-01

Background Patients receiving high-dose chemotherapy and hematopoietic stem cell transplantation (HSCT) experience considerable reductions in physical activity and deterioration of their health status. Objective The purpose of this pilot study was to test the effects of strength training compared to usual activity on physical activity, muscle strength, fatigue, health status perceptions, and quality of life following HSCT. Interventions/Methods Nineteen subjects were randomized to the exercise or control group. Moderate intensity strength training began following discharge from the hospital. Dependent variables included physical activity, muscle strength, fatigue, health status perceptions and quality of life. Variables were measured prior to admission to the hospital for HSCT, day 8 following HSCT, and six weeks following discharge from the hospital. Results Significant time effects were noted for many variables with anticipated declines in physical activity, muscle strength, fatigue, and health status perceptions immediately after HSCT with subsequent improvements six weeks following hospital discharge. One group effect was noted with subjects in the exercise group reporting less fatigue than subjects in the control group. Although no significant interactions were detected, the trends suggest that the exercise group may be more physically active following the intervention compared to the usual activity group. Conclusions This study demonstrates the potential positive effects of strength training on physical activity, fatigue, and quality of life in people receiving high-dose chemotherapy and HSCT. Implications for Practice Preliminary evidence is provided for using strength training to enhance early recovery following HSCT. Elastic resistance bands are easy to use and relatively inexpensive. PMID:21116175

Multi-Criteria Optimization of Regulation in Metabolic Networks

PubMed Central

Higuera, Clara; Villaverde, Alejandro F.; Banga, Julio R.; Ross, John; Morán, Federico

2012-01-01

Determining the regulation of metabolic networks at genome scale is a hard task. It has been hypothesized that biochemical pathways and metabolic networks might have undergone an evolutionary process of optimization with respect to several criteria over time. In this contribution, a multi-criteria approach has been used to optimize parameters for the allosteric regulation of enzymes in a model of a metabolic substrate-cycle. This has been carried out by calculating the Pareto set of optimal solutions according to two objectives: the proper direction of flux in a metabolic cycle and the energetic cost of applying the set of parameters. Different Pareto fronts have been calculated for eight different “environments” (specific time courses of end product concentrations). For each resulting front the so-called knee point is identified, which can be considered a preferred trade-off solution. Interestingly, the optimal control parameters corresponding to each of these points also lead to optimal behaviour in all the other environments. By calculating the average of the different parameter sets for the knee solutions more frequently found, a final and optimal consensus set of parameters can be obtained, which is an indication on the existence of a universal regulation mechanism for this system.The implications from such a universal regulatory switch are discussed in the framework of large metabolic networks. PMID:22848435

HSCT materials and structures: An MDC perspective

NASA Technical Reports Server (NTRS)

Sutton, Jay O.

1992-01-01

The key High Speed Civil Transport (HSCT) features which control the materials selection are discussed. Materials are selected based on weight and production economics. The top-down and bottoms-up approaches to material selection are compared for the Mach 2.4 study baseline aircraft. The key materials and structures related tasks which remain to be accomplished prior to proceeding with the building of the HSCT aircraft are examined.

Short-term Assessment of HSCT Effects on the Hypothalamus-Pituitary Axis in Pediatric Thalassemic Patients.

PubMed

Hamidieh, Amir Ali; Mohseni, Fariba; Behfar, Maryam; Hamidi, Zohreh; Alimoghaddam, Kamran; Pajouhi, Mohamad; Larijani, Bagher; Mohajeri-Tehrani, Mohammad-Reza; Ghavamzadeh, Ardeshir

2018-02-01

Beta thalassemia major (BTM) and its treatment by hematopoietic stem cell transplantation (HSCT) may have deleterious effects on the endocrine systems. We assessed endocrine complications of HSCT in pediatric patients for 3 months. In 20 (6 female) pediatric major thalassemic patients (mean age of 10.8 ± 3.9 years old), prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), T4, T3, thyroid-stimulating hormone (TSH), IGF-1, testosterone (in males) or estradiol (in females) were measured as a batch at the Endocrinology and Metabolism Research Center (EMRC) of Tehran University of Medical Sciences (TUMS) laboratories before HSCT and 1 and 3 months afterwards. The cosyntropin test for all and the clonidine test for short stature patients was conducted before HSCT. Before HSCT, delayed puberty and hypogonadotropic hypogonadism was found in 10% and 20% of patients, respectively. GH deficiency, low IGF1 and short stature was found in 25%, 55% and 40% of patients, respectively. Hypocortisolism, hypothyroidism and panhypopituitarism was found in 15%, 10% and 15% of patients, respectively. Prevalence of hypogonadotropic hypogonadism, low IGF1, hypothyroidism and panhypopituitarism was found in 20%, 40%, 10% and 10% of patients after 3 months, respectively (delayed puberty and short stature prevalence do not change after 3 months). HSCT caused lower T3 and estradiol and higher TSH. Corticosteroid users (15) had higher GH and lower T3 and testosterone or estradiol. Ferritin had a significant (negative) correlation with (before) prolactin and a significant correlation with T3 and T4 after HSCT. Age and acute graft-versus-host disease (GVHD) had no significant effect. Considering the small sample size and short duration of the study, it is difficult to reach any conclusion however it seems HSCT does not appear to have an overall positive or negative effect on prevalence of pituitary- hypothalamus axis disorders in pediatric thalassemic patients in 3 months. © 2018 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Three sides to a story: Child, parent, and nurse perspectives on the child's experience during hematopoietic stem cell transplantation.

PubMed

Ullrich, Christina K; Rodday, Angie Mae; Bingen, Kristin M; Kupst, Mary Jo; Patel, Sunita K; Syrjala, Karen L; Harris, Lynnette L; Recklitis, Christopher J; Chang, Grace; Guinan, Eva C; Terrin, Norma; Tighiouart, Hocine; Phipps, Sean; Parsons, Susan K

2017-08-15

The experience of children undergoing hematopoietic stem cell transplantation (HSCT), including the ways in which different participants (ie, children, parents, and nurses) contribute to the overall picture of a child's experience, is poorly characterized. This study evaluated parent, child, and nurse perspectives on the experience of children during HSCT and factors contributing to interrater differences. Participants were enrolled in a multicenter, prospective study evaluating child and parent health-related quality of life over the year after HSCT. Children (n = 165) and their parents and nurses completed the Behavioral, Affective, and Somatic Experiences Scale (BASES) at baseline (before/during conditioning), 7 days after the stem cell infusion (day+7), and 21 days after the stem cell infusion (day+21). The BASES domains included Somatic Distress, Mood Disturbance, Cooperation, and Getting Along. Higher scores indicated more distress/impairment. Repeated measures models by domain assessed differences by raters and changes over time and identified other factors associated with raters' scores. Completion rates were high (≥73% across times and raters). Multivariate models revealed significant time-rater interactions, which varied by domain. For example, parent-rated Somatic Distress scores increased from baseline to day+7 and remained elevated at day+21 (P < .001); children's scores were lower than parents' scores across time points. Nurses' baseline scores were lower than parents' baseline scores, although by day+21 they were similar. Older child age was associated with higher Somatic Distress and Mood Disturbance scores. Worse parent emotional functioning was associated with lower scores across raters and domains except for Cooperation. Multirater assessments are highly feasible during HSCT. Ratings differ by several factors; considering ratings in light of such factors may deepen our understanding of the child's experience. Cancer 2017;123:3159-66. © 2017 American Cancer Society. © 2017 American Cancer Society.

The Hematopoietic Stem Cell Therapy for Exploration of Space

NASA Astrophysics Data System (ADS)

Ohi, S.

Departments of Biochemistry &Molecular Biology, Genetics &Human Genetics, Pediatrics &Child Long-duration space missions require countermeasures against severe/invasive disorders in astronauts that are caused by space environments, such as hematological/cardiac abnormalities, bone/muscle losses, immunodeficiency, neurological disorders, and cancer. Some, if not all, of these disorders may be amenable to hematopoietic stem cell therapy and gene therapy. Growing evidence indicates that hematopoietic stem cells (HSCs) possess extraordinary plasticity to differentiate not only to all types of blood cells but also to various tissues, including bone, muscle, skin, liver and neuronal cells. Therefore, our working hypothesis is that the hematopoietic stem cell-based therapy, herein called as the hematopoietic stem cell therapy (HSCT), might provide countermeasure/prevention for hematological abnormalities, bone and muscle losses in space, thereby maintaining astronauts' homeostasis. Our expertise lies in recombinant adeno-associated virus (rAAV)-mediated gene therapy for the hemoglobinopathies, -thalassemia and sickle cell disease (Ohi S, Kim BC, J Pharm Sci 85: 274-281, 1996; Ohi S, et al. Grav Space Biol Bull 14: 43, 2000). As the requisite steps in this protocol, we established procedures for purification of HSCs from both mouse and human bone marrow in 1 G. Furthermore, we developed an easily harvestable, long-term liquid suspension culture system, which lasts more than one year, for growing/expanding HSCs without stromal cells. Human globin cDNAs/gene were efficiently expressed from the rAAVs in the mouse HSCs in culture. Additionally, the NASA Rotating Wall Vessel (RWV) culture system is being optimized for the HSC growth/expansion. Thus, using these technologies, the above hypothesis is being investigated by the ground-based experiments as follows: 1) -thalassemic mice (C57BL/6-Hbbth/Hbbth, Hbd-minor) are transplanted with normal isologous HSCs to correct the hematological abnormalities. To date, the - thalassemic mice have been successfully HSC-transplanted to produce chimerism of hemoglobin species (Ohi S, J Grav Physiol 7: 67-68, 2000); 2) Transgenic HSCs harboring green fluorescent protein (GFP) gene or -galactosidase gene are/will be transplanted to hindlimb suspended mice, and differentiation of HSCs to bone will be traced by the marker gene expression. Repair/prevention of bone loss by the HSCT will be investigated by analyzing physical/biochemical parameters; 3) Similarly, the efficacy of HSCT for muscle loss in the unloaded mouse is being studied. In addition, using the hindlimb suspension model, effects of exercise on the HSCT for bone and muscle losses are being investigated. Our long-term goal is to automate/robotize the HSCT protocols so that astronauts would be able to treat themselves during long-duration space missions. Such a program will be also beneficial to the earth people as a self-care health system. Upon optimization of the condition of HSC growth in the RWV culture system, it is in our plan to conduct the similar experiments as above in the International Space Station in future. (Supported in part by grant from NASA Institute for Advanced Concepts/USRA.

Hematopoietic stem cell transplantation for HIV cure.

PubMed

Kuritzkes, Daniel R

2016-02-01

The apparent cure of an HIV-infected person following hematopoietic stem cell transplantation (HSCT) from an allogeneic donor homozygous for the ccr5Δ32 mutation has stimulated the search for strategies to eradicate HIV or to induce long-term remission without requiring ongoing antiretroviral therapy. A variety of approaches, including allogeneic HSCT from CCR5-deficient donors and autologous transplantation of genetically modified hematopoietic stem cells, are currently under investigation. This Review covers the experience with HSCT in HIV infection to date and provides a survey of ongoing work in the field. The challenges of developing HSCT for HIV cure in the context of safe, effective, and convenient once-daily antiretroviral therapy are also discussed.

A Phase I Study of Reduced-Intensity Conditioning and Allogeneic Stem Cell Transplantation Followed by Dose Escalation of Targeted Consolidation Immunotherapy with Gemtuzumab Ozogamicin in Children and Adolescents with CD33+ Acute Myeloid Leukemia.

PubMed

Zahler, Stacey; Bhatia, Monica; Ricci, Angela; Roy, Sumith; Morris, Erin; Harrison, Lauren; van de Ven, Carmella; Fabricatore, Sandra; Wolownik, Karen; Cooney-Qualter, Erin; Baxter-Lowe, Lee Ann; Luisi, Paul; Militano, Olga; Kletzel, Morris; Cairo, Mitchell S

2016-04-01

Myeloablative conditioning and allogeneic hematopoietic stem cell transplant (alloHSCT) in children with acute myeloid leukemia (AML) in first complete remission (CR1) may be associated with significant acute toxicity and late effects. Reduced-intensity conditioning (RIC) and alloHSCT in children is safe, feasible, and may be associated with less adverse effects. Gemtuzumab ozogamicin (GO) induces a response in 30% of patients with CD33+ relapsed/refractory AML. The dose of GO is significantly lower when combined with chemotherapy. We examined the feasibility and toxicity of RIC alloHSCT followed by GO targeted immunotherapy in children with CD33+ AML in CR1/CR2. Conditioning consisted of fludarabine 30 mg/m2 × 6 days, busulfan 3.2 to 4 mg/kg × 2 days ± rabbit antithymocyte globulin 2 mg/kg × 4 days followed by alloHSCT from matched related/unrelated donors. GO was administered ≥60 days after alloHSCT in 2 doses (8 weeks apart), following a dose-escalation design (4.5, 6, 7.5, and 9 mg/m2). Fourteen patients with average risk AML received RIC alloHSCT and post-GO consolidation: median age 13.5 years at transplant (range, 1 to 21), male-to-female 8:6, and disease status at alloHSCT 11 CR1 and 3 CR2. Eleven patients received alloHSCT from 5-6/6 HLA-matched family donors: 8 received peripheral blood stem cells, 2 received bone marrow, and 1 received related cord blood transplantation. Three patients received an unrelated allograft (two 4-5/6 and one 9/10) from unrelated cord blood unit and bone marrow, respectively. Neutrophil and platelet engraftment was observed in all assessable patients (100%), achieved at median 15.5 days (range, 7 to 31) and 21 days (range, 10 to 52), respectively. Three patients received GO at dose level 1 (4.5 mg/m2 per dose), 5 at dose level 2 (6 mg/m2 per dose), 3 at dose level 3 (7.5 mg/m2 per dose), and 3 at dose level 4 (9 mg/m2 per dose). Three of 14 patients received only 1 dose of GO after alloHSCT. One patient experienced grade III transaminitis, which resolved; no grade IV transaminitis, no grade III/IV hyperbilirubinemia, or sinusoidal obstructive syndrome were observed. The second dose of GO was given at median of 143 days (range, 120 to 209) after alloHSCT. Probability of grades II to IV acute and chronic graft-versus-host disease were 21% and 33.5%, respectively. Probability of overall survival after RIC alloHSCT and GO consolidation at 1 and 5 years was 78% and 61%, respectively. Probability of 5-year event-free survival after RIC alloHSCT and GO consolidation in patients in CR1 was 78%. No dose-limiting toxicities probably or directly related to GO were observed in this cohort. This preliminary data demonstrate that RIC followed by alloHSCT and consolidation with GO appears to be safe in children and adolescents with CD33+ AML in CR1/CR2. A phase II trial is currently underway investigating this approach with a GO dose of 9 mg/m2 per dose. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Fabrication and Optimization of Bilayered Nanoporous Anodic Alumina Structures as Multi-Point Interferometric Sensing Platform

PubMed Central

Nemati, Mahdieh; Santos, Abel

2018-01-01

Herein, we present an innovative strategy for optimizing hierarchical structures of nanoporous anodic alumina (NAA) to advance their optical sensing performance toward multi-analyte biosensing. This approach is based on the fabrication of multilayered NAA and the formation of differential effective medium of their structure by controlling three fabrication parameters (i.e., anodization steps, anodization time, and pore widening time). The rationale of the proposed concept is that interferometric bilayered NAA (BL-NAA), which features two layers of different pore diameters, can provide distinct reflectometric interference spectroscopy (RIfS) signatures for each layer within the NAA structure and can therefore potentially be used for multi-point biosensing. This paper presents the structural fabrication of layered NAA structures, and the optimization and evaluation of their RIfS optical sensing performance through changes in the effective optical thickness (EOT) using quercetin as a model molecule. The bilayered or funnel-like NAA structures were designed with the aim of characterizing the sensitivity of both layers of quercetin molecules using RIfS and exploring the potential of these photonic structures, featuring different pore diameters, for simultaneous size-exclusion and multi-analyte optical biosensing. The sensing performance of the prepared NAA platforms was examined by real-time screening of binding reactions between human serum albumin (HSA)-modified NAA (i.e., sensing element) and quercetin (i.e., analyte). BL-NAAs display a complex optical interference spectrum, which can be resolved by fast Fourier transform (FFT) to monitor the EOT changes, where three distinctive peaks were revealed corresponding to the top, bottom, and total layer within the BL-NAA structures. The spectral shifts of these three characteristic peaks were used as sensing signals to monitor the binding events in each NAA pore in real-time upon exposure to different concentrations of quercetin. The multi-point sensing performance of BL-NAAs was determined for each pore layer, with an average sensitivity and low limit of detection of 600 nm (mg mL−1)−1 and 0.14 mg mL−1, respectively. BL-NAAs photonic structures have the capability to be used as platforms for multi-point RIfS sensing of biomolecules that can be further extended for simultaneous size-exclusion separation and multi-analyte sensing using these bilayered nanostructures. PMID:29415436

Cargo and Container X-Ray Inspection with Intra-Pulse Multi-Energy Method for Material Discrimination

NASA Astrophysics Data System (ADS)

Saverskiy, Aleksandr Y.; Dinca, Dan-Cristian; Rommel, J. Martin

The Intra-Pulse Multi-Energy (IPME) method of material discrimination mitigates main disadvantages of the traditional "interlaced" approach: ambiguity caused by sampling different regions of cargo and reduction of effective scanning speed. A novel concept of creating multi-energy probing pulses using a standing-wave structure allows maintaining a constant energy spectrum while changing the time duration of each sub-pulse and thus enables adaptive cargo inspection. Depending on the cargo density, the dose delivered to the inspected object is optimized for best material discrimination, maximum material penetration, or lowest dose to cargo. A model based on Monte-Carlo simulation and experimental reference points were developed for the optimization of inspection conditions.

Seamline Determination Based on PKGC Segmentation for Remote Sensing Image Mosaicking

PubMed Central

Dong, Qiang; Liu, Jinghong

2017-01-01

This paper presents a novel method of seamline determination for remote sensing image mosaicking. A two-level optimization strategy is applied to determine the seamline. Object-level optimization is executed firstly. Background regions (BRs) and obvious regions (ORs) are extracted based on the results of parametric kernel graph cuts (PKGC) segmentation. The global cost map which consists of color difference, a multi-scale morphological gradient (MSMG) constraint, and texture difference is weighted by BRs. Finally, the seamline is determined in the weighted cost from the start point to the end point. Dijkstra’s shortest path algorithm is adopted for pixel-level optimization to determine the positions of seamline. Meanwhile, a new seamline optimization strategy is proposed for image mosaicking with multi-image overlapping regions. The experimental results show the better performance than the conventional method based on mean-shift segmentation. Seamlines based on the proposed method bypass the obvious objects and take less time in execution. This new method is efficient and superior for seamline determination in remote sensing image mosaicking. PMID:28749446

Unrelated Hematopoietic Cell Transplantation in a Patient with Combined Immunodeficiency with Granulomatous Disease and Autoimmunity Secondary to RAG Deficiency.

PubMed

John, Tami; Walter, Jolan E; Schuetz, Catherina; Chen, Karin; Abraham, Roshini S; Bonfim, Carmem; Boyce, Thomas G; Joshi, Avni Y; Kang, Elizabeth; Carvalho, Beatriz Tavares Costa; Mahajerin, Arash; Nugent, Diane; Puthenveetil, Geetha; Soni, Amit; Su, Helen; Cowan, Morton J; Notarangelo, Luigi; Buchbinder, David

2016-10-01

The use of HLA-identical hematopoietic stem cell transplantation (HSCT) demonstrates overall survival rates greater than 75 % for T-B-NK+ severe combined immunodeficiency secondary to pathogenic mutation of recombinase activating genes 1 and 2 (RAG1/2). Limited data exist regarding the use of HSCT in patients with hypomorphic RAG variants marked by greater preservation of RAG activity and associated phenotypes such as granulomatous disease in combination with autoimmunity. We describe a 17-year-old with combined immunodeficiency and immune dysregulation characterized by granulomatous lung disease and autoimmunity secondary to compound heterozygous RAG mutations. A myeloablative reduced toxicity HSCT was completed using an unrelated bone marrow donor. With the increasing cases of immune dysregulation being discovered with hypomorphic RAG variants, the use of HSCT may advance to the forefront of treatment. This case serves to discuss indications of HSCT, approaches to preparative therapy, and the potential complications in this growing cohort of patients with immune dysregulation and RAG deficiency.

[Hematopoietic stem cell transplantation. Indications, foundations and perspective].

PubMed

Buchholz, S; Ganser, A

2009-05-01

The hematopoietic stem cell transplantation (HSCT) has become a standard therapy for many inherited and acquired disorders of the bone marrow and immune system. Autologous HSCT is mainly done as part of the primary therapy in multiple myeloma and as part of relapse therapy in malignant lymphoma. In contrast, allogeneic HSCT is predominantly performed in patients with acute leukemias. The selection process for allogeneic HSCT takes disease-specific as well as patient-specific factors into account. Risk factors which can predict for poor response to chemotherapy can now be identified in acute myeloid as well as lymphoid leukemia, based on phenotype, cytogenetics, molecular genetics and response to therapy. In these patients allogeneic HSCT can improve overall survival from 0-20% to 30-60%. New conditioning protocols have now raised the upper age limit for transplantation to 70 years. In elderly patients the selection of patients based on absence of comorbidities becomes especially important. The increasing number of long-term survivors requires knowledge of organ-specific late toxicities including secondary malignancies.

Utilization of Collaborative Practice Agreements between Physicians and Pharmacists as a Mechanism to Increase Capacity to Care for Hematopoietic Stem Cell Transplant Recipients

PubMed Central

Merten, Julianna A.; Shapiro, Jamie F.; Gulbis, Alison M.; Rao, Kamakshi V.; Bubalo, Joseph; Lanum, Scott; Engemann, Ashley Morris; Shayani, Sepideh; Williams, Casey; Leather, Helen; Walsh-Chocolaad, Tracey

2013-01-01

Survival following hematopoietic stem cell transplantation (HSCT) has improved and the number of allogeneic HSCTs performed annually in the United States is expected to reach 10,000 by 2015. The National Marrow Donor Program created the System Capacity Initiative to formulate mechanisms to care for the growing number of HSCT recipients. One proposed method to increase capacity is utilization of pharmacists to manage drug therapy via collaborative practice agreements (CPAs). Pharmacists have managed drug therapy in oncology patients with CPAs for decades; however, there are limited HSCT centers that employ this practice. Engaging in collaborative practice and billing agreements with credentialed pharmacists to manage therapeutic drug monitoring, chronic medical conditions and supportive care in HSCT recipients may be cost-effective and enable physicians to spend more time on new or more complex patients. The goal of this paper is to provide a framework for implementation of a CPA and address how it may improve HSCT program capacity. PMID:23419976

Absence of VOD in paediatric thalassaemic HSCT recipients using defibrotide prophylaxis and intravenous Busulphan.

PubMed

Cappelli, Barbara; Chiesa, Robert; Evangelio, Costanza; Biffi, Alessandra; Roccia, Tito; Frugnoli, Ilaria; Biral, Erika; Noè, Anna; Fossati, Marco; Finizio, Valentina; Miniero, Roberto; Napolitano, Sara; Ferrua, Francesca; Soliman, Clara; Ciceri, Fabio; Roncarolo, Maria G; Marktel, Sarah

2009-11-01

Hepatic veno-occlusive disease (VOD) is a common complication of haematopoietic stem cell transplantation (HSCT), with reported incidences of 5-40% in children. Recently, defibrotide (DF) has been successfully used as prophylaxis and treatment of VOD. This study reports data on 63 human leucocyte antigen-matched HSCT performed in 57 children affected by beta thalassemia at very high risk for developing VOD (liver fibrosis, iron overload, hepatitis C virus infections, busulphan-based conditioning, methotraexate + ciclosporine). All patients received a busulphan-based conditioning regimen, either orally (four HSCT) or intravenously (59 HSCT). All patients received oral DF (40 mg/kg per day, final dose) as VOD prophylaxis from median day -9 to median day +29. In order to overcome the lack of oral paediatric formulations, a galenic formulation was administered. DF was well tolerated. Only one patient fulfilled Seattle Criteria for VOD diagnosis. This patient had discontinued DF 6 d prior to VOD onset, due to high risk of haemorrhage. We concluded that oral defibrotide prophylaxis and i.v. busulphan safely abated VOD incidence in high-risk patients who had undergone HSCT. A galenic preparation of oral DF also permits this treatment in low-weight patients. Costs of DF prophylaxis are acceptable considering the reduced incidence of VOD.

Evolving Hematopoietic Stem Cell Transplantation Strategies in Severe Aplastic Anemia

PubMed Central

Dietz, Andrew C.; Lucchini, Giovanna; Samarasinghe, Sujith; Pulsipher, Michael A.

2016-01-01

Purpose of Review Significant improvements in unrelated donor hematopoietic stem cell transplantation (HSCT) in recent years has solidified its therapeutic role in severe aplastic anemia (SAA) and led to evolution of treatment algorithms, particularly for children. Recent Findings Advances in understanding genetics of inherited bone marrow failure syndromes (IBMFS) have allowed more confidence in accurately diagnosing SAA and avoiding treatments that could be dangerous and ineffective in individuals with IBMFS, which can be diagnosed in 10–20% of children presenting with a picture of SAA. Additionally long-term survival after matched sibling donor (MSD) and matched unrelated donor (MUD) HSCT now exceed 90% in children. Late effects after HSCT for SAA are minimal with current strategies and compare favorably to late effects after up-front immunosuppressive therapy (IST), except for patients with chronic graft versus host disease (GVHD). Summary 1) Careful assessment for signs or symptoms of IBMFS along with genetic screening for these disorders is of major importance. 2) MSD HSCT is already considered standard of care for up-front therapy and some groups are evaluating MUD HSCT as primary therapy. 3) Ongoing studies will continue to challenge treatment algorithms and may lead to an even more expanded role for HSCT in SAA. PMID:26626557

Unmanipulated haploidentical haematopoietic stem cell transplantation for children with severe aplastic anaemia.

PubMed

Zhu, Hua; Luo, Rong Mu; Luan, Zuo; Lee, Vincent; Zhu, Yi Ping; Luo, Cheng Juan; Tang, Xiang Feng; Si, Ying Jian; Chen, Jing

2016-09-01

Haploidentical haematopoietic stem cell transplantation (haplo-HSCT) used to be a third-line treatment option for childhood severe aplastic anaemia (SAA). We conducted this retrospective study of 36 children (38 transplants) who received haplo-HSCT from human leucocyte antigen (HLA)-mismatched related donors between July 2002 and November 2013 at five HSCT centres in China, including 17 cases that were 5/6 HLA matched (Group 1) and 21 that were 4/6 or 3/6 HLA matched (Group 2). Although patients in Group 2 had a higher incidence of grade II-IV acute graft-versus-host disease (57·9% vs. 5·9%, P = 0·001), they had similar rates of graft failure (5·3% vs. 5·9%, P = 0·742) and overall survival (80·8% vs. 93·8%, P = 0·234) as Group 1. Unmanipulated haplo-HSCT is an effective treatment for SAA children with satisfactory outcome of this cohort, especially in the 5/6 HLA-matched group. For patients in critical situations, such as unresponsive to immunosuppressive therapy, refractory infection and failing first HSCT, to bring forward the timing of haplo-HSCT is a feasible salvage strategy with better and faster donor accessibility. © 2016 John Wiley & Sons Ltd.

A human monoclonal antibody drug and target discovery platform for B-cell chronic lymphocytic leukemia based on allogeneic hematopoietic stem cell transplantation and phage display.

PubMed

Baskar, Sivasubramanian; Suschak, Jessica M; Samija, Ivan; Srinivasan, Ramaprasad; Childs, Richard W; Pavletic, Steven Z; Bishop, Michael R; Rader, Christoph

2009-11-12

Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only potentially curative treatment available for patients with B-cell chronic lymphocytic leukemia (B-CLL). Here, we show that post-alloHSCT antibody repertoires can be mined for the discovery of fully human monoclonal antibodies to B-CLL cell-surface antigens. Sera collected from B-CLL patients at defined times after alloHSCT showed selective binding to primary B-CLL cells. Pre-alloHSCT sera, donor sera, and control sera were negative. To identify post-alloHSCT serum antibodies and subsequently B-CLL cell-surface antigens they recognize, we generated a human antibody-binding fragment (Fab) library from post-alloHSCT peripheral blood mononuclear cells and selected it on primary B-CLL cells by phage display. A panel of Fab with B-CLL cell-surface reactivity was strongly enriched. Selection was dominated by highly homologous Fab predicted to bind the same antigen. One Fab was converted to immunoglobulin G1 and analyzed for reactivity with peripheral blood mononuclear cells from B-CLL patients and healthy volunteers. Cell-surface antigen expression was restricted to primary B cells and up-regulated in primary B-CLL cells. Mining post-alloHSCT antibody repertoires offers a novel route to discover fully human monoclonal antibodies and identify antigens of potential therapeutic relevance to B-CLL and possibly other cancers. Trials described herein were registered at www.clinicaltrials.gov as nos. NCT00055744 and NCT00003838.

Ciprofloxacin decreased polyoma BK virus load in patients who underwent allogeneic hematopoietic stem cell transplantation.

PubMed

Leung, Anskar Y H; Chan, Maggie T L; Yuen, Kwok-Yung; Cheng, Vincent C C; Chan, Kwok-Hung; Wong, Chris L P; Liang, Raymond; Lie, Albert K W; Kwong, Yok-Lam

2005-02-15

Polyoma BK virus (BKV) is associated with hemorrhagic cystitis during hematopoietic stem cell transplantation (HSCT). The objective of this study was to test whether standard-dose ciprofloxacin might suppress reactivation of BKV infection during HSCT. Sixty-eight patients received ciprofloxacin or a cephalosporin as antibiotic prophylaxis after undergoing allogeneic HSCT. Urine samples were collected weekly from day 7 before HSCT to day 50 after HSCT. Laboratory investigations included quantification of BKV load and urinary ciprofloxacin levels and in vitro drug sensitivity of BKV. Twenty-two patients received ciprofloxacin, 21 received cephalosporins, 12 received concomitant corticosteroids and antibiotics (9 received ciprofloxacin, and 3 received cephalosporins), and 13 received interrupted ciprofloxacin therapy. Ciprofloxacin recipients developed a significantly lower peak BKV load, compared with cephalosporin recipients (median, 3x10(5) copies/mL vs. 2.6x10(9) copies/mL; P=.021), irrespective of concomitant receipt of corticosteroid therapy. Fewer ciprofloxacin recipients than cephalosporin recipients (P=.013) developed BKV viruria with a > or =3-log increase in BKV load during HSCT, which was associated with significantly more cases of hemorrhagic cystitis (8 of 29 patients with a peak increase of > or =3 log vs. 0 of 39 patients without a peak increase of this level; P<.001). Ciprofloxacin recipients excreted ciprofloxacin in urine at a mean 24-h rate of 71.7 microg/mL (range, 23.0-152.9 microg/mL), which was comparable with the in vitro inhibitory concentration of 125-250 microg/mL of ciprofloxacin found for 3 of 7 BKV isolates. Ciprofloxacin decreased urinary BKV reactivation after HSCT.

Disturbances in dental development and craniofacial growth in children treated with hematopoietic stem cell transplantation.

PubMed

Vesterbacka, M; Ringdén, O; Remberger, M; Huggare, J; Dahllöf, G

2012-02-01

To investigate the correlation between age, degree of disturbances in dental development, and vertical growth of the face in children treated with hematopoietic stem cell transplantation (HSCT). 39 long-term survivors of HSCT performed in childhood and transplanted before the age of 12, at a mean age of 6.8±3.3 years. Panoramic and cephalometric radiographs were taken at a mean age of 16.2 years. For each patient two age- and sex-matched healthy controls were included. The area of three mandibular teeth was measured and a cephalometric analysis was performed. The mean area of the mandibular central incisor, first and second molar was significantly smaller in the HSCT group, and the vertical growth of the face was significantly reduced, especially in the lower third, compared to healthy controls. A statistically significant correlation between age at HSCT, degree of disturbances in dental development, and vertical growth of the face was found. Children subjected to pre-HSCT chemotherapy protocols had significantly more growth reduction in vertical craniofacial variables compared to children without pre-HSCT chemotherapy. Conditioning regimens including busulfan or total body irradiation had similar deleterious effects on tooth area reduction and craniofacial parameters. The younger the child is at HSCT, the greater the impairment in dental and vertical facial development. This supports the suggestion that the reduction in lower facial height found in SCT children mainly is a result of impaired dental development and that young age is a risk factor for more severe disturbances. © 2012 John Wiley & Sons A/S.

Minor histocompatibility antigen HA-1 and HA-2 polymorphisms in Taiwan: frequency and application in hematopoietic stem cell transplantation.

PubMed

Lio, Hoi-Yan; Tang, Jih-Luh; Wu, Jui; Wu, Shang-Ju; Lin, Chun-Ying; Yang, Ya-Chien

2010-09-01

Minor histocompatibility antigens influence the occurrence of graft-vs.-host disease and graft-vs.-leukemia effects after hematopoietic stem cell transplantation (HSCT). We determined the population frequencies of HA-1 and HA-2 alleles in Taiwan and exploited their potential applications in allogeneic HSCT. HA-1 and HA-2 were genotyped using polymerase chain reaction and restriction fragment length polymorphism in healthy controls (221 for HA-1 and 306 for HA-2) and HLA-matched donor-recipient sibling pairs with HSCT (92 for HA-1 and 38 for HA-2). The association of genetic polymorphisms with HSCT outcome was evaluated by univariate and multivariate analyses. The allele frequencies in controls were 35.3% and 64.7% for HA-1(H) and HA-1(R), and 89.0% and 11.0% for HA-2(V) and HA-2(M), respectively. HA-1 disparity was denoted in 16.3% of HLA-matched donor-recipient sibling pairs, while it was not associated with HSCT outcome. HA-2 disparity was not observed in the donor-recipient pairs studied. The possibilities of using HA-1 and HA-2 variabilities as molecular markers for hematopoietic chimerism after HSCT were 39.2% and 18.4%, respectively. Our data provide the information on allele and genotype frequencies of HA-1 and HA-2 in a Taiwanese population, and suggest that prospective genomic typing for HA-1 and HA-2 alleles of the donor and recipient could be a useful approach for molecular identification of hematopoietic chimerism after HSCT, rather than prognosis of clinical outcome.

Economics and Outcome After Hematopoietic Stem Cell Transplantation: A Retrospective Cohort Study.

PubMed

Gratwohl, Alois; Sureda, Anna; Baldomero, Helen; Gratwohl, Michael; Dreger, Peter; Kröger, Nicolaus; Ljungman, Per; McGrath, Eoin; Mohty, Mohamad; Nagler, Arnon; Rambaldi, Alessandro; de Elvira, Carmen Ruiz; Snowden, John A; Passweg, Jakob; Apperley, Jane; Niederwieser, Dietger; Stijnen, Theo; Brand, Ronald

2015-12-01

Hematopoietic stem cell transplantation (HSCT) is a lifesaving expensive medical procedure. Hence, more transplants are performed in more affluent countries. The impact of economic factors on patient outcome is less defined. We analyzed retrospectively a defined cohort of 102,549 patients treated with an allogeneic (N = 37,542; 37%) or autologous (N = 65,007; 63%) HSCT. They were transplanted by one of 404 HSCT centers in 25 European countries between 1999 and 2006. We searched for associations between center-specific microeconomic or country-specific macroeconomic factors and outcome. Center patient-volume and center program-duration were significantly and systematically associated with improved survival after allogeneic HSCT (HR 0·87; 0·84-0·91 per 10 patients; p < 0·0001; HR 0·90;0·85-0·90 per 10 years; p < 0·001) and autologous HSCT (HR 0·91;0·87-0·96 per 10 patients; p < 0·001; HR 0·93;0·87-0·99 per 10 years; p = 0·02). The product of Health Care Expenditures by Gross National Income/capita was significantly associated in multivariate analysis with all endpoints (R(2) = 18%; for relapse free survival) after allogeneic HSCT. Data indicate that country- and center-specific economic factors are associated with distinct, significant, systematic, and clinically relevant effects on survival after HSCT. They impact on center expertise in long-term disease and complication management. It is likely that these findings apply to other forms of complex treatments.

Confirmed efficacy of etoposide and dexamethasone in HLH treatment: long-term results of the cooperative HLH-2004 study

PubMed Central

Bergsten, Elisabet; Horne, AnnaCarin; Aricó, Maurizio; Astigarraga, Itziar; Egeler, R. Maarten; Filipovich, Alexandra H.; Ishii, Eiichi; Janka, Gritta; Ladisch, Stephan; Lehmberg, Kai; McClain, Kenneth L.; Minkov, Milen; Montgomery, Scott; Nanduri, Vasanta; Rosso, Diego

2017-01-01

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome comprising familial/genetic HLH (FHL) and secondary HLH. In the HLH-94 study, with an estimated 5-year probability of survival (pSu) of 54% (95% confidence interval, 48%-60%), systemic therapy included etoposide, dexamethasone, and, from week 9, cyclosporine A (CSA). Hematopoietic stem cell transplantation (HSCT) was indicated in patients with familial/genetic, relapsing, or severe/persistent disease. In HLH-2004, CSA was instead administered upfront, aiming to reduce pre-HSCT mortality and morbidity. From 2004 to 2011, 369 children aged <18 years fulfilled HLH-2004 inclusion criteria (5 of 8 diagnostic criteria, affected siblings, and/or molecular diagnosis in FHL-causative genes). At median follow-up of 5.2 years, 230 of 369 patients (62%) were alive (5-year pSu, 61%; 56%-67%). Five-year pSu in children with (n = 168) and without (n = 201) family history/genetically verified FHL was 59% (52%-67%) and 64% (57%-71%), respectively (familial occurrence [n = 47], 58% [45%-75%]). Comparing with historical data (HLH-94), using HLH-94 inclusion criteria, pre-HSCT mortality was nonsignificantly reduced from 27% to 19% (P = .064 adjusted for age and sex). Time from start of therapy to HSCT was shorter compared with HLH-94 (P = .020 adjusted for age and sex) and reported neurological alterations at HSCT were 22% in HLH-94 and 17% in HLH-2004 (using HLH-94 inclusion criteria). Five-year pSu post-HSCT overall was 66% (verified FHL, 70% [63%-78%]). Additional analyses provided specific suggestions on potential pre-HSCT treatment improvements. HLH-2004 confirms that a majority of patients may be rescued by the etoposide/dexamethasone combination but intensification with CSA upfront, adding corticosteroids to intrathecal therapy, and reduced time to HSCT did not improve outcome significantly. PMID:28935695

Participation in clinical research: perspectives of adult patients and parents of pediatric patients undergoing hematopoietic stem cell transplantation.

PubMed

Keusch, Florian; Rao, Rohini; Chang, Lawrence; Lepkowski, James; Reddy, Pavan; Choi, Sung Won

2014-10-01

Despite major improvements over the past several decades, many patients undergoing hematopoietic stem cell transplantations (HSCT) continue to suffer from significant treatment-related morbidity and mortality. Clinical research studies (trials) have been integral to advancing the standard of care in HSCT. However, 1 of the biggest challenges with clinical trials is the low participation rate. Although barriers to participation in cancer clinical trials have been previously explored, studies specific to HSCT are lacking. The current study was undertaken to examine the knowledge, attitudes, and perceptions of HSCT patients regarding clinical trials. As members of focus groups, participants responded to open-ended questions that assessed factors influencing decision-making about HSCT clinical trials. Suggestions for improvements in the recruitment process were also solicited among participants. Seventeen adult HSCT patients and 6 parents of pediatric HSCT patients participated in the study. The median age was 56 years (range, 18 to 70) and 44 years (range, 28 to 54) for adult patients and parents, respectively. Participants universally indicated that too much information was provided within the informed consents and they were intimidated by the medical and legal language. Despite the large amount of information provided to them at the time of study enrollment, the participants had limited knowledge retention and recall of study details. Nevertheless, participants reported overall positive experiences with clinical trial participation and many would readily choose to participate again. A common concern among participants was the uncertainty of study outcome and general lack of feedback about results at the end of the study. Participants suggested that investigators provide more condensed and easier to understand informed consents and follow-up of study findings. These findings could be used to help guide the development of improved consent documents and enhanced participation in research studies, thereby affecting the future design of HSCT research protocols. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Designing a Methodology for Future Air Travel Scenarios

NASA Technical Reports Server (NTRS)

Wuebbles, Donald J.; Baughcum, Steven L.; Gerstle, John H.; Edmonds, Jae; Kinnison, Douglas E.; Krull, Nick; Metwally, Munir; Mortlock, Alan; Prather, Michael J.

1992-01-01

The growing demand on air travel throughout the world has prompted several proposals for the development of commercial aircraft capable of transporting a large number of passengers at supersonic speeds. Emissions from a projected fleet of such aircraft, referred to as high-speed civil transports (HSCT's), are being studied because of their possible effects on the chemistry and physics of the global atmosphere, in particular, on stratospheric ozone. At the same time, there is growing concern about the effects on ozone from the emissions of current (primarily subsonic) aircraft emissions. Evaluating the potential atmospheric impact of aircraft emissions from HSCT's requires a scientifically sound understanding of where the aircraft fly and under what conditions the aircraft effluents are injected into the atmosphere. A preliminary set of emissions scenarios are presented. These scenarios will be used to understand the sensitivity of environment effects to a range of fleet operations, flight conditions, and aircraft specifications. The baseline specifications for the scenarios are provided: the criteria to be used for developing the scenarios are defined, the required data base for initiating the development of the scenarios is established, and the state of the art for those scenarios that have already been developed is discussed. An important aspect of the assessment will be the evaluation of realistic projections of emissions as a function of both geographical distribution and altitude from an economically viable commercial HSCT fleet. With an assumed introduction date of around the year 2005, it is anticipated that there will be no HSCT aircraft in the global fleet at that time. However, projections show that, by 2015, the HSCT fleet could reach significant size. We assume these projections of HSCT and subsonic fleets for about 2015 can the be used as input to global atmospheric chemistry models to evaluate the impact of the HSCT fleets, relative to an all-subsonic future fleet. The methodology, procedures, and recommendations for the development of future HSCT and the subsonic fleet scenarios used for this evaluation are discussed.

Phase I Trial of Maintenance Sorafenib after Allogeneic Hematopoietic Stem Cell Transplantation for FLT3-ITD AML

PubMed Central

Chen, Yi-Bin; Li, Shuli; Lane, Andrew A.; Connolly, Christine; Del Rio, Candice; Valles, Betsy; Curtis, Morgan; Ballen, Karen; Cutler, Corey; Dey, Bimalangshu R.; El-Jawahri, Areej; Fathi, Amir T.; Ho, Vincent T.; Joyce, Amy; McAfee, Steven; Rudek, Michelle; Rajkhowa, Trivikram; Verselis, Sigitas; Antin, Joseph H.; Spitzer, Thomas R.; Levis, Mark; Soiffer, Robert

2014-01-01

The FLT3-ITD mutation is associated with a high relapse rate for patients with AML even after allogeneic hematopoietic stem cell transplantation (HSCT). Sorafenib is a tyrosine kinase inhibitor which inhibits the FLT3 tyrosine kinase and has shown encouraging activity in FLT3-ITD AML. We conducted a phase I trial of maintenance sorafenib after HSCT in patients with FLT3-ITD AML (ClinicalTrials.gov NCT01398501). Patients received a variety of conditioning regimens and graft sources. A dose escalation 3+3 cohort design was used to define the maximum tolerated dose (MTD) with an additional 10 patients treated at the MTD. Sorafenib was initiated between days 45 and 120 after HSCT continued for twelve 28-day cycles. Twenty-two patients were enrolled (status at HSCT: CR1=16, CR2=3, refractory=3). The MTD was established at 400 mg BID with one DLT observed (pericardial effusion). Two patients died of transplant-related causes, both unrelated to sorafenib. Two patients stopped sorafenib after relapse and 5 stopped due to attributable toxicities after the DLT period. Median follow-up for surviving patients is 16.7 months after HSCT (range, 8.1–35.0). There was one case of grade II acute GVHD after starting sorafenib and the 12-month cumulative incidence of chronic GVHD was 38% (90% CI, 21%–56%). For all patients, one-year progression-free survival (PFS) is 85% (90% CI, 66%–94%) and one-year overall survival (OS) is 95% (90% CI, 79%–99%) after HSCT. For patients in CR1 / CR2 prior to HSCT (n=19), one-year PFS is 95% (90% CI, 76%–99%) and one-year OS is 100% with only one patient who has relapsed. Sorafenib is safe after HSCT for FLT3-ITD AML and merits further investigation for the prevention of relapse. PMID:25239228

Development of methodologies for the estimation of thermal properties associated with aerospace vehicles

NASA Technical Reports Server (NTRS)

Scott, Elaine P.

1993-01-01

Thermal stress analyses are an important aspect in the development of aerospace vehicles such as the National Aero-Space Plane (NASP) and the High-Speed Civil Transport (HSCT) at NASA-LaRC. These analyses require knowledge of the temperature within the structures which consequently necessitates the need for thermal property data. The initial goal of this research effort was to develop a methodology for the estimation of thermal properties of aerospace structural materials at room temperature and to develop a procedure to optimize the estimation process. The estimation procedure was implemented utilizing a general purpose finite element code. In addition, an optimization procedure was developed and implemented to determine critical experimental parameters to optimize the estimation procedure. Finally, preliminary experiments were conducted at the Aircraft Structures Branch (ASB) laboratory.

Development of methodologies for the estimation of thermal properties associated with aerospace vehicles

NASA Astrophysics Data System (ADS)

Scott, Elaine P.

1993-12-01

Thermal stress analyses are an important aspect in the development of aerospace vehicles such as the National Aero-Space Plane (NASP) and the High-Speed Civil Transport (HSCT) at NASA-LaRC. These analyses require knowledge of the temperature within the structures which consequently necessitates the need for thermal property data. The initial goal of this research effort was to develop a methodology for the estimation of thermal properties of aerospace structural materials at room temperature and to develop a procedure to optimize the estimation process. The estimation procedure was implemented utilizing a general purpose finite element code. In addition, an optimization procedure was developed and implemented to determine critical experimental parameters to optimize the estimation procedure. Finally, preliminary experiments were conducted at the Aircraft Structures Branch (ASB) laboratory.

Tuning rules for robust FOPID controllers based on multi-objective optimization with FOPDT models.

PubMed

Sánchez, Helem Sabina; Padula, Fabrizio; Visioli, Antonio; Vilanova, Ramon

2017-01-01

In this paper a set of optimally balanced tuning rules for fractional-order proportional-integral-derivative controllers is proposed. The control problem of minimizing at once the integrated absolute error for both the set-point and the load disturbance responses is addressed. The control problem is stated as a multi-objective optimization problem where a first-order-plus-dead-time process model subject to a robustness, maximum sensitivity based, constraint has been considered. A set of Pareto optimal solutions is obtained for different normalized dead times and then the optimal balance between the competing objectives is obtained by choosing the Nash solution among the Pareto-optimal ones. A curve fitting procedure has then been applied in order to generate suitable tuning rules. Several simulation results show the effectiveness of the proposed approach. Copyright © 2016. Published by Elsevier Ltd.

Multi-step optimization strategy for fuel-optimal orbital transfer of low-thrust spacecraft

NASA Astrophysics Data System (ADS)

Rasotto, M.; Armellin, R.; Di Lizia, P.

2016-03-01

An effective method for the design of fuel-optimal transfers in two- and three-body dynamics is presented. The optimal control problem is formulated using calculus of variation and primer vector theory. This leads to a multi-point boundary value problem (MPBVP), characterized by complex inner constraints and a discontinuous thrust profile. The first issue is addressed by embedding the MPBVP in a parametric optimization problem, thus allowing a simplification of the set of transversality constraints. The second problem is solved by representing the discontinuous control function by a smooth function depending on a continuation parameter. The resulting trajectory optimization method can deal with different intermediate conditions, and no a priori knowledge of the control structure is required. Test cases in both the two- and three-body dynamics show the capability of the method in solving complex trajectory design problems.

Efficacy, safety and feasibility of antifungal prophylaxis with posaconazole tablet in paediatric patients after haematopoietic stem cell transplantation.

PubMed

Döring, Michaela; Cabanillas Stanchi, Karin Melanie; Queudeville, Manon; Feucht, Judith; Blaeschke, Franziska; Schlegel, Patrick; Feuchtinger, Tobias; Lang, Peter; Müller, Ingo; Handgretinger, Rupert; Heinz, Werner J

2017-07-01

Paediatric recipients of haematopoietic stem cell transplantation (HSCT) have a high risk for invasive fungal infections. Posaconazole oral suspension has proven to be effective in antifungal prophylaxis in adult and paediatric patients. A new posaconazole tablet formulation with absorption independent of the gastric conditions was approved by the FDA in 2013. This is the first report on the use of posaconazole tablets in paediatric patients. This single-centre study included 63 paediatric patients with haemato-oncological malignancies who received posaconazole for antifungal prophylaxis after HSCT. They were analysed for efficacy, feasibility and the safety of posaconazole. Out of 63 patients, 31 received posaconazole oral suspension and 32 received posaconazole tablets up to 200 days after transplantation. Analyses of the posaconazole trough levels were determined. No possible, probable or proven invasive fungal infection was observed in either group. Posaconazole trough levels were significantly higher in the tablet group than in the suspension group at all analysed time points. Drug-related adverse events were similarly low in both groups. Posaconazole tablets are effective in preventing invasive fungal infections in paediatric patients. As early as day 3 after starting posaconazole tablets, over 50% of the posaconazole trough levels were >500 ng/mL, while this was observed on day 14 after start with posaconazole suspension. The administration of posaconazole tablets was safe, effective and feasible as antifungal prophylaxis in paediatric patients after HSCT.

Point Cloud Refinement with a Target-Free Intrinsic Calibration of a Mobile Multi-Beam LIDAR System

NASA Astrophysics Data System (ADS)

Nouiraa, H.; Deschaud, J. E.; Goulettea, F.

2016-06-01

LIDAR sensors are widely used in mobile mapping systems. The mobile mapping platforms allow to have fast acquisition in cities for example, which would take much longer with static mapping systems. The LIDAR sensors provide reliable and precise 3D information, which can be used in various applications: mapping of the environment; localization of objects; detection of changes. Also, with the recent developments, multi-beam LIDAR sensors have appeared, and are able to provide a high amount of data with a high level of detail. A mono-beam LIDAR sensor mounted on a mobile platform will have an extrinsic calibration to be done, so the data acquired and registered in the sensor reference frame can be represented in the body reference frame, modeling the mobile system. For a multibeam LIDAR sensor, we can separate its calibration into two distinct parts: on one hand, we have an extrinsic calibration, in common with mono-beam LIDAR sensors, which gives the transformation between the sensor cartesian reference frame and the body reference frame. On the other hand, there is an intrinsic calibration, which gives the relations between the beams of the multi-beam sensor. This calibration depends on a model given by the constructor, but the model can be non optimal, which would bring errors and noise into the acquired point clouds. In the litterature, some optimizations of the calibration parameters are proposed, but need a specific routine or environment, which can be constraining and time-consuming. In this article, we present an automatic method for improving the intrinsic calibration of a multi-beam LIDAR sensor, the Velodyne HDL-32E. The proposed approach does not need any calibration target, and only uses information from the acquired point clouds, which makes it simple and fast to use. Also, a corrected model for the Velodyne sensor is proposed. An energy function which penalizes points far from local planar surfaces is used to optimize the different proposed parameters for the corrected model, and we are able to give a confidence value for the calibration parameters found. Optimization results on both synthetic and real data are presented.

Human herpesvirus types 6 and 7 infection in pediatric hematopoietic stem cell transplant recipients.

PubMed

Fule Robles, Joseph Delano; Cheuk, Daniel Ka Leung; Ha, Shau Yin; Chiang, Alan Kwok Shing; Chan, Godfrey Chi Fung

2014-06-02

The immunosuppressed state in patients undergoing hematopoietic stem cell transplantation (HSCT) predisposes them to activation of latent viral infections such as herpesvirus types 6 and 7 (HHV6 and HHV7). We aimed to evaluate the incidence, manifestations, outcomes, and risk factors of HHV 6 and HHV 7 infections after pediatric hematopoietic stem cell transplantation. We performed 106 HSCTs (86 allogeneic and 20 autologous) on 94 children (56 boys, median age 7.1 years) during 2006-2012. Patients suspected to have HHV6 or HHV7 infections were tested using polymerase chain reaction on serum and/or cerebrospinal fluid. Among the 63 patients tested for HHV, 10 patients (15.9%) were infected (HHV-6 (n=6), HHV-7 (n=4)) at a median of 18 days post-HSCT (cumulative incidence 11.5% at 1 year). Manifestations included fever (90%), rash (70%), hepatitis (80%), pneumonitis (50%), central nervous system (CNS) manifestations (40%), and graft failure (10%). One patient had persistent CNS infection despite treatment with foscarnet, ganciclovir, and cidofovir. Seven patients cleared herpesvirus after a median of 22 days. Four patients died (relapse of malignancy [n=3], acute graft-versus-host disease [aGVHD] [n=1]). Herpesvirus infections were associated with adenovirus infection (p=0.001) and severe (grade III-IV) aGVHD (p=0.037). We concluded that HHV6 and HHV7 infections are common after pediatric HSCT. Most infections were self-limited and could be associated with adenovirus infection and severe aGVHD. Further studies are needed to evaluate predictors of severe morbidity or mortality, and define optimal prophylaxis and treatment.

Smart grid initialization reduces the computational complexity of multi-objective image registration based on a dual-dynamic transformation model to account for large anatomical differences

NASA Astrophysics Data System (ADS)

Bosman, Peter A. N.; Alderliesten, Tanja

2016-03-01

We recently demonstrated the strong potential of using dual-dynamic transformation models when tackling deformable image registration problems involving large anatomical differences. Dual-dynamic transformation models employ two moving grids instead of the common single moving grid for the target image (and single fixed grid for the source image). We previously employed powerful optimization algorithms to make use of the additional flexibility offered by a dual-dynamic transformation model with good results, directly obtaining insight into the trade-off between important registration objectives as a result of taking a multi-objective approach to optimization. However, optimization has so far been initialized using two regular grids, which still leaves a great potential of dual-dynamic transformation models untapped: a-priori grid alignment with image structures/areas that are expected to deform more. This allows (far) less grid points to be used, compared to using a sufficiently refined regular grid, leading to (far) more efficient optimization, or, equivalently, more accurate results using the same number of grid points. We study the implications of exploiting this potential by experimenting with two new smart grid initialization procedures: one manual expert-based and one automated image-feature-based. We consider a CT test case with large differences in bladder volume with and without a multi-resolution scheme and find a substantial benefit of using smart grid initialization.

Distributed Learning, Extremum Seeking, and Model-Free Optimization for the Resilient Coordination of Multi-Agent Adversarial Groups

DTIC Science & Technology

2016-09-07

been demonstrated on maximum power point tracking for photovoltaic arrays and for wind turbines . 3. ES has recently been implemented on the Mars...high-dimensional optimization problems . Extensions and applications of these techniques were developed during the realization of the project. 15...studied problems of dynamic average consensus and a class of unconstrained continuous-time optimization algorithms for the coordination of multiple

Optimization Strategies for Single-Stage, Multi-Stage and Continuous ADRs

NASA Technical Reports Server (NTRS)

Shirron, Peter J.

2014-01-01

Adiabatic Demagnetization Refrigerators (ADR) have many advantages that are prompting a resurgence in their use in spaceflight and laboratory applications. They are solid-state coolers capable of very high efficiency and very wide operating range. However, their low energy storage density translates to larger mass for a given cooling capacity than is possible with other refrigeration techniques. The interplay between refrigerant mass and other parameters such as magnetic field and heat transfer points in multi-stage ADRs gives rise to a wide parameter space for optimization. This paper first presents optimization strategies for single ADR stages, focusing primarily on obtaining the largest cooling capacity per stage mass, then discusses the optimization of multi-stage and continuous ADRs in the context of the coordinated heat transfer that must occur between stages. The goal for the latter is usually to obtain the largest cooling power per mass or volume, but there can also be many secondary objectives, such as limiting instantaneous heat rejection rates and producing intermediate temperatures for cooling of other instrument components.

Hyperthyroidism After Allogeneic Hematopoietic Stem Cell Transplantation: A Report of Four Cases

PubMed Central

Sağ, Erdal; Gönç, Nazlı; Alikaşifoğlu, Ayfer; Kuşkonmaz, Barış; Uçkan, Duygu; Özön, Alev; Kandemir, Nurgün

2015-01-01

Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for many hematological disorders, primary immunodeficiencies, and metabolic disorders. Thyroid dysfunction is one of the frequently seen complications of HSCT. However, hyperthyroidism due to Graves’ disease, autoimmune thyroiditis, and thyrotoxicosis are rare. Herein, we report a series of 4 patients who were euthyroid before HSCT but developed hyperthyroidism (3 of them developed autoimmune thyroid disease) after transplantation. PMID:26777050

Successful Reduced Intensity Allogeneic Transplant With Full Donor Chimerism and Good Quality of Life in Adolescent Patient With Wiskott-Aldrich Syndrome.

PubMed

Ali, Salah; Gacsadi, Anna; McDougall, Elizabeth; Armstrong, Christine; Krueger, Joerg; Schechter, Tal; Ali, Muhammad

2017-07-01

Wiskott-Aldrich syndrome (WAS) is an X-linked disease characterized by microthrombocytopenia, eczema, immune deficiency, and autoimmune phenomena. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment. Myeloablative conditioning is the most common regimen used for HSCT in patients with WAS to avoid the risk of mixed donor chimerism and autoimmunity post-HSCT. There is limited data on the use of reduced intensity conditioning for HSCT in patients with WAS. Here, we report a case with severe phenotype of WAS transplanted successfully with reduced intensity conditioning, which is an acceptable conditioning regimen and can be considered in patients with WAS with significantly impaired organ functions.

Immunizations in solid organ and hematopoeitic stem cell transplant patients: A comprehensive review

PubMed Central

L'Huillier, Arnaud G; Kumar, Deepali

2015-01-01

The Solid Organ Transplantation (SOT) and Haematopoietic Stem Cell Transplantation (HSCT) population is continuously increasing as a result of broader indications for transplant and improved survival. Infectious diseases, including vaccine-preventable diseases, are a significant threat for this population, primarily after but also prior to transplantation. As a consequence, clinicians must ensure that patients are optimally immunized before transplantation, to provide the best protection during the early post-transplantation period, when immunosuppression is the strongest and vaccine responses are poor. After 3–6 months, inactivated vaccines immunization can be resumed. By contrast, live-attenuated vaccines are lifelong contraindicated in SOT patients, but can be considered in HSCT patients at least 2 years after transplantation, if there is no immunosuppression or graft-versus-host-disease. However, because of the advantages of live-attenuated over inactivated vaccines - and also sometimes the absence of an inactivated alternative - an increasing number of prospective studies on live vaccine immunization after transplantation are performed and give new insights about safety and immunogenicity in this population. PMID:26291740

Preliminary results from the High Speed Airframe Integration Research project

NASA Technical Reports Server (NTRS)

Coen, Peter G.; Sobieszczanski-Sobieski, Jaroslaw; Dollyhigh, Samuel M.

1992-01-01

A review is presented of the accomplishment of the near term objectives of developing an analysis system and optimization methods during the first year of the NASA Langley High Speed Airframe Integration Research (HiSAIR) project. The characteristics of a Mach 3 HSCT transport have been analyzed utilizing the newly developed process. In addition to showing more detailed information about the aerodynamic and structural coupling for this type of vehicle, this exercise aided in further refining the data requirements for the analysis process.

Robust multi-model control of an autonomous wind power system

NASA Astrophysics Data System (ADS)

Cutululis, Nicolas Antonio; Ceanga, Emil; Hansen, Anca Daniela; Sørensen, Poul

2006-09-01

This article presents a robust multi-model control structure for a wind power system that uses a variable speed wind turbine (VSWT) driving a permanent magnet synchronous generator (PMSG) connected to a local grid. The control problem consists in maximizing the energy captured from the wind for varying wind speeds. The VSWT-PMSG linearized model analysis reveals the resonant nature of its dynamic at points on the optimal regimes characteristic (ORC). The natural frequency of the system and the damping factor are strongly dependent on the operating point on the ORC. Under these circumstances a robust multi-model control structure is designed. The simulation results prove the viability of the proposed control structure. Copyright

Stochastic Methods for Aircraft Design

NASA Technical Reports Server (NTRS)

Pelz, Richard B.; Ogot, Madara

1998-01-01

The global stochastic optimization method, simulated annealing (SA), was adapted and applied to various problems in aircraft design. The research was aimed at overcoming the problem of finding an optimal design in a space with multiple minima and roughness ubiquitous to numerically generated nonlinear objective functions. SA was modified to reduce the number of objective function evaluations for an optimal design, historically the main criticism of stochastic methods. SA was applied to many CFD/MDO problems including: low sonic-boom bodies, minimum drag on supersonic fore-bodies, minimum drag on supersonic aeroelastic fore-bodies, minimum drag on HSCT aeroelastic wings, FLOPS preliminary design code, another preliminary aircraft design study with vortex lattice aerodynamics, HSR complete aircraft aerodynamics. In every case, SA provided a simple, robust and reliable optimization method which found optimal designs in order 100 objective function evaluations. Perhaps most importantly, from this academic/industrial project, technology has been successfully transferred; this method is the method of choice for optimization problems at Northrop Grumman.

Design Optimization of a Centrifugal Fan with Splitter Blades

NASA Astrophysics Data System (ADS)

Heo, Man-Woong; Kim, Jin-Hyuk; Kim, Kwang-Yong

2015-05-01

Multi-objective optimization of a centrifugal fan with additionally installed splitter blades was performed to simultaneously maximize the efficiency and pressure rise using three-dimensional Reynolds-averaged Navier-Stokes equations and hybrid multi-objective evolutionary algorithm. Two design variables defining the location of splitter, and the height ratio between inlet and outlet of impeller were selected for the optimization. In addition, the aerodynamic characteristics of the centrifugal fan were investigated with the variation of design variables in the design space. Latin hypercube sampling was used to select the training points, and response surface approximation models were constructed as surrogate models of the objective functions. With the optimization, both the efficiency and pressure rise of the centrifugal fan with splitter blades were improved considerably compared to the reference model.

High speed civil transport aerodynamic optimization

NASA Technical Reports Server (NTRS)

Ryan, James S.

1994-01-01

This is a report of work in support of the Computational Aerosciences (CAS) element of the Federal HPCC program. Specifically, CFD and aerodynamic optimization are being performed on parallel computers. The long-range goal of this work is to facilitate teraflops-rate multidisciplinary optimization of aerospace vehicles. This year's work is targeted for application to the High Speed Civil Transport (HSCT), one of four CAS grand challenges identified in the HPCC FY 1995 Blue Book. This vehicle is to be a passenger aircraft, with the promise of cutting overseas flight time by more than half. To meet fuel economy, operational costs, environmental impact, noise production, and range requirements, improved design tools are required, and these tools must eventually integrate optimization, external aerodynamics, propulsion, structures, heat transfer, controls, and perhaps other disciplines. The fundamental goal of this project is to contribute to improved design tools for U.S. industry, and thus to the nation's economic competitiveness.

Investigation of nutrient feeding strategies in a countercurrent mixed-acid multi-staged fermentation: experimental data.

PubMed

Smith, Aaron Douglas; Lockman, Nur Ain; Holtzapple, Mark T

2011-06-01

Nutrients are essential for microbial growth and metabolism in mixed-culture acid fermentations. Understanding the influence of nutrient feeding strategies on fermentation performance is necessary for optimization. For a four-bottle fermentation train, five nutrient contacting patterns (single-point nutrient addition to fermentors F1, F2, F3, and F4 and multi-point parallel addition) were investigated. Compared to the traditional nutrient contacting method (all nutrients fed to F1), the near-optimal feeding strategies improved exit yield, culture yield, process yield, exit acetate-equivalent yield, conversion, and total acid productivity by approximately 31%, 39%, 46%, 31%, 100%, and 19%, respectively. There was no statistical improvement in total acid concentration. The traditional nutrient feeding strategy had the highest selectivity and acetate-equivalent selectivity. Total acid productivity depends on carbon-nitrogen ratio.

A cost-utility and budget impact analysis of allogeneic hematopoietic stem cell transplantation for severe thalassemic patients in Thailand.

PubMed

Leelahavarong, Pattara; Chaikledkaew, Usa; Hongeng, Suradej; Kasemsup, Vijj; Lubell, Yoel; Teerawattananon, Yot

2010-07-16

Hematopoietic stem cell transplantation (HSCT) is the only curative treatment available to severe thalassemic patients. The treatment, however, is very costly, particularly in the context of low and middle income countries, and no studies have been carried out to explore its economic justifiability. This study aimed to estimate the cost-utility of HSCT compared with blood transfusions combined with iron chelating therapy (BT-ICT) for severe thalassemia in Thailand, and to investigate the affordability of HSCT using a budget impact analysis. A Markov model was used to estimate the relevant costs and health outcomes over the patients' lifetimes taking a societal perspective as recommended by Thailand's health technology assessment guidelines. All future costs and outcomes were discounted at a rate of 3% per annum. Primary outcomes of interest were lifetime costs, quality adjusted life years (QALYs) gained, and the incremental cost-effectiveness ratio (ICER) in Thai baht (THB) per QALY gained. Compared to BT-ICT, the incremental cost-effectiveness ratio increased with patient age from 80,700 to 183,000 THB per QALY gained for related HSCT and 209,000 to 953,000 THB per QALY gained for unrelated HSCT among patients aged 1 to 15 years (US$1= 34 THB). The governmental budget impact analysis showed that providing 200 related HSCT to patients aged 1 to 10 years, in accordance with the current infrastructure limitations, would initially require approximately 90 million additional THB per year. At a societal willingness to pay of 100,000 THB per QALY gained, related HSCT was likely to be a cost-effective and affordable treatment for young children with severe thalassemia in Thailand.

Selective T cell-depleted haploidentical hematopoietic stem cell transplantation for relapsed/refractory neuroblastoma.

PubMed

Liu, Anthony P Y; Lee, Pamela P W; Kwok, Janette S Y; Leung, Rock Y Y; Chiang, Alan K S; Ha, Shau-Yin; Cheuk, Daniel K L; Chan, Godfrey C F

2018-06-19

Relapsed/refractory NB carries a bleak outcome, warranting novel treatment options. HaploHSCT induces a graft-versus-NB effect via natural killer cell alloreactivity. Review of patients with relapsed/refractory NB who underwent haploHSCT with ex vivo T-cell depletion in our unit from 2013 through 2018. Ten patients were identified (male=5; median age at haploHSCT=6.45 y, range: 3.49-11.02 y). Indications were relapsed in 7 and refractoriness in 3; disease status at haploHSCT was CR in 2, PR in 6, and PD in 2. All patients received peripheral blood stem cell grafts after ex vivo T-cell depletion (CD3/CD19-depletion=1; TCR-αβ/CD19-depletion=4; CD3/CD45RA-depletion=4; and TCR-αβ/CD45RA-depletion=1). Conditioning regimens were fludarabine-based. Neutrophils engrafted on median D + 10 (range: D + 9 to +13), and platelets engrafted (≥20 × 10 9 /L) on median D + 8 (range: D + 5 to D + 14). Early T- and NK-cell recovery were evident. Of the 10 patients, acute rejection developed in 1 (who died of PD despite rescue HSCT), and 1 died of sepsis before engraftment; 8 experienced full donor-chimerism post-HSCT. Among the 8, 6 experienced CR, 1 died of PD, and 1 died of pulmonary hypertensive crisis before evaluation. At publication, 4 were in remission (2.8, 7.4, 28.5, and 58.9 months). No significant GvHD occurred. HaploHSCT with selective ex vivo T-cell depletion may be a safe and useful salvage strategy for relapsed/refractory NB. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Assessment of cardiotoxicity during haemopoietic stem cell transplantation with plasma brain natriuretic peptide.

PubMed

Snowden, J A; Hill, G R; Hunt, P; Carnoutsos, S; Spearing, R L; Espiner, E; Hart, D N

2000-08-01

Cardiac failure is a known complication of haemopoietic stem cell transplantation (HSCT) and is often difficult to diagnose as patients may have multiple medical problems. Since brain natriuretic peptide (BNP) is largely a hormone of cardiac ventricular origin and is released early in the course of ventricular dysfunction, we have examined the value of serial plasma BNP levels for detecting cardiac failure in patients undergoing cytotoxic conditioning for HSCT. Fifteen patients undergoing HSCT were evaluated (10 undergoing autologous HSCT; five undergoing allogeneic HSCT). BNP was measured by radioimmunoassay prior to therapy and weekly for 5 weeks. Seven patients had a significant rise in BNP level (above a previously established threshold of 43 pmol/l associated with cardiac failure), occurring 1-4 weeks post commencement of conditioning. In three of these patients, cardiac failure was subsequently diagnosed clinically 3, 9 and 23 days after a BNP level of 43 pmol/l had been detected. These three patients had the highest peak BNP levels for the group and in each case elevation in BNP level occurred for a period exceeding 1 week. Although numbers were relatively small, a BNP >43 pmol/l was significantly associated with the inclusion of high-dose cyclophosphamide in the preparative regimen (P = 0.02). BNP levels showed no relationship to febrile episodes. In conclusion, these results show that plasma BNP may be used as a marker for early detection of cardiac dysfunction in patients undergoing HSCT, particularly if levels are increased for periods exceeding 1 week. Measurement of BNP during HSCT may be helpful in patients at risk of cardiac failure, in complex clinical situations and in monitoring the cardiotoxicity of preparative regimens.

Prospective Randomized Trial Comparing Efficacy of Topical Loteprednol Etabonate 0.5% Versus Cyclosporine-A 0.05% for Treatment of Dry Eye Syndrome Following Hematopoietic Stem Cell Transplantation.

PubMed

Boynton, Grace E; Raoof, Duna; Niziol, Leslie M; Hussain, Munira; Mian, Shahzad I

2015-07-01

To evaluate the safety and efficacy of topical loteprednol etabonate (LE) 0.5% compared with cyclosporine A (CsA) 0.05% for the prophylaxis and treatment of dry eye syndrome (DES) after hematopoietic stem cell transplantation (HSCT). Seventy-five patients were randomized to LE (n = 76 eyes of 38 patients) or CsA (n = 74 eyes of 37 patients) pre-HSCT. Lissamine green and fluorescein staining, tear break-up time, tear osmolarity (Osm), Schirmer score (Sch), intraocular pressure, visual acuity, and Ocular Surface Disease Index were assessed pre-HSCT, 3, 6, 9, and 12 months post-HSCT. There were no differences in DES incidence (P = 0.22; log-rank test) or progression (P = 0.41; log-rank test) between the 2 treatment arms during the course of the study. Among eyes with no DES at enrollment, the Kaplan-Meier analysis yielded a 90% rate of DES development in cyclosporine-treated eyes and a 79% rate of DES development in LE-treated eyes by 12 months post-HSCT. The Kaplan-Meier analysis of eyes with DES at enrollment demonstrated a 38% rate of disease progression among cyclosporine-treated eyes and a 26% rate of disease progression among loteprednol-treated eyes by 12 months. No patient in either group had an elevation of 10 mm Hg or greater from baseline at any study visit, and no patients had their treatment discontinued for elevation in intraocular pressure. Pre-HSCT initiation of LE 0.5% appears to be safe and may be as effective as CsA 0.5% for the treatment and prophylaxis of DES following HSCT.

Diagnosis of toxoplasmosis after allogeneic stem cell transplantation: results of DNA detection and serological techniques.

PubMed

Fricker-Hidalgo, Hélène; Bulabois, Claude-Eric; Brenier-Pinchart, Marie-Pierre; Hamidfar, Rebecca; Garban, Frédéric; Brion, Jean-Paul; Timsit, Jean-François; Cahn, Jean-Yves; Pelloux, Hervé

2009-01-15

The biological diagnosis of toxoplasmosis after allogeneic hematopoietic stem cell transplantation (HSCT) is based on the detection of Toxoplasma gondii DNA in blood specimens or other samples. Serological testing is used mainly to define the immunity status of the patient before HSCT. The aim of our study was to examine the performance of polymerase chain reaction (PCR) and serological techniques in the diagnosis of toxoplasmosis after HSCT. Seventy patients underwent allogeneic HSCT from September 2004 through September 2006. DNA was detected by PCR, and immunoglobulin G and immunoglobulin M were detected by enzyme-linked immunosorbent assay. The results of immunoglobulin G detection before allogeneic HSCT were positive in 40 (57.1%) of the patients and negative in 30 (42.9%). After HSCT, 57 patients (81.4%) had test results that were negative for immunoglobulin M and had negative results of DNA detection, without toxoplasmosis infection. Four patients (5.7%) had at least 4 samples with positive PCR results and/or test results positive for immunoglobulin M against T. gondii; toxoplasmosis was then confirmed by clinical symptoms. Nine patients (12.9%) with positive PCR results and 1 or 2 samples with test results negative for immunoglobulin M were considered to have asymptomatic T. gondii infection. Reactivation of latent infection was the cause of toxoplasmosis in 3 of the 4 patients, and toxoplasmosis occurred as a primary infection in 1 patient. The detection of specific anti-T. gondii immunoglobulin M was the only biological evidence of toxoplasmosis in 2 patients, and samples were positive for immunoglobulin M before PCR was performed in 1 patient. Thus, after HSCT, all patients were at risk for toxoplasmosis; all patients who receive HSCTs should be followed up with biological testing that combines PCR and serological techniques.

Clinical and virological characteristics of 15 patients with chronic active Epstein-Barr virus infection treated with hematopoietic stem cell transplantation.

PubMed

Gotoh, Kensei; Ito, Yoshinori; Shibata-Watanabe, Yukiko; Kawada, Jun-ichi; Takahashi, Yoshiyuki; Yagasaki, Hiroshi; Kojima, Seiji; Nishiyama, Yukihiro; Kimura, Hiroshi

2008-05-15

Chronic active Epstein-Barr virus (EBV) infection is characterized by recurrent infectious mononucleosis-like symptoms, and infected patients have high viral loads in their peripheral blood. Standard therapy for the disease has not yet been established. Recently, hematopoietic stem cell transplantation (HSCT) has been introduced and has the potential to become a standard treatment, although guidelines for HSCT to treat chronic active EBV infection have not yet been proposed. Fifteen patients were retrospectively analyzed, both clinically and virologically, to investigate the factors associated with prognosis of chronic active EBV infection treated with HSCT. After HSCT, 7 patients died after survival periods that ranged from 1 to 16 months (mean duration of survival after HSCT, 5 months). Three patients were considered to have died of transplantation-related complications. The duration between infection onset and diagnosis was significantly longer in patients who died than in those who survived. Five of the 7 patients who died experienced > or =3 life-threatening complications. The plasma concentrations of interferon-gamma, interleukin-10, thrombomodulin, and soluble E-selectin did not differ significantly between the groups of patients. With regard to sequence variations in the EBV latent membrane protein 1 gene, no specific patterns were found in the patients who died. Importantly, the plasma EBV load at diagnosis was significantly higher in patients who died than in living patients. Moreover, plasma viral load was shown to be an important factor to monitor during follow-up for patients after HSCT. The number of life-threatening complications and plasma viral load are indicative of the stage of disease progression and may be useful factors for predicting the outcome of HSCT.

A cost-utility and budget impact analysis of allogeneic hematopoietic stem cell transplantation for severe thalassemic patients in Thailand

PubMed Central

2010-01-01

Background Hematopoietic stem cell transplantation (HSCT) is the only curative treatment available to severe thalassemic patients. The treatment, however, is very costly, particularly in the context of low and middle income countries, and no studies have been carried out to explore its economic justifiability. This study aimed to estimate the cost-utility of HSCT compared with blood transfusions combined with iron chelating therapy (BT-ICT) for severe thalassemia in Thailand, and to investigate the affordability of HSCT using a budget impact analysis. Methods A Markov model was used to estimate the relevant costs and health outcomes over the patients' lifetimes taking a societal perspective as recommended by Thailand's health technology assessment guidelines. All future costs and outcomes were discounted at a rate of 3% per annum. Primary outcomes of interest were lifetime costs, quality adjusted life years (QALYs) gained, and the incremental cost-effectiveness ratio (ICER) in Thai baht (THB) per QALY gained. Results Compared to BT-ICT, the incremental cost-effectiveness ratio increased with patient age from 80,700 to 183,000 THB per QALY gained for related HSCT and 209,000 to 953,000 THB per QALY gained for unrelated HSCT among patients aged 1 to 15 years (US$1= 34 THB). The governmental budget impact analysis showed that providing 200 related HSCT to patients aged 1 to 10 years, in accordance with the current infrastructure limitations, would initially require approximately 90 million additional THB per year. Conclusions At a societal willingness to pay of 100,000 THB per QALY gained, related HSCT was likely to be a cost-effective and affordable treatment for young children with severe thalassemia in Thailand. PMID:20633303

High rate of long-term survival for high-risk lymphoma patients treated with hematopoietic stem cell transplantation as consolidation or salvage therapy.

PubMed

Espigado, I; Ríos, E; Marín-Niebla, A; Carmona, M; Parody, R; Pérez-Hurtado, J M; Márquez, F J; Urbano-Ispizua, A

2008-11-01

Patients with high-relapse-risk lymphomas or those relapsing after initial therapy have a limited probability of cure with conventional treatment. There is recent inconclusive evidence that, in such cases, intensification or salvage treatment with high-dose chemotherapy followed by hematopoietic stem cell transplantation (HSCT) increases the response rate and may improve survival. Nevertheless, published data on long-term follow-up of high-risk lymphoma patients treated with HSCT are scarce. We analyzed 101 consecutive patients receiving high-dose chemotherapy followed by HSCT after induction with standard chemotherapy. The median age was 38 years (range, 12-63 years). The diagnoses were Hodgkin's disease (n = 32), follicular lymphoma (n = 33), diffuse large B-cell lymphoma (n = 12), mantle cell lymphoma (n = 7), T-cell lymphoma (n = 14), and others (n = 3). Patients received either an autologous graft (n = 72) in first complete remission (1CR; n = 23) or in advanced stages (AS; n = 49), or an allogeneic graft (n = 29) in 1CR (n = 7) or in AS (n = 22). We concluded that transplant-related mortality was 2.7% for patients receiving an autologous HSCT and 27% for patients receiving an allogeneic HSCT. The main etiologies were graft-versus-host disease and infection in the allogeneic setting, and infection in the autologous setting. The probability of long-term (12-year) overall survival was 71%, higher than that described for high-relapse-risk lymphoma patients treated without HSCT and significantly better (P < .05) for patients who received the transplant in 1CR (89%) than in AS (65%). Finally, the probability of long-term survival was significantly better for patients treated with HSCT during the period from 2000-2007 (85%) compared with the period from 1989-1999 (72%).

Economics and Outcome After Hematopoietic Stem Cell Transplantation: A Retrospective Cohort Study

PubMed Central

Gratwohl, Alois; Sureda, Anna; Baldomero, Helen; Gratwohl, Michael; Dreger, Peter; Kröger, Nicolaus; Ljungman, Per; McGrath, Eoin; Mohty, Mohamad; Nagler, Arnon; Rambaldi, Alessandro; de Elvira, Carmen Ruiz; Snowden, John A.; Passweg, Jakob; Apperley, Jane; Niederwieser, Dietger; Stijnen, Theo; Brand, Ronald

2015-01-01

Hematopoietic stem cell transplantation (HSCT) is a lifesaving expensive medical procedure. Hence, more transplants are performed in more affluent countries. The impact of economic factors on patient outcome is less defined. We analyzed retrospectively a defined cohort of 102,549 patients treated with an allogeneic (N = 37,542; 37%) or autologous (N = 65,007; 63%) HSCT. They were transplanted by one of 404 HSCT centers in 25 European countries between 1999 and 2006. We searched for associations between center-specific microeconomic or country-specific macroeconomic factors and outcome. Center patient-volume and center program-duration were significantly and systematically associated with improved survival after allogeneic HSCT (HR 0·87; 0·84–0·91 per 10 patients; p < 0·0001; HR 0·90;0·85–0·90 per 10 years; p < 0·001) and autologous HSCT (HR 0·91;0·87–0·96 per 10 patients; p < 0·001; HR 0·93;0·87–0·99 per 10 years; p = 0·02). The product of Health Care Expenditures by Gross National Income/capita was significantly associated in multivariate analysis with all endpoints (R2 = 18%; for relapse free survival) after allogeneic HSCT. Data indicate that country- and center-specific economic factors are associated with distinct, significant, systematic, and clinically relevant effects on survival after HSCT. They impact on center expertise in long-term disease and complication management. It is likely that these findings apply to other forms of complex treatments. PMID:26844291

Global Search of a Three-dimensional Low Solidity Circular Cascade Diffuser for Centrifugal Blowers by Meta-model Assisted Optimization

NASA Astrophysics Data System (ADS)

Sakaguchi, Daisaku; Sakue, Daiki; Tun, Min Thaw

2018-04-01

A three-dimensional blade of a low solidity circular cascade diffuser in centrifugal blowers is designed by means of a multi-point optimization technique. The optimization aims at improving static pressure coefficient at a design point and at a small flow rate condition. Moreover, a clear definition of secondary flow expressed by positive radial velocity at hub side is taken into consideration in constraints. The number of design parameters for three-dimensional blade reaches to 10 in this study, such as a radial gap, a radial chord length and mean camber angle distribution of the LSD blade with five control points, control point between hub and shroud with two design freedom. Optimization results show clear Pareto front and selected optimum design shows good improvement of pressure rise in diffuser at small flow rate conditions. It is found that three-dimensional blade has advantage to stabilize the secondary flow effect with improving pressure recovery of the low solidity circular cascade diffuser.

Allogeneic haematopoietic stem cell transplantation for infant acute lymphoblastic leukaemia with KMT2A (MLL) rearrangements: a retrospective study from the paediatric acute lymphoblastic leukaemia working group of the Japan Society for Haematopoietic Cell Transplantation.

PubMed

Kato, Motohiro; Hasegawa, Daiichiro; Koh, Katsuyoshi; Kato, Keisuke; Takita, Junko; Inagaki, Jiro; Yabe, Hiromasa; Goto, Hiroaki; Adachi, Souichi; Hayakawa, Akira; Takeshita, Yasufumi; Sawada, Akihisa; Atsuta, Yoshiko; Kato, Koji

2015-02-01

Allogeneic haematopoietic stem cell transplantation (HSCT) is still considered to play an important role as a consolidation therapy for high-risk infants with acute lymphoblastic leukaemia (ALL). Here, we retrospectively analysed outcomes of HSCT in infants with ALL based on nationwide registry data of the Japan Society for Haematopoietic Cell Transplantation. A total of 132 allogeneic HSCT for infant ALL with KMT2A (MLL) gene rearrangements, which were performed in first complete remission (CR1), were analysed. The 5-year overall survival rate after transplantation was 67·4 ± 4·5%). Although recent HSCT (after 2004) had a trend toward better survival, no statistical correlation was observed between outcomes and each factor, including age at diagnosis, initial leucocyte count, cytogenetics, donor types or conditioning of HSCT. Myeloablative conditioning with total body irradiation did not provide a better survival (60·7 ± 9·2%) over that with busulfan (BU; 67·8 ± 5·7%). Two of the 28 patients treated with irradiation, but none of the 90 BU-treated patients, developed a secondary malignant neoplasm. In conclusion, allogeneic HSCT using BU was a valuable option for infant ALL with KMT2A rearrangements in CR1. © 2014 John Wiley & Sons Ltd.

Evaluation of COBAS AmpliPrep/COBAS TaqMan CMV Test for use in hematopoietic stem cell transplant recipients.

PubMed

Ramanan, Poornima; Razonable, Raymund R

2017-07-01

Cytomegalovirus (CMV) is a common opportunistic infection that contributes to poor outcomes in hematopoietic stem cell transplant (HSCT) recipients. Prevention of CMV end-organ disease in allogeneic HSCT recipients is commonly achieved by preemptive antiviral therapy of asymptomatic CMV reactivation that is detected by serial nucleic acid testing (NAT). However, there was no standardized CMV NAT until the development of the World Health Organization (WHO) International Standard. Areas covered: This article provides a comprehensive review on COBAS AmpliPrep/TaqMan (CAP/CTM) CMV assay (Roche) and emphasizes the limitations in the clinical use of CMV NAT in HSCT recipients. Expert commentary: The CAP/CTM CMV Test is the first US FDA approved commercial quantitative NAT for CMV viral load monitoring of plasma samples in solid organ transplant and HSCT recipients. The CAP/CTM assay has wide linear range of DNA quantification and demonstrates colinearity to the WHO International Standard. Studies of CAP/CTM CMV assay in HSCT recipients are still limited, but are now being reported to define viral thresholds for diagnosis, surveillance and monitoring. Results from these early studies in HSCT recipients suggest that, while the WHO IS has improved the inter-laboratory result variances, there are still important factors that continue to contribute to assay variability. This lack of harmony among NAT highlights the need for further standardization.

Outcome of children with high-risk acute myeloid leukemia given autologous or allogeneic hematopoietic cell transplantation in the aieop AML-2002/01 study.

PubMed

Locatelli, F; Masetti, R; Rondelli, R; Zecca, M; Fagioli, F; Rovelli, A; Messina, C; Lanino, E; Bertaina, A; Favre, C; Giorgiani, G; Ripaldi, M; Ziino, O; Palumbo, G; Pillon, M; Pession, A; Rutella, S; Prete, A

2015-02-01

We analyzed the outcome of 243 children with high-risk (HR) AML in first CR1 enrolled in the AIEOP-2002/01 protocol, who were given either allogeneic (ALLO; n=141) or autologous (AUTO; n=102) hematopoietic SCT (HSCT), depending on the availability of a HLA-compatible sibling. Infants, patients with AML-M7, or complex karyotype or those with FLT3-ITD, were eligible to be transplanted also from alternative donors. All patients received a myeloablative regimen combining busulfan, cyclophosphamide and melphalan; [corrected] AUTO-HSCT patients received BM cells in most cases, while in children given ALLO-HSCT stem cell source was BM in 96, peripheral blood in 19 and cord blood in 26. With a median follow-up of 57 months (range 12-130), the probability of disease-free survival (DFS) was 73% and 63% in patients given either ALLO- or AUTO-HSCT, respectively (P=NS). Although the cumulative incidence (CI) of relapse was lower in ALLO- than in AUTO-HSCT recipients (17% vs 28%, respectively; P=0.043), the CI of TRM was 7% in both groups. Patients transplanted with unrelated donor cord blood had a remarkable 92.3% 8-year DFS probability. Altogether, these data confirm that HSCT is a suitable option for preventing leukemia recurrence in HR children with CR1 AML.

High incidence of BK virus-associated hemorrhagic cystitis in children after second or third allogeneic hematopoietic stem cell transplantation.

PubMed

Umeda, Katsutsugu; Kato, Itaru; Kawaguchi, Koji; Tasaka, Keiji; Kamitori, Tatsuya; Ogata, Hideto; Mikami, Takashi; Hiramatsu, Hidefumi; Saito, Ryoichi; Ogawa, Osamu; Takahashi, Takayuki; Adachi, Souichi

2018-06-01

BKV-HC is a serious complication of allogeneic HSCT. To characterize the incidence, risk factors, and clinical outcomes of post-HSCT BKV-HC, we retrospectively analyzed 112 patients who underwent one or more allogeneic HSCTs at our hospital between 2001 and 2017. Twenty underwent second or third HSCT thereafter. Ten patients developed BKV-HC at a median of 30 days after HSCT. The 100-day cumulative incidences of grade 0-4 and grade 2-4 BKV-HC were 7.8% and 6.2%, respectively. HSCTs performed in 2011-2017 associated with significantly higher 100-day cumulative incidence of grade 2-4 BKV-HC (14.0%) than HSCTs performed in 2001-2010 (1.3%, P = 0.004). On multivariate analysis, second or third HSCT was the only independent significant risk factor for development of grade 2-4 BKV-HC (P = 0.015). Serial PCR monitoring of urine and blood BKV load did not predict BKV-HC. The recent increase in the incidence of BKV-HC may reflect recent innovations in transplant technologies that facilitate second or third HSCT, which are known to cause prolonged immune deficiency. If safe and effective treatment or prophylaxis becomes available, it could be used to target the high-risk patients for BKV-HC. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Hematopoietic Stem Cell Transplantation Activity Worldwide in 2012 and a SWOT Analysis of the Worldwide Network for Blood and Marrow Transplantation Group (WBMT) including the global survey

PubMed Central

Niederwieser, Dietger; Baldomero, Helen; Szer, Jeff; Gratwohl, Michael; Aljurf, Mahmoud; Atsuta, Yoshiko; Bouzas, Luis Fernando; Confer, Dennis; Greinix, Hildegard; Horowitz, Mary; Iida, Minako; Lipton, Jeff; Mohty, Mohamad; Novitzky, Nicolas; Nunez, José; Passweg, Jakob; Pasquini, Marcelo C.; Kodera, Yoshihisa; Apperley, Jane; Seber, Adriana; Gratwohl, Alois

2016-01-01

Data on 68,146 hematopoietic stem cell transplants (HSCT) (53% autologous and 47% allogeneic) gathered by 1566 teams from 77 countries and reported through their regional transplant organizations were analyzed by main indication, donor type and stem cell source for the year 2012. With transplant rates ranging from 0.1 to 1001 per 10 million inhabitants, more HSCT were registered from unrelated 16,433 than related 15,493 donors. Grafts were collected from peripheral blood (66%), bone marrow (24%; mainly non-malignant disorders) and cord blood (10%). Compared to 2006, an increase of 46% total (57% allogeneic and 38% autologous) was observed. Growth was due to an increase in reporting teams (18%) and median transplant activity/team (from 38 to 48 HSCT/team). An increase of 67% was noted in mismatched/haploidentical family HSCT. A SWOT analysis revealed the global perspective of WBMT to be its major strength and identified potential to be the key professional body for patients and authorities. The limited data collection remains its major weakness and threat. In conclusion, global HSCT grows over the years without plateauing (allogeneic>autologous) and at different rates in the four WHO regions. Major increases were observed in allogeneic, haploidentical HSCT and, to a lesser extent, in cord blood. PMID:26901703

Clinical endpoints in allogeneic hematopoietic stem cell transplantation studies: the cost of freedom.

PubMed

Kim, Haesook T; Armand, Philippe

2013-06-01

When designing a study for allogeneic hematopoietic stem cell transplantation (HSCT), many choices must be made, including conditioning regimen, stem cell source, and graft-versus-host disease (GVHD) prevention method. For each of these, there are a growing number of options, which can be combined into a bewildering number of possible HSCT protocols. To properly interpret the results of a given strategy and compare them with others, it is essential that there be agreement on the definitions and estimation methods of HSCT endpoints. We report a survey of the recent HSCT literature that confirms the heterogeneity of endpoint definitions and estimation methods used. Unfortunately, this heterogeneity may lead to significant biases in the estimates of key endpoints, including nonrelapse mortality, relapse, GVHD, or engraftment. This can preclude adequate comparisons among studies, even though such comparisons are the major tool with which to improve HSCT outcome. In the context of our survey, we discuss some of the statistical issues that arise when dealing with HSCT endpoints and the ramifications of the choice of endpoint definition, when the endpoint occurs in the context of competing risks. Our hope is to generate discussion and motivate a search for consensus among those who perform transplantations and statisticians. Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Autoimmune hemolytic anemia after allogeneic hematopoietic stem cell transplantation: analysis of 533 adult patients who underwent transplantation at King's College Hospital.

PubMed

Wang, Meng; Wang, Wenjia; Abeywardane, Ayesha; Adikarama, Malinthi; McLornan, Donal; Raj, Kavita; de Lavallade, Hugues; Devereux, Stephen; Mufti, Ghulam J; Pagliuca, Antonio; Potter, Victoria T; Mijovic, Aleksandar

2015-01-01

Autoimmune hemolytic anemia (AIHA) is a recognized complication of hematopoietic stem cell transplantation (HSCT); it is often refractory to treatment and carries a high mortality. To improve understanding of the incidence, risk factors, and clinical outcome of post-transplantation AIHA, we analyzed 533 patients who received allogeneic HSCT, and we identified 19 cases of AIHA after HSCT (overall incidence, 3.6%). The median time to onset, from HSCT to AIHA, was 202 days. AIHA was associated with HSCT from unrelated donors (hazard ratio [HR], 5.28; 95% confidence interval [CI], 1.22 to 22.9; P = .026). In the majority (14 of 19; 74%) of AIHA patients, multiple agents for treatment were required, with only 9 of 19 (47%) patients achieving complete resolution of AIHA. Patients with post-transplantation AIHA had a higher overall mortality (HR, 2.48; 95% CI, 1.33 to 4.63; P = .004), with 36% (4 of 11 cases) of deaths attributable to AIHA. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Life in Limbo: Experiences of Iranian Hematopoietic Stem Cell Transplantation Recipient Patients and Nurses in a Qualitative Study

PubMed Central

Zamanzadeh, Vahid; Valizadeh, Leila; Sayadi, Leila; Taleghani, Fariba; Jeddian, Alireza

2013-01-01

Background This study explored the state of hematopoietic stem cell transplantation (HSCT) recipient patients and problems experienced by them and nurse about these state and problems, in Iran. Methods Qualitative content analysis was used for analyzing semi-structured interviews with 12 HSCT recipient patients and 18 nurses. Results Three main categories described the HSCT state and problems: shadow of death, living with uncertainty, and immersion in problems. Patients treated with risk variety in continuity with probability of death. The patients lived with uncertainty. Consequently these resulted immersion in problems with four sub-categories including: (a) Physical problems, (b) money worries, (c) life disturbances, and (d) emotional strain. Conclusion HSCT patients live in a state of limbo between life and death with multidimensional problems. Establish centers for supporting and educating of patients and their families, education of health care providers, enhancement of public knowledge about HSCT along with allocating more budgets to take care of these patients can help patients for passing from this limbo. PMID:24505532

Complete neurologic and cognitive recovery after plasmapheresis in a patient with chronic inflammatory demyelinating polyneuropathy after allogeneic hematopoietic stem cell transplantation.

PubMed

Vogl, Ursula; Leitner, Gerda; Dal-Bianco, Assunta; Bojic, Marija; Mitterbauer, Margit; Rabitsch, Werner; Kalhs, Peter; Schulenburg, Axel

2016-05-01

Neurologic complications after allogeneic hematopoietic stem cell transplantation (HSCT) are rare but poorly understood. We present a case report of a 57-year-old-male patient who was diagnosed in 2009 with acute myeloid leukemia (AML). He received two standard induction chemotherapies, as well as a following consolidation. Six months later, an allogeneic HSCT was performed. Shortly after HSCT the patient developed progressive polyneuropathy of the lower legs and hypoesthesia. Five months later a severe dementia followed. All images of the brain and spine showed no specific pathologies. High dose corticosteroids and immunoglobulins did not improve the neurologic symptoms. Due to severe worsening of the neuropsychiatric status and the clinical presentation, chronic inflammatory demyelinating polyneuropathy (CIDP) was suspected. Therefore, the patient received ten cycles of plasmapheresis. The patient showed a significant improvement of the neuropsychiatric symptoms and cognitive status. Immune mediated neuropathies after allogeneic HSCT, such as CIDP, have great variability in symptoms and presentation and are challenging to diagnose and treat. Plasmapheresis is a safe and efficient treatment for patients with unclear persisting autoimmune neuropathy after HSCT.

New insights into hematopoietic stem cell transplantation for chronic lymphocytic leukemia: a 2015 perspective.

PubMed

McClanahan, Fabienne; Gribben, John

2015-09-01

A considerable body of evidence demonstrates that allogeneic hematopoietic stem cell transplantation (HSCT) offers the only potentially curative treatment option for patients with chronic lymphocytic leukemia (CLL). However, this approach is suitable for only a minority of CLL patients, owing to its significant treatment-related mortality and morbidity. Until recently, internationally accepted guidelines suggested that HSCT should be considered in physically fit CLL patients who carry poor-risk features, such as TP53 abnormalities, or who had a short response to previous immunochemotherapy. However, several new agents and alternative treatment strategies are available that demonstrate impressive and durable responses, even in CLL patients who previously might have been candidates for transplant. The decision about which patients merit HSCT therefore remains important, and HSCT must now be considered in light of other less toxic therapies. Until data on the long-term efficacy of novel treatment approaches mature, the choice of HSCT vs alternative strategies must be assessed on a patient-by-patient basis, and treatment in the setting of randomized clinical trials should be pursued whenever possible.

Hematopoietic stem cell transplantation for chronic lymphocytic leukemia.

PubMed

Gladstone, Douglas E; Fuchs, Ephraim

2012-03-01

Although hematopoietic stem cell transplantation (HSCT) is the treatment of choice for many aggressive hematologic malignancies, the role of HSCT in chronic lymphocytic leukemia (CLL) has remained controversial. Now in the era of improved conventional treatment and better prognostication of long-term outcome, a review of autologous and allogeneic HSCT in CLL treatment is warranted. Despite an improved disease-free survival in some patients, multiple, prospective, randomized autologous HSCT CLL trials fail to demonstrate an overall survival benefit as compared to conventional therapy. Allogeneic bone marrow transplantation, although limited by donor availability, can successfully eradicate CLL with adverse prognostic features. In the older CLL patients, nonmyeloablative allogeneic transplants are better tolerated than myeloablative transplants. Nonmyeloablative allogeneic transplants are less effective in heavily diseased burdened patients. Outside of a clinical protocol, autologous HSCT for CLL cannot be justified. Nonmyeloablative allogeneic transplantation should be considered in high-risk populations early in the disease process, when disease burden is most easily controlled. Alternative donor selection using haploidentical donors and posttransplantation cyclophosphamide has the potential to vastly increase the availability of curative therapy in CLL while retaining a low treatment-related toxicity.

NCI First International Workshop on the Biology, Prevention and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation: Report from the Committee on Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation

PubMed Central

Porter, David L.; Alyea, Edwin P.; Antin, Joseph H.; DeLima, Marcos; Estey, Eli; Falkenburg, J.H. Frederik; Hardy, Nancy; Kroeger, Nicolaus; Leis, Jose; Levine, John; Maloney, David G.; Peggs, Karl; Rowe, Jacob M.; Wayne, Alan S.; Giralt, Sergio; Bishop, Michael R.; van Besien, Koen

2010-01-01

Relapse is a major cause of treatment failure after allogeneic hematopoietic stem cell transplantation (alloHSCT). Treatment options for relapse have been inadequate and the majority of patients ultimately die of their disease. There is no standard approach to treating relapse after alloHSCT. Withdrawal of immune suppression and donor lymphocyte infusions (DLI) are commonly used for all diseases; although these interventions are remarkably effective for relapsed CML, they have limited efficacy in other hematologic malignancies. Conventional and novel chemotherapy, monoclonal antibody therapy, targeted therapies, and second transplants have been utilized in a variety of relapsed diseases, but reports on these therapies are generally anecdotal and retrospective. As such there is an immediate need for well designed, disease-specific trials for treatment of relapse after alloHSCT. This report summarizes current treatment options under investigation for relapse after alloHSCT in a disease-specific manner. In addition, recommendations are provided for specific areas of research necessary in the treatment of relapse after alloHSCT. PMID:20699125

[Allogeneic hematopoietic stem cell transplantation using myeloablative conditioning including total body irradiation for pediatric acute lymphoblastic leukemia: a single-center retrospective analysis].

PubMed

Honda, Mamoru; Arakawa, Yuki; Kawakami, Ryota; Itabashi, Toshikazu; Yanagi, Masato; Sasaki, Koji; Watanabe, Kentaro; Isobe, Kiyotaka; Mori, Makiko; Hanada, Ryoji; Koh, Katsuyoshi

2018-01-01

This study aimed to investigate the clinical outcomes of hematopoietic stem cell transplantation (HSCT) with total body irradiation-based myeloablative conditioning (TBI-MAC) in pediatric patients with acute lymphoblastic leukemia (ALL). We retrospectively examined patients with ALL who underwent HSCT with TBI-MAC from January 2000 to August 2016 at our institute. We enrolled 67 patients with a median follow-up period of 8 years. The 5-year event-free survival (EFS) and overall survival (OS) were 51.2% and 59.6%, respectively. At the first complete remission, HSCT exhibited significantly superior EFS and OS in our patients than that in patients with other diseases. We encountered 57.9% of patients with at least one late complication. Major late complications were short stature (26.3%) and hypogonadism (18.4%). While late complications were observed in several recipients of HSCT, late complication-related deaths occurred in three patients. The TBI-MAC regimen led to favorable clinical outcomes in pediatric patients with ALL who underwent HSCT. Thus, proper evaluation and management of late complications are mandatory.

Gut microbiota and graft-versus-host disease: broad-spectrum antibiotic use increases post-allogeneic hematopoietic stem cell transplant graft-versus-host disease-related mortality.

PubMed

Shono, Yusuke

2017-01-01

Intestinal bacteria can modulate the risk of infection and graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Allo-HSCT recipients often develop neutropenic fever, which is treated with antibiotics that may target anaerobic bacteria in the gut. We retrospectively examined 857 allo-HSCT recipients and found that treatment using broad-spectrum antibiotics was associated with increased GVHD-related mortality at 5 years. Analysis of stool specimens from allo-HSCT recipients showed that broad-spectrum antibiotic administration was associated with perturbation of gut microbial composition. Studies in mice also demonstrated aggravated GVHD mortality with broad-spectrum antibiotics use. Broad-spectrum antibiotics treatment of mice with GVHD led to a loss of the protective mucus lining of the colon, compromised intestinal barrier function, as well as increased a commensal bacterium with mucus-degrading capabilities, raising the possibility that mucus degradation may contribute to murine GVHD. We demonstrate an underappreciated risk of antibiotics in allo-HSCT recipients that may exacerbate GVHD in the colon.

Newly identified poor prognostic factors for adult T-cell leukemia-lymphoma treated with allogeneic hematopoietic stem cell transplantation.

PubMed

Tokunaga, Masahito; Uto, Hirofumi; Takeuchi, Shogo; Nakano, Nobuaki; Kubota, Ayumu; Tokunaga, Mayumi; Takatsuka, Yoshifusa; Seto, Masao; Ido, Akio; Utsunomiya, Atae

2017-01-01

To explore pre-transplantation prognostic factors for adult T-cell leukemia-lymphoma (ATL), we retrospectively analyzed allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 70 patients at our institute (63 acute type and seven lymphoma type patients). Forty-five patients died after HSCT and the three-year overall survival (OS) rate was 35.2%. By univariate analysis, the adverse prognostic factors for OS were performance status ≥2, hematopoietic cell transplantation-specific comorbidity index (HCT-CI) score ≥3, European Group for Blood and Marrow Transplantation (EBMT) risk score ≥5, HSCT from an HLA-mismatched donor, serum soluble interleukin-2 receptor (sIL-2R) level ≥10,000 U/mL, lymphocyte count ≥4000/μL, and hemoglobin <9 g/dL at the time of HSCT. EBMT risk score and sIL-2R were identified as significant adverse prognostic factors using multivariate analysis. This analysis clearly demonstrates for the first time that HCT-CI and EBMT risk scores are reliable prognostic factors for ATL patients receiving allo-HSCT.

Optimal platform design using non-dominated sorting genetic algorithm II and technique for order of preference by similarity to ideal solution; application to automotive suspension system

NASA Astrophysics Data System (ADS)

Shojaeefard, Mohammad Hassan; Khalkhali, Abolfazl; Faghihian, Hamed; Dahmardeh, Masoud

2018-03-01

Unlike conventional approaches where optimization is performed on a unique component of a specific product, optimum design of a set of components for employing in a product family can cause significant reduction in costs. Increasing commonality and performance of the product platform simultaneously is a multi-objective optimization problem (MOP). Several optimization methods are reported to solve these MOPs. However, what is less discussed is how to find the trade-off points among the obtained non-dominated optimum points. This article investigates the optimal design of a product family using non-dominated sorting genetic algorithm II (NSGA-II) and proposes the employment of technique for order of preference by similarity to ideal solution (TOPSIS) method to find the trade-off points among the obtained non-dominated results while compromising all objective functions together. A case study for a family of suspension systems is presented, considering performance and commonality. The results indicate the effectiveness of the proposed method to obtain the trade-off points with the best possible performance while maximizing the common parts.

Current Review of Iron Overload and Related Complications in Hematopoietic Stem Cell Transplantation

PubMed Central

Atilla, Erden; Toprak, Selami K.; Demirer, Taner

2017-01-01

Iron overload is an adverse prognostic factor for patients undergoing hematopoietic stem cell transplantation (HSCT). In the HSCT setting, pretransplant and early posttransplant ferritin and transferrin saturation were found to be highly elevated due to high transfusion requirements. In addition to that, post-HSCT iron overload was shown to be related to infections, hepatic sinusoidal obstruction syndrome, mucositis, liver dysfunction, and acute graft-versus-host disease. Hyperferritinemia causes decreased survival rates in both pre- and posttransplant settings. Serum ferritin levels, magnetic resonance imaging, and liver biopsy are diagnostic tools for iron overload. Organ dysfunction due to iron overload may cause high mortality rates and therefore sufficient iron chelation therapy is recommended in this setting. In this review the management of iron overload in adult HSCT is discussed. PMID:27956374

Hematopoietic stem cell transplantation in Niemann-Pick disease type B monitored by chitotriosidase activity.

PubMed

Quarello, Paola; Spada, Marco; Porta, Francesco; Vassallo, Elena; Timeus, Fabio; Fagioli, Franca

2018-02-01

Here, we report a patient with Niemann-Pick disease type B, with early severe onset of disease and pulmonary involvement, treated with hematopoietic stem cell transplant (HSCT) from a bone marrow matched unrelated donor. We confirm that HSCT is feasible and potentially beneficial for patients with severe phenotype. Noteworthy, we discussed the potential usefulness of the activity of peripheral chitotriosidase for the longitudinal evaluation of HSCT success and effectiveness. © 2017 Wiley Periodicals, Inc.

On the development of HSCT tail sizing criteria using linear matrix inequalities

NASA Technical Reports Server (NTRS)

Kaminer, Isaac

1995-01-01

This report presents the results of a study to extend existing high speed civil transport (HSCT) tail sizing criteria using linear matrix inequalities (LMI). In particular, the effects of feedback specifications, such as MIL STD 1797 Level 1 and 2 flying qualities requirements, and actuator amplitude and rate constraints on the maximum allowable cg travel for a given set of tail sizes are considered. Results comparing previously developed industry criteria and the LMI methodology on an HSCT concept airplane are presented.

The heterogeneous HLA genetic composition of the Brazilian population and its relevance to the optimization of hematopoietic stem cell donor recruitment.

PubMed

Fabreti-Oliveira, R A; Nascimento, E; Fonseca, C G; Santos, M A

2014-08-01

The aim of this study was to investigate the human leukocyte antigen (HLA) molecular variation across the Brazilian population in order to determine possible regional differences, which would be highly relevant to optimizing donor recruitment strategies in hematopoietic stem cell transplantation (HSCT) and understanding the population genetic background of this heterogeneous country. HLA data of 551 HSCT donors from five Brazilian regions were characterized by high-resolution DNA alleles at the HLA-A, -B, -C, -DRB1 and -DQB1 loci and compared with other populations in Brazil and worldwide populations. Allele and haplotype frequencies were estimated. The analysis was performed to assess Hardy-Weinberg equilibrium (HWE) and linkage disequilibrium (LD) among different loci in each recruitment center. Genetic variation was explored through genetic distance analyzed by using a new algorithm based on linear algebra, taking into account geographic regions of Brazil. The results indicated a heterogeneous genetic composition of the Brazilian population, such that HLA allele and haplotype frequencies exhibit different distributions among Brazilian regions, which has important implications for donor matching. In addition, a pronounced differentiation was observed by the absence of clustering of the regional populations in the reduced-dimension space. These data may be useful for increasing donor recruitment with more genetic representativeness in the Brazilian Volunteer Bone Marrow Donors Registry (REDOME). © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Frequent occurrence of cytomegalovirus retinitis during immune reconstitution warrants regular ophthalmic screening in high-risk pediatric allogeneic hematopoietic stem cell transplant recipients.

PubMed

Hiwarkar, Prashant; Gajdosova, Eva; Qasim, Waseem; Worth, Austen; Breuer, Judith; Chiesa, Robert; Ridout, Deborah; Edelsten, Clive; Moore, Anthony; Amrolia, Persis; Veys, Paul; Rao, Kanchan

2014-06-01

Although cytomegalovirus (CMV) retinitis (CMVR) is a well-recognized complication after allogeneic hematopoietic stem cell transplantation (HSCT), standard operating procedures for ophthalmic monitoring are variable. In particular, authors perceived a greater risk of CMVR after pediatric HSCT for inherited immunodeficiencies, in patients who often have pretransplantation viremia. This study was therefore performed to identify high-risk pediatric HSCT recipients who would benefit from regular ophthalmic monitoring. During a 5-year study period, we retrospectively analyzed findings in 56 of 304 consecutive HSCT recipients (age range, 0.5-197 months) in whom significant CMV viremia developed (CMV level at PCR, ≥4000 copies/mL). All HSCT recipients with significant CMV viremia underwent retinal examination weekly (inpatients) or every other week (outpatients), with examinations performed by a skilled ophthalmologist. CMVR developed in 13 (4%) of 304 HSCT recipients, 23% (13 of 56) of those with significant CMV viremia. Pretransplant viremia (odds ratio, 11.3; P < .01), acute (grade ≥2) graft-vs-host disease (odds ratio, 8.2; P < .02) and mismatched graft (odds ratio, 8; P < .02) were identified as independent risk factors. Compared with other invasive CMV diseases, CMVR was more often a late-onset disease, occurring at a median of 199 days after HSCT. At diagnosis, a significantly higher CD4 T-cell count (≥200/µL; P < .03) and a lower CMV load (P < .004) was observed in children with CMVR, compared with those in whom lung, gut, or liver CMV disease developed. We report an increased risk of CMVR in high-risk pediatric HSCT recipients. This form of CMV disease differs from other invasive CMV disease in its relationship to immune reconstitution and viral dynamics. We have studied the relationship between these variables and suggested a risk-stratified ophthalmic screening strategy. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Relationship of pretransplantation polyoma BK virus serologic findings and BK viral reactivation after hematopoietic stem cell transplantation.

PubMed

Wong, Anders S Y; Chan, Kwok-Hung; Cheng, Vincent C C; Yuen, Kwok-Yung; Kwong, Yok-Lam; Leung, Anskar Y H

2007-03-15

Reactivation of polyoma BK virus (BKV) infection is consistently associated with hemorrhagic cystitis in persons who undergo hematopoietic stem cell transplantation (HSCT). In this study, we examined the relationship of reactivation of BKV infection with pre-HSCT serologic findings of BKV antibody. Serial urine samples (n=1118) obtained from 140 HSCT recipients were prospectively obtained, and BKV loads were quantified by quantitative polymerase chain reaction. Pre-HSCT anti-BKV immunoglobulin G (IgG) levels were determined by indirect immunofluorescence. In 68 patients, there was significant peaking (i.e., > or = 3-log increase) in the urine BKV load (median peak, 1.7x10(9) copies/mL; range, 1.1x10(4) to 3.2x10(14) copies/mL) occurring at a median time of 24.5 days (range, 7-49 days). In 72 patients, low-level BKV viruria occurred without peaking (median BKV load, 10 copies/mL; range, 9.9x10(3) to 1.2x10(10) copies/mL) at a median time of 24.5 days (range, 7-49 days). Pre-HSCT anti-BKV IgG was positively related to elevated urine BKV load during HSCT (P<.001). Binary logistic regression revealed that pre-HSCT anti-BKV IgG level was the only statistically significant factor (P=.009) to be associated with a > or = 3-log increase in the peak urine BKV load (positive and negative predictive values, 69% and 68%, respectively). Nine patients developed hemorrhagic cystitis at a median of 56 days (range, 29-160); 7 of these patients were evaluable and were found to have a > or = 3-log increase in the peak BKV load. In binary logistic regression, peaking of the urine BKV load (P=.026) and graft-versus-host disease (P=.033) were found to be statistically significant risks for hemorrhagic cystitis. The identification of the serologic status of BKV as a significant risk factor for BKV viruria suggests that it should be included as an integral part of the pre-HSCT evaluation.

TRPM7 channel regulates PDGF-BB-induced proliferation of hepatic stellate cells via PI3K and ERK pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fang, Ling, E-mail: fangling_1984@126.com; Zhan, Shuxiang; Huang, Cheng

2013-11-01

TRPM7, a non-selective cation channel of the TRP channel superfamily, is implicated in diverse physiological and pathological processes including cell proliferation. Recently, TRPM7 has been reported in hepatic stellate cells (HSCs). Here, we investigated the contribution role of TRPM7 in activated HSC-T6 cell (a rat hepatic stellate cell line) proliferation. TRPM7 mRNA and protein were measured by RT-PCR and Western blot in rat model of liver fibrosis in vivo and PDGF-BB-activated HSC-T6 cells in vitro. Both mRNA and protein of TRPM7 were dramatically increased in CCl{sub 4}-treated rat livers. Stimulation of HSC-T6 cells with PDGF-BB resulted in a time-dependent increasemore » of TRPM7 mRNA and protein. However, PDGF-BB-induced HSC-T6 cell proliferation was inhibited by non-specific TRPM7 blocker 2-aminoethoxydiphenyl borate (2-APB) or synthetic siRNA targeting TRPM7, and this was accompanied by downregulation of cell cycle proteins, cyclin D1, PCNA and CDK4. Blockade of TRPM7 channels also attenuated PDGF-BB induced expression of myofibroblast markers as measured by the induction of α-SMA and Col1α1. Furthermore, the phosphorylation of ERK and AKT, associated with cell proliferation, decreased in TRPM7 deficient HSC-T6 cells. These observations suggested that TRPM7 channels contribute to perpetuated fibroblast activation and proliferation of PDGF-BB induced HSC-T6 cells via the activation of ERK and PI3K pathways. Therefore, TRPM7 may constitute a useful target for the treatment of liver fibrosis. - Highlights: • Upregulation of TRPM7 mRNA and protein in the fibrotic livers from CCl{sub 4}-treated rats. • Increasing expression of TRPM7 mRNA and protein during HSC activation. • Blockade of TRPM7 inhibited the PDGF-BB induced proliferation of HSC-T6 cells. • Blockade of TRPM7 decreased α-SMA and Col1α1 expressions in activated HSC-T6 cells. • TRPM7 up-regulation contributes to the activation of ERK and AKT pathways.« less

Tolerance induction between two different strains of parental mice prevents graft-versus-host disease in haploidentical hematopoietic stem cell transplantation to F1 mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo, Yixian; Zhang, Lanfang; Wan, Suigui

Highlights: • Injection of UVB-irradiated iDCs induces alloantigen tolerance. • This alloantigen tolerance may be associated regulatory T cell induction. • Tolerant mice serve as bone marrow donors reduces GVHD to their F1 recipients in allo-HSCT. • Tolerance is maintained in F1 recipients for long time post HSCT. - Abstract: Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) has been employed worldwide in recent years and led to favorable outcome in a group of patients who do not have human leukocyte antigen (HLA)-matched donors. However, the high incidence of severe graft-versus-host disease (GVHD) is a major problem for Haplo-HSCT. In the currentmore » study, we performed a proof of concept mouse study to test whether induction of allogeneic tolerance between two different parental strains was able to attenuate GVHD in Haplo-HSCT to the F1 mice. We induced alloantigen tolerance in C3H mice (H-2k) using ultraviolet B (UVB) irradiated immature dendritic cells (iDCs) derived from the cultures of Balb/c bone marrow cells. Then, we performed Haplo-HSCT using tolerant C3H mice as donors to F1 mice (C3H × Balb/c). The results demonstrated that this approach markedly reduced GVHD-associated death and significantly prolonged the survival of recipient mice in contrast to the groups with donors (C3H mice) that received infusion of non-UVB-irradiated DCs. Further studies showed that there were enhanced Tregs in the tolerant mice and alloantigen-specific T cell response was skewed to more IL-10-producing T cells, suggesting that these regulatory T cells might have contributed to the attenuation of GVHD. This study suggests that it is a feasible approach to preventing GVHD in Haplo-HSCT in children by pre-induction of alloantigen tolerance between the two parents. This concept may also lead to more opportunities in cell-based immunotherapy for GVHD post Haplo-HSCT.« less

Nonlinear Burn Control and Operating Point Optimization in ITER

NASA Astrophysics Data System (ADS)

Boyer, Mark; Schuster, Eugenio

2013-10-01

Control of the fusion power through regulation of the plasma density and temperature will be essential for achieving and maintaining desired operating points in fusion reactors and burning plasma experiments like ITER. In this work, a volume averaged model for the evolution of the density of energy, deuterium and tritium fuel ions, alpha-particles, and impurity ions is used to synthesize a multi-input multi-output nonlinear feedback controller for stabilizing and modulating the burn condition. Adaptive control techniques are used to account for uncertainty in model parameters, including particle confinement times and recycling rates. The control approach makes use of the different possible methods for altering the fusion power, including adjusting the temperature through auxiliary heating, modulating the density and isotopic mix through fueling, and altering the impurity density through impurity injection. Furthermore, a model-based optimization scheme is proposed to drive the system as close as possible to desired fusion power and temperature references. Constraints are considered in the optimization scheme to ensure that, for example, density and beta limits are avoided, and that optimal operation is achieved even when actuators reach saturation. Supported by the NSF CAREER award program (ECCS-0645086).

Post-remission treatment with allogeneic stem cell transplantation in patients aged 60 years and older with acute myeloid leukaemia: a time-dependent analysis.

PubMed

Versluis, Jurjen; Hazenberg, Carin L E; Passweg, Jakob R; van Putten, Wim L J; Maertens, Johan; Biemond, Bart J; Theobald, Matthias; Graux, Carlos; Kuball, Jurgen; Schouten, Harry C; Pabst, Thomas; Löwenberg, Bob; Ossenkoppele, Gert; Vellenga, Edo; Cornelissen, Jan J

2015-10-01

Acute myeloid leukaemia mainly affects elderly people, with a median age at diagnosis of around 70 years. Although about 50-60% of patients enter first complete remission upon intensive induction chemotherapy, relapse remains high and overall outcomes are disappointing. Therefore, effective post-remission therapy is urgently needed. Although often no post-remission therapy is given to elderly patients, it might include chemotherapy or allogeneic haemopoietic stem cell transplantation (HSCT) following reduced-intensity conditioning. We aimed to assess the comparative value of allogeneic HSCT with other approaches, including no post-remission therapy, in patients with acute myeloid leukaemia aged 60 years and older. For this time-dependent analysis, we used the results from four successive prospective HOVON-SAKK acute myeloid leukaemia trials. Between May 3, 2001, and Feb 5, 2010, a total of 1155 patients aged 60 years and older were entered into these trials, of whom 640 obtained a first complete remission after induction chemotherapy and were included in the analysis. Post-remission therapy consisted of allogeneic HSCT following reduced-intensity conditioning (n=97), gemtuzumab ozogamicin (n=110), chemotherapy (n=44), autologous HSCT (n=23), or no further treatment (n=366). Reduced-intensity conditioning regimens consisted of fludarabine combined with 2 Gy of total body irradiation (n=71), fludarabine with busulfan (n=10), or other regimens (n=16). A time-dependent analysis was done, in which allogeneic HSCT was compared with other types of post-remission therapy. The primary endpoint of the study was 5-year overall survival for all treatment groups, analysed by a time-dependent analysis. 5-year overall survival was 35% (95% CI 25-44) for patients who received an allogeneic HSCT, 21% (17-26) for those who received no additional post-remission therapy, and 26% (19-33) for patients who received either additional chemotherapy or autologous HSCT. Overall survival at 5 years was strongly affected by the European LeukemiaNET acute myeloid leukaemia risk score, with patients in the favourable risk group (n=65) having better 5-year overall survival (56% [95% CI 43-67]) than those with intermediate-risk (n=131; 23% [19-27]) or adverse-risk (n=444; 13% [8-20]) acute myeloid leukaemia. Multivariable analysis with allogeneic HSCT as a time-dependent variable showed that allogeneic HSCT was associated with better 5-year overall survival (HR 0·71 [95% CI 0·53-0·95], p=0·017) compared with non-allogeneic HSCT post-remission therapies or no post-remission therapy, especially in patients with intermediate-risk (0·82 [0·58-1·15]) or adverse-risk (0.39 [0·21-0·73]) acute myeloid leukaemia. Collectively, the results from these four trials suggest that allogeneic HSCT might be the preferred treatment approach in patients 60 years of age and older with intermediate-risk and adverse-risk acute myeloid leukaemia in first complete remission, but the comparative value should ideally be shown in a prospective randomised study. None. Copyright © 2015 Elsevier Ltd. All rights reserved.

Inner loop flight control for the High-Speed Civil Transport

NASA Technical Reports Server (NTRS)

Newman, Brett A.

1994-01-01

High-speed aerospace vehicles which employ high strength, light weight, yet deformable materials may exhibit significant interaction between the rigid-body and vibrational dynamics. Preliminary High-Speed Civil Transport (HSCT) configurations are a prime example. Traditionally, separate control systems have been used to augment the rigid-body and vibrational dynamics. In the HSCT arena, the highly coupled motions may not allow this design freedom. The research activity addresses two specific issues associated with the design and development of an integrated flight control system (FCS) for HSCT configurations, which are discussed next. The HSCT is expected to have a short period instability at subsonic speeds. Flight vehicles with this characteristic (i.e., F-16, F-22, X-29, Space Shuttle) are stabilized with what is called a superaugmented pitch rate loop. One concern is 'Will this stability augmentation logic work for a HSCT?' Studies show that an idealized pitch rate design would be acceptable, but is not realistic. Investigations using a contaminated pitch rate design reveal serious hurdles to overcome in the FCS design. Mounting location for the pitch rate sensor is critical. Results indicate a forward location leads to destabilizing pick-up of aeroelastic modes, while aft locations lead to undesirable coupling of the dominate pitch mode with the first aeroelastic mode. Intermediate locations for the sensor may not be acceptable. The source of the problem is the presence of low frequency aeroelastic modes in HSCT configurations, which are not present in vehicles currently using the superaugmented logic. To say the least, a conventional superaugmented pitch rate loop strategy may have undesirable characteristics. An unconventional strategy, which attempts to eliminate the above deficiencies by blending several pitch rate signals, indicates an improvement in the FCS architecture feasibility, but is still lacking in some respects. The HSCT configuration does not have aerodynamic surfaces in the vicinity of the nose (i.e., no canard or vane). A second concern is 'Can the fuselage bending/torsion aeroelastic modes be effectively augmented without sufficient control input near the vehicle nose?' The superaugmented FCS results above may be suggesting the necessity of a secondary feedback loop to achieve an acceptable integrated FCS. Preliminary analysis of HSCT aeroelastic mode shapes indicate the use of existing wing leading edge devices as a second control input may be lacking in control authority for the rigid-body attitude and aeroelastic modes. An effort is underway to incorporate generic wing leading edge devices and canards into a generic HSCT model for the purpose of assessing additional control authority and it's use in candidate FCS designs. A generic HSCT mathematical model was necessary for the studies above. A HSCT category model is available in NASA-CR-172201. This model describes the linear, longitudinal dynamics about the following flight condition: ascent, W = 730,000 lbs, h = 6,500 ft, M = 0.6. The model incorporates the full rigid-body variable set, as well as eighteen aeroelastic modes. Elevator deflection serves as the control input. Modifications to the model include the incorporation of relaxed static stability (i.e., static margin from -7.3% to +10%) and additional control inputs.

Evolutionary algorithms for multi-objective optimization: fuzzy preference aggregation and multisexual EAs

NASA Astrophysics Data System (ADS)

Bonissone, Stefano R.

2001-11-01

There are many approaches to solving multi-objective optimization problems using evolutionary algorithms. We need to select methods for representing and aggregating preferences, as well as choosing strategies for searching in multi-dimensional objective spaces. First we suggest the use of linguistic variables to represent preferences and the use of fuzzy rule systems to implement tradeoff aggregations. After a review of alternatives EA methods for multi-objective optimizations, we explore the use of multi-sexual genetic algorithms (MSGA). In using a MSGA, we need to modify certain parts of the GAs, namely the selection and crossover operations. The selection operator groups solutions according to their gender tag to prepare them for crossover. The crossover is modified by appending a gender tag at the end of the chromosome. We use single and double point crossovers. We determine the gender of the offspring by the amount of genetic material provided by each parent. The parent that contributed the most to the creation of a specific offspring determines the gender that the offspring will inherit. This is still a work in progress, and in the conclusion we examine many future extensions and experiments.

Computational wing optimization and comparisons with experiment for a semi-span wing model

NASA Technical Reports Server (NTRS)

Waggoner, E. G.; Haney, H. P.; Ballhaus, W. F.

1978-01-01

A computational wing optimization procedure was developed and verified by an experimental investigation of a semi-span variable camber wing model in the NASA Ames Research Center 14 foot transonic wind tunnel. The Bailey-Ballhaus transonic potential flow analysis and Woodward-Carmichael linear theory codes were linked to Vanderplaats constrained minimization routine to optimize model configurations at several subsonic and transonic design points. The 35 deg swept wing is characterized by multi-segmented leading and trailing edge flaps whose hinge lines are swept relative to the leading and trailing edges of the wing. By varying deflection angles of the flap segments, camber and twist distribution can be optimized for different design conditions. Results indicate that numerical optimization can be both an effective and efficient design tool. The optimized configurations had as good or better lift to drag ratios at the design points as the best designs previously tested during an extensive parametric study.

Neurological outcomes after hematopoietic stem cell transplantation for cerebral X-linked adrenoleukodystrophy, late onset metachromatic leukodystrophy and Hurler syndrome.

PubMed

Saute, Jonas Alex Morales; Souza, Carolina Fischinger Moura de; Poswar, Fabiano de Oliveira; Donis, Karina Carvalho; Campos, Lillian Gonçalves; Deyl, Adriana Vanessa Santini; Burin, Maira Graeff; Vargas, Carmen Regla; Matte, Ursula da Silveira; Giugliani, Roberto; Saraiva-Pereira, Maria Luiza; Vedolin, Leonardo Modesti; Gregianin, Lauro José; Jardim, Laura Bannach

2016-12-01

To describe survival and neurological outcomes after HSCT for these disorders. Seven CALD, 2 MLD and 2 MPS-IH patients underwent HSCT between 2007 and 2014. Neurological examinations, magnetic resonance imaging, molecular and biochemical studies were obtained at baseline and repeated when appropriated. Favorable outcomes were obtained with 4/5 related and 3/6 unrelated donors. Two patients died from procedure-related complications. Nine transplanted patients were alive after a median of 3.7 years: neurological stabilization was obtained in 5/6 CALD, 1/2 MLD, and one MPS-IH patient. Brain lesions of the MPS-IH patient were reduced four years after HSCT. Good outcomes were obtained when HSCT was performed before adulthood, early in the clinical course, and/or from a related donor.

Role of Pharmacogenetics in Hematopoietic Stem Cell Transplantation Outcome in Children

PubMed Central

Franca, Raffaella; Stocco, Gabriele; Favretto, Diego; Giurici, Nagua; Decorti, Giuliana; Rabusin, Marco

2015-01-01

Hematopoietic stem cell transplantation (HSCT) is an established therapeutic procedure for several congenital and acquired disorders, both malignant and nonmalignant. Despite the great improvements in HSCT clinical practices over the last few decades, complications, such as graft vs. host disease (GVHD) and sinusoidal obstructive syndrome (SOS), are still largely unpredictable and remain the major causes of morbidity and mortality. Both donor and patient genetic background might influence the success of bone marrow transplantation and could at least partially explain the inter-individual variability in HSCT outcome. This review summarizes some of the recent studies on candidate gene polymorphisms in HSCT, with particular reference to pediatric cohorts. The interest is especially focused on pharmacogenetic variants affecting myeloablative and immunosuppressive drugs, although genetic traits involved in SOS susceptibility and transplant-related mortality are also reviewed. PMID:26266406

Feasibility of a Symptom Management Intervention for Adolescents Recovering from a Hematopoietic Stem Cell Transplant

PubMed Central

Rodgers, Cheryl C.; Krance, Robert; Street, Richard L.; Hockenberry, Marilyn J.

2015-01-01

Background Adolescents undergoing a hematopoietic stem cell transplant (HSCT) experience a variety of side effects and eating difficulties. Few interventions exist to assist patients with self-care after HSCT hospitalization. The Eating After Transplant (EAT!) program is a mobile phone application developed to assist adolescents with self-management of common eating related issues during HSCT recovery. Objective This study examined the acceptability and usability of the EAT! program among adolescents and assessed the competency of the participants using the program after hospital discharge through the first 100 days post HSCT. Methods A repeated measures design was used to evaluate the EAT! application with 16 adolescent patients recovering from an allogeneic HSCT. Participants provided verbal feedback and used a Likert-scale to rate acceptability and usability of the application. Additionally, a tracking device monitored use of the application. Competency was measured with orientation time and independent demonstration of use of the application. Results Acceptability remained high throughout the study, but use significantly decreased over time. Patients reported familiarity with the program’s content as the reason for the declining use. Competency was excellent with a short orientation period and independent demonstration throughout the study. Conclusions A mobile phone application is a feasible intervention to educate adolescents with symptom management strategies. Future research needs to examine factors affecting sustainability of use over time. Implications for Practice Healthcare providers need to continue to develop and evaluate innovative methods to educate adolescents on effective self-care strategies throughout HSCT recovery. PMID:23842522

Breaking tolerance to self, circulating natural killer cells expressing inhibitory KIR for non-self HLA exhibit effector function after T cell-depleted allogeneic hematopoietic cell transplantation.

PubMed

Yu, Junli; Venstrom, Jeffrey M; Liu, Xiao-Rong; Pring, James; Hasan, Reenat S; O'Reilly, Richard J; Hsu, Katharine C

2009-04-16

Alloreactive natural killer (NK) cells are an important influence on hematopoietic stem cell transplantation (HSCT) outcome. In HLA-mismatched HSCT, alloreactivity occurs when licensed donor NK cells expressing inhibitory killer Ig-like receptors (KIR) for donor MHC class I ligands recognize the lack of the class I ligands in the mismatched recipient ("missing self"). Studies in HLA-matched HSCT, however, have also demonstrated improved outcome in patients lacking class I ligands for donor inhibitory KIR ("missing ligand"), indicating that classically nonlicensed donor NK cells expressing KIR for non-self MHC class I ligands may exhibit functional competence in HSCT. We examined NK function in 16 recipients of T cell-depleted allografts from HLA-identical or KIR-ligand matched donors after myeloablative therapy. After HSCT, nonlicensed NK cells expressing inhibitory KIR for non-self class I exhibit robust intracellular IFN-gamma and cytotoxic response to target cells lacking cognate ligand, gradually becoming tolerized to self by day 100. These findings could not be correlated with cytokine environment or phenotypic markers of NK development, nor could they be attributed to non-KIR receptors such as CD94/NKG2A. These findings confirm that NK alloreactivity can occur in HLA-matched HSCT, where tolerance to self is either acquired by the stem cell-derived NK cell after exiting the bone marrow or where tolerance to self can be temporarily overcome.

Second cancers and late mortality in Australian children treated by allogeneic HSCT for haematological malignancy.

PubMed

Nelson, A S; Ashton, L J; Vajdic, C M; Le Marsney, R E; Daniels, B; Nivison-Smith, I; Wilcox, L; Dodds, A J; O'Brien, T A

2015-02-01

We examined risk of second cancer and late mortality in a population-based Australian cohort of 717 pediatric allogeneic stem cell transplant (HSCT) recipients treated for a malignant disease during 1982-2007. Record linkage with population-based death and cancer registries identified 17 second cancers at a median of 7.9 years post HSCT; thyroid cancer being the most common malignancy (n=8). The cumulative incidence of second cancer was 8.7% at follow-up, and second cancers occurred 20 times more often than in the general population (standardised incidence ratio 20.3, 95% confidence interval (CI)=12.6-32.7). Transplantation using radiation-based conditioning regimens was associated with increased second cancer risk. A total of 367 patients survived for at least 2 years post HSCT and of these 44 (12%) died at a median of 3.1 years after HSCT. Relapse was the most common cause of late mortality (n=32). The cumulative incidence of late mortality was 14.7%. The observed rate of late mortality was 36 times greater than in the matched general population (standardised mortality ratio 35.9, 95% CI=26.7-48.3). Recipients who relapsed or who had radiation-based conditioning regimens were at higher risk of late mortality. Second cancers and late mortality continue to be a risk for pediatric patients undergoing HSCT, and these results highlight the need for effective screening and survivorship programs.

Allogeneic hematopoietic stem cell transplantation for severe, refractory juvenile idiopathic arthritis

PubMed Central

Ladomenou, Fani; Carpenter, Ben; Chandra, Sharat; Sedlacek, Petr; Formankova, Renata; Grandage, Vicky; Friswell, Mark; Cant, Andrew J.; Nademi, Zohreh; Slatter, Mary A.; Gennery, Andrew R.; Hambleton, Sophie; Flood, Terence J.; Lucchini, Giovanna; Chiesa, Robert; Rao, Kanchan; Amrolia, Persis J.; Brogan, Paul; Wedderburn, Lucy R.; Glanville, Julie M.; Hough, Rachael; Marsh, Rebecca; Abinun, Mario; Veys, Paul

2018-01-01

Patients with juvenile idiopathic arthritis (JIA) can experience a severe disease course, with progressive destructive polyarthritis refractory to conventional therapy with disease-modifying antirheumatic drugs including biologics, as well as life-threatening complications including macrophage activation syndrome (MAS). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative immunomodulatory strategy for patients with such refractory disease. We treated 16 patients in 5 transplant centers between 2007 and 2016: 11 children with systemic JIA and 5 with rheumatoid factor–negative polyarticular JIA; all were either refractory to standard therapy, had developed secondary hemophagocytic lymphohistiocytosis/MAS poorly responsive to treatment, or had failed autologous HSCT. All children received reduced toxicity fludarabine-based conditioning regimens and serotherapy with alemtuzumab. Fourteen of 16 patients are alive with a median follow-up of 29 months (range, 2.8-96 months). All patients had hematological recovery. Three patients had grade II-IV acute graft-versus-host disease. The incidence of viral infections after HSCT was high, likely due to the use of alemtuzumab in already heavily immunosuppressed patients. All patients had significant improvement of arthritis, resolution of MAS, and improved quality of life early following allo-HSCT; most importantly, 11 children achieved complete drug-free remission at the last follow-up. Allo-HSCT using alemtuzumab and reduced toxicity conditioning is a promising therapeutic option for patients with JIA refractory to conventional therapy and/or complicated by MAS. Long-term follow-up is required to ascertain whether disease control following HSCT continues indefinitely. PMID:29618462

The Perceived Threat in Adults with Leukemia Undergoing Hematopoietic Stem Cell Transplantation

PubMed Central

Farsi, Zahra; Dehghan Nayeri, Nahid; Negarandeh, Reza

2013-01-01

Background: Leukemia and hematopoietic stem cell transplantation (HSCT) create physical, psychological, social, and spiritual distresses in patients. Understanding this threatening situation in adults with leukemia undergoing HSCT will assist health care professionals in providing holistic care to the patients. Objectives: The aim of the present study was exploring the perceived threat in adults with leukemia undergoing HSCT. Patients and Methods: This article is part of a longitudinal qualitative study which used the grounded theory approach and was conducted in 2009-2011. Ten adults with acute leukemia scheduled for HSCT were recruited from the Hematology–Oncology Research Center and Stem Cell Transplantation, Shariati Hospital in Tehran, Iran. A series of pre-transplant and post-transplant in-depth interviews were held in the hospital’s HSCT wards. Totally, 18 interviews were conducted. Three written narratives were also obtained from the participants. The Corbin and Strauss approach was used to analyze the data. Results: Perceived threat was one of the main categories that emerged from the data. This category included four subcategories, "inattention to the signs and symptoms", "doubt and anxiety", "perception of danger and time limitation" and "change of life conditions", which occurred in linear progression over time. Conclusion: Suffering from leukemia and experiencing HSCT are events that are uniquely perceived by patients. This threatening situation can significantly effect perception of patients and cause temporary or permanent alterations in patients' lives. Health care professionals can help these patients by deeper understanding of their experiences and effective interventions. PMID:25414863

Defibrotide for the treatment of sinusoidal obstruction syndrome: evaluation of response to therapy and patient outcomes.

PubMed

Coutsouvelis, John; Avery, Sharon; Dooley, Michael; Kirkpatrick, Carl; Spencer, Andrew

2018-03-01

Defibrotide is an agent used to treat sinusoidal obstruction syndrome (SOS/VOD) in patients undergoing haemopoietic stem cell transplantation. The aim of this study was to evaluate the effectiveness of defibrotide used within institutional guidelines for the treatment of SOS/VOD in patients undergoing haemopoietic stem cell transplantation (HSCT). Data for 23 patients was retrospectively reviewed to evaluate the effectiveness of defibrotide and the utility of response criteria to direct therapy as specified within institution guidelines. Patients met institutional criteria for a diagnosis of SOS/VOD based on predominantly Baltimore criteria and received defibrotide. Stabilisation or improvement in symptoms and biochemical markers was required for continuation of therapy with defibrotide. Overall, 14 patients responded to therapy. Survival at day 100 post HSCT was 70%. Median serum (total) bilirubin concentrations in all evaluable patients had decreased at days 5 and 10 (p < 0.001). There was a proportional reduction in median weight of 4% by day 5 and 6.6% by day 10 (p < 0.001). On cessation of defibrotide, there was a decrease in the proportion of patients exhibiting hepatomegaly (p = 0.02), ascites (p < 0.01) and requiring oxygen supplementation (p < 0.01), with 70% survival at day 100 post HSCT. Defibrotide to treat SOS/VOD and continued based on attainment of early response was effective management of this condition. Defibrotide should be considered in any consensus protocol providing guidance on the management of SOS/VOD, with future studies considered to assess appropriate time points for response to therapy during treatment.

Fault-Tolerant Control of ANPC Three-Level Inverter Based on Order-Reduction Optimal Control Strategy under Multi-Device Open-Circuit Fault.

PubMed

Xu, Shi-Zhou; Wang, Chun-Jie; Lin, Fang-Li; Li, Shi-Xiang

2017-10-31

The multi-device open-circuit fault is a common fault of ANPC (Active Neutral-Point Clamped) three-level inverter and effect the operation stability of the whole system. To improve the operation stability, this paper summarized the main solutions currently firstly and analyzed all the possible states of multi-device open-circuit fault. Secondly, an order-reduction optimal control strategy was proposed under multi-device open-circuit fault to realize fault-tolerant control based on the topology and control requirement of ANPC three-level inverter and operation stability. This control strategy can solve the faults with different operation states, and can works in order-reduction state under specific open-circuit faults with specific combined devices, which sacrifices the control quality to obtain the stability priority control. Finally, the simulation and experiment proved the effectiveness of the proposed strategy.

Bone Density and Structure in Long-Term Survivors of Pediatric Allogeneic Hematopoietic Stem Cell Transplantation

PubMed Central

Mostoufi-Moab, Sogol; Ginsberg, Jill P.; Bunin, Nancy; Zemel, Babette; Shults, Justine; Leonard, Mary B.

2015-01-01

Children requiring allogeneic hematopoietic stem cell transplantation (alloHSCT) have multiple risk factors for impaired bone accrual. The impact of alloHSCT on volumetric bone mineral density (vBMD) and cortical structure has not been addressed. Tibia peripheral quantitative computed tomography (pQCT) scans were obtained in 55 alloHSCT recipients, ages 5–26 years, a median of 7 (range 3–16) years after alloHSCT. pQCT outcomes were converted to sex- and race- specific Z-scores relative to age based on reference data in >700 concurrent healthy participants. Cortical section modulus (Zp; a summary measure of cortical bone structure and strength), muscle and fat area Z-scores were further adjusted for tibia length for age Z-scores. AlloHSCT survivors had lower height Z-scores (−1.21 ± 1.25 vs. 0.23 ± 0.92; p<0.001), vs. reference participants; BMI Z-scores did not differ. AlloHSCT survivors had lower trabecular vBMD [−1.05 (95% CI −1.33, −0.78), p<0.001], cortical Zp [−0.63 (−0.91, −0.35), p<0.001], and muscle [−1.01 (−1.30, −0.72), p<0.001] Z-scores and greater fat [0.82 (0.54,1.11), p<0.001] Z-scores, vs. reference participants. Adjustment for muscle deficits eliminated Zp deficits in alloHSCT. Total body irradiation (TBI) was associated with lower trabecular vBMD (−1.30 ± 1.40 vs. −0.49 ± 0.88; p=0.01) and muscle (−1.34 ± 1.42 vs. −0.34 ± 0.87; p<0.01) Z-scores. Growth hormone deficiency (GHD) was associated with lower Zp Z-scores (−1.64 ± 2.47 vs. −0.28 ± 1.24; p=0.05); however, muscle differences were not significant (−1.69 ± 1.84 vs. −0.78 ± 1.01; p=0.09). History of graft vs. host disease was not associated with pQCT outcomes. In summary, alloHSCT was associated with significant deficits in trabecular vBMD, cortical geometry, and muscle area years after transplantation. TBI and GHD were significant risk factors for musculoskeletal deficits. Future studies are needed to determine the metabolic and fracture implications of these deficits, and to identify therapies to improve bone accrual following alloHSCT during childhood. PMID:22189761

Outcome of Second Transplantation Using Umbilical Cord Blood for Graft Failure after Allogeneic Hematopoietic Stem Cell Transplantation for Aplastic Anemia.

PubMed

Onishi, Yasushi; Mori, Takehiko; Kako, Shinichi; Koh, Hideo; Uchida, Naoyuki; Kondo, Tadakazu; Kobayashi, Takeshi; Yabe, Hiromasa; Miyamoto, Toshihiro; Kato, Koji; Suzuki, Ritsuro; Nakao, Shinji; Yamazaki, Hirohito

2017-12-01

Graft failure (GF) is the most critical life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT) for aplastic anemia, for which a second transplantation is the only effective treatment. Optimal procedures have not been established for the second transplantation in this setting, however. Here we retrospectively analyzed the outcomes of 22 patients with aplastic anemia, age ≥16 years, who underwent umbilical cord blood transplantation for GF after the first HSCT using the registry database of the Japan Society for Hematopoietic Cell Transplantation. The median age of patients was 36 years (range, 16 to 72 years), and the median time from the first to the second transplant was 77 days (range, 29 to 1061 days). The cumulative incidence of neutrophil engraftment at day 60 post-transplantation was 45.5% (95% confidence interval [CI], 23.6% to 65.0%). With a median follow-up of 50 months, the 4-year overall survival (OS) was 38.5% (95% CI, 18.4% to 58.5%). Mycofenolate mofetil-based graft-versus-host disease prophylaxis demonstrated greater neutrophil recovery than prophylaxis with calcineurin inhibitor alone or methotrexate-based prophylaxis (66.7% versus 37.5%; P = .04). The use of such conditioning regimens as fludarabine + melphalan or cyclophosphamide + low-dose total body irradiation was associated with better engraftment (58.3% versus 30%; P = .05) and better 4-year OS (55.6% versus 20%; P = .05) than other regimens. Although further investigation is needed, umbilical cord blood could be an effective and promising option for stem cell source for urgent second transplantation in patients with aplastic anemia who develop GF after the first HSCT. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Vitamin D Deficiency in Pediatric Hematopoietic Stem Cell Transplantation Patients Despite Both Standard and Aggressive Supplementation.

PubMed

Wallace, Gregory; Jodele, Sonata; Myers, Kasiani C; Dandoy, Christopher E; El-Bietar, Javier; Nelson, Adam; Taggart, Cynthia B; Daniels, Pauline; Lane, Adam; Howell, Jonathan; Teusink-Cross, Ashley; Davies, Stella M

2016-07-01

We recently reported that more than 70% of pediatric and young adult patients had a vitamin D (VD) deficiency at the time of their hematopoietic stem cell transplantation (HSCT). Moreover, VD deficiency was associated with inferior survival at 100 days after transplantation. The goal of the present study was to evaluate the VD requirements needed to maintain an optimal VD level (30 to 60 ng/mL) during the first 3 months after transplantation using real-time VD monitoring and personalized VD supplementation. We examined 2 cohorts in this study: cohort 1, the "preintervention" cohort (n = 35), who were treated according to National Kidney Foundation guidelines for VD therapy, and cohort 2, the "intervention" cohort (n = 25) who were treated with high-dose VD with an aggressive dosage increase in those who remained VD-insufficient. Results from cohort 1 showed that despite aggressive monitoring and VD supplementation, therapeutic vitamin D levels were difficult to achieve and maintain in HSCT recipients during the early post-transplantation period. Only 43% of cohort 1 achieved a therapeutic VD level, leading to our intervention in cohort 2. Outcomes improved in cohort 2, but still only 64% of cohort 2 patients achieved a therapeutic VD level despite receiving >200 IU/kg/day of VD enterally. The median VD level in patients who did achieve sufficient levels was 40 ng/mL, with only 1 patient in each cohort achieving a supratherapeutic but nontoxic level. These data indicate that standard guidelines for VD replacement are inadequate in HSCT recipients, and further work is needed to define more appropriate dosing in this clinical setting. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Aircraft integrated design and analysis: A classroom experience

NASA Technical Reports Server (NTRS)

1988-01-01

AAE 451 is the capstone course required of all senior undergraduates in the School of Aeronautics and Astronautics at Purdue University. During the past year the first steps of a long evolutionary process were taken to change the content and expectations of this course. These changes are the result of the availability of advanced computational capabilities and sophisticated electronic media availability at Purdue. This presentation will describe both the long range objectives and this year's experience using the High Speed Commercial Transport (HSCT) design, the AIAA Long Duration Aircraft design and a Remotely Piloted Vehicle (RPV) design proposal as project objectives. The central goal of these efforts was to provide a user-friendly, computer-software-based, environment to supplement traditional design course methodology. The Purdue University Computer Center (PUCC), the Engineering Computer Network (ECN), and stand-alone PC's were used for this development. This year's accomplishments centered primarily on aerodynamics software obtained from the NASA Langley Research Center and its integration into the classroom. Word processor capability for oral and written work and computer graphics were also blended into the course. A total of 10 HSCT designs were generated, ranging from twin-fuselage and forward-swept wing aircraft, to the more traditional delta and double-delta wing aircraft. Four Long Duration Aircraft designs were submitted, together with one RPV design tailored for photographic surveillance. Supporting these activities were three video satellite lectures beamed from NASA/Langley to Purdue. These lectures covered diverse areas such as an overview of HSCT design, supersonic-aircraft stability and control, and optimization of aircraft performance. Plans for next year's effort will be reviewed, including dedicated computer workstation utilization, remote satellite lectures, and university/industrial cooperative efforts.

Apparatus and method for optimal phase balancing using dynamic programming with spatial consideration

DOEpatents

Robertazzi, Thomas G.; Skiena, Steven; Wang, Kai

2017-08-08

Provided are an apparatus and method for load-balancing of a three-phase electric power distribution system having a multi-phase feeder, including obtaining topology information of the feeder identifying supply points for customer loads and feeder sections between the supply points, obtaining customer information that includes peak customer load at each of the points between each of the feeder sections, performing a phase balancing analysis, and recommending phase assignment at the customer load supply points.

Multi-point objective-oriented sequential sampling strategy for constrained robust design

NASA Astrophysics Data System (ADS)

Zhu, Ping; Zhang, Siliang; Chen, Wei

2015-03-01

Metamodelling techniques are widely used to approximate system responses of expensive simulation models. In association with the use of metamodels, objective-oriented sequential sampling methods have been demonstrated to be effective in balancing the need for searching an optimal solution versus reducing the metamodelling uncertainty. However, existing infilling criteria are developed for deterministic problems and restricted to one sampling point in one iteration. To exploit the use of multiple samples and identify the true robust solution in fewer iterations, a multi-point objective-oriented sequential sampling strategy is proposed for constrained robust design problems. In this article, earlier development of objective-oriented sequential sampling strategy for unconstrained robust design is first extended to constrained problems. Next, a double-loop multi-point sequential sampling strategy is developed. The proposed methods are validated using two mathematical examples followed by a highly nonlinear automotive crashworthiness design example. The results show that the proposed method can mitigate the effect of both metamodelling uncertainty and design uncertainty, and identify the robust design solution more efficiently than the single-point sequential sampling approach.

Hematopoietic Stem Cell Transplantation for Systemic Lupus Erythematosus

PubMed Central

Marmont du Haut Champ, Alberto M.

2012-01-01

Two streams of research are at the origin of the utilization of hematopoietic stem cell transplantation (HSCT) for severe autoimmune diseases (SADs). The allogeneic approach came from experimental studies on lupus mice, besides clinical results in coincidental diseases. The autologous procedure was encouraged by researches on experimental neurological and rheumatic disorders. At present the number of allogeneic HSCT performed for human SADs can be estimated to not over 100 patients, and the results are not greatly encouraging, considering the significant transplant-related mortality (TRM) and the occasional development of a new autoimmune disorder and/or relapses notwithstanding full donor chimerism. Autologous HSCT for refractory SLE has become a major target. Severe cases have been salvaged, TRM is low and diminishing, and prolonged clinical remissions are obtainable. Two types of immune resetting have been established, “re-education” and regulatory T cell (Tregs) normalization. Allogeneic HSCT for SLE seems best indicated for patients with disease complicated by an oncohematologic malignancy. Autologous HSCT is a powerful salvage therapy for otherwise intractable SLE. The duration of remission in uncertain, but a favorable response to previously inactive treatments is a generally constant feature. The comparison with new biological agents, or the combination of both, are to be ascertained. PMID:22969816

Clinical and immunologic outcome of patients with cartilage hair hypoplasia after hematopoietic stem cell transplantation.

PubMed

Bordon, Victoria; Gennery, Andrew R; Slatter, Mary A; Vandecruys, Els; Laureys, Genevieve; Veys, Paul; Qasim, Waseem; Waseem, Qasim; Friedrich, Wilhelm; Wulfraat, Nico M; Scherer, Franziska; Cant, Andrew J; Fischer, Alain; Cavazzana-Calvo, Marina; Cavazanna-Calvo, Marina; Bredius, Robbert G M; Notarangelo, Luigi D; Mazzolari, Evelina; Neven, Benedicte; Güngör, Tayfun; Tayfun, Güngör

2010-07-08

Cartilage-hair hypoplasia (CHH) is a rare autosomal recessive disease caused by mutations in the RMRP gene. Beside dwarfism, CHH has a wide spectrum of clinical manifestations including variable grades of combined immunodeficiency, autoimmune complications, and malignancies. Previous reports in single CHH patients with significant immunodeficiencies have demonstrated that allogeneic hematopoietic stem cell transplantation (HSCT) is an effective treatment for the severe immunodeficiency, while growth failure remains unaffected. Because long-term experience in larger cohorts of CHH patients after HSCT is currently unreported, we performed a European collaborative survey reporting on 16 patients with CHH and immunodeficiency who underwent HSCT. Immune dysregulation, lymphoid malignancy, and autoimmunity were important features in this cohort. Thirteen patients were transplanted in early childhood ( approximately 2.5 years). The other 3 patients were transplanted at adolescent age. Of 16 patients, 10 (62.5%) were long-term survivors, with a median follow-up of 7 years. T-lymphocyte numbers and function have normalized, and autoimmunity has resolved in all survivors. HSCT should be considered in CHH patients with severe immunodeficiency/autoimmunity, before the development of severe infections, major organ damage, or malignancy might jeopardize the outcome of HSCT and the quality of life in these patients.

Level of Granzyme B-positive T-regulatory cells is a strong predictor biomarker of acute Graft-versus-host disease after day +30 after allo-HSCT.

PubMed

Drokov, Mikhail Y; Davydova, Julia O; Kuzmina, Larisa A; Galtseva, Irina V; Kapranov, Nikolay M; Vasilyeva, Vera A; Dubnyak, Darya S; Koroleva, Olga M; Mikhalcova, Ekaterina D; Popova, Natalia N; Parovichnikova, Elena N; Savchenko, Valery G

2017-03-01

Acute Graft-versus-host-disease (aGVHD), the major complication and one of the main causes of poor outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Nowadays there are no widely accepted cell, plasma or another biomarker that can be used for aGVHD prediction. We hypothesized that a level of Granzyme B-positive T regulatory (GZMB-positive Treg) cells on day+30 after allo-HSCT could be the measure of immune response suppression and could predict aGVHD development after day +30. We applied a widespread and easy-to-perform method of multicolor flow cytometry to measure level of GZMB-positive Treg cells. Levels of GZMB-positive Tregs on day +30 after allo-HSCT were significantly higher in those patients who never developed aGVHD in comparison with the other group of patient with aGVHD after day +30 (p=0.0229). We conclude that the level of GZMB-positive Treg cells is a strong predictor of acute Graft-versus-host disease after day +30 after allo-HSCT. Copyright © 2017 Elsevier Ltd. All rights reserved.

The impact of posttraumatic stress symptoms on social support and social conflict during hematopoietic stem cell transplant.

PubMed

Gerhart, James I; Asvat, Yasmin; Lillis, Teresa A; Fung, Henry; Grosse, Johanna; Hobfoll, Stevan E

2018-01-01

Social support and its relationship to psychological distress are of interest in hematopoietic stem cell transplant (HSCT) as patients are dependent on caregivers pre-, during, and posttransplant.  Although social support is critical for managing stress and trauma, posttraumatic stress symptoms (PTSS) may erode social support and evoke conflict and abandonment within the support system. This study aimed to evaluate whether PTSS were associated with lower support and social conflict in a sample of patients undergoing HSCT. Prospective relationships between PTSS, perceived social support, and social conflict were assessed in 88 participants across the first three months of HSCT (T0 Baseline; T1 +30; T2 +60; T3 +90). When individuals experienced increase above their own average levels of PTSS, they reported concurrent increase in social conflict (p < .001) and subsequent increase in social support in the following month (p = .026). Results suggest PTSS during stem cell transplantation may evoke social conflict, but over time, the support system may recalibrate to be more supportive. Patients undergoing HSCT may benefit from family and social-level interventions that specifically target the incidence of interpersonal conflict as it unfolds during the initial stages of HSCT.

The role of community pharmacists in the management of hematopoietic stem cell transplant recipients: knowledge and training.

PubMed

Prot-Labarthe, Sonia; Stil-Baudry, Julien; Fahd, Mony; Brion, Françoise; Bourdon, Olivier

2013-04-01

The patients receiving hematopoietic stem cell transplantation (HSCT) require routine management: the role of the pharmacist has not been extensively considered. This study had 2 aims: to explore the knowledge of community pharmacists relating to pediatric HSCT and to evaluate their expectations in terms of training needs. We interviewed 40 community pharmacists in May and June 2010 in Paris (France) with a 3 parts questionnaire: information concerning the community pharmacy, analysis of 2 pediatric prescriptions and knowledge about HSCT and professional training. Twenty-nine (72.5%) of the 40 community pharmacies agreed to participate in the study. When asked what pharmacological advice they would give for an episode of fever, 13% of the pharmacists asked said that they would deliver acetaminophen without asking any further questions. Concerning hypertrichosis in patients treated with corticosteroids and ciclosporin, none mentioned the role of ciclosporin. The erroneous indications for HSCT given included road accidents (1 pharmacist; 3.4%) and hemophilia (3 pharmacists; 10.3%). Almost 80% of the pharmacists questioned considered their HSCT knowledge insufficient for their professional practice. An E-learning session adapted to their needs was of interest to almost three quarters of the pharmacists questioned.

Spirituality and the Recovery of Quality of Life Following Hematopoietic Stem Cell Transplantation

PubMed Central

Leeson, Laura A.; Nelson, Ashley M.; Rathouz, Paul J.; Juckett, Mark B.; Coe, Christopher L.; Caes, Elizabeth W.; Costanzo, Erin S.

2015-01-01

Objective Spirituality has been linked to improved adjustment and functioning in individuals with cancer; however, its effect on quality of life following hematopoietic stem cell transplantation (HSCT) has not been well-studied. This study investigated changes in spirituality in hematologic cancer patients recovering from HSCT and relationships between spirituality and dimensions of quality of life following HSCT. Methods Participants (N = 220) completed measures of two dimensions of spirituality (meaning/peace and religious faith), depression, anxiety, fatigue, pain, and physical and functional well-being prior to transplant and at 1, 3, 6, and 12 months post-transplant. Results Meaning/peace declined at 1 month post-transplant and returned to pre-transplant levels by 6 months post-transplant, and faith increased from pre-transplant to 6 months post-transplant. Mixed-effects linear regression models indicated that greater pre-transplant meaning/peace, but not religious faith, predicted less depression, anxiety, and fatigue, and better physical and functional well-being during the 12 months following transplant. Conclusions The capacity to find meaning and peace may facilitate recovery following HSCT. Results suggest that spirituality may be a resilience factor that could be targeted to improve quality of life for HSCT recipients. PMID:25545043

Site Selection and Resource Allocation of Oil Spill Emergency Base for Offshore Oil Facilities

NASA Astrophysics Data System (ADS)

Li, Yunbin; Liu, Jingxian; Wei, Lei; Wu, Weihuang

2018-02-01

Based on the analysis of the historical data about oil spill accidents in the Bohai Sea, this paper discretizes oil spilled source into a limited number of spill points. According to the probability of oil spill risk, the demand for salvage forces at each oil spill point is evaluated. Aiming at the specific location of the rescue base around the Bohai Sea, a cost-benefit analysis is conducted to determine the total cost of disasters for each rescue base. Based on the relationship between the oil spill point and the rescue site, a multi-objective optimization location model for the oil spill rescue base in the Bohai Sea region is established. And the genetic algorithm is used to solve the optimization problem, and determine the emergency rescue base optimization program and emergency resources allocation ratio.

Engine technology challenges for a 21st Century High-Speed Civil Transport

NASA Technical Reports Server (NTRS)

Shaw, Robert J.; Gilkey, Samuel; Hines, Richard

1993-01-01

Ongoing NASA-funded studies by Boeing, McDonnell-Douglas, General Electric, and Pratt & Whitney indicate that an opportunity exists for a 21st Century High-Speed Civil Transport (HSCT) to become a major part of the international air transportation system. However, before industry will consider an HSCT product launch and an investment estimated to be over $15 billion for design and certification, major technology advances must be made. An overview of the propulsion-specific technology advances that must be in hand before an HSCT product launch could be considered is presented.

Community noise technology needs: Boeing's perspective

NASA Technical Reports Server (NTRS)

Nihart, Gene L.

1992-01-01

Airport community acceptance of High Speed Civil Transport (HSCT) noise levels will depend on the relative noise levels of airplanes flying at the time of introduction. The 85 dBA noise contours for the range of large subsonic airplanes that are expected to be in service in the early 21st century are shown as a shaded area. A certifiable HSCT noise contour as shown, would be somewhat wider along the runway, but about the same in the residential areas downrange. An HSCT noise rule should insure this noise capability.

Scalability of surrogate-assisted multi-objective optimization of antenna structures exploiting variable-fidelity electromagnetic simulation models

NASA Astrophysics Data System (ADS)

Koziel, Slawomir; Bekasiewicz, Adrian

2016-10-01

Multi-objective optimization of antenna structures is a challenging task owing to the high computational cost of evaluating the design objectives as well as the large number of adjustable parameters. Design speed-up can be achieved by means of surrogate-based optimization techniques. In particular, a combination of variable-fidelity electromagnetic (EM) simulations, design space reduction techniques, response surface approximation models and design refinement methods permits identification of the Pareto-optimal set of designs within a reasonable timeframe. Here, a study concerning the scalability of surrogate-assisted multi-objective antenna design is carried out based on a set of benchmark problems, with the dimensionality of the design space ranging from six to 24 and a CPU cost of the EM antenna model from 10 to 20 min per simulation. Numerical results indicate that the computational overhead of the design process increases more or less quadratically with the number of adjustable geometric parameters of the antenna structure at hand, which is a promising result from the point of view of handling even more complex problems.

Optimization of Turbine Engine Cycle Analysis with Analytic Derivatives

NASA Technical Reports Server (NTRS)

Hearn, Tristan; Hendricks, Eric; Chin, Jeffrey; Gray, Justin; Moore, Kenneth T.

2016-01-01

A new engine cycle analysis tool, called Pycycle, was recently built using the OpenMDAO framework. This tool uses equilibrium chemistry based thermodynamics, and provides analytic derivatives. This allows for stable and efficient use of gradient-based optimization and sensitivity analysis methods on engine cycle models, without requiring the use of finite difference derivative approximation methods. To demonstrate this, a gradient-based design optimization was performed on a multi-point turbofan engine model. Results demonstrate very favorable performance compared to an optimization of an identical model using finite-difference approximated derivatives.

Cost utility analysis of reduced intensity hematopoietic stem cell transplantation in adolescence and young adult with severe thalassemia compared to hypertransfusion and iron chelation program.

PubMed

Sruamsiri, Rosarin; Chaiyakunapruk, Nathorn; Pakakasama, Samart; Sirireung, Somtawin; Sripaiboonkij, Nintita; Bunworasate, Udomsak; Hongeng, Suradej

2013-02-05

Hematopoieticic stem cell transplantation is the only therapeutic option that can cure thalassemia disease. Reduced intensity hematopoietic stem cell transplantation (RI-HSCT) has demonstrated a high cure rate with minimal complications compared to other options. Because RI-HSCT is very costly, economic justification for its value is needed. This study aimed to estimate the cost-utility of RI-HSCT compared with blood transfusions combined with iron chelating therapy (BT-ICT) for adolescent and young adult with severe thalassemia in Thailand. A Markov model was used to estimate the relevant costs and health outcomes over the patients' lifetimes using a societal perspective. All future costs and outcomes were discounted at a rate of 3% per annum. The efficacy of RI-HSCT was based a clinical trial including a total of 18 thalassemia patients. Utility values were derived directly from all patients using EQ-5D and SF-6D. Primary outcomes of interest were lifetime costs, quality adjusted life-years (QALYs) gained, and the incremental cost-effectiveness ratio (ICER) in US ($) per QALY gained. One-way and probabilistic sensitivity analyses (PSA) were conducted to investigate the effect of parameter uncertainty. In base case analysis, the RI-HSCT group had a better clinical outcomes and higher lifetime costs. The incremental cost per QALY gained was US $3,236 per QALY. The acceptability curve showed that the probability of RI-HSCT being cost-effective was 71% at the willingness to pay of 1 time of Thai Gross domestic product per capita (GDP per capita), approximately US $4,210 per QALY gained. The most sensitive parameter was utility of severe thalassemia patients without cardiac complication patients. At a societal willingness to pay of 1 GDP per capita, RI-HSCT was a cost-effective treatment for adolescent and young adult with severe thalassemia in Thailand compared to BT-ICT.

Oral manifestations compatible with chronic graft-versus-host disease in patients with Fanconi anemia.

PubMed

Grein Cavalcanti, Laura; Fuentes Araújo, Renata L; Bonfim, Carmem; Torres-Pereira, Cassius C

2015-02-01

Fanconi anemia (FA) is a genetic disease that is characterized by several congenital abnormalities and progressive bone marrow failure and is associated with an increased susceptibility to malignant disorders. Currently, the only potential cure for hematological disorders is hematopoietic stem cell transplantation (HSCT). However, 1 of the most common complications after HSCT is the development of oral chronic graft-versus-host disease (cGVHD), which is also a risk factor for the development of cancer, particularly oral squamous cell carcinoma. Therefore, the purpose of this study was to describe the prevalence and characteristics of oral manifestations compatible with cGVHD in patients diagnosed with FA according to the National Institutes of Health (NIH) consensus criteria. A total of 96 patients (51 females, 45 males; median age, 16 years) with FA, who were in medical follow-up after HSCT at the outpatient clinic of the bone marrow transplantation unit (Hospital de Clínicas from the Universidade Federal do Paraná) underwent an oral evaluation between January 2013 and December 2013. Post-HSCT periods varied from 1 to 261 months and were divided into 3 periods: immediate post-HSCT period; intermediate post-HSC period, and late post-HSCT period. Among the evaluated patients, 40 of 96 (42%) presented with oral manifestations of cGVHD, with 29 of 40 (73%) of these patients in the late post-HSCT period. NIH scale scores varied from 0 to 10, and lichenoid and hyperkeratotic lesions were the abnormalities most frequently observed (100%). Overall, a high prevalence of oral manifestations was observed for cGVHD patients with FA. These data highlight the importance of monitoring oral manifestations compatible with cGVHD to identify and treat individuals with a higher risk of developing oral cancer. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Cost utility analysis of reduced intensity hematopoietic stem cell transplantation in adolescence and young adult with severe thalassemia compared to hypertransfusion and iron chelation program

PubMed Central

2013-01-01

Background Hematopoieticic stem cell transplantation is the only therapeutic option that can cure thalassemia disease. Reduced intensity hematopoietic stem cell transplantation (RI-HSCT) has demonstrated a high cure rate with minimal complications compared to other options. Because RI-HSCT is very costly, economic justification for its value is needed. This study aimed to estimate the cost-utility of RI-HSCT compared with blood transfusions combined with iron chelating therapy (BT-ICT) for adolescent and young adult with severe thalassemia in Thailand. Methods A Markov model was used to estimate the relevant costs and health outcomes over the patients’ lifetimes using a societal perspective. All future costs and outcomes were discounted at a rate of 3% per annum. The efficacy of RI-HSCT was based a clinical trial including a total of 18 thalassemia patients. Utility values were derived directly from all patients using EQ-5D and SF-6D. Primary outcomes of interest were lifetime costs, quality adjusted life-years (QALYs) gained, and the incremental cost-effectiveness ratio (ICER) in US ($) per QALY gained. One-way and probabilistic sensitivity analyses (PSA) were conducted to investigate the effect of parameter uncertainty. Results In base case analysis, the RI-HSCT group had a better clinical outcomes and higher lifetime costs. The incremental cost per QALY gained was US $ 3,236 per QALY. The acceptability curve showed that the probability of RI-HSCT being cost-effective was 71% at the willingness to pay of 1 time of Thai Gross domestic product per capita (GDP per capita), approximately US $ 4,210 per QALY gained. The most sensitive parameter was utility of severe thalassemia patients without cardiac complication patients. Conclusion At a societal willingness to pay of 1 GDP per capita, RI-HSCT was a cost-effective treatment for adolescent and young adult with severe thalassemia in Thailand compared to BT-ICT. PMID:23379888

Genetics-based control of a mimo boiler-turbine plant

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dimeo, R.M.; Lee, K.Y.

1994-12-31

A genetic algorithm is used to develop an optimal controller for a non-linear, multi-input/multi-output boiler-turbine plant. The algorithm is used to train a control system for the plant over a wide operating range in an effort to obtain better performance. The results of the genetic algorithm`s controller designed from the linearized plant model at a nominal operating point. Because the genetic algorithm is well-suited to solving traditionally difficult optimization problems it is found that the algorithm is capable of developing the controller based on input/output information only. This controller achieves a performance comparable to the standard linear quadratic regulator.

Automatic digital surface model (DSM) generation from aerial imagery data

NASA Astrophysics Data System (ADS)

Zhou, Nan; Cao, Shixiang; He, Hongyan; Xing, Kun; Yue, Chunyu

2018-04-01

Aerial sensors are widely used to acquire imagery for photogrammetric and remote sensing application. In general, the images have large overlapped region, which provide a lot of redundant geometry and radiation information for matching. This paper presents a POS supported dense matching procedure for automatic DSM generation from aerial imagery data. The method uses a coarse-to-fine hierarchical strategy with an effective combination of several image matching algorithms: image radiation pre-processing, image pyramid generation, feature point extraction and grid point generation, multi-image geometrically constraint cross-correlation (MIG3C), global relaxation optimization, multi-image geometrically constrained least squares matching (MIGCLSM), TIN generation and point cloud filtering. The image radiation pre-processing is used in order to reduce the effects of the inherent radiometric problems and optimize the images. The presented approach essentially consists of 3 components: feature point extraction and matching procedure, grid point matching procedure and relational matching procedure. The MIGCLSM method is used to achieve potentially sub-pixel accuracy matches and identify some inaccurate and possibly false matches. The feasibility of the method has been tested on different aerial scale images with different landcover types. The accuracy evaluation is based on the comparison between the automatic extracted DSMs derived from the precise exterior orientation parameters (EOPs) and the POS.

Manifestations of fulminant CD8 T-cell post-transplant lymphoproliferative disorder following the administration of rituximab for lymphadenopathy with a high level of Epstein-Barr Virus (EBV) replication after allogeneic hematopoietic stem cell transplantation.

PubMed

Tanaka, Tomoyuki; Takizawa, Jun; Miyakoshi, Shukuko; Kozakai, Takashi; Fuse, Kyoko; Shibasaki, Yasuhiko; Moriyama, Masato; Ohshima, Koichi; Toba, Ken; Furukawa, Tatsuo; Sone, Hirohito; Masuko, Masayoshi

2014-01-01

We herein report the case of a 22-year-old woman with severe aplastic anemia who underwent allogeneic hematopoietic stem cell transplantation (HSCT). After HSCT, the Epstein-Barr virus (EBV)-DNA load in the peripheral blood gradually increased, and the patient presented with a fever and lymphadenopathy on day 56 post-HSCT. Although we administered rituximab, her clinical condition worsened. After rituximab treatment, CD8 T-cells emerged and became dominant in the peripheral blood, some of which were positive on an EBV-specific tetramer analysis. However, an open biopsy of the lymphadenopathy lesions revealed the CD8 T-cells to be infected with EBV, exhibiting proliferation with oligoclonality. The patient ultimately died of multiple organ failure on day 99 post-HSCT.

Hematopoietic Stem Cell Transplantation in Thalassemia and Sickle Cell Anemia

PubMed Central

Lucarelli, Guido; Isgrò, Antonella; Sodani, Pietro; Gaziev, Javid

2012-01-01

The globally widespread single-gene disorders β-thalassemia and sickle cell anemia (SCA) can only be cured by allogeneic hematopoietic stem cell transplantation (HSCT). HSCT treatment of thalassemia has substantially improved over the last two decades, with advancements in preventive strategies, control of transplant-related complications, and preparative regimens. A risk class–based transplantation approach results in disease-free survival probabilities of 90%, 84%, and 78% for class 1, 2, and 3 thalassemia patients, respectively. Because of disease advancement, adult thalassemia patients have a higher risk for transplant-related toxicity and a 65% cure rate. Patients without matched donors could benefit from haploidentical mother-to-child transplantation. There is a high cure rate for children with SCA who receive HSCT following myeloablative conditioning protocols. Novel non-myeloablative transplantation protocols could make HSCT available to adult SCA patients who were previously excluded from allogeneic stem cell transplantation. PMID:22553502

Effects of Sonic Booms on Marine Mammals: Problem Review and Recommended Research

NASA Technical Reports Server (NTRS)

Bowles, Ann E.

1996-01-01

By flying the High-Speed Civil Transport (HSCT) exclusively over uninhabited areas and mo over water, human annoyance will be reduced to acceptable levels. However, this strategy will for HSCT proponents to contend with the potential effects of sonic booms on animals, particularly ma mammals. What follows is a summary of the environmental regulations that must be addressed, the scientific community's concerns about the potential effects of the HSCT, and recommendations fox research to address the most important concerns. The recommendations included herein are based both on existing scientific evidence and regulatory needs. One cannot over-emphasize the importance of obtaining the appropriate information prior to substantial public exposure. Recent controversies over other human-made acoustic sources in the ocean suggest that the HSCT will receive intense scrutiny. It seems certain that an Environmental Impact Statement (EIS) and Incidental Harassment Authorization (IHA) under the Marine Mammal Protection Act (MMPA) or its equivalent will be necessary.

The Association of Combined GSTM1 and CYP2C9 Genotype Status with the Occurrence of Hemorrhagic Cystitis in Pediatric Patients Receiving Myeloablative Conditioning Regimen Prior to Allogeneic Hematopoietic Stem Cell Transplantation

PubMed Central

Uppugunduri, Chakradhara Rao S.; Storelli, Flavia; Mlakar, Vid; Huezo-Diaz Curtis, Patricia; Rezgui, Aziz; Théorêt, Yves; Marino, Denis; Doffey-Lazeyras, Fabienne; Chalandon, Yves; Bader, Peter; Daali, Youssef; Bittencourt, Henrique; Krajinovic, Maja; Ansari, Marc

2017-01-01

Hemorrhagic cystitis (HC) is one of the complications of busulfan-cyclophosphamide (BU-CY) conditioning regimen during allogeneic hematopoietic stem cell transplantation (HSCT) in children. Identifying children at high risk of developing HC in a HSCT setting could facilitate the evaluation and implementation of effective prophylactic measures. In this retrospective analysis genotyping of selected candidate gene variants was performed in 72 children and plasma Sulfolane (Su, water soluble metabolite of BU) levels were measured in 39 children following treatment with BU-CY regimen. The cytotoxic effects of Su and acrolein (Ac, water soluble metabolite of CY) were tested on human urothelial cells (HUCs). The effect of Su was also tested on cytochrome P 450 (CYP) function in HepaRG hepatic cells. Cumulative incidences of HC before day 30 post HSCT were estimated using Kaplan–Meier curves and log-rank test was used to compare the difference between groups in a univariate analysis. Multivariate Cox regression was used to estimate hazard ratios with 95% confidence intervals (CIs). Multivariate analysis included co-variables that were significantly associated with HC in a univariate analysis. Cumulative incidence of HC was 15.3%. In the univariate analysis, HC incidence was significantly (p < 0.05) higher in children older than 10 years (28.6 vs. 6.8%) or in children with higher Su levels (>40 vs. <11%) or in carriers of both functional GSTM1 and CYP2C9 (33.3 vs. 6.3%) compared to the other group. In a multivariate analysis, combined GSTM1 and CYP2C9 genotype status was associated with HC occurrence with a hazards ratio of 4.8 (95% CI: 1.3–18.4; p = 0.02). Ac was found to be toxic to HUC cells at lower concentrations (33 μM), Su was not toxic to HUC cells at concentrations below 1 mM and did not affect CYP function in HepaRG cells. Our observations suggest that pre-emptive genotyping of CYP2C9 and GSTM1 may aid in selection of more effective prophylaxis to reduce HC development in pediatric patients undergoing allogeneic HSCT. Article summary: (1) Children carrying functional alleles in GSTM1 and CYP2C9 are at high risk for developing hemorrhagic cystitis following treatment with busulfan and cyclophosphamide based conditioning regimen. (2) Identification of children at high risk for developing hemorrhagic cystitis in an allogeneic HSCT setting will enable us to evaluate and implement optimal strategies for its prevention. Trial registration: This study is a part of the trail “clinicaltrials.gov identifier: NCT01257854.” PMID:28744217

The Association of Combined GSTM1 and CYP2C9 Genotype Status with the Occurrence of Hemorrhagic Cystitis in Pediatric Patients Receiving Myeloablative Conditioning Regimen Prior to Allogeneic Hematopoietic Stem Cell Transplantation.

PubMed

Uppugunduri, Chakradhara Rao S; Storelli, Flavia; Mlakar, Vid; Huezo-Diaz Curtis, Patricia; Rezgui, Aziz; Théorêt, Yves; Marino, Denis; Doffey-Lazeyras, Fabienne; Chalandon, Yves; Bader, Peter; Daali, Youssef; Bittencourt, Henrique; Krajinovic, Maja; Ansari, Marc

2017-01-01

Hemorrhagic cystitis (HC) is one of the complications of busulfan-cyclophosphamide (BU-CY) conditioning regimen during allogeneic hematopoietic stem cell transplantation (HSCT) in children. Identifying children at high risk of developing HC in a HSCT setting could facilitate the evaluation and implementation of effective prophylactic measures. In this retrospective analysis genotyping of selected candidate gene variants was performed in 72 children and plasma Sulfolane (Su, water soluble metabolite of BU) levels were measured in 39 children following treatment with BU-CY regimen. The cytotoxic effects of Su and acrolein (Ac, water soluble metabolite of CY) were tested on human urothelial cells (HUCs). The effect of Su was also tested on cytochrome P 450 (CYP) function in HepaRG hepatic cells. Cumulative incidences of HC before day 30 post HSCT were estimated using Kaplan-Meier curves and log-rank test was used to compare the difference between groups in a univariate analysis. Multivariate Cox regression was used to estimate hazard ratios with 95% confidence intervals (CIs). Multivariate analysis included co-variables that were significantly associated with HC in a univariate analysis. Cumulative incidence of HC was 15.3%. In the univariate analysis, HC incidence was significantly ( p < 0.05) higher in children older than 10 years (28.6 vs. 6.8%) or in children with higher Su levels (>40 vs. <11%) or in carriers of both functional GSTM1 and CYP2C9 (33.3 vs. 6.3%) compared to the other group. In a multivariate analysis, combined GSTM1 and CYP2C9 genotype status was associated with HC occurrence with a hazards ratio of 4.8 (95% CI: 1.3-18.4; p = 0.02). Ac was found to be toxic to HUC cells at lower concentrations (33 μM), Su was not toxic to HUC cells at concentrations below 1 mM and did not affect CYP function in HepaRG cells. Our observations suggest that pre-emptive genotyping of CYP2C9 and GSTM1 may aid in selection of more effective prophylaxis to reduce HC development in pediatric patients undergoing allogeneic HSCT. Article summary : (1) Children carrying functional alleles in GSTM1 and CYP2C9 are at high risk for developing hemorrhagic cystitis following treatment with busulfan and cyclophosphamide based conditioning regimen. (2) Identification of children at high risk for developing hemorrhagic cystitis in an allogeneic HSCT setting will enable us to evaluate and implement optimal strategies for its prevention. Trial registration : This study is a part of the trail "clinicaltrials.gov identifier: NCT01257854."

Engine Technology Challenges for the High-Speed Civil Transport Plane

NASA Technical Reports Server (NTRS)

Plencner, Robert M.; Misra, Ajay; Graber, Edwin J., Jr.; Shaw, Robert J.; Seng, Gary T.

1998-01-01

Ongoing NASA-funded and privately funded studies continue to indicate that an opportunity exists for a second generation supersonic commercial airliner, or High-Speed Civil Transport (HSCT), to become a key part of the 21 st century international air transportation system. Long distance air travel is projected to be the fastest growing segment of the air transportation market by the turn of the century with increases at about 5 percent per annum over the next two decades. This projection suggests that by the year 2015, more than 600,000 passengers per day will be traveling long distances, predominantly over water. These routes would provide the greatest potential for an HSCT to become a significant part of the international air transportation system. The potential market for an HSCT is currently projected to be anywhere from 500-1500 aircraft over the 2005-2030 time period. Such an aircraft fleet size would represent a considerable share of the potential long-range aircraft market. However, this projected HSCT fleet can become a reality only if technologies are developed which will allow an HSCT design that is (1) environmentally compatible and (2) economically viable. Simply stated, the HSCT will be a technology driven airplane. Without significant advances in airframe and propulsion technologies over the levels currently available, there will be no second generation supersonic airliner! This paper will briefly describe the propulsion technology challenges which must be met prior to any product launch decision being made by industry and the progress toward meeting these challenges through NASAs High-Speed Research (HSR) Program, a partnership between NASA and Boeing, General Electric and Pratt & Whitney.

Development of tumor-reactive T cells after nonmyeloablative allogeneic hematopoietic stem cell transplant for chronic lymphocytic leukemia.

PubMed

Nishida, Tetsuya; Hudecek, Michael; Kostic, Ana; Bleakley, Marie; Warren, Edus H; Maloney, David; Storb, Rainer; Riddell, Stanley R

2009-07-15

Allogeneic nonmyeloablative hematopoietic stem cell transplant (NM-HSCT) can result in durable remission of chronic lymphocytic leukemia (CLL). It is thought that the efficacy of NM-HSCT is mediated by recognition of tumor cells by T cells in the donor stem cell graft. We evaluated the development of CTLs specific for CLL after NM-HSCT to determine if their presence correlated with antitumor efficacy. Peripheral blood mononuclear cells obtained from 12 transplant recipients at intervals after NM-HSCT were stimulated in vitro with CLL cells. Polyclonal T-cell lines and CD8(+) T-cell clones were derived from these cultures and evaluated for lysis of donor and recipient target cells including CLL. The presence and specificity of responses was correlated with clinical outcomes. Eight of the 12 patients achieved remission or a major antitumor response and all 8 developed CD8(+) and CD4(+) T cells specific for antigens expressed by CLL. A clonal analysis of the CD8(+) T-cell response identified T cells specific for multiple minor histocompatibility (H) antigens expressed on CLL in six of the responding patients. A significant fraction of the CD8(+) T-cell response in some patients was also directed against nonshared tumor-specific antigens. By contrast, CLL-reactive T cells were not detected in the four patients who had persistent CLL after NM-HSCT, despite the development of graft-versus-host disease. The development of a diverse T-cell response specific for minor H and tumor-associated antigens expressed by CLL predicts an effective graft-versus-leukemia response after NM-HSCT.

The Hematopoietic Stem Cell Therapy for Exploration of Space

NASA Technical Reports Server (NTRS)

Roach, Allana Nicole; Brezo, Jelena

2002-01-01

Astronauts experience severe/invasive disorders caused by space environments. These include hematological/cardiac abnormalities, bone and muscle losses, immunodeficiency, neurological disorders and cancer. While the cause of these symptoms are not yet fully delineated, one possible explanation could be the inhibition of hematopoietic stem cell (HSC) growth and hematopoiesis in space. HSCs differentiate into all types of blood cells, and growing evidence indicates that the HSCs also have the ability to transdifferentiate to various tissues, including muscle, skin, liver, neuronal cells and possibly bone. Therefore, a hypothesis was advanced in this laboratory that the hematopoietic stem cell-based therapy, herein called the hematopoietic stem cell therapy (HSCT), could mitigate some of the disorders described above. Due to the magnitude of this project our laboratory has subdivided it into 3 sections: a) HSCT for space anemia; b) HSCT for muscle and bone losses; and c) HSCT for immunodeficiency. Toward developing the HSCT protocol for space anemia, the HSC transplantation procedure was established using a mouse model of beta thalassemia. In addition, the NASA Rotating Wall Vessel (RWV) culture system was used to grow HSCs in space condition. To investigate the HSCT for muscle loss and bone loss, donor HSCs were genetically marked either by transfecting the beta-galactosidase-containing plasmid, pCMV.SPORT-beta-gal or by preparing from b-galactosidase transgenic mice. The transdifferentiation of HSCs to muscle is traced by the reporter gene expression in the hindlimb suspended mice with some positive outcome, as studied by the X-gal staining procedure. The possible structural contribution of HSCs against muscle loss is being investigated histochemically.

Longitudinal Analysis of the Relationships Between Social Support and Health-Related Quality of Life in Hematopoietic Stem Cell Transplant Recipients.

PubMed

Liang, Yongchun; Wang, Haifang; Niu, Meie; Zhu, Xiaming; Cai, Jianzheng; Wang, Xiubei

2018-06-22

The correlation between social support and health-related quality of life (HRQOL) has been well documented, but whether social support changes or whether social support consistently plays a significant role in the various phases of the treatment process remains unknown among hematopoietic stem cell transplantation (HSCT) patients. The aims of this study were to assess the changing trends of HRQOL and social support and evaluate the relationship between HRQOL and social support before and after transplantation. Measures were completed by 122 HSCT patients before and after transplantation. The measures administered included the Perceived Social Support Scale and the Functional Assessment of Cancer Therapy-Bone Marrow Transplant questionnaire. The social support score presented a marked downward trend (F = 17.090, P < .001). The overall HRQOL was the lowest, 103.61 (SD, 19.14) at 1 month and increased steadily over time to 108.10 (SD, 19.58) at 3 months and 110.02 (SD, 18.00) at 6 months after HSCT. The generalized estimating equation models showed that social support consistently had a positive impact on HRQOL in the 6-month period post-HSCT. We confirmed a significant positive association between social support and HRQOL in HSCT recipients. However, it is noteworthy that the social support score declined during the 6-month period even while the HRQOL scores were increasing. Social support is closely related to the HRQOL; thus, clinicians should give close attention to social support to improve the HRQOL of HSCT patients. Social support should not be overlooked during the first 6 months after transplantation.

U.S. Supersonic Commercial Aircraft: Assessing NASA's High Speed Research Program

NASA Technical Reports Server (NTRS)

1997-01-01

The legislatively mandated objectives of the National Aeronautics and Space Administration (NASA) include "the improvement of the usefulness, performance, speed, safety, and efficiency of aeronautical and space vehicles" and "preservation of the United States' preeminent position in aeronautics and space through research and technology development related to associated manufacturing processes." Most of NASA's activities are focused on the space-related aspects of these objectives. However, NASA also conducts important work related to aeronautics. NASA's High Speed Research (HSR) Program is a focused technology development program intended to enable the commercial development of a high speed (i.e., supersonic) civil transport (HSCT). However, the HSR Program will not design or test a commercial airplane (i.e., an HSCT); it is industry's responsibility to use the results of the HSR Program to develop an HSCT. An HSCT would be a second generation aircraft with much better performance than first generation supersonic transports (i.e., the Concorde and the Soviet Tu-144). The HSR Program is a high risk effort: success requires overcoming many challenging technical problems involving the airframe, propulsion system, and integrated aircraft. The ability to overcome all of these problems to produce an affordable HSCT is far from certain. Phase I of the HSR Program was completed in fiscal year 1995; it produced critical information about the ability of an HSCT to satisfy environmental concerns (i-e., noise and engine emissions). Phase II (the final phase according to current plans) is scheduled for completion in 2002. Areas of primary emphasis are propulsion, airframe materials and structures, flight deck systems, aerodynamic performance, and systems integration.

T cells for viral infections after allogeneic hematopoietic stem cell transplant

PubMed Central

Heslop, Helen E.

2016-01-01

Despite recent advances in the field of allogeneic hematopoietic stem cell transplantation (HSCT), viral infections are still a major complication during the period of immune suppression that follows the procedure. Adoptive transfer of donor-derived virus-specific cytotoxic T cells (VSTs) is a strategy to rapidly restore virus-specific immunity to prevent or treat viral diseases after HSCT. Early proof of principle studies demonstrated that the administration of donor-derived T cells specific for cytomegalovirus or Epstein-Barr virus (EBV) could effectively restore virus-specific immunity and control viral infections. Subsequent studies using different expansion or direct selection techniques have shown that donor-derived VSTs confer protection in vivo after adoptive transfer in 70% to 90% of recipients. Because a major cause of failure is lack of immunity to the infecting virus in a naïve donor, more recent studies have infused closely matched third-party VSTs and reported response rates of 60% to 70%. Current efforts have focused on broadening the applicability of this approach by: (1) extending the number of viral antigens being targeted, (2) simplifying manufacture, (3) exploring strategies for recipients of virus-naïve donor grafts, and (4) developing and optimizing “off the shelf” approaches. PMID:27207801

Third-line treatment with second-generation tyrosine kinase inhibitors (dasatinib or nilotinib) in patients with chronic myeloid leukemia after two prior TKIs: real-life data on a single center experience along with the review of the literature.

PubMed

Ongoren, Seniz; Eskazan, Ahmet Emre; Suzan, Veysel; Savci, Sercan; Erdogan Ozunal, Isil; Berk, Selin; Yalniz, Fevzi Fırat; Elverdi, Tugrul; Salihoglu, Ayse; Erbilgin, Yucel; Iseri, Sibel Aylin; Ar, Muhlis Cem; Baslar, Zafer; Aydin, Yildiz; Tuzuner, Nukhet; Ozbek, Ugur; Soysal, Teoman

2018-05-01

Newer tyrosine kinase inhibitors (TKIs) (bosutinib, ponatinib) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be utilized as a salvage therapy in patients with chronic myeloid leukemia (CML) who failed two lines (imatinib → nilotinib or imatinib → dasatinib) of TKI therapy. However, these TKIs are not available in many countries and not all patients can undergo allo-HSCT. In this study, CML patients who received dasatinib or nilotinib as a third-line treatment were retrospectively evaluated. Out of 209 patients, third-line dasatinib/nilotinib was administered in 21. During the follow-up, 16 out of 21 patients gained and/or maintained an optimal response, and 4 patients died due to progression. Seventeen patients were alive at the time of the analysis, of which 13 were still on TKI, whereas 4 patients quit treatment. In patients failing two lines of TKI, dasatinib or nilotinib can be beneficial and safely administered as a third-line treatment especially in nations with restricted resources.

Adoptive immunotherapy for B-cell malignancies with autologous chimeric antigen receptor modified tumor targeted T cells.

PubMed

Park, Jae H; Brentjens, Renier J

2010-04-01

Chemotherapy-resistant B-cell hematologic malignancies may be cured with allogeneic hematopoietic stem cell transplantation (HSCT), demonstrating the potential susceptibility of these tumors to donor T-cell mediated immune responses. However, high rates of transplant-related morbidity and mortality limit this approach. For this reason, there is an urgent need for less-toxic forms of immune-based cellular therapy to treat these malignancies. Adoptive transfer of autologous T cells genetically modified to express chimeric antigen receptors (CARs) targeted to specific tumor-associated antigens represents an attractive means of overcoming the limitations of conventional HSCT. To this end, investigators have generated CARs targeted to various antigens expressed by B-cell malignancies, optimized the design of these CARs to enhance receptor mediated T cell signaling, and demonstrated significant anti-tumor efficacy of the resulting CAR modified T cells both in vitro and in vivo mouse tumor models. These encouraging preclinical data have justified the translation of this approach to the clinical setting with currently 12 open clinical trials and one completed clinical trial treating various B-cell malignancies utilizing CAR modified T cells targeted to either the CD19 or CD20 B-cell specific antigens.

Risk factors for cytomegalovirus retinitis in patients with cytomegalovirus viremia after hematopoietic stem cell transplantation.

PubMed

Jeon, Sohee; Lee, Won Ki; Lee, Yongeun; Lee, Dong Gun; Lee, Jong Wook

2012-09-01

To evaluate the risk factors for cytomegalovirus (CMV) retinitis in patients with CMV viremia after hematopoietic stem cell transplantation (HSCT). Retrospective cohort study. We included all patients with CMV viremia detected by polymerase chain reaction after HSCT between April 2009 and August 2011. Risk factors for CMV retinitis were evaluated in the cohort of 270 patients with CMV viremia, who survived ≥ 12 weeks after HSCT and were screened for CMV retinitis. Retrospective review of clinical records and laboratory results. Survival analysis of patients in the cohort and frequency of CMV retinitis in relation to various factors. Variables analyzed were demographics, human leukocyte antigen (HLA) matched versus mismatched, related versus unrelated donor, preconditioning regimens, delayed engraftment of lymphocyte, presence of acute or chronic graft-versus-host disease, highest CMV DNA level in blood (copies/ml), cumulative period of CMV viremia (weeks), and CMV infection verified by culture or immunohistology in bronchoalveolar lavage or visceral biopsy specimens. Of the 708 patients who underwent HSCT during the study period, 363 (51%) developed CMV viremia after HSCT. Of the 363 patients with CMV viremia, 270 underwent retinal examination for CMV retinitis. We detected CMV retinitis in 15 of 270 patients with CMV viremia. In the univariate analysis, HLA-mismatched HSCT, HSCT from an unrelated donor, engraftment day, peak CMV DNA level, and duration of viremia were associated with the development of CMV retinitis. In the adjusted multivariate analysis, only peak CMV DNA blood levels predicted the development of CMV retinitis (hazard ratio, 25.0; 95% confidence interval, 3.0-210.8). An additional validity analysis by receiver operating characteristic area under curve suggested that a cutoff of 7.64 × 10(4) copies/mL best predicted the development of CMV retinitis by CMV DNA levels in blood. The development of CMV retinitis should be carefully monitored in patients with a significant viral load, which is represented by a peak CMV DNA level >7.64 × 10(4) copies/ml and a long duration of CMV viremia, especially when patients received HSCT from an unrelated or HLA-mismatched donor and showed delayed lymphocyte engraftment. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Multi-Objective Hybrid Optimal Control for Multiple-Flyby Interplanetary Mission Design Using Chemical Propulsion

NASA Technical Reports Server (NTRS)

Englander, Jacob; Vavrina, Matthew

2015-01-01

The customer (scientist or project manager) most often does not want just one point solution to the mission design problem Instead, an exploration of a multi-objective trade space is required. For a typical main-belt asteroid mission the customer might wish to see the trade-space of: Launch date vs. Flight time vs. Deliverable mass, while varying the destination asteroid, planetary flybys, launch year, etcetera. To address this question we use a multi-objective discrete outer-loop which defines many single objective real-valued inner-loop problems.

CFD research, parallel computation and aerodynamic optimization

NASA Technical Reports Server (NTRS)

Ryan, James S.

1995-01-01

Over five years of research in Computational Fluid Dynamics and its applications are covered in this report. Using CFD as an established tool, aerodynamic optimization on parallel architectures is explored. The objective of this work is to provide better tools to vehicle designers. Submarine design requires accurate force and moment calculations in flow with thick boundary layers and large separated vortices. Low noise production is critical, so flow into the propulsor region must be predicted accurately. The High Speed Civil Transport (HSCT) has been the subject of recent work. This vehicle is to be a passenger vehicle with the capability of cutting overseas flight times by more than half. A successful design must surpass the performance of comparable planes. Fuel economy, other operational costs, environmental impact, and range must all be improved substantially. For all these reasons, improved design tools are required, and these tools must eventually integrate optimization, external aerodynamics, propulsion, structures, heat transfer and other disciplines.

Randomized Clinical Trial of Therapeutic Music Video Intervention for Resilience Outcomes in Adolescents/Young Adults Undergoing Hematopoietic Stem Cell Transplant: A Report from the Children’s Oncology Group

PubMed Central

Robb, Sheri L.; Burns, Debra S.; Stegenga, Kristin A.; Haut, Paul R.; Monahan, Patrick O.; Meza, Jane; Stump, Timothy E.; Cherven, Brooke O.; Docherty, Sharron L.; Hendricks-Ferguson, Verna L.; Kintner, Eileen K.; Haight, Ann E.; Wall, Donna A.; Haase, Joan E.

2013-01-01

Background To reduce the risk of adjustment problems associated with Hematopoietic Stem Cell Transplant (HSCT) for adolescents/young adults (AYA), we examined efficacy of a therapeutic music video (TMV) intervention delivered during the acute phase of HSCT to: (a) increase protective factors of spiritual perspective, social integration, family environment, courageous coping, and hope-derived meaning; (b) decrease risk factors of illness-related distress and defensive coping; and (c) increase outcomes of self-transcendence and resilience. Methods A multi-site, randomized controlled trial (COG-ANUR0631) conducted at 8 Children’s Oncology Group sites involving 113 AYA aged 11–24 years undergoing myeloablative HSCT. Participants, randomized to the TMV or low-dose control (audiobooks) group, completed 6 sessions over 3 weeks with a board-certified music therapist. Variables were based on Haase’s Resilience in Illness Model. Participants completed measures related to latent variables of illness-related distress, social integration, spiritual perspective, family environment, coping, hope-derived meaning and resilience at baseline (T1), post-intervention (T2), and 100-days post-transplant (T3). Results At T2, the TMV group reported significantly better courageous coping (ES=0.505; P=0.030). At T3, the TMV group reported significantly better social integration (ES=0.543; P=.028) and family environment (ES=0.663; P=0.008), as well as moderate non-significant effect sizes for spiritual perspective (E=0.450; P=0.071) and self-transcendence (ES=0.424; P=0.088). Conclusion The TMV intervention improves positive health outcomes of courageous coping, social integration, and family environment during a high risk cancer treatment. We recommend the TMV be examined in a broader population of AYA with high risk cancers. PMID:24469862

Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients with Myelodysplastic Syndrome Harboring Trisomy 8.

PubMed

Konuma, Takaaki; Miyazaki, Yasushi; Uchida, Naoyuki; Ohashi, Kazuteru; Kondo, Tadakazu; Nakamae, Hirohisa; Takahashi, Satoshi; Mori, Takehiko; Ozawa, Yukiyasu; Kato, Chiaki; Iwato, Koji; Fukuda, Takahiro; Ichinohe, Tatsuo; Atsuta, Yoshiko; Ishiyama, Ken

2017-01-01

Trisomy 8 (+8) is 1 of the most common cytogenetic abnormalities in adult patients with myelodysplastic syndrome (MDS). However, the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) in adult patients with MDS harboring +8 remains unclear. To evaluate the outcome and prognostic factors in patients with MDS harboring +8 as the sole cytogenetic abnormality or in association with other abnormalities, we retrospectively analyzed the Japanese registration data of 381 adult patients with MDS harboring +8 treated with allogeneic HSCT between 1990 and 2013. With a median follow-up period of 53 months, the probability of overall survival and cumulative incidence of relapse at 4 years were 51% and 22%, respectively. In the multivariate analysis, age > 50 years, 2 or more additional cytogenetic abnormalities, and a high risk at the time of HSCT according to the FAB/WHO classification were significantly associated with a higher overall mortality. Nevertheless, no significant impact of the outcome was observed in patients with 1 cytogenetic abnormality in addition to +8. Although 221 patients (58%) had advanced MDS at the time of HSCT, allogeneic HSCT offered a curative option for adult patients with MDS harboring +8. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

A systematic review of acute kidney injury in pediatric allogeneic hematopoietic stem cell recipients.

PubMed

Didsbury, Madeleine S; Mackie, Fiona E; Kennedy, Sean E

2015-08-01

The process of allogeneic HSCT in children is associated with frequent AKI and mortality, but the epidemiology is not widely reported. The aim of this review was to summarize the available evidence on incidence, risk factors, timing, and prognosis of AKI in children following HSCT. We systematically reviewed all observational studies reporting incidence and outcomes of AKI in pediatric allogenic HSCT recipients. The minimum criteria for AKI were defined as an increase in sCr ≥ x1.5 or urine output ≤0.5 mL/kg/min over six h. Medline and Embase were searched until March 2014. From 993 electronic records, five were eligible for inclusion (n = 571 patients). The average incidence of AKI within the first 100 days following HSCT was 21.7% (range 11-42%), and the average time of onset was 4-6 wk post-transplant. Risk factors for AKI included cyclosporine toxicity, amphotericin B and foscarnet, SOS, and having a mismatched donor. There were conflicting reports on whether AKI was associated with the development of CKD. AKI is a common and potentially life-threatening complication following HSCT in children. Further quality observational studies are needed to accurately determine the epidemiology and prognosis of AKI in this population. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

High-Speed Civil Transport Forecast: Simulated Airlines Scenarios for Mach 1.6, Mach 2.0, and Mach 2.4 Configurations for Year 2015

NASA Technical Reports Server (NTRS)

Metwally, Munir

1996-01-01

The report describes the development of a database of fuel burn and emissions from projected High Speed Civil Transport (HSCT) fleets that reflect actual airlines' networks, operational requirement, and traffic flow as operated by simulated world wide airlines for Mach 1.6, 2.0, and 2.4 HSCT configurations. For the year 2015, McDonnell Douglas Corporation created two supersonic commercial air traffic networks consisting of origin-destination city pair routes and associated traffic levels. The first scenario represented a manufacturing upper limit producible HSCT fleet availability by year 2015. The fleet projection of the Mach 2.4 configuration for this scenario was 1059 units with a traffic capture of 70 percent. The second scenario focused on the number of units that can minimally be produced by the year 2015. Using realistic production rates, the HSCT fleet projection amounts to 565 units. The traffic capture associated with this fleet was estimated at 40 percent. The airlines network was extracted from the actual networks of 21 major world airlines. All the routes were screened for suitability for HSCT operations. The route selection criteria included great circle distance, difference between flight path distance and great circle distance to avoid overland operations, and potential flight frequency.

Maintaining high autopsy rates in a Canadian blood and marrow transplant program: preserving a diagnostic and research tool.

PubMed

Allan, D S; Bélanger, R; Busque, L; Cohen, S; Fish, D; Roy, D C; Roy, J

2005-04-01

Autopsy series have revealed patterns of injury in graft-versus-host disease and provided insight into infectious and toxic complications following hematopoietic stem cell transplantation (HSCT). Overall autopsy rates have declined significantly in recent decades including specialized services such as neonatal medicine and cardiac care. However, rates of post-mortem exams at HSCT centers have not been specifically documented. We reviewed hospital records between 1992 and 2002 to determine overall autopsy rates at our hospital and within the HSCT program. Although the overall autopsy rate declined steadily from 24% in 1992 to 9% in 2002, rates of post-mortem exams in the HSCT program remained relatively stable at 32% (24-46%). Autopsy rates were not significantly different for recipients of allogeneic vs autologous transplants and no clear difference was observed for the proportion of autopsies requested on weekdays compared with weekends. Autopsies confirmed major clinical diagnoses and/or suspected causes of death in 45 of 61 autopsies (74%) and yielded major or minor disagreements in clinical diagnosis in 10 cases (16%) and seven cases (11%), respectively. The preservation of high rates of autopsy within our HSCT program demonstrates that specialized programs are able to maintain elevated rates of post-mortem examinations despite overall declining rates.

Bone density and structure in long-term survivors of pediatric allogeneic hematopoietic stem cell transplantation.

PubMed

Mostoufi-Moab, Sogol; Ginsberg, Jill P; Bunin, Nancy; Zemel, Babette; Shults, Justine; Leonard, Mary B

2012-04-01

Children requiring allogeneic hematopoietic stem cell transplantation (alloHSCT) have multiple risk factors for impaired bone accrual. The impact of alloHSCT on volumetric bone mineral density (vBMD) and cortical structure has not been addressed. Tibia peripheral quantitative computed tomography (pQCT) scans were obtained in 55 alloHSCT recipients, ages 5 to 26 years, a median of 7 (range, 3-16) years after alloHSCT. pQCT outcomes were converted to sex- and race- specific Z-scores relative to age based on reference data in >700 concurrent healthy participants. Cortical section modulus (Zp; a summary measure of cortical bone structure and strength), and muscle and fat area Z-scores were further adjusted for tibia length for age Z-scores. AlloHSCT survivors had lower height Z-scores (-1.21 ± 1.25 versus 0.23 ± 0.92; p < 0.001), versus reference participants; BMI Z-scores did not differ. AlloHSCT survivors had lower trabecular vBMD (-1.05; 95% confidence interval [CI], -1.33 to -0.78; p < 0.001), cortical Zp (-0.63; 95% CI, -0.91 to -0.35; p < 0.001), and muscle (-1.01; 95% CI, -1.30 to -0.72; p < 0.001) Z-scores and greater fat (0.82; 95% CI, 0.54-1.11; p < 0.001) Z-scores, versus reference participants. Adjustment for muscle deficits eliminated Zp deficits in alloHSCT. Total body irradiation (TBI) was associated with lower trabecular vBMD (-1.30 ± 1.40 versus -0.49 ± 0.88; p = 0.01) and muscle (-1.34 ± 1.42 versus -0.34 ± 0.87; p < 0.01) Z-scores. Growth hormone deficiency (GHD) was associated with lower Zp Z-scores (-1.64 ± 2.47 versus -0.28 ± 1.24; p = 0.05); however, muscle differences were not significant (-1.69 ± 1.84 versus -0.78 ± 1.01; p = 0.09). History of graft versus host disease was not associated with pQCT outcomes. In summary, alloHSCT was associated with significant deficits in trabecular vBMD, cortical geometry, and muscle area years after transplantation. TBI and GHD were significant risk factors for musculoskeletal deficits. Future studies are needed to determine the metabolic and fracture implications of these deficits, and to identify therapies to improve bone accrual following alloHSCT during childhood. Copyright © 2012 American Society for Bone and Mineral Research.

Robust design of multiple trailing edge flaps for helicopter vibration reduction: A multi-objective bat algorithm approach

NASA Astrophysics Data System (ADS)

Mallick, Rajnish; Ganguli, Ranjan; Seetharama Bhat, M.

2015-09-01

The objective of this study is to determine an optimal trailing edge flap configuration and flap location to achieve minimum hub vibration levels and flap actuation power simultaneously. An aeroelastic analysis of a soft in-plane four-bladed rotor is performed in conjunction with optimal control. A second-order polynomial response surface based on an orthogonal array (OA) with 3-level design describes both the objectives adequately. Two new orthogonal arrays called MGB2P-OA and MGB4P-OA are proposed to generate nonlinear response surfaces with all interaction terms for two and four parameters, respectively. A multi-objective bat algorithm (MOBA) approach is used to obtain the optimal design point for the mutually conflicting objectives. MOBA is a recently developed nature-inspired metaheuristic optimization algorithm that is based on the echolocation behaviour of bats. It is found that MOBA inspired Pareto optimal trailing edge flap design reduces vibration levels by 73% and flap actuation power by 27% in comparison with the baseline design.

Multi-objective optimization of chromatographic rare earth element separation.

PubMed

Knutson, Hans-Kristian; Holmqvist, Anders; Nilsson, Bernt

2015-10-16

The importance of rare earth elements in modern technological industry grows, and as a result the interest for developing separation processes increases. This work is a part of developing chromatography as a rare earth element processing method. Process optimization is an important step in process development, and there are several competing objectives that need to be considered in a chromatographic separation process. Most studies are limited to evaluating the two competing objectives productivity and yield, and studies of scenarios with tri-objective optimizations are scarce. Tri-objective optimizations are much needed when evaluating the chromatographic separation of rare earth elements due to the importance of product pool concentration along with productivity and yield as process objectives. In this work, a multi-objective optimization strategy considering productivity, yield and pool concentration is proposed. This was carried out in the frame of a model based optimization study on a batch chromatography separation of the rare earth elements samarium, europium and gadolinium. The findings from the multi-objective optimization were used to provide with a general strategy for achieving desirable operation points, resulting in a productivity ranging between 0.61 and 0.75 kgEu/mcolumn(3), h(-1) and a pool concentration between 0.52 and 0.79 kgEu/m(3), while maintaining a purity above 99% and never falling below an 80% yield for the main target component europium. Copyright © 2015 Elsevier B.V. All rights reserved.

Piston Bowl Optimization for RCCI Combustion in a Light-Duty Multi-Cylinder Engine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hanson, Reed M; Curran, Scott; Wagner, Robert M

2012-01-01

Reactivity Controlled Compression Ignition (RCCI) is an engine combustion strategy that that produces low NO{sub x} and PM emissions with high thermal efficiency. Previous RCCI research has been investigated in single-cylinder heavy-duty engines. The current study investigates RCCI operation in a light-duty multi-cylinder engine at 3 operating points. These operating points were chosen to cover a range of conditions seen in the US EPA light-duty FTP test. The operating points were chosen by the Ad Hoc working group to simulate operation in the FTP test. The fueling strategy for the engine experiments consisted of in-cylinder fuel blending using port fuel-injectionmore » (PFI) of gasoline and early-cycle, direct-injection (DI) of diesel fuel. At these 3 points, the stock engine configuration is compared to operation with both the original equipment manufacturer (OEM) and custom machined pistons designed for RCCI operation. The pistons were designed with assistance from the KIVA 3V computational fluid dynamics (CFD) code. By using a genetic algorithm optimization, in conjunction with KIVA, the piston bowl profile was optimized for dedicated RCCI operation to reduce unburned fuel emissions and piston bowl surface area. By reducing these parameters, the thermal efficiency of the engine was improved while maintaining low NOx and PM emissions. Results show that with the new piston bowl profile and an optimized injection schedule, RCCI brake thermal efficiency was increased from 37%, with the stock EURO IV configuration, to 40% at the 2,600 rev/min, 6.9 bar BMEP condition, and NOx and PM emissions targets were met without the need for exhaust after-treatment.« less

A Performance Assessment of Eight Low-Boom High-Speed Civil Transport Concepts

NASA Technical Reports Server (NTRS)

Baize, Daniel G.; McElroy, Marcus O.; Fenbert, James A.; Coen, Peter G.; Ozoroski, Lori P.; Domack, Chris S.; Needleman, Kathy E.; Geiselhart, Karl A.

1999-01-01

A performance assessment of eight low-boom high speed civil transport (HSCT) configurations and a reference HSCT configuration has been performed. Although each of the configurations was designed with different engine concepts, for consistency, a year 2005 technology, 0.4 bypass ratio mixed-flow turbofan (MFTF) engine was used for all of the performance assessments. Therefore, all original configuration nacelles were replaced by a year 2005 MFRF nacelle design which corresponds to the engine deck utilized. The engine thrust level was optimized to minimize vehicle takeoff gross weight. To preserve the configuration's sonic-boom shaping, wing area was not optimized or altered from its original design value. Performance sizings were completed when possible for takeoff balanced field lengths of 11,000 ft and 12,000 ft, not considering FAR Part 36 Stage III noise compliance. Additionally, an arbitrary sizing with thrust-to-weight ratio equal to 0.25 was performed, enabling performance levels to be compared independent of takeoff characteristics. The low-boom configurations analyzed included designs from the Boeing Commercial Airplane Group, Douglas Aircraft Company, Ames Research Center, and Langley Research Center. This paper discusses the technology level assumptions, mission profile, analysis methodologies, and the results of the assessment. The results include maximum lift-to-drag ratios, total fuel consumption, number of passengers, optimum engine sizing plots, takeoff performance, mission block time, and takeoff gross weight for all configurations. Results from the low-boom configurations are also compared with a non-low-boom reference configuration. Configuration dependent advantages or deficiencies are discussed as warranted.

Different Procoagulant Activity of Therapeutic Mesenchymal Stromal Cells Derived from Bone Marrow and Placental Decidua.

PubMed

Moll, Guido; Ignatowicz, Lech; Catar, Rusan; Luecht, Christian; Sadeghi, Behnam; Hamad, Osama; Jungebluth, Philipp; Dragun, Duska; Schmidtchen, Artur; Ringdén, Olle

2015-10-01

While therapeutic mesenchymal stromal/stem cells (MSCs) have usually been obtained from bone marrow, perinatal tissues have emerged as promising new sources of cells for stromal cell therapy. In this study, we present a first safety follow-up on our clinical experience with placenta-derived decidual stromal cells (DSCs), used as supportive immunomodulatory and regenerative therapy for patients with severe complications after allogeneic hematopoietic stem cell transplantation (HSCT). We found that DSCs are smaller, almost half the volume of MSCs, which may favor microvascular passage. DSCs also show different hemocompatibility, with increased triggering of the clotting cascade after exposure to human blood and plasma in vitro. After infusion of DSCs in HSCT patients, we observed a weak activation of the fibrinolytic system, but the other blood activation markers remained stable, excluding major adverse events. Expression profiling identified differential levels of key factors implicated in regulation of hemostasis, such as a lack of prostacyclin synthase and increased tissue factor expression in DSCs, suggesting that these cells have intrinsic blood-activating properties. The stronger triggering of the clotting cascade by DSCs could be antagonized by optimizing the cell graft reconstitution before infusion, for example, by use of low-dose heparin anticoagulant in the cell infusion buffer. We conclude that DSCs are smaller and have stronger hemostatic properties than MSCs, thus triggering stronger activation of the clotting system, which can be antagonized by optimizing the cell graft preparation before infusion. Our results highlight the importance of hemocompatibility safety testing for every novel cell therapy product before clinical use, when applied using systemic delivery.

A risk-based multi-objective model for optimal placement of sensors in water distribution system

NASA Astrophysics Data System (ADS)

Naserizade, Sareh S.; Nikoo, Mohammad Reza; Montaseri, Hossein

2018-02-01

In this study, a new stochastic model based on Conditional Value at Risk (CVaR) and multi-objective optimization methods is developed for optimal placement of sensors in water distribution system (WDS). This model determines minimization of risk which is caused by simultaneous multi-point contamination injection in WDS using CVaR approach. The CVaR considers uncertainties of contamination injection in the form of probability distribution function and calculates low-probability extreme events. In this approach, extreme losses occur at tail of the losses distribution function. Four-objective optimization model based on NSGA-II algorithm is developed to minimize losses of contamination injection (through CVaR of affected population and detection time) and also minimize the two other main criteria of optimal placement of sensors including probability of undetected events and cost. Finally, to determine the best solution, Preference Ranking Organization METHod for Enrichment Evaluation (PROMETHEE), as a subgroup of Multi Criteria Decision Making (MCDM) approach, is utilized to rank the alternatives on the trade-off curve among objective functions. Also, sensitivity analysis is done to investigate the importance of each criterion on PROMETHEE results considering three relative weighting scenarios. The effectiveness of the proposed methodology is examined through applying it to Lamerd WDS in the southwestern part of Iran. The PROMETHEE suggests 6 sensors with suitable distribution that approximately cover all regions of WDS. Optimal values related to CVaR of affected population and detection time as well as probability of undetected events for the best optimal solution are equal to 17,055 persons, 31 mins and 0.045%, respectively. The obtained results of the proposed methodology in Lamerd WDS show applicability of CVaR-based multi-objective simulation-optimization model for incorporating the main uncertainties of contamination injection in order to evaluate extreme value of losses in WDS.

Methods, systems and apparatus for optimization of third harmonic current injection in a multi-phase machine

DOEpatents

Gallegos-Lopez, Gabriel

2012-10-02

Methods, system and apparatus are provided for increasing voltage utilization in a five-phase vector controlled machine drive system that employs third harmonic current injection to increase torque and power output by a five-phase machine. To do so, a fundamental current angle of a fundamental current vector is optimized for each particular torque-speed of operating point of the five-phase machine.

SOP: parallel surrogate global optimization with Pareto center selection for computationally expensive single objective problems

DOE PAGES

Krityakierne, Tipaluck; Akhtar, Taimoor; Shoemaker, Christine A.

2016-02-02

This paper presents a parallel surrogate-based global optimization method for computationally expensive objective functions that is more effective for larger numbers of processors. To reach this goal, we integrated concepts from multi-objective optimization and tabu search into, single objective, surrogate optimization. Our proposed derivative-free algorithm, called SOP, uses non-dominated sorting of points for which the expensive function has been previously evaluated. The two objectives are the expensive function value of the point and the minimum distance of the point to previously evaluated points. Based on the results of non-dominated sorting, P points from the sorted fronts are selected as centersmore » from which many candidate points are generated by random perturbations. Based on surrogate approximation, the best candidate point is subsequently selected for expensive evaluation for each of the P centers, with simultaneous computation on P processors. Centers that previously did not generate good solutions are tabu with a given tenure. We show almost sure convergence of this algorithm under some conditions. The performance of SOP is compared with two RBF based methods. The test results show that SOP is an efficient method that can reduce time required to find a good near optimal solution. In a number of cases the efficiency of SOP is so good that SOP with 8 processors found an accurate answer in less wall-clock time than the other algorithms did with 32 processors.« less

Physical and psychosocial aspects of adolescent and young adults after allogeneic hematopoietic stem-cell transplantation: results from a prospective multicenter trial.

PubMed

Pulewka, Kristin; Wolff, Daniel; Herzberg, Philipp Y; Greinix, Hildegard; Heussner, Pia; Mumm, Friederike H A; von Harsdorf, Stephanie; Rieger, Kathrin; Hemmati, Philipp; Hochhaus, Andreas; Hilgendorf, Inken

2017-08-01

Allogeneic hematopoietic stem-cell transplantation (alloHSCT) is physically and psychosocially demanding. Among transplant recipients, adolescent and young adults (AYA) represent a special group, as disease occurs early in life, resulting in the prospect of long survival time and high burden of alloHSCT sequelae. However, data focusing on AYA undergoing alloHSCT are rare. Data resulting from a prospective multicenter trial initially focusing on graft-versus-host disease (GvHD) after alloHSCT were reused to analyse the differences between AYA and elderly patients. In total, data of 205 alloHSCT recipients were evaluated. Patients completed the FACT-BMT, HAP, SF-36, 24-AM, LOT-R, BSSS, HADS, and GvHD questionnaires. Median age of AYA and non-AYA patients was 29 and 52 years. Using 24-AM-Test, evaluating personality traits, non-AYA reported to be more conscientious (p = 0.033). However, AYA described higher quality of life regarding physical role functioning (p = 0.001), physical functioning (p = 0.002), bodily pain (p = 0.023), and emotional role function (p = 0.027) in the SF-36. General health perception, vitality, social role functioning, and mental health were comparable among both groups. On HAP scale, AYA reported higher maximum (p = 0.003) and adjusted activity scores (p = 0.002), but showed similar restrictions regarding activity, self-supply, and self-determination. AYA represent a particular group characterized by higher physical well-being and activity scores, and significantly vary from non-AYA patients in psychosocial aspects. Studies covering distinctive features of AYA undergoing alloHSCT are warranted to improve awareness of the special needs of this group.

Cytomegalovirus Retinitis in Pediatric Stem Cell Transplants: Report of a Recent Cluster and the Development of a Screening Protocol.

PubMed

Larochelle, Marissa B; Phan, Ryan; Craddock, John; Abzug, Mark J; Curtis, Donna; Robinson, Christine C; Giller, Roger H; Cosgrove, Shaun; Siringo, Frank; McCourt, Emily; Palestine, Alan G

2017-03-01

The incidence of cytomegalovirus (CMV) retinitis in the pediatric allogeneic hematopoietic stem cell transplant (HSCT) population is unknown. We report a cluster of 5 pediatric patients with CMV retinitis diagnosed in a 12-month period and compare this to the rate of CMV viremia and retinitis in the 4 years prior. Presented is the ophthalmic screening protocol developed in response to this experience. Retrospective cross-sectional study. A retrospective chart review was performed on patients at Children's Hospital of Colorado (CHCO) who received allogeneic HSCT between January 2010 and December 2014. Fisher exact test was used to compare the proportion of CMV viremia and CMV retinitis in patients transplanted between January 2010 and December 2013 with those transplanted in 2014. A total of 101 patients underwent allogeneic HSCT from January 2010 to December 2013; 32 (32%) tested positive for CMV viremia. No cases of CMV retinitis were identified. From January 2014 to December 2014, 28 patients underwent allogeneic HSCT; 13 patients (46%) had CMV viremia, not a statistically significant increase (P = .18). There were 5 cases of CMV retinitis diagnosed in those transplanted in 2014, a statistically significant increase compared with those transplanted in 2010-2013 (P = .0004). A multidisciplinary team was formed to review the literature and an ophthalmic screening protocol was developed. Our recent cluster of CMV retinitis in pediatric allogeneic HSCT patients may suggest a rise in incidence of CMV retinitis. We propose an ophthalmic screening protocol to diagnose retinitis in pediatric HSCT patients in the early, often asymptomatic stage. Copyright © 2016 Elsevier Inc. All rights reserved.

Immune Reconstitution After Autologous Hematopoietic Stem Cell Transplantation in Crohn’s Disease: Current Status and Future Directions. A Review on Behalf of the EBMT Autoimmune Diseases Working Party and the Autologous Stem Cell Transplantation In Refractory CD—Low Intensity Therapy Evaluation Study Investigators

PubMed Central

Pockley, Alan Graham; Lindsay, James O.; Foulds, Gemma A.; Rutella, Sergio; Gribben, John G.; Alexander, Tobias; Snowden, John A.

2018-01-01

Patients with treatment refractory Crohn’s disease (CD) suffer debilitating symptoms, poor quality of life, and reduced work productivity. Surgery to resect inflamed and fibrotic intestine may mandate creation of a stoma and is often declined by patients. Such patients continue to be exposed to medical therapy that is ineffective, often expensive and still associated with a burden of adverse effects. Over the last two decades, autologous hematopoietic stem cell transplantation (auto-HSCT) has emerged as a promising treatment option for patients with severe autoimmune diseases (ADs). Mechanistic studies have provided proof of concept that auto-HSCT can restore immunological tolerance in chronic autoimmunity via the eradication of pathological immune responses and a profound reconfiguration of the immune system. Herein, we review current experience of auto-HSCT for the treatment of CD as well as approaches that have been used to monitor immune reconstitution following auto-HSCT in patients with ADs, including CD. We also detail immune reconstitution studies that have been integrated into the randomized controlled Autologous Stem cell Transplantation In refractory CD—Low Intensity Therapy Evaluation trial, which is designed to test the hypothesis that auto-HSCT using reduced intensity mobilization and conditioning regimens will be a safe and effective means of inducing sustained control in refractory CD compared to standard of care. Immunological profiling will generate insight into the pathogenesis of the disease, restoration of responsiveness to anti-TNF therapy in patients with recurrence of endoscopic disease and immunological events that precede the onset of disease in patients that relapse after auto-HSCT. PMID:29670622

Telecommunication system for children undergoing stem cell transplantation.

PubMed

Higuchi, Kazumi; Nakazawa, Yozo; Sakata, Nobuhiro; Takizawa, Masaomi; Ohso, Keiko; Tanaka, Miyuki; Yanagisawa, Ryu; Koike, Kenichi

2011-12-01

Isolation in a germ-free unit is a stressful experience for pediatric patients undergoing hematopoietic stem cell transplantation (HSCT). To reduce the psychological distress of such children, a Web-based telecommunications system was developed. The authors developed a telecommunication system that linked a laminar air flow (LAF) room that had a high efficiency particulate air filter with the hospital school/patients' homes via the Internet. Fifteen children isolated in the LAF room for allogeneic HSCT were enrolled in this study. The present study evaluated whether the system was feasible for the patients during the acute phase of HSCT. In 10 patients, the proportion of days when they telecommunicated with teachers and/or other patients in the hospital school was 64.6 ± 32.3%. The telecommunication with the hospital school facilitated the continuation of school study under teachers' guidance, reducing the problem of lost schooling. In 13 patients, the proportion of days when they telecommunicated with their homes was 68.0 ± 34.8%. Ten of them frequently telecommunicated with their family members (especially siblings), and three patients called out to their pets at home. The incidence of telecommunication on the days when the patients had HSCT-related symptoms including vomiting did not differ from that of telecommunication on the days when no symptoms were evident. A telecommunication system linked to a hospital school and/or the patients' homes is feasible for children undergoing HSCT, and may improve their health-related quality of life. A larger, prospective study is required to evaluate whether the telecommunication system can reduce HSCT-associated psychological and psychiatric symptoms. © 2011 The Authors. Pediatrics International © 2011 Japan Pediatric Society.

Spiritual absence and 1-year mortality after hematopoietic stem cell transplant.

PubMed

Pereira, Deidre B; Christian, Lisa M; Patidar, Seema; Bishop, Michelle M; Dodd, Stacy M; Athanason, Rebecca; Wingard, John R; Reddy, Vijay S

2010-08-01

Religiosity and spirituality have been associated with better survival in large epidemiologic studies. This study examined the relationship between spiritual absence and 1-year all-cause mortality in allogeneic hematopoietic stem cell transplant (HSCT) recipients. Depression and problematic compliance were examined as possible mediators of a significant spiritual absence-mortality relationship. Eighty-five adults (mean = 46.85 years old, SD = 11.90 years) undergoing evaluation for allogeneic HSCT had routine psychologie evaluation prior to HSCT admission. The Millon Behavioral Medicine Diagnostic was used to assess spiritual absence, depression, and problematic compliance, the psychosocial predictors of interest. Patient status at 1 year and survival time in days were abstracted from medical records. Cox regression analysis was used to examine the relationship between the psychosocial factors of interest and mortality after adjusting for relevant biobehavioral factors. Twenty-nine percent (n = 25) of participants died within 1 year of HSCT. After covarying for disease type, individuals with the highest spiritual absence and problematic compliance scores were significantly more likely to die 1-year post-HSCT (hazard ratio [HR] = 2.49, P = .043 and HR = 3.74, P = .029, respectively), particularly secondary to infection, sepsis, or graft-versus-host disease (GVHD) (HR = 4.56, P = .01 and HR = 5.61, P = .014), relative to those without elevations on these scales. Depression was not associated with 1-year mortality, and problematic compliance did not mediate the relationship between spiritual absence and mortality. These preliminary results suggest that both spiritual absence and problematic compliance may be associated with poorer survival following HSCT. Future research should examine these relations in a larger sample using a more comprehensive assessment of spirituality.

Lower hospital mortality and complications after pediatric hematopoietic stem cell transplantation.

PubMed

Bratton, Susan L; Van Duker, Heather; Statler, Kimberly D; Pulsipher, Michael A; McArthur, Jennifer; Keenan, Heather T

2008-03-01

To assess protective and risk factors for mortality among pediatric patients during initial care after hematopoietic stem cell transplantation (HSCT) and to evaluate changes in hospital mortality. Retrospective cohort using the 1997, 2000, and 2003 Kids Inpatient Database, a probabilistic sample of children hospitalized in the United States with a procedure code for HSCT. Hospitalized patients in the United States submitted to the database. Age, <19 yrs. None. Hospital mortality significantly decreased from 12% in 1997 to 6% in 2003. Source of stem cells changed with increased use of cord blood. Rates of sepsis, graft versus host disease, and mechanical ventilation significantly decreased. Compared with autologous HSCT, patients who received an allogenic HSCT without T-cell depletion were more likely to die (adjusted odds ratio, 2.4; 95% confidence interval, 1.5, 3.9), while children who received cord blood HSCT were at the greatest risk of hospital death (adjusted odds ratio, 4.8; 95% confidence interval, 2.6, 9.1). Mechanical ventilation (adjusted odds ratio, 26.32; 95% confidence interval, 16.3-42.2), dialysis (adjusted odds ratio, 12.9; 95% confidence interval, 4.7-35.4), and sepsis (adjusted odds ratio, 3.9; 95% confidence interval, 2.5-6.1) were all independently associated with death, while care in 2003 was associated with decreased risk (adjusted odds ratio, 0.4; 95% confidence interval, 0.2-0.7) of death. Hospital mortality after HSCT in children decreased over time as did complications including need for mechanical ventilation, graft versus host disease, and sepsis. Prevention of complications is essential as the need for invasive support continues to be associated with high mortality risk.

An Individualized Dyadic Problem-Solving Education Intervention for Patients and Family Caregivers During Allogeneic HSCT: A Feasibility Study

PubMed Central

Bevans, Margaret; Castro, Kathleen; Prince, Patricia; Shelburne, Nonniekaye; Prachenko, Olena; Loscalzo, Matthew; Soeken, Karen; Zabora, James

2010-01-01

Background Allogeneic hematopoietic stem cell transplantation (HSCT) generates multiple problems that vary in complexity and create significant distress for both patients and their caregivers. Interventions that address patient and caregiver distress during allogeneic HSCT have not been tested. Objective To evaluate the feasibility of conducting an individualized dyadic problem-solving education (PSE) intervention during HSCT and estimate a preliminary effect size on problem-solving skills and distress. Intervention/Methods: The PSE intervention consisted of four sessions of the Prepared Family Caregiver PSE model. Data were collected with an interventionist log, subject interviews and standardized questionnaires. Results Of the thirty-four adult dyads screened, twenty-four were ineligible primarily due to non-English speaking (n=11) and inconsistent caregivers (n=10). Ten dyads (n=20) were enrolled and eight dyads (n=16) completed the intervention. Of the thirty-one sessions, 29 were completed (94%). Worsening patient condition was the primary reason for sessions to be incomplete. Patients attended 90% of the sessions; caregivers attended 74%. Reasons for missed sessions included patient symptom distress and limited caregiver availability. Dyads reported being very satisfied (4.8±0.61; range 1–5) stating “an opportunity to talk” and “creative thinking” were most beneficial. Conclusion Results suggest that dyads can participate in PSE during HSCT and view it as beneficial. Participants identified the active process of solving problems as helpful. Implications for Practice Targeted interventions that promote effective, meaningful behaviors are needed to guide patients and caregivers through HSCT. Future research recommendations include: testing a version of PSE with fewer sessions, including spousal and non-spousal caregivers and those who are non-English speaking. PMID:20142739

Epigenetic programming of T cells impacts immune reconstitution in hematopoietic stem cell transplant recipients.

PubMed

Hardy, Kristine; Smith, Corey; Tu, Wen Juan; McCuaig, Robert; Panikkar, Archana; Dasari, Vijayendra; Wu, Fan; Tey, Siok-Keen; Hill, Geoffrey R; Khanna, Rajiv; Rao, Sudha

2018-03-27

Immune reconstitution following hematopoietic stem cell transplantation (HSCT) is critical in preventing harmful sequelae in recipients with cytomegalovirus (CMV) infection. To understand the molecular mechanisms underlying immune reconstitution kinetics, we profiled the transcriptome-chromatin accessibility landscape of CMV-specific CD8 + T cells from HCST recipients with different immune reconstitution efficiencies. CMV-specific T cells from HSCT recipients with stable antiviral immunity expressed higher levels of interferon/defense response and cell cycle genes in an interconnected network involving PI3KCG , STAT5B , NFAT , RBPJ , and lower HDAC6 , increasing chromatin accessibility at the enhancer regions of immune and T-cell receptor signaling pathway genes. By contrast, the transcriptional and epigenomic signatures of CMV-specific T cells from HSCT recipients with unstable immune reconstitution showed commonalities with T-cell responses in other nonresolving chronic infections. These signatures included higher levels of EGR and KLF factors that, along with lower JARID2 expression, maintained higher accessibility at promoter and CpG-rich regions of genes associated with apoptosis. Furthermore, epigenetic targeting via inhibition of HDAC6 or JARID2 enhanced the transcription of genes associated with differential responses, suggesting that drugs targeting epigenomic modifiers may have therapeutic potential for enhancing immune reconstitution in HSCT recipients. Taken together, these analyses demonstrate that transcription factors and chromatin modulators create different chromatin accessibility landscapes in T cells of HSCT recipients that not only affect immediate gene expression but also differentially prime cells for responses to additional signals. Epigenetic therapy may be a promising strategy to promote immune reconstitution in HSCT recipients. © 2018 by The American Society of Hematology.

Management of Risks From Water and Ice From Ice Machines for the Very Immunocompromised Host: A Process Improvement Project Prompted by an Outbreak of Rapidly Growing Mycobacteria on a Pediatric Hematopoietic Stem Cell Transplant (Hsct) Unit.

PubMed

Guspiel, Amanda; Menk, Jeremiah; Streifel, Andrew; Messinger, Keith; Wagner, John; Ferrieri, Patricia; Kline, Susan

2017-07-01

BACKGROUND In 2011, pediatric hematopoietic stem cell transplant (HSCT) patients were moved from an older hospital to a new children's hospital. To minimize bacterial growth in the new hospital's water during construction, the plumbing system was flushed and disinfected before occupancy. However, 6 months after occupancy, an increased incidence of rapidly growing mycobacteria (RGM) was detected in clinical cultures. Over 10 months, 15 pediatric HSCT patients were infected, while no pediatric HSCT patients had been infected in the preceding 12 months. OBJECTIVE To determine the cause of the outbreak and to interrupt patient acquisition of RGM. METHODS Water samples were collected from water entering the hospital and from drinking water and ice machines (DWIMs) from the old and new hospitals. Total heterotrophic plate counts (HPCs, CFU/mL) of water were undertaken, and select isolates were identified as RGM. RESULTS The cause of the outbreak was increased bacterial levels in the water (including RGM) in the DWIMs in the new (2011) hospital. Tests revealed higher HPCs in drinking water and ice from the DWIMs in the new hospital than in the DWIMs in the old hospital. Ultimately, HPCs were reduced by several different interventions. CONCLUSION In response to an RGM outbreak, HSCT patients were banned from ingesting DWIM ice and water and bottled water was provided. Since this interverntion 4 years ago, no additional RGM isolates have been identified in HSCT patient cultures. Our measures to reduce HPCs to goal levels in drinking water from DWIMs were successful, but the HPCs for ice have not consistently reached the goal of <500 CFU/mL. Infect Control Hosp Epidemiol 2017;38:792-800.

Risks and outcomes of invasive fungal infections in pediatric allogeneic hematopoietic stem cell transplant recipients receiving fluconazole prophylaxis: a multicenter cohort study by the Turkish Pediatric Bone Marrow Transplantation Study Group.

PubMed

Hazar, Volkan; Karasu, Gülsün Tezcan; Uygun, Vedat; Öztürk, Gülyüz; Kiliç, Suar Çaki; Küpesiz, Alphan; Daloglu, Hayriye; Aksoylar, Serap; Atay, Didem; Ince, Elif Ünal; Karakükçü, Musa; Özbek, Namik; Tayfun, Funda; Kansoy, Savas; Özyürek, Emel; Akçay, Arzu; Gürsel, Orhan; Haskologlu, Sule; Kaya, Zühre; Yilmaz, Sebnem; Tanyeli, Atila; Yesilipek, Akif

2018-03-27

Invasive fungal infections (IFIs) are a major cause of infection-related morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Data from pediatric settings are scarce. To determine the incidence, risk factors and outcomes of IFIs in a 180-day period post-transplantation, 408 pediatric patients who underwent allogeneic HSCT were retrospectively analyzed. The study included only proven and probable IFIs. The cumulative incidences of IFI were 2.7%, 5.0%, and 6.5% at 30, 100, and 180 days post-transplantation, respectively. According to the multivariate analysis, the factors associated with increased IFI risk in the 180-day period post-HSCT were previous HSCT history (hazard ratio [HR], 4.57; 95% confidence interval [CI] 1.42-14.71; P = .011), use of anti-thymocyte globulin (ATG) (HR, 2.94; 95% CI 1.27-6.80; P = .012), grade III-IV acute graft-versus-host-disease (GVHD) (HR, 2.91; 95% CI 1.24-6.80; P = .014) and late or no lymphocyte engraftment (HR, 2.71; 95% CI 1.30-5.62; P = .007). CMV reactivation was marginally associated with an increased risk of IFI development (HR, 1.91; 95% CI 0.97-3.74; P = .063). IFI-related mortality was 1.5%, and case fatality rate was 27.0%.The close monitoring of IFIs in pediatric patients with severe acute GVHD who receive ATG during conditioning is critical to reduce morbidity and mortality after allogeneic HSCT, particularly among those with prior HSCT and no or late lymphocyte engraftment.

Identification of Suitable Reference Genes for mRNA Studies in Bone Marrow in a Mouse Model of Hematopoietic Stem Cell Transplantation.

PubMed

Li, H; Chen, C; Yao, H; Li, X; Yang, N; Qiao, J; Xu, K; Zeng, L

2016-10-01

Bone marrow micro-environment changes during hematopoietic stem cell transplantation (HSCT) with subsequent alteration of genes expression. Quantitative polymerase chain reaction (q-PCR) is a reliable and reproducible technique for the analysis of gene expression. To obtain more accurate results, it is essential to find a reference during HSCT. However, which gene is suitable during HSCT remains unclear. This study aimed to identify suitable reference genes for mRNA studies in bone marrow after HSCT. C57BL/6 mice were treated with either total body irradiation (group T) or busulfan/cyclophosphamide (BU/CY) (group B) followed by infusion of bone marrow cells. Normal mice without treatments were served as a control. All samples (group T + group B + control) were defined as group G. On days 7, 14, and 21 after transplantation, transcription levels of 7 candidate genes, ACTB, B2M, GAPDH, HMBS, HPRT, SDHA, and YWHAZ, in bone marrow cells were measured by use of real-time quantitative PCR. The expression stability of these 7 candidate reference genes were analyzed by 2 statistical software programs, GeNorm and NormFinder. Our results showed that ACTB displayed the highest expression in group G, with lowest expression of PSDHA in group T and HPRT in groups B and G. Analysis of expression stability by use of GeNorm or NormFinder demonstrated that expression of B2M in bone marrow were much more stable during HSCT, compared with other candidate genes including commonly used reference genes GAPDH and ACTB. ACTB could be used as a suitable reference gene for mRNA studies in bone marrow after HSCT. Copyright © 2016 Elsevier Inc. All rights reserved.

Socially disadvantaged parents of children treated with allogeneic haematopoietic stem cell transplantation (HSCT): report from a supportive intervention study, Denmark.

PubMed

Larsen, Hanne Bækgaard; Heilmann, Carsten; Johansen, Christoffer; Adamsen, Lis

2013-06-01

This study was undertaken to test a daily Family Navigator Nurse (FNN) conducted intervention program, to support parents during the distressful experience of their child's Allogeneic Haematopoietic Stem Cell Transplantation (HSCT). A qualitative analysis of the supportive intervention program for parents whose child is under HSCT treatment while hospitalized. Parents to 25 children were included in the intervention group. Twenty-five parents were included in a participant observational study and 21 of these completed a semi-structured interview 100 days following HSCT. Three main problems faced by all parents included 1) the emotional strain of the child's HSCT; 2) re-organizing of the family's daily life to include hospitalization with the child; and 3) the financial strain of manoeuvring within the Danish welfare system. The FNN performed daily intervention rounds to ease each of these problems during the study period. Having the following pre-existing risk factors, negatively influenced the parents' ability to address these problems: 1) being a single parents; 2) low-level income; 3) low-level education; 4) low-level network support: 5) being a student or unemployed; 6) physical/psychiatric illness; and 7) ethnicity. Six families with 4 or more risk factors had complex emotional, social and financial problems that required extensive intervention by the FNN and that impacted their ability to provide care for the child. The parents' pre-existing risk factors were further complicated by their children's HSCT. A recommendation for clinical practice is to identify families with multiple interrelated problems and allocate resources to support these families. Copyright © 2012 Elsevier Ltd. All rights reserved.

Reducing Second Gram-Negative Antibiotic Therapy on Pediatric Oncology and Hematopoietic Stem Cell Transplantation Services.

PubMed

Wattier, Rachel L; Levy, Emily R; Sabnis, Amit J; Dvorak, Christopher C; Auerbach, Andrew D

2017-09-01

OBJECTIVE To evaluate interventions to reduce avoidable antibiotic use on pediatric oncology and hematopoietic stem cell transplantation (HSCT) services. DESIGN Interrupted time series. SETTING Academic pediatric hospital with separate oncology and HSCT services. PARTICIPANTS Children admitted to the services during baseline (October 2011-August 2013) and 2 intervention periods, September 2013-June 2015 and July 2015-June 2016, including 1,525 oncology hospitalizations and 301 HSCT hospitalizations. INTERVENTION In phase 1, we completed an update of the institutional febrile neutropenia (FN) guideline for the pediatric oncology service, recommending first-line β-lactam monotherapy rather than routine use of 2 gram-negative agents. Phase 2 included updating the HSCT service FN guideline and engagement with a new pediatric antimicrobial stewardship program. The use of target antibiotics (tobramycin and ciprofloxacin) was measured in days of therapy per 1,000 patient days collected from administrative data. Intervention effects were evaluated using interrupted time series with segmented regression. RESULTS Phase 1 had mixed effects-long-term reduction in tobramycin use (97% below projected at 18 months) but rebound with increasing slope in ciprofloxacin use (+18% per month). Following phase 2, tobramycin and ciprofloxacin use on the oncology service were both 99% below projected levels at 12 months. On the HSCT service, tobramycin use was 99% below the projected level and ciprofloxacin use was 96% below the projected level at 12 months. CONCLUSIONS Locally adapted guidelines can facilitate practice changes in oncology and HSCT settings. More comprehensive and ongoing interventions, including follow-up education, feedback, and engagement of companion services may be needed to sustain changes. Infect Control Hosp Epidemiol 2017;38:1039-1047.

Vehicle Routing Problem Using Genetic Algorithm with Multi Compartment on Vegetable Distribution

NASA Astrophysics Data System (ADS)

Kurnia, Hari; Gustri Wahyuni, Elyza; Cergas Pembrani, Elang; Gardini, Syifa Tri; Kurnia Aditya, Silfa

2018-03-01

The problem that is often gained by the industries of managing and distributing vegetables is how to distribute vegetables so that the quality of the vegetables can be maintained properly. The problems encountered include optimal route selection and little travel time or so-called TSP (Traveling Salesman Problem). These problems can be modeled using the Vehicle Routing Problem (VRP) algorithm with rating ranking, a cross order based crossing, and also order based mutation mutations on selected chromosomes. This study uses limitations using only 20 market points, 2 point warehouse (multi compartment) and 5 vehicles. It is determined that for one distribution, one vehicle can only distribute to 4 market points only from 1 particular warehouse, and also one such vehicle can only accommodate 100 kg capacity.

Multi-Robot Coalitions Formation with Deadlines: Complexity Analysis and Solutions

PubMed Central

2017-01-01

Multi-robot task allocation is one of the main problems to address in order to design a multi-robot system, very especially when robots form coalitions that must carry out tasks before a deadline. A lot of factors affect the performance of these systems and among them, this paper is focused on the physical interference effect, produced when two or more robots want to access the same point simultaneously. To our best knowledge, this paper presents the first formal description of multi-robot task allocation that includes a model of interference. Thanks to this description, the complexity of the allocation problem is analyzed. Moreover, the main contribution of this paper is to provide the conditions under which the optimal solution of the aforementioned allocation problem can be obtained solving an integer linear problem. The optimal results are compared to previous allocation algorithms already proposed by the first two authors of this paper and with a new method proposed in this paper. The results obtained show how the new task allocation algorithms reach up more than an 80% of the median of the optimal solution, outperforming previous auction algorithms with a huge reduction of the execution time. PMID:28118384

Multi-Robot Coalitions Formation with Deadlines: Complexity Analysis and Solutions.

PubMed

Guerrero, Jose; Oliver, Gabriel; Valero, Oscar

2017-01-01

Multi-robot task allocation is one of the main problems to address in order to design a multi-robot system, very especially when robots form coalitions that must carry out tasks before a deadline. A lot of factors affect the performance of these systems and among them, this paper is focused on the physical interference effect, produced when two or more robots want to access the same point simultaneously. To our best knowledge, this paper presents the first formal description of multi-robot task allocation that includes a model of interference. Thanks to this description, the complexity of the allocation problem is analyzed. Moreover, the main contribution of this paper is to provide the conditions under which the optimal solution of the aforementioned allocation problem can be obtained solving an integer linear problem. The optimal results are compared to previous allocation algorithms already proposed by the first two authors of this paper and with a new method proposed in this paper. The results obtained show how the new task allocation algorithms reach up more than an 80% of the median of the optimal solution, outperforming previous auction algorithms with a huge reduction of the execution time.

Gradient design for liquid chromatography using multi-scale optimization.

PubMed

López-Ureña, S; Torres-Lapasió, J R; Donat, R; García-Alvarez-Coque, M C

2018-01-26

In reversed phase-liquid chromatography, the usual solution to the "general elution problem" is the application of gradient elution with programmed changes of organic solvent (or other properties). A correct quantification of chromatographic peaks in liquid chromatography requires well resolved signals in a proper analysis time. When the complexity of the sample is high, the gradient program should be accommodated to the local resolution needs of each analyte. This makes the optimization of such situations rather troublesome, since enhancing the resolution for a given analyte may imply a collateral worsening of the resolution of other analytes. The aim of this work is to design multi-linear gradients that maximize the resolution, while fulfilling some restrictions: all peaks should be eluted before a given maximal time, the gradient should be flat or increasing, and sudden changes close to eluting peaks are penalized. Consequently, an equilibrated baseline resolution for all compounds is sought. This goal is achieved by splitting the optimization problem in a multi-scale framework. In each scale κ, an optimization problem is solved with N κ  ≈ 2 κ variables that are used to build the gradients. The N κ variables define cubic splines written in terms of a B-spline basis. This allows expressing gradients as polygonals of M points approximating the splines. The cubic splines are built using subdivision schemes, a technique of fast generation of smooth curves, compatible with the multi-scale framework. Owing to the nature of the problem and the presence of multiple local maxima, the algorithm used in the optimization problem of each scale κ should be "global", such as the pattern-search algorithm. The multi-scale optimization approach is successfully applied to find the best multi-linear gradient for resolving a mixture of amino acid derivatives. Copyright © 2017 Elsevier B.V. All rights reserved.

Unrelated Hematopoietic Cell Transplantation in a Patient with Combined Immunodeficiency with Granulomatous Disease and Autoimmunity Secondary to RAG Deficiency

PubMed Central

Walter, Jolan E.; Schuetz, Catherina; Chen, Karin; Abraham, Roshini S.; Bonfim, Carmem; Boyce, Thomas G.; Joshi, Avni Y.; Kang, Elizabeth; Carvalho, Beatriz Tavares Costa; Mahajerin, Arash; Nugent, Diane; Puthenveetil, Geetha; Soni, Amit; Su, Helen; Cowan, Morton J.; Notarangelo, Luigi; Buchbinder, David

2016-01-01

The use of HLA-identical hematopoietic stem cell transplantation (HSCT) demonstrates overall survival rates greater than 75 % for T-B-NK+ severe combined immunodeficiency secondary to pathogenic mutation of recombinase activating genes 1 and 2 (RAG1/2). Limited data exist regarding the use of HSCT in patients with hypomorphic RAG variants marked by greater preservation of RAG activity and associated phenotypes such as granulomatous disease in combination with autoimmunity. We describe a 17-year-old with combined immunodeficiency and immune dysregulation characterized by granulomatous lung disease and autoimmunity secondary to compound heterozygous RAG mutations. A myeloablative reduced toxicity HSCTwas completed using an unrelated bone marrow donor. With the increasing cases of immune dysregulation being discovered with hypomorphic RAG variants, the use of HSCT may advance to the forefront of treatment. This case serves to discuss indications of HSCT, approaches to preparative therapy, and the potential complications in this growing cohort of patients with immune dysregulation and RAG deficiency. PMID:27539235

Exhaust Nozzle Materials Development for the High Speed Civil Transport

NASA Technical Reports Server (NTRS)

Grady, J. E.

1999-01-01

The United States has embarked on a national effort to develop the technology necessary to produce a Mach 2.4 High Speed Civil Transport (HSCT) for entry into service by the year 2005. The viability of this aircraft is contingent upon its meeting both economic and environmental requirements. Two engine components have been identified as critical to the environmental acceptability of the HSCT. These include a combustor with significantly lower emissions than are feasible with current technology, and a lightweight exhaust nozzle that meets community noise standards. The Enabling Propulsion Materials (EPM) program will develop the advanced structural materials, materials fabrication processes, structural analysis and life prediction tools for the HSCT combustor and low noise exhaust nozzle. This is being accomplished through the coordinated efforts of the NASA Lewis Research Center, General Electric Aircraft Engines and Pratt & Whitney. The mission of the EPM Exhaust Nozzle Team is to develop and demonstrate this technology by the year 1999 to enable its timely incorporation into HSCT propulsion systems.

Alterations of the bone marrow stromal microenvironment in adult patients with acute myeloid and lymphoblastic leukemias before and after allogeneic hematopoietic stem cell transplantation.

PubMed

Shipounova, Irina N; Petinati, Nataliya A; Bigildeev, Alexey E; Drize, Nina J; Sorokina, Tamara V; Kuzmina, Larisa A; Parovichnikova, Elena N; Savchenko, Valeri G

2017-02-01

Bone marrow (BM) derived adult multipotent mesenchymal stromal cells (MMSCs) and fibroblast colony-forming units (CFU-Fs) of 20 patients with acute myeloid leukemia (AML) and 15 patients with acute lymphoblastic leukemia (ALL) before and during 1 year after receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) were studied. The growth characteristics of MMSCs of all patients before allo-HSCT were not altered; however, relative expression level (REL) of some genes in MMSCs, but not in CFU-Fs, from AML and ALL patients significantly changed. After allo-HSCT, CFU-F concentration and MMSC production were significantly decreased for 1 year; REL of several genes in MMSCs and CFU-F-derived colonies were also significantly downregulated. Thus, chemotherapy that was used for induction of remission did not impair the function of stromal precursors, but gene expression levels were altered. Allo-HSCT conditioning regimens significantly damaged MMSCs and CFU-Fs, and the effect lasted for at least 1 year.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krityakierne, Tipaluck; Akhtar, Taimoor; Shoemaker, Christine A.

This paper presents a parallel surrogate-based global optimization method for computationally expensive objective functions that is more effective for larger numbers of processors. To reach this goal, we integrated concepts from multi-objective optimization and tabu search into, single objective, surrogate optimization. Our proposed derivative-free algorithm, called SOP, uses non-dominated sorting of points for which the expensive function has been previously evaluated. The two objectives are the expensive function value of the point and the minimum distance of the point to previously evaluated points. Based on the results of non-dominated sorting, P points from the sorted fronts are selected as centersmore » from which many candidate points are generated by random perturbations. Based on surrogate approximation, the best candidate point is subsequently selected for expensive evaluation for each of the P centers, with simultaneous computation on P processors. Centers that previously did not generate good solutions are tabu with a given tenure. We show almost sure convergence of this algorithm under some conditions. The performance of SOP is compared with two RBF based methods. The test results show that SOP is an efficient method that can reduce time required to find a good near optimal solution. In a number of cases the efficiency of SOP is so good that SOP with 8 processors found an accurate answer in less wall-clock time than the other algorithms did with 32 processors.« less

Ultra-Sensitive Droplet Digital PCR for the Assessment of Microchimerism in Cellular Therapies.

PubMed

Kliman, David; Castellano-Gonzalez, Gloria; Withers, Barbara; Street, Janine; Tegg, Elizabeth; Mirochnik, Oksana; Lai, Joey; Clancy, Leighton; Gottlieb, David; Blyth, Emily

2018-05-01

Current techniques to assess chimerism after hematopoietic stem cell transplantation (HSCT) are limited in both sensitivity and precision. These drawbacks are problematic in the context of cellular therapies that frequently result in microchimerism (donor chimerism <1%). We have developed a highly sensitive droplet digital PCR (ddPCR) assay using commercially available regents with good performance throughout the range of clinically relevant chimerism measurements, including microchimerism. We tested the assay using spiked samples of known donor-recipient ratios and in clinical samples from HSCT recipients and patients enrolled on clinical trials of microtransplantation and third-party virus-specific T cells (VSTs). The levels of detection and quantification of the assay were .008% and .023%, with high levels of precision with samples of DNA content ranging from 1 to 300 ng DNA. From the panel of 29 insertion-deletion probes multiple informative markers were found for each of 43 HSCT donor-recipient pairs. In the case of third-party cellular therapies in which there were 3 DNA contributors (recipient, HSCT donor, and T-cell donor), a marker to detect the cellular product in a background of recipient and donor cells was available for 11 of 12 cases (92%). Chimerism by ddPCR was able to quantify chimerism in HSCT recipients and comparison against standard STR analysis in 8 HSCT patients demonstrated similar results, with the advantage of fast turnaround time. Persistence of donor microchimerism in patients undergoing microtransplantation for acute myeloid leukemia was detectable for up to 57 days in peripheral blood and bone marrow. The presence of microtransplant product DNA in bone marrow T cells after cell sorting was seen in the 1 patient tested. In patients receiving third-party VSTs for treatment of refractory viral infections, VST donor DNA was detected at low levels in 7 of 9 cases. ddPCR offers advantages over currently available methods for assessment of chimerism in standard HSCT and cellular therapies. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Long-term survival of beta thalassemia major patients treated with hematopoietic stem cell transplantation compared with survival with conventional treatment.

PubMed

Caocci, Giovanni; Orofino, Maria Grazia; Vacca, Adriana; Piroddi, Antonio; Piras, Eugenia; Addari, Maria Carmen; Caria, Rossella; Pilia, Maria Paola; Origa, Raffaella; Moi, Paolo; La Nasa, Giorgio

2017-12-01

Allogeneic hematopoietic stem cell transplantation (HSCT) in thalassemia remains a challenge. We reported a single-centre case-control study of a large cohort of 516 children and adult patients treated with HSCT or blood transfusion support and iron chelation therapy; 258 patients (median age 12, range 1-45) underwent sibling (67%) or unrelated (33%) HSCT; 97 patients were adults (age ≥ 16 years). The median follow-up after HSCT was 11 years (range 1-30). The conditioning regimen was busulfan (80.6%) or treosulfan-based (19.4%). A cohort of 258 age-sex matched conventionally treated (CT) patients was randomly selected. In transplanted patients the 30-year overall survival (OS) and thalassemia-free survival (TFS) were 82.6 ± 2.7% and 77.8 ± 2.9%, compared to the OS of 85.3 ± 2.7% in CT patients (P = NS); The incidence of grade II-IV acute and chronic graft versus host disease (GvHD) was 23.6% and 12.9% respectively. The probability of rejection was 6.9%. Transplant-related mortality (TRM) (13.8%) was similar to the probability of dying of cardiovascular events in CT patients (12.2%). High-risk Pesaro score (class 3) was associated with lower OS (OR = 1.99, 95% C.I.=1.31-3.03) and TFS (OR = 1.54, 95% C.I.=1.12-2.12). In adult patients, the 23-years OS and TFS after HSCT were 70 ± 5% and 67.3 ± 5%, compared to 71.2 ± 5% of OS in CT (P = NS). Finally, treosulfan was associated with lower risk of acute GvHD (P = .004; OR = 0.28, 95% C.I.=0.12-0.67). In conclusion, the 30-year survival rate of ex-thalassemia patients after HSCT was similar to that expected in CT thalassemia patients, with the vast majority of HSCT survivors cured from thalassemia. © 2017 Wiley Periodicals, Inc.

Epidemiology, outcomes, and mortality predictors of invasive mold infections among transplant recipients: a 10-year, single-center experience.

PubMed

Neofytos, D; Treadway, S; Ostrander, D; Alonso, C D; Dierberg, K L; Nussenblatt, V; Durand, C M; Thompson, C B; Marr, K A

2013-06-01

The epidemiology of invasive mold infections (IMI) in transplant recipients differs based on geography, hosts, preventative strategies, and methods of diagnosis. We conducted a retrospective observational study to evaluate the epidemiology of proven and probable IMI, using prior definitions, among all adult hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients in the era of "classic" culture-based diagnostics (2000-2009). Epidemiology was evaluated before and after an initiative was begun to increase bronchoscopy in HSCT recipients after 2005. In total, 106 patients with one IMI were identified. Invasive aspergillosis (IA) was the most common IMI (69; 65.1%), followed by mucormycosis (9; 8.5%). The overall rate of IMI (and IA) was 3.5% (2.5%) in allogeneic HSCT recipients. The overall incidence for IMI among lung, kidney, liver, and heart transplant recipients was 49, 2, 11, and 10 per 1000 person-years, respectively. The observed rate of IMI among human leukocyte antigen-matched unrelated and haploidentical HSCT recipients increased from 0.6% annually to 3.0% after bronchoscopy initiation (P < 0.05). The 12-week mortality among allogeneic HSCT, liver, kidney, heart, and lung recipients with IMI was 52.4%, 47.1%, 27.8%, 16.7%, and 9.5%, respectively. Among allogeneic HSCT (odds ratio [OR]: 0.07, P = 0.007) and SOT (OR: 0.22, P = 0.05) recipients with IA, normal platelet count was associated with improved survival. Male gender (OR: 14.4, P = 0.007) and elevated bilirubin (OR: 5.7, P = 0.04) were significant predictors of mortality for allogeneic HSCT and SOT recipients with IA, respectively. During the era of culture-based diagnostics, observed rates of IMI were low among all transplants except lung transplant recipients, with relatively higher mortality rates. Diagnostic aggressiveness and host variables impact the reported incidence and outcome of IMI and likely account for institutional variability in multicenter studies. Definitions to standardize diagnoses among SOT recipients are needed. © 2013 John Wiley & Sons A/S.

[A comparative study of unrelated donor and matched-sibling donor allogeneic hematopoietic stem cell transplantation in children and adolescents with acquired severe aplastic anemia].

PubMed

Zhou, J; Fu, Y W; Liang, L J; Wang, Q; Han, L J; Zu, Y L; Zhang, Yanli; Zhu, X H; Yu, F K; Fang, B J; Wei, X D; Song, Y P

2016-12-01

Objective: To evaluate the efficacy of unrelated donor allogeneic hematopoietic stem cell transplantation(URD allo-HSCT) for children and adolescents with severe aplastic anemia (SAA). Methods: Clinical data of 34 SAA children and adolescents undergoing allo-HSCT were retrospectively analyzed from October 2001 to October 2015. According to the source of donor, the patients were divided into matched sibling donor allo-HSCT group (MSD group) and unrelated donor group (URD group). The clinical outcome of SAA children and adolescents receiving URD allo-HSCT was assessed, and patients in MSD allo-HSCT group were enrolled as control at the same period. Results: The rate of hematopoietic reconstitution, the time of neutrophil and platelet engraftment, incidence of chimerism and graft rejection between two groups were not statistically different.The incidence of acute graft-versus-host disease (GVHD) in URD group was significantly higher than that in MSD group [42.9%(6/14) vs 10.5%(2/19), P =0.047]. The incidence of grade Ⅱ-Ⅳ acute GVHD and chronic GVHD in URD were higher than those in MSD group [21.4%(3/14) vs 5.3%(1/19), P =0.288; 35.7%(5/14) vs 5.3%(1/19), P =0.062, respectively], yet without significant difference between two groups. Other transplant-related complications including pulmonary complications, hemorrhagic cystitis, incidence of EBV and CMV reactivation and venous occlusive disease were comparable with two regimens. Estimated 5-years overall survival (OS) rate and disease free survival (DFS) rate were not statistically significant between URD group and MSD group [(84.4±6.6)% vs (89.4±7.1)%, (82.5±5.4)% vs (82.1±4.3)%; P =0.766, P =0.884, respectively]. Conclusions: By multivariate analysis, the outcome of URD allo-HSCT in SAA children and adolescent is similar to MSD allo-HSCT. It could be an alternative option as the first-line treatment for SAA children and adolescents without HLA matched sibling donors.

Motor skill delays in pre-school children with leukemia one year after treatment: Hematopoietic stem cell transplantation therapy as an important risk factor.

PubMed

Taverna, Livia; Tremolada, Marta; Bonichini, Sabrina; Tosetto, Barbara; Basso, Giuseppe; Messina, Chiara; Pillon, Marta

2017-01-01

CNS-directed therapies for the treatment of leukemia can adversely affect the acquisition of new skills, such as reading/writing and math. Two years after the end of treatments, children show gross and fine motor skill delays that may persist even when patients are considered healed. The goal of the present study was to assess motor skills difficulties in pre-school children with leukemia one year after treatment. Particular attention has been paid to those patients who had undergone Hematopoietic Stem Cell Transplantation (HSCT) and to the relationship between motor delays and age bands. Participants were 60 children (median age of 5; inter quartile range: 3.07-5.76), including 31 females and 29 males, 91.7% of them were affected by acute lymphoblastic leukemia (ALL), and 8.3% by acute myeloid leukemia (AML). Five children had undergone HCST. Parents were interviewed by Vineland Adaptive Behavior Scales (VABS) on children's motor skills and filled in the Italian Temperament Questionnaire (QUIT). VABS's total scores were converted into equivalent mental age scores (EMA). A score difference of at least three months between current age and equivalent mental age was considered a developmental delay. Non-parametric analyses were run to understand if HSCT treatment and a specific age band influence children's motor skills. Significant delays were found in global motor skills (56.7%) as well as in fine and gross motor domains. Mann Whitney U tests showed that children with HSCT were reported to have lower gross motor mean ranks (U = 62; p = 0.004; Mean rank = 15.40) than peers without HSCT (Mean rank = 31.87) and lower mean rank values on motor temperament scale (U = 9; p = 0.003; HSCT Mean rank = 4.75 versus no HSCT Mean rank = 27.81). Kruskal Wallis' tests identified the high risk treatment showing that HSCT experience negatively impacted the motor skills and temperamental motor activity of pre-school children one year after the diagnosis of leukemia.

Motor skill delays in pre-school children with leukemia one year after treatment: Hematopoietic stem cell transplantation therapy as an important risk factor

PubMed Central

Bonichini, Sabrina; Tosetto, Barbara; Basso, Giuseppe; Messina, Chiara; Pillon, Marta

2017-01-01

CNS-directed therapies for the treatment of leukemia can adversely affect the acquisition of new skills, such as reading/writing and math. Two years after the end of treatments, children show gross and fine motor skill delays that may persist even when patients are considered healed. The goal of the present study was to assess motor skills difficulties in pre-school children with leukemia one year after treatment. Particular attention has been paid to those patients who had undergone Hematopoietic Stem Cell Transplantation (HSCT) and to the relationship between motor delays and age bands. Participants were 60 children (median age of 5; inter quartile range: 3.07–5.76), including 31 females and 29 males, 91.7% of them were affected by acute lymphoblastic leukemia (ALL), and 8.3% by acute myeloid leukemia (AML). Five children had undergone HCST. Parents were interviewed by Vineland Adaptive Behavior Scales (VABS) on children’s motor skills and filled in the Italian Temperament Questionnaire (QUIT). VABS’s total scores were converted into equivalent mental age scores (EMA). A score difference of at least three months between current age and equivalent mental age was considered a developmental delay. Non-parametric analyses were run to understand if HSCT treatment and a specific age band influence children’s motor skills. Significant delays were found in global motor skills (56.7%) as well as in fine and gross motor domains. Mann Whitney U tests showed that children with HSCT were reported to have lower gross motor mean ranks (U = 62; p = 0.004; Mean rank = 15.40) than peers without HSCT (Mean rank = 31.87) and lower mean rank values on motor temperament scale (U = 9; p = 0.003; HSCT Mean rank = 4.75 versus no HSCT Mean rank = 27.81). Kruskal Wallis’ tests identified the high risk treatment showing that HSCT experience negatively impacted the motor skills and temperamental motor activity of pre-school children one year after the diagnosis of leukemia. PMID:29065156

Long-term outcomes after allogeneic hematopoietic stem cell transplantation for metachromatic leukodystrophy: the largest single-institution cohort report.

PubMed

Boucher, Alexander A; Miller, Weston; Shanley, Ryan; Ziegler, Richard; Lund, Troy; Raymond, Gerald; Orchard, Paul J

2015-08-07

Metachromatic Leukodystrophy (MLD) is a rare, fatal demyelinating disorder with limited treatment options. Published outcomes after hematopoietic stem cell transplantation (HSCT) are scant and mixed. We report survival and function following HSCT for a large, single-center MLD cohort. Transplant-related data, survival and serial measures (brain MRI, nerve conduction velocity (NCV), neurologic and neuropsychology evaluations) were reviewed. When possible, parental interviews informed current neurologic status, quality-of-life, and adaptive functioning. Gross motor and expressive functions for late-infantile (LI-MLD) and juvenile (J-MLD) patients were described using previously reported, MLD-specific scales. Forty patients with confirmed MLD have undergone HSCT at our center. Twenty-one (53 %) survive at a median 12 years post-HSCT. Most deaths (n = 17) were treatment-related; two died from disease progression. Survival did not depend upon MLD subtype or symptom status at transplant. LI-MLD patients survive beyond reported life expectancy in untreated disease. Abnormal brain MRI and peripheral nerve conduction velocities (NCV) were common before HSCT. Following transplant, fewer patients experienced MRI progression compared to NCV deterioration. Sixteen LI-MLD and J-MLD survivors were evaluable for long-term gross motor and/or expressive language functioning using existing MLD clinical scoring systems. While most J-MLD patients regressed, the aggregate cohort demonstrated superior retention of function compared to published natural history. Seventeen LI-MLD, J-MLD and adult subtype (A-MLD) survivors were evaluable for long-term adaptive functioning, activities of daily living, and/or cognition. Relative cognitive sparing was observed despite overall global decline. Five sibling pairs (one LI-MLD and four J-MLD), in which at least one underwent transplant in our cohort, were evaluable. Within each familial dyad, survival or function was superior for the treated sibling, or if both siblings were transplanted, for the pre-symptomatic sibling. HSCT is a viable treatment option for MLD, but has significant limitations. Later-onset phenotypes may benefit most from early, pre-symptomatic transplant. Until superior, novel treatment strategies are demonstrated, MLD patients should be carefully considered for HSCT.

Multidisciplinary optimization of an HSCT wing using a response surface methodology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giunta, A.A.; Grossman, B.; Mason, W.H.

1994-12-31

Aerospace vehicle design is traditionally divided into three phases: conceptual, preliminary, and detailed. Each of these design phases entails a particular level of accuracy and computational expense. While there are several computer programs which perform inexpensive conceptual-level aircraft multidisciplinary design optimization (MDO), aircraft MDO remains prohibitively expensive using preliminary- and detailed-level analysis tools. This occurs due to the expense of computational analyses and because gradient-based optimization requires the analysis of hundreds or thousands of aircraft configurations to estimate design sensitivity information. A further hindrance to aircraft MDO is the problem of numerical noise which occurs frequently in engineering computations. Computermore » models produce numerical noise as a result of the incomplete convergence of iterative processes, round-off errors, and modeling errors. Such numerical noise is typically manifested as a high frequency, low amplitude variation in the results obtained from the computer models. Optimization attempted using noisy computer models may result in the erroneous calculation of design sensitivities and may slow or prevent convergence to an optimal design.« less

Status of an inlet configuration trade study for the Douglas HSCT

NASA Technical Reports Server (NTRS)

Jones, Jay R.; Welge, H. Robert

1992-01-01

An inlet concept integration trade study for an HSCT is being conducted under contract to NASA LeRC. The HSCT mission has a supersonic cruise Mach number of 2.4 and a subsonic cruise Mach number of 0.95. The engine selected for this study is the GE VCE (variable cycle engine) with FLADE (fan on blade). Six inlet configurations will be defined. Inlet configurations will be axisymmetric and rectangular mixed-compression inlets in single-engine nacelles. Airplane performance for each inlet configuration will be estimated and then compared. The most appropriate inlet configuration for this airplane/engine combination will be determined by Sep. 1991.

Efforts to enhance blood stem cell engraftment: Recent insights from zebrafish hematopoiesis

PubMed Central

Perlin, Julie R.; Robertson, Anne L.

2017-01-01

Hematopoietic stem cell transplantation (HSCT) is an important therapy for patients with a variety of hematological malignancies. HSCT would be greatly improved if patient-specific hematopoietic stem cells (HSCs) could be generated from induced pluripotent stem cells in vitro. There is an incomplete understanding of the genes and signals involved in HSC induction, migration, maintenance, and niche engraftment. Recent studies in zebrafish have revealed novel genes that are required for HSC induction and niche regulation of HSC homeostasis. Manipulation of these signaling pathways and cell types may improve HSC bioengineering, which could significantly advance critical, lifesaving HSCT therapies. PMID:28830909

Eosinophilic Pustular Folliculitis in Children after Stem Cell Transplantation: An Eruption Distinct from Graft-Versus-Host Disease.

PubMed

Theiler, Martin; Oza, Vikash S; Mathes, Erin F; Dvorak, Christopher C; McCalmont, Timothy H; Yeh, Iwei; Sidbury, Robert; Cordoro, Kelly M

2017-05-01

Eosinophilic pustular folliculitis (EPF) is a rare cutaneous disorder that typically occurs in three clinical contexts: men, individuals who are immunosuppressed or have human immunodeficiency virus, and infants. A fourth subtype occurring 2 to 3 months after hematopoietic stem cell transplantation (HSCT) has recently been described in several adults. We report two cases of EPF arising in children after HSCT. It is important to recognize this form of EPF after HSCT and differentiate it from graft-versus-host disease since it responds readily to topical steroids and appears to have an excellent prognosis. © 2017 Wiley Periodicals, Inc.

Multi-point contact of the high-speed vehicle-turnout system dynamics

NASA Astrophysics Data System (ADS)

Ren, Zunsong

2013-05-01

The wheel-rail contact problems, such as the number, location and the track of contact patches, are very important for optimizing the spatial structure of the rails and lowering the vehicle-turnout system dynamics. However, the above problems are not well solved currently because of having the difficulties in how to determine the multi-contact, to preciously present the changeable profiles of the rails and to establish an accurate spatial turnout system dynamics model. Based on a high-speed vehicle-turnout coupled model in which the track is modeled as flexible with rails and sleepers represented by beams, the line tracing extreme point method is introduced to investigate the wheel-rail multiple contact conditions and the key sections of the blade rail, longer nose rail, shorter rail in the switch and nose rail area are discretized to represent the varying profiles of rails in the turnout. The dynamic interaction between the vehicle and turnout is simulated for cases of the vehicle divergently passing the turnout and the multi-point contact is obtained. The tracks of the contact patches on the top of the rails are presented and the wheel-rail impact forces are offered in comparison with the contact patches transference on the rails. The numerical simulation results indicate that the length of two-point contact occurrence of a worn wheel profile and rails is longer than that of the new wheel profile and rails; The two-point contact definitely occurs in the switch and crossing area. Generally, three-point contact doesn't occur for the new rail profile, which is testified by the wheel-rails interpolation distance and the first order derivative function of the tracing line extreme points. The presented research is not only helpful to optimize the structure of the turnout, but also useful to lower the dynamics of the high speed vehicle-turnout system.

[Molecular diagnosis and hematopoietic stem cell transplantation in 17 children with inherited bone marrow failure syndrome].

PubMed

Li, Qian; Li, Benshang; Luo, Changying; Wang, Jianmin; Luo, Chengjuan; Ding, Lixia; Chen, Jing

2015-11-01

To enrich our national database with data of rare diseases by analyzing molecular diagnosis and hematopoietic stem cell transplantation (HSCT) in children with inherited bone marrow failure syndromes (IBMFS). Next-generation sequencing (NGS)-based genetic diagnosis panel was applied for the clinical diagnosis and management of IBMFS. Retrospective analysis was performed on clinical and genetic data of 17 consecutive children who received HSCT over a long time interval (November. 2005-June 2015). Three patients were diagnosed only by clinical manifestation before 2012. After that NGS-based genetic diagnosis panel was used to identify IBMFS-related genes in 12/14.IBMFS patients (except two Diamond-Blackfan anemia (DBA) patients). Two Fanconi anemia (FA) patients were confirmed to be new variations through family-genotype-analysis and 3 families accepted prenatal diagnosis to avoid birth of affected fetuses. Seventeen IBMFS patients (10 FA,5 DBA and 2 dyskeratosis congenital (DKC)) were treated with HSCT from matched sibling donors (n=2), matched unrelated donors (n=8) or mismatched unrelated donors (n=7). The source of stem cells for transplantation included peripheral blood (n=12) and cord blood (n=5). With regard to the conditioning regimens, FA and DKC patients received fludarabine-based reduced intensity conditioning, while DBA patients received classical busulfan-based myeloablative conditioning. Median age at the time of HSCT was 36 months (7-156 months). The number of infused mononuclear cells and CD34⁺ cells was (10.6 ± 6.7) × 10⁸ and (5.9 ± 7.0) × 10⁶ per kilogram of recipient body weight, respectively. The median number of days to neutrophil recovery was 13 days after HSCT (range: 10-19 days). Platelet recovery was faster in the PBSCT group than in the CBT group ((16.3 ± 6.0) days vs. (30.0 ± 17.1) days,t=-2.487,P=0.026). During a median follow-up of 17 months (range: 2-114 months), except one FA patient who was transplanted with HLA-matched unrelated cord blood (CB) died from pneumonia and heart failure because of engraftment failure, other 16 children are alive after the successful HSCT. The failure-free survival rate of the patients three years after HSCT was 94%. NGS-based molecular diagnosis technology and effective HSCT have significantly facilitated the treatment of children with IBMFS in our country, and our national database about this rare disease is to be further exploited.

TGF-β1-elevated TRPM7 channel regulates collagen expression in hepatic stellate cells via TGF-β1/Smad pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fang, Ling, E-mail: fangling_1984@126.com; Institute for Liver Diseases of Anhui Medical University, Mei Shan Road, Hefei, Anhui Province 230032; Key Laboratory of Anti-inflammatory and Immune Medicine, Anhui Medical University, Ministry of Education, Mei Shan Road, Hefei, Anhui Province 230032

Transdifferentiation of hepatic stellate cells (HSCs) into myofibroblasts plays a critical role in the development of liver fibrosis, since myofibroblasts are the key cells responsible for excessive deposition of ECM proteins. Transient receptor potential melastatin 7 (TRPM7), a non-selective cation channel with protein serine/threonine kinase activity, has been demonstrated to function in the proliferation of activated HSCs. Here, we investigated the functional role of TRPM7 in collagen deposition in activated HSC-T6 cells (a rat hepatic stellate cell line). TRPM7 mRNA and protein were measured by Real-time PCR and Western blot in TGF-β1-activated HSC-T6 cells in vitro. Results demonstrated that TRPM7more » protein was dramatically increased in fibrotic human livers. Stimulation of HSC-T6 cells with TGF-β1 increased TRPM7 mRNA and protein level in a time-dependent manner. Nevertheless, TGF-β1-elicited upregulation of TRPM7 in HSC-T6 cells was abrogated by SB431542 (TGF-β1 receptor blocker) or SIS3 (inhibitor of Smad3 phosphorylation). Additionally, blockade of TRPM7 channels with non-specific TRPM7 blocker 2-APB or synthetic siRNA targeting TRPM7 attenuated TGF-β1-induced expression of myofibroblast markers, as measured by the induction of α-SMA and Col1α1. Silencing TRPM7 also increased the ratio of MMPs/TIMPs by increasing MMP-13 expression and decreasing TIMP-1 and TIMP-2 levels. Strikingly, phosphorylation of p-Smad2 and p-Smad3, associated with collagen production, was decreased in TRPM7 deficient HSC-T6 cells. These observations suggested that TGF-β1 elevates TRPM7 expression in HSCs via Smad3-dependant mechanisms, which in turn contributes Smad protein phosphorylation, and subsequently increases fibrous collagen expression. Therefore, TRPM7 may constitute a useful target for the treatment of liver fibrosis. - Highlights: • Upregulation of TRPM7 protein in human fibrotic livers • Upregulation of TRPM7 by TGF-β1 elicited Smad signaling in HSC-T6 cells • Blockade of TRPM7 decreased α-SMA and Col1α1 expressions in activated HSC-T6 cells • Silencing of TRPM7 led to collagen degradation in TGF-β1 stimulated HSC-T6 cells • TRPM7 upregulation contributes to the activation of TGF-β1/Smad pathway.« less

Computation of the target state and feedback controls for time optimal consensus in multi-agent systems

NASA Astrophysics Data System (ADS)

Mulla, Ameer K.; Patil, Deepak U.; Chakraborty, Debraj

2018-02-01

N identical agents with bounded inputs aim to reach a common target state (consensus) in the minimum possible time. Algorithms for computing this time-optimal consensus point, the control law to be used by each agent and the time taken for the consensus to occur, are proposed. Two types of multi-agent systems are considered, namely (1) coupled single-integrator agents on a plane and, (2) double-integrator agents on a line. At the initial time instant, each agent is assumed to have access to the state information of all the other agents. An algorithm, using convexity of attainable sets and Helly's theorem, is proposed, to compute the final consensus target state and the minimum time to achieve this consensus. Further, parts of the computation are parallelised amongst the agents such that each agent has to perform computations of O(N2) run time complexity. Finally, local feedback time-optimal control laws are synthesised to drive each agent to the target point in minimum time. During this part of the operation, the controller for each agent uses measurements of only its own states and does not need to communicate with any neighbouring agents.

Clinical Usefulness of Monitoring Cytomegalovirus-Specific Immunity by Quantiferon-CMV in Pediatric Allogeneic Hematopoietic Stem Cell Transplantation Recipients.

PubMed

Lee, Sae Mi; Kim, Yae Jean; Yoo, Keon Hee; Sung, Ki Woong; Koo, Hong Hoe; Kang, Eun Suk

2017-05-01

Cytomegalovirus (CMV) is a well-established cause of morbidity and mortality in pediatric recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). CD8⁺ T-cells are important for controlling CMV infection. We conducted a prospective pilot study to investigate the clinical utility of measuring the CMV-specific T-cell immune response using the QuantiFERON-CMV assay (QF-CMV) in pediatric allo-HSCT recipients. Overall, 16 of 25 (64%) patients developed CMV infection. QF-CMV was evaluated in these 16 patients during the early and late phases of the first CMV infection post allo-HSCT. Whereas the initial QF-CMV results during the early phase of CMV infection did not correlate with the course of the corresponding infection, the QF-CMV results post resolution of the first CMV infection correlated with the recurrence of CMV infection until 12 months post allo-HSCT; no recurrent infections occurred in the four QF-CMV-positive patients, while recurrent infections manifested in five of eight QF-CMV-negative (62.5%) and all three QF-CMV-indeterminate patients (P=0.019). In spite of the small number of patients examined, this study supports the potential application of monitoring CMV-specific T-cell immunity using the QF-CMV assay to predict the recurrence of CMV infection in pediatric allo-HSCT recipients. © The Korean Society for Laboratory Medicine.

Dioscin Inhibits HSC-T6 Cell Migration via Adjusting SDC-4 Expression: Insights from iTRAQ-Based Quantitative Proteomics.

PubMed

Yin, Lianhong; Qi, Yan; Xu, Youwei; Xu, Lina; Han, Xu; Tao, Xufeng; Song, Shasha; Peng, Jinyong

2017-01-01

Hepatic stellate cells (HSCs) migration, an important bioprocess, contributes to the development of liver fibrosis. Our previous studies have found the potent activity of dioscin against liver fibrosis by inhibiting HSCs proliferation, triggering the senescence and inducing apoptosis of activated HSCs, but the molecular mechanisms associated with cell migration were not clarified. In this work, iTRAQ (isobaric tags for relative and absolution quantitation)-based quantitative proteomics study was carried out, and a total of 1566 differentially expressed proteins with fold change ≥2.0 and p < 0.05 were identified in HSC-T6 cells treated by dioscin (5.0 μg/mL). Based on Gene Ontology classification, String and KEGG pathway assays, the effects of dioscin to inhibit cell migration via regulating SDC-4 were carried out. The results of wound-healing, cell migration and western blotting assays indicated that dioscin significantly inhibit HSC-T6 cell migration through SDC-4-dependent signal pathway by affecting the expression levels of Fn, PKCα, Src, FAK, and ERK1/2. Specific SDC-4 knockdown by shRNA also blocked HSC-T6 cell migration, and dioscin slightly enhanced the inhibiting effect. Taken together, the present work showed that SDC-4 played a crucial role on HSC-T6 cell adhesion and migration of dioscin against liver fibrosis, which may be one potent therapeutic target for fibrotic diseases.

Successful Sequential Liver and Hematopoietic Stem Cell Transplantation in a Child With CD40 Ligand Deficiency and Cryptosporidium-Induced Liver Cirrhosis.

PubMed

Quarello, Paola; Tandoi, Francesco; Carraro, Francesca; Vassallo, Elena; Pinon, Michele; Romagnoli, Renato; David, Ezio; Dell Olio, Dominic; Salizzoni, Mauro; Fagioli, Franca; Calvo, Pier Luigi

2018-05-01

Hematopoietic stem cell transplantation (HSCT) is curative in patients with primary immunodeficiencies. However, pre-HSCT conditioning entails unacceptably high risks if the liver is compromised. The presence of a recurrent opportunistic infection affecting the biliary tree and determining liver cirrhosis with portal hypertension posed particular decisional difficulties in a 7-year-old child with X-linked CD40-ligand deficiency. We aim at adding to the scanty experience available on such rare cases, as successful management with sequential liver transplantation (LT) and HSCT has been reported in detail only in 1 young adult to date. A closely sequential strategy, with a surgical complication-free LT, followed by reduced-intensity conditioning, allowed HSCT to be performed only one month after LT, preventing Cryptosporidium parvum recolonization of the liver graft. Combined sequential LT and HSCT resolved the cirrhotic evolution and corrected the immunodeficiency so that the infection responsible for the progressive sclerosing cholangitis did not recur. Hopefully, this report of the successful resolution of a potentially fatal combination of immunodeficiency and chronic opportunistic infection with end-stage organ damage in a child will encourage others to adapt a sequential transplant approach to this highly complex pathology. However, caution is to be exercised to carefully balance the risks intrinsic to transplant surgery and immunosuppression in primary immunodeficiencies.

Full myeloablative conditioning and an unrelated HLA mismatched donor increase the risk for BK virus-positive hemorrhagic cystitis in allogeneic hematopoetic stem cell transplanted patients.

PubMed

Dalianis, Tina; Ljungman, Per

2011-03-01

BK virus (BKV)-associated hemorrhagic cystitis (HC), varying from mild hematuria with or without dysuria to life-threating bleeding and clots that may cause urinary obstruction and renal failure, causes significant morbidity and mortality in haematopoetic stem cell transplanted (HSCT) patients. Unfortunately, its development is difficult to predict since BK viruria is very common after HSCT and can be present in patients with and without HC. There is therefore the need to identify risk factors that may increase the risk of developing HC after HSCT. The viral load of BK-viruria, as well as BK viremia, has been monitored for this purpose. Moreover, having full myeoblative conditioning (MC) versus reduced intensity conditioning (RIC) prior to HSCT and an HLA-matched or -mismatched graft from an unrelated donor in contrast to an HLA-matched graft from a related donor have been studied as risk factors for HC. In addition, graft versus host disease has been examined, but has not been defined as a definite risk factor for HC. We conclude that the present evidence suggests that HSCT patients with BK viruria, receiving MC and an unrelated donor graft that is HLA-mismatched have an increased risk for developing HC in comparison to patients receiving RIC and an HLA-matched related donor graft.

Forty years of haematopoietic stem cell transplantation: a review of the Basel experience.

PubMed

O'Meara, Alix; Holbro, Andreas; Meyer, Sara; Martinez, Maria; Medinger, Michael; Buser, Andreas; Halter, Jörg; Heim, Dominik; Gerull, Sabine; Bucher, Christoph; Rovo, Alicia; Kühne, Thomas; Tichelli, André; Gratwohl, Alois; Stern, Martin; Passweg, Jakob R

2014-02-24

The purpose of this study was to examine changes in haematopoietic stem cell transplant (HSCT) characteristics and outcome in our combined paediatric and adult programme over the past four decades, since its implementation in 1973. The total number of transplant procedures rose from 109 in the first decade (1973-82) to 939 in the last decade (2003-12). Transplant characteristics changed significantly over time: patient age increased, peripheral blood largely replaced bone marrow as stem cell source, unrelated donors became an alternative to matched siblings, and patients are increasingly transplanted in more advanced disease stages. Advances such as improved supportive care and histocompatibility typing resulted in a steady decrease of transplant-related mortality after allogeneic HSCT (43% in the first decade, 22% in the last decade). Despite this, unadjusted survival rates were stable in the last three decades for allogeneic HSCT (approximately 50% 5-year survival) and in the last two decades for autologous HSCT (approximately 60% 5-year survival). After adjustment for covariates such as donor type, age and stage, the relative risk of treatment failure continuously dropped (for allogeneic HSCT: first decade 1.0, second decade 0.58, third decade 0.51, last decade 0.41). Collectively, these data suggest that improvements in peri- and post-transplant care have allowed considerable extension of transplant indications without having a negative impact on outcome.

Epidemiologic Profile of Patients Transplanted With Hematopoietic Stem Cells in a Reference Service in the State of Rio Grande do Norte, Brazil.

PubMed

Campos de Azevedo, I; Ferreira Júnior, M A; Pereira de Aquino, L A; de Oliveira, A A; Cruz, G K P; de Queiroz Cardoso, A I; Ivo, M L; Santos, V E P

2018-04-01

Hematopoietic stem cell transplantation (HSCT) consists of the intravenous infusion of healthy hematopoietic stem cells to restore the medullary and immunologic function of patients affected by a series of hematologic, oncologic, immunologic, malignant and nonmalignant inherited or acquired diseases, with the possibility of cure or increase of disease-free survival. To characterize the epidemiologic profile and the cases of death of patients who underwent HSCT. This is a cohort quantitative study, nested with a retrospective, descriptive, and analytical study of a hospital-based cohort that included the patients who underwent HSCT at a referral service in the state of Rio Grande do Norte, a region of northeastern Brazil. There was a slight male prevalence (52.94%), the age of the patients ranged from 2 to 73 years old, 18.38% were brown, 47.06% were married, 15.07% were students, 78.31% had a diagnosis of multiple myeloma, 93.38% developed gastrointestinal toxicities, all patients received chemotherapeutic treatment, 54.78% had allogeneic HSCT, and the cause of the most recorded deaths was septic shock (48.19%). This study showed relevant scientific evidence on the clinical and epidemiologic profile of patients who underwent HSCT. In general, sociodemographic data are similar to national and international research results. Copyright © 2018 Elsevier Inc. All rights reserved.

Control of infectious mortality due to carbapenemase-producing Klebsiella pneumoniae in hematopoietic stem cell transplantation.

PubMed

Forcina, A; Baldan, R; Marasco, V; Cichero, P; Bondanza, A; Noviello, M; Piemontese, S; Soliman, C; Greco, R; Lorentino, F; Giglio, F; Messina, C; Carrabba, M; Bernardi, M; Peccatori, J; Moro, M; Biancardi, A; Nizzero, P; Scarpellini, P; Cirillo, D M; Mancini, N; Corti, C; Clementi, M; Ciceri, F

2017-01-01

Carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) infections are an emerging cause of death after hematopoietic stem cell transplantation (HSCT). In allogeneic transplants, mortality rate may rise up to 60%. We retrospectively evaluated 540 patients receiving a transplant from an auto- or an allogeneic source between January 2011 and October 2015. After an Institutional increase in the prevalence of KPC-Kp bloodstream infections (BSI) in June 2012, from July 2012, 366 consecutive patients received the following preventive measures: (i) weekly rectal swabs for surveillance; (ii) contact precautions in carriers (iii) early-targeted therapy in neutropenic febrile carriers. Molecular typing identified KPC-Kp clone ST512 as the main clone responsible for colonization, BSI and outbreaks. After the introduction of these preventive measures, the cumulative incidence of KPC-Kp BSI (P=0.01) and septic shocks (P=0.01) at 1 year after HSCT was significantly reduced. KPC-Kp infection-mortality dropped from 62.5% (pre-intervention) to 16.6% (post-intervention). Day 100 transplant-related mortality and KPC-Kp infection-related mortality after allogeneic HSCT were reduced from 22% to 10% (P=0.001) and from 4% to 1% (P=0.04), respectively. None of the pre-HSCT carriers was excluded from transplant. These results suggest that active surveillance, contact precautions and early-targeted therapies, may efficiently control KPC-Kp spread and related mortality even after allogeneic HSCT.

Travelling activity and travel-related risks after allogeneic haematopoietic stem cell transplantation - a single centre survey.

PubMed

Hollenstein, Yvonne; Elzi, Luigia; Hatz, Christoph; Passweg, Jakob; Weisser, Maja; Stöckle, Marcel; Halter, Joerg P; Egli, Adrian

2015-01-01

Travel activity and travel-related risks of patients after allogeneic haematopoietic stem cell transplantation (allo-HSCT) remain largely unknown. The aim of our study was to examine travel activity after allo-HSCT including travel behaviour and travel patterns. We analysed travel characteristics of allo-HSCT recipients by using a retrospective cross-sectional survey. Allo-HSCT patients were asked to complete a questionnaire during their annual health visits from 2010 to 2012. Overall, 118/153 (77%) participating patients reported travel activity for a total of 201 travelling episodes. Travellers versus non-travellers were receiving immunosuppressive treatment in 35.6% versus 65.7% (p=0.002), and had graft-versus-host-disease (GvHD) in 52.5% versus 62.9% (p=0.17). In a multivariate analysis, the time between the transplantation and the survey was the only factor associated with travel activity (p<0.0001) and taking pretravel advice (p<0.0001). In 34.8% of travel episodes pretravel advice was sought. Patients with pretravel advice reported travel-related symptoms more frequently. Minor respiratory (27/201) and gastrointestinal (23/201) symptoms were most frequently indicated. Four percent (8/201) of the patients were hospitalised while travelling. We conclude that travelling after allo-HSCT is frequent and linked to the time since transplantation. We could not define specific risks for any destination. Nevertheless, pretravel advice and preparation are highly recommended for immunosuppressed patients.

Low Noise Exhaust Nozzle Technology Development

NASA Technical Reports Server (NTRS)

Majjigi, R. K.; Balan, C.; Mengle, V.; Brausch, J. F.; Shin, H.; Askew, J. W.

2005-01-01

NASA and the U.S. aerospace industry have been assessing the economic viability and environmental acceptability of a second-generation supersonic civil transport, or High Speed Civil Transport (HSCT). Development of a propulsion system that satisfies strict airport noise regulations and provides high levels of cruise and transonic performance with adequate takeoff performance, at an acceptable weight, is critical to the success of any HSCT program. The principal objectives were to: 1. Develop a preliminary design of an innovative 2-D exhaust nozzle with the goal of meeting FAR36 Stage III noise levels and providing high levels of cruise performance with a high specific thrust for Mach 2.4 HSCT with a range of 5000 nmi and a payload of 51,900 lbm, 2. Employ advanced acoustic and aerodynamic codes during preliminary design, 3. Develop a comprehensive acoustic and aerodynamic database through scale-model testing of low-noise, high-performance, 2-D nozzle configurations, based on the preliminary design, and 4. Verify acoustic and aerodynamic predictions by means of scale-model testing. The results were: 1. The preliminary design of a 2-D, convergent/divergent suppressor ejector nozzle for a variable-cycle engine powered, Mach 2.4 HSCT was evolved, 2. Noise goals were predicted to be achievable for three takeoff scenarios, and 3. Impact of noise suppression, nozzle aerodynamic performance, and nozzle weight on HSCT takeoff gross weight were assessed.

Defibrotide: a review of its use in severe hepatic veno-occlusive disease following haematopoietic stem cell transplantation.

PubMed

Keating, Gillian M

2014-12-01

Defibrotide (Defitelio(®)) was recently approved in the EU for the treatment of severe hepatic veno-occlusive disease (VOD), also known as sinusoidal obstructive syndrome, in haematopoietic stem cell transplantation (HSCT) therapy. It is indicated in adults, adolescents, children and infants over 1 month of age. Defibrotide is also available in the US via an expanded-access protocol. Defibrotide is thought to protect endothelial cells and restore the thrombo-fibrinolytic balance in VOD. In a multicentre, phase III trial, the complete response rate by day +100 (primary endpoint) was significantly higher, and mortality at day +100 was significantly lower, in patients with severe hepatic VOD and multiorgan failure following HSCT who received intravenous defibrotide 6.25 mg/kg every 6 h than in a group of historical controls. The efficacy of defibrotide in severe hepatic VOD following HSCT was also supported by findings from a phase II dose-finding study, compassionate-use data and information provided from an independent transplant registry. Intravenous defibrotide was generally well tolerated in patients with severe hepatic VOD following HSCT, and was not associated with an increased risk of haemorrhagic adverse events. In conclusion, defibrotide is the only agent approved (in the EU) for use in severe hepatic VOD following HSCT and represents a useful advance in the treatment of this condition.

Hematopoietic Stem Cell Transplantation in Late-Onset Krabbe Disease: No Evidence of Worsening Demyelination and Axonal Loss 4 Years Post-allograft.

PubMed

Laule, Cornelia; Vavasour, Irene M; Shahinfard, Elham; Mädler, Burkhard; Zhang, Jing; Li, David K B; MacKay, Alex L; Sirrs, Sandra M

2018-05-01

Late-onset adult Krabbe disease is a very rare demyelinating leukodystrophy, affecting less than 1 in a million people. Hematopoietic stem cell transplantation (HSCT) strategies can stop the accumulation of toxic metabolites that damage myelin-producing cells. We used quantitative advanced imaging metrics to longitudinally assess the impact of HSCT on brain abnormalities in adult-onset Krabbe disease. A 42-year-old female with late-onset Krabbe disease and an age/sex-matched healthy control underwent annual 3T MRI (baseline was immediately prior to HSCT for the Krabbe subject). Imaging included conventional scans, myelin water imaging, diffusion tensor imaging, and magnetic resonance spectroscopy. Brain abnormalities far beyond those visible on conventional imaging were detected, suggesting a global pathological process occurs in Krabbe disease with adult-onset etiology, with myelin being more affected than axons, and evidence of wide-spread gliosis. After HSCT, our patient showed clinical stability in all measures, as well as improvement in gait, dysarthria, and pseudobulbar affect at 7.5 years post-transplant. No MRI evidence of worsening demyelination and axonal loss was observed up to 4 years post-allograft. Clinical evidence and stability of advanced MR measures related to myelin and axons supports HSCT as an effective treatment strategy for stopping progression associated with late-onset Krabbe disease. Copyright © 2018 by the American Society of Neuroimaging.

Vascular and perivascular niches, but not the osteoblastic niche, are numerically restored following allogeneic hematopoietic stem cell transplantation in patients with aplastic anemia.

PubMed

Wu, Liangliang; Mo, Wenjian; Zhang, Yuping; Zhou, Ming; Li, Yumiao; Zhou, Ruiqing; Xu, Shiling; Pan, Shiyi; Deng, Hui; Mao, Ping; Wang, Shunqing

2017-07-01

Bone marrow (BM) niches, including the osteoblastic, vascular, and perivascular niches, are numerically impaired in patients with aplastic anemia (AA). It remains unclear whether these niches are numerically restored in AA patients after allogenic hematopoietic stem cell transplantation (allo-HSCT). To investigate changes in BM niches, we monitored 52 patients with AA who had undergone allo-HSCT and performed immunohistochemical studies of BM niches using antibodies against CD34, CD146, and osteopontin. After allo-HSCT, patients with AA exhibited a remarkable increase in the number of cellular elements in the BM niches, including the vascular and perivascular cells. However, no significant differences in endosteal cells were detected. We explored the cause of this restoration by analyzing the origin of BM mesenchymal stem cells (BM-MSCs) and the expression of cytokines in BM plasma. STR-PCR revealed that the BM-MSCs were derived from the host, not the donor. In addition, significantly elevated levels of vascular endothelial growth factor (VEGF) were found after allo-HSCT. Our data indicates that vascular and perivascular niches are numerically restored, but the endosteal niche remains numerically impaired in patients with AA after allo-HSCT, and that levels of VEGF, but not donor-derived BM-MSCs, may correlate with the restoration of BM niches.

Excellent outcome of matched unrelated donor transplantation in paediatric aplastic anaemia following failure with immunosuppressive therapy: a United Kingdom multicentre retrospective experience.

PubMed

Samarasinghe, Sujith; Steward, Colin; Hiwarkar, Prashant; Saif, Muhammad Ameer; Hough, Rachael; Webb, David; Norton, Alice; Lawson, Sarah; Qureshi, Amrana; Connor, Philip; Carey, Peter; Skinner, Rod; Vora, Ajay; Pelidis, Maria; Gibson, Brenda; Stewart, Graham; Keogh, Steve; Goulden, Nick; Bonney, Denise; Stubbs, Mathew; Amrolia, Persis; Rao, Kanchan; Meyer, Stefan; Wynn, Rob; Veys, Paul

2012-05-01

We retrospectively analysed the outcome of consecutive children with idiopathic severe aplastic anaemia in the United Kingdom who received immunosuppressive therapy (IST) or matched unrelated donor (MUD) haematopoietic stem cell transplantation (HSCT). The 6-month cumulative response rate following rabbit antithymocyte globulin (ATG)/ciclosporin (IST) was 32·5% (95% CI 19·3-46·6) (n = 43). The 5-year estimated failure-free survival (FFS) following IST was 13·3% (95% confidence interval [CI] 4·0-27·8). In contrast, in 44 successive children who received a 10-antigen (HLA-A, -B, -C, -DRB1, -DQB1) MUD HSCT there was an excellent estimated 5-year FFS of 95·01% (95% CI 81·38-98·74). Forty of these children had failed IST previously. HSCT conditioning was a fludarabine, cyclophosphamide and alemtuzumab (FCC) regimen and did not include radiotherapy. There were no cases of graft failure. Median donor chimerism was 100% (range 88-100%). A conditioning regimen, such as FCC that avoids total body irradiation is ideally suited in children. Our data suggest that MUD HSCT following IST failure offers an excellent outcome and furthermore, if a suitable MUD can be found quickly, MUD HSCT may be a reasonable alternative to IST. © 2012 Blackwell Publishing Ltd.

Topology Optimization - Engineering Contribution to Architectural Design

NASA Astrophysics Data System (ADS)

Tajs-Zielińska, Katarzyna; Bochenek, Bogdan

2017-10-01

The idea of the topology optimization is to find within a considered design domain the distribution of material that is optimal in some sense. Material, during optimization process, is redistributed and parts that are not necessary from objective point of view are removed. The result is a solid/void structure, for which an objective function is minimized. This paper presents an application of topology optimization to multi-material structures. The design domain defined by shape of a structure is divided into sub-regions, for which different materials are assigned. During design process material is relocated, but only within selected region. The proposed idea has been inspired by architectural designs like multi-material facades of buildings. The effectiveness of topology optimization is determined by proper choice of numerical optimization algorithm. This paper utilises very efficient heuristic method called Cellular Automata. Cellular Automata are mathematical, discrete idealization of a physical systems. Engineering implementation of Cellular Automata requires decomposition of the design domain into a uniform lattice of cells. It is assumed, that the interaction between cells takes place only within the neighbouring cells. The interaction is governed by simple, local update rules, which are based on heuristics or physical laws. The numerical studies show, that this method can be attractive alternative to traditional gradient-based algorithms. The proposed approach is evaluated by selected numerical examples of multi-material bridge structures, for which various material configurations are examined. The numerical studies demonstrated a significant influence the material sub-regions location on the final topologies. The influence of assumed volume fraction on final topologies for multi-material structures is also observed and discussed. The results of numerical calculations show, that this approach produces different results as compared with classical one-material problems.

Minimum impulse three-body trajectories.

NASA Technical Reports Server (NTRS)

D'Amario, L.; Edelbaum, T. N.

1973-01-01

A rapid and accurate method of calculating optimal impulsive transfers in the restricted problem of three bodies has been developed. The technique combines a multi-conic method of trajectory integration with primer vector theory and an accelerated gradient method of trajectory optimization. A unique feature is that the state transition matrix and the primer vector are found analytical without additional integrations or differentiations. The method has been applied to the determination of optimal two and three impulse transfers between the L2 libration point and circular orbits about both the earth and the moon.

PCTO-SIM: Multiple-point geostatistical modeling using parallel conditional texture optimization

NASA Astrophysics Data System (ADS)

Pourfard, Mohammadreza; Abdollahifard, Mohammad J.; Faez, Karim; Motamedi, Sayed Ahmad; Hosseinian, Tahmineh

2017-05-01

Multiple-point Geostatistics is a well-known general statistical framework by which complex geological phenomena have been modeled efficiently. Pixel-based and patch-based are two major categories of these methods. In this paper, the optimization-based category is used which has a dual concept in texture synthesis as texture optimization. Our extended version of texture optimization uses the energy concept to model geological phenomena. While honoring the hard point, the minimization of our proposed cost function forces simulation grid pixels to be as similar as possible to training images. Our algorithm has a self-enrichment capability and creates a richer training database from a sparser one through mixing the information of all surrounding patches of the simulation nodes. Therefore, it preserves pattern continuity in both continuous and categorical variables very well. It also shows a fuzzy result in its every realization similar to the expected result of multi realizations of other statistical models. While the main core of most previous Multiple-point Geostatistics methods is sequential, the parallel main core of our algorithm enabled it to use GPU efficiently to reduce the CPU time. One new validation method for MPS has also been proposed in this paper.

Donor Selection for Allogenic Hemopoietic Stem Cell Transplantation: Clinical and Ethical Considerations

PubMed Central

Pascale, Natascha; La Russa, Raffaele; Liso, Arcangelo; Salerno, Monica

2017-01-01

Allogenic hematopoietic progenitor cell transplantation (allo-HSCT) is an established treatment for many diseases. Stem cells may be obtained from different sources: mobilized peripheral blood stem cells, bone marrow, and umbilical cord blood. The progress in transplantation procedures, the establishment of experienced transplant centres, and the creation of unrelated adult donor registries and cord blood banks gave those without an human leucocyte antigen- (HLA-) identical sibling donor the opportunity to find a donor and cord blood units worldwide. HSCT imposes operative cautions so that the entire donation/transplantation procedure is safe for both donors and recipients; it carries with it significant clinical, moral, and ethical concerns, mostly when donors are minors. The following points have been stressed: the donation should be excluded when excessive risks for the donor are reasonable, donors must receive an accurate information regarding eventual adverse events and health burden for the donors themselves, a valid consent is required, and the recipient's risks must be outweighed by the expected benefits. The issue of conflict of interest, when the same physician has the responsibility for both donor selection and recipient care, is highlighted as well as the need of an adequate insurance protection for all the parties involved. PMID:28680446

Optimal ballistically captured Earth-Moon transfers

NASA Astrophysics Data System (ADS)

Ricord Griesemer, Paul; Ocampo, Cesar; Cooley, D. S.

2012-07-01

The optimality of a low-energy Earth-Moon transfer terminating in ballistic capture is examined for the first time using primer vector theory. An optimal control problem is formed with the following free variables: the location, time, and magnitude of the transfer insertion burn, and the transfer time. A constraint is placed on the initial state of the spacecraft to bind it to a given initial orbit around a first body, and on the final state of the spacecraft to limit its Keplerian energy with respect to a second body. Optimal transfers in the system are shown to meet certain conditions placed on the primer vector and its time derivative. A two point boundary value problem containing these necessary conditions is created for use in targeting optimal transfers. The two point boundary value problem is then applied to the ballistic lunar capture problem, and an optimal trajectory is shown. Additionally, the problem is then modified to fix the time of transfer, allowing for optimal multi-impulse transfers. The tradeoff between transfer time and fuel cost is shown for Earth-Moon ballistic lunar capture transfers.

Multi-objective optimization of hole characteristics during pulsed Nd:YAG laser microdrilling of gamma-titanium aluminide alloy sheet

NASA Astrophysics Data System (ADS)

Biswas, R.; Kuar, A. S.; Mitra, S.

2014-09-01

Nd:YAG laser microdrilled holes on gamma-titanium aluminide, a newly developed alloy having wide applications in turbine blades, engine valves, cases, metal cutting tools, missile components, nuclear fuel and biomedical engineering, are important from the dimensional accuracy and quality of hole point of view. Keeping this in mind, a central composite design (CCD) based on response surface methodology (RSM) is employed for multi-objective optimization of pulsed Nd:YAG laser microdrilling operation on gamma-titanium aluminide alloy sheet to achieve optimum hole characteristics within existing resources. The three characteristics such as hole diameter at entry, hole diameter at exit and hole taper have been considered for simultaneous optimization. The individual optimization of all three responses has also been carried out. The input parameters considered are lamp current, pulse frequency, assist air pressure and thickness of the job. The responses at predicted optimum parameter level are in good agreement with the results of confirmation experiments conducted for verification tests.

A Parallel Particle Swarm Optimization Algorithm Accelerated by Asynchronous Evaluations

NASA Technical Reports Server (NTRS)

Venter, Gerhard; Sobieszczanski-Sobieski, Jaroslaw

2005-01-01

A parallel Particle Swarm Optimization (PSO) algorithm is presented. Particle swarm optimization is a fairly recent addition to the family of non-gradient based, probabilistic search algorithms that is based on a simplified social model and is closely tied to swarming theory. Although PSO algorithms present several attractive properties to the designer, they are plagued by high computational cost as measured by elapsed time. One approach to reduce the elapsed time is to make use of coarse-grained parallelization to evaluate the design points. Previous parallel PSO algorithms were mostly implemented in a synchronous manner, where all design points within a design iteration are evaluated before the next iteration is started. This approach leads to poor parallel speedup in cases where a heterogeneous parallel environment is used and/or where the analysis time depends on the design point being analyzed. This paper introduces an asynchronous parallel PSO algorithm that greatly improves the parallel e ciency. The asynchronous algorithm is benchmarked on a cluster assembled of Apple Macintosh G5 desktop computers, using the multi-disciplinary optimization of a typical transport aircraft wing as an example.

Materials Research for High Speed Civil Transport and Generic Hypersonics-Metals Durability

NASA Technical Reports Server (NTRS)

Schulz, Paul; Hoffman, Daniel

1996-01-01

This report covers a portion of an ongoing investigation of the durability of titanium alloys for the High Speed Civil Transport (HSCT). Candidate alloys need to possess an acceptable combination of properties including strength and toughness as well as fatigue and corrosion resistance when subjected to the HSCT operational environment. These materials must also be capable of being processed into required product forms while maintaining their properties. Processing operations being considered for this airplane include forming, welding, adhesive bonding, and superplastic forming with or without diffusion bonding. This program was designed to develop the material properties database required to lower the risk of using advanced titanium alloys on the HSCT.

A 54-Year-Old Woman with Donor Cell Origin of Multiple Myeloma after Allogeneic Hematopoietic Stem Cell Transplantation for the Treatment of CML

PubMed Central

Maestas, Erika; Jain, Shikha; Stiff, Patrick

2016-01-01

Chronic myeloid leukemia is a myeloproliferative disorder that may be treated with hematopoietic stem cell transplantation (HSCT). While posttransplantation relapse of disease resulting from a failure to eradicate the patient's original leukemia could occur, patients may also rarely develop a secondary malignancy or myelodysplastic syndrome (MDS) of donor origin termed donor cell leukemia (DCL). Cases of donor-derived acute myeloid leukemia (AML) or MDS after HSCT or solid tumor transplantation have been published. However, very few cases of donor-derived multiple myeloma (MM) exist. We describe a patient who developed a donor-derived MM following allogeneic HSCT from a sibling donor. PMID:26989529

Successful Treatment of Pediatric Epstein-Barr Virus-positive Aggressive Natural Killer-Cell Leukemia.

PubMed

Kim, Bo Kyung; Hong, Kyung Taek; Kang, Hyoung Jin; An, Hong Yul; Choi, Jung Yoon; Hong, Che Ry; Park, Kyung Duk; Lee, Dong Soon; Shin, Hee Young

2018-06-08

Epstein-Barr virus (EBV)-positive aggressive natural killer-cell leukemia (ANKL) is a rare malignancy of mature natural killer cells, with a very poor survival rate. Patients have a rapidly declining clinical course and a poor prognosis, with a median survival of only a few months. Herein, we describe a 16-year-old boy who was diagnosed with EBV-positive ANKL and successfully treated using combination chemotherapy and a subsequent allogeneic hematopoietic stem cell transplantation (alloHSCT). The patient is disease free 4 years and 9 months after alloHSCT. Thus, combination chemotherapy followed by alloHSCT seems to be a promising therapeutic option for EBV-positive ANKL.

T cells for viral infections after allogeneic hematopoietic stem cell transplant.

PubMed

Bollard, Catherine M; Heslop, Helen E

2016-06-30

Despite recent advances in the field of allogeneic hematopoietic stem cell transplantation (HSCT), viral infections are still a major complication during the period of immune suppression that follows the procedure. Adoptive transfer of donor-derived virus-specific cytotoxic T cells (VSTs) is a strategy to rapidly restore virus-specific immunity to prevent or treat viral diseases after HSCT. Early proof of principle studies demonstrated that the administration of donor-derived T cells specific for cytomegalovirus or Epstein-Barr virus (EBV) could effectively restore virus-specific immunity and control viral infections. Subsequent studies using different expansion or direct selection techniques have shown that donor-derived VSTs confer protection in vivo after adoptive transfer in 70% to 90% of recipients. Because a major cause of failure is lack of immunity to the infecting virus in a naïve donor, more recent studies have infused closely matched third-party VSTs and reported response rates of 60% to 70%. Current efforts have focused on broadening the applicability of this approach by: (1) extending the number of viral antigens being targeted, (2) simplifying manufacture, (3) exploring strategies for recipients of virus-naïve donor grafts, and (4) developing and optimizing "off the shelf" approaches. © 2016 by The American Society of Hematology.

Multi-point Adjoint-Based Design of Tilt-Rotors in a Noninertial Reference Frame

NASA Technical Reports Server (NTRS)

Jones, William T.; Nielsen, Eric J.; Lee-Rausch, Elizabeth M.; Acree, Cecil W.

2014-01-01

Optimization of tilt-rotor systems requires the consideration of performance at multiple design points. In the current study, an adjoint-based optimization of a tilt-rotor blade is considered. The optimization seeks to simultaneously maximize the rotorcraft figure of merit in hover and the propulsive efficiency in airplane-mode for a tilt-rotor system. The design is subject to minimum thrust constraints imposed at each design point. The rotor flowfields at each design point are cast as steady-state problems in a noninertial reference frame. Geometric design variables used in the study to control blade shape include: thickness, camber, twist, and taper represented by as many as 123 separate design variables. Performance weighting of each operational mode is considered in the formulation of the composite objective function, and a build up of increasing geometric degrees of freedom is used to isolate the impact of selected design variables. In all cases considered, the resulting designs successfully increase both the hover figure of merit and the airplane-mode propulsive efficiency for a rotor designed with classical techniques.

G6PD deficiency from lyonization after hematopoietic stem cell transplantation from female heterozygous donors.

PubMed

Au, W-Y; Pang, A; Lam, K K Y; Song, Y-Q; Lee, W-M; So, J C C; Kwong, Y-L

2007-10-01

To determine whether during hematopoietic stem cell transplantation (HSCT), X-chromosome inactivation (lyonization) of donor HSC might change after engraftment in recipients, the glucose-6-phosphate dehydrogenase (G6PD) gene of 180 female donors was genotyped by PCR/allele-specific primer extension, and MALDI-TOF mass spectrometry/Sequenom MassARRAY analysis. X-inactivation was determined by semiquantitative PCR for the HUMARA gene before/after HpaII digestion. X-inactivation was preserved in most cases post-HSCT, although altered skewing of lyonization might occur to either of the X-chromosomes. Among pre-HSCT clinicopathologic parameters analyzed, only recipient gender significantly affected skewing. Seven donors with normal G6PD biochemically but heterozygous for G6PD mutants were identified. Owing to lyonization changes, some donor-recipient pairs showed significantly different G6PD levels. In one donor-recipient pair, extreme lyonization affecting the wild-type G6PD allele occurred, causing biochemical G6PD deficiency in the recipient. In HSCT from asymptomatic female donors heterozygous for X-linked recessive disorders, altered lyonization might cause clinical diseases in the recipients.

Antiviral T Cells for Adenovirus in the Pretransplant Period: A Bridge Therapy for Severe Combined Immunodeficiency.

PubMed

Miller, Holly K; Hanley, Patrick J; Lang, Haili; Lazarski, Christopher A; Chorvinsky, Elizabeth A; McCormack, Sarah; Roesch, Lauren; Albihani, Shuroug; Dean, Marcus; Hoq, Fahmida; Adams, Roberta H; Bollard, Catherine M; Keller, Michael D

2018-05-09

Viral infections can be life threatening in patients with severe combined immunodeficiency (SCID) and other forms of profound primary immunodeficiency disorders both before and after hematopoietic stem cell transplantation (HSCT). Adoptive immunotherapy with virus-specific T cells (VSTs) has been utilized in many patients in the setting of HSCT, but has very rarely been attempted for treatment of viral infections before HSCT. Here we describe the use of VSTs in an infant with RAG1 SCID who had developed disseminated adenovirus which failed to improve on cidofovir. Adenovirus cleared following 2 doses of VSTs and marrow infusion from a matched unrelated donor, without incidence of graft versus host disease. T cell receptor-b sequencing demonstrated expansion of adenovirus-specific T cell fraction of the VSTs, suggesting that infusion facilitated viral clearance. This report suggests that VSTs are likely safe in the pre-HSCT period, and may be a useful bridge therapy for infants with SCID and persistent viral infections. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Adoptive T Cell Immunotherapy for Patients with Primary Immunodeficiency Disorders.

PubMed

McLaughlin, Lauren P; Bollard, Catherine M; Keller, Michael

2017-01-01

Primary immunodeficiency disorders (PID) are a group of inborn errors of immunity with a broad range of clinical severity but often associated with recurrent and serious infections. While hematopoietic stem cell transplantation (HSCT) can be curative for some forms of PID, chronic and/or refractory viral infections remain a cause of morbidity and mortality both before and after HSCT. Although antiviral pharmacologic agents exist for many viral pathogens, these are associated with significant costs and toxicities and may not be effective for increasingly drug-resistant pathogens. Thus, the emergence of adoptive immunotherapy with virus-specific T lymphocytes (VSTs) is an attractive option for addressing the underlying impaired T cell immunity in many PID patients. VSTs have been utilized for PID patients following HSCT in many prior phase I trials, and may potentially be beneficial before HSCT in patients with chronic viral infections. We review the various methods of generating VSTs, clinical experience using VSTs for PID patients, and current limitations as well as potential ways to broaden the clinical applicability of adoptive immunotherapy for PID patients.

Short- and long-term outcomes of adult allogeneic hematopoietic stem cell transplant patients admitted to the intensive care unit in the peritransplant period.

PubMed

Mayer, Sebastian; Pastores, Stephen M; Riedel, Elyn; Maloy, Molly; Jakubowski, Ann A

2017-02-01

Survival of allogeneic hematopoietic stem cell transplant (aHSCT) recipients in the intensive care unit (ICU) has been poor. We retrospectively analyzed the short- and long-term outcomes of aHSCT patients admitted to the ICU over a 12-year period. Of 1235 adult patients who had aHSCT between 2002 and 2013, 161 (13%) were admitted to the ICU. The impact of clinical parameters was assessed and outcomes were compared for the periods 2002-2007 and 2008-2013. The ICU, in-hospital, 1- and 5-year survival rates were 64.6%, 46%, 33% and 20%, respectively. Mechanical ventilation and vasopressor use predicted for worse hospital- and overall survival (OS). After 2008, the requirement for mechanical ventilation and vasopressors, and the diagnosis of sepsis were reduced. While hospital mortality decreased from 69% to 44%, long-term survival (LTS) remained unchanged. Late deaths, due to causes not associated with the ICU such as relapse and graft-versus-host disease, increased. As thresholds for transplant are lowered, improvements in ICU outcomes for aHSCT recipients may be limited.

How We Manage Adenosine Deaminase-Deficient Severe Combined Immune Deficiency (ADA SCID).

PubMed

Kohn, Donald B; Gaspar, H Bobby

2017-05-01

Adenosine deaminase-deficient severe combined immune deficiency (ADA SCID) accounts for 10-15% of cases of human SCID. From what was once a uniformly fatal disease, the prognosis for infants with ADA SCID has improved greatly based on the development of multiple therapeutic options, coupled with more frequent early diagnosis due to implementation of newborn screening for SCID. We review the various treatment approaches for ADA SCID including allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen-matched sibling or family member or from a matched unrelated donor or a haplo-identical donor, autologous HSCT with gene correction of the hematopoietic stem cells (gene therapy-GT), and enzyme replacement therapy (ERT) with polyethylene glycol-conjugated adenosine deaminase. Based on growing evidence of safety and efficacy from GT, we propose a treatment algorithm for patients with ADA SCID that recommends HSCT from a matched family donor, when available, as a first choice, followed by GT as the next option, with allogeneic HSCT from an unrelated or haplo-identical donor or long-term ERT as other options.

Critical care of the hematopoietic stem cell transplant recipient.

PubMed

Afessa, Bekele; Azoulay, Elie

2010-01-01

An estimated 50,000 to 60,000 patients undergo hematopoietic stem cell transplantation (HSCT) worldwide annually, of which 15.7% are admitted to the intensive care unit (ICU). The most common reason for ICU admission is respiratory failure and almost all develop single or multiorgan failure. Most HSCT recipients admitted to ICU receive invasive mechanical ventilation (MV). The overall short-term mortality rate of HSCT recipients admitted to ICU is 65%, and 86.4% for those receiving MV. Patient outcome has improved over time. Poor prognostic indicators include advanced age, poor functional status, active disease at transplant, allogeneic transplant, the severity of acute illness, and the development of multiorgan failure. ICU resource limitations often lead to triage decisions for admission. For HSCT recipients, the authors recommend (1) ICU admission for full support during their pre-engraftment period and when there is no evidence of disease recurrence; (2) no ICU admission for patients who refuse it and those who are bedridden with disease recurrence and without treatment options except palliation; (3) a trial ICU admission for patients with unknown status of disease recurrence with available treatment options.

The potential use of mesenchymal stem cells in hematopoietic stem cell transplantation

PubMed Central

Kim, Eun-Jung; Kim, Nayoun; Cho, Seok-Goo

2013-01-01

In the last 10 years, mesenchymal stem cells (MSCs) have emerged as a therapeutic approach to regenerative medicine, cancer, autoimmune diseases, and many more due to their potential to differentiate into various tissues, to repair damaged tissues and organs, and also for their immunomodulatory properties. Findings in vitro and in vivo have demonstrated immune regulatory function of MSCs and have facilitated their application in clinical trials, such as those of autoimmune diseases and chronic inflammatory diseases. There has been an increasing interest in the role of MSCs in allogeneic hematopoietic stem cell transplantation (HSCT), including hematopoietic stem cell engraftment and the prevention and treatment of graft-versus-host disease (GVHD), and their therapeutic potential has been reported in numerous clinical trials. Although the safety of clinical application of MSCs is established, further modifications to improve their efficacy are required. In this review, we summarize advances in the potential use of MSCs in HSCT. In addition, we discuss their use in clinical trials of the treatment of GVHD following HSCT, the immunomodulatory capacity of MSCs, and their regenerative and therapeutic potential in the field of HSCT. PMID:23306700

Early recovery of T-cell function predicts improved survival after T-cell depleted allogeneic transplant.

PubMed

Goldberg, Jenna D; Zheng, Junting; Ratan, Ravin; Small, Trudy N; Lai, Kuan-Chi; Boulad, Farid; Castro-Malaspina, Hugo; Giralt, Sergio A; Jakubowski, Ann A; Kernan, Nancy A; O'Reilly, Richard J; Papadopoulos, Esperanza B; Young, James W; van den Brink, Marcel R M; Heller, Glenn; Perales, Miguel-Angel

2017-08-01

Infection, relapse, and GVHD can complicate allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although the effect of poor immune recovery on infection risk is well-established, there are limited data on the effect of immune reconstitution on relapse and survival, especially following T-cell depletion (TCD). To characterize the pattern of immune reconstitution in the first year after transplant and its effects on survival and relapse, we performed a retrospective study in 375 recipients of a myeloablative TCD allo-HSCT for hematologic malignancies. We noted that different subsets recover sequentially, CD8 + T cells first, followed by total CD4 + and naïve CD4 + T cells, indicating thymic recovery during the first year after HSCT. In the multivariate model, a fully HLA-matched donor and recovery of T-cell function, assessed by PHA response at 6 months, were the only factors independently associated with OS and EFS. In conclusion, T-cell recovery is an important predictor of outcome after TCD allo-HSCT.

Quality of life concerns and depression among hematopoietic stem cell transplant survivors.

PubMed

Mosher, Catherine E; DuHamel, Katherine N; Rini, Christine; Corner, Geoffrey; Lam, Joanne; Redd, William H

2011-09-01

This study examined quality of life, transplant-related concerns, and depressive symptoms and their demographic and medical correlates at 1 to 3 years following hematopoietic stem cell transplantation (HSCT). HSCT survivors (N=406) completed telephone-administered questionnaires that assessed demographic variables, functional status, quality of life, transplant-related concerns, and depressive symptoms. The most prevalent concerns among HSCT survivors included physical symptoms (e.g., fatigue and pain), maintaining current health status and employment, changes in appearance, and lack of sexual interest and satisfaction. In addition, almost one-third (32%) of survivors age 40 years and younger reported concern about their ability to have children. Unemployed survivors and those with lower incomes and worse functional status were more likely to experience poorer quality of life in multiple domains. Fifteen percent of the sample reported moderate to severe depressive symptoms, and these symptoms were higher among allogeneic transplant recipients and those with lower functional status. Results suggest that interventions are needed to address physical symptoms, coping with an uncertain future, infertility, and sexual issues during the early phase of HSCT survivorship.

Patient, virus, and treatment-related risk factors in pediatric adenovirus infection after stem cell transplantation: results of a routine monitoring program.

PubMed

Mynarek, Martin; Ganzenmueller, Tina; Mueller-Heine, Annika; Mielke, Christopher; Gonnermann, Andrea; Beier, Rita; Sauer, Martin; Eiz-Vesper, Britta; Kohstall, Ute; Sykora, Karl-Walter; Heim, Albert; Maecker-Kolhoff, Britta

2014-02-01

Human adenovirus (HAdV) infection after hematopoietic stem cell transplantation (HSCT) is associated with significant morbidity and mortality in children. The optimal surveillance and treatment strategies are under discussion. Here, we present data from 238 consecutive pediatric allogeneic HSCT recipients who underwent transplantation in a single center who were included in a prospective, weekly HAdV DNAemia monitoring program by quantitative PCR. HAdV loads >1000 copies/mL were detected in 15.5% of all patients. Despite a low mortality directly attributed to HAdV infection (2 patients, 0.84%), blood HAdV loads >10,000 copies/mL (6.7% of all patients) were significant and independent risk factors for poor survival. We searched for patient, virus, and treatment-related risk factors of HAdV DNAemia and disease. Detection of HAdV in blood before day 50 post transplantation was a major independent risk factor for the development of blood HAdV loads >10,000 copies/mL. HAdV typing revealed A31, C1, and C2 as the predominant pathogens among several other HAdV strains with type C species detected in most patients with severe HAdV disease. Stool HAdV loads were prospectively monitored in 111 patients and correlated with but did not significantly precede detection in blood. Treatment with cidofovir led to stable or reduced viral load in 70% of patients with blood HAdV loads >1000 copies/mL. Thus, early occurrence of HAdV-DNA in blood of pediatric HSCT recipients predisposes for development of high viral loads. Control of HAdV infections was attempted by preemptive cidofovir treatment of patients with high blood HAdV loads or with symptomatic organ infections and correlated with low HAdV-attributed mortality. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Effect of sertraline on complications and survival after hematopoietic stem-cell transplantation, a double-blind, placebo-controlled clinical study.

PubMed

Tavakoli-Ardakani, Maria; Kheshti, Raziyeh; Maryam, Mehrpooya

2017-12-01

Previous studies have found a connection between psychiatric problems and post-hematopoietic stem-cell transplantation (HSCT) complications. We sought to evaluate the effect of sertraline on engraftment time, hospitalization period, mortality, and post-transplantation complications in HSCT recipients with depression and/or anxiety. We recruited adults aged 18-60, who were candidates for autologous or allogeneic HSCT with major depression and/or anxiety disorder. They were administered 50 mg of sertraline or placebo daily for the first week, and then 100 mg for the following seven weeks. We documented occurrence and severity of early post-HSCT complications, including infection, mucositis, nausea and vomiting, diarrhea, pain, renal toxicities and liver complications, acute graft-versus-host disease, and veno-occlusive disease, as well as time to engraftment, length of hospitalization and 6-month mortality. Overall, 56 patients participated in the study (sertraline group n = 30, placebo group n = 26). Of the complications, only mortality and readmission up to 6 months post-transplantation were significantly higher in the placebo group compared to sertraline group (P values = 0.040, 0.028, respectively). There were no significant differences for other complications between the groups. Mean engraftment time was significantly lower in the sertraline group (P value = 0.048). This study provides evidence that sertraline positively influences engraftment time, readmission, and mortality after HSCT.