42 CFR 493.941 - Hematology (including routine hematology and coagulation).

Code of Federal Regulations, 2010 CFR

2010-10-01

... of a laboratory's responses for qualitative and quantitative hematology tests or analytes, the...) of this section. (2) For quantitative hematology tests or analytes, the program must determine the...

42 CFR 493.941 - Hematology (including routine hematology and coagulation).

Code of Federal Regulations, 2012 CFR

2012-10-01

... of a laboratory's responses for qualitative and quantitative hematology tests or analytes, the...) of this section. (2) For quantitative hematology tests or analytes, the program must determine the...

42 CFR 493.941 - Hematology (including routine hematology and coagulation).

Code of Federal Regulations, 2011 CFR

2011-10-01

... of a laboratory's responses for qualitative and quantitative hematology tests or analytes, the...) of this section. (2) For quantitative hematology tests or analytes, the program must determine the...

Cisplatin-Based Chemotherapy versus Cetuximab in Concurrent Chemoradiotherapy for Locally Advanced Head and Neck Cancer Treatment

PubMed Central

Hu, Ming-Hung; Wang, Ling-Wei; Lu, Hsueh-Ju; Chu, Pen-Yuan; Tai, Shyh-Kuan; Lee, Tsung-Lun; Chen, Ming-Huang; Yang, Muh-Hwa; Chang, Peter Mu-Hsin

2014-01-01

Background and Purpose. This study aimed to analyze survival, clinical responses, compliance, and adverse effects in locally advanced head and neck cancer (LAHNC) patients treated with split-dose cisplatin-based concurrent chemoradiation therapy (SD-CCRT) or cetuximab with concurrent radiation therapy (BioRT). Materials and Methods. We retrospectively evaluated 170 LAHNC patients diagnosed between January 1, 2009, and July 31, 2012: 116 received CCRT and 54 received BioRT. Results. Complete response rates were similar in the SD-CCRT and BioRT groups (63.8% versus 59.3%; P = 0.807), and locoregional relapse rates were 18.1% and 13.0%, respectively (P = 0.400). The 3-year relapse-free survival rate was 65.8% in the SD-CCRT group and 65.5% in the BioRT group, respectively (P = 0.647). The 3-year overall survival rate was 78.5% in the SD-CCRT group and 70.9% in the BioRT group, respectively (P = 0.879). Hematologic side effects were significantly more frequent in the SD-CCRT than in the BioRT group. Mucositis frequency was similar. Conclusions. Primary SD-CCRT and BioRT both showed good clinical response and survival. Hematologic toxicities were more frequent, but tolerable, in the SD-CCRT group. Both groups showed good compliance. PMID:25110705

Cetuximab Plus Various Chemotherapy Regimens for Patients with KRAS Wild-Type Metastatic Colorectal Cancer.

PubMed

Azadeh, Payam; Mortazavi, Nafiseh; Tahmasebi, Arezoo; Hosseini Kamal, Farnaz; Novin, Kambiz

2016-01-01

The aim of this study was to compare the efficacy and hematologic toxicity of cetuximab combined with various types of chemotherapy regimens in patients with KRAS wild-type metastatic colorectal cancer (mCRC). The response rate, progression-free survival (PFS) and overall survival of the patients were analyzed. In total, 45 patients were included in the study. The overall response rate for the combination of cetuximab and FOLFOX, FOLFIRI and CAPOX was 20, 46 and 30%, respectively, but the differences were not statistically significant. The median PFS for the three groups were 8, 6 and 3.5 months, respectively, but again these differences were not significant. All-grade leukopenia and anemia for the cetuximab plus FOLFOX group were significantly higher than for the other chemotherapy regimens. Our findings suggest that the combination of cetuximab and the three standard chemotherapy regimens resulted in the same outcomes in our patient population of mCRC, with higher hematologic toxicities among the FOLFOX subgroup. © 2015 S. Karger AG, Basel.

ITP: hematology's Cosette from Les Misérables.

PubMed

Rao, V Koneti

2013-03-14

In this issue of Blood, Gudbrandsdottir et al from Denmark report that in the largest multicenter cohort to date comprising newly diagnosed adults with primary immune thrombocytopenia (ITP), addition of rituximab (RTX) to high-dose dexamethasone (DEX) as first-line therapy yields higher sustained response rates.

Transthoracic ultrasonography for the immunocompromised patient. A pilot project that introduces transthoracic ultrasonography for the follow-up of hematological patients in Romania.

PubMed

Frinc, Ioana; Ilies, Petru; Zaharie, Florin; Dima, Delia; Tanase, Alina; Petrov, Ljubomir; Irimie, Alexandru; Berce, Cristian; Lisencu, Cosmin; Berindan-Neagoe, Ioana; Tomuleasa, Ciprian; Bojan, Anca

2017-06-01

In the past decade, there has been significant progress in clinical hematology with the discovery of targeted molecules and thus the achievement of both hematologic and molecular responses. Nevertheless, chemotherapy remains the treatment of choice for many types of hematological malignancies. Aggressive chemotherapy leads to immunosuppression, accompanied by a high rate of infections and an increased rate of treatment-related mortality. Invasive fungal infections as well as more common bacterial and viral infections are frequent in immunocompromised patients as they are difficult to diagnose and treat. Pleuropulmonary infections in immunocompromised patients are diagnosed using clinical examination, imaging and laboratory tests. Many laboratory tests are run for several days before a final result is given and are expensive. Computer tomography is a reliable technique, but it is encumbered by high irradiation and high cost, and can assess lesions larger than 1 cm. Transthoracic ultrasound is a modern method, used in the diagnostic algorithm of pleuropulmonary pathology. It allows the diagnosis of small lesions, can be performed at the patients' bedside, with acceptable costs and no irradiation. A fast, informed and accurate medical decision is essential for a favorable outcome in immunosuppressed patients with an adjacent infection. In the current case series we present the implementation of a new protocol for the follow-up of immunocompromised patients using transthoracic ultrasonography, of great potential use in the clinic.

The Promise of Chimeric Antigen Receptor Engineered T cells in the Treatment of Hematologic Malignancies

PubMed Central

Nagle, Sarah J.; Garfall, Alfred L.; Stadtmauer, Edward A.

2015-01-01

Relapsed and refractory hematologic malignancies have a very poor prognosis. Chimeric antigen receptor (CAR) T cells are emerging as a powerful therapy in this setting. Early clinical trials of genetically modified T cells for the treatment of non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia (ALL) have shown high complete response rates in patients with few therapeutic options. Exploration is ongoing for other hematologic malignancies including multiple myeloma (MM), acute myeloid leukemia (AML) and Hodgkin lymphoma (HL). At the same time, the design and production of CAR T cells is being advanced so that this therapy can be more widely utilized. Cytokine release syndrome (CRS) and neurotoxicity are common, but they are treatable and fully reversible. This review will review currently available data as well as future developments and challenges in the field. PMID:26841014

Improved Adherence Rates and Clinical Outcomes of an Integrated, Closed-Loop, Pharmacist-Led Oral Chemotherapy Management Program.

PubMed

Muluneh, Benyam; Schneider, Molly; Faso, Aimee; Amerine, Lindsey; Daniels, Rowell; Crisp, Brett; Valgus, John; Savage, Scott

2018-06-01

To address the growing use of oral anticancer therapy, an integrated, closed-loop, pharmacist-led oral chemotherapy management program was created within an academic medical center. An integrated, closed-loop, pharmacy-led oral chemotherapy management program was established. From September 2014 until June 2015, demographic information, rates of adherence, patient understanding of treatment, pharmacist interventions, patient and provider satisfaction, and molecular response rates in patients with chronic myeloid leukemia (CML) were collected. After full implementation, 107 patients were enrolled in our oral chemotherapy management program from September 2014 until June 2015. All patients were educated before starting oral chemotherapy, and using pre- and postassessment tests, comprehension of oral chemotherapy treatment increased from 43% to 95%. Patient-reported adherence was 86% and 94.7% for the GI/breast and malignant hematology patient populations, respectively, and these were validated with medication possession ratio, revealing adherence rates of 85% and 93.9% for the GI/breast and malignant hematology patient populations, respectively. A total of 350 encounters with a clinical pharmacist and 318 adverse effects were reported, which led to 235 interventions. This program led to a higher major molecular response rate (83%) in our CML population compared with published clinical trials (average major molecular response rates, 40% and 60% with 1- and 2-year follow-up, respectively). An innovative model was developed and resulted in improved patient knowledge regarding oral chemotherapy, improved adherence rates that exceeded nationally established thresholds, and superior major molecular response outcomes for patients with CML compared with published literature. As a result, this model has produced the gold standard in managing patients receiving oral chemotherapy.

Behavioral and hematological responses of broiler chickens administered with betaine and ascorbic acid during hot-dry season.

PubMed

Egbuniwe, Ifeanyichukwu C; Ayo, Joseph O; Kawu, Mohammed U; Mohammed, Aliyu

2018-02-05

Heat stress is a major problem in poultry production in tropical regions. Assessing the impact of thermally stressful environmental conditions on the welfare of broiler chickens is of great importance. Behavioral responses in a novel environment and hematology of broiler chickens administered with betaine and/or ascorbic acid (AA) during the hot-dry season were evaluated. Broiler chickens were randomly divided into four groups: Group I (control) was given sterile water, Group II was given betaine, Group III was given AA, and Group IV received betaine + AA orally and daily for 42 days. An open-field test was used to assess behavior. Hematological parameters were obtained using a hematology auto-analyzer. The natural environmental conditions were predominantly outside the thermoneutral zone for broiler chickens. Results demonstrated that treated groups exhibited improved ability to adjust faster to a new environment and better hematological responses than controls, evidenced by enhanced behavioral responses, oxygen-carrying capacity, and immune responses of broiler chickens under unfavorable environmental conditions. Betaine and/or AA administration to broiler chickens improved some behavioral responses, hemoglobin concentrations, packed cell volume, and total leukocyte count during the hot-dry season.

Hematological toxicity and therapeutic efficacy of lomustine in 20 tumor-bearing cats: critical assessment of a practical dosing regimen.

PubMed

Fan, Timothy M; Kitchell, Barbara E; Dhaliwal, Ravinder S; Jones, Pamela D; Hintermeister, John G; Paria, Biman C

2002-01-01

Twenty cats with spontaneously arising tumors received oral lomustine at a dose range of 32 to 59 mg/m2 every 21 days. Due to biohazard concerns associated with lomustine capsule reformulation, a standardized 10-mg capsule dosage was used for all cats regardless of body weight. Severe hematological toxicity was infrequent, with the incidence of either grade III or IV neutropenia and thrombocytopenia being 4.1% and 1.0%, respectively. Cats receiving higher cumulative doses of lomustine trended toward a greater likelihood for progressive neutropenia (P=0.07). Two cats with lymphoma, two cats with fibrosarcoma, and one cat with multiple myeloma achieved a measurable partial response to lomustine therapy. Cats treated with higher dosages of lomustine trended toward statistically significant higher response rates (P=0.07).

A Review of Player Monitoring Approaches in Basketball: Current Trends and Future Directions.

PubMed

Fox, Jordan L; Scanlan, Aaron T; Stanton, Robert

2017-07-01

Fox, JL, Scanlan, AT, and Stanton, R. A review of player monitoring approaches in basketball: current trends and future directions. J Strength Cond Res 31(7): 2021-2029, 2017-Effective monitoring of players in team sports such as basketball requires an understanding of the external demands and internal responses, as they relate to training phases and competition. Monitoring of external demands and internal responses allows coaching staff to determine the dose-response associated with the imposed training load (TL), and subsequently, if players are adequately prepared for competition. This review discusses measures reported in the literature for monitoring the external demands and internal responses of basketball players during training and competition. The external demands of training and competition were primarily monitored using time-motion analysis, with limited use of microtechnology being reported. Internal responses during training were typically measured using hematological markers, heart rate, various TL models, and perceptual responses such as rating of perceived exertion (RPE). Heart rate was the most commonly reported indicator of internal responses during competition with limited reporting of hematological markers or RPE. These findings show a large discrepancy between the reporting of external and internal measures and training and competition demands. Microsensors, however, may be a practical and convenient method of player monitoring in basketball to overcome the limitations associated with current approaches while allowing for external demands and internal responses to be recorded simultaneously. The triaxial accelerometers of microsensors seem well suited for basketball and warrant validation to definitively determine their place in the monitoring of basketball players. Coaching staff should make use of this technology by tracking individual player responses across the annual plan and using real-time monitoring to minimize factors such as fatigue and injury risk.

Italian real life experience with ibrutinib: results of a large observational study on 77 relapsed/refractory mantle cell lymphoma.

PubMed

Broccoli, Alessandro; Casadei, Beatrice; Morigi, Alice; Sottotetti, Federico; Gotti, Manuel; Spina, Michele; Volpetti, Stefano; Ferrero, Simone; Spina, Francesco; Pisani, Francesco; Merli, Michele; Visco, Carlo; Paolini, Rossella; Zilioli, Vittorio Ruggero; Baldini, Luca; Di Renzo, Nicola; Tosi, Patrizia; Cascavilla, Nicola; Molica, Stefano; Ilariucci, Fiorella; Rigolin, Gian Matteo; D'Alò, Francesco; Vanazzi, Anna; Santambrogio, Elisa; Marasca, Roberto; Mastrullo, Lucia; Castellino, Claudia; Desabbata, Giovanni; Scortechini, Ilaria; Trentin, Livio; Morello, Lucia; Argnani, Lisa; Zinzani, Pier Luigi

2018-05-04

Although sometimes presenting as an indolent lymphoma, mantle cell lymphoma (MCL) is an aggressive disease, hardly curable with standard chemo-immunotherapy. Current approaches have greatly improved patients' outcomes, nevertheless the disease is still characterized by high relapse rates. Before approval by EMA, Italian patients with relapsed/refractory MCL were granted ibrutinib early access through a Named Patient Program (NPP). An observational, retrospective, multicenter study was conducted. Seventy-seven heavily pretreated patients were enrolled. At the end of therapy there were 14 complete responses and 14 partial responses, leading to an overall response rate of 36.4%. At 40 months overall survival was 37.8% and progression free survival was 30%; disease free survival was 78.6% at 4 years: 11/14 patients are in continuous complete response with a median of 36 months of follow up. Hematological toxicities were manageable, and main extra-hematological toxicities were diarrhea (9.4%) and lung infections (9.0%). Overall, 4 (5.2%) atrial fibrillations and 3 (3.9%) hemorrhagic syndromes occurred. In conclusions, thrombocytopenia, diarrhea and lung infections are the relevant adverse events to be clinically focused on; regarding effectiveness, ibrutinib is confirmed to be a valid option for refractory/relapsed MCL also in a clinical setting mimicking the real world.

Extracorporeal photopheresis for graft-versus-host disease: the role of patient, transplant, and classification criteria and hematologic values on outcome-results from a large single-center study.

PubMed

Berger, Massimo; Albiani, Roberto; Sini, Bruno; Fagioli, Franca

2015-04-01

Extracorporeal photopheresis (ECP) has been shown as active therapy for graft-versus-host disease (GVHD). The aim was to ascertain the role of ECP in 71 patients with steroid-refractory or -dependent acute and chronic GVHD (aGVHD and cGVHD) with special focus on hematologic variables and GVHD staging classification. A total of 34 patients were treated for aGVHD and 37 for cGVHD. The overall response rate (ORR) for aGVHD was 65% and the complete aGVHD-free survival was 50% (95% confidence interval [CI], 36%-70%). The ORR for cGVHD response was 81% while the complete cGVHD-free survival was 50% (95% CI, 34%-73%). The aGVHD-free survival was associated with aGVHD grading (Grade II 81%, Grade III 33%, and Grade IV 0%, p ≤ 0.00) and the absence of visceral involvement (77% vs. 33%, p = 0.03). The cGVHD-free survival was associated with the female sex (67% vs. 25%, p = 0.01) and with the limited form according to the Seattle classification (67% vs. 20%, p = 0.003). No role for hematologic values or apheresis cell count was found, except for the cGVHD ORR (p = 0.037). Transplant-related mortality and overall survival were associated with ECP response 0% versus 54% (p = 0.0001) and 77% versus 45% (p = 0.03) for aGVHD patients and 7% versus 14% (p = 0.02) and 73% versus 20% (p = 0.0003) for cGVHD patients, respectively. While confirming a higher probability of GVHD responses for early GVHD, our study shows no role of hematologic values or apheresis cell count on GVHD response. © 2014 The Authors. Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.

[Treatment of transfusion-dependent nonsevere aplastic anemia with cyclosporine A plus ATG/ALG versus cyclosporine A plus androgens: a retrospective single center study].

PubMed

Song, L; Peng, G X; Wu, Z J; Zhang, L; Jing, L P; Zhou, K; Li, Y; Li, Y; Ye, L; Li, J P; Fan, H H; Zhao, X; Yang, W R; Yang, Y; Zhang, F K

2016-11-14

Objective: To determine whether cyclosporine A (CsA) plus androgens was as effective as the current standard immunosuppressive therapy (IST) for transfusion-dependent nonsevere aplastic anemia (TD-NSAA). Methods: The records of 125 consecutive TD-NSAA patients who were treated between Aug. 2007 and Sept. 2014, with either CsA plus androgen or ALG/ATG plus CsA regimen were reviewed. The 3-month and 6-month hematologic responses and survival were evaluated. Results: There were 125 TD-NSAA patients (70 were male and 55 female, 1.25∶1). Median age was 27 (6-66) years. There was no significant difference in early mortality between 48 treated by ATG/ALG plus CsA and 77 by CsA plus androgen patients (1/48 vs 0/77, P =0.384). Both the total hematologic response and the better hematological response rates at 3-month (70.8% vs 45.5%, P =0.006 and 27.1% vs 10.4%, P =0.015, respectively) and 6-month (75.0% vs 55.8%, P =0.031 and 41.7% vs 22.1% P =0.020, respectively) after treatment were much higher in the standard IST group than that in CsA plus androgen group. The median time to transfusion independent of 36.5 (0-149) days in the standard IST group was significantly shorter than 98 (14-180) days in CsA plus androgen group ( P <0.001). Survival was comparable between the two groups (97.9% vs 100.0%, P =0.227). It was superior (71.2% vs 59.5%) but not significantly ( P =0.227) in event-free survival in standard IST group. Conclusions: CsA plus androgen was inferior to the standard IST of ATG/ALG and CsA regimen in treating TD-NSAA in terms of the hematologic response and the quality of response, despite of comparable short-term survival.

SUBACTUTE HEMATOLOGICAL RESPONSES OF THE YUCATAN SAILFIN MOLLY (POECILIA VELIFERA) EXPOSED TO CADMIUM CHLORIDE

EPA Science Inventory

This study focuses on the subacute hematological responses of the Yucatan sailfin molly, Poecilia velifera, exposed to cadmium chloride. Previous studies in other teleosts and mammals have suggested that exposure to cadmium chloride results in a leucocytic response. Fish were exp...

SUBACUTE HEMATOLOGICAL RESPONSES OF THE YUCATAN SAILFIN MOLLY (POECILIA VELIFERA) EXPOSED TO CADMIUM CHLORIDE

EPA Science Inventory

This study focuses on the subacute hematological responses of the Yucatan sailfin molly, Poecilia velifera, exposed to cadmium chloride. Previous studies in other teleosts and mammals have suggested that exposure to cadmium chloride results in a leucocytic response. Fish were exp...

The Effects of Altitude Training on Erythropoietic Response and Hematological Variables in Adult Athletes: A Narrative Review

PubMed Central

Płoszczyca, Kamila; Langfort, Józef; Czuba, Miłosz

2018-01-01

Background: One of the goals of altitude training is to increase blood oxygen-carrying capacity in order to improve sea-level endurance performance in athletes. The elevated erythropoietin (EPO) production in hypoxia is a key factor in the achievement of enhanced hematological variables. The level of the EPO increase and acceleration of erythropoiesis depend on the duration of exposure and degree of hypoxia. Furthermore, many other factors may affect the hematological response to altitude training. Aim: The purpose of this narrative review was to: (1) analyze the kinetics of EPO and hematological variables during and after altitude training; (2) summarize the current state of knowledge about the possible causes of individual or cohort differences in EPO and hematological response to altitude training; (3) formulate practical guidelines for athletes to improve the efficiency of altitude training. Methods: A narrative review was performed following an electronic search of the databases PubMed/MEDLINE and SPORTDiscus via EBSCO for all English-language articles published between 1997 and 2017. Results: Complete unification of results from studies on EPO kinetics was difficult due to different time and frequency of blood sampling by different researchers during and after altitude training, but the data presented in the reviewed literature allowed us to detect certain trends. The results of the reviewed studies were divergent and indicated either increase or no change of hematological variables following altitude training. Factors that may affect the hematological response to altitude training include hypoxic dose, training content, training background of athletes, and/or individual variability of EPO production. Conclusions: Despite the potential benefits arising from altitude training, its effectiveness in improving hematological variables is still debatable. Further research and better understanding of factors influencing the response to altitude, as well as factors affecting the suitable measurement and interpretation of study results, are needed. PMID:29695978

The Bruton tyrosine kinase inhibitor ibrutinib with chemoimmunotherapy in patients with chronic lymphocytic leukemia.

PubMed

Brown, Jennifer R; Barrientos, Jacqueline C; Barr, Paul M; Flinn, Ian W; Burger, Jan A; Tran, Anh; Clow, Fong; James, Danelle F; Graef, Thorsten; Friedberg, Jonathan W; Rai, Kanti; O'Brien, Susan

2015-05-07

The safety and efficacy of ibrutinib, an oral inhibitor of Bruton tyrosine kinase, were evaluated with chemoimmunotherapy (CIT) in a multicenter phase 1b study. Patients with relapsed/refractory chronic lymphocytic leukemia received bendamustine and rituximab (BR) or fludarabine, cyclophosphamide, and rituximab (FCR) for up to 6 cycles with daily ibrutinib (420 mg) until progressive disease or unacceptable toxicity. Enrollment to FCR-ibrutinib closed early due to a lack of fludarabine-naïve previously treated patients. No patients treated with BR-ibrutinib (n = 30) or FCR-ibrutinib (n = 3) experienced prolonged hematologic toxicity in cycle 1 (primary end point). Tolerability was as expected with either CIT or single-agent ibrutinib. The overall response rate (ORR) with BR-ibrutinib was 93.3%, including 16.7% complete responses (CRs) initially, which increased to 40% with the extension period. Including 1 patient with partial response with lymphocytosis, the best ORR was 96.7%. Sixteen of 21 patients with baseline cytopenias had sustained hematologic improvement. At 12 and 36 months, 86.3% and 70.3% remained progression-free, respectively. All 3 patients treated with ibrutinib-FCR achieved CR. Ibrutinib may enhance CIT efficacy without additive toxicities, providing the rationale for studying this combination in an ongoing phase 3 trial. The study is registered to www.clinicaltrials.gov as #NCT01292135. © 2015 by The American Society of Hematology.

Chemical Immobilization of Sloth Bears (Melursus ursinus) with Ketamine Hydrochloride and Xylazine Hydrochloride: Hematology and Serum Biochemical Values

PubMed Central

Veeraselvam, M.; Sridhar, R.; Perumal, P.; Jayathangaraj, M. G.

2014-01-01

The present study was conducted to define the physiological responses of captive sloth bears immobilized with ketamine hydrochloride and xylazine hydrochloride and to determine and compare the values of hematology and serum biochemical parameters between sexes. A total of 15 sloth bears were immobilized using combination of ketamine hydrochloride and xylazine hydrochloride drugs at the dose rate of 5.0 milligram (mg) per kg body weight and 2.0 mg per kg body weight, respectively. The use of combination of these drugs was found satisfactory for the chemical immobilization of captive sloth bears. There were no significant differences observed in induction time and recovery time and physiological parameters such as heart rate, respiratory rate, and rectal temperature between sexes. Health related parameters comprising hematological values like packed cell volume (PCV), hemoglobin (Hb), red blood cell count (RBC), erythrocyte indices, and so forth and biochemical values like total protein, blood urea nitrogen (BUN), creatinine, alkaline amino-transferase (ALT), aspartate amino-transferase (AST), and so forth were estimated in 11 (5 males and 6 females) apparently healthy bears. Comparison between sexes revealed significant difference in PCV (P < 0.05) and mean corpuscular hemoglobin concentration (MCHC) (P < 0.05). The study might help to evaluate health profiles of sloth bears for appropriate line treatment. PMID:24876990

Use of rituximab as a treatment for systemic lupus erythematosus: retrospective review

PubMed Central

Machado, Roberta Ismael Lacerda; Scheinberg, Morton Aaron; de Queiroz, Maria Yvone Carlos Formiga; de Brito, Danielle Christinne Soares Egypto; Guimarães, Maria Fernanda Brandao de Resende; Giovelli, Raquel Altoé; Freire, Eutilia Andrade Medeiros

2014-01-01

ABSTRACT Objective: To report the experience in three Brazilian institutions with the use of rituximab in patients with different clinical forms of lupus erythematosus systemic in activity. Methods: The study consisted of a sample of 17 patients with LES, who were already being treated, but that at some stage of the disease showed refractory symptoms. The patients were subdivided into groups according to the clinical manifestation, and the responses for the use of rituximab were rated as complete, partial or no response. Data were collected through a spreadsheet, and used specific parameters for each group. The treatment was carried on by using therapeutic dose of 1g, and repeating the infusion within an interval of 15 days. Results: The clinical responses to rituximab of the group only hematological and of the group only osteoarticular were complete in all cases. In the renal group there was a clinical complete response, two partial and one absent. In the renal and hematological group complete response, there was one death and a missing response. The pulmonary group presented a complete response and two partial. Conclusion: The present study demonstrated that rituximab can bring benefits to patients with lupus erythematosus systemic, with good tolerability and mild side effects; it presented, however, variable response according to the system affected. PMID:24728244

Modeling study of radiation effects on thrombocytopoietic and granulocytopoietic systems in human

NASA Astrophysics Data System (ADS)

Smirnova, Olga

Biophysical models describing the dynamics of thrombocytopoiesis and granulocytopoiesis in nonirradiated and irradiated human are developed. These models, being based on conventional biological theories, are implemented as the systems of nonlinear differential equations whose variables and constant parameters have clear biological meaning. Thorough analytical and nu-merical analysis of the proposed models is performed. It is revealed that the models in hand are capable of describing the dynamical regimes which are typical for these hematological lines in the norm and in the case of hematological disorders, such as cyclic thrombocytopenia and cyclic neutropenia. The models reproduce, on quantitative level, the dynamics of thrombocytopoiesis and granulocytopoiesis in acutely irradiated human. Modeling assessment for the critical dose rate of chronic irradiation, which leads to the complete extinction of the most radiosensitive hematological line (thrombocytopoiesis), agrees with the real dose rates of lethal irradiation for human. The models are applied for simulating the dynamics of thrombocytopoietic and granulocytopoietic systems in astronauts exposed to space radiation during long-term missions such as voyages to Mars. The dose rate equivalents for the Galactic Cosmic Rays (GCR) and for Solar Particles Event (SPE) are taken as the variable parameters of the models. It is found that effects of GCR on the hematological lines under consideration are negligible. It is also revealed that SPE causes damped oscillations of "effective" radiosensitivity of the thrombocy-topoiesis and granulocytopoiesis that, in turn, defines the strength of response of these systems to the subsequent SPE. Specifically, the preceding SPE can induce either radiosensitization or radioprotection effects on these hematological lines, depending on the time interval between SPEs. All this testifies to the efficiency of employment of the developed models in investigation and prediction of effects of space radiation on the thrombocytopoiesis and granulocytopoiesis, whose damages can lead to development of hemorrhages and infections, respectively. The devel-oped biophysical models of these vital body systems provide a better understanding of the risks to health from the Solar Particles Events and enable one to evaluate the need of operational applications of countermeasures for astronauts in the long-term space missions.

21 CFR 864.5800 - Automated sedimentation rate device.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Automated sedimentation rate device. 864.5800 Section 864.5800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Automated and Semi-Automated Hematology Devices...

21 CFR 864.5800 - Automated sedimentation rate device.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Automated sedimentation rate device. 864.5800 Section 864.5800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Automated and Semi-Automated Hematology Devices...

21 CFR 864.5800 - Automated sedimentation rate device.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Automated sedimentation rate device. 864.5800 Section 864.5800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Automated and Semi-Automated Hematology Devices...

21 CFR 864.5800 - Automated sedimentation rate device.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Automated sedimentation rate device. 864.5800 Section 864.5800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Automated and Semi-Automated Hematology Devices...

21 CFR 864.5800 - Automated sedimentation rate device.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Automated sedimentation rate device. 864.5800 Section 864.5800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Automated and Semi-Automated Hematology Devices...

REFERENCE RANGES AND AGE-RELATED AND DIVING EXERCISE EFFECTS ON HEMATOLOGY AND SERUM CHEMISTRY OF FEMALE STELLER SEA LIONS ( EUMETOPIAS JUBATUS).

PubMed

Gerlinsky, Carling D; Haulena, Martin; Trites, Andrew W; Rosen, David A S

2018-03-01

Decreased health may have lowered the birth and survival rates of Steller sea lions ( Eumetopias jubatus) in the Gulf of Alaska and Aleutian Islands over the past 30 yr. Reference ranges for clinical hematology and serum chemistry parameters needed to assess the health of wild sea lion populations are limited. Here, blood parameters were serially measured in 12 captive female Steller sea lions ranging in age from 3 wk to 16 yr to establish baseline values and investigate age-related changes. Whether diving activity affects hematology parameters in animals swimming in the ocean compared with animals in a traditional aquarium setting was also examined. Almost all blood parameters measured exhibited significant changes with age. Many of the age-related changes reflected developmental life history changes, including a change in diet during weaning, an improvement of diving capacity, and the maturity of the immune system. Mean corpuscular hemoglobin and mean corpuscular volume were also higher in the ocean diving group compared with the aquarium group, likely reflecting responses to increased exercise regimes. These data provide ranges of hematology and serum chemistry values needed to evaluate and compare the health and nutritional status of captive and wild Steller sea lions.

Report of chronic myeloid leukemia SMS Medical College Hospital, Jaipur

PubMed Central

Malhotra, Hemant; Sharma, Rajesh; Singh, Yogender; Chaturvedi, Hemant

2013-01-01

This is a retrospective analysis of patients of chronic myeloid leukemia (CML) registered and under treatment at the Leukemia Lymphoma Clinic at the Birla Cancer Center, SMS Medical College Hospital, Jaipur. Approximately, two-thirds of the patients are getting imatinib mesylate (IM) through the Glivec International Patient Assistance Program while the rest are on generic IM. In addition to comparison of hematological and molecular responses in the Glivec versus the genetic group, in this analysis, an attempt is also made to assess the socio-economic (SE) status of the patients and its effect on the response rates. Of the 213 patients studied, most (28.6%) are in the age group between 30 years and 40 years and the mean age of the patients in 39 years, a good decade younger that in the west. There is a suggestion that patients in lower SE class present with higher Sokal scores and with more disease burden. Possibly hematological responses are similar with both Glivec and generic IM. No comment can be made with regards to molecular response between the two groups as a significant number of patients in the Glivec arm (42%) do not have molecular assessment because of economic reasons. CML is a common and challenging disease in the developing world with patients presenting at an earlier age with more advanced disease. SE factors play a significant role in therapy and disease monitoring decision making and may impact on response rates and prognosis. PMID:24516303

Report of chronic myeloid leukemia SMS Medical College Hospital, Jaipur.

PubMed

Malhotra, Hemant; Sharma, Rajesh; Singh, Yogender; Chaturvedi, Hemant

2013-07-01

This is a retrospective analysis of patients of chronic myeloid leukemia (CML) registered and under treatment at the Leukemia Lymphoma Clinic at the Birla Cancer Center, SMS Medical College Hospital, Jaipur. Approximately, two-thirds of the patients are getting imatinib mesylate (IM) through the Glivec International Patient Assistance Program while the rest are on generic IM. In addition to comparison of hematological and molecular responses in the Glivec versus the genetic group, in this analysis, an attempt is also made to assess the socio-economic (SE) status of the patients and its effect on the response rates. Of the 213 patients studied, most (28.6%) are in the age group between 30 years and 40 years and the mean age of the patients in 39 years, a good decade younger that in the west. There is a suggestion that patients in lower SE class present with higher Sokal scores and with more disease burden. Possibly hematological responses are similar with both Glivec and generic IM. No comment can be made with regards to molecular response between the two groups as a significant number of patients in the Glivec arm (42%) do not have molecular assessment because of economic reasons. CML is a common and challenging disease in the developing world with patients presenting at an earlier age with more advanced disease. SE factors play a significant role in therapy and disease monitoring decision making and may impact on response rates and prognosis.

Effect of granulocyte-colony stimulating factor on empiric therapy with flomoxef sodium and tobramycin in febrile neutropenic patients with hematological malignancies. Kan-etsu Hematological Disease and Infection Study Group.

PubMed

Yoshida, M; Karasawa, M; Naruse, T; Fukuda, M; Hirashima, K; Oh, H; Ninomiya, H; Abe, T; Saito, K; Shishido, H; Moriyama, Y; Shibata, A; Motoyoshi, K; Nagata, N; Miura, Y

1999-02-01

The clinical effects of concomitant use of granulocyte-colony stimulating factor (G-CSF) on empiric antibiotic therapy in febrile neutropenic patients were evaluated in a randomized fashion. Two hundred and fourteen neutropenic febrile episodes (neutrophil counts < 1.0 x 10(9)/l) were treated with flomoxef sodium and tobramycin with or without G-CSF. The resolution of fever at day 4 (excellent response) or at day 7 (good response) was deemed effective. Among 157 evaluable episodes, the observed excellent responses were 31 (38.8%) and the good responses were 20 (25.0%) in the G-CSF group; those in the control group were 26 (33.8%) and 25 (32.5%), respectively. The overall efficacy rate was 63.8% (51/80) in the G-CSF group and 66.2% (51/77) in the control group (not significant). The initial neutrophil count was 0.186 +/- 0.249 x 10(9)/l in the G-CSF group and 0.235 +/- 0.290 x 10(9)/l in the control group, and rose to 2.889 +/- 4.198 x 10(9)/l and 0.522 +/- 0.844 x 10(9)/l, respectively, at day 7. These results indicate that G-CSF does not affect the rate of response to empiric antibiotic therapy in febrile neutropenic patients, although a significant effect of G-CSF was observed on neutrophil recovery.

Effects of hydration level and heat stress on thermoregulatory responses, hematological and blood rheological properties in growing pigs.

PubMed

Waltz, Xavier; Baillot, Michelle; Connes, Philippe; Bocage, Bruno; Renaudeau, David

2014-01-01

Heat stress is one of the major limiting factors of production efficiency in the swine industry. The aims of the present study were 1) to observe if hemorheological and hematological parameters could be associated to physiological acclimation during the first days of heat stress exposure and 2) to determine if water restriction could modulate the effect of thermal heat stress on physiological, hematological and hemorheological parameters. Twelve Large White male pigs were divided into an ad libitum and a water restricted group. All pigs were submitted to one week at 24 °C (D-7 to D-1). Then, at D0, temperature was progressively increased until 32 °C and maintained during one week (D1 to D7). We performed daily measurements of water and feed intake. Physiological (i.e., skin temperature, rectal temperature, respiratory rate), hematological and hemorheological parameters were measured on D-6, D-5, D0, D1, D2 and D7. Water restriction had no effect on physiological, hematological and hemorheological parameters. The first days of heat stress caused an increase in the three physiological parameters followed by a reduction of these parameters suggesting a successful acclimation of pigs to heat stress. We showed an increase in hematocrit, red blood cell aggregation and red blood cell aggregation strength during heat stress. Further, we observed an important release of reticulocytes, an increase of red blood cell deformability and a reduction of feed intake and blood viscosity under heat stress. This study suggests that physiological acute adaptation to heat stress is accompanied by large hematological and hemorheological changes.

Immunotherapy with rituximab in follicular lymphomas.

PubMed

Saguna, Carmen; Mut, Ileana Delia; Lupu, Anca Roxana; Tevet, Mihaela; Bumbea, Horia; Dragan, Cornel

2011-04-01

Non-Hodgkin Lymphomas (NHL) represent a recent and fascinating domain of hemato-oncology, in which remarkable progress has been made. The conventional treatments of indolent lymphomas do not extend the survival rate, nor do they cure. Recent directions are centered on using several new drugs that are capable of overcoming the mechanisms that are resistant to recovery. The initiation of immunotherapy (Rituximab in 1997) seems to have changed the natural evolution of follicular lymphomas (FL). It is possible that resistance to healing in follicular lymphomas may be neutralized with Rituximab by suppressing STAT-1 positive macrophages that are present in the cellular microenvironment.Thereinafter, the re-evaluation of recent models of prognostic and therapeutic paradigmas that were used in FL became compulsory.The purpose of the paper is to compare the evolution of patients with follicular lymphoma and the period of response, according to the treatments. The study group consisted of the 71 patients diagnosed with follicular lymphoma, out of a total of 767 malignant lymphatic proliferations with B cells, for a period of 7 years (2002-2008), at the Hematology Department, Hospital Coltea, Bucharest and Hematology Department, Universitary Hospital, BucharestResults and conclusions: Combining chemotherapy with Rituximab had better results compared to the same chemotherapy, administered alone, both in induction and in case of relapse. The overall response rate in our study group was 74.7%, out of which 42.3% complete remissions. The overall response rate was 84.61% in the Rituximab group, compared to 68.88% in patients without Rituximab.

Hematological Adverse Events in Clozapine-Treated Children and Adolescents

ERIC Educational Resources Information Center

Gerbino-Rosen, Ginny; Roofeh, David; Tompkins, D. Andrew; Feryo, Doug; Nusser, Laurie; Kranzler, Harvey; Napolitano, Barbara; Frederickson, Anne; Henderson, Inika; Rhinewine, Joe; Kumra, Sanjiv

2005-01-01

Objective: To retrospectively examine rates of hematological adverse events (HAEs) in psychiatrically ill, hospitalized children treated with clozapine. Method: Clozapine treatment was administered in an open-label fashion using a flexible titration schedule, and data from weekly complete blood counts was obtained. The rate of neutropenia and…

Infective and thrombotic complications of central venous catheters in patients with hematological malignancy: prospective evaluation of nontunneled devices.

PubMed

Worth, Leon J; Seymour, John F; Slavin, Monica A

2009-07-01

Central venous catheter (CVC)-related bloodstream infection (CR-BSI) is a significant complication in hematology patients. A range of CVC devices may be used, and risks for the development of complications are not uniform. The objectives of this study were to determine the natural history and rate of CVC-related complications and risk factors for CR-BSI and to compare device-specific complications in a hematology population. An observational cohort of patients with hematologic malignancy was prospectively studied following CVC insertion. Participants were reviewed until a CVC-related complication necessitated device removal, completion of therapy, death, or defined end-of-study date. The National Nosocomial Infection Surveillance definition for CR-BSI was used. Overall and device-specific rates of infective and noninfective complications were calculated and potential risk factors were captured. One hundred six CVCs (75 peripherally inserted central venous catheters [PICCs], 31 nontunneled CVCs) were evaluated in 66 patients, over 2,399 CVC days. Thrombosis occurred in 16 cases (15.1%), exit-site infection in two (1.9%), and CR-BSI in 18 (7.5 per 1,000 CVC days). No significant differences were found when complication rates in PICC and nontunneled devices were compared. An underlying diagnosis of acute myeloid leukemia was negatively associated with CR-BSI (odds ratio (OR) 0.14, p = 0.046), and a previous diagnosis of fungal infection was associated with infection (OR 22.82, p = 0.031). CR-BSI rates in our hematology population are comparable to prior reports. A low rate of exit-site infection and high proportion of thrombotic complications were observed. No significant differences in thrombotic or infective complications were evident when PICC and nontunneled devices were compared. PICC devices are a practical and safe option for management of hematology patients.

DCB - Cancer Immunology, Hematology, and Etiology Research

Cancer.gov

Part of NCI’s Division of Cancer Biology’s research portfolio, studies supported include the characterization of basic mechanisms relevant to anti-tumor immune responses and hematologic malignancies.

Hematology oncology practice in the Asia-Pacific APHCON survey results from the 6th international hematologic malignancies conference: bridging the gap 2015, Beijing, China.

PubMed

Huang, Xiao Jun; Liu, Kaiyan; Ritchie, David; Andersson, Borje; Lu, Jin; Hou, Jian; Burguera, Adolfo de la Fuente; Wang, JianXiang; Yeoh, Allen; Yan, Chenhua; Zhou, Daobin; Tan, Daryl; Kim, Dong Wook; Wu, Depei; Shpall, Elizabeth; Kornblau, Stephen; Neelapu, Sattava; Hongeng, Suradej; Li, Jianyong; Hu, Jiong; Zhang, Lian Sheng; Wang, Michael; Malhotra, Pankaj; Jiang, Qian; Qin, Yazhen; Wong, Raymond; Champlin, Richard; Hagemeister, Frederick; Westin, Jason; Iyer, Swaminathan; Mathews, Vikram; Wang, Yu; Hu, Yu; Xiao, Zhijian; Shao, Zonghong; Orlowski, Robert Z; Chim, Chor Sang; Mulligan, Stephen; Sanz, Miguel; Ozawa, Keiya; Parmar, Simrit; Issaragrisil, Surapol

2017-06-20

This report serves as a snapshot of the state-of-knowledge in the Asia Pacific (APAC) Hematology Oncology community, and establishes a baseline for longitudinal investigations to follow changes in best practices over time. The objective of this study was to understand the approach to hematologic diseases, common standards of care and best practices, issues that remain controversial or debated, and educational or resource gaps that warrant attention. We used mobile application to disseminate and distribute questionnaires to delegates during the 6th international hematologic malignancies conference hosted by the APAC Hematology Consortium at Beijing, China. User responses were collected in an anonymous fashion. We report survey results in two ways: the overall responses, and responses as stratified between Chinese physicians and "Other" represented nationalities. Overall geographical concordance in survey responses was positive and strong. Perhaps more interesting than instances of absolute agreement, these data provide a unique opportunity to identify topics in which physician knowledge or opinions diverge. We assigned questions from all modules to broad categories of: patient information; diagnosis; treatment preference; transplantation; and general knowledge/opinion. On average, we observed a geographic difference of 15% for any particular answer choice, and this was fairly constant across survey modules. These results reveal utility and need for widespread and ongoing initiatives to assess knowledge and provide evidence-based education in real time. The data will be made more valuable by longitudinal participation, such that we can monitor changes in the state of the art over time.

Approval summary for imatinib mesylate capsules in the treatment of chronic myelogenous leukemia.

PubMed

Cohen, Martin H; Williams, Grant; Johnson, John R; Duan, John; Gobburu, Jogarao; Rahman, Atiqur; Benson, Kimberly; Leighton, John; Kim, Sung K; Wood, Rebecca; Rothmann, Mark; Chen, Gang; U, Khin Maung; Staten, Ann M; Pazdur, Richard

2002-05-01

Chronic myelogenous leukemia (CML) results from the breakpoint cluster region-Abl fusion gene product, a tyrosine kinase involved in cell division and apoptosis. Imatinib, an orally administered inhibitor of the breakpoint cluster region-Abl tyrosine kinase, is capable of blocking proliferation and inducing apoptosis in CML cell lines. In this report, we describe the preclinical profile of imatinib and the data submitted in the New Drug Application that led to its marketing approval. Chemistry manufacturing and controls, animal toxicology, and biopharmaceutical data are described. Results of Phase I and Phase II clinical studies in patients with CML in blast crisis (CML-BC), in accelerated phase (CML-AP), and in chronic phase disease-resistant or intolerant to IFN-alpha (CML-CP) are summarized. The basis for marketing approval and postmarketing commitments by the pharmaceutical company are discussed. Toxicology studies in the rat, dog, and monkey show the hematological, renal, and hepatobiliary toxicity of imatinib. Pharmacokinetic studies in patients with CML demonstrate 98% imatinib bioavailability. The elimination half-lives of the parent drug and the major active metabolite, CGP74588, from plasma are approximately 18 and 40 h, respectively. Approximately 81% of the drug is eliminated in 7 days, 68% in the feces and 13% in the urine. Cytochrome P-450 3A4 is the main enzyme responsible for imatinib metabolism. Phase I and II clinical studies were conducted. The Phase I study, in 83 CML patients, evaluated oral imatinib doses from 25 to 1000 mg/day. Dose-limiting toxicity was not observed. The three Phase II studies, in CML-CP, CML-AP, and CML-BC, enrolled 1027 patients. CML-CP patients received 400 mg/day imatinib, whereas CML-AP and CML-BC patients generally received 600 mg/day imatinib. Primary study endpoints were cytogenetic response rate (CML-CP) and hematological response rate (CML-AP and CML-BC). The cytogenetic response rate for CML-CP patients was 49%. The hematological response rate of CML-AP and CML-BC patients was 63 and 26%, respectively. The most common imatinib adverse events were nausea, vomiting, myalgia, edema, and diarrhea. Elevated liver enzymes and/or bilirubin were reported in 27 patients (2.6%). On May 10, 2001, imatinib mesylate (Gleevec, formerly known as STI-571 and Glivec), manufactured and distributed by Novartis Pharmaceuticals, East Hanover, NJ, was approved by the United States Food and Drug Administration for the treatment of CML in three clinical settings: CML-BC, CML-AP, and CML-CP. This report summarizes the Food and Drug Administration's review of the New Drug Application.

[Therapeutic effects of a combination treatment with flomoxef and tobramycin against infections complicated with hematological disorders].

PubMed

Yamane, T; Tanaka, K; Hasuike, T; Hirai, M; Misu, K; Ota, K; Ohira, H; Nakao, Y; Yasui, Y; Inoue, T

1992-08-01

The efficacy and safety of a combination regimen using flomoxef (FMOX) and tobramycin (TOB) were evaluated in the treatment of infections complicated with hematological disorders. The primary diseases in 40 patients included acute leukemia, malignant lymphoma and others. Complicated infections included 35 cases with suspected septicemia, 4 cases with septicemia and 1 case with pleuritis. Clinical responses were excellent in 10 (25.0%), good in 14 (35.0%), fair in 2 (5.0%) and poor in 14 (35.0%). The efficacy rate was 73.1% in patients with neutrophil counts higher than 501/microliters after administration, but it was 35.7% in patients with counts less than 501/microliters; the difference was statistically significant. No side effects were observed in any of the 40 patients. Abnormal laboratory data in liver functions were identified in 1 patient (2.5%). Degree of this abnormality was very slight, and the continuation of treatment was not disturbed. In conclusion, this combination therapy of FMOX and TOB thus appears to be useful and safe in therapies for infections complicated with hematological disorders.

[Therapeutic Effects on Chemotherapy-Induced Granulocytopenia in Hematologic Malignacies, a Comparison Between Lishengsu and Filgrastim

PubMed

Huang, Honghui; Chen, Fangyuan

2000-06-01

A multi-center, open controlled study was performed to observe the effects of Lishengsu, a rhG-CSF preparation manufactured by Beijing Shuanglu Biopharmaceutical Co., Ltd. on chemotherapy-induced granulocytopenia in patients with hematological malignancies. The results showed the total response rates were similar between Lishengsu- and Filgrastim-treated groups (98.8% vs 100%), recovery of peripheral ANC and WBC was also similar between the two groups, with the peaks appeared both at the 12th day after rhG-CSF treatment. No differences were observed in the duration for ANC to recover to normal level between Lishengsu- and Filgrastim-treated groups (7 and 8 days respectively). Our results indicated Lishengsu is as effective as Filgrastim in accelerating the recovery of chemotherapy-induced granulocytopenia.

Central venous catheter-associated bloodstream infections in pediatric hematology-oncology patients and effectiveness of antimicrobial lock therapy.

PubMed

Tsai, Hsing-Chen; Huang, Li-Min; Chang, Luan-Yin; Lee, Ping-Ing; Chen, Jong-Ming; Shao, Pei-Lan; Hsueh, Po-Ren; Sheng, Wang-Huei; Chang, Yu-Ching; Lu, Chun-Yi

2015-12-01

Central line-associated bloodstream infection (CLABSI) is a serious complication in hematology-oncology patients. This study aimed to analyze the prevalence of CLABSI and the effectiveness of antimicrobial lock therapy (ALT) in pediatric patients. BSIs of all pediatric hematology-oncology patients admitted to a children's hospital between January 2009 and December 2013 were reviewed. The United States National Healthcare Safety Network and Infectious Diseases Society of America guidelines were used to define CLABSI and catheter-related BSI (CRBSI). The incidence, laboratory and microbiology characteristics, poor outcome, and effectiveness of ALT were analyzed. There were 246 cases of CLABSI in 146 patients (mean age, 10.0 years), including 66 (26.8%) cases of CRBSI. The incidence of CLABSI was 4.49/1000 catheter-days, and the infection was responsible for 32.9% of the complications these patients developed and 9.3% of contributable mortality. Patients with acute myeloid leukemia had the highest infection density (5.36/1000 patient-days). Enterobacteriaceae (40.2%) and coagulase-negative staphylococci (CoNS; 20.7%) were the predominant pathogens. In multivariate analysis, older age, male sex, elevated C-reactive protein, acute lymphoblastic leukemia, and candidemia were associated with poor outcome. The success rate of ALT was 58.6% (17/29) for the treatment of CoNS and 78.3% (29/37) for Enterobacteriaceae infections. Patients with candidemia (n = 18) had the highest mortality (33.4%) and catheter removal rate (66.7%). Chlorhexidine as the disinfectant decreased the 1-year CLABSI rate from 13.7/1000 to 8.4/1000 catheter-days (p = 0.02). CoNS and Enterobacteriaceae are the predominant pathogens in CLABSI among pediatric hematology-oncology patients. ALT is effective and showed no significant side effect. New disinfection practice and infection control measures can decrease CLABSI. Copyright © 2014. Published by Elsevier B.V.

Factors modifying the response of large animals to low-intensity radiation exposure

NASA Technical Reports Server (NTRS)

Page, N. P.; Still, E. T.

1972-01-01

In assessing the biological response to space radiation, two of the most important modifying factors are dose protraction and dose distribution to the body. Studies are reported in which sheep and swine were used to compare the hematology and lethality response resulting from radiation exposure encountered in a variety of forms, including acute (high dose-rate), chronic (low dose-rate), combinations of acute and chronic, and whether received as a continuous or as fractionated exposure. While sheep and swine are basically similar in response to acute radiation, their sensitivity to chronic irradiation is markedly different. Sheep remain relatively sensitive as the radiation exposure is protracted while swine are more resistant and capable of surviving extremely large doses of chronic irradiation. This response to chronic irradiation correlated well with changes in radiosensitivity and recovery following an acute, sublethal exposure.

Pentostatin and Rituximab Therapy for Previously Untreated B-CLL

PubMed Central

Kay, Neil E.; Wu, Wenting; Kabat, Brian; LaPlant, Betsy; Lin, Thomas S.; Byrd, John C.; Jelinek, Diane F.; Grever, Michael R.; Zent, Clive S.; Call, Timothy G.; Shanafelt, Tait D.

2010-01-01

We have shown that the combination of pentostatin (P), cyclophosphamide (C) and rituximab (R) achieves an overall response (OR) rate >90% with more than 40% complete responses (CR) in patients with untreated CLL. To evaluate if the tolerability of this regimen could be enhanced without sacrificing efficacy, we conducted a phase II trial of P and R without cyclophosphamide, using a higher P dose (4 mg/m2). Among the 33 patients enrolled, 82% were male, median age was 65 (9 patients ≥70 years) and 64% were Rai stage III-IV. The OR rate was 76% with 9 CR (27%), 5 nPR, and 11 PRs. At the time of this analysis, 29/33 patients are still alive and the median follow up for patients still alive is 14 months (range: 1-34.8 months). Four (12%) patients experienced grade 3 or higher hematologic toxicity and 5 (15%) experienced grade 3 or higher non-hematologic toxicity. Comparison of this trial to our previous PCR trial showed that patients treated with PCR had a higher OR rate (91% vs. 76%) and CR rate (41% vs. 27%) compared to patients treated with PR. Median treatment-free survival for all accrued patients was notably longer in PCR treated patients compared to PR (30 vs. 16 months). These findings suggest that increasing the dose of the purine nucleoside analogue does not eliminate the need for cyclophosphamide in chemoimmunotherapy for treatment of CLL. PMID:20187101

Stem cell transplantation compared with melphalan plus dexamethasone in the treatment of immunoglobulin light-chain amyloidosis.

PubMed

Gertz, Morie A; Lacy, Martha Q; Dispenzieri, Angela; Buadi, Francis K; Dingli, David; Hayman, Suzanne R; Kumar, Shaji K; Leung, Nelson; Lust, John; Rajkumar, S Vincent; Russell, Stephen J; Suman, Vera J; Le-Rademacher, Jennifer G; Hogan, William J

2016-07-15

Autologous stem cell transplantation (SCT) is a common management strategy for select patients with immunoglobulin light-chain amyloidosis, but no trials have documented improved overall survival. Eighty-nine patients with biopsy-proven immunoglobulin light-chain amyloidosis were allowed to select treatment with melphalan plus dexamethasone (n = 34) or SCT (n = 55); all patients were transplant eligible. Treatment preference resulted in imbalanced study arms. Patients who selected SCT were younger, more frequently had an Eastern Cooperative Oncology Group performance status score less than 2, had lower-stage amyloidosis, and had a lower incidence of cardiac amyloidosis. Patients receiving melphalan plus dexamethasone had a 3-year progression-free survival rate of 29.1% and an overall survival rate of 58.8%. Patients undergoing SCT had a 3-year progression-free survival rate of 51.7% and an overall survival rate of 83.6%. An attempt to match patients between the 2 arms in terms of risk produced 24 matched triplet sets (2 SCT patients for each melphalan-dexamethasone patient); there was no difference in hematologic response, but there was better survival after autologous SCT. A propensity score-matched analysis of the cohorts (melphalan plus dexamethasone vs SCT) showed an overall mortality hazard ratio of 2.56 (P < .01). Although the study had limitations, similar hematologic responses and improved survival were observed after SCT versus melphalan plus dexamethasone. Cancer 2016;122:2197-205. © 2016 American Cancer Society. © 2016 American Cancer Society.

Treatment With Bortezomib-based Therapy, Followed by Autologous Stem Cell Transplantation, Improves Outcomes in Light Chain Amyloidosis: A Retrospective Study.

PubMed

Jain, Tania; Kosiorek, Heidi E; Kung, Shu T; Shah, Vishal S; Dueck, Amylou C; Gonzalez-Calle, Veronica; Luft, Susan; Reeder, Craig B; Adams, Roberta; Noel, Pierre; Larsen, Jeremy T; Mikhael, Joseph; Bergsagel, Leif; Stewart, A Keith; Fonseca, Rafael

2018-05-04

The hematologic response is critical in patients with light chain amyloidosis because a good response is known to improve organ response and overall survival. We present a retrospective analysis to compare the hematologic and organ response in patients who received bortezomib-based therapy before autologous stem cell transplantation (ASCT) versus those who received non-bortezomib-based therapy before ASCT and those who underwent ASCT at diagnosis. Of a total of 63 patients who underwent ASCT for light chain amyloidosis, 34 received bortezomib-based therapy before ASCT (Bor-ASCT) and 29 did not receive bortezomib therapy (non-Bor-ASCT). A greater number of patients had involvement of ≥ 3 organs and cardiac involvement in the Bor-ASCT group, suggesting a greater risk at baseline in the Bor-ASCT group. At 3, 6, and 12 months after ASCT, the hematologic response was better in the Bor-ASCT group, with a statistically significance difference at 6 months (partial response or better in 82% vs. 20%; P = .002) and 12 months (partial response or better in 76% vs. 33%; P = .02). Organ responses (66% vs. 21%; P < .001) and median overall survival (not reached vs. 53 months; P = .001) were also greater in the Bor-ASCT group. Our study has shown that bortezomib-based therapy before ASCT improves the hematologic response, organ response and overall survival, potentially by decreasing the light chain load before ASCT. Copyright © 2018 Elsevier Inc. All rights reserved.

Impact of heat stress and hypercapnia on physiological, hematological, and behavioral profile of Tharparkar and Karan Fries heifers

PubMed Central

Pandey, Priyanka; Hooda, O. K.; Kumar, Sunil

2017-01-01

Aim: The present investigation was undertaken to study the impact of heat stress and hypercapnia on physiological, hematological, and behavioral profile of Tharparkar and Karan Fries (KF) heifers. Materials and Methods: The animals of both the breeds of Tharparkar and KF were exposed at different temperatures and CO2 levels. Exposure conditions of 25°C, 400 ppm CO2 level, and 60% relative humidity (RH) were taken as a control condition. The exposure conditions 40°C with two levels of CO2 500 ppm and 600 ppm with RH 55±5% and exposure conditions 42°C with two levels of CO2 500 ppm and 600 ppm with RH 55±5% were taken as treatments. The exposure period in each condition was 4 h daily for 5 consecutive days. Results: Physiological responses (respiration rate [RR], pulse rate [PR], and rectal temperature [RT]) were significantly (p<0.01) higher and different during all exposure conditions compared to control condition in both the breeds of cattle. KF heifers had higher RR, PR, and RT than Tharparkar heifers. Hematological parameters, namely, red blood cell, hemoglobin, and packed cell volume were significantly higher and different during all exposure condition than control in both the breeds, whereas no significant changes were observed in total leukocyte count and differential leukocyte count. Blood pH increased with increase in temperature and CO2 levels and was significantly higher than control conditions. PCO2 and base excess were significantly (p<0.05) lower, and PO2 was higher during different exposure conditions than control in both breeds. Restlessness and excitement signs were observed in all the exposure conditions as compared to control condition in both the breeds. Conclusion: Changes in physiological responses, behavioral pattern, and hematological parameters reflect the current functional status of the body system, and it can be used as an index for assessing the adaptation capacity of cattle to predict changes occurring in climate variables due to increasing CO2 levels and environmental temperature. PMID:29062208

Oxytocin treatment does not change cardiovascular parameters, hematology and plasma electrolytes in parturient horse mares.

PubMed

Nagel, Christina; Trenk, Lisa; Wulf, Manuela; Ille, Natascha; Aurich, Jörg; Aurich, Christine

2017-03-15

In mares, foaling is associated with changes in hematology, plasma electrolytes, blood pressure and heart rate and it has been hypothesized that these are induced by oxytocin. To test this hypothesis, mares (n = 8-14/group) were treated with oxytocin (OT; 20 I.U.) or saline (CON) at 1 h (test A) and 12 h after foaling (test B) and during first postpartum diestrus (test C). Heart rate, heart rate variability (HRV), atrioventricular blocks, salivary cortisol concentration, blood pressure, plasma electrolytes and blood count were determined. Heart rate decreased from test A to C (P < 0.001) but at no time differed between groups. The HRV, blood pressure and occurrence of atrioventricular blocks did not change in response to oxytocin. Cortisol concentration decreased from test A to C (P < 0.001). Oxytocin induced a cortisol release in test B (time x treatment P < 0.001, time x test P < 0.001). Plasma sodium and chloride concentrations decreased from test A to C (P < 0.001) but did not differ between groups. In test A, potassium concentration increased in CON but not OT mares (time P < 0.01, time x test P < 0.01, time x treatment P < 0.05). Polymorphnuclear cell (PMN) numbers in blood decreased from test A to C (P < 0.001) while lymphocytes increased (P < 0.05). At no time PMN and lymphocytes differed between groups. Oxytocin treatment had no effect on skin temperature. In conclusion, except for a limited effect on cortisol release, oxytocin was without effect and the hypothesis of oxytocin-induced alterations in cardiac parameters, plasma electrolytes and hematology of foaling mares was not verified. Copyright © 2016 Elsevier Inc. All rights reserved.

A Feasibility Study of Virtual Reality Exercise in Elderly Patients with Hematologic Malignancies Receiving Chemotherapy.

PubMed

Tsuda, Kenji; Sudo, Kazuaki; Goto, Goro; Takai, Makiko; Itokawa, Tatsuo; Isshiki, Takahiro; Takei, Naoko; Tanimoto, Tetsuya; Komatsu, Tsunehiko

2016-01-01

Adherence to rehabilitation exercise is much lower in patients with hematologic malignancies (22.5-45.8%) than in patients with solid tumors (60-85%) due to the administration of more intensive chemotherapeutic regimens in the former. Virtual reality exercise can be performed even in a biological clean room and it may improve the adherence rates in elderly patients with hematologic malignancies. Thus, in this pilot study, we aimed to investigate the feasibility and safety of virtual reality exercise intervention using Nintendo Wii Fit in patients with hematologic malignancies receiving chemotherapy. In this feasibility study, 16 hospitalized patients with hematologic malignancies aged ≥60 years performed virtual reality exercise for 20 minutes using the Nintendo Wii Fit once a day, five times a week, from the start of chemotherapy until hospital discharge. The adherence rate, safety, and physical and psychological performances were assessed. The adherence rate for all 16 patients was 66.5%. Nine patients completed the virtual reality exercise intervention with 88 sessions, and the adherence rate was 62.0%. No intervention-related adverse effects >Grade 2, according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0, were observed. We noted maintenance of the physical performance (e.g., Barthel index, handgrip strength, knee extension strength, one-leg standing time, and the scores of timed up and go test and Instrumental Activities of Daily Living) and psychosocial performance (e.g., score of hospital anxiety and depression scale). Virtual reality exercise using the Wii Fit may be feasible, safe and efficacious, as demonstrated in our preliminary results, for patients with hematologic malignancies receiving chemotherapy.

Meta-analysis of whole-brain radiotherapy plus temozolomide compared with whole-brain radiotherapy for the treatment of brain metastases from non-small-cell lung cancer.

PubMed

Xin, Yong; Guo, WenWen; Yang, Chun Sheng; Huang, Qian; Zhang, Pei; Zhang, Long Zhen; Jiang, Guan

2018-04-01

The aim of this meta-analysis was to compare the efficiency of whole-brain radiotherapy (WBRT) plus temozolomide (TMZ) with WBRT for the treatment of brain metastases from non-small-cell lung cancer (NSCLC). For dichotomous variables, outcomes were reported as relative risk ratio (RR) and 95% confidence interval (CI) was used to investigate the following outcome measures: overall response rate, headache, gastrointestinal adverse reactions, and hematological adverse reactions. Twelve randomized controlled trials involving 925 participants (480 received WBRT plus TMZ; 445 received WBRT) were included in the meta-analysis. There was a significant difference between the overall response rate (RR = 1.40, 95% CI 1.24-1.57; Z = 5.51; P < 0.00001), gastrointestinal adverse reactions (RR = 1.46, 95% CI 1.05-2.04; Z = 2.27; P = 0.02), and hematological adverse reactions (RR = 1.45, 95% CI 1.04-2.02; Z = 2.21; P = 0.03) of patients treated with WBRT plus TMZ compared with patients treated with WBRT alone. There was no significant difference between headaches (RR = 1.11, 95% CI 0.93-1.02; Z = 1.13; P = 0.26) in patients treated with WBRT plus TMZ compared with patients treated with WBRT alone. In conclusion, the currently available evidence shows that WBRT plus TMZ increases the overall response rate in patients with brain metastases of NSCLC compared with WBRT alone. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Immunotherapy with Rituximab in Follicular Lymphomas

PubMed Central

SAGUNA, Carmen; MUT, Ileana Delia; LUPU, Anca Roxana; TEVET, Mihaela; BUMBEA, Horia; DRAGAN, Cornel

2011-01-01

ABSTRACT Background: Non-Hodgkin Lymphomas (NHL) represent a recent and fascinating domain of hemato-oncology, in which remarkable progress has been made. The conventional treatments of indolent lymphomas do not extend the survival rate, nor do they cure. Recent directions are centered on using several new drugs that are capable of overcoming the mechanisms that are resistant to recovery. The initiation of immunotherapy (Rituximab in 1997) seems to have changed the natural evolution of follicular lymphomas (FL). It is possible that resistance to healing in follicular lymphomas may be neutralized with Rituximab by suppressing STAT-1 positive macrophages that are present in the cellular microenvironment.Thereinafter, the re-evaluation of recent models of prognostic and therapeutic paradigmas that were used in FL became compulsory. The purpose of the paper is to compare the evolution of patients with follicular lymphoma and the period of response, according to the treatments. Material and method: The study group consisted of the 71 patients diagnosed with follicular lymphoma, out of a total of 767 malignant lymphatic proliferations with B cells, for a period of 7 years (2002-2008), at the Hematology Department, Hospital Coltea, Bucharest and Hematology Department, Universitary Hospital, Bucharest Results and conclusions: Combining chemotherapy with Rituximab had better results compared to the same chemotherapy, administered alone, both in induction and in case of relapse. The overall response rate in our study group was 74.7%, out of which 42.3% complete remissions. The overall response rate was 84.61% in the Rituximab group, compared to 68.88% in patients without Rituximab. PMID:22205891

Targeting B7x and B7-H3 as New Immunotherapies for Prostate Cancer

DTIC Science & Technology

2017-11-01

treat rheumatoid arthritis and prevent acute kidney transplant rejection (Fiocco et al., 2008; Vincenti et al., 2011). The past decade has witnessed a...cell lines. The first Phase I trial with pidilizumab recruited patients with hematologic malignancies, including acute myeloid leukemia (AML), chronic... radiation , chemotherapy, other coinhibi- tory antibodies, or vaccines can improve the response rate in cancers. Predictive biomarkers need to be developed

Catheter-associated bloodstream infections in pediatric hematology-oncology patients.

PubMed

Celebi, Solmaz; Sezgin, Melike Evim; Cakır, Deniz; Baytan, Birol; Demirkaya, Metin; Sevinir, Betul; Bozdemir, Sefika Elmas; Gunes, Adalet Meral; Hacimustafaoglu, Mustafa

2013-04-01

Catheter-associated bloodstream infections (CABSIs) are common complications encountered with cancer treatment. The aims of this study were to analyze the factors associated with recurrent infection and catheter removal in pediatric hematology-oncology patients. All cases of CABSIs in patients attending the Department of Pediatric Hematology-Oncology between January 2008 and December 2010 were reviewed. A total of 44 episodes of CABSIs, including multiple episodes involving the same catheter, were identified in 31 children with cancer. The overall CABSIs rate was 7.4 infections per 1000 central venous catheter (CVC) days. The most frequent organism isolated was coagulase-negative Staphylococcus (CONS). The CVC was removed in nine (20.4%) episodes. We found that hypotension, persistent bacteremia, Candida infection, exit-side infection, neutropenia, and prolonged duration of neutropenia were the factors for catheter removal. There were 23 (52.2%) episodes of recurrence or reinfection. Mortality rate was found to be 9.6% in children with CABSIs. In this study, we found that CABSIs rate was 7.4 infections per 1000 catheter-days. CABSIs rates in our hematology-oncology patients are comparable to prior reports. Because CONS is the most common isolated microorganism in CABSIs, vancomycin can be considered part of the initial empirical regimen.

Effects of dietary levels of vitamin A on growth, hematology, immune response and resistance of Nile tilapia (Oreochromis niloticus) to Streptococcus iniae

USDA-ARS?s Scientific Manuscript database

This study was conducted to evaluate the effect of supplemental levels of vitamin A (0, 2,500, 5,000, 10,000, and 20,000 IU/kg diet) on the growth performance, hematology, immune response and resistance of Nile tilapia, Oreochromis niloticus to Streptococcus iniae challenge. Each diet was fed to Nil...

[Immunosuppressive therapy using antithymocyte globulin and cyclosporin A with or without human granulocyte colony-stimulating factor in children with acquired severe aplastic anemia].

PubMed

Liu, Xiaoming; Zou, Yao; Wang, Shuchun; Zhang, Li; Yang, Wenyu; Zhang, Jiayuan; Liu, Fang; Liu, Tianfeng; Chen, Xiaojuan; Ruan, Min; Zhou, Jianfeng; Cai, Xiaojin; Qi, Benquan; Chang, Lixian; An, Wenbin; Guo, Ye; Chen, Yumei; Zhu, Xiaofan

2014-02-01

To compare the efficacy and safety of four different regimens for pediatric severe aplastic anemia (SAA) with immuno-suppressive therapy (IST) with or without combined human granulocyte colony-stimulating factor (G-CSF). The authors retrospectively analyzed 105 children with SAA treated with IST with or without G-CSF in the hospital from February 2000 to September 2010. Regimen A, without G-CSF in the whole treatment, was used to treat Group A patients, n = 27; Regimen B, G-CSF, was initiated in Group B, n = 24, before the IST until hematologic recovery; Regimen C, G-CSF, was used together with the IST for Group C patients, n = 24, until hematologic recovery; Regimen D,G-CSF was used for Group D, n = 30, after the end of IST until hematologic recovery. The response rate, relapse rate, mortality, infection rate, infection-related death rate, risk of evolving into MDS/AML, survival rate, factors affecting the time of event-free survival and so on. (1) The response (CR+PR) rates 4, 6, 12 and 24 months after IST of the whole series of 105 SAA children were 50.5% (7.6%+42.9%) , 60.0% (21.9%+38.1%) , 67.6% (38.1%+29.5%) and 69.5% (40.0%+29.5%) respectively. The 2-year survival rate was 90.5%; the follow-up of the patients for 13 years showed that the whole survival rate was 87.6%. (2) The differences of the response rates 4, 6, 12 and 24 months after IST of the 4 groups were not significant (P > 0.05). (3) No significant differences were found in the mortalities 4, 6, 12 and 24 months among the 4 groups (P > 0.05). (4) Of the 105 patients, 4 children had relapsed disease in the period of time from 6 to 24 months after IST. All the four patients belonged to the groups with G-CSF. (5) The use of G-CSF could not decrease the infection period before IST (day) (P = 0.273), and it had no impact on the infection rate after IST (P = 0.066). It did not reduce the rates of septicemia and infectious shock. And to the infection-related death rate no significant conclusion can be made. (6) Follow up of the patients for 13 years, showed that 2 had the evolution to MDS/AML in the 105 patients and the two children belonged to the groups with G-CSF. (7) Kaplan-meier curve analysis did not show any differences in the survival rates of the four groups. (8) Cox regression analysis showed that the use of G-CSF had no benefit to the patients' long term survival. While the age of diagnosis and the infection history before IST were significantly related to the patients' long term survival. The use of G-CSF did not contribute to the early response and could not reduce the infection rate, infection-related death rate and the patients' long term survival. There were no significant differences in the survival rates of the four groups. Attention should be paid to the risk of the evolution to MDS/AML.

[Testing the hemalog D in a hematology department of a general hospital in Paris (author's transl)].

PubMed

Lortholary, P; Lejeune, F; Ganon, J P; Mathiot, C; Turpin, F

1978-06-10

Europe's firs Hemalog D was installed in the Hematology Laboratory of the Franco-Musulman Hospital at Bobigny, just outside Paris, in March 1975. The authors' experience with the apparatus since that date has enabled them to analyze the significance of "alarms", "high peroxidase", "large unstained cells", "remainder" and "low rate" in patients with and without hematologic disorders. On the basis of these results it has been possible to define the fate of the various blood cells in the Hemalog D, the role of the apparatus in the ivestigation of hematologic disorders and the type of "cooperation" between the hematologist and the Hemalog D.

Hematologic Complications of Pregnancy

PubMed Central

Townsley, Danielle M.

2013-01-01

Pregnancy induces a number of physiologic changes that affect the hematologic indices, either directly or indirectly. Recognizing and treating hematologic disorders that occur during pregnancy is difficult owing to the paucity of evidence available to guide consultants. This paper specifically reviews the diagnosis and management of benign hematologic disorders occurring during pregnancy. Anemia secondary to iron deficiency is the most frequent hematologic complication and is easily treated with oral iron formulations,; however care must be taken not to miss other causes of anemia, such as sickle cell disease. Thrombocytopenia is also a common reason for consulting the hematologist and distinguishing gestational thrombocytopenia from immune thrombocytopenia (ITP), preeclampsia, HELLP syndrome, or thrombotic thrombocytopenic purpura (TTP) is essential since the treatment differs widely. Occasionally the management of mother and infant involves the expeditious recognition of neonatal alloimmune thrombocytopenia (NAIT), a condition that is responsible for severe life-threatening bleeding of the newborn. Additionally, inherited and acquired bleeding disorders affect pregnant women disproportionately and often require careful monitoring of coagulation parameters in order to prevent bleeding in the puerperium. Finally, venous thromboembolism (VTE) during pregnancy is still largely responsible for mortality during pregnancy and the diagnosis, treatment options and guidelines for prevention of VTE during pregnancy are explored. PMID:23953339

Comparison study of the rates of manual peripheral blood smear review from 3 automated hematology analyzers, Unicel DxH 800, ADVIA 2120i, and XE 2100, using international consensus group guidelines.

PubMed

Kim, Sue Jung; Kim, Yoonjung; Shin, Saeam; Song, Jaewoo; Choi, Jong Rak

2012-11-01

In the clinical laboratory, it is important both to reduce the number of peripheral blood slide reviews to save time and money and to avoid reporting false results. To determine differences in the slide review rates of 3 widely used automated hematologic analyzers, the Unicel DxH 800 (Beckman Coulter Inc, Fullerton, California), ADVIA 2120i (Siemens Diagnostics, Tarrytown, New York), and XE 2100 (Sysmex, Kobe, Japan), using International Consensus Group for Hematology Review guidelines. A total of 1485 samples were tested, and 300 were manually reviewed. Slide review rates, sensitivity, specificity, and false-positive and false-negative rates were estimated using consensus group rules and compared using χ(2) tests, Fisher exact tests, or generalized estimating equations. Unicel DxH 800, ADVIA 2120i, and XE 2100 showed 22.8%, 20.2%, and 28.6% slide review rates; 14.3%, 14.3%, and 9.7% false-negative rates; and 13.7, 11.3%, and 17.3% false-positive rates, respectively. All analyzers showed significantly higher false-negative rates than that of the consensus group (2.9%). False-negative rates were higher than the recommended levels. Among 3 automated hematologic analyzers, XE 2100 showed the highest rate of slide review. Because the present study clearly shows that the slide review rates have distinct characteristics among the studied analyzers, each individual laboratory should consider selecting the most appropriate analyzer according to clinical characteristics. Analyzers with high sensitivity may be advantageous in outpatient settings for screening patients, whereas analyzers with high specificity may be beneficial in inpatient settings for efficient patient care.

Peptide receptor radionuclide therapy of treatment-refractory metastatic thyroid cancer using 90Yttrium and 177Lutetium labeled somatostatin analogs: toxicity, response and survival analysis

PubMed Central

Budiawan, Hendra; Salavati, Ali; Kulkarni, Harshad R; Baum, Richard P

2014-01-01

The overall survival rate of non-radioiodine avid differentiated (follicular, papillary, medullary) thyroid carcinoma is significantly lower than for patients with iodine-avid lesions. The purpose of this study was to evaluate toxicity and efficacy (response and survival) of peptide receptor radionuclide therapy (PRRT) in non-radioiodine-avid or radioiodine therapy refractory thyroid cancer patients. Sixteen non-radioiodine-avid and/or radioiodine therapy refractory thyroid cancer patients, including follicular thyroid carcinoma (n = 4), medullary thyroid carcinoma (n = 8), Hürthle cell thyroid carcinoma (n = 3), and mixed carcinoma (n = 1) were treated with PRRT by using 90Yttrium and/or 177Lutetium labeled somatostatin analogs. 68Ga somatostatin receptor PET/CT was used to determine the somatostatin receptor density in the residual tumor/metastatic lesions and to assess the treatment response. Hematological profiles and renal function were periodically examined after treatment. By using fractionated regimen, only mild, reversible hematological toxicity (grade 1) or nephrotoxicity (grade 1) were seen. Response assessment (using EORTC criteria) was performed in 11 patients treated with 2 or more (maximum 5) cycles of PRRT and showed disease stabilization in 4 (36.4%) patients. Two patients (18.2%) showed partial remission, in the remaining 5 patients (45.5%) disease remained progressive. Kaplan-Meier analysis resulted in a mean survival after the first PRRT of 4.2 years (95% CI, range 2.9-5.5) and median progression free survival of 25 months (inter-quartiles: 12-43). In non-radioiodine-avid/radioiodine therapy refractory thyroid cancer patients, PRRT is a promising therapeutic option with minimal toxicity, good response rate and excellent survival benefits. PMID:24380044

Curative Chemoradiotherapy in Patients With Stage IVB Cervical Cancer Presenting With Paraortic and Left Supraclavicular Lymph Node Metastases

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

Kim, Ji-Yoon; Kim, Joo-Young; Kim, Jin Hee

2012-11-01

Purpose: To evaluate the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) with curative intent in patients with stage IVB cervical cancer initially presenting with paraortic and left supraclavicular lymph node metastases. Methods and Materials: The medical records of 25 patients with both paraortic and left supraclavicular lymph nodal metastases (group I) were reviewed and compared with those of 101 women with paraortic lymph node metastases alone (group II). Group I received a mean 59.4 Gy to the paraortic and left supraclavicular areas and 50.4 Gy to the pelvis, followed by 30 Gy of high-dose-rate brachytherapy in 6 fractions. Group IImore » received the same dose to the paraortic area and pelvis followed by intracavitary brachytherapy. All patients received platinum-based chemotherapy simultaneously. Results: Of the 25 patients in group I, 16 (64%) experienced acute grade 3-4 hematologic toxicities, and 1 had a late grade 3 genitourinary toxicity. Complete responses, including the primary mass and pelvic, paraortic, and left supraclavicular lymph nodes, were observed in 13 patients (52%). At a median follow-up of 32 months for surviving patients, 3 experienced in-field failure, 6 showed distant failure, and 9 showed both. The 3-year overall and disease-free survival rates were 49% and 33%, respectively. In comparison, of the 101 patients in group II, 16 showed in-field failure, 14 experienced distant failure, and 11 showed both. The 3-year overall and disease-free survival rates were 69% and 57%, respectively. Conclusions: Curative CCRT is feasible in patients with stage IVB cervical cancer presenting with paraortic and left supraclavicular lymph nodal metastases, with acceptable late toxicity and high response rates, despite high rates of acute hematologic toxicity.« less

Population Based Analysis of Hematologic Malignancy Referrals to a Comprehensive Cancer Center, Referrals for Blood and Marrow Transplantation, and Participation in Clinical Trials, Survey and Biospecimen Research by Race

PubMed Central

Clay, Alyssa; Peoples, Brittany; Zhang, Yali; Moysich, Kirsten; Ross, Levi; McCarthy, Philip; Hahn, Theresa

2017-01-01

Racial and ethnic disparities have been reported in clinical trial/research participation, utilization of autologous and allogeneic BMT and availability of allogeneic donors. We performed a population-based cohort study to investigate adult hematologic malignancy referrals to a U.S tertiary cancer center, utilization of BMT and participation in clinical trials, survey and biospecimen research, by race. U.S. Census Data and the New York State Public Access Cancer Epidemiology Database identified the racial distribution of the general population and new hematologic malignancy cases in the primary catchment area. From 2005–2011, 1,106 patients aged 18–75 years were referred for BMT consultation; while the rate of BMT among hematologic malignancy referrals did not differ by race, the reasons for not receiving a BMT did. Participation in biospecimen research did not vary by race, however African-Americans and other minorities were significantly less likely to participate in survey research than European-Americans. While rates of hematologic malignancy referrals and use of BMT for minorities appear low (<10%), they closely reflect the race distribution of all hematologic malignancy cases and the Western New York population. African-Americans are equally likely as other races to participate in biospecimen banking, but further study is needed to understand reasons for lower participation in survey research. PMID:25899454

Weekly infusional high-dose 5-fluorouracil and leucovorin and biweekly cisplatin: a convenient treatment option in advanced gastric cancer.

PubMed

Kundel, Yulia; Purim, Ofer; Figer, Arie; Stemmer, Salomon M; Tichler, Thomas; Sulkes, Jaqueline; Sulkes, Aaron; Brenner, Baruch

2008-04-01

To summarize our experience using a regimen of weekly 5-FU and leucovorin (LV) and biweekly cisplatin (CDDP) in advanced gastric cancer (AGC). Patients had previously untreated histologically confirmed AGC. Treatment consisted of intravenous weekly infusional 5-FU and LV and biweekly CDDP, given for 6 weeks followed by a 2-week rest. Initially, a lower dose level was used (5-FU 2000 mg/m(2), LV 500 mg/m(2), CDDP 40 mg/m(2)), which was later increased (5-FU 2600 mg/m(2), LV 500 mg/m(2), CDDP 50 mg/m(2)). Forty-five patients were treated, 18 at the lower dose level and 27 at the higher dose level. The median age was 67 years and 55% were male. Grade > or =3 toxicity was documented in 37% of patients but toxicity related hospitalizations or treatment discontinuation occurred in only 22% and 13%, respectively. There were no toxic deaths. The most common hematological toxicities were anemia and neutropenia and the most common non-hematological toxicities were nausea, vomiting and fatigue. Of the 39 patients evaluable for response, 13 (33%) had partial response (PR) and 11 (28%) had stable disease (SD). Control of disease (PR+SD) was achieved in 61%. The higher dose level was associated with a higher response rate (p=0.07) and an increased toxicity (p=0.01), mostly hematological and gastrointestinal. Median progression-free survival and overall survival were 3.5 and 9.2 months, respectively. This regimen appears safe, with a manageable toxicity profile. Efficacy data resemble those reported for more complex and toxic regimens. The higher dose level had enhanced activity, at the expense of increased toxicity.

Anorectal Complications During Neutropenic Period in Patients with Hematologic Diseases

PubMed Central

Solmaz, Soner; Korur, Aslı; Gereklioğlu, Çiğdem; Asma, Süheyl; Büyükkurt, Nurhilal; Kasar, Mutlu; Yeral, Mahmut; Kozanoğlu, İlknur; Boğa, Can; Ozdoğu, Hakan

2016-01-01

Background Neutropenic patients are susceptible to any anorectal disease, and symptomatic anorectal disease afflicts 2–32% of oncology patients. Perianal infections are the most feared complication, considering the lack of natural defense against infectious microorganisms. When septic complications develop, the anorectal disease is potentially fatal, especially in neutropenic patients in whom mortality rates range between 11–57%. Although anorectal diseases are a frequent complication with potentially fatal outcomes among patients with hematologic diseases, sufficient data are not available in the literature. In this study, we aimed to investigate the anorectal complications developing during the neutropenic period in patients with hematologic diseases. Methods A total of 79 patients whose neutropenic period (absolute neutrophil count <500/mcL) continued for 7 days, or longer were included in the study. Results A total of 34 patients out of 79 (43%) were detected to develop anorectal complications, of them 6 (7.6%) developed an anorectal infection. The patients were characterized according to the hematological disease and its status (active or not), the type of treatment and the presence of a history of an anorectal pathology before the onset of the hematologic disease. Nineteen (24.1%) patients had the history of anorectal disturbances before diagnosis of the hematologic disease, and recurrence of an anorectal pathology was found in 14 out of 19 patients(73.7%). In addition, the overall mortality rate was higher among the patients who developed anorectal complications compared to another group (41.2% vs. 22.2%, p=0.059). Conclusion Anorectal pathology is a common complication with high recurrence rate in neutropenic patients. Perianal infections are important as they can cause life-threatening outcomes although they are relatively rare among all anorectal complications. Therefore perianal signs and symptoms should be meticulously evaluated concerning early diagnosis and treatment. PMID:26977278

Inhaled concentrated ambient particles are associated with hematologic and bronchoalveolar lavage changes in canines.

PubMed Central

Clarke, R W; Coull, B; Reinisch, U; Catalano, P; Killingsworth, C R; Koutrakis, P; Kavouras, I; Murthy, G G; Lawrence, J; Lovett, E; Wolfson, J M; Verrier, R L; Godleski, J J

2000-01-01

Pulmonary inflammatory and hematologic responses of canines were studied after exposure to concentrated ambient particles (CAPs) using the Harvard ambient particle concentrator (HAPC). For pulmonary inflammatory studies, normal dogs were exposed in pairs to either CAPs or filtered air (paired studies) for 6 hr/day on 3 consecutive days. For hematologic studies, dogs were exposed for 6 hr/day for 3 consecutive days with one receiving CAPs while the other was simultaneously exposed to filtered air; crossover of exposure took place the following week (crossover studies). Physicochemical characterization of CAPs exposure samples included measurements of particle mass, size distribution, and composition. No statistical differences in biologic responses were found when all CAPs and all sham exposures were compared. However, the variability in biologic response was considerably higher with CAPs exposure. Subsequent exploratory graphical analyses and mixed linear regression analyses suggested associations between CAPs constituents and biologic responses. Factor analysis was applied to the compositional data from paired and crossover experiments to determine elements consistently associated with each other in CAPs samples. In paired experiments, four factors were identified; in crossover studies, a total of six factors were observed. Bronchoalveolar lavage (BAL) and hematologic data were regressed on the factor scores. Increased BAL neutrophil percentage, total peripheral white blood cell (WBC) counts, circulating neutrophils, and circulating lymphocytes were associated with increases in the aluminum/silicon factor. Increased circulating neutrophils and increased BAL macrophages were associated with the vanadium/nickel factor. Increased BAL neutrophils were associated with the bromine/lead factor when only the compositional data from the third day of CAPs exposure were used. Significant decreases in red blood cell counts and hemoglobin levels were correlated with the sulfur factor. BAL or hematologic parameters were not associated with increases in total CAPs mass concentration. These data suggest that CAPs inhalation is associated with subtle alterations in pulmonary and systemic cell profiles, and specific components of CAPs may be responsible for these biologic responses. PMID:11133399

Low-tar and high-tar cigarettes

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

Holt, P.G.; Chalmer, J.E.; Roberts, L.M.

Mice were exposed for 7 to 8 minutes on weekdays to fresh smoke from high-tar (HT) or low-tar (LT) cigarettes for varying periods of up to 36 weeks. Mice exposed to HT cigarettes exhibited more marked alterations in humoral immune responsiveness, hematological profiles, and pulmonary pathologic findings than those exposed to LT cigarettes. However, cell-mediated immune responsiveness to both bacterial and tumor-specific antigens was depressed similarly in animals exposed to HT or LT cigarettes. Furthermore, the growth rates of subcutaneously established tumors were enhanced similarly in the two groups, with respect to those in control animals.

Behavioral-Physiological Effects of Red Phosphorus Smoke Inhalation on Two Wildlife Species. Task 3. (RP/BR Aerosol Effects upon the Spontaneous Activity, Startle Response, Pulmonary Function and Blood Chemistry/Hematology of Black-Tailed Prairie Dogs (Cynomys ludovicianus) and Rock Doves (Columba livia)

DTIC Science & Technology

1989-09-01

physiological effects of multiple exposures~-to..a red phosphorus- butyl rubber (RP/BR) military smoke product in 2 wildlife species -- bhack-tailed...effects on any pulmonary function variable of prairie dogs. There was a significant Concentration X Day interaction effect for carbon dioxide production ...dioxide production (Vco 2), respiratory exchange ratio (RER), and metabolic rate (MR) of rock doves. The interactions were associated with responses of

A phase 1b trial of the combination of the antiangiogenic agent sunitinib and radiation therapy for patients with primary and metastatic central nervous system malignancies.

PubMed

Wuthrick, Evan J; Kamrava, Mitchell; Curran, Walter J; Werner-Wasik, Maria; Camphausen, Kevin A; Hyslop, Terry; Axelrod, Rita; Andrews, David W; Glass, Jon; Machtay, Mitchell; Dicker, Adam P

2011-12-15

In this phase 1 trial, the authors evaluated sunitinib combined with radiation therapy (RT) for the treatment of primary or metastatic central nervous system (CNS) malignancies. Eligible patients had CNS malignancies that required a (minimum) 2-week course of RT. Sunitinib (37.5 mg) was administered daily for the duration of RT with optional treatment extension of 1 month. Urine was collected at 3 time points for correlative biomarker studies. The primary endpoint was acute toxicity defined according to Common Toxicity Criteria version 3. Fifteen patients were enrolled (12 with CNS metastasis and 3 with primary tumors). RT doses ranged from 14 Gray (Gy) to 70 Gy (1.8-3.5 Gy per fraction). Acute toxicities included hematologic, nausea, hyperglycemia, fatigue, hypocalcemia, and diarrhea. Six patients (40%) developed grade ≤ 2 toxicities. Grade 3 toxicities occurred in 7 patients (47%) and included hematologic toxicity, fatigue, deep vein thrombosis, dysphasia, hyperglycemia, and hyponatremia. No grade 3 through 5 hypertensive events or intracerebral hemorrhages occurred. Two grade 5 adverse events attributed to disease progression occurred. The median follow-up was 34.2 months. Two patients (13%) achieved a partial response, 9 patients (60%) had stable disease, and 2 patients (13%) patients had progressive disease. The 6-month progression-free survival rate for patients who had brain metastasis was 58%. Grade 3 hematologic toxicity was correlated with greater changes in vascular endothelial growth factor levels changes between baseline and the completion of RT. Continuous 37.5-mg sunitinib combined with RT in patients who had CNS malignancies yielded acceptable toxicities and adverse events. The current results indicated that changes in urine vascular endothelial growth factor levels are associated with hematologic toxicity, and this association should be analyzed in a larger cohort. The feasibility, safety, and early response results warrant a phase 2 trial. Copyright © 2011 American Cancer Society.

Effect of heat stress on blood rheology in different pigs breeds.

PubMed

Waltz, Xavier; Baillot, Michelle; Connes, Philippe; Gourdine, Jean-Luc; Philibert, Lucien; Beltan, Eric; Chalabi, Tawfik; Renaudeau, David

2014-01-01

The main objectives of the present work were to test the effects of heat stress on blood rheology and to determine whether the responses can change according to the pig breeds. Thirty-six pigs from three pig's lines (n = 12 for each line) with assumed different tolerance to heat stress were compared: Large White (LW, little tolerance), Creole (CR, good tolerance) and LW × CR pigs (produced from a cross between LW and CR lines). In a first period, all pigs were exposed to a 9-d period of thermo-neutral environment (24°C; d-9 to d-1; P0). At the end of P0, six pigs from each line were slaughtered (n = 18). Then in a second period, the remaining pigs (6/breed; n = 18) were exposed to a 5-d period of heat stress (32°C; d + 1 -d + 5; P1) and thereafter slaughtered at d + 5. Rectal and skin temperatures, as well as respiratory rate, were recorded on d-1 and d + 5. At slaughter, blood was sampled for hematological and hemorheological measurements. Heat stress caused a rise of the skin temperature and respiratory rate without any changes in the rectal temperature or on the hematological and hemorheological parameters when all pigs' lines were considered. We observed a pig line effect on blood viscosity at high shear rate (375 s-1) and red blood cell deformability at 30 Pa with CR pigs having lower blood viscosity and higher red blood cell deformability than LW pigs. While the changes of blood viscosity under heat stress did not reach statistical significance in LW and CR lines, blood viscosity (at 375 s-1) increased above the temperate values in the LW × CR line. Red blood cell deformability at 30 Pa was higher in CR pigs exposed to heat stress compared to LW pigs in the same condition. In conclusion, thermal loading caused physiological stress but did not widely change the hematological and hemorheological profiles. Although some blood rheological parameters seem to vary with the pig breeds, the responses to heat stress are very similar.

Population-Based Analysis of Hematologic Malignancy Referrals to a Comprehensive Cancer Center, Referrals for Blood and Marrow Transplantation, and Participation in Clinical Trial, Survey, and Biospecimen Research by Race.

PubMed

Clay, Alyssa; Peoples, Brittany; Zhang, Yali; Moysich, Kirsten; Ross, Levi; McCarthy, Philip; Hahn, Theresa

2015-08-01

Racial and ethnic disparities have been reported in clinical trial/research participation, utilization of autologous and allogeneic blood and marrow transplantation (BMT), and availability of allogeneic donors. We performed a population-based cohort study to investigate adult hematologic malignancy referrals to a US tertiary cancer center, utilization of BMT, and participation in clinical trial, survey, and biospecimen research by race. US Census Data and the New York State Public Access Cancer Epidemiology Database identified the racial distribution of the general population and new hematologic malignancy cases in the primary catchment area. From 2005 to 2011, 1106 patients aged 18 to 75 years were referred for BMT consultation; although the rate of BMT among hematologic malignancy referrals did not differ by race, the reasons for not receiving a BMT did. Participation in biospecimen research did not vary by race; however, African Americans and other minorities were significantly less likely to participate in survey research than European Americans. Although rates of hematologic malignancy referrals and use of BMT for minorities appear to be low (<10%), they closely reflect the race distribution of all hematologic malignancy cases and the western New York population. African Americans are equally likely as other races to participate in biospecimen banking, but further study is needed to understand reasons for lower participation in survey research. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Hematologic complications of pregnancy.

PubMed

Townsley, Danielle M

2013-07-01

Pregnancy induces a number of physiologic changes that affect the hematologic indices, either directly or indirectly. Recognizing and treating hematologic disorders that occur during pregnancy is difficult owing to the paucity of evidence available to guide consultants. This review discusses specifically the diagnosis and management of benign hematologic disorders occurring during pregnancy. Anemia secondary to iron deficiency is the most frequent hematologic complication and is easily treated with oral iron formulations; however, care must be taken not to miss other causes of anemia, such as sickle cell disease. Thrombocytopenia is also a common reason for consulting the hematologist, and distinguishing gestational thrombocytopenia from immune thrombocytopenia (ITP), preeclampsia, HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets), or thrombotic thrombocytopenic purpura (TTP) is essential since the treatment differs widely. Occasionally the management of mother and infant involves the expeditious recognition of neonatal alloimmune thrombocytopenia (NAIT), a condition that is responsible for severe life-threatening bleeding of the newborn. Additionally, inherited and acquired bleeding disorders affect pregnant women disproportionately and often require careful monitoring of coagulation parameters to prevent bleeding in the puerperium. Finally, venous thromboembolism (VTE) during pregnancy is still largely responsible for mortality during pregnancy, and the diagnosis, treatment options and guidelines for prevention of VTE during pregnancy are explored. Published by Elsevier Inc.

Long-term follow-up of MCL patients treated with single-agent ibrutinib: updated safety and efficacy results.

PubMed

Wang, Michael L; Blum, Kristie A; Martin, Peter; Goy, Andre; Auer, Rebecca; Kahl, Brad S; Jurczak, Wojciech; Advani, Ranjana H; Romaguera, Jorge E; Williams, Michael E; Barrientos, Jacqueline C; Chmielowska, Ewa; Radford, John; Stilgenbauer, Stephan; Dreyling, Martin; Jedrzejczak, Wieslaw Wiktor; Johnson, Peter; Spurgeon, Stephen E; Zhang, Liang; Baher, Linda; Cheng, Mei; Lee, Dana; Beaupre, Darrin M; Rule, Simon

2015-08-06

Ibrutinib, an oral inhibitor of Bruton tyrosine kinase, is approved for patients with mantle cell lymphoma (MCL) who have received one prior therapy. We report the updated safety and efficacy results from the multicenter, open-label phase 2 registration trial of ibrutinib (median 26.7-month follow-up). Patients (N = 111) received oral ibrutinib 560 mg once daily, and those with stable disease or better could enter a long-term extension study. The primary end point was overall response rate (ORR). The median patient age was 68 years (range, 40-84), with a median of 3 prior therapies (range, 1-5). The median treatment duration was 8.3 months; 46% of patients were treated for >12 months, and 22% were treated for ≥2 years. The ORR was 67% (23% complete response), with a median duration of response of 17.5 months. The 24-month progression-free survival and overall survival rates were 31% (95% confidence interval [CI], 22.3-40.4) and 47% (95% CI, 37.1-56.9), respectively. The most common adverse events (AEs) in >30% of patients included diarrhea (54%), fatigue (50%), nausea (33%), and dyspnea (32%). The most frequent grade ≥3 infections included pneumonia (8%), urinary tract infection (4%), and cellulitis (3%). Grade ≥3 bleeding events in ≥2% of patients were hematuria (2%) and subdural hematoma (2%). Common all-grade hematologic AEs were thrombocytopenia (22%), neutropenia (19%), and anemia (18%). The prevalence of infection, diarrhea, and bleeding was highest for the first 6 months of therapy and less thereafter. With longer follow-up, ibrutinib continues to demonstrate durable responses and favorable safety in relapsed/refractory MCL. The trial is registered to www.ClinicalTrials.gov as #NCT01236391. © 2015 by The American Society of Hematology.

Updated efficacy and toxicity analysis of irinotecan and oxaliplatin (IROX) : intergroup trial N9741 in first-line treatment of metastatic colorectal cancer.

PubMed

Ashley, Amanda C; Sargent, Daniel J; Alberts, Steven R; Grothey, Axel; Campbell, Megan E; Morton, Roscoe F; Fuchs, Charles S; Ramanathan, Ramesh K; Williamson, Stephen K; Findlay, Brian P; Pitot, Henry C; Goldberg, Richard M

2007-08-01

Efficacy and toxicity of oxaliplatin (Eloxatin; Sanofi-Aventis, Paris, France) combined with irinotecan (IROX) were examined in 383 patients enrolled on the IROX arm of Intergroup Study N9741. This IROX regimen was oxaliplatin 85 mg/m(2) and irinotecan 200 mg/m(2) administered every 3 weeks. The relation between adverse events on IROX to selected characteristics was analyzed. Time to progression (TTP), response rate, and overall survival for patients treated with IROX compared with patients treated with oxaliplatin with 5- fluorouracil (FOLFOX) were updated in this article. Grade >or=3 gastrointestinal and hematologic toxicities were common with 39% patients experiencing neutropenia, 28% diarrhea, and 21% vomiting. Patients ages >70 years experienced higher rates of grade >or=3 toxicity, with significantly higher rates of grade >or=3 hematologic toxicities (P = .02). Long-term toxicity was uncommon, and nearly all cases of grade >or=3 neurotoxicity resolved within 10 months. Fifty-two percent of patients required dose reductions for adverse events, and 26% experienced 119 hospitalizations related to complications of treatment or their disease, with 5 treatment-related deaths. This analysis confirmed prior findings that FOLFOX is superior to IROX in terms of response rate (43% vs 36%, p = 0.002), TTP (9.2 months vs 6.7 months, P < .0001), and overall survival (19.5 months vs 17.3 months, P = .0001). IROX was found to be less active than FOLFOX but with a similar toxicity profile except in patients ages >70 years. Although IROX may be considered in patients intolerant of 5-FU or in patients known to have a dihydropyrimidine dehydrogenase (DPD) deficiency, it should be used with caution in older patients. (c) 2007 American Cancer Society.

What do cardiovascular nurses know about the hematological management of patients with Eisenmenger syndrome?

PubMed

Moons, Philip; Fleck, Desiree; Jaarsma, Tiny; Norekval, Tone M; Smith, Karen; Stromberg, Anna; Thompson, David R; Budts, Werner

2009-10-01

We investigated the level of knowledge of hematological management of patients with Eisenmenger syndrome among general cardiovascular nurses and nurses who specialize in congenital heart disease (CHD). We conducted a survey at two international conferences attended by cardiovascular nurses. Nurses were asked to complete a questionnaire comprising two questions and three clinical case scenarios. Overall, 89 nurses participated (response rate 90.8%), 43 of whom specialized in CHD. The level of knowledge displayed among cardiovascular nurses is poor. About one-third of nurses not specialized in CHD recognized the definition of Eisenmenger syndrome and knew what normal hematocrit levels are. With respect to the cases presented, less than 10% of the nurses could give a correct answer. The level of knowledge of specialized nurses was significantly higher, but also here, important gaps in the level of knowledge could be observed. Less than two-thirds knew the reference values of hematocrit and knew the appropriate management in two cases. Less than half of the specialized nurses knew about the procedure of isovolumic phlebotomy. The level of knowledge displayed by cardiovascular nurses regarding the hematological management of patients with Eisenmenger syndrome is poor. Also the knowledge of nurses specialized in CHD could be improved.

Morbillivirus and Toxoplasma exposure and association with hematological parameters for southern Beaufort Sea polar bears: potential response to infectious agents in a sentinel species.

PubMed

Kirk, Cassandra M; Amstrup, Steven; Swor, Rhonda; Holcomb, Darce; O'Hara, Todd M

2010-09-01

Arctic temperatures are increasing in response to greenhouse gas forcing and polar bears have already responded to changing conditions. Declines in body stature and vital rates have been linked to warming-induced loss of sea-ice. As food webs change and human activities respond to a milder Arctic, exposure of polar bears and other arctic marine organisms to infectious agents may increase. Because of the polar bear's status as arctic ecosystem sentinel, polar bear health could provide an index of changing pathogen occurrence throughout the Arctic, however, exposure and monitoring protocols have yet to be established. We examine prevalence of antibodies to Toxoplasma gondii, and four morbilliviruses (canine distemper [CDV], phocine distemper [PDV], dolphin morbillivirus [DMV], porpoise morbillivirus [PMV]) including risk factors for exposure. We also examine the relationships between antibody levels and hematologic values established in the previous companion article. Antibodies to Toxoplasma gondii and morbilliviruses were found in both sample years. We found a significant inverse relationship between CDV titer and total leukocytes, neutrophils, monocytes, and eosinophils, and a significant positive relationship between eosinophils and Toxoplasma gondii antibodies. Morbilliviral prevalence varied significantly among age cohorts, with 1-2 year olds least likely to be seropositive and bears aged 5-7 most likely. Data suggest that the presence of CDV and Toxoplasma gondii antibodies is associated with polar bear hematologic values. We conclude that exposure to CDV-like antigen is not randomly distributed among age classes and suggest that differing behaviors among life history stages may drive probability of specific antibody presence.

Boceprevir or Telaprevir Based Triple Therapy against Chronic Hepatitis C in HIV Coinfection: Real-Life Safety and Efficacy

PubMed Central

Neukam, Karin; Munteanu, Daniela I.; Rivero-Juárez, Antonio; Lutz, Thomas; Fehr, Jan; Mandorfer, Mattias; Bhagani, Sanjay; López-Cortés, Luis F.; Haberl, Annette; Stoeckle, Marcel; Márquez, Manuel; Scholten, Stefan; de los Santos-Gil, Ignacio; Mauss, Stefan; Rivero, Antonio; Collado, Antonio; Delgado, Marcial; Rockstroh, Juergen K.; Pineda, Juan A.

2015-01-01

Background and Aims Clinical trials of therapy against chronic hepatitis C virus (HCV) infection including boceprevir (BOC) or telaprevir (TVR) plus pegylated interferon and ribavirin (PR) have reported considerably higher response rates than those achieved with PR alone. This study sought to evaluate the efficacy and safety of triple therapy including BOC or TVR in combination with PR in HIV/HCV-coinfected patients under real-life conditions. Methods In a multicentre study conducted in 24 sites throughout five European countries, all HIV/HCV-coinfected patients who initiated a combination of BOC or TVR plus PR and who had at least 60 weeks of follow-up, were analyzed. Sustained virologic response 12 weeks after the scheduled end of therapy date (SVR12) and the rate of discontinuations due to adverse events (AE) were evaluated. Results Of the 159 subjects included, 127 (79.9%) were male, 45 (34.4%) were treatment-naïve for PR and 60 (45.4%) showed cirrhosis. SVR12 was observed in 31/46 (67.4%) patients treated with BOC and 69/113 (61.1%) patients treated with TVR. Overall discontinuations due to AE rates were 8.7% for BOC and 8% for TVR. Grade 3 or 4 hematological abnormalities were frequently observed; anemia 7%, thrombocytopenia 17.2% and neutropenia 16.4%. Conclusion The efficacy and safety of triple therapy including BOC or TVR plus PR under real-life conditions of use in the HIV/HCV-coinfected population was similar to what is observed in clinical trials. Hematological side effects are frequent but manageable. PMID:25923540

Hematology/immunology (M110 series). [human hemodynamic response to weightlessness simulation

NASA Technical Reports Server (NTRS)

1973-01-01

The hematology/immunology experiments in the Skylab mission study various aspects of the red blood cell, including its metabolism and life span, and blood volume changes under zero gravity conditions to determine the precise mechanism of the transient changes which have been seen on the relatively brief missions of the past.

An exploratory study of the relation of population density and agricultural activity to hematologic malignancies in North Dakota.

PubMed

Watkins, Patricia L; Watkins, John M

2013-02-01

Established risk factors for hematologic cancers include exposure to ionizing radiation, organic solvents, and genetic mutation; however, the potential roles of environmental and sociological factors are not well explored. As North Dakota engages in significant agricultural activity, the present investigation seeks to determine whether an association exists between the incidence of hematologic cancers and either population density or agricultural occupation for residents of south central North Dakota. The present study is a retrospective analysis. Cases of hematologic malignancies and associated pre-malignant conditions were collected from the regional Central North Dakota Cancer Registry, and analysis of study-specific demographic factors was performed. Significantly higher incidence of hematologic cancers and pre-malignant disorders was associated with residence in an "urban" county and rural city/town. Within the latter designation, there was a higher rate of self-reported agricultural occupation (40% vs 10%, P < 0.0001). The increased incidence of hematologic cancer in low population density areas of south central North Dakota supports the need for more detailed prospective research centered on agricultural exposures.

Weekly irinotecan in patients with metastatic colorectal cancer failing 5-fluorouracil-based chemotherapy: efficacy and prognostic factors.

PubMed

Karaoğlu, Aziz; Yalcin, Suayib; Tekuzman, Gülten; Kars, Ayse; Celik, Ismail; Güler, Nilüfer; Ozişik, Yavuz; Türker, Alev; Barişta, Ibrahim; Güllü, Ibrahim

2003-01-01

We evaluated the efficacy and tolerability of weekly irinotecan as a second-line treatment in patients with colorectal cancer failing 5-fluorouracil-based chemotherapy and searched for predictive and prognostic factors. A total of 36 patients were included. Median age was 53 years (range, 33-72). One treatment cycle consisted of irinotecan, 100 mg/m2 weekly, for 4 weeks followed by a 2-week rest. Gender, age, primary site, number of metastatic sites, histologic subtype, differentiation, pretreatment CEA, CA 19-9 and lactate dehydrogenase levels and marker response to treatment were investigated as predictive factors for response to treatment and as prognostic factors in the overall survival and time to progression of the patients. A total of 120 cycles (median, 3 cycles) was delivered. An overall 14% objective response rate (1 complete and 4 partial responses) was achieved. The median response duration was 4 months (range, 2-7). Another 36% of the patients had stable disease for a median duration of 4 months (range, 2-8). Median time-to-disease progression was 4 months and overall median survival was 12 months (95% confidence interval, 9-15). Pretreatment serum CA 19-9 level and marker response to two courses of treatment were found to be clinically significant in time to progression and overall survival. Younger age (< or = 45 years) was a poor prognostic factor associated with a shorter time to progression. The major toxicity was grade 3-4 diarrhea, which occurred in 28% of the patients, and treatment was discontinued in 3 (8%) patients due to toxicity. Other hematological and non-hematological toxicities were mild and manageable. We concluded that weekly irinotecan at the dose of 100 mg/m2 is an effective and tolerable treatment option, with a 50% disease control rate, for patients with colorectal cancer failing previous 5-fluorouracil-based chemotherapy.

IIVP salvage regimen induces high response rates in patients with relapsed lymphoma before autologous stem cell transplantation.

PubMed

Abali, Huseyin; Oyan, Basak; Koc, Yener; Kars, Ayse; Barista, Ibrahim; Uner, Aysegul; Turker, Alev; Demirkazik, Figen; Tekin, Fatma; Tekuzman, Gulten; Kansu, Emin

2005-06-01

Patients with relapsed lymphoma can be cured with high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HSCT). New therapeutic approaches with better cytoreductive capacity are needed for relapsed patients to keep their chance for cure with transplantation. We report 30 patients with relapsed lymphoma, median age 43 years, treated with IIVP salvage regimen consisting of ifosfamide, mesna, idarubicin, and etoposide for 2 or 3 cycles. Seventeen patients had non-Hodgkin lymphoma (NHL) and 13 patients had Hodgkin disease (HD). Fourteen (47%) patients were at their first relapse. Overall response rate was 86.6% (n = 26) with 19 patients (63.3%) achieving complete response. Overall response rate was 92% in patients with HD and 82% in NHL. The most frequent side effects observed were grade III-IV neutropenia (87%) and thrombocytopenia (73%). IIVP regimen is a highly effective salvage therapy for patients with relapsed HD or NHL who are candidates for autologous HSCT. Close follow up is necessary because of the high incidence of grade III-IV hematologic toxicity.

Hematological indicators of stress in longline-captured sharks.

PubMed

Marshall, Heather; Field, Lyndsay; Afiadata, Achankeng; Sepulveda, Chugey; Skomal, Gregory; Bernal, Diego

2012-06-01

For many shark species, little information exists about the stress response to capture and release in commercial longline fisheries. Recent studies have used hematological profiling to assess the secondary stress response, but little is known about how, and to what degree, these indicators vary interspecifically. Moreover, there is little understanding of the extent to which the level of relative swimming activity (e.g., sluggish vs. active) or the general ecological classification (e.g., coastal vs. pelagic) correlates to the magnitude of the exercise-induced (capture-related) stress response. This study compared plasma electrolytes (Na(+), Cl(-), Mg(2+), Ca(2+), and K(+)), metabolites (glucose and lactate), blood hematocrit, and heat shock protein (Hsp70) levels between 11 species of longline-captured sharks (n=164). Statistical comparison of hematological parameters revealed species-specific differences in response to longline capture, as well as differences by ecological classification. Taken together, the blood properties of longline-captured sharks appear to be useful indicators of interspecific variation in the secondary stress response to capture, and may prove useful in the future for predicting survivorship of longline-captured sharks where new technologies (i.e., pop-up satellite tags) can verify post-release mortality. Copyright © 2012 Elsevier Inc. All rights reserved.

Practical Murine Hematopathology: A Comparative Review and Implications for Research

PubMed Central

O'Connell, Karyn E; Mikkola, Amy M; Stepanek, Aaron M; Vernet, Andyna; Hall, Christopher D; Sun, Chia C; Yildirim, Eda; Staropoli, John F; Lee, Jeannie T; Brown, Diane E

2015-01-01

Hematologic parameters are important markers of disease in human and veterinary medicine. Biomedical research has benefited from mouse models that recapitulate such disease, thus expanding knowledge of pathogenetic mechanisms and investigative therapies that translate across species. Mice in health have many notable hematologic differences from humans and other veterinary species, including smaller erythrocytes, higher percentage of circulating reticulocytes or polychromasia, lower peripheral blood neutrophil and higher peripheral blood and bone marrow lymphocyte percentages, variable leukocyte morphologies, physiologic splenic hematopoiesis and iron storage, and more numerous and shorter-lived erythrocytes and platelets. For accurate and complete hematologic analyses of disease and response to investigative therapeutic interventions, these differences and the unique features of murine hematopathology must be understood. Here we review murine hematology and hematopathology for practical application to translational investigation. PMID:25926395

Incidence of colonization and bloodstream infection with carbapenem-resistant Enterobacteriaceae in children receiving antineoplastic chemotherapy in Italy.

PubMed

Caselli, Desiree; Cesaro, Simone; Fagioli, Franca; Carraro, Francesca; Ziino, Ottavio; Zanazzo, Giulio; Meazza, Cristina; Colombini, Antonella; Castagnola, Elio

2016-02-01

Few data are available on the incidence of carbapenemase-producing Enterobacteriaceae (CPE) infection or colonization in children receiving anticancer chemotherapy. We performed a nationwide survey among centers participating in the pediatric hematology-oncology cooperative study group (Associazione Italiana Ematologia Oncologia Pediatrica, AIEOP). During a 2-year observation period, we observed a threefold increase in the colonization rate, and a fourfold increase of bloodstream infection episodes, caused by CPE, with a 90-day mortality of 14%. This first nationwide Italian pediatric survey shows that the circulation of CPE strains in the pediatric hematology-oncology environment is increasing. Given the mortality rate, which is higher than for other bacterial strains, specific monitoring should be applied and the results should have implications for health-care practice in pediatric hematology-oncology.

Investigating the Cellular and Metabolic Responses of World-Class Canoeists Training: A Sportomics Approach

PubMed Central

Coelho, Wagner Santos; Viveiros de Castro, Luis; Deane, Elizabeth; Magno-França, Alexandre; Bassini, Adriana; Cameron, Luiz-Claudio

2016-01-01

(1) Background: We have been using the Sportomics approach to evaluate biochemical and hematological changes in response to exercise. The aim of this study was to evaluate the metabolic and hematologic responses of world-class canoeists during a training session; (2) Methods: Blood samples were taken at different points and analyzed for their hematological properties, activities of selected enzymes, hormones, and metabolites; (3) Results: Muscle stress biomarkers were elevated in response to exercise which correlated with modifications in the profile of white blood cells, where a leukocyte rise was observed after the canoe session. These results were accompanied by an increase in other exercise intensity parameters such as lactatemia and ammonemia. Adrenocorticotropic hormone and cortisol increased during the exercise sessions. The acute rise in both erythrocytes and white blood profile were probably due to muscle cell damage, rather than hepatocyte integrity impairment; (4) Conclusion: The cellular and metabolic responses found here, together with effective nutrition support, are crucial to understanding the effects of exercise in order to assist in the creation of new training and recovery planning. Also we show that Sportomics is a primal tool for training management and performance improvement, as well as to the understanding of metabolic response to exercise. PMID:27845704

Relapsed chronic lymphocytic leukemia retreated with rituximab: interim results of the PERLE study.

PubMed

Chaoui, Driss; Choquet, Sylvain; Sanhes, Laurence; Mahé, Béatrice; Hacini, Maya; Fitoussi, Olivier; Arkam, Yazid; Orfeuvre, Hubert; Dilhuydy, Marie-Sarah; Barry, Marly; Jourdan, Eric; Dreyfus, Brigitte; Tempescul, Adrian; Leprêtre, Stéphane; Bardet, Aurélie; Leconte, Pierre; Maynadié, Marc; Delmer, Alain

2017-06-01

This prospective non-interventional study assessed the management of relapsed/refractory CLL after one or two treatments with rituximab, and retreatment with a rituximab-based regimen. An interim analysis was performed at the end of the induction period in 192 evaluable patients. Median age was 72 years [35-89], first relapse (55%), and second relapse (45%). Rituximab administered during first (68%), second (92%), or both treatment lines (20%). R-bendamustine administered in 56% of patients, R-purine analogs (21%), and R-alkylating agents (19%). The overall response rate (ORR) was 74.6%, in favor of R-purine analogs (90%), R-bendamustine (75%), and R-alkylating agents (69%). Lower ORR in Del 17p patients (43%) and third time rituximab (31%). Most frequent adverse events were hematological (23% patients) including neutropenia (11%) and infections (12%); grade 3/4 AEs (23% patients), mainly hematological (18%); death during induction treatment (7%). This first large study focusing on relapsed/refractory CLL patients retreated with rituximab-based regimens is still ongoing.

Mucorales-Specific T Cells in Patients with Hematologic Malignancies.

PubMed

Potenza, Leonardo; Vallerini, Daniela; Barozzi, Patrizia; Riva, Giovanni; Gilioli, Andrea; Forghieri, Fabio; Candoni, Anna; Cesaro, Simone; Quadrelli, Chiara; Maertens, Johan; Rossi, Giulio; Morselli, Monica; Codeluppi, Mauro; Mussini, Cristina; Colaci, Elisabetta; Messerotti, Andrea; Paolini, Ambra; Maccaferri, Monica; Fantuzzi, Valeria; Del Giovane, Cinzia; Stefani, Alessandro; Morandi, Uliano; Maffei, Rossana; Marasca, Roberto; Narni, Franco; Fanin, Renato; Comoli, Patrizia; Romani, Luigina; Beauvais, Anne; Viale, Pier Luigi; Latgè, Jean Paul; Lewis, Russell E; Luppi, Mario

2016-01-01

Invasive mucormycosis (IM) is an emerging life-threatening fungal infection. It is difficult to obtain a definite diagnosis and to initiate timely intervention. Mucorales-specific T cells occur during the course of IM and are involved in the clearance of the infection. We have evaluated the feasibility of detecting Mucorales-specific T cells in hematological patients at risk for IM, and have correlated the detection of such cells with the clinical conditions of the patients. By using an enzyme linked immunospot assay, the presence of Mucorales-specific T cells in peripheral blood (PB) samples has been investigated at three time points during high-dose chemotherapy for hematologic malignancies. Mucorales-specific T cells producing interferon-γ, interleukin-10 and interleukin-4 were analysed in order to detect a correlation between the immune response and the clinical picture. Twenty-one (10.3%) of 204 patients, accounting for 32 (5.3%) of 598 PB samples, tested positive for Mucorales-specific T cells. Two groups could be identified. Group 1, including 15 patients without signs or symptoms of invasive fungal diseases (IFD), showed a predominance of Mucorales-specific T cells producing interferon-gamma. Group 2 included 6 patients with a clinical picture consistent with invasive fungal disease (IFD): 2 cases of proven IM and 4 cases of possible IFD. The proven patients had significantly higher number of Mucorales-specific T cells producing interleukin-10 and interleukin-4 and higher rates of positive samples by using derived diagnostic cut-offs when compared with the 15 patients without IFD. Mucorales-specific T cells can be detected and monitored in patients with hematologic malignancies at risk for IM. Mucorales-specific T cells polarized to the production of T helper type 2 cytokines are associated with proven IM and may be evaluated as a surrogate diagnostic marker for IM.

Morbillivirus and Toxoplasma exposure and association with hematological parameters for southern Beaufort Sea polar bears: potential response to infectious agents in a sentinel species

USGS Publications Warehouse

Kirk, Cassandra M.; Amstrup, Steven C.; Swor, Rhonda; Holcomb, Darce; O'Hara, Todd M.

2010-01-01

Arctic temperatures are increasing in response to greenhouse gas forcing and polar bears have already responded to changing conditions. Declines in body stature and vital rates have been linked to warming-induced loss of sea-ice. As food webs change and human activities respond to a milder Arctic, exposure of polar bears and other arctic marine organisms to infectious agents may increase. Because of the polar bear’s status as arctic ecosystem sentinel, polar bear health could provide an index of changing pathogen occurrence throughout the Arctic, however, exposure and monitoring protocols have yet to be established. We examine prevalence of antibodies to Toxoplasma gondii, and four morbilliviruses (canine distemper [CDV], phocine distemper [PDV], dolphin morbillivirus [DMV], porpoise morbillivirus [PMV]) including risk factors for exposure. We also examine the relationships between antibody levels and hematologic values established in the previous companion article. Antibodies to Toxoplasma gondii and morbilliviruses were found in both sample years. We found a significant inverse relationship between CDV titer and total leukocytes, neutrophils, monocytes, and eosinophils, and a significant positive relationship between eosinophils and Toxoplasma gondii antibodies. Morbilliviral prevalence varied significantly among age cohorts, with 1–2 year olds least likely to be seropositive and bears aged 5–7 most likely. Data suggest that the presence of CDV and Toxoplasma gondii antibodies is associated with polar bear hematologic values. We conclude that exposure to CDV-like antigen is not randomly distributed among age classes and suggest that differing behaviors among life history stages may drive probability of specific antibody presence.

The Bruton tyrosine kinase inhibitor ibrutinib with chemoimmunotherapy in patients with chronic lymphocytic leukemia

PubMed Central

Barrientos, Jacqueline C.; Barr, Paul M.; Flinn, Ian W.; Burger, Jan A.; Tran, Anh; Clow, Fong; James, Danelle F.; Graef, Thorsten; Friedberg, Jonathan W.; Rai, Kanti; O’Brien, Susan

2015-01-01

The safety and efficacy of ibrutinib, an oral inhibitor of Bruton tyrosine kinase, were evaluated with chemoimmunotherapy (CIT) in a multicenter phase 1b study. Patients with relapsed/refractory chronic lymphocytic leukemia received bendamustine and rituximab (BR) or fludarabine, cyclophosphamide, and rituximab (FCR) for up to 6 cycles with daily ibrutinib (420 mg) until progressive disease or unacceptable toxicity. Enrollment to FCR-ibrutinib closed early due to a lack of fludarabine-naïve previously treated patients. No patients treated with BR-ibrutinib (n = 30) or FCR-ibrutinib (n = 3) experienced prolonged hematologic toxicity in cycle 1 (primary end point). Tolerability was as expected with either CIT or single-agent ibrutinib. The overall response rate (ORR) with BR-ibrutinib was 93.3%, including 16.7% complete responses (CRs) initially, which increased to 40% with the extension period. Including 1 patient with partial response with lymphocytosis, the best ORR was 96.7%. Sixteen of 21 patients with baseline cytopenias had sustained hematologic improvement. At 12 and 36 months, 86.3% and 70.3% remained progression-free, respectively. All 3 patients treated with ibrutinib-FCR achieved CR. Ibrutinib may enhance CIT efficacy without additive toxicities, providing the rationale for studying this combination in an ongoing phase 3 trial. The study is registered to www.clinicaltrials.gov as #NCT01292135. PMID:25755291

Hematology from embryo to adult in the bobwhite quail (Colinus virginianus): Differential effects in the adult of clutch, sex and hypoxic incubation.

PubMed

Flores-Santin, Josele; Rojas Antich, Maria; Tazawa, Hiroshi; Burggren, Warren W

2018-04-01

Hematology and its regulation in developing birds have been primarily investigated in response to relatively short-term environmental challenges in the embryo. Yet, whether any changes induced in the embryo persist into adulthood as a hematological form of "fetal programming" is unknown. We hypothesized that: 1) chronic as opposed to acute hypoxic incubation will alter hematological respiratory variables in embryos of bobwhite quail (Colinus virginianus), and 2) alterations first appearing in the embryo will persist into hatchlings through into adulthood. To test these hypotheses, we first developed an embryo-to-adult profile of normal hematological development by measuring hematocrit (Hct), red blood cell concentration ([RBC]), hemoglobin concentration ([Hb]), mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration, as well plasma osmolality. Hct, [RBC] and [Hb] in normoxic-incubated birds (controls) steadily increased from ~22%, ~1.6 × 10 6  μL -1 and ~7 g% in day 12 embryos to almost double the values at maturity in adult birds. Both cohort and sex affected hematology of normoxic-incubated birds. A second population, incubated from day 0 (d0) in 15% O 2 , surprisingly revealed little or no significant difference from controls in hematology in embryos. In hatchlings and adults, hypoxic incubation caused no significant modification to any variables. Compared to major hematological effects caused by hypoxic incubation in chickens, the hematology of the bobwhite quail embryo appears to be minimally affected by hypoxic incubation, with very few effects induced during hypoxic incubation actually persisting into adulthood. Copyright © 2018 Elsevier Inc. All rights reserved.

Residential radon exposure and risk of incident hematologic malignancies in the Cancer Prevention Study-II Nutrition Cohort.

PubMed

Teras, Lauren R; Diver, W Ryan; Turner, Michelle C; Krewski, Daniel; Sahar, Liora; Ward, Elizabeth; Gapstur, Susan M

2016-07-01

Dosimetric models show that radon, an established cause of lung cancer, delivers a non-negligible dose of alpha radiation to the bone marrow, as well as to lymphocytes in the tracheobronchial epithelium, and therefore could be related to risk of hematologic cancers. Studies of radon and hematologic cancer risk, however, have produced inconsistent results. To date there is no published prospective, population-based study of residential radon exposure and hematologic malignancy incidence. We used data from the American Cancer Society Cancer Prevention Study-II Nutrition Cohort established in 1992, to examine the association between county-level residential radon exposure and risk of hematologic cancer. The analytic cohort included 140,652 participants (66,572 men, 74,080 women) among which 3019 incident hematologic cancer cases (1711 men, 1308 women) were identified during 19 years of follow-up. Cox proportional hazard regression was used to calculate multivariable-adjusted hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for radon exposure and hematologic cancer risk. Women living in counties with the highest mean radon concentrations (>148Bq/m(3)) had a statistically significant higher risk of hematologic cancer compared to those living in counties with the lowest (<74Bq/m(3)) radon levels (HR=1.63, 95% CI:1.23-2.18), and there was evidence of a dose-response relationship (HRcontinuous=1.38, 95% CI:1.15-1.65 per 100Bq/m(3); p-trend=0.001). There was no association between county-level radon and hematologic cancer risk among men. The findings of this large, prospective study suggest residential radon may be a risk factor for lymphoid malignancies among women. Further study is needed to confirm these findings. Copyright © 2016 Elsevier Inc. All rights reserved.

Gemcitabine-oxaliplatin (GEMOX) for epithelial ovarian cancer patients resistant to platinum-based chemotherapy.

PubMed

Elshebeiny, Mohamed; Almorsy, Walid

2016-09-01

Patients with platinum-resistant epithelial ovarian cancer (EOC) experience poor outcome. Currently, no clearly superior management strategy exists for platinum-resistant EOC patients. Analyze the efficacy and safety of gemcitabine-oxaliplatin (GEMOX) in platinum resistant EOC patients. Thirty-two patients with platinum-based resistant EOC were included. Studied patients had received GEM at the dose of 1000mg/m(2) on days 1 and 8 and OX 100mg/m(2) on day 1, administered over 2h 30min after GEM infusion of 3week treatment cycle. In the evaluation of tumor response, none of patients had achieved CR while PR, SD, were observed in 7 (21.9%), 9 (28.1%) respectively, clinical benefit (CR+PR+SD) was recorded in 50% of patients while PD was observed in 16 (50%) patients. In regard to survival, the median value of OS was 10.5months (range, 2.2-17.5months). The median value of PFS was 6.37months (range, 1-17.5months). The one-year OS rate was 34.4% and the one-year PFS rate was 12.5%. Concerning hematological toxicity grade 3 neutropenia was recorded in 4 (12.5%) patients while grade 4 febrile neutropenia was recorded in 2 (6.3%) patients and grade 4 anemia was represented by 3.1%. Grade 1-2 fatigue was the most common non-hematological toxicity and represented by 65.6% of patients. Grade 3 non hematological toxicity was recorded with nausea/vomiting and hepatic toxicity represented by 3.1% for both. The GEMOX combination is a regimen with a moderate therapeutic efficacy and tolerable toxic side effects in patients with platinum-resistant EOC. Copyright © 2016. Production and hosting by Elsevier B.V.

Epirubicin versus mitoxantrone in combination chemotherapy for metastatic breast cancer.

PubMed

Pavesi, L; Preti, P; Da Prada, G; Pedrazzoli, P; Poggi, G; Robustelli della Cuna, G

1995-01-01

As valid therapeutic alternatives to adriamycin, with a more favourable safety profile, epirubicin (E) and novantrone (N) were compared in combination with fluorouracil (F) and cyclophosphamide (C) in a prospective randomized clinical trial as first-line treatment for metastatic breast cancer (mbc). 158 women with mbc were randomly allocated to receive FEC or FNC regimen; the dosage in mg/m2 was as follows: 500 for C and F, 75 for E and 10 for N. All drugs were administered iv. on day 1 and recycled on day 21. In 141 evaluable patients the response rate (CR+PR) was better in the FEC (43.6%) than in the FNC regimen (30.3%) (95% C.I. of 32% to 55% versus 14% to 34%), without any statistically significant difference. Differences in response rate were significantly in favour of FEC group in previously untreated patients (57.6% versus 25%, p = .02), and in postmenopausal women (46.1% versus 23.6%, p = .01). No significant differences between the two treatment arms were observed in terms of either time to progression or duration of response and survival. The most important dose-limiting toxicity was hematological (leuko-and thrombocytopenia were significantly higher in FNC-treated patients). This difference in hematological toxicity sustained a significantly different incidence of delays in administering chemotherapy courses, which precluded the administration of comparable doses of all drugs in both groups. The incidence of complete alopecia was significantly higher in FEC-treated patients, while no clinical or instrumental evidence of CHF was observed with either regimen. Due to its more favourable therapeutic profile, the E-containing regimen seems a suitable first-line treatment for previously untreated patients with mbc, while the FNC combination should be offered to women refusing hair loss.

[Clinical study on a concomitant therapy with fluconazole and human recombinant granulocyte colony stimulating factor in the treatment of systemic fungal infections with hematological disorders].

PubMed

Kitamura, K; Miyagawa, K; Urabe, A; Sato, H; Obayashi, Y; Aoki, I; Takaku, F; Togawa, A; Shindou, E; Wakabayashi, Y; Ohshima, T; Horikoshi, A; Nomura, T; Ohki, I; Suzuki, K; Kamakura, M; Oguchi, A; Toyama, K; Yaguchi, M; Aoki, N; Kato, A; Mizoguchi, H; Masuda, M; Irie, S; Fujioka, S

1996-12-01

The clinical efficacy and the safety of concomitant therapy with fluconazole and recombinant human granulocyte colony stimulating factor (rhG-CSF) was compared with fluconazole monotherapy in neutropenic patients with hematological disorders. The clinical efficacy rate was 73.5% (25/34) in the combination therapy and 48.1% (37/77) in monotherapy. The difference between the two is statistically significant. Side effects were not observed in the combination group, but laboratory abnormalities were found in 6 patients with an incident rate of 11%. The combination therapy with fluconazole and rhG-CSF may be selected as empiric therapy for systemic fungal infection associated with hematological disorders, since this combination therapy showed high efficacy and low incident of side effects. Some patients, however, did not show increased neutrophil counts in spite of rhG-CSF administration.

Continuous IV Crotalidae Polyvalent Immune Fab (Ovine) (FabAV) for selected North American rattlesnake bite patients.

PubMed

Bush, Sean P; Seifert, Steven A; Oakes, Jennifer; Smith, Susan D; Phan, Tammy H; Pearl, Sarah R; Reibling, Ellen T

2013-07-01

In patients bitten by North American rattlesnakes and treated with Crotalidae Polyvalent Immune Fab (Ovine) (FabAV), late hematologic abnormalities-persistent, recurrent, or late, new onset of hypofibrinogenemia, prolonged PT/INR, prolonged PTT, and/or thrombocytopenia beyond 48 h post-envenomation-are common, difficult to manage, and may result in morbidity and mortality are common, difficult to manage, and may result in morbidity and mortality. The optimal management of late hematologic abnormalities, particularly the use of further treatment with antivenom, has not been well defined. The current FabAV treatment regimen is to give antivenom as a bolus dose over a one-hour period. We describe our experience using a continuous intravenous infusion of FabAV for late hematologic effects and/or associated bleeding complications in rattlesnake envenomation. This is a retrospective, observational case series of patients envenomated by North American rattlesnakes at three medical centers managed with a continuous intravenous infusion of FabAV for late hematologic abnormalities and/or associated bleeding complications. Indications, dilution and infusion protocols, and duration of therapy were individualized. Five cases were identified between July 2010 and September 2011. All patients had profound late hematologic abnormalities and/or were associated with bleeding complications. Several patients had received repeat bolus infusions of FabAV, with or without human blood products, with either inadequate or only transient beneficial response. All patients were then managed with a continuous intravenous infusion of FabAV and all appeared to respond to the continuous intravenous infusion of FabAV, titrated to effect, with cessation of progression and, in most cases, improvement in hematologic abnormalities. Rates of infusion varied from 2 to 4 vials per 24 h (mean = 3.1 ± 0.4 vials/day). The termination of FabAV infusion was between day 6 and day 14 from the time of envenomation (mean = 10 ± 3 days), after which hematologic values were normalized or were normalizing in all patients and continued to do so. The use of FabAV as a continuous intravenous infusion, particularly after the acute phase of envenomation has passed, provides a continuous source of circulating antibodies to neutralize venom components reaching circulation from tissue stores and allows natural replenishment of hematologic factors such as platelets and/or fibrinogen. This method is an efficient use of FabAV, avoiding the wasteful excess of a bolus dose, may be more effective, eliminating the potential for destruction of hematologic factors when protective antivenom levels are lost between bolus FabAV doses, and appears to be safe. Further assessments of the stability and sterility of the product during infusion are needed. The need to continue hospitalization is the major drawback, but continued observation and inpatient care may be needed for other indications (e.g. bleeding) in this subset of patients. A continuous intravenous infusion of FabAV between 2 and 4 vials per day, titrated to effect, and continued for 6-14 days post-envenomation appeared to be associated with reversal of late hematologic effects of rattlesnake envenomation and, when combined with indicated human blood products, control of significant bleeding. Continuous intravenous infusion of FabAV may be safer, more efficacious, and more cost-effective than observation without FabAV treatment or as-needed bolus dosing in selected patients with late hematologic abnormalities. Copyright © 2013 Elsevier Ltd. All rights reserved.

Pandemic (H1N1) 2009 Outbreak at Camp for Children with Hematologic and Oncologic Conditions

PubMed Central

Morrison, Cori; Maurtua-Neumann, Paola; Myint, Myo Thwin; Drury, Stacy S.

2011-01-01

An outbreak of influenza A pandemic (H1N1) 2009 occurred among campers and staff at a summer camp attended by children with hematologic and oncologic conditions. The overall attack rate was 36% and was highest among children and adolescents (43%), persons with cancer (48%), and persons with sickle cell disease (82%). PMID:21192861

Correlation of Neutrophil to Lymphocyte Ratio and Absolute Neutrophil Count With Outcomes With PD-1 Axis Inhibitors in Patients With Advanced Non-Small-Cell Lung Cancer.

PubMed

Zer, Alona; Sung, Mike R; Walia, Preet; Khoja, Leila; Maganti, Manjula; Labbe, Catherine; Shepherd, Frances A; Bradbury, Penelope A; Feld, Ronald; Liu, Geoffrey; Iazzi, Melissa; Zawisza, Dianne; Nouriany, Nazanin; Leighl, Natasha B

2018-05-08

Programmed death-1 (PD-1) axis inhibitors have become standard therapy in advanced non-small-cell lung cancer (NSCLC). Response might be delayed and pseudo-progression occasionally occurs in patients who eventually benefit from treatment. Additional markers beyond programmed death ligand 1 (PD-L1) expression are needed to assist in patient selection, response evaluation, and treatment decisions. The relationship between prospectively collected clinical outcomes (response, disease control rate [DCR], treatment duration, overall survival) and hematologic parameters (neutrophil to lymphocyte ratio [NLR], absolute neutrophil count [ANC], and platelet to lymphocyte ratio [PLR]) was explored retrospectively in advanced NSCLC patients treated with PD-1 axis inhibitors at a major cancer center from May 2013 to August 2016. Hematologic parameters at baseline and during treatment (week 2 or 3 and week 8) were included. Of 88 patients treated with PD-1 axis inhibitors, 22 (25%) experienced partial response. Baseline NLR ≤4 was associated with superior DCR (74% vs. 50%; P = .025), treatment duration (P = .037), time to progression (P = .053), and overall survival (P = .019), with no differential association according to PD-L1 tumor expression. Lower NLR and ANC during treatment were also associated with response to treatment (P = .025 and P = .017, respectively), and treatment duration (P = .036 and P = .008). No association was found between baseline PLR and DCR, response, treatment duration, nor overall survival. Baseline NLR ≤4 and lower NLR and ANC during treatment might correlate with disease control and treatment response and should be explored further as potential predictors of treatment benefit in larger studies. Copyright © 2018. Published by Elsevier Inc.

Effects of whirling disease on selected hematological parameters in rainbow trout

USGS Publications Warehouse

Densmore, Christine L.; Blazer, V.S.; Waldrop, T.B.; Pooler, P.S.

2001-01-01

Hematological responses to whirling disease in rainbow trout (Oncorhynchus mykiss) were investigated. Two-mo-old fingerling rainbow trout were exposed to cultured triactinomyxon spores of Myxobolus cerebralis at 9,000 spores/fish in December, 1997. Twenty-four wks post-exposure, fish were taken from infected and uninfected groups for peripheral blood and cranial tissue sampling. Histological observations on cranial tissues confirmed M. cerebralis infection in all exposed fish. Differences in hematological parameters between the two groups included significantly lower total leukocyte and small lymphocyte counts for the infected fish. No effects on hematocrit, plasma protein concentration, or other differential leukocyte counts were noted.

Moxa-stick suffumigation for disinfecting air in hematology and hematopoietic stem cell transplantation wards with class 100 laminar flow.

PubMed

He, Jing-song; Yang, Qing; Huang, Wei-jia; Hu, Xiao-rong

2014-04-01

To evaluate the effect of moxa-stick suffumigation in the hematology and hematopoietic stem cell transplantation (HSCT) wards with luminar flow. The plate exposure method was used to measure the effect of air-disinfection of moxa-stick suffumigation in hematology and HSCT wards. The yearly average qualified rates of air sampling in HSCT wards were evaluated from 2007 to 2010. To further investigate the disinfecting effect of moxa-stick suffumigation, the colony counts of common pathogens (including Staphylcoccus aureus and Pseudomonas aeruginosa) before and after moxa-stick suffumigation were compared. The mean air quality rates of the HSCT wards with class 100 laminar flow were all above 90.0% (91.2%-96.2%) from 2007 to 2010. Moxa-stick suffumigation effectively decreased the presence of bacteria in the hematology ward's air (P<0.01). The most notable effect was the drastic reduction in the colony counts of Staphylococcus aureus and Pseudomonas aeruginosa on the blood plates exposed to air treated with moxa-stick suffumigation (77.1±52.9 cfu/m(2) vs 196.1±87.5 cfu/m(2), P<0.01; and 100.2±35.3 cfu/m(2) vs 371.5±35.3 cfu/m(2), P<0.01). Moxa-stick suffumigation proved to be a reliable and effective airdisinfection method for hematology and HSCT wards, and hence, it should be employed extensively.

Incidence and survival of hematological cancers among adults ages ≥75 years.

PubMed

Krok-Schoen, Jessica L; Fisher, James L; Stephens, Julie A; Mims, Alice; Ayyappan, Sabarish; Woyach, Jennifer A; Rosko, Ashley E

2018-04-13

Evaluating population-based data of hematologic malignancies (HMs) in older adults provides prognostic information for this growing demographic. Incidence rates and one- and five-year relative survival rates were examined for specific HMs among adults ages ≥75 years using data from the Surveillance, Epidemiology and End Results (SEER) Program. Hematologic malignancy cases (Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), multiple myeloma (MM), acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML)) were reported to one of 18 SEER registries. Recent average annual (2010-2014) incidence rates and incidence trends from 1973 to 2014 were examined for cases ages ≥75 years. One- and five-year relative cancer survival rates were examined for adults ages ≥75 years diagnosed 2007-2013, with follow-up into 2014. From 1973 to 2014, incidence rates increased for NHL, MM, and AML, decreased for HL, and remained relatively stable for ALL, CLL, and CML among adults ages ≥75 years. The highest one- and five-year relative survival rates were observed among adults with CLL ages 75-84 years (1 year: 91.8% (95% CI = 91.8-90.8)) and 5 years: 76.5% (95% CI = 74.2-78.6)). The lowest one- and five-year survival rates were observed among adults with AML ages 75-84 (1 year: 18.2% (95% CI = 74.2-78.6) and 5 years: 2.7% (95% CI = 2.0-3.6)). Survival for older adults ages ≥75 years with HMs is poor, particularly for acute leukemia. Understanding the heterogeneity in HM outcomes among older patients may help clinicians better address the hematological cancer burden and mortality in the aging population. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Serological & molecular diagnostic surveys combined with examining hematological profiles suggest increased levels of infection & hematological response of cattle to babesiosis infections compared to native buffaloes in Egypt

USDA-ARS?s Scientific Manuscript database

Background: Babesiosis threatens the development of the cattle and buffaloes industries in Egypt and improved control is needed. The main objectives of this study are surveying the presence of bovine babesiosis in distinct selected bovine and buffalo populations in Egypt using novel molecular and pr...

Exploring Therapeutic Potentials of Baicalin and Its Aglycone Baicalein for Hematological Malignancies

PubMed Central

Chen, Haijun; Gao, Yu; Wu, Jianlei; Chen, Yingyu; Chen, Buyuan; Hu, Jianda; Zhou, Jia

2014-01-01

Despite tremendous advances in the targeted therapy for various types of hematological malignancies with successful improvements in the survival rates, emerging resistance issues are startlingly high and novel therapeutic strategies are urgently needed. In addition, chemoprevention is currently becoming an elusive goal. Plant-derived natural products have garnered considerable attention in recent years due to the potential dual functions as chemotherapeutics and dietary chemoprevention. One of the particularly ubiquitous families is the polyphenolic flavonoids. Among them, baicalin and its aglycone baicalein have been widely investigated in hematological malignancies because both of them exhibit remarkable pharmacological properties. This review focuses on the recent achievements in drug discovery research associated with baicalin and baicalein for hematological malignancy therapies. The promising anticancer activities of these two flavonoids targeting diverse signaling pathways and their potential biological mechanisms in different types of hematological malignancies, as well as the combination strategy with baicalin or baicalein as chemotherapeutic adjuvants for recent therapies in these intractable diseases are discussed. Meanwhile, the biotransformation of baicalin and baicalein and the relevant approaches to improve their bioavailability are also summarized. PMID:25128647

Hematological remission and long term hematological control of acute myeloblastic leukemia induced and maintained by granulocyte-colony stimulating factor (G-CSF) therapy.

PubMed

Xavier, Luciana; Cunha, Manuel; Gonçalves, Cristina; Teixeira, Maria dos Anjos; Coutinho, Jorge; Ribeiro, António Carlos Pinto; Lima, Margarida

2003-12-01

We describe a case of a patient with CD34+, TdT+, CD13-, CD33-, MPO- undifferentiated acute leukemia who refused chemotherapy and who achieved complete hematological remission 14 months after the diagnosis, during a short course of granulocyte-colony stimulating factor (G-CSF) for neutropenia and life threatening infection. Relapse occurred approximately one year later and G-CSF was reintroduced, being maintained for 4 months, at a dose and frequency adapted to maintain normal blood counts, a complete hematological remission being achieved again. Five months after withdrawing the G-CSF therapy a second relapse was observed; G-CSF was tried again with success, resulting in a very good hematological response that was sustained by G-CSF maintenance therapy. One year latter there was the need of increasing the doses of G-CSF in order to obtain the same hematological effect, at same time blast cells acquired a more mature CD34+, TdT-, CD13+, CD33-, MPO+ myeloid phenotype. Finally, the patient developed progressive neutropenia, anemia, thrombocytopenia and acute leukemia in spite of G-CSF therapy, dying 64 months after initial diagnosis (50 months after starting G-CSF therapy) with overt G-CSF resistant acute myeloblastic leukemia (AML), after failure of conventional induction chemotherapy.

Factors affecting response and tolerability to ferumoxytol in nondialysis chronic kidney disease patients.

PubMed

Fishbane, Steven; Bolton, W Kline; Winkelmayer, Wolfgang C; Strauss, William; Li, Zhu; Pereira, Brian J G

2012-09-01

Ferumoxytol is a unique intravenous (i.v.) iron therapy. This report examines factors affecting hemoglobin response to i.v. ferumoxytol, and the relationship between hematologic parameters, concomitant erythropoiesis-stimulating agents (ESA), and adverse events (AEs) in nondialysis CKD patients. A series of post-hoc efficacy and safety analyses were performed using pooled data from two identically designed Phase III studies in 608 nondialysis CKD patients randomized to receive two 510 mg i.v. injections of ferumoxytol within 5 ± 3 days versus oral iron. Ferumoxytol resulted in a significant increase in hemoglobin in the presence and absence of ESA, and across a range of baseline hemoglobin, transferrin saturation, ferritin, and reticulocyte hemoglobin content levels. Adverse event rates with ferumoxytol were similar across quartiles of change in hemoglobin; there were no trends suggesting an increased rate of cardiovascular AEs with higher maximum achieved hemoglobin or faster rate of hemoglobin rise. There was no meaningful difference in the rate of AEs, serious AEs, and cardiovascular AEs between patients receiving or not receiving ESA. These analyses add to the knowledge of predictors of response and safety outcomes associated with i.v. iron therapy in nondialysis CKD patients.

Hematological features of pediatric systemic lupus erythematosus: suggesting management strategies in children.

PubMed

Gokce, M; Bilginer, Y; Besbas, N; Ozaltin, F; Cetin, M; Gumruk, F; Ozen, S

2012-07-01

The aim of this study was to analyze the hematological features in children with systemic lupus erythematosus (SLE) and to review our current treatment protocols. We evaluated hematological findings of 43 children with SLE diagnosed and followed at the Pediatric Rheumatology Division of Hacettepe University, Turkey. Thirty-seven patients with hematological abnormalities were analyzed in detail. Median age at presentation was 13 years. Hematological involvement was seen in 86% of patients. The most common hematological finding was anemia (n = 30). Anemia was either a Coombs (+) hemolytic one, or was due to other causes. Hemolytic anemia was treated with steroids and intravenous gamma globulin (IVIG). Leucopenia and thrombocytopenia were detected in 35.1 % and 37.8 %, respectively. Bone marrow aspiration was performed in 15, mainly for cytopenia. Secondary dysplastic changes were common. Acute lymphoblastic leukemia (ALL) was diagnosed in one patient. Six patients were diagnosed as having macrophage activation syndrome (MAS). One patient died due to secondary infections and multiorgan failure despite aggressive treatment. In patients diagnosed early, treatment with steroids and cyclosporine resulted in an excellent response. Thrombotic microangiopathy was detected in two patients. Both were treated successfully with steroids and plasma exchange. Antiphospholipid and anticardiolipin antibodies were positive in 12 and 15 of the patients, respectively. Five developed deep vein thrombosis (DVT), one cerebral sinus thrombosis and one presented with purpura fulminans. They were effectively treated with anticoagulation protocol. Hematological findings should be carefully assessed and treated vigorously to prevent the morbidity and possible mortality.

Pretreatment Hematologic Findings as Novel Predictive Markers for Facial Palsy Prognosis.

PubMed

Wasano, Koichiro; Kawasaki, Taiji; Yamamoto, Sayuri; Tomisato, Shuta; Shinden, Seiichi; Ishikawa, Toru; Minami, Shujiro; Wakabayashi, Takeshi; Ogawa, Kaoru

2016-10-01

To examine the relationship between prognosis of 2 different facial palsies and pretreatment hematologic laboratory values. Multicenter case series with chart review. Three tertiary care hospitals. We examined the clinical records of 468 facial palsy patients who were treated with an antiviral drug in combination with either oral or intravenous corticosteroids in participating hospitals between 2010 and 2014. Patients were divided into a Bell's palsy group or a Hunt's palsy group. We used the Yanagihara facial nerve grading system to grade the severity of facial palsy. "Recovery" from facial palsy was defined as achieving a Yanagihara score ≥36 points within 6 months of onset and having no accompanying facial contracture or synkinesis. We collected information about pretreatment hematologic findings, demographic data, and electrophysiologic test results of the Bell and Hunt group patients who recovered and those who did not. We then compared these data across the 2 palsy groups. In the Bell's palsy group, recovered and unrecovered patients differed significantly in age, sex, electroneuronography score, stapedial muscle reflex, neutrophil rate, lymphocyte rate, neutrophil-to-lymphocyte ratio, and initial Yanagihara score. In the Hunt's palsy group, recovered and unrecovered patients differed in age, electroneuronography score, stapedial muscle reflex, monocyte rate, platelet count, mean corpuscular volume, and initial Yanagihara score. Pretreatment hematologic findings, which reflect the severity of inflammation and bone marrow dysfunction caused by a virus infection, are useful for predicting the prognosis of facial palsy. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

Effects of dietary Spirulina platensis on growth performance, hematological and serum biochemical parameters, hepatic antioxidant status, immune responses and disease resistance of Coral trout Plectropomus leopardus (Lacepede, 1802).

PubMed

Yu, Wei; Wen, Guoliang; Lin, Heizhao; Yang, Yukai; Huang, Xiaolin; Zhou, Chuanpeng; Zhang, Zaiwang; Duan, Yafei; Huang, Zhong; Li, Tao

2018-03-01

The present study investigated the effects of dietary Spirulina platensis supplementation on growth performance, hematological and serum biochemical parameters, hepatic antioxidant status, immune responses and resistance to the pathogen infection in Coral trout Plectropomus leopardus. The fish were fed for 8-week with diets containing different levels of S. platensis: 0% (C), 2% (SP2), 4% (SP4), 6% (SP6), 8% (SP8) and 10% (SP10) as treatment groups, followed by a Vibrio harveyi infection test for 14 d. The study indicated that dietary supplementation with Spirulina platensis could significantly improve growth performance, and the highest weight gain rate (WGR) and specific growth rate (SGR) were observed in group SP10 (P < .05). Red cell count (RBC), white cell count (WBC), hemoglobin (Hb) and total antioxidant capacity (T-AOC) in the S. platensis supplemented groups were significantly higher than those of group C (P < .05). However, the levels of cholesterol, triglyceride and malondialdehyde (MDA) contents, and superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activities decreased with the increasing of dietary S. platensis levels. Compared with group C, the lysozyme (LYZ) and respiratory burst activities (RBA), and immunoglobulin (Ig) and complement contents in group SP4, SP6, SP8 and SP10 increased significantly than those of group C respectively (P < .05). After challenge with V. harveyi, the survival rate in group SP4, SP6, SP8 and SP10 was significantly higher than that of group C, and the highest survival rate was in group SP10 (P < .05). These results indicated that P. leopardus fed a diet supplemented with S. platensis (especially at 10%) could significantly promote its growth performance, improve its hepatic antioxidant status, and enhance its immune ability and resistance to V. harveyi infection. Copyright © 2018 Elsevier Ltd. All rights reserved.

Pemetrexed combined with paclitaxel in patients with advanced or metastatic non-small-cell lung cancer: a phase I-II trial.

PubMed

Stathopoulos, George P; Dimitroulis, John; Toubis, Michael; Katis, Costas; Karaindros, Dimitris; Stathopoulos, John; Koutandos, John

2007-07-01

Pemetrexed, a novel multi-targeted agent established for the treatment of mesothelioma, has been under investigation for other malignancies, and in recent years particularly for non-small-cell lung cancer (NSCLC). In the present trial we investigated pemetrexed in combination with paclitaxel as front-line treatment in advanced or metastatic NSCLC. Our objectives were to determine the response rate, median and overall survival and toxicity. From April 2005 until May 2006, 51 patients with advanced or metastatic NSCLC were enrolled and 48 were considered evaluable. There were 39 males and nine females, median age 62 years (range 37-81 years), one patient stage IIIA N(2), 23 patients, IIIB and 24, stage IV. All patients had a cytologically- or histologically-confirmed diagnosis. Pemetrexed was administered at a standard dose of 500mg/m(2) and paclitaxel at an escalating dose starting at 135mg/m(2), then 150mg/m(2) and ending at a dose of 175mg/m(2); the level was increased every three patients. Both agents were administered on day 1, repeated every 3 weeks for six courses. A 39.6% partial response rate was observed with a median survival of 14 months. Toxicity was mild with 8.3% grade 3 and 4 neutropenia and other very mild hematologic and non-hematologic adverse reactions. The combination of pemetrexed and paclitaxel at doses of 500mg/m(2) and 175mg/m(2), respectively, has been shown to be an effective combination with very limited toxicity.

Functional Cardiac Recovery and Hematologic Response to Chemotherapy in Patients With Light-Chain Amyloidosis (from the Stanford University Amyloidosis Registry).

PubMed

Tuzovic, Mirela; Kobayashi, Yukari; Wheeler, Matthew; Barrett, Christopher; Liedtke, Michaela; Lafayette, Richard; Schrier, Stanley; Haddad, Francois; Witteles, Ronald

2017-10-15

Cardiac involvement is common in patients with light-chain (AL) amyloidosis and portends a poor prognosis, although little is known about the changes in cardiac mechanics after chemotherapy. We sought to explore the relation between amyloidosis staging and baseline cardiac mechanics and to investigate short-term changes in cardiac mechanics after chemotherapy. We identified 41 consecutive patients from the Stanford Amyloid Center who had echocardiograms and free light-chain values before and after chemotherapy, along with 40 age- and gender-matched controls. Echocardiographic assessment included left ventricular global longitudinal strain, E/e' ratio, and left atrial (LA) stiffness. Hematologic response to chemotherapy was defined as ≥50% reduction in the difference between the involved and the uninvolved free light chain (dFLC). The mean age was 66.9 ± 8.4 years and 66% were men. Before chemotherapy, global longitudinal strain, E/e' ratio, and LA stiffness were impaired in patients with amyloidosis compared with controls, and the severity of impairment worsened with advanced staging. After chemotherapy, hematologic response was observed in 30 (73%) patients. There was a significant association between the change in dFLC and cardiac function (E/e' ratio: r = -0.43, p = 0.01; LA stiffness: r = -0.35, p = 0.05). There was no significant improvement in cardiac mechanics in patients without a hematologic response to chemotherapy. In conclusion, amyloidosis stage correlated with noninvasive measurements of cardiac mechanics, and improvement in dFLC correlated with cardiac improvement on short-term follow-up echocardiography. Copyright © 2017 Elsevier Inc. All rights reserved.

Female Representation in the Academic Oncology Physician Workforce: Radiation Oncology Losing Ground to Hematology Oncology

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

Ahmed, Awad A.; Hwang, Wei-Ting; Holliday, Emma B.

Purpose: Our purpose was to assess comparative female representation trends for trainees and full-time faculty in the academic radiation oncology and hematology oncology workforce of the United States over 3 decades. Methods and Materials: Simple linear regression models with year as the independent variable were used to determine changes in female percentage representation per year and associated 95% confidence intervals for trainees and full-time faculty in each specialty. Results: Peak representation was 48.4% (801/1654) in 2013 for hematology oncology trainees, 39.0% (585/1499) in 2014 for hematology oncology full-time faculty, 34.8% (202/581) in 2007 for radiation oncology trainees, and 27.7% (439/1584) inmore » 2015 for radiation oncology full-time faculty. Representation significantly increased for trainees and full-time faculty in both specialties at approximately 1% per year for hematology oncology trainees and full-time faculty and 0.3% per year for radiation oncology trainees and full-time faculty. Compared with radiation oncology, the rates were 3.84 and 2.94 times greater for hematology oncology trainees and full-time faculty, respectively. Conclusion: Despite increased female trainee and full-time faculty representation over time in the academic oncology physician workforce, radiation oncology is lagging behind hematology oncology, with trainees declining in recent years in radiation oncology; this suggests a de facto ceiling in female representation. Whether such issues as delayed or insufficient exposure, inadequate mentorship, or specialty competitiveness disparately affect female representation in radiation oncology compared to hematology oncology are underexplored and require continued investigation to ensure that the future oncologic physician workforce reflects the diversity of the population it serves.« less

Female Representation in the Academic Oncology Physician Workforce: Radiation Oncology Losing Ground to Hematology Oncology.

PubMed

Ahmed, Awad A; Hwang, Wei-Ting; Holliday, Emma B; Chapman, Christina H; Jagsi, Reshma; Thomas, Charles R; Deville, Curtiland

2017-05-01

Our purpose was to assess comparative female representation trends for trainees and full-time faculty in the academic radiation oncology and hematology oncology workforce of the United States over 3 decades. Simple linear regression models with year as the independent variable were used to determine changes in female percentage representation per year and associated 95% confidence intervals for trainees and full-time faculty in each specialty. Peak representation was 48.4% (801/1654) in 2013 for hematology oncology trainees, 39.0% (585/1499) in 2014 for hematology oncology full-time faculty, 34.8% (202/581) in 2007 for radiation oncology trainees, and 27.7% (439/1584) in 2015 for radiation oncology full-time faculty. Representation significantly increased for trainees and full-time faculty in both specialties at approximately 1% per year for hematology oncology trainees and full-time faculty and 0.3% per year for radiation oncology trainees and full-time faculty. Compared with radiation oncology, the rates were 3.84 and 2.94 times greater for hematology oncology trainees and full-time faculty, respectively. Despite increased female trainee and full-time faculty representation over time in the academic oncology physician workforce, radiation oncology is lagging behind hematology oncology, with trainees declining in recent years in radiation oncology; this suggests a de facto ceiling in female representation. Whether such issues as delayed or insufficient exposure, inadequate mentorship, or specialty competitiveness disparately affect female representation in radiation oncology compared to hematology oncology are underexplored and require continued investigation to ensure that the future oncologic physician workforce reflects the diversity of the population it serves. Copyright © 2017 Elsevier Inc. All rights reserved.

Bloodstream infections in pediatric oncology outpatients: a new healthcare systems challenge.

PubMed

Smith, Theresa L; Pullen, Gregg T; Crouse, Vonda; Rosenberg, Jon; Jarvis, William R

2002-05-01

To investigate a perceived increase in central venous catheter (CVC)-associated bloodstream infections (BSIs) among pediatric hematology-oncology outpatients. A case-control study. A pediatric hematology-oncology outpatient clinic at Fresno Children's Hospital. Pediatric hematology-oncology clinic outpatients with CVCs at Fresno Children's Hospital between November 1994 and October 1997. A case-patient was defined as any hematology-oncology outpatient with a CVC-associated BSI at Fresno Children's Hospital from November 1996 to October 1997 (study period) without a localizable infection. To identify case-patients, we reviewed Fresno Children's Hospital records for all hematology-oncology clinic patients, those with CVCs and those with CVCs and BSIs. Control-patients were randomly selected hematology-oncology outpatients with a CVC but no BSI during the study period. Case-patient and control-patient demographics, diagnoses, caretakers, catheter types, catheter care, and water exposure were compared. Twenty-five case-patients had 42 CVC-associated BSIs during the study period. No significant increase in CVC-associated BSI rates occurred among pediatric hematology-oncology patients. However, there was a statistically significant increase in nonendogenous, gram-negative (eg, Pseudomonas species) BSIs during summer months (May-October) compared with the rest of the year. Case-patients and control-patients differed only in catheter type; case-patients were more likely than control-patients to have a transcutaneous CVC. Summertime recreational water exposures were similar and high in the two groups. Hematology-oncology clinic patients with transcutaneous CVCs are at greater risk for CVC-associated BSI, particularly during the summer. Caretakers should be instructed on proper care of CVCs, particularly protection of CVCs during bathing and recreational summer water activities, to reduce the risk of nonendogenous, gram-negative BSIs.

Detection of JAK2 V617F mutation increases the diagnosis of myeloproliferative neoplasms

PubMed Central

ZHANG, SHU-PENG; LI, HUI; LAI, REN-SHENG

2015-01-01

The Janus kinase (JAK)2 gene, which is located on chromosome 9p24, is involved in the signaling transduction pathways of the hematopoietic and immune system. Mutations in the JAK2 gene have served as disease markers for myeloproliferative neoplasms (MPNs). The aim of the present study was to investigate the occurrence of the JAK2 gene mutation in 140 clinical samples, and to evaluate its clinical significance in MPNs and other hematological diseases. Genomic DNA was extracted from the peripheral blood leukocytes or bone marrow karyocytes of 140 clinical samples, which included 130 patients with various types of hematological disease and 10 control patients. In addition, exons 12 and 14 of the JAK2 gene were analyzed by direct sequencing and the mutation rates of various MPN subtypes were evaluated. Of the 140 samples, exons 12 and 14 were tested in 74 samples, however, exon 14 only was tested in 66 samples. No mutations were identified in exon 12. The V617F mutation rate in polycythemia vera was 82.1% (23/28), and the mutation rates in essential thrombocythemia histiocytosis, primary myelofibrosis and other MPNs were 53.1% (17/32), 40.0% (4/10) and 60.0% (6/10), respectively. Therefore, the total mutation rate of the JAK2 gene in MPN was 62.5% (50/80). For non-MPN hematological diseases, four V617F mutations were detected in samples of leukocytosis of unknown origin (4/12), however, no JAK2 V617F mutations were identified in the 10 controls. Therefore, JAK2 V617F mutations may present a novel marker for diagnosis of MPNs. Furthermore, the direct sequencing method appeared to be satisfactory for the clinical gene testing of hematological samples. PMID:25624900

LEUKEMIA, LYMPHOMA AND MULTIPLE MYELOMA MORTALITY (1950–1999) AND INCIDENCE (1969–1999) IN THE ELDORADO URANIUM WORKERS COHORT

PubMed Central

Zablotska, Lydia B.; Lane, Rachel S.D.; Frost, Stanley E.; Thompson, Patsy A.

2014-01-01

Uranium workers are chronically exposed to low levels of radon decay products (RDP) and gamma (γ) radiation. Risks of leukemia from acute and high doses of γ-radiation are well-characterized, but risks from lower doses and dose-rates and from RDP exposures are controversial. Few studies have evaluated risks of other hematologic cancers in uranium workers. The purpose of this study was to analyze radiation-related risks of hematologic cancers in the cohort of Eldorado uranium miners and processors first employed in 1932–1980 in relation to cumulative RDP exposures and γ-ray doses. The average cumulative RDP exposure was 100.2 working level months and the average cumulative whole-body γ-radiation dose was 52.2 millisievert. We identified 101 deaths and 160 cases of hematologic cancers in the cohort. Overall, male workers had lower mortality and cancer incidence rates for all outcomes compared with the general Canadian male population, a likely healthy worker effect. No statistically significant association between RDP exposure or γ-ray doses, or a combination of both, and mortality or incidence of any hematologic cancer was found. We observed consistent but non-statistically significant increases in risks of chronic lymphocytic leukemia (CLL) and Hodgkin lymphoma (HL) incidence and non-Hodgkin lymphoma (NHL) mortality with increasing γ-ray doses. These findings are consistent with recent studies of increased risks of CLL and NHL incidence after γ-radiation exposure. Further research is necessary to understand risks of other hematologic cancers from low-dose exposures to γ-radiation. PMID:24583244

A phase II trial of fixed-dosed rate gemcitabine in platinum-resistant ovarian cancer: a GEICO (Grupo Español de Investigación en Cáncer de Ovario) Trial.

PubMed

Ojeda Gonzalez, Belen; Gonzalez Martin, Antonio; Bover Barcelo, Isabel; Fabregat i Mayol, Xavier; Mellado, Begoña; Rubio Perez, María Jesus; Alonso Carrion, Lorenzo; Casado Herraez, Antonio; Calvo Garcia, Elisa; Churruca Galaz, Cristina; Arcusa Lanza, Angels; Herrero Ibañez, Ana; Adrover Cebrian, Encarna; Poveda Velasco, Andres

2008-10-01

Gemcitabine has well-recognized activity in the treatment of ovarian cancer. Fixed-dose rate (FDR) delivery has been proposed as a more rationale way to administer gemcitabine, to avoid saturation of the enzyme that catalyzes its intracellular transformation into the active metabolites, difluorodeoxycitidine biphosphate, and triphosphate. Our aim was to assess clinical activity of gemcitabine delivered by FDR infusion in patients with platinum resistant ovarian cancer. Patients with platinum-resistant ovarian cancer received gemcitabine 1000 mg/m(2) over 120 minutes on days 1 and 8 of each cycle. Cycles were repeated every 3 weeks, and up to 6 cycles were delivered. Forty-eight patients were included in the study. Among 41 patients evaluable for response, 9 clinical responses (1 complete response and 8 partial responses) were observed, achieving a global response rate of 22%. Grade 3 to 4 hematological toxicity consisted of anemia (15% of patients), neutropenia (24%), and thrombopenia (10%). One patient died due to septic shock. The main grade 3 to 4 nonhematological toxicity was asthenia (7 patients, 17%). Activity of gemcitabine administered by FDR infusion in patients with platinum-resistant ovarian cancer seems similar to that achieved using 30-minute infusions, with higher toxicity.

In-line filtration minimizes organ dysfunction: new aspects from a prospective, randomized, controlled trial.

PubMed

Boehne, Martin; Jack, Thomas; Köditz, Harald; Seidemann, Kathrin; Schmidt, Florian; Abura, Michaela; Bertram, Harald; Sasse, Michael

2013-02-06

Infused particles induce thrombogenesis, impair microcirculation and modulate immune response. We have previously shown in critically ill children, that particle-retentive in-line filtration reduced the overall complication rate of severe events, length of stay and duration of mechanical ventilation. We now evaluated the influence of in-line filtration on different organ function and thereby elucidated the potential underlying pathophysiological effects of particle infusion. In this single-centre, prospective, randomized controlled trial 807 critically ill children were assigned to either control (n = 406) or filter group (n = 401), the latter receiving in-line filtration for complete infusion therapy. Both groups were compared regarding the differences of incidence rates and its 95% confidence interval (CI) of different organ dysfunction as defined by the International Pediatric Sepsis Consensus Conference 2005. The incidence rates of respiratory (-5.06%; 95% CI, -9.52 to -0.59%), renal (-3.87%; 95% CI, -7.58 to -0.15%) and hematologic (-3.89%; 95% CI, -7.26 to -0.51%) dysfunction were decreased in the filter group. No difference was demonstrated for the occurrence rates of cardiovascular, hepatic, or neurologic dysfunction between both groups. In-line filtration has beneficial effects on the preservation of hematologic, renal and respiratory function in critically ill patients. The presented clinical data further support our hypothesis regarding potential harmful effects of particles. In critically ill patients infused particles may lead to further deterioration of the microcirculation, induce a systemic hypercoagulability and inflammation with consecutive negative effects on organ function. ClinicalTrials.gov number; NCT00209768.

HEALTH STATUS OF RED-FOOTED BOOBIES ( SULA SULA) DETERMINED BY HEMATOLOGY, BIOCHEMISTRY, BLOOD GASES, AND PHYSICAL EXAMINATION.

PubMed

Lewbart, Gregory A; Ulloa, Catalina; Deresienski, Diane; Regalado, Cristina; Muñoz-Pérez, Juan-Pablo; Garcia, Juan; Hardesty, Britta Denise; Valle, Carlos A

2017-12-01

The red-footed booby ( Sula sula) is a widely distributed sulid native to the Galápagos archipelago. Hematology and blood chemistry parameters have been published for this species, but not from the San Cristóbal rookery. Analyses were run on blood samples drawn from 31 manually restrained red-footed boobies that were captured by hand from their nests at Punta Pitt on San Cristóbal Island. A portable blood analyzer (iSTAT) was used to obtain near immediate field results for pH, partial pressure of oxygen, partial pressure of carbon dioxide, bicarbonate, hematocrit, hemoglobin, sodium, potassium, ionized calcium, and glucose. Blood lactate was measured using a portable Lactate Plus™ analyzer. Average heart rate, respiratory rate, body weight, body temperature, and biochemistry and hematology parameters were comparable to those of healthy individuals of other sulids. The reported results provide baseline data that can be used for comparisons among populations and in detecting changes in health status among Galápagos red-footed boobies.

Peripherally Inserted Central Venous Catheters in Pediatric Hematology/Oncology Patients in Tertiary Care Setting: A Developing Country Experience.

PubMed

Fadoo, Zehra; Nisar, Muhammad I; Iftikhar, Raza; Ali, Sajida; Mushtaq, Naureen; Sayani, Raza

2015-10-01

Peripherally inserted central venous catheters (PICC) have been successfully used to provide central access for chemotherapy and frequent transfusions. The purpose of this study was to assess the feasibility of PICCs and determine PICC-related complications in pediatric hematology/oncology patients in a resource-poor setting. All pediatric patients (age below 16 y) with hematologic and malignant disorders who underwent PICC line insertion at Aga Khan University Hospital from January 2008 to June 2010 were enrolled in the study. Demographic features, primary diagnosis, catheter days, complications, and reasons for removal of device were recorded. Total of 36 PICC lines were inserted in 32 pediatric patients. Complication rate of 5.29/1000 catheter days was recorded. Our study showed comparable complication profile such as infection rate, occlusion, breakage, and dislodgement. The median catheter life was found to be 69 days. We conclude that PICC lines are feasible in a resource-poor setting and recommend its use for chemotherapy administration and prolonged venous access.

Prospective evaluation of the effect of deferasirox on hematologic response in transfusion-dependent patients with low-risk MDS and iron overload.

PubMed

Rose, Christian; Lenoir, Caroline; Gyan, Emmanuel; Hacini, Maya; Amé, Shanti; Corront, Bernadette; Beyne-Rauzy, Odile; Adiko, Didier; Loppinet, Elena; Ali-Ammar, Nadia; Laribi, Kamel; Wattel, Eric; Dreyfus, François; Roué, Claire S; Cheze, Stephane

2018-05-02

To assess the reduction of transfusions rate in transfusion-dependent patients with low-risk myelodysplastic syndrome (MDS) with iron overload treated with deferasirox. Prospective observational study. Primary endpoint was reduction in transfusion requirements (RTR) at 3 months, (assessed on 8-week period). Secondary endpoints were hematologic improvement according to International Working Group (IWG) 2006 criteria at 3, 6, and 12 months. Fifty-seven patients were evaluable. After 3 months of chelation, no effect was seen on transfusion requirement (5.9 packed red blood cells (PRBC) vs 5.8 before chelation). According to the Kaplan-Meier analysis, the probability of RTR at 3, 6, and 12 months was assessed as 3.5%, 9.1%, and 18.7%, respectively. Median duration of RTR was 182 days. However, during the 12-month follow-up after deferasirox initiation, 17 patients (31.5%) achieved minor erythroid response [HI-E] according to IWG criteria, 10 of whom having achieved Hb improvement at month 12. After 3 months of treatment, deferasirox had no impact on transfusion requirement in regularly transfused patients with low-risk MDS. However, deferasirox could induce 31% of erythroid response during the 12-month follow-up period thus suggesting that iron chelation therapy with deferasirox may induce an effect on hematopoiesis in a subset of patients with MDS and iron overload. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Eviction from the sanctuary: Development of targeted therapy against cell adhesion molecules in acute lymphoblastic leukemia.

PubMed

Barwe, Sonali P; Quagliano, Anthony; Gopalakrishnapillai, Anilkumar

2017-04-01

Acute lymphoblastic leukemia (ALL) is a malignant hematological disease afflicting hematopoiesis in the bone marrow. While 80%-90% of patients diagnosed with ALL will achieve complete remission at some point during treatment, ALL is associated with high relapse rate, with a 5-year overall survival rate of 68%. The initial remission failure and the high rate of relapse can be attributed to intrinsic chemoprotective mechanisms that allow persistence of ALL cells despite therapy. These mechanisms are mediated, at least in part, through the engagement of cell adhesion molecules (CAMs) within the bone marrow microenvironment. This review assembles CAMs implicated in protection of leukemic cells from chemotherapy. Such studies are limited in ALL. Therefore, CAMs that are associated with poor outcomes or are overexpressed in ALL and have been shown to be involved in chemoprotection in other hematological cancers are also included. It is likely that these molecules play parallel roles in ALL because the CAMs identified to be a factor in ALL chemoresistance also work similarly in other hematological malignancies. We review the signaling mechanisms activated by the engagement of CAMs that provide protection from chemotherapy. Development of targeted therapies against CAMs could improve outcome and raise the overall cure rate in ALL. Copyright © 2017 Elsevier Inc. All rights reserved.

A Quasi-Experimental Study Analyzing the Effectiveness of Portable High-Efficiency Particulate Absorption Filters in Preventing Infections in Hematology Patients during Construction

PubMed Central

Özen, Mehmet; Yılmaz, Gülden; Coşkun, Belgin; Topçuoğlu, Pervin; Öztürk, Bengi; Gündüz, Mehmet; Atilla, Erden; Arslan, Önder; Özcan, Muhit; Demirer, Taner; İlhan, Osman; Konuk, Nahide; Balık, İsmail; Gürman, Günhan; Akan, Hamdi

2016-01-01

Objective: The increased risk of infection for patients caused by construction and renovation near hematology inpatient clinics is a major concern. The use of high-efficiency particulate absorption (HEPA) filters can reduce the risk of infection. However, there is no standard protocol indicating the use of HEPA filters for patients with hematological malignancies, except for those who have undergone allogeneic hematopoietic stem cell transplantation. This quasi-experimental study was designed to measure the efficacy of HEPA filters in preventing infections during construction. Materials and Methods: Portable HEPA filters were placed in the rooms of patients undergoing treatment for hematological malignancies because of large-scale construction taking place near the hematology clinic. The rates of infection during the 6 months before and after the installation of the portable HEPA filters were compared. A total of 413 patients were treated during this 1-year period. Results: There were no significant differences in the antifungal prophylaxis and treatment regimens between the groups. The rates of infections, clinically documented infections, and invasive fungal infections decreased in all of the patients following the installation of the HEPA filters. When analyzed separately, the rates of invasive fungal infections were similar before and after the installation of HEPA filters in patients who had no neutropenia or long neutropenia duration. HEPA filters were significantly protective against infection when installed in the rooms of patients with acute lymphocytic leukemia, patients who were undergoing consolidation treatment, and patients who were neutropenic for 1-14 days. Conclusion: Despite the advent of construction and the summer season, during which environmental Aspergillus contamination is more prevalent, no patient or patient subgroup experienced an increase in fungal infections following the installation of HEPA filters. The protective effect of HEPA filters against infection was more pronounced in patients with acute lymphocytic leukemia, patients undergoing consolidation therapy, and patients with moderate neutropenia. PMID:26376622

A Quasi-Experimental Study Analyzing the Effectiveness of Portable High-Efficiency Particulate Absorption Filters in Preventing Infections in Hematology Patients during Construction.

PubMed

Özen, Mehmet; Yılmaz, Gülden; Coşkun, Belgin; Topçuoğlu, Pervin; Öztürk, Bengi; Gündüz, Mehmet; Atilla, Erden; Arslan, Önder; Özcan, Muhit; Demirer, Taner; İlhan, Osman; Konuk, Nahide; Balık, İsmail; Gürman, Günhan; Akan, Hamdi

2016-03-05

The increased risk of infection for patients caused by construction and renovation near hematology inpatient clinics is a major concern. The use of high-efficiency particulate absorption (HEPA) filters can reduce the risk of infection. However, there is no standard protocol indicating the use of HEPA filters for patients with hematological malignancies, except for those who have undergone allogeneic hematopoietic stem cell transplantation. This quasi-experimental study was designed to measure the efficacy of HEPA filters in preventing infections during construction. Portable HEPA filters were placed in the rooms of patients undergoing treatment for hematological malignancies because of large-scale construction taking place near the hematology clinic. The rates of infection during the 6 months before and after the installation of the portable HEPA filters were compared. A total of 413 patients were treated during this 1-year period. There were no significant differences in the antifungal prophylaxis and treatment regimens between the groups. The rates of infections, clinically documented infections, and invasive fungal infections decreased in all of the patients following the installation of the HEPA filters. When analyzed separately, the rates of invasive fungal infections were similar before and after the installation of HEPA filters in patients who had no neutropenia or long neutropenia duration. HEPA filters were significantly protective against infection when installed in the rooms of patients with acute lymphocytic leukemia, patients who were undergoing consolidation treatment, and patients who were neutropenic for 1-14 days. Despite the advent of construction and the summer season, during which environmental Aspergillus contamination is more prevalent, no patient or patient subgroup experienced an increase in fungal infections following the installation of HEPA filters. The protective effect of HEPA filters against infection was more pronounced in patients with acute lymphocytic leukemia, patients undergoing consolidation therapy, and patients with moderate neutropenia.

Hematologic responses to hypobaric hyperoxia.

NASA Technical Reports Server (NTRS)

Larkin, E. C.; Adams, J. D.; Williams, W. T.; Duncan, D. M.

1972-01-01

Study of the effects of hypoxia, activity, and G forces on human hematopoiesis in an attempt to elucidate these phenomena more precisely. Eight subjects were exposed to an atmosphere of 100% O2 at 258 mm Hg for 30 days, and thereafter immediately exposed to transverse G forces, simulating the Gemini flights' reentry profile. All subjects displayed a significant continuous decline in red cell mass during the exposure period, as measured by the carbon monoxide-dilution method. The Cr51 method also indicated a decline in red blood corpuscle mass. The decrease in red cell mass was due to suppression of erythropoiesis and to hemolysis. After exposure to hyperoxia, all subjects exhibited elevated plasma hemoglobin levels, decreased reticulocyte counts, and decreased red cell survivals. CO production rates and urine erythropoietin levels were unchanged. Two hours after termination of exposure to hyperoxia, all subjects exhibited increased reticulocyte counts which were sustained for longer than two weeks. The progressive decrease in red cell mass was promptly arrested on return to ground level atmospheres. Within 116 days after exposure to hyperoxia, the hematologic parameters of all eight subjects had returned to control levels.

Combining antiangiogenic therapy with neoadjuvant chemotherapy increases treatment efficacy in stage IIIA (N2) non-small cell lung cancer without increasing adverse effects.

PubMed

Zhao, Xiaoliang; Su, Yanjun; You, Jian; Gong, Liqun; Zhang, Zhenfa; Wang, Meng; Zhao, Zhenqing; Zhang, Zhen; Li, Xiaolin; Wang, Changli

2016-09-20

To evaluate the safety and efficacy of combining Endostar antiangiogenic therapy with neoadjuvant chemotherapy for the treatment of stage IIIA (N2) NSCLC, we conducted a randomized, controlled, open-label clinical study of 30 NSCLC patients. Patients were randomly assigned to the test or control groups, which received either two cycles of an NP neoadjuvant chemotherapy regimen combined with Endostar or the NP regimen alone, respectively, at a 2:1 ratio. Efficacy was assessed after 3 weeks, and surgical resection occurred within 4 weeks, in the 26 patients who successfully completed treatment. While total response rates (RR) and clinical benefit rates (CBR) did not differ between the experimental groups, total tumor regression rates (TRR) were higher in the test group than in the control group. Median DFS and OS also did not differ between the test and control groups. Clinical perioperative indicators, including intraoperative blood loss, number of dissected lymph node groups, duration of postoperative indwelling catheter use, and time to postoperative discharge, were comparable in the test and control groups. Finally, hematological and non-hematological toxicities and postoperative pathological indicators, including down-staging ratio, complete resection ratio, and metastatic lymph node ratio, also did not differ between the groups. Overall, combining Endostar with NP neoadjuvant chemotherapy increased therapeutic efficacy without increasing adverse effects in stage IIIA-N2 NSCLC patients. This study is registered with ClinicalTrials.gov (number NCT02497118).

Randomized controlled trial of care bundles with chlorhexidine dressing and advanced dressings to prevent catheter-related bloodstream infections in pediatric hematology-oncology patients.

PubMed

Gerçeker, Gülçin Özalp; Yardımcı, Figen; Aydınok, Yeşim

2017-06-01

To compare the effects of the care bundles including chlorhexidine dressing and advanced dressings on the catheter-related bloodstream infection (CRBSI) rates in pediatric hematology-oncology patients with central venous catheters (CVCs). Twenty-seven PHO patients were recruited to participate in a prospective, randomized study in Turkey. The researcher used care bundles with chlorhexidine dressing in the experimental group (n = 14), and care bundles with advanced dressings in the control group (n = 13). According to the study results, 28.6% of the patients in the experimental group had CRBSI, while this rate was 38.5% in the control group patients. The CRBSI rate in the experimental group was 3.9, and the control group had 4.4 per 1000 inpatient catheter days. There was no exit-site infection in the experimental group. However, the control group had 1.7 per 1000 inpatient catheter days. Even though there was no difference between the two groups in which the researcher implemented care bundles with chlorhexidine dressing and advanced dressings in terms of CRBSI development, there was reduction in the CRBSI rates thanks to the care bundle approach. It is possible to control the CRBSI rates using care bundles in pediatric hematology-oncology patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Musculoskeletal Imaging Findings of Hematologic Malignancies.

PubMed

Navarro, Shannon M; Matcuk, George R; Patel, Dakshesh B; Skalski, Matthew; White, Eric A; Tomasian, Anderanik; Schein, Aaron J

2017-01-01

Hematologic malignancies comprise a set of prevalent yet clinically diverse diseases that can affect every organ system. Because blood components originate in bone marrow, it is no surprise that bone marrow is a common location for both primary and metastatic hematologic neoplasms. Findings of hematologic malignancy can be seen with most imaging modalities including radiography, computed tomography (CT), technetium 99m ( 99m Tc) methylene diphosphonate (MDP) bone scanning, fluorine 18 ( 18 F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT, and magnetic resonance (MR) imaging. Because of the diversity of imaging appearances and clinical behavior of this spectrum of disease, diagnosis can be challenging, and profound understanding of the underlying pathophysiologic changes and current treatment modalities can be daunting. The appearance of normal bone marrow at MR imaging and FDG PET/CT is also varied due to dynamic compositional changes with normal aging and in response to hematologic demand or treatment, which can lead to false-positive interpretation of imaging studies. In this article, the authors review the normal maturation and imaging appearance of bone marrow. Focusing on lymphoma, leukemia, and multiple myeloma, they present the spectrum of imaging findings of hematologic malignancy affecting the musculoskeletal system and the current imaging tools available to the radiologist. They discuss the imaging findings of posttreatment bone marrow and review commonly used staging systems and consensus recommendations for appropriate imaging for staging, management, and assessment of clinical remission. © RSNA, 2017.

Utilizing cell-based therapeutics to overcome immune evasion in hematologic malignancies.

PubMed

Sun, Chuang; Dotti, Gianpietro; Savoldo, Barbara

2016-06-30

Hematologic malignancies provide a suitable testing environment for cell-based immunotherapies, which were pioneered by the development of allogeneic hematopoietic stem cell transplant. All types of cell-based therapies, from donor lymphocyte infusion to dendritic cell vaccines, and adoptive transfer of tumor-specific cytotoxic T cells and natural killer cells, have been clinically translated for hematologic malignancies. The recent success of chimeric antigen receptor-modified T lymphocytes in B-cell malignancies has stimulated the development of this approach toward other hematologic tumors. Similarly, the remarkable activity of checkpoint inhibitors as single agents has created enthusiasm for potential combinations with other cell-based immune therapies. However, tumor cells continuously develop various strategies to evade their immune-mediated elimination. Meanwhile, the recruitment of immunosuppressive cells and the release of inhibitory factors contribute to the development of a tumor microenvironment that hampers the initiation of effective immune responses or blocks the functions of immune effector cells. Understanding how tumor cells escape from immune attack and favor immunosuppression is essential for the improvement of immune cell-based therapies and the development of rational combination approaches. © 2016 by The American Society of Hematology.

Critical values in hematology of 862 institutions in China.

PubMed

Ye, Y Y; Zhao, H J; Fei, Y; Wang, W; He, F L; Zhong, K; Yuan, S; Wang, Z G

2017-10-01

A national survey on critical values in hematology of China laboratories was conducted to determine the current practice and assess the quality indicators so as to obtain a quality improvement. Laboratories participating were asked to submit the general information, the practice of critical value reporting, and the status of timeliness of critical value reporting. A total of 862 laboratories submitted the results. The majority of participants have included white blood cell count, blood platelet count, hemoglobin, prothrombin time, and activated partial thromboplastin time in their critical value lists. Many sources are used for establishing a critical value policy, and some of the laboratories consult with clinicians. The unreported critical value rate, late critical value reporting rate, and clinically unacknowledged rate in China are relatively low, and the median of critical value reporting time is 8-9 minutes. There exists a wide variety for critical value reporting in hematology in China. Laboratories should establish a policy of critical value reporting suited for their own situations and consult with clinicians to set critical value lists. Critical values are generally reported in a timely manner in China, but some measures should be taken to further improve the timeliness of critical value reporting. © 2017 John Wiley & Sons Ltd.

Mold colonization of fiberglass insulation of the air distribution system: effects on patients with hematological malignancies.

PubMed

Takuma, Takahiro; Okada, Kaoru; Yamagata, Akihiro; Shimono, Nobuyuki; Niki, Yoshihito

2011-02-01

We investigated mold colonization of air handling units (AHUs) of heating, ventilating, and air conditioning (HVAC) systems and its effects, including invasive pulmonary mycoses and febrile neutropenia, in patients with hematological malignancies. Sample collection with transparent adhesive tape and culture swabs revealed that AHUs were heavily colonized with molds, including thermotolerant, variously distributed Penicillium spp. Cases of nosocomial invasive pulmonary mycosis were not clustered in specific patient rooms but did occur frequently when the HVAC systems were not in use, prior to intervention (i.e., sealing and disuse of AHUs in private room), and during construction of a new hospital building. Multivariate logistic regression analysis of initial episodes of febrile neutropenia showed that the rate of febrile neutropenia was significantly associated with the duration of neutropenia (odds ratio [OR]: 1.16; 95% confidence interval [CI]: 1.07-1.27) and with sex (OR: 0.469; CI: 0.239-0.902). An evaluation of private rooms showed that female patients also had a lower rate of fever after intervention (OR: 0.0016; 95% CI: 0.000-0.209). The reduced rate of febrile neutropenia after intervention suggests that mold colonization of AHUs had adverse effects on patients with hematological malignancies.

Hematological and biochemical features of postpartum fever in the heavy draft mare.

PubMed

Aoki, Takahiro; Kimura, Yuki; Oya, Anna; Chiba, Akiko; Ishii, Mitsuo; Nambo, Yasuo

2016-01-01

Heavy draft mares potentially have a higher risk of suffering from postpartum fever (PF) than light breed mares. The purpose of this study was to compare hematological and biochemical features between clinically healthy mares (n=40) and PF-affected mares (n=16). Mares were classified as having PF when their rectal temperature rose to >38.5°C within 96 hr of foaling. The numbers of leukocytes, lymphocytes, and neutrophils and the serum magnesium level were significantly lower in PF-affected mares. The serum SAA and NEFA levels were significantly higher in PF-affected mares. Strong inflammation responses, fat mobilization associated with negative energy balance and possibly endotoxin participate in hematological and biochemical features of PF in heavy draft mares.

Morphological and hematological studies of Trypanosoma spp. infecting ornamental armored catfish from Guamá River-PA, Brazil.

PubMed

Fujimoto, Rodrigo Y; Neves, Mikaelle S; Santos, Rudã F B; Souza, Natalino C; Do Couto, Márcia V S; Lopes, Josiane N S; Diniz, Daniel G; Eiras, Jorge C

2013-09-01

A total of 281 specimens of freshwater armored ornamental fish species (Leporacanthicus galaxias,Lasiancistrus saetiger, Cochliodon sp., Hypostomus sp., Pseudacanthicus spinosus, Ancistrus sp. and Rineloricaria cf. lanceolata) were captured at the hydrological basin of Guamá River, Pará, Brazil. The infection by Trypanosoma spp. was inspected. The morphological and morphometric characterization of the parasites and the hematological parameters were determined. Leporacanthicus galaxias and Pseudacanthicus spinosus presented 100% infection prevalence, and the other species showed a variable prevalence of infection. The parasites showed clearly different morphotypes and dimensions, and probably belong to different species. The hematological response to the infection varied with the host. Cochliodon sp. showed no differences between infected and not infected fish. In other species several modifications on some hematological parameters were found, but apparently without causing disease. It is emphasized the possibility of introduction of the parasites in new environments due to the artificial movements of these ornamental fish.

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

Popp, R.A.; Enlow, M.K.

The clinical hematologic change in 2 groups of progeny from mice carrying radiation-induced strain SEC ..cap alpha..-chain deficiencies was found to be similar to the hematologic alterations in persons with ..cap alpha..-thalassemia. The heterozygous deletion or inactivation of the ..cap alpha..-chain gene in mice caused an anemia similar to ..cap alpha..-thalassemina minor in persons. The ..cap alpha..-chain deficiency in mice created an erythrocytosis, reticulocytosis, and microcytic, hypochromic anemia comparable with the changes in human ..cap alpha..-thalassemia minor resulting from deletion of the ..cap alpha..-chain gene. These mouse mutants are the only known animal models of human thalassemia. A comparison ofmore » hematologic values obtained from progeny possessing an ..cap alpha..-chain gene deficiency and from progeny possessing a ..beta..-chain duplication suggested that the deficiency of ..cap alpha..-chain synthesis, rather than a simple imbalance between the amounts of ..cap alpha..- and ..beta..-chains produced, was primarily responsible for the altered hematologic characteristics in these ..cap alpha..-thalassemic mice.« less

[Hematological changes in adolescent anorexia nervosa].

PubMed

Bühren, Katharina; Gärtner, Laura; Kennes, Lieven N; Seitz, Jochen; Hagenah, Ulrich; Herpertz-Dahlmann, Beate

2014-01-01

Hematological changes often occur in patients with acute anorexia nervosa (AN). However, the relationship between these disturbances and other clinical parameters remains unclear. Leucocyte, erythrocyte, and thrombocyte counts as well as hematocrit, hemoglobin, and differential blood counts were collected at admission and after weight restoration in 88 female adolescent patients with the diagnosis of AN according to DSM-IV. These were then compared to clinical parameters. At admission, there were mild changes in the blood count, most of which, however, were reversible after weight gain. Patients with a greater weight loss, a lower age-adjusted BMI, and a history of taking psychotropic drugs were more likely to develop hematological abnormalities. Although most of the hematological changes in adolescent patients with AN were mild, patients with high weight loss and/or low age-adjusted BMI as well as those on psychotropic medication should be monitored carefully in order to avoid severe medical complications. An altered immune function in adult patients with chronic AN might contribute to a higher rate of infections and thus to an increased mortality.

Evaluation of Hematological Parameters in the Differentiation of Subarachnoid Hemorrhage and Other Headache Syndromes.

PubMed

Goktekin, Mehmet C; Yilmaz, Mustafa

2018-06-01

In this research, the aim was to compare hematological data for the differentiation of subarachnoid hemorrhage, migraine attack, and other headache syndromes during consultation in emergency service. In this research, which was designed as retrospective case control study, hematological parameters (WBC, HgB, HCT, PLT, lymphocyte and neutrophile counts and neutrophile/lymphocyte rates) of the patients consulting to emergency service with SAH and migraine and other consulting patients complaining mainly from headache and having normal cranial CT were analysed. Sixty migraine attack patients (F/M:47/13), 57 SAH patients (F/M:30/27), and 53 patients except migraine having normal brain CT (F/M:36/17) who were consulted to emergency service with headache complaint were included in our research. WBC, Hct, HgB, MCV, PLT, MPV, LY, Neu counts, and NY/LY rates were found to differentiate between SAH and migraine. WBC, PLT, MPV, LY, and Neu rates were found to differentiate between SAH and HS patients. Only Hct, HgB, MCV, and NY/LY rates were found to differ meaningfully between SAH and migraine patients but these rates were not found to have meaningful difference between SAH and HS patients. In addition, an increase in WBC counts and NY/LY rates and decrease in MPV counts in ROC analysis were found to be more specific for SAH. WBC, HgB, HCT, PLT, lymphocyte and Neu counts, and NY/LY rates can indicate distinguishing SAH and migraine. WBC, HgB, HCT, PLT, lymphocyte and Neu counts can indicate to the clinician a differentiation of SAH and other headache syndromes.

Preventing CLABSIs among pediatric hematology/oncology inpatients: national collaborative results.

PubMed

Bundy, David G; Gaur, Aditya H; Billett, Amy L; He, Bing; Colantuoni, Elizabeth A; Miller, Marlene R

2014-12-01

Central lines (CLs) are essential for the delivery of modern cancer care to children. Nonetheless, CLs are subject to potentially life-threatening complications, including central line-associated bloodstream infections (CLABSIs). The objective of this study was to assess the feasibility of a multicenter effort to standardize CL care and CLABSI tracking, and to quantify the impact of standardizing these processes on CLABSI rates among pediatric hematology/oncology inpatients. We conducted a multicenter quality improvement collaborative starting in November 2009. Multidisciplinary teams at participating sites implemented a standardized bundle of CL care practices and adopted a common approach to CLABSI surveillance. Thirty-two units participated in the collaborative and reported a mean, precollaborative CLABSI rate of 2.85 CLABSIs per 1000 CL-days. Self-reported adoption of the CL care bundle was brisk, with average compliance approaching 80% by the end of the first year of the collaborative and exceeding 80% thereafter. As of August 2012, the mean CLABSI rate during the collaborative was 2.04 CLABSIs per 1000 CL-days, a reduction of 28% (relative risk: 0.71 [95% confidence interval: 0.55-0.92]). Changes in self-reported CL care bundle compliance were not statistically associated with changes in CLABSI rates, although there was little variability in bundle compliance rates after the first year of the collaborative. A multicenter quality improvement collaborative found significant reductions in observed CLABSI rates in pediatric hematology/oncology inpatients. Additional interventions will likely be required to bring and sustain CLABSI rates closer to zero for this high-risk population. Copyright © 2014 by the American Academy of Pediatrics.

Leukemia, lymphoma and multiple myeloma mortality (1950-1999) and incidence (1969-1999) in the Eldorado uranium workers cohort.

PubMed

Zablotska, Lydia B; Lane, Rachel S D; Frost, Stanley E; Thompson, Patsy A

2014-04-01

Uranium workers are chronically exposed to low levels of radon decay products (RDP) and gamma (γ) radiation. Risks of leukemia from acute and high doses of γ-radiation are well-characterized, but risks from lower doses and dose-rates and from RDP exposures are controversial. Few studies have evaluated risks of other hematologic cancers in uranium workers. The purpose of this study was to analyze radiation-related risks of hematologic cancers in the cohort of Eldorado uranium miners and processors first employed in 1932-1980 in relation to cumulative RDP exposures and γ-ray doses. The average cumulative RDP exposure was 100.2 working level months and the average cumulative whole-body γ-radiation dose was 52.2 millisievert. We identified 101 deaths and 160 cases of hematologic cancers in the cohort. Overall, male workers had lower mortality and cancer incidence rates for all outcomes compared with the general Canadian male population, a likely healthy worker effect. No statistically significant association between RDP exposure or γ-ray doses, or a combination of both, and mortality or incidence of any hematologic cancer was found. We observed consistent but non-statistically significant increases in risks of chronic lymphocytic leukemia (CLL) and Hodgkin lymphoma (HL) incidence and non-Hodgkin lymphoma (NHL) mortality with increasing γ-ray doses. These findings are consistent with recent studies of increased risks of CLL and NHL incidence after γ-radiation exposure. Further research is necessary to understand risks of other hematologic cancers from low-dose exposures to γ-radiation. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Mucorales-Specific T Cells in Patients with Hematologic Malignancies

PubMed Central

Forghieri, Fabio; Candoni, Anna; Cesaro, Simone; Quadrelli, Chiara; Maertens, Johan; Rossi, Giulio; Morselli, Monica; Codeluppi, Mauro; Mussini, Cristina; Colaci, Elisabetta; Messerotti, Andrea; Paolini, Ambra; Maccaferri, Monica; Fantuzzi, Valeria; Del Giovane, Cinzia; Stefani, Alessandro; Morandi, Uliano; Maffei, Rossana; Marasca, Roberto; Narni, Franco; Fanin, Renato; Comoli, Patrizia; Romani, Luigina; Beauvais, Anne; Viale, Pier Luigi; Latgè, Jean Paul; Luppi, Mario

2016-01-01

Background Invasive mucormycosis (IM) is an emerging life-threatening fungal infection. It is difficult to obtain a definite diagnosis and to initiate timely intervention. Mucorales-specific T cells occur during the course of IM and are involved in the clearance of the infection. We have evaluated the feasibility of detecting Mucorales-specific T cells in hematological patients at risk for IM, and have correlated the detection of such cells with the clinical conditions of the patients. Methods and Findings By using an enzyme linked immunospot assay, the presence of Mucorales-specific T cells in peripheral blood (PB) samples has been investigated at three time points during high-dose chemotherapy for hematologic malignancies. Mucorales-specific T cells producing interferon-γ, interleukin-10 and interleukin-4 were analysed in order to detect a correlation between the immune response and the clinical picture. Twenty-one (10.3%) of 204 patients, accounting for 32 (5.3%) of 598 PB samples, tested positive for Mucorales-specific T cells. Two groups could be identified. Group 1, including 15 patients without signs or symptoms of invasive fungal diseases (IFD), showed a predominance of Mucorales-specific T cells producing interferon-gamma. Group 2 included 6 patients with a clinical picture consistent with invasive fungal disease (IFD): 2 cases of proven IM and 4 cases of possible IFD. The proven patients had significantly higher number of Mucorales-specific T cells producing interleukin-10 and interleukin-4 and higher rates of positive samples by using derived diagnostic cut-offs when compared with the 15 patients without IFD. Conclusions Mucorales-specific T cells can be detected and monitored in patients with hematologic malignancies at risk for IM. Mucorales-specific T cells polarized to the production of T helper type 2 cytokines are associated with proven IM and may be evaluated as a surrogate diagnostic marker for IM. PMID:26871570

Central line-associated bloodstream infections in adult hematology patients with febrile neutropenia: an evaluation of surveillance definitions using differential time to blood culture positivity.

PubMed

Freeman, Joshua T; Elinder-Camburn, Anna; McClymont, Catherine; Anderson, Deverick J; Bilkey, Mary; Williamson, Deborah A; Berkahn, Leanne; Roberts, Sally A

2013-01-01

We used differential time to positivity between central and peripheral blood cultures to evaluate the positive predictive value (PPV) of the National Healthcare Safety Network central line-associated bloodstream infection (CLABSI) surveillance definition among hematology patients with febrile neutropenia. The PPV was 27.7%, which suggests that, when the definition is applied to this population, CLABSI rates will be substantially overestimated.

Efficacy and Safety of Neoadjuvant Treatment with Bevacizumab, Liposomal Doxorubicin, Cyclophosphamide and Paclitaxel Combination in Locally/Regionally Advanced, HER2-Negative, Grade III at Premenopausal Status Breast Cancer: A Phase II Study.

PubMed

Tampaki, Ekaterini C; Tampakis, Athanasios; Alifieris, Constantinos E; Krikelis, Dimitrios; Pazaiti, Anastasia; Kontos, Michalis; Trafalis, Dimitrios T

2018-05-09

In the era of personalized therapy, targeted treatment in specific patient populations is mandated. We evaluated the efficacy and safety of neoadjuvant treatment on locally advanced breast cancer (LABC) with a monoclonal agent against vascular endothelial growth factor (VEGF), bevacizumab plus chemotherapy combination of liposomal doxorubicin, cyclophosphamide and paclitaxel (PLAC-B). Patients enrolled were at premenopausal status and characterized by human epidermal growth factor receptor 2 (HER2)-negative, hormone-receptor positive (estrogen receptor/progesterone receptor-positive [ER/PR+]) or triple-negative (TNBC), LABC (T > 3 cm), with high-grade ductal carcinoma. Patients had to have a measurable disease and Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, with adequate hematologic, renal, and hepatic function. Patients received intravenous liposomal doxorubicin 30 mg/m 2 , cyclophosphamide 600 mg/m 2 , paclitaxel 120 mg/m 2 , and bevacizumab 8 mg/kg on day 1 of 15-day cycles for four cycles (four administrations as neoadjuvant treatment). The primary endpoint was complete clinical (cCR) and pathologic (pCR) response rates, while secondary endpoints included safety, breast-conserving surgery (BCS) conversion rate, and disease-free survival (DFS). Sixty-two women were enrolled; 20 were ER/PR+ and 42 had TNBC. All underwent surgery, six received mastectomy, and 56 (90.3%) received BCS, with an equal conversion rate from initial indication for mastectomy. cCR was 25.8%. pCR in the breast and axilla occurred in 24 patients (38.7%). pCR was 42.9% for TNBC and 30% for ER/PR+. Hematologic adverse events (AEs) included neutropenia (74.2% total; 22.6% grade 3 [G3]) and febrile neutropenia (6.5% G3); non-hematologic G3 AEs included nausea (6.5%), mucositis (9.7%), and infection (3.2%), all of which were managed without negative sequelae. Over a 3-year follow-up, all patients were alive and DFS was 87.1%. PLAC-B as neoadjuvant treatment of this subpopulation with TNBC and ER/PR+ patients is effective and safe. Further studies are necessitated.

Addition of cyclophosphamide and higher doses of dexamethasone do not improve outcomes of patients with AL amyloidosis treated with bortezomib.

PubMed

Kastritis, E; Gavriatopoulou, M; Roussou, M; Fotiou, D; Ziogas, D C; Migkou, M; Eleutherakis-Papaiakovou, E; Panagiotidis, I; Kanellias, N; Psimenou, E; Papadopoulou, E; Pamboucas, C; Manios, E; Gakiopoulou, H; Ntalianis, A; Tasidou, A; Giannouli, S; Terpos, E; Dimopoulos, M A

2017-06-16

Bortezomib, in combination with dexamethasone (VD) or with the addition of cyclophosphamide (VCD), is highly effective in patients with amyloid light-chain (AL) amyloidosis. Currently, VCD is considered as a primary regimen for patients with AL, but it is not clear whether the addition of cyclophosphamide to VD further and significantly improves efficacy, given the substantial activity of bortezomib itself. We retrospectively compared the outcomes of 101 patients with AL amyloidosis who received VD (n=59) or VCD (n=42) in two consecutive periods. Early mortality after adjustment for Mayo stage was similar. On intent to treat, a hematologic response rate was 68% for patients treated with VD and 78% for VCD (P=0.26), while complete response+very good partial response (CR+VGPR) rate was 47.5% and 35%, respectively. Higher doses of dexamethasone or twice-weekly bortezomib were not associated with significantly higher CR+VGPR rates. Organ responses occurred in similar rates between the two groups. Median survival was similar (33 vs 36 months, P=0.45) even after adjustment for Mayo stage and dose and schedule of bortezomib and dexamethasone. In conclusion, bortezomib even with low doses of dexamethasone is effective for the treatment of AL amyloidosis; higher doses of dexamethasone and addition of cyclophosphamide do not seem to have a profound effect on efficacy and survival.

Performance evaluation of the latest fully automated hematology analyzers in a large, commercial laboratory setting: a 4-way, side-by-side study.

PubMed

Bourner, G; Dhaliwal, J; Sumner, J

2005-01-01

Gamma-Dynacare is a Canadian-based community laboratory partnership formed in the mid-1990s through the merger of 3 prominent Ontario medical diagnostic laboratories. Laboratory Corporation of America acquired an interest in the GD partnership in mid 2002. We service more than 10,000 community-based Canadian clinicians, hospital partners, and private clients with an integrated customer-focused system that includes specimen collection, transportation, and results reporting services. With more than 1,700 highly qualified medical, technical, and support staff and a network of laboratories, Gamma Dynacare aims to be at the forefront of technological innovation to better service the clinician base and ultimately deliver better patient care. We were looking for a hematology analyzer that would allow. (1) standardization throughout Ontario in our 4 largest sites and (2) better performance to effectively handle aged samples and minimize slide review. To select the best, most productive hematology analyzer for our environment, it was decided to perform a side-by-side comparison of the top hematology analyzers from Abbott (Cell-Dyn 3500), Beckman Coulter (LH 750), Bayer (Advia 120), and Sysmex (XE 2100), utilizing the same samples. CBC, differential and reticulocyte parameters were all evaluated according to CLSI (formerly NCCLS) and established hematology analyzer evaluation guidelines. We assessed each analyzer for precision, linearity, carryover, stability, differential capabilities, slide review rates, and throughput (clean bench studies). Two hundred samples were assessed for differential and morphology flagging on each analyzer using the reference 400 cell manual differential for comparison. Throughput was assessed by analyzing 700 consecutive samples representative of our workload mix. Stability studies at 24 hours showed that the Beckman Coulter LH 750 was least affected by EDTA, effect with minimal changes in the mean corpuscular volume (MCV) and hematocrit. Both the Bayer Advia 120 and Sysmex XE 2100 showed an elevation of the MCV (up to 5 fL) and Hematocrit over the 24 hours. Analysis of the 200 randomly selected patient samples showed that, while the false-negative rates on each of the instruments were comparable, there were significant differences in the false-positive rates. This has important implications for slide review rates. For our specimen mix, the Sysmex XE 2100 had the highest false-positive rate (15%), followed by the Cell-Dyn 3500 (8%), Advia 120 (6.5%) and the Beckman Coulter LH 750 (1.5%). Reticulocyte analysis performance was observed to be satisfactory with the Beckman Coulter LH 750, Cell-Dyn 3500, and XE 2100, while the Bayer Advia 120 showed a decrease in retic values after 12 hours. In conclusion, many laboratories will not be able to perform a 4-way evaluation such as described here due to time, space, and resource constraints. For our laboratories, result quality, sample stability performance, slide review rates, and efficiency were the primary criteria in selection of the most suitable hematology analyzer. Our 4-way evaluation resulted in selection of the Beckman Coulter LH 750 for Gamma-Dynacare Laboratories because it enabled the lowest slide review rate and handled aged samples better than the other analyzers.

Acute Hematological and Inflammatory Responses to High-intensity Exercise Tests: Impact of Duration and Mode of Exercise.

PubMed

Minuzzi, Luciele G; Carvalho, Humberto M; Brunelli, Diego T; Rosado, Fatima; Cavaglieri, Cláudia R; Gonçalves, Carlos E; Gaspar, Joana M; Rama, Luís M; Teixeira, Ana M

2017-07-01

The purpose of this study was to investigate the hematological and inflammatory responses to 4 maximal high-intensity protocols, considering energy expenditure in each test. 9 healthy volunteers performed 4 high-intensity exercise tests of short [Wingate (WANT); Repeated-sprints (RSA)] and long durations [Continuous VO 2 test (VCONT); intermittent VO 2 test (VINT)] in a cycle-ergometer, until exhaustion. Hematological parameters and IL-6, IL-10 and creatine kinase (CK) levels were determined before (PRE), POST, 30 min, 1, 2, 12 and 24 h after the end of the protocols. Additionally, energy expenditure was determined. Leucocytes, erythrocytes and lymphocytes increased at POST and returned to PRE values at 30 min for all protocols. Lymphocytes had a second decreased at 2 h and granulocytes increased at 2 h when compared to PRE. Both variables returned to PRE values between 12-24 h into recovery. The magnitude of response for IL-6 was greater in VINT and for IL-10 in VCONT. There was no association of energy expenditure within each exercise protocol with the pattern of IL-6, IL-10 and CK responses to the exercise protocols. The present finding support that similar responses after continuous or intermittent acute protocols are observed when exercises are performed to volitional failure, regardless of the duration and mode of exercise. © Georg Thieme Verlag KG Stuttgart · New York.

Concurrent chemoradiotherapy with elective lymph node irradiation for esophageal cancer: a systemic review and pooled analysis of the literature.

PubMed

Du, Dexi; Song, Tao; Liang, Xiaodong; Fang, Min; Wu, Shixiu

2017-02-01

Concurrent chemoradiotherapy (CCRT) has been accepted as the standard non-surgical treatment for esophageal cancer. However, no consistent conclusions have been reached whether elective lymph node irradiation (ENI) should be delivered. Therefore, we performed a systematic review and pooled analysis to evaluate the value of CCRT with ENI. A literature search based on PubMed, Embase and Google Scholar was carried out and all of the studies were evaluated carefully regarding with survival outcomes, response rates, patterns of failure rates and acute/late toxicities. Twenty-two studies were identified based on the criteria: median overall survival time was 21.0 months; pooled response rates were 56.8% (CR) and 85.8% (CR+PR), respectively; residual disease rate, local-regional recurrence rate, distant failure rate and both (local-regional recurrence plus distant failure) rate was 28%, 21%, 11%, and 7%, respectively; hematologic toxicities were the most sever acute toxicities and esophagus-related toxicity was the most common radiation-related toxicity both in acute (15.7%) and late (6.2%) phase. In conclusion, ENI is feasible with acceptable toxicities in esophageal carcinoma and the efficacy should be verified in randomized trials. © 2016 International Society for Diseases of the Esophagus.

Reactive Oxygen Species Response to Exercise Training and Weight Loss in Sedentary Overweight and Obese Female Adults.

PubMed

Bianchi, Vittorio E; Ribisl, Paul M

2015-01-01

Reactive oxygen species (ROS) are implicated in cardiovascular disease and in the pathogenesis of type 2 diabetes and its complications, and it has been shown to increase insulin resistance. The purpose of this study was to examine the effect of aerobic exercise training and weight loss on ROS in overweight and obese patients as applied in a community clinical setting. Fifty healthy female clinic patients (M ± SEM: age, 41.0 ± 1.8 years; body mass index, 28.2 ± 0.8 kg/m2), free of cardiovascular events and not on drug therapy were evaluated before and after 3 months of dietary restriction (∼150 to 300 kcal/day deficit) and aerobic training (3 days/week for 1 hour at ∼75% VO2max). Measures included ROS, maximal power (kg/min) on cycle ergometry, postexercise heart rate recovery responses at 1 and 2 minutes, and selected anthropometric and hematologic variables. Significant (P < .01) improvements were observed after aerobic training and weight loss in body weight in kilograms (-7.1%); maximal power in kg/min (+32.6%), ROS in U.CARR (Carratelli units) (-25.7%); and heart rate recovery 1 minute in beats per minute (-37.6%) following the program. Significant improvements were also noted in other anthropometric, cardiovascular, and hematologic measures. A 12-week program of nutritional and exercise intervention in overweight/obese sedentary women improves levels of oxidative stress when accompanied by weight loss and improved fitness. More than restricted caloric intake, physical activity at a relatively high intensity was effective in improving cardiovascular risk markers. The reduction in ROS may be an additional mechanism by which physical activity may contribute to preventing metabolic syndrome and subsequent atherosclerotic disease.

Phase 2 Open-Label Study of Bortezomib, Cladribine, and Rituximab in Advanced, Newly Diagnosed, and Relapsed/Refractory Mantle-Cell and Indolent Lymphomas.

PubMed

Puvvada, Soham D; Guillen-Rodriguez, José; Kumar, Abhijeet; Inclán, Lora; Heard, Kara; Rivera, Xavier I; Anwer, Faiz; Schatz, Jonathan H; Mahadevan, Daruka; Persky, Daniel O

2018-01-01

Mantle-cell lymphoma (MCL) and indolent non-Hodgkin lymphoma (iNHL) are incurable heterogeneous diseases characterized by relapse. There is a need for newer treatments in MCL and iNHL, especially in the relapsed/refractory (R/R) setting. We therefore investigated the novel combination of bortezomib (Velcade), cladribine, and rituximab (VCR) in front-line and R/R settings in MCL and iNHL (NCT00980395). Eligible patients included adults with biopsy-proven CD20-positive MCL and iNHL who met the criteria for treatment. Rituximab 375 mg/m 2 intravenous (IV) day 1, cladribine 4 mg/m 2 IV days 1 to 5, and bortezomib 1.3 mg/m 2 IV days 1 and 4 were administered every 28 days for 6 cycles. Twenty-four patients were enrolled onto the study with a median follow-up of 38.5 months. Median age was 66.5 years, and 46% had MCL. The most common adverse events were hematologic, with febrile neutropenia in 3 patients. Neuropathy was noted in 17% of patients, of which 8% was grade 3 or above. The overall response rate was 92%. For the entire cohort, and for MCL patients, the median progression-free survival and the median overall survival were not reached. The 2-year progression-free survival was 82% for the MCL group and 54% for the iNHL group; it was 80% for treatment-naive patients and 57% for R/R patients. VCR is effective in MCL and iNHL. Although hematologic toxicity can be an issue, this study demonstrates a high response rate to a novel combination and provides an alternative option in transplant-ineligible R/R MCL and iNHL. Copyright © 2017 Elsevier Inc. All rights reserved.

Phase II Dose Escalation Study of Caspofungin for Invasive Aspergillosis ▿ §

PubMed Central

Cornely, O. A.; Vehreschild, J. J.; Vehreschild, M. J. G. T.; Würthwein, G.; Arenz, D.; Schwartz, S.; Heussel, C. P.; Silling, G.; Mahne, M.; Franklin, J.; Harnischmacher, U.; Wilkens, A.; Farowski, F.; Karthaus, M.; Lehrnbecher, T.; Ullmann, A. J.; Hallek, M.; Groll, A. H.

2011-01-01

Our objective was to evaluate the maximum tolerated dose of caspofungin for invasive aspergillosis (IA). The safety and pharmacokinetics of escalating dosages of caspofungin were investigated in IA. Eight patients each received caspofungin 70, 100, 150, or 200 mg once a day (QD). Dose-limiting toxicity (DLT) was defined as the same non-hematological treatment-related adverse event of grade ≥4 in 2 of 8 patients or ≥3 in 4 of 8 patients in a cohort. A total of 46 patients (median age, 61 years; 21 female; 89% with hematological malignancies) received caspofungin (9, 8, 9, and 20 patients in the 70-, 100-, 150-, and 200-mg cohorts) for a median of 24.5 days. Plasma pharmacokinetics were linear across the investigated dosages and followed a two-compartment model, with weight as the covariate on clearance and sex as the covariate on central volume of distribution. Simulated peak plasma concentrations at steady state ranged from 14.2 to 40.6 mg/liter (28%), trough concentrations from 4.1 to 11.8 mg/liter (58%), and area under the concentration-time curve from 175 to 500 mg/liter/h (32%) (geometric mean, geometric coefficient of variation). Treatment was well tolerated without dose-limiting toxicity. The rate of complete or partial responses was 54.3%, and the overall mortality at 12-week follow-up was 28.3%. In first-line treatment of invasive aspergillosis, daily doses of up to 200 mg caspofungin were well tolerated and the maximum tolerated dose was not reached. Pharmacokinetics was linear. Response rates were similar to those previously reported for voriconazole and liposomal amphotericin. PMID:21911573

Childhood cancer survivorship educational resources in North American pediatric hematology/oncology fellowship training programs: a survey study.

PubMed

Nathan, Paul C; Schiffman, Joshua D; Huang, Sujuan; Landier, Wendy; Bhatia, Smita; Eshelman-Kent, Debra; Wright, Jennifer; Oeffinger, Kevin C; Hudson, Melissa M

2011-12-15

Childhood cancer survivors require life-long care by clinicians with an understanding of the specific risks arising from the prior cancer and its therapy. We surveyed North American pediatric hematology/oncology training programs to evaluate their resources and capacity for educating medical trainees about survivorship. An Internet survey was sent to training program directors and long-term follow-up clinic (LTFU) directors at the 56 US and Canadian centers with pediatric hematology/oncology fellowship programs. Perceptions regarding barriers to and optimal methods of delivering survivorship education were compared among training program and LTFU clinic directors. Responses were received from 45/56 institutions of which 37/45 (82%) programs require that pediatric hematology/oncology fellows complete a mandatory rotation focused on survivorship. The rotation is 4 weeks or less in 21 programs. Most (36/45; 80%) offer didactic lectures on survivorship as part of their training curriculum, and these are considered mandatory for pediatric hematology/oncology fellows at 26/36 (72.2%). Only 10 programs (22%) provide training to medical specialty trainees other than pediatric hematology/oncology fellows. Respondents identified lack of time for trainees to spend learning about late effects as the most significant barrier to providing survivorship teaching. LTFU clinic directors were more likely than training program directors to identify lack of interest in survivorship among trainees and survivorship not being a formal or expected part of the fellowship training program as barriers. The results of this survey highlight the need to establish standard training requirements to promote the achievement of basic survivorship competencies by pediatric hematology/oncology fellows. Copyright © 2011 Wiley Periodicals, Inc.

Increasing bone sclerosis during bortezomib therapy in multiple myeloma patients: results of a reduced-dose whole-body MDCT study.

PubMed

Schulze, Maximilian; Weisel, Katja; Grandjean, Caroline; Oehrlein, Katharina; Zago, Manola; Spira, Daniel; Horger, Marius

2014-01-01

The objective of our study was to assess the frequency, location, extent, and patterns of bone sclerosis occurring in patients with multiple myeloma (MM) during bortezomib-based therapy. From June 2003 through December 2011, 593 whole-body reduced-dose MDCT studies were performed of 79 consecutive patients receiving bortezomib. The median surveillance time was 21 months (range, 3-67 months). Baseline studies were compared with follow-up studies during therapy (follow-up 1), at the end of therapy (follow-up 2), and 12 months after cessation of bortezomib therapy (follow-up 3). We recorded any sclerotic change occurring inside or along the margins of the osteolytic lesions, in the cancellous bone, or inside preexistent medullary or extramedullary lesions. The time point of occurrence of bone sclerosis was correlated with the best hematologic response category. Fourteen (17.7%) patients developed focal (n = 11) or diffuse (n = 3) bone sclerosis. The time window from bortezomib initiation to radiographic detection of bone sclerosis was 8 months (SD, 7 months). Sclerosis occurred at multiple sites (n = 7) or at an isolated site (n = 7). On subsequent whole-body reduced-dose MDCT studies, sclerosis further increased in seven (50%) patients. Hematologic best response during bortezomib treatment was complete response (n = 1), very good partial response (n = 2), partial response (n = 8), and stable disease (n = 3). Radiologic response at the time of sclerosis detection was partial response (n = 8), stable disease (n = 2), and progressive disease (n = 4). Bone remineralization may occur during bortezomib-based therapy for MM in a substantial proportion of patients. The extent, location, and patterns of sclerosis differ among patients and are unpredictable. Sclerosis was documented even in patients showing suboptimal hematologic response.

Early versus Deferred Treatment for Smoldering Multiple Myeloma: A Meta-Analysis of Randomized, Controlled Trials

PubMed Central

Tompkins, Van S.; Gao, Lu; Wu, Xiaosong; Tao, Yi; Hu, Xiaojing; Hou, Jun; Han, Ying; Xu, Hongwei; Zhan, Fenghuang; Shi, Jumei

2014-01-01

Purpose Whether patients with smoldering multiple myeloma (SMM) needed to receive early interventional treatment remains controversial. Herein, we conducted a meta-analysis comparing the efficacy and safety of early treatment over deferred treatment for patients with SMM. Methods MEDLINE and Cochrane Library were searched to May 2014 for randomized controlled trials (RCTs) that assessed the effect of early treatment over deferred treatment. Primary outcome measure was mortality, and secondary outcome measures were progression, response rate, and adverse events. Results Overall, 5 trials including 449 patients were identified. There was a markedly reduced risk of disease progression with early treatment (Odds Ratio [OR] = 0.13, 95% confidence interval [CI] = 0.07 to 0.24). There were no significant differences in mortality and response rate (OR = 0.85, 95% CI = 0.45 to 1.60, and OR = 0.63, 95% CI = 0.32 to 1.23, respectively). More patients in the early treatment arm experienced gastrointestinal toxicities (OR = 10.02, 95%CI = 4.32 to 23.23), constipation (OR = 8.58, 95%CI = 3.20 to 23.00) and fatigue or asthenia (OR = 2.72, 95%CI = 1.30 to 5.67). No significant differences were seen with the development of acute leukemia (OR = 2.80, 95%CI = 0.42 to 18.81), hematologic cancer (OR = 2.07, 95%CI = 0.43 to 10.01), second primary tumors (OR = 3.45, 95%CI = 0.81 to 14.68), nor vertebral compression (OR = 0.18, 95%CI = 0.02 to 1.59). Conclusions Early treatment delayed disease progression but increased the risk of gastrointestinal toxicities, constipation and fatigue or asthenia. The differences on vertebral compression, acute leukemia, hematological cancer and second primary tumors were not statistically significant. Based on the current evidence, early treatment didn’t significantly affect mortality and response rate. However, further much larger trials were needed to provide more evidence. PMID:25279718

Treatment of chronic myelogenous leukemia with interleukin-2: a phase II study in 21 patients.

PubMed

Vey, N; Blaise, D; Lafage, M; Olive, D; Viens, P; Baume, D; Camerlo, J; Stoppa, A M; Gabus, R; Brandely, M; Hercend, T; Maraninchi, D

1999-03-01

We designed a phase II study to assess the activity of recombinant interleukin-2 (rIL-2) in patients with chronic myelogenous leukemia (CML). Study population included 11 patients in the chronic phase of CML (6 in hematologic remission and 5 with active disease), 6 patients in the accelerated phase, and 4 in blastic phase of CML. Patients received three 5-day cycles administrated every other week. rIL-2 was given as intravenous bolus infusions of 8 x 10(6) IU/m2 three times a day during cycle 1 and twice a day during cycles 2 and 3. Response to rIL-2 was assessed on day 45. No hematologic response was achieved in the patients with evaluable disease. One patient in hematologic remission with rIL-2 achieved a major response (from 72% to 9% Ph+ metaphases), and two patients had some degree of reduction of Ph+ metaphases. Responses were short-lived (< 6 months), but two of these three patients achieved a new cytogenetic response with interferon given post-rIL-2. A significant immune activation was achieved with rIL-2 including a marked increase in CD3+/CD25+ cells, CD56+ cells, and in natural killer/lymphokine activated killer cell cytotoxic activity. These results confirm preclinical studies, which showed that IL-2 has antileukemic activity in CML. However, the responses observed were short lived and restricted to a subgroup of patients with low disease burden. This invites further studies testing its impact in situations of minimal disease or in combination with other cytokines.

Radiation-induced cytogenetic and hematologic effects on aquatic biota within the Chernobyl exclusion zone.

PubMed

Gudkov, D I; Shevtsova, N L; Pomortseva, N A; Dzyubenko, E V; Kaglyan, A E; Nazarov, A B

2016-01-01

During 1998-2014 the rate of chromosomal aberrations in embryo tissues of the pond snail (Lymnaea stagnalis) and root meristems of higher aquatic plants, and also hematologic indexes of mantle liquid of the adult snails and peripheral blood of fishes in water bodies within the Chernobyl exclusion zone (EZ) was studied. The absorbed dose rate for hydrobionts from water bodies of the EZ registered in a range from 0.25 to 420 μGy h(-1) and in the reference ones - up to 0.09 μGy h(-1). The level of chromosomal aberrations in the molluscs from the most contaminated water bodies of the EZ was registered within range of 18-27% and for the molluscs from the reference lakes this index was on the average 1.5% with the maximal values 2.3%. The rate of chromosomal aberrations in root meristematic cells of higher aquatic plants from the contaminated lakes of the EZ was in range of 7-17% and in the plants from reference water bodies was not exceed 2.1%. The positive correlation between chromosomal aberration rate and absorbed dose rate in the pond snail's embryos and root meristems of higher aquatic plants in water bodies of the EZ was registered. Analysis of hemolymph structure of snails from the most contaminated water bodies showed a high rate of dead and phagocytic cells as well as decrease of the young amoebocytes quantity. Hematologic research of fish allows to determine on the one hand an insignificant changes of leukogram structure, and from the other hand a high level of red cells with different abnormalities in the peripheral blood of fishes from the water bodies with high levels of radioactive contamination. It is suppose that qualitative indexes of red cells in peripheral blood of fish are more sensitive to long-term radiation impact in comparison with elements of white blood, which can be used for conducting of the hematologic monitoring of radioactive contaminated water bodies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Residential radon exposure and risk of incident hematologic malignancies in the Cancer Prevention Study-II Nutrition Cohort

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

Teras, Lauren R., E-mail: lauren.teras@cancer.org; Diver, W. Ryan; Turner, Michelle C.

Dosimetric models show that radon, an established cause of lung cancer, delivers a non-negligible dose of alpha radiation to the bone marrow, as well as to lymphocytes in the tracheobronchial epithelium, and therefore could be related to risk of hematologic cancers. Studies of radon and hematologic cancer risk, however, have produced inconsistent results. To date there is no published prospective, population-based study of residential radon exposure and hematologic malignancy incidence. We used data from the American Cancer Society Cancer Prevention Study-II Nutrition Cohort established in 1992, to examine the association between county-level residential radon exposure and risk of hematologic cancer.more » The analytic cohort included 140,652 participants (66,572 men, 74,080 women) among which 3019 incident hematologic cancer cases (1711 men, 1308 women) were identified during 19 years of follow-up. Cox proportional hazard regression was used to calculate multivariable-adjusted hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for radon exposure and hematologic cancer risk. Women living in counties with the highest mean radon concentrations (>148 Bq/m{sup 3}) had a statistically significant higher risk of hematologic cancer compared to those living in counties with the lowest (<74 Bq/m{sup 3}) radon levels (HR=1.63, 95% CI:1.23–2.18), and there was evidence of a dose-response relationship (HR{sub continuous}=1.38, 95% CI:1.15–1.65 per 100 Bq/m{sup 3}; p-trend=0.001). There was no association between county-level radon and hematologic cancer risk among men. The findings of this large, prospective study suggest residential radon may be a risk factor for lymphoid malignancies among women. Further study is needed to confirm these findings. - Highlights: • This is the first prospective, general population study of residential radon and risk of hematologic cancer. • Findings from this study suggest that residential radon exposure may be a risk factor for lymphoid malignancies. • The biologic mechanism for the association between radon exposure and lymphoma risk may be different than for lung cancer. • Confirmation of this association would warrant strengthened public health efforts to mitigate residential radon risks.« less

SEIFEM 2017: from real life to an agreement on the use of granulocyte transfusions and colony-stimulating factors for prophylaxis and treatment of infectious complications in patients with hematologic malignant disorders.

PubMed

Busca, Alessandro; Cesaro, Simone; Teofili, Luciana; Delia, Mario; Cattaneo, Chiara; Criscuolo, Marianna; Marchesi, Francesco; Fracchiolla, Nicola Stefano; Valentini, Caterina Giovanna; Farina, Francesca; Di Blasi, Roberta; Prezioso, Lucia; Spolzino, Angelica; Candoni, Anna; Del Principe, Maria Ilaria; Verga, Luisa; Nosari, Annamaria; Aversa, Franco; Pagano, Livio

2018-02-01

The rapid spread of severe infections mainly due to resistant pathogens, justifies the search for therapies aiming to restore immune functions severely compromised in patients with hematologic malignancies. Areas covered: The present review summarizes the current knowledge on the role of granulocyte transfusions and colony-stimulating factors as treatment strategy for hematologic patients with serious infectious complications. In addition, a survey among 21 hematologic centers, to evaluate the clinical practice for the use of G-CSF originator and biosimilars was performed. Expert commentary: Granulocyte transfusions with a target dose of at least 1.5-3 × 10 8 cells/kg, may be considered as an approach to bridge the gap between marrow suppression and recovery of granulocytes. G-CSF shortens the period of neutropenia, the hospitalization, the use of antibiotics and the rate of febrile neutropenia (FN) in adult and pediatric patients with non-Hodgkin lymphoma, and in adults with acute myeloid leukemia where these advantages nevertheless, did not translate into a clinical benefit. G-CSF biosimilar showed equivalence or non-inferiority to filgrastim. There are no data supporting the use of GM-CSF, eltrombopag and erythropoietin for preventing or treating infectious complications in patients with hematologic disorders.

Randomized phase II study of a bendamustine monotherapy schedule for relapsed or refractory low-grade B-cell non-Hodgkin lymphoma or mantle cell lymphoma (RABBIT-14).

PubMed

Itoh, Kuniaki; Igarashi, Tadahiko; Irisawa, Hiroyuki; Aotsuka, Nobuyuki; Masuda, Shinichi; Utsu, Yoshikazu; Tsujimura, Hideki; Tsukasaki, Kunihiro; Wakita, Hisashi

2017-10-30

The aim of this randomized phase II study was to improve the treatment delays and discontinuations associated with bendamustine use by comparing the effect of Benda-14 (intravenous bendamustine, 120 mg/m 2 on days 1 and 15, repeated every 4 weeks for a total of 6 cycles) with those of the standard treatment in relapsed indolent lymphoma and/or mantle cell lymphoma. Forty-six patients were randomly assigned to the treatments from September 2012 to February 2016. Treatment accomplishment rate and median relative dose intensity were similar in both arms: 38 and 63.4% in the Benda-14 arm and 41 and 66.3% in the standard treatment arm, respectively. The overall response rate and median progression-free survival, respectively, were 83% and 21.0 months for Benda-14, and 77% and 15.5 months for the standard treatment. Benda-14 induced favorable responses with less frequent hematological toxicities.

Frontline strategy for follicular lymphoma: are we ready to abandon chemotherapy?

PubMed

Fowler, Nathan

2016-12-02

Chemotherapy combinations have been the backbone of therapy for follicular lymphoma, and are associated with high initial response rates. Unfortunately, toxicity and secondary malignancies remain concerns, and most advanced-stage patients still relapse within 5 years, regardless of the regimen. Advances in the understanding of lymphoma biology have resulted in a new generation of noncytotoxic therapeutics with significant activity in follicular lymphoma. Recent studies exploring biological and targeted combinations in the frontline have shown promise, with response rates similar to chemotherapy. However, these regimens are also associated with significant cost as well as a unique toxicity profile. Large randomized studies are underway to compare noncytotoxic regimens with chemotherapy in the frontline, and several new combinations are being tested in the phase 2 setting. Ongoing work to identify predictive biomarkers and investment in mechanistic studies will ultimately lead to the personalization of therapy in the frontline setting for follicular lymphoma. © 2016 by The American Society of Hematology. All rights reserved.

Venetoclax: A novel B-cell lymphoma-2 inhibitor for chronic lymphocytic leukemia and other hematologic malignancies.

PubMed

Olin, Jacqueline L; Griffiths, Carrie L; Smith, Morgan B

2017-01-01

Patients with chronic lymphocytic leukemia with the 17p deletion have a poor prognosis and treatment options are limited. Venetoclax, a novel B-cell lymphoma-2 inhibitor, has been approved for treatment-experienced chronic lymphocytic leukemia patients with the 17p deletion. A phase 1 dose-escalation study to 400 mg daily showed overall response rates across all doses of 79% with a complete response achieved in 20%. A phase 2 multicenter open-label study demonstrated overall response rate of 79.4% of patients (95% confidence interval 70.5-86.6) with median duration of follow-up of 12.1 months (IQR 10.1-14.2). Tumor lysis syndrome has been observed during initiation and titration. Assessing risk of tumor lysis syndrome prior to therapy initiation is essential to provide appropriate prophylactic medications. Neutropenia, potentially warranting dose reduction or discontinuation, has been observed. Venetoclax has demonstrated activity in other leukemias, multiple myeloma, and lymphomas. Venetoclax has shown response, and is well tolerated in patients with highly resistant chronic lymphocytic leukemia. It has the potential to be part of the treatment armamentarium for other malignancies.

Energy metabolism and hematology of white-tailed deer fawns

USGS Publications Warehouse

Rawson, R.E.; DelGiudice, G.D.; Dziuk, H.E.; Mech, L.D.

1992-01-01

Resting metabolic rates, weight gains and hematologic profiles of six newborn, captive white-tailed deer (Odocoileus virginianus) fawns (four females, two males) were determined during the first 3 mo of life. Estimated mean daily weight gain of fawns was 0.2 kg. The regression equation for metabolic rate was: Metabolic rate (kcal/kg0.75/day) = 56.1 +/- 1.3 (age in days), r = 0.65, P less than 0.001). Regression equations were also used to relate age to red blood cell count (RBC), hemoglobin concentration (Hb), packed cell volume, white blood cell count, mean corpuscular volume, mean corpuscular hemoglobin concentration (MCHC), and mean corpuscular hemoglobin. The age relationships of Hb, MCHC, and smaller RBC's were indicative of an increasing and more efficient oxygen-carrying and exchange capacity to fulfill the increasing metabolic demands for oxygen associated with increasing body size.

Leukemia, lymphoma and multiple myeloma mortality (1950–1999) and incidence (1969–1999) in the Eldorado uranium workers cohort

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

Zablotska, Lydia B., E-mail: Lydia.Zablotska@ucsf.edu; Lane, Rachel S.D.; Frost, Stanley E.

Uranium workers are chronically exposed to low levels of radon decay products (RDP) and gamma (γ) radiation. Risks of leukemia from acute and high doses of γ-radiation are well-characterized, but risks from lower doses and dose-rates and from RDP exposures are controversial. Few studies have evaluated risks of other hematologic cancers in uranium workers. The purpose of this study was to analyze radiation-related risks of hematologic cancers in the cohort of Eldorado uranium miners and processors first employed in 1932–1980 in relation to cumulative RDP exposures and γ-ray doses. The average cumulative RDP exposure was 100.2 working level months andmore » the average cumulative whole-body γ-radiation dose was 52.2 millisievert. We identified 101 deaths and 160 cases of hematologic cancers in the cohort. Overall, male workers had lower mortality and cancer incidence rates for all outcomes compared with the general Canadian male population, a likely healthy worker effect. No statistically significant association between RDP exposure or γ-ray doses, or a combination of both, and mortality or incidence of any hematologic cancer was found. We observed consistent but non-statistically significant increases in risks of chronic lymphocytic leukemia (CLL) and Hodgkin lymphoma (HL) incidence and non-Hodgkin lymphoma (NHL) mortality with increasing γ-ray doses. These findings are consistent with recent studies of increased risks of CLL and NHL incidence after γ-radiation exposure. Further research is necessary to understand risks of other hematologic cancers from low-dose exposures to γ-radiation. - Highlights: • We analyzed long-term follow-up for hematologic cancers of the Eldorado uranium workers. • Workers were exposed to a unique combination of radon decay products (RDP) and gamma (γ) ray doses. • Exposures to RDP and γ-ray doses were not associated with significantly increased risks of cancers. • Radiation risks of chronic lymphocytic leukemia (CLL) and Hodgkin lymphoma were increased. • Study findings provide additional support for radiation-related risks of CLL.« less

Atrial Fibrillation in Hematologic Malignancies, Especially After Autologous Hematopoietic Stem Cell Transplantation: Review of Risk Factors, Current Management, and Future Directions.

PubMed

Mathur, Pankaj; Paydak, Hakan; Thanendrarajan, Sharmilan; van Rhee, Frits

2016-02-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with significant morbidity and mortality worldwide. In addition to well-established risk factors, cancer has been increasingly associated with the development of AF. Its increased occurrence in those with hematologic malignancies has been attributed to chemotherapeutic agents and autologous hematopoietic stem cell transplantation (AHSCT). Recently, a few studies have attempted to define the etiopathogenesis of AF in hematologic malignancies. The management of AF in these patients is challenging because of the concurrent complicating factors, such as thrombocytopenia, orthostatic hypotension, and cardiac amyloidosis. More studies are needed to define the management of AF, especially rate versus rhythm control and anticoagulation. Arrhythmias, in particular, AF, have been associated with an increased length of stay, increased intensive care unit admissions, and greater cardiovascular mortality. In the present review, we describe AF in patients with hematologic malignancies, the risk factors, especially after AHSCT, and the current management of AF. Copyright © 2016 Elsevier Inc. All rights reserved.

Meta-Analysis of the Safety and Efficacy of Interferon Combined With Dacarbazine Versus Dacarbazine Alone in Cutaneous Malignant Melanoma.

PubMed

Xin, Yong; Huang, Qian; Zhang, Pei; Yang, Ming; Hou, Xiao-Yang; Tang, Jian-Qin; Zhang, Long Zhen; Jiang, Guan

2016-04-01

The aim of this study was to compare the efficacy and safety of interferon (IFN) combined with dacarbazine (DTIC) (experimental group) versus DTIC alone (control group) in cutaneous malignant melanoma. After searching all available databases, eligible articles were identified and subjected to quality assessment. Meta-analysis was performed using RevMan 5.3; combined relative risk (RR) and 95% confidence intervals (95% CIs) were calculated for survival rates, response rates, and adverse events. Eight randomized controlled trials published between 1990 and 2014 involving 795 patients were included in the meta-analysis. Compared with DTIC alone, IFN combined with DTIC significantly increased the overall response rate (RR = 1.59, 95% CI 1.21-2.08, P = 0.0008),the complete response rate (RR = 3.30, 95% CI 1.89-5.76, P < 0.0001), 2-year survival (RR = 1.59, 95% CI 0.99-2.54, P = 0.050) grade ≥3 hematologic toxicity (RR = 2.30, 95% CI 1.32-4.02, P = 0.003), neurotoxicity (RR = 18.15, 95% CI 5.34-61.74, P < 0.00001), and flu-like symptoms (RR = 6.31, 95% CI 1.95-20.39, P = 0.002). The partial response rate, grade ≥3 nausea and vomiting, treatment-related, and 1- and 3-year survival were not significantly different between IFN combined with DTIC and DTIC alone. IFN combined with DTIC may moderately improve the complete response rate, but increases the incidence of adverse events and has no significant effect on 1- and 3-year survival in cutaneous malignant melanoma.

Meta-Analysis of the Safety and Efficacy of Interferon Combined With Dacarbazine Versus Dacarbazine Alone in Cutaneous Malignant Melanoma

PubMed Central

Xin, Yong; Huang, Qian; Zhang, Pei; Yang, Ming; Hou, Xiao-Yang; Tang, Jian-Qin; Zhang, Long Zhen; Jiang, Guan

2016-01-01

Abstract The aim of this study was to compare the efficacy and safety of interferon (IFN) combined with dacarbazine (DTIC) (experimental group) versus DTIC alone (control group) in cutaneous malignant melanoma. After searching all available databases, eligible articles were identified and subjected to quality assessment. Meta-analysis was performed using RevMan 5.3; combined relative risk (RR) and 95% confidence intervals (95% CIs) were calculated for survival rates, response rates, and adverse events. Eight randomized controlled trials published between 1990 and 2014 involving 795 patients were included in the meta-analysis. Compared with DTIC alone, IFN combined with DTIC significantly increased the overall response rate (RR = 1.59, 95% CI 1.21–2.08, P = 0.0008),the complete response rate (RR = 3.30, 95% CI 1.89–5.76, P < 0.0001), 2-year survival (RR = 1.59, 95% CI 0.99–2.54, P = 0.050) grade ≥3 hematologic toxicity (RR = 2.30, 95% CI 1.32–4.02, P = 0.003), neurotoxicity (RR = 18.15, 95% CI 5.34–61.74, P < 0.00001), and flu-like symptoms (RR = 6.31, 95% CI 1.95–20.39, P = 0.002). The partial response rate, grade ≥3 nausea and vomiting, treatment-related, and 1- and 3-year survival were not significantly different between IFN combined with DTIC and DTIC alone. IFN combined with DTIC may moderately improve the complete response rate, but increases the incidence of adverse events and has no significant effect on 1- and 3-year survival in cutaneous malignant melanoma. PMID:27100429

Acute Hematological Effects in Mice Exposed to the Expected Doses, Dose-rates, and Energies of Solar Particle Event-like Proton Radiation.

PubMed

Sanzari, Jenine K; Cengel, Keith A; Wan, X Steven; Rusek, Adam; Kennedy, Ann R

2014-07-01

NASA has funded several projects that have provided evidence for the radiation risk in space. One radiation concern arises from solar particle event (SPE) radiation, which is composed of energetic electrons, protons, alpha particles and heavier particles. SPEs are unpredictable and the accompanying SPE radiation can place astronauts at risk of blood cell death, contributing to a weakened immune system and increased susceptibility to infection. The doses, dose rates, and energies of the proton radiation expected to occur during a SPE have been simulated at the NASA Space Radiation Laboratory, Brookhaven National Laboratory, delivering total body doses to mice. Hematological values were evaluated at acute time points, up to 24 hrs. post-radiation exposure.

Acute hematological effects in mice exposed to the expected doses, dose-rates, and energies of solar particle event-like proton radiation

NASA Astrophysics Data System (ADS)

Sanzari, Jenine K.; Cengel, Keith A.; Steven Wan, X.; Rusek, Adam; Kennedy, Ann R.

2014-07-01

NASA has funded several projects that have provided evidence for the radiation risk in space. One radiation concern arises from solar particle event (SPE) radiation, which is composed of energetic electrons, protons, alpha particles and heavier particles. SPEs are unpredictable and the accompanying SPE radiation can place astronauts at risk of blood cell death, contributing to a weakened immune system and increased susceptibility to infection. The doses, dose rates, and energies of the proton radiation expected to occur during an SPE have been simulated at the NASA Space Radiation Laboratory, Brookhaven National Laboratory, delivering total body doses to mice. Hematological values were evaluated at acute time points, up to 24 hours post-radiation exposure.

The safety and efficacy of single-agent pemetrexed in platinum-resistant advanced urothelial carcinoma: a large single-institution experience.

PubMed

Bambury, Richard M; Benjamin, David J; Chaim, Joshua L; Zabor, Emily C; Sullivan, John; Garcia-Grossman, Ilana R; Regazzi, Ashley M; Ostrovnaya, Irina; Apollo, Aryln; Xiao, Han; Voss, Martin H; Iyer, Gopa; Bajorin, Dean F; Rosenberg, Jonathan E

2015-05-01

Pemetrexed is a commonly used treatment for platinum-resistant advanced urothelial carcinoma (UC) based on objective response rates of 8% and 28% in two small phase II studies. To address the discrepancy in reported response rates and to assess efficacy and toxicity outside of a clinical trial setting, we performed a large retrospective analysis of pemetrexed use at Memorial Sloan Kettering Cancer Center. We also investigated candidate prognostic factors for overall survival in this setting to explore whether the neutrophil-lymphocyte ratio (NLR) had independent prognostic significance. Patients receiving pemetrexed for platinum-resistant advanced UC between 2008 and 2013 were identified. The Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) were used to determine response rate. Kaplan-Meier and Cox regression analyses were used to examine the association of various factors with efficacy and survival outcomes. Hematologic toxicity and laboratory abnormalities were recorded. One hundred and twenty-nine patients were treated with pemetrexed. The objective response rate was 5% (95% confidence interval: 1%-9%), and the median duration of response was 8 months. Median progression-free survival (PFS) was 2.4 months, and the 6-month PFS rate was 14%. There was no significant difference in response rate by age, Eastern Cooperative Oncology Group (ECOG) performance status, or number of prior therapies. On multivariable analysis, ECOG performance status (p < .01), liver metastases (p = .02), and NLR (p < .01) had independent prognostic significance for overall survival. This 129-patient series is the largest reported data set describing pemetrexed use in advanced UC. Activity was modest, although discovery of molecular biomarkers predictive of response would be valuable to identify the small subset of patients who do gain significant benefit. Overall, the data highlight the urgent need to develop novel therapies for these patients. ©AlphaMed Press.

The Safety and Efficacy of Single-Agent Pemetrexed in Platinum-Resistant Advanced Urothelial Carcinoma: A Large Single-Institution Experience

PubMed Central

Benjamin, David J.; Chaim, Joshua L.; Zabor, Emily C.; Sullivan, John; Garcia-Grossman, Ilana R.; Regazzi, Ashley M.; Ostrovnaya, Irina; Apollo, Aryln; Xiao, Han; Voss, Martin H.; Iyer, Gopa; Bajorin, Dean F.; Rosenberg, Jonathan E.

2015-01-01

Background. Pemetrexed is a commonly used treatment for platinum-resistant advanced urothelial carcinoma (UC) based on objective response rates of 8% and 28% in two small phase II studies. To address the discrepancy in reported response rates and to assess efficacy and toxicity outside of a clinical trial setting, we performed a large retrospective analysis of pemetrexed use at Memorial Sloan Kettering Cancer Center. We also investigated candidate prognostic factors for overall survival in this setting to explore whether the neutrophil-lymphocyte ratio (NLR) had independent prognostic significance. Patients and Methods. Patients receiving pemetrexed for platinum-resistant advanced UC between 2008 and 2013 were identified. The Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) were used to determine response rate. Kaplan-Meier and Cox regression analyses were used to examine the association of various factors with efficacy and survival outcomes. Hematologic toxicity and laboratory abnormalities were recorded. Results. One hundred and twenty-nine patients were treated with pemetrexed. The objective response rate was 5% (95% confidence interval: 1%–9%), and the median duration of response was 8 months. Median progression-free survival (PFS) was 2.4 months, and the 6-month PFS rate was 14%. There was no significant difference in response rate by age, Eastern Cooperative Oncology Group (ECOG) performance status, or number of prior therapies. On multivariable analysis, ECOG performance status (p < .01), liver metastases (p = .02), and NLR (p < .01) had independent prognostic significance for overall survival. Conclusion. This 129-patient series is the largest reported data set describing pemetrexed use in advanced UC. Activity was modest, although discovery of molecular biomarkers predictive of response would be valuable to identify the small subset of patients who do gain significant benefit. Overall, the data highlight the urgent need to develop novel therapies for these patients. PMID:25845990

Hematology and immunology studies - The second manned Skylab mission

NASA Technical Reports Server (NTRS)

Kimzey, S. L.; Johnson, P. C.; Ritzman, S. E.; Mengel, C. E.

1976-01-01

The hematologic and immunologic functions of the Skylab 3 astronauts were monitored during the preflight, inflight, and postflight phases of the mission. Plasma protein profiles showed high consistency in all phases. A transient suppression of lymphocyte responsiveness was observed postflight. A reduction in the circulating blood volume due to drops in both the plasma volume and red cell mass was found. The loss of red cell mass is most likely a suppressed erythrypoiesis. The functional integrity of the circulating red cells did not appear to be compromised in the course of flight.

Phase 2 trial of bortezomib in combination with rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with bortezomib, rituximab, methotrexate, and cytarabine for untreated mantle cell lymphoma.

PubMed

Romaguera, Jorge E; Wang, Michael; Feng, Lei; Fayad, Luis E; Hagemeister, Frederick; McLaughlin, Peter; Rodriguez, M Alma; Fanale, Michelle; Orlowski, Robert; Kwak, Larry W; Neelapu, Sattva; Oki, Yasuhiro; Pro, Barbara; Younes, Anas; Samaniego, Felipe; Fowler, Nathan; Hartig, Kimberly; Valentinetti, Marisa; Smith, Judy; Ford, Peggy; Naig, Adam; Medeiros, L Jeffrey; Kantarjian, Hagop M; Goy, Andre

2018-05-03

Although the outcomes of patients with mantle cell lymphoma (MCL) have improved, there is still no cure. Bortezomib has a 33% response rate in relapsed/refractory MCL and has shown additive and/or synergistic effects in preclinical trials with known effective agents. This is a report of a prospective phase 2 trial of bortezomib added to rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (BzR-hyperCVAD)/rituximab, high-dose methotrexate, and high-dose cytarabine (BzR-MA) for 95 patients with newly diagnosed MCL. The overall and complete response rates were 100% and 82%, respectively. Hematologic toxicity was high but expected and did not lead to an increased incidence of neutropenic fever or dose reductions in comparison with a similar reported regimen without bortezomib. After a median follow-up of 44 months, the median overall survival had not been reached, and the time to treatment failure (TTF) was 55 months, which is not different from that of historical controls. BzR-hyperCVAD/BzR-MA at the dose and schedule studied produced high rates of response and a TTF similar to that of historical reports without bortezomib. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

Immune function and hematology of male cotton rats (Sigmodon hispidus) in response to food supplementation and methionine

USGS Publications Warehouse

Webb, R.E.; Leslie, David M.; Lochmiller, R.L.; Masters, R.E.

2003-01-01

We examined effects of supplementation of food quantity and quality (=enhanced methionine) on hematologic and immunologic parameters of wild, but enclosed, adult male cotton rats (Sigmodon hispidus) in north-central Oklahoma. Sheet metal enclosures were stocked with a high density of wild-caught cotton rats (160 animals/ha) and randomly assigned a treatment of no supplementation, mixed-ration supplementation or methionine-enhanced supplementation. Aside from small increases in counts of red blood cells and hematocrit levels, most indices of erythrocytic characteristics were not affected by supplementation with the mixed-ration or enhanced methionine. In contrast, platelet counts were highest in mixed-ration and methionine treatments and counts of total white blood cells were highest with methionine supplementation, albeit relative proportions of different leukocytes did not differ among treatments. Immunologically, neither delayed-type hypersensitivity response nor hemolytic-complement activity differed among treatments. Supplementation of food quantity and quality did not broadly affect hematologic parameters and immune function of male cotton rats, but enhanced platelet and leukocyte counts may confer advantages to overall health. Clarification of the role of such effects on population limitation or regulation requires additional research.

TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients.

PubMed

Bejar, Rafael; Lord, Allegra; Stevenson, Kristen; Bar-Natan, Michal; Pérez-Ladaga, Albert; Zaneveld, Jacques; Wang, Hui; Caughey, Bennett; Stojanov, Petar; Getz, Gad; Garcia-Manero, Guillermo; Kantarjian, Hagop; Chen, Rui; Stone, Richard M; Neuberg, Donna; Steensma, David P; Ebert, Benjamin L

2014-10-23

Only a minority of myelodysplastic syndrome (MDS) patients respond to hypomethylating agents (HMAs), but strong predictors of response are unknown. We sequenced 40 recurrently mutated myeloid malignancy genes in tumor DNA from 213 MDS patients collected before treatment with azacitidine (AZA) or decitabine (DEC). Mutations were examined for association with response and overall survival. The overall response rate of 47% was not different between agents. Clonal TET2 mutations predicted response (odds ratio [OR] 1.99, P = .036) when subclones unlikely to be detected by Sanger sequencing (allele fraction <10%) were treated as wild-type (WT). Response rates were highest in the subset of TET2 mutant patients without clonal ASXL1 mutations (OR 3.65, P = .009). Mutations of TP53 (hazard ratio [HR] 2.01, P = .002) and PTPN11 (HR 3.26, P = .006) were associated with shorter overall survival but not drug response. Murine-competitive bone marrow transplantation followed by treatment with AZA demonstrated that Tet2-null cells have an engraftment advantage over Tet2-WT cells. AZA significantly decreased this advantage for Tet2-null cells (P = .002) but not Tet2-WT cells (P = .212). Overall, Tet2 loss appears to sensitize cells to treatment with AZA in vivo, and TET2 mutations can identify patients more likely to respond to HMAs. © 2014 by The American Society of Hematology.

Efficacy and Biological Correlates of Response in a Phase 2 Study of Venetoclax Monotherapy in Patients with Acute Myelogenous Leukemia

PubMed Central

Konopleva, Marina; Pollyea, Daniel A.; Potluri, Jalaja; Chyla, Brenda; Hogdal, Leah; Busman, Todd; McKeegan, Evelyn; Salem, Ahmed Hamed; Zhu, Ming; Ricker, Justin L.; Blum, William; DiNardo, Courtney D.; Kadia, Tapan; Dunbar, Martin; Kirby, Rachel; Falotico, Nancy; Leverson, Joel; Humerickhouse, Rod; Mabry, Mack; Stone, Richard; Kantarjian, Hagop; Letai, Anthony

2017-01-01

We present a phase 2, single-arm study evaluating 800 mg daily venetoclax, a highly selective, oral small-molecule B-cell leukemia/lymphoma-2 (BCL-2) inhibitor in patients with high-risk relapsed/refractory acute myelogenous leukemia (AML) or unfit for intensive chemotherapy. Responses were evaluated following revised International Working Group (IWG) criteria. The overall response rate was 19%; an additional 19% of patients demonstrated anti-leukemic activity not meeting IWG criteria (partial bone marrow response and incomplete hematologic recovery). Twelve (38%) patients had isocitrate dehydrogenase 1/2 mutations, of whom 4 (33%) achieved complete response/complete response with incomplete blood count recovery. Six (19%) patients had BCL-2–sensitive protein index at screening, which correlated with time on study. BH3 profiling was consistent with on-target BCL-2 inhibition and identified potential resistance mechanisms. Common adverse events included nausea, diarrhea and vomiting (all grades), and febrile neutropenia and hypokalemia (grade 3/4). Venetoclax demonstrated activity and acceptable tolerability in patients with AML and adverse features. PMID:27520294

Post-tonsillectomy hemorrhagic outcomes in children with bleeding disorders at a single institution.

PubMed

Patel, Priyesh N; Arambula, Alexandra M; Wheeler, Allison P; Penn, Edward B

2017-09-01

To report on the post-tonsillectomy bleeding outcomes and factors associated with hemorrhage among children with pre- or post-operatively diagnosed bleeding disorders treated with an institutional protocol. Retrospective cohort study of patients with hematologic disorders who underwent tonsillectomy between 2003 and 2016 and were treated with perioperative desmopressin or factor replacement and/or aminocaproic acid. Postoperative outcomes were compared to controls matched for age, sex, and indication for surgery. Analysis of factors associated with hemorrhage was performed in patients with bleeding disorders using Mann-Whitney U or chi-squared tests. 45 patients with hematologic disorders met inclusion criteria. Platelet dysfunction, including von Willebrand Disease (vWD), was the most common diagnosis (77.8%). Most patients had a preoperative diagnosis of a bleeding disorder and received perioperative hematologic medications (86.7%). Compared to matched controls, patients with hematologic disorders experienced more postoperative bleeding (15.5%; 12 bleeds, 7 patients vs. 1.7%; 1 bleed, 1 patient, p = 0.05) and had longer postoperative stays (1.3 days vs. 0.4 days, p < 0.001). Among the patients with hematologic disorders, patients who experienced a postoperative bleed were significantly more likely to have a factor deficiency (e.g. Hemophilia over vWD) and have a postoperative diagnosis (compared to preoperative diagnosis) for which they did not receive perioperative hematologic medication. Of patients with a postoperative bleed, all those diagnosed postoperatively required at least one surgical intervention to control bleeding compared to 33% of patients with a preoperative diagnosis. A history of post-surgical bleeding, male sex, age at surgery, and pharyngitis as surgical indication were not associated with higher hemorrhage rates in this group. This study suggests a clinically important magnitude of increased bleeding risk in patients with hematologic disease. This risk appears to decrease with the use of an institutional protocol consisting of desmopressin or factor replacement and an antifibrinolytic agent extending through postoperative day 10. Copyright © 2017 Elsevier B.V. All rights reserved.

The Effects of Acute High-Intensity Interval Training on Hematological Parameters in Sedentary Subjects.

PubMed

Belviranli, Muaz; Okudan, Nilsel; Kabak, Banu

2017-07-19

The objective of the study was to determine the effects of acute high-intensity interval training (HIIT) on hematological parameters in sedentary men. Ten healthy, non-smoker, and sedentary men aged between 18 and 24 years participated in the study. All subjects performed four Wingate tests with 4 min intervals between the tests. Blood samples were collected at pre-exercise, immediately after, 3 and 6 h after the fourth Wingate test. Hematological parameters were analyzed in these samples. The results showed that hematocrit percentage, hemoglobin values, red cell count, mean cell volume, platelet count, total white cell count, and counts of the white cell subgroups increased immediately after the acute HIIT and their values began to return to resting levels 3 h after exercise, and completely returned to resting levels 6 h after exercise. In conclusion, acute HIIT causes an inflammatory response in blood.

Atypical Presentation of Herpes Simplex Virus Type 2 Infection Refractory to Treatment With Acyclovir in 2 Hematologic Patients.

PubMed

Nieto Rodríguez, D; Sendagorta Cudós, E; Rueda Carnero, J M; Herranz Pinto, P

2017-12-01

Herpesvirus infections are not uncommon in hematologic patients. Our first patient, diagnosed with chronic lymphatic leukemia, presented extensive genital herpes infection refractory to treatment with acyclovir and with a partial response to foscarnet, which had to be withdrawn due to systemic adverse effects. The second patient, diagnosed with follicular Hodgkin lymphoma, presented hypertrophic herpes infection refractory to treatment with acyclovir but that responded to intralesional cidofovir and topical imiquimod. As in other immunodepressed patients, herpesvirus infection in hematologic patients can present atypical manifestations, as well as resistance to treatments that act via the viral thymidine kinase. A high level of clinical suspicion is therefore needed to make an early diagnosis, together with extensive knowledge of the different treatments available. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Oceans of opportunity: exploring vertebrate hematopoiesis in zebrafish.

PubMed

Carroll, Kelli J; North, Trista E

2014-08-01

Exploitation of the zebrafish model in hematology research has surged in recent years, becoming one of the most useful and tractable systems for understanding regulation of hematopoietic development, homeostasis, and malignancy. Despite the evolutionary distance between zebrafish and humans, remarkable genetic and phenotypic conservation in the hematopoietic system has enabled significant advancements in our understanding of blood stem and progenitor cell biology. The strengths of zebrafish in hematology research lie in the ability to perform real-time in vivo observations of hematopoietic stem, progenitor, and effector cell emergence, expansion, and function, as well as the ease with which novel genetic and chemical modifiers of specific hematopoietic processes or cell types can be identified and characterized. Further, myriad transgenic lines have been developed including fluorescent reporter systems to aid in the visualization and quantification of specified cell types of interest and cell-lineage relationships, as well as effector lines that can be used to implement a wide range of experimental manipulations. As our understanding of the complex nature of blood stem and progenitor cell biology during development, in response to infection or injury, or in the setting of hematologic malignancy continues to deepen, zebrafish will remain essential for exploring the spatiotemporal organization and integration of these fundamental processes, as well as the identification of efficacious small molecule modifiers of hematopoietic activity. In this review, we discuss the biology of the zebrafish hematopoietic system, including similarities and differences from mammals, and highlight important tools currently utilized in zebrafish embryos and adults to enhance our understanding of vertebrate hematology, with emphasis on findings that have impacted our understanding of the onset or treatment of human hematologic disorders and disease. Copyright © 2014 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

CHOEP-21 chemotherapy for newly diagnosed nodal peripheral T-cell lymphomas (PTCLs) in Maharaj Nakorn Chiang Mai Hospital.

PubMed

Rattarittamrong, Ekarat; Norasetthada, Lalita; Tantiworawit, Adisak; Chai-Adisaksopha, Chatree; Nawarawong, Weerasak

2013-11-01

To determine the effectiveness and tolerability of the combination of chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) with the addition of etoposide (CHOEP-21) for newly diagnosed nodal peripheral T-cell lymphomas (PTCLs). Between January 2009 and October 2011, patients aged 18 to 60 years with newly diagnosed nodal PTCLs at the Maharaj Nakorn Chiang Mai Hospital were enrolled to receive CHOEP-21 every three weeks for eight cycles. G-CSF prophylaxis was given to all patients. Twenty-four patients were enrolled. Twenty of them were male with a median age of 49 years. The majority of patients (66.7%) had PTCL, not otherwise specified (PTCL, NOS), and 95.8% of the patients were in stage III or IV. The overall response rate was 58% with 42% having complete response. The response rates were better among patients with ALK-negative anaplastic large cell lymphoma (ALCL; 100%) and angioimmunoblastic T-cell lymphoma (AITL; 85%) than those with PTCL, NOS (44%). With a median follow-up of 21 months, the patients had an estimated 2-year event-free survival, and an overall survival rate of 37.6% and 54.4%, respectively. The most common adverse effects were infection and hematologic toxicities that was manageable. Although CHOEP-21 induced favorable responses in patients with ALK-negative ALCL and AITL, the responses were not durable and further therapy is mandated in management of patients with nodal PTCL.

Factors Associated With the Career Choices of Hematology and Medical Oncology Fellows Trained at Academic Institutions in the United States

PubMed Central

Horn, Leora; Koehler, Elizabeth; Gilbert, Jill; Johnson, David H.

2011-01-01

Purpose Factors that influence hematology-oncology fellows' choice of academic medicine as a career are not well defined. We undertook a survey of hematology-oncology fellows training at cancer centers designated by the National Cancer Institute (NCI) and the National Comprehensive Cancer Network (NCCN) to understand the factors fellows consider when making career decisions. Methods Program directors at all NCI and NCCN cancer centers were invited to participate in the study. For the purpose of analysis, fellows were grouped into three groups on the basis of interest in an academic career. Demographic data were tested with the Kruskal-Wallis test and χ2 test, and nondemographic data were tested by using the multiscale bootstrap method. Results Twenty-eight of 56 eligible fellowship programs participated, and 236 fellows at participating institutions responded (62% response rate). Approximately 60% of fellows graduating from academic programs in the last 5 years chose academic career paths. Forty-nine percent of current fellows ranked an academic career as extremely important. Fellows choosing an academic career were more likely to have presented and published their research. Additional factors associated with choosing an academic career included factors related to mentorship, intellect, and practice type. Fellows selecting nonacademic careers prioritized lifestyle in their career decision. Conclusion Recruitment into academic medicine is essential for continued progress in the field. Our data suggest that fewer than half the current fellows training at academic centers believe a career in academic medicine is important. Efforts to improve retention in academics should include focusing on mentorship, research, and career development during fellowship training and improving the image of academic physicians. PMID:21911716

Automated in-clinic hematology instruments for small animal practitioners: what is available, what can they really do, and how do i make a choice?

PubMed

Welles, Elizabeth G

2012-01-01

To have an in-clinic hematology instrument in your practice and how it is used are decisions that precede the purchase of an instrument. Advantages and limitations of the various instruments should be considered. Initial purchase cost, reagent/disposable costs, costs of training personnel in the use and care of the instrument, and service/repair contract costs need to be considered. Once the decision is made to have an in-office hematology instrument in your practice you should benefit from having nearly immediate CBC data results that enable you to provide better quality medicine, more rapid clinical decisions, more closely monitor patients for complications of disease or response to treatment. It should also generate revenue and allow some of your staff members to expand and develop their technical skills as they learn the nuances of a new diagnostic tool and how to provide you with the most accurate CBC information. In the final assessment, the addition of an in-office hematology instrument should improve the quality and efficiency of the medical care you provide patients and generate additional practice income.

Bromelain has significant clinical benefits after extraction of the third molar during chemotherapy in patients with hematologic tumor.

PubMed

Tan, Yi; Li, Ping

2018-03-01

The purpose of this study was to investigate the application of bromelain in the treatment of pain, swelling, and limited mouth opening in patients with hematologic tumor after extraction of the third molar during chemotherapy. We recruited 72 patients with hematologic tumor who were treated by oral and maxillofacial surgery in our hospital, and third molar extraction was performed under local anesthesia. After extraction, patients in the control group were treated with cold - hot compress and patients in the experimental group were treated by oral administration of bromelain. One, three, and seven days after extraction, pain, swelling, and mouth opening in the experimental group improved compared to the control group. Additionally, the levels of IL-25 and TNF-α in the experimental group were significantly lower than in the control group, suggesting less inflammatory response. On the other hand, EGFR and β-FGF were significantly higher in the experimental group, supporting the activation of tissue repair pathways. Quality of life scores were significantly better in the experimental group. Overall, bromelain improves the quality of life, alleviates pain, swelling, and mouth opening, and effectively prevent postoperative complications in patients with hematologic tumors after third molar extraction during chemotherapy.

Hematology journals do not sufficiently adhere to reporting guidelines: a systematic review.

PubMed

Wayant, C; Smith, C; Sims, M; Vassar, M

2017-04-01

Essentials Reporting guidelines and trial/review registration aim to limit bias in research. We systematically reviewed hematology journals to examine the use of these policies. Forty-eight percent of journals made no use of these policies. Improving the use of reporting guidelines will improve research for all stakeholders. Background Reporting guidelines and trial/review registration policies have been instituted in order to minimize bias and improve research practices. Objective The objective of this study was to investigate the policies of hematology journals concerning reporting guideline adoption and trial/review registration. Methods We performed a web-based data abstraction from the Instructions for Authors of 67 hematology journals catalogued in the Expanded Science Citation Index of the 2014 Journal Citation Reports to identify whether each journal required, recommended or made no mention of the following reporting guidelines: EQUATOR, ICMJE, CONSORT, MOOSE, QUOROM, PRISMA, STARD, STROBE, ARRIVE and CARE. We also extracted whether journals required or recommended trial or systematic review registration. We e-mailed editors three times to determine which types of studies their journal accepts. Results Forty-eight per cent (32/67) of hematology journals do not adhere to any reporting guidelines. For responding journals, the QUOROM statement, MOOSE, CARE and PROSPERO were the least often mentioned, whereas the ICMJE guidelines, CONSORT statement and general trial registration were most often mentioned. Discussion Reporting guidelines are infrequently required or recommended by hematology journals. Furthermore, few require clinical trial or systematic review database registration. A higher rate of adherence to reporting guidelines can prevent bias from entering the literature. Participation from all stakeholders, including authors and journal editors, to improve reporting guideline and policy practices is required. © 2017 International Society on Thrombosis and Haemostasis.

Phase 2 randomized study of bortezomib-melphalan-prednisone with or without siltuximab (anti–IL-6) in multiple myeloma

PubMed Central

San-Miguel, Jesús; Bladé, Joan; Shpilberg, Ofer; Grosicki, Sebastian; Maloisel, Frédéric; Min, Chang-Ki; Polo Zarzuela, Marta; Robak, Tadeusz; Prasad, Sripada V. S. S.; Tee Goh, Yeow; Laubach, Jacob; Spencer, Andrew; Mateos, María-Victoria; Palumbo, Antonio; Puchalski, Tom; Reddy, Manjula; Uhlar, Clarissa; Qin, Xiang; van de Velde, Helgi; Xie, Hong; Orlowski, Robert Z.

2014-01-01

Because interleukin-6 (IL-6) is considered important in the proliferation of early multiple myeloma (MM), we hypothesized that the addition of the anti-IL-6 monoclonal antibody siltuximab to the bortezomib-melphalan-prednisone (VMP) regimen would improve outcomes in transplant-ineligible patients with newly diagnosed MM. One hundred and six patients were randomized to receive 9 cycles of VMP or VMP plus siltuximab (11 mg/kg every 3 weeks) followed by siltuximab maintenance. Baseline characteristics were well balanced except for immunoglobulin A subtype and 17p deletions. With a complete response (CR) rate of 27% on siltuximab plus VMP (S+VMP) and 22% on VMP, the study did not confirm its hypothesis that the addition of siltuximab would increase the CR rate by at least 10%. Overall response rate was 88% on S+VMP and 80% on VMP, and at least very good partial response rates were 71% and 51% (P = .0382), respectively. Median progression-free survival (17 months) and 1-year overall survival (88%) were identical in the 2 arms. Grade ≥3 adverse-event incidence was 92% on S+VMP and 81% on VMP (P = .09), with trends toward more hematologic events and infections on S+VMP. Maintenance therapy with siltuximab was well tolerated. In conclusion, the addition of siltuximab to VMP did not improve the CR rate or long-term outcomes. This study was registered at http://clinicaltrials.gov as #NCT00911859. PMID:24833354

Clinical outcome and prognostic markers for patients with gynecologic malignancies in phase 1 clinical trials: a single institution experience from 1999 to 2010.

PubMed

Hou, June Y; Aparo, Santiago; Ghalib, Mohammad; Chaudhary, Imran; Shah, Umang; Swami, Umang; Einstein, Mark; Goldberg, Gary L; Mani, Sridhar; Goel, Sanjay

2013-10-01

There is a scarcity of outcome data regarding phase 1 trials for patients with gynecologic malignancy. The objective of this study was to assess toxicity, clinical benefit and prognosticators in gynecologic oncology patients participating in phase 1 trials. All phase 1 oncology trials conducted at Albert Einstein Cancer Center from 1999 to 2010 were reviewed and extracted for relevant demographic and clinical data concerning patients with gynecologic malignancy. Cox-proportional and logistic regression modeling were used for multivariate analysis. 120 distinct patients with gynecologic malignancy participated in 41 trials, constituting 30.6% of all phase 1 patients enrolled in the same time period. The median age is 59 years. Out of the 184 patients enrolled, 160 individual responses were evaluable. Seventeen DLT events (9.2%) occurred, including 1 (0.5%) treatment-related mortality. There were 27.2%≥ grade 3 hematologic and 24.4% non-hematologic toxicity. Eighty patients had stable disease (SD, 50%), including 21.9% with SD ≥ 4 months, 11 (6.3%) with partial response (PR), and 3 (1.9%) achieving complete response (CR). The clinical benefit rate (CBR=SD+CR+PR) was 58.1%. Albumin (Alb)≤ 3.5 g/dL and abnormal ANC were independent negative prognosticators of survival. We also found a continuous correlation between changes in Albumin (p=0.02) and LDH (p=0.02) and odds of achieving CBR≥4month. Our clinical outcome and safety data suggested that phase 1 trials may be a reasonable option for patients with advanced and recurrent gynecologic cancer. The potential prognosticators identified should be further validated in larger trials. © 2013.

[Comparison of 1 mg/body and 3 mg/body of intravenous granisetron for the prevention of chemotherapy-induced nausea and vomiting and adverse events in hematological malignancy patients].

PubMed

Motohashi, Shinya; Hori, Katsuhito; Ono, Takaaki; Ohnishi, Kazunori; Kawakami, Junichi

2012-01-01

Granisetron is a selective 5-hydroxy tryptamine3 receptor antagonist and widely used for chemotherapy-induced nausea and vomiting (CINV). Recommended dose of intravenous granisetron in the USA and Europe has been set at 0.01 mg/kg (1 mg/body) in the antiemetic treatment guidelines established by the American Society of Clinical Oncology and National Comprehension Cancer Network. In contrast, the approved dose in Japan is 0.04 mg/kg (3 mg/body). Randomized controlled trials (RCTs) which compared 1 mg/body with 3 mg/body of intravenous granisetron for CINV had been reported in Japan. In these RCTs, however, hematological malignancy patients were excluded. We performed observational retrospective study to compare 1 mg/body with 3 mg/body of intravenous granisetron for the prevention of CINV and adverse events in hematological malignancy patients. Number of the patients and chemotherapy courses were 15 and 30 in the 1 mg/body group, and 15 and 27 in the 3 mg/body group, respectively. No nausea rates in the 1 and 3 mg/body group were 83% and 89% of courses, respectively. No vomiting rates in the 1 and 3 mg/body group were 97% and 100% of courses, respectively. The incidences of constipation in the 1 and 3 mg/body group were 34% and 45% of courses, respectively. Anaphylaxis and headache did not occur in both groups. Our findings suggested that 1 mg/body of intravenous granisetron can prevent from CINV in hematological malignancy patients, as well as 3 mg/body.

Potential drug interactions and chemotoxicity in older patients with cancer receiving chemotherapy.

PubMed

Popa, Mihaela A; Wallace, Kristie J; Brunello, Antonella; Extermann, Martine; Balducci, Lodovico

2014-07-01

Increased risk of drug interactions due to polypharmacy and aging-related changes in physiology among older patients with cancer is further augmented during chemotherapy. No previous studies examined potential drug interactions (PDIs) from polypharmacy and their association with chemotherapy tolerance in older patients with cancer. This study is a retrospective medical chart review of 244 patients aged 70+ years who received chemotherapy for solid or hematological malignancies. PDI among all drugs, supplements, and herbals taken with the first chemotherapy cycle were screened for using the Drug Interaction Facts software, which classifies PDIs into five levels of clinical significance with level 1 being the highest. Descriptive and correlative statistics were used to describe rates of PDI. The association between PDI and severe chemotoxicity was tested with logistic regressions adjusted for baseline covariates. A total of 769 PDIs were identified in 75.4% patients. Of the 82 level 1 PDIs identified among these, 32 PDIs involved chemotherapeutics. A large proportion of the identified PDIs were of minor clinical significance. The risk of severe non-hematological toxicity almost doubled with each level 1 PDI (OR=1.94, 95% CI: 1.22-3.09), and tripled with each level 1 PDI involving chemotherapeutics (OR=3.08, 95% CI: 1.33-7.12). No association between PDI and hematological toxicity was found. In this convenience sample of older patients with cancer receiving chemotherapy we found notable rates of PDI and a substantial adjusted impact of PDI on risk of non-hematological toxicity. These findings warrant further research to optimize chemotherapy outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

Acute Hematological Effects in Mice Exposed to the Expected Doses, Dose-rates, and Energies of Solar Particle Event-like Proton Radiation

PubMed Central

Sanzari, Jenine K.; Cengel, Keith A.; Wan, X. Steven; Rusek, Adam; Kennedy, Ann R.

2014-01-01

NASA has funded several projects that have provided evidence for the radiation risk in space. One radiation concern arises from solar particle event (SPE) radiation, which is composed of energetic electrons, protons, alpha particles and heavier particles. SPEs are unpredictable and the accompanying SPE radiation can place astronauts at risk of blood cell death, contributing to a weakened immune system and increased susceptibility to infection. The doses, dose rates, and energies of the proton radiation expected to occur during a SPE have been simulated at the NASA Space Radiation Laboratory, Brookhaven National Laboratory, delivering total body doses to mice. Hematological values were evaluated at acute time points, up to 24 hrs. post-radiation exposure. PMID:25202654

Bortezomib in multiple myeloma and lymphoma: a systematic review and clinical practice guideline.

PubMed

Reece, D; Imrie, K; Stevens, A; Smith, C A

2006-10-01

In patients with multiple myeloma, Waldenström macroglobulinemia, or lymphoma, what is the efficacy of bortezomib alone or in combination as measured by survival, quality of life, disease control (for example, time to progression), response duration, or response rate?What is the toxicity associated with the use of bortezomib?Which patients are more or less likely to benefit from treatment with bortezomib? Evidence was selected and reviewed by two members of the Hematology Disease Site Group and by methodologists from the Program in Evidence-based Care (pebc) at Cancer Care Ontario. The practice guideline report was reviewed and approved by the Hematology Disease Site Group, which comprises hematologists, medical and radiation oncologists, and a patient representative. As part of an external review process, the report was disseminated to practitioners throughout Ontario to obtain their feedback. Outcomes of interest were overall survival, quality of life, response rates and duration, and rates of adverse events. A systematic search was conducted of the medline, embase, HealthStar, cinahl, and Cochrane Library databases for primary articles and practice guidelines. The resulting evidence informed the development of clinical practice recommendations. Those recommendations were appraised by a sample of practitioners in Ontario and modified in response to the feedback received. The systematic review and modified recommendations were approved by a review body w theithin pebc. The literature review found one randomized controlled trial (rct)-the only published rct of bortezomib in relapsed myeloma. A number of phase ii studies were also retrieved, including a randomized phase ii study. No randomized trials were retrieved for lymphoma. The rct found bortezomib to be superior to high-dose dexamethasone for median time to progression and 1-year survival in patients with relapsed myeloma, although grade 3 adverse events were more common in the bortezomib arm. Bortezomib is recommended as the preferred treatment option in patients with myeloma relapsing within 1 year of the conclusion of initial treatment; it may also be a reasonable option in patients relapsing at least 1 year after autologous stem-cell transplantation. This evidence-based series applies to adult patients with myeloma, Waldenström macroglobulinemia, or lymphoma of any type, stage, histology, or performance status. Based on the results of a large well-conducted rct, which represents the only published randomized study in relapsed myeloma, the Hematology Disease Site Group (dsg) offers the following recommendations: For patients with myeloma refractory to or relapsing within 1 year of the conclusion of initial or subsequent treatment or treatments, including autologous stem-cell transplantation, and who are candidates for further chemotherapy, bortezomib is recommended as the preferred treatment option.Bortezomib is also a reasonable option for patients relapsing at least 1 year after autologous stem-cell transplantation. The dsg is aware that thalidomide, alkylating agents, or repeat transplantation may also be options for these patients. However, evaluation of these other options is beyond the scope of this practice guideline.For patients with myeloma relapsing at least 1 year after the conclusion of alkylating agent-based chemotherapy who are candidates for further chemotherapy, further treatment with alkylating agent-based chemotherapy is recommended.Evidence is insufficient to support the use of bortezomib in patients with non-Hodgkin lymphoma or Waldenström macroglobulinemia outside of clinical trials. Limited evidence supports the appropriateness of a specific time-to-relapse period as being indicative of treatment-insensitive disease. The 1-year threshold provided in the foregoing recommendations is based on the opinion of the Hematology dsg. For specific details related to the administration of bortezomib therapy, the dsg suggests that clinicians refer to the protocols used in major trials. Some of those details are provided here for informational purposes. Bortezomib 1.3,g/m(2) is given as a rapid intravenous bolus over 3-5 seconds on days 1, 4, 8, and 11 of a 21-day cycle; a minimum of 72 hours between doses is required to allow for recovery of normal proteasome function. Vital signs should be checked before and after each dose. A complete blood count is recommended before each dose, with blood chemistries (including electrolyte and creatinine levels) monitored at a minimum on days 1 and 8 of each cycle. The dose of bortezomib should be reduced or held immediately upon development of painful neuropathy, as described in the product monograph; dose modification may also be required for peripheral sensory neuropathy without pain or for other toxicities. Most toxicities are reversible if dose modification guidelines are followed. RESPONSE TO TREATMENT: Responses are usually apparent by 6 weeks (2 cycles). For patients achieving complete remission (determined by negative electrophoresis and immunofixation), bortezomib should be given for 2 additional cycles beyond the date of confirmed complete remission. In patients with progressive disease after 2 cycles or stable disease after 4 cycles, dexamethasone added to the bortezomib regimen (20 mg by mouth the day of and the day after each bortezomib dose) may produce an objective response. Bortezomib (with or without dexamethasone) should be continued in patients showing benefit from therapy (excluding those in complete remission) unless disease progression or significant toxicity is observed. Therapy should be discontinued in patients who do not respond to bortezomib alone if disease progression is seen within 2 cycles of the addition of dexamethasone. The Hematology dsg recognizes that thalidomide is an active agent in multiple myeloma patients who have relapsed after autologous stem-cell transplantation or who are refractory to alkylating agent-based chemotherapy. To date, no reported rcts have evaluated thalidomide in this role, and specifically, no trials have compared thalidomide with bortezomib. Given these limitations, the members of the Hematology dsg regard thalidomide or bortezomib as therapy alternatives to dexamethasone.

Erythrocyte Sedimentation Rate Levels among a Sample of Pregnant Women Attending Health Centers in Erbil-Iraq

ERIC Educational Resources Information Center

Khazal, Suhad Ali; Zangana, Jwan M. Sabir

2016-01-01

There are so many significant hematological changes occurring in pregnancy, erythrocyte sedimentation rate (ESR) is one of them. The objectives of this study were to determine the range of erythrocyte sedimentation rate values obtained in healthy pregnant women and to examine the effect of gestational age and hemoglobin concentration on…

Physical and Physiological Characteristics of Judo Athletes: An Update

PubMed Central

Torres-Luque, Gema; Hernández-García, Raquel; Escobar-Molina, Raquel; Garatachea, Nuria; Nikolaidis, Pantelis T.

2016-01-01

Judo competition is characterized structurally by weight category, which raises the importance of physiological control training in judo. The aim of the present review was to examine scientific papers on the physiological profile of the judokas, maintenance or loss of weight, framing issues, such as anthropometric parameters (body fat percentage), heart rate responses to training and combat, maximal oxygen uptake, hematological, biological and hormones indicators. The values shown in this review should be used as a reference for the evaluation of physical fitness and the effectiveness of training programs. Hence, this information is expected to contribute to the development of optimal training interventions aiming to achieve maximum athletic performance and to maintain the health of judokas.

Rituximab, methotrexate, procarbazine, vincristine and intensified cytarabine consolidation for primary central nervous system lymphoma (PCNSL) in the elderly: a LOC network study.

PubMed

Houillier, Caroline; Ghesquières, Hervé; Chabrot, Cécile; Soussain, Carole; Ahle, Guido; Choquet, Sylvain; Nicolas-Virelizier, Emmanuelle; Bay, Jacques-Olivier; Vargaftig, Jacques; Gaultier, Claude; Touitou, Valérie; Martin-Duverneuil, Nadine; Cassoux, Nathalie; Le Garff-Tavernier, Magali; Costopoulos, Myrto; Faurie, Pierre; Hoang-Xuan, Khê

2017-06-01

Primary CNS lymphoma (PCNSL) is chemosensitive to high-dose methotrexate-based chemotherapy. However, responses in the elderly are short-lasting and outcome is poor. Given that radiotherapy and intensive chemotherapy expose elderly to severe toxicities, alternative consolidation approaches need to be evaluated. In this multicenter study, we retrospectively analyzed consecutive patients with newly-diagnosed PCNSL, aged >60, treated with a (R)-MPV-AAA regimen. The regimen consisted of three 28-day cycles of methotrexate (3.5 g/m 2 D1, D15), procarbazine, vincristine, followed by three 28-day cycles of cytarabine consolidation (3 g/m 2 D1-2). Addition of rituximab (375 mg/m 2 D1) was optional. The results were compared with the historical MPV-A regimen. Ninety patients received the (R)-MPV-AAA regimen with (n = 39) or without (n = 51) rituximab. Median age was 68 and median KPS 60. 55% of patients achieved a complete response, 8% a partial response and 37% progressed. The median PFS was 10 months, the median OS 28.1 months. Toxicity was mainly hematological, with 54 and 51% of grade III-IV neutropenia and thrombopenia. The response rate was higher in patients receiving rituximab (77 vs. 53%; p = 0.03), whereas no difference was observed in terms of PFS or OS. When comparing the results to the historical MPV-A, there was no difference in terms of response rate, PFS or OS, but a higher rate of hematotoxicity. This study suggests that extending cytarabine consolidation after methotrexate-based chemotherapy does not improve the MPV-A efficacy but increases toxicity in the elderly. The addition of rituximab may improve the response rate, but its impact on final outcome remains unclear.

[Adriamycin, cyclophosphamide, ftorafur and tamoxifen (ACFT) in patients with advanced breast cancer].

PubMed

Imajo, K; Ogawa, M; Horikoshi, N; Inoue, K; Mukaiyama, T; Ozeki, H; Nagamine, D; Shinagawa, K; Fukutani, H

1988-01-01

One hundred and six patients with advanced breast cancer were treated with chemoendocrine therapy consisting of adriamycin (40 mg/m2) i.v. on day 1 and cyclophosphamide (130 mg/m2) i.v. daily for 5 days every 3 weeks, ftorafur (500 mg/m2) and tamoxifen (40 mg) orally daily. Of 82 evaluable patients, 16 showed complete response (20%), 32 partial response (39%), 32 no change (39%), and two progressive disease (2%). The overall response rate was 59%, and the median duration of response was 16.3 (3.5-67+) months with a median survival time from the start of chemoendocrine therapy of 25.5 (3.5-67+) months. The median survival time of responders (32.5 months) was significantly longer than that of non-responders (15.3 months). The major toxicities were hair loss, G1 symptoms, and hematological toxicity, but these were clinically well tolerated. No serious cardiac, renal or liver damage was seen. These results indicated that the addition of tamoxifen to the ACF regimen increased the number of complete responses and prolonged the survival time of responders.

Post-marketing surveillance of thrombomodulin alfa, a novel treatment of disseminated intravascular coagulation - safety and efficacy in 1,032 patients with hematologic malignancy.

PubMed

Asakura, Hidesaku; Takahashi, Hoyu; Tsuji, Hajime; Matsushita, Tadashi; Ninomiya, Hideyuki; Honda, Goichi; Mimuro, Jun; Eguchi, Yutaka; Kitajima, Isao; Sakata, Yoichi

2014-03-01

Post-marketing surveillance of thrombomodulin alfa (TM-α) was performed to evaluate safety and efficacy in patients with disseminated intravascular coagulation (DIC) with hematologic malignancy. All patients treated with TM-α from May 2008 to April 2010 in Japan were included. Information about baseline characteristics, safety, and efficacy were collected. The DIC resolution rate, survival rate on Day 28 after the last TM-α administration, and changes in DIC score and coagulation tests were evaluated. The underlying diseases associated with DIC were acute myeloid leukemia (except for acute promyelocytic leukemia, n=350), lymphoma (n=199), acute promyelocytic leukemia (n=172), acute lymphoblastic leukemia (n=156), myelodysplastic syndromes (n=61), and other (n=94). The incidence rates of bleeding-related adverse events and adverse drug reactions were 17.8% and 4.6%, respectively. In subjects with bleeding symptoms at baseline, 55.0% were assessed as disappeared or improved based on symptoms after TM-α treatment. The DIC resolution and survival rates were 55.9% and 70.7%, respectively. The DIC score and coagulation tests including thrombin-antithrombin complex (TAT) were significantly improved. Coagulation tests were significantly improved after TM-α treatment even in subjects whose clinical course of underlying disease was assessed as unchanged or exacerbated. This surveillance confirmed the safety and efficacy of TM-α in clinical practice, thus TM-α may be an ideal treatment for patients with DIC based upon hematologic malignancy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Utilization of stat test priority in the clinical laboratory: a College of American Pathologists q-probes study of 52 institutions.

PubMed

Volmar, Keith E; Wilkinson, David S; Wagar, Elizabeth A; Lehman, Christopher M

2013-02-01

Utilization of stat testing priority is a balance between safe, efficient patient management and resource expenditure. To determine the rate of stat testing, compare rates among institutions, and determine the distribution of turnaround time expectations for different turnaround time priorities. During a 7-day period, participants prospectively determined the total number of chemistry, hematology, and coagulation billable tests from inpatients and emergency department patients. Among these, the total numbers of billable tests performed stat were identified. Laboratories also reported the levels of test priority they offered and turnaround expectations for each level of test priority. Fifty institutions submitted data for the study, with 2 additional participants submitting partial results. Participants identified 639 589 chemistry, hematology, and coagulation billable tests, with 229 896 (35.9%) performed stat. The stat rate varied from 21.3% at the 10th percentile to 55.4% at the 90th percentile, with a median of 37.0% of participants' tests performed stat. Laboratories include a mean of 206 tests in chemistry, hematology, and coagulation test menus, with 67% of these tests offered stat. The fraction of the test menu offered stat varied from 29.0% at the 10th percentile to 97.8% at the 90th percentile, with a median of 73.3% of tests on the menu offered stat. The most common number of testing priorities offered by participating laboratories was 3 (44.2%). Among the 52 participating laboratories, the median stat testing rate was 37.0% and a median 73.3% of the test menu was offered stat.

Nosocomial infections among pediatric hematology/oncology patients: results of a prospective incidence study.

PubMed

Urrea, Mireya; Rives, Susana; Cruz, Ofelia; Navarro, Albert; García, Juan José; Estella, Jesús

2004-06-01

Nosocomial infections (NI) are an important clinical complication in adult and children patients at the different hospital wards. NI cause considerable morbidity and mortality and are associated with prolonged hospital stay and increased health care costs. The objective of this study was to describe the incidence of NI in pediatric patients with neoplastic disease as a first step toward improving infection control policies. A prospective surveillance study from March through May 2001 was performed in the pediatric hematology/oncology unit at the University Hospital in Barcelona. The Centers for Disease Control and Prevention criteria were used as standard definition for NI. NI rates were calculated as a density incidence rate (per 100 patient-days). Fifty-one patients were admitted during the study period. Twelve patients had a total of 18 NI. The incidence of NI was 1.77 per 100 patient-days. Patients with acute lymphoblastic leukemia had the highest NI rate (2.71 per 100 patient-days). The most frequent episodes of NI were bacteremia (55.5%) and fever of unknown origin (16.6%). The most frequently isolated microorganisms were gram-positive bacteria (78.6%). Coagulase-negative Staphylococci were the most common isolates in bacteremias (70%). The extrinsic risk factors related with the highest incidence rates of NI per 100 patient-days were central venous catheterization (1.7 infections) and parenteral nutrition (3.2 infections). Extrinsic risk factors associated with NI have been identified in this high-risk population. These findings suggest the need to evaluate the infection control measures to reduce the morbidity and mortality in a hematology/oncology unit.

Randomized phase II trial of carboplatin versus paclitaxel and carboplatin in platinum-sensitive recurrent advanced ovarian carcinoma: a GEICO (Grupo Espanol de Investigacion en Cancer de Ovario) study.

PubMed

González-Martín, A J; Calvo, E; Bover, I; Rubio, M J; Arcusa, A; Casado, A; Ojeda, B; Balañá, C; Martínez, E; Herrero, A; Pardo, B; Adrover, E; Rifá, J; Godes, M J; Moyano, A; Cervantes, A

2005-05-01

The aim of this study was to determine whether the response rate for the paclitaxel-carboplatin combination is superior to carboplatin alone in the treatment of patients with platinum-sensitive recurrent ovarian carcinoma. Patients with recurrent ovarian carcinoma, 6 months after treatment with a platinum-based regimen and with no more than two previous chemotherapy lines, were randomized to receive carboplatin area under the curve (AUC) 5 (arm A) or paclitaxel 175 mg/m(2) + carboplatin AUC 5 (arm B). The primary end point was objective response, following a 'pick up the winner' design. Secondary end points included time to progression (TTP), overall survival, tolerability and quality of life (QoL). Eighty-one patients were randomized and included in the intention-to-treat analysis. The response rate in arm B was 75.6% [26.8% complete response (CR) + 48.8% partial response (PR)] [95% confidence interval (CI) 59.7% to 87.6%] and 50% in arm A (20% CR + 30% PR) (95% CI 33.8% to 66.2%). No significant differences were observed in grade 3-4 hematological toxicity. Conversely, mucositis, myalgia/arthralgia and peripheral neurophaty were more frequent in arm B. Median TTP was 49.1 weeks in arm B (95% CI 36.9-61.3) and 33.7 weeks in arm A (95% CI 25.8-41.5). No significant differences were found in the QoL analysis. Paclitaxel-carboplatin combination is a tolerable regimen with a higher response rate than carboplatin monotherapy in platinum-sensitive recurrent ovarian carcinoma.

Effect of feeding different levels of Azolla pinnata on blood biochemicals, hematology and immunocompetence traits of Chabro chicken

PubMed Central

Mishra, Deepesh Bharat; Roy, Debashis; Kumar, Vinod; Bhattacharyya, Amitav; Kumar, Muneendra; Kushwaha, Raju; Vaswani, Shalini

2016-01-01

Aim: The present study was conducted to see the effect of feeding different levels of Azolla meal on blood biochemicals, hematology and immunocompetence traits of Chabro chicken. Materials and Methods: The study was conducted on 160 Chabro chicks, which were randomly divided into four treatment groups each with four replicates of 10 birds. The first treatment (T1) served as a control in which basal diets was offered without Azolla supplementation while in T2, T3, and T4 groups, basal diet was replaced with Azolla meal at 5%, 7.5%, and 10% levels, respectively. A feeding trial was conducted upto 8 weeks. At the last week of trial, blood samples were collected randomly from one bird of each replicate and plasma was separated to estimate certain biochemical parameters, some blood metabolites, minerals and enzymes like alanine aminotransferase and aspartate aminotransferase (AST). Hematological parameters such as hemoglobin, packed cell volume, total leukocytes count and differential leukocytes count were estimated in fresh blood just after collection. The humoral immune response was measured against sheep red blood cells,and cell-mediated immune response was measured against phyto hemagglutinin lectin from Phaseolus vulgaris (PHA-P). Results: The study showed that hematological profile of the Chabro bird was not affected by any treatment except heterophil and lymphocyte which was found higher in T2 and T3 groups and eosinophil was found higher in a T3 group than control. Blood glucose, creatinine, cholesterol, total protein, albumin, uric acid, and triglycerides were found similar in all the groups and within the normal values for broiler chicken. Liver enzymes and macro mineral content in blood were found similar in all the treatment groups and within normal physiological range. Although AST was found higher in 10% replacement group than control, the value was within normal range for broiler chicken. Although antibody titer was found similar in all the experimental groups in the present study, cell-mediate immune response (response to PHA-P) was found higher in 5%, 7.5%, and 10% replacement groups than control(p<0.05). Conclusion: Similar blood biochemical parameters and higher cell-mediated immune response in Azolla replacement group indicated immune-modulatory effect of Azolla meal without any toxicity. PMID:27051207

Effect of feeding different levels of Azolla pinnata on blood biochemicals, hematology and immunocompetence traits of Chabro chicken.

PubMed

Mishra, Deepesh Bharat; Roy, Debashis; Kumar, Vinod; Bhattacharyya, Amitav; Kumar, Muneendra; Kushwaha, Raju; Vaswani, Shalini

2016-02-01

The present study was conducted to see the effect of feeding different levels of Azolla meal on blood biochemicals, hematology and immunocompetence traits of Chabro chicken. The study was conducted on 160 Chabro chicks, which were randomly divided into four treatment groups each with four replicates of 10 birds. The first treatment (T1) served as a control in which basal diets was offered without Azolla supplementation while in T2, T3, and T4 groups, basal diet was replaced with Azolla meal at 5%, 7.5%, and 10% levels, respectively. A feeding trial was conducted upto 8 weeks. At the last week of trial, blood samples were collected randomly from one bird of each replicate and plasma was separated to estimate certain biochemical parameters, some blood metabolites, minerals and enzymes like alanine aminotransferase and aspartate aminotransferase (AST). Hematological parameters such as hemoglobin, packed cell volume, total leukocytes count and differential leukocytes count were estimated in fresh blood just after collection. The humoral immune response was measured against sheep red blood cells,and cell-mediated immune response was measured against phyto hemagglutinin lectin from Phaseolus vulgaris (PHA-P). The study showed that hematological profile of the Chabro bird was not affected by any treatment except heterophil and lymphocyte which was found higher in T2 and T3 groups and eosinophil was found higher in a T3 group than control. Blood glucose, creatinine, cholesterol, total protein, albumin, uric acid, and triglycerides were found similar in all the groups and within the normal values for broiler chicken. Liver enzymes and macro mineral content in blood were found similar in all the treatment groups and within normal physiological range. Although AST was found higher in 10% replacement group than control, the value was within normal range for broiler chicken. Although antibody titer was found similar in all the experimental groups in the present study, cell-mediate immune response (response to PHA-P) was found higher in 5%, 7.5%, and 10% replacement groups than control(p<0.05). Similar blood biochemical parameters and higher cell-mediated immune response in Azolla replacement group indicated immune-modulatory effect of Azolla meal without any toxicity.

Relationship of Salmonella infection and inflammatory intestinal response with hematological and serum biochemical values in laying hens.

PubMed

Soria, Mario Alberto; Bonnet, María Agustina; Bueno, Dante Javier

2015-06-15

There are few studies about the blood serum of laying hens infected with Salmonella. The differential leukocyte count and blood chemistry values are an important aid in the diagnosis of human diseases, but blood parameters in the avian species are not well known. On the other hand, invasive forms of bacterial gastroenteritis, like Salmonella, often cause intestinal inflammation so this study was undertaken to find a biomarker of Salmonella infection and inflammatory intestinal response in the hematological or serum biochemical parameters in laying hens. Furthermore, we evaluated the association of some farm characteristics with Salmonella infection and fecal leukocytes (FL). A fecal sample with at least one fecal leukocyte per field was considered positive for inflammatory intestinal response. False positive serum reactions for Salmonella infection, by serum plate agglutination (SPA) test, were reduced by heating the sample to 56°C for 30 min and then diluting it 5-fold. The range of hematological and biochemical parameter values was very wide, in addition, there was a poor agreement between the SPA and FL results. Comparison of the positive and negative samples in SPA and FL showed that 1.3% and 79.8% of the laying hens were positive and negative in both tests, respectively. Hens with a positive SPA result showed a higher percentage of monocytes than those with a negative SPA result. Hens with a positive FL test had a higher percentage of heterophils, ratio of heterophils to lymphocytes and aspartate aminotransferase values, while the percentage of lymphocytes was significantly lower (P < 0.05) than those with a negative FL test. The risk of Salmonella infection increased when the age of laying hens and the number of hens per poultry house was greater than or equal to 18 months old and 10,000 laying hens, compared to less than 18 months old and 10,000 laying hens, respectively. On the other hand, the risk of inflammatory intestinal response was higher in laying hens ≥ 18 months old than in hens < 18 months old. Despite the fact that we did not find any specific biomarker of Salmonella infection, this is the first report about the change of Salmonella infection and inflammatory response in hematological/serum biochemical values for laying hens. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of High Levels of Deoxynivalenol and Zearalenone on Growth Performance, and Hematological and Immunological Parameters in Pigs

PubMed Central

Reddy, Kondreddy Eswar; Song, Jaeyong; Lee, Hyun-Jeong; Kim, Minseok; Kim, Dong-Wook; Jung, Hyun Jung; Kim, Bumseok; Lee, Yookyung; Yu, Dongjo; Kim, Dong-Woon; Oh, Young Kyoon; Lee, Sung Dae

2018-01-01

Background: Deoxynivalenol (DON) and zearalenone (ZEN) are common food contaminants produced by Fusarium sp. Mycotoxins are a potential health hazard because of their toxicological effects on both humans and farmed animals. Methods: We analyzed three groups of pigs: a control group (fed a standard diet), and the DON and ZEN groups, fed a diet containing 8 mg/kg DON and 0.8 mg/kg ZEN respectively, for four weeks. Results: DON and ZEN exposure decreased body weight (BW), average daily feed intake (ADFI), food conversion rate (FCR), and the serum levels of immunoglobulin (Ig)G and IgM. The total antioxidant levels significantly decreased in serum and increased in urine samples of both treatment groups. Additionally, DON and ZEN exposure increased serotonin levels in urine. Hematological parameters were not affected by the investigated toxins. Microscopic lesions were evident in sections of kidneys from either treatment group: we found sporadic interstitial nephritis in the DON group and renal glomerulus atrophy in the ZEN group. The expression levels of inflammatory cytokines and chemokine marker genes were reduced in tissues from DON- and ZEN-exposed pigs. Conclusions: chronic ingestion of high doses of DON and ZEN alters the immune response and causes organs damage, and might be associated with various diseases in pigs. PMID:29518941

Brentuximab vedotin for relapsed or refractory CD30+ hematologic malignancies: the German Hodgkin Study Group experience.

PubMed

Rothe, Achim; Sasse, Stephanie; Goergen, Helen; Eichenauer, Dennis A; Lohri, Andreas; Jäger, Ulrich; Bangard, Christopher; Böll, Boris; von Bergwelt Baildon, Michael; Theurich, Sebastian; Borchmann, Peter; Engert, Andreas

2012-08-16

The CD30-targeting Ab-drug conjugate brentuximab vedotin (SGN-35) was recently approved for the treatment of relapsed Hodgkin lymphoma and anaplastic large-cell lymphoma by the Food and Drug Administration. In the present study, we report the experience of the German Hodgkin Study Group with brentuximab vedotin as single agent in 45 patients with refractory or relapsed CD30(+) Hodgkin lymphoma who were treated either in a named patient program (n = 34) or in the context of a safety study associated with the registration program of this drug. In these very heavily pretreated patients, an objective response rate of 60%, including 22% complete remissions, could be documented. The median duration of response was 8 months. This retrospective analysis supports the previously reported excellent therapeutic efficacy of brentuximab vedotin in heavily pretreated CD30(+) malignancies.

High-dose melphalan and autologous stem cell transplantation for AL amyloidosis: recent trends in treatment-related mortality and 1-year survival at a single institution

PubMed Central

Seldin, D. C.; Andrea, N.; Berenbaum, I.; Berk, J. L.; Connors, L.; Dember, L. M.; Doros, G.; Fennessey, S.; Finn, K.; Girnius, S.; Lerner, A.; Libbey, C.; Meier-Ewert, H. K.; O’Connell, R.; O’Hara, C.; Quillen, K.; Ruberg, F. L.; Sam, F.; Segal, A.; Shelton, A.; Skinner, M.; Sloan, J. M.; Wiesman, J. F.; Sanchorawala, V.

2017-01-01

Treatment with high-dose melphalan chemotherapy supported by hematopoietic rescue with autologous stem cells produces high rates of hematologic responses and improvement in survival and organ function for patients with AL amyloidosis. Ongoing clinical trials explore pre-transplant induction regimens, post-transplant consolidation or maintenance approaches, and compare transplant to non-transplant regimens. To put these studies into context, we reviewed our recent experience with transplant for AL amyloidosis in the Amyloid Treatment and Research Program at Boston Medical Center and Boston University School of Medicine. Over the past 10 years, there was a steady reduction in rates of treatment-related mortality and improvement in 1-year survival, now approximately 5% and 90%, respectively, based upon an intention-to-treat analysis. Median overall survival of patients treated with this approach at our center exceeds 7.5 years. PMID:21838459

The Effects of Gamma and Proton Radiation Exposure on Hematopoietic Cell Counts in the Ferret Model

PubMed Central

Sanzari, Jenine K.; Wan, X. Steven; Krigsfeld, Gabriel S.; Wroe, Andrew J.; Gridley, Daila S.; Kennedy, Ann R.

2014-01-01

Exposure to total-body radiation induces hematological changes, which can detriment one's immune response to wounds and infection. Here, the decreases in blood cell counts after acute radiation doses of γ-ray or proton radiation exposure, at the doses and dose-rates expected during a solar particle event (SPE), are reported in the ferret model system. Following the exposure to γ-ray or proton radiation, the ferret peripheral total white blood cell (WBC) and lymphocyte counts decreased whereas neutrophil count increased within 3 hours. At 48 hours after irradiation, the WBC, neutrophil, and lymphocyte counts decreased in a dose-dependent manner but were not significantly affected by the radiation type (γ-rays verses protons) or dose rate (0.5 Gy/minute verses 0.5 Gy/hour). The loss of these blood cells could accompany and contribute to the physiological symptoms of the acute radiation syndrome (ARS). PMID:25356435

[Invasive mould disease in haematological patients].

PubMed

Ruiz-Camps, Isabel; Jarque, Isidro

2014-01-01

Invasive mould infections (IMI) are a persistent problem with high morbidity and mortality rates among patients receiving chemotherapy for hematological malignancies and hematopoietic stem cell transplant recipients. Management of IMI in this setting has become increasingly complex with the advent of new antifungal agents and diagnostic tests, which have resulted in different therapeutic strategies (prophylactic, empirical, pre-emptive, and directed). A proper assessment of the individual risk for IMI appears to be critical in order to use the best prophylactic and therapeutic approach and increase the survival rates. Among the available antifungal drugs, the most frequently used in the hematologic patient are fluconazole, mould-active azoles (itraconazole, posaconazole and voriconazole), candins (anidulafungin, caspofungin and micafungin), and lipid formulations of amphotericin B. Specific recommendations for their use, and criteria for selecting the antifungal agents are discussed in this paper. Copyright © 2014. Published by Elsevier Espana.

Current status of sperm banking for young cancer patients in Japanese nationwide survey.

PubMed

Yumura, Yasushi; Tsujimura, Akira; Okada, Hiroshi; Ota, Kuniaki; Kitazawa, Masahumi; Suzuki, Tatsuya; Kakinuma, Tosiyuki; Takae, Seido; Suzuki, Nao; Iwamoto, Teruaki

2018-02-02

This study aimed to ascertain the current status of Japanese sperm banking for young cancer patients. During 2015, we mailed the directors of 695 institutes where sperm cryopreservation might be performed with questionnaires requesting information on the number of patients, age, precryopreservation chemotherapy, semen analyses results and diagnoses, cryopreservation success rate, and causes of unsuccessful cryopreservation. Of these 695 institutes, 92 had cryopreserved sperm before chemotherapy within the study period. In all, 820 cancer patients (237 testicular, 383 hematological, 46 bone and soft tissue, 20 brain, and 134 other malignancy) consulted the responding institutes for sperm cryopreservation. Except for testicular tumor, the number of patients whose sperm was preserved before cancer treatment was low compared to that of young cancer patients. Approximately 20% of patients with malignancies other than testicular tumor underwent chemotherapy before cryopreservation. The success rate of cryopreservation in hematological malignancy was 82.5%, significantly lower than that of both the testicular cancer (93.6%) and other malignancy groups (95.6%) (P < 0.05). The primary reasons for preservation failure were azoospermia and poor semen quality. Patients with hematological malignancies had a higher rate of unsuccessful cryopreservation compared to those in other groups, possibly due to the large number of patients requesting sperm cryopreservation after chemotherapy induction. In Japan, information regarding sperm banking prior to cancer treatment appears to be lacking. Information regarding sperm preservation before chemotherapy should be provided to all Japanese oncologists.

Successful management of chronic disseminated candidiasis in hematologic patients treated with high-dose liposomal amphotericin B: a retrospective study of the SEIFEM registry.

PubMed

Della Pepa, Roberta; Picardi, M; Sorà, F; Stamouli, M; Busca, A; Candoni, A; Delia, M; Fanci, R; Perriello, V; Zancanella, M; Nosari, A; Salutari, P; Marchesi, F; Pane, F; Pagano, L

2016-09-01

Chronic disseminated candidiasis (CDC) is a complication of Candida infection in immunocompromised patients, involving the liver and spleen, and rarely other organs. The aim of the study is to identify the best antifungal drug for hematologic immunocompromised patients with CDC. In this multicentric retrospective study, the charts of 20 patients with CDC following cytotoxic agent protocols for hematological malignancies, diagnosed from 2003 to 2013, were analyzed. The response to systemic antifungal therapy within 90 days from CDC diagnosis and the possible delay in chemotherapy plan, due to the infection, were evaluated. Six patients were treated with high-dose (HD; 5 mg/kg/daily) liposomal amphotericin B (L-AmB), whereas three received standard-dose (SD) L-AmB (3 mg/kg/daily). Azoles were given to six patients; the remaining five were treated with echinocandins. All patients treated with HD L-AmB (6/6-100 %) achieved complete resolution of CDC; one of them had to interrupt the chemotherapy program for the infection. In the SD L-AmB group, treatment failed in the 100 % of cases and one patient had to delay chemotherapy for the infection. Of the six patients who received azoles, two achieved complete resolution of the infection, four experienced treatment failure, and only three performed chemotherapy as planned. Echinocandins treatment resulted in complete resolution of the infection in 2/5 cases, partial response in 2/5 cases, and failure in one case. In this group, 3/5 patients completed chemotherapy as planned. This study shows that HD L-AmB was particularly effective against CDC in hematologic patients, allowing most patients to continue cytotoxic agent program.

[The molecular-cytogenetic characterization and tyrosine kinase inhibitors efficacy in newly diagnosed chronic phase CML patients with variant Philadelphia chromosomes].

PubMed

Zhao, J J; Zhang, Y L; Zhang, S J; Zhou, J; Yu, F K; Zu, Y L; Zhao, H F; Li, Z; Song, Y P

2018-03-14

Objective: To investigate the molecular-cytogenetic characterization and impact on tyrosine kinase inhibitors (TKIs) therapy in chronic phase of chronic myeloid leukemia (CML-CP) patients with variant Ph chromosome (vPh). Methods: The clinical data of 32 patients with vPh chromosomes were collected and compared with 703 patients with typical Ph chromosome in newly diagnosed CML-CP who were on first-line imatinib (IM) and with BCR-ABL transcript of P210. Results: There was no significant difference in demographic and hematological characteristics between vPh and classic Ph patients. 3(9.4%) of the 32 vPh cases were simple variant translocations. Among the remaining 29 cases with complex variant translocations, 28 cases (87.5%) involved 3 chromosomes, and only 1 (3.1%) involved 4 chromosomes. Except for 8, 15, 18, X, and Y chromosomes, the other chromosomes were involved. The frequency of chromosome 12q(15.5%) and 1p (12.1%) were higher involved. The most common FISH signal pattern was 2G2R1Y (74.1%), followed by 1G1R2F (14.8%), 2G1R1Y (3.7%), 1G2R1Y (3.7%), 1G1R1Y (3.7%). The comparison of complete cytogenetic response (CCyR) ( P =0.269), major molecular response (MMR) ( P =0.391) were carried out between simple and complex mechanisms, without difference. Compared with the classic Ph, the patients with vPh had higher IM primary resistance rate ( χ 2 =3.978, P =0.046), especially primary hematological resistance ( χ 2 =7.870, P =0.005), but the difference of CCyR ( χ 2 =0.192, P =0.661), MMR ( χ 2 =0.822, P =0.365), EFS ( χ 2 =0.509, P =0.476), OS ( χ 2 =3.485, P =0.062) were not statistically significant, and multivariate analysis showed that the presence of vPh did not affect OS ( RR =0.692, 95% CI 0.393-1.765, P =0.658)、EFS ( RR =0.893, 95% CI 0.347-2.132, P =0.126) and PFS ( RR =1.176, 95% CI 0.643-2.682, P =0.703). Conclusion: CML-CP patients with vPh and classic Ph had similar demographic and hematological characteristics. Except for 22q11, 9q34, the frequency of chromosome 12q and 1p were higher involved. The most common FISH signal pattern was 2G2R1Y, and different mechanisms had no impact on TKIs therapy. Compared with cases with classic Ph chromosomes, the patients with vPh chromosomes had higher risk of IM primary resistance, especially primary hematological resistance, which can obtain deeper molecular response quickly after changing to second-generation TKIs and didn't affect long-term outcomes and OS.

Dose and dose rate effects of whole-body proton-irradiation on lymphocyte blastogenesis and hematological variables: part II

NASA Technical Reports Server (NTRS)

Pecaut, Michael J.; Gridley, Daila S.; Smith, Anna L.; Nelson, Gregory A.

2002-01-01

The goal of part II of this study was to evaluate functional characteristics of leukocytes and circulating blood cell parameters after whole-body proton irradiation at varying doses and at low- and high-dose-rates (LDR and HDR, respectively). C57BL/6 mice (n=51) were irradiated and euthanized at 4 days post-exposure for assay. Significant radiation dose- (but not dose-rate-) dependent decreases were observed in splenocyte responses to T and B cell mitogens when compared to sham-irradiated controls (P<0.001). Spontaneous blastogenesis, also significantly dose-dependent, was increased in both blood and spleen (P<0.001). Red blood cell counts, hemoglobin concentration, and hematocrit were decreased in a dose-dependent manner (P<0.05), whereas thrombocyte numbers were only slightly affected. Comparison of proton- and gamma-irradiated groups (both receiving 3 Gy at HDR) showed a higher level of spontaneous blastogenesis in blood leukocytes and a lower splenocyte response to concanavalin A following proton irradiation (P<0.05). There were no dose rate effects. Collectively, the data demonstrate that the measurements in blood and spleen were largely dependent upon the total dose of proton radiation and that an 80-fold difference in the dose rate was not a significant factor. A difference, however, was found between protons and gamma-rays in the degree of change induced in some of the measurements.

Food intake and nutritional status influence outcomes in hospitalized hematology-oncology patients.

PubMed

Calleja Fernández, Alicia; Pintor de la Maza, Begoña; Vidal Casariego, Alfonso; Villar Taibo, Rocío; López Gómez, Juan José; Cano Rodríguez, Isidoro; Ballesteros Pomar, María D

2015-06-01

Malnutrition in oncology and hematology-oncology patients is important due to its prevalence and associated mortality and morbidity. The aims of the study were to assess the prevalence of malnutrition in oncology and hematology patients and determine if intake or malnutrition influences hospitalization outcomes. A cohort study was performed in all patients admitted to the oncology and hematology wards in a 30-day period. Nutritional assessment was performed within 24-hours of admission and repeated after 7 days of hospitalization, including Subjective Global Assessment, anthropometry, dietary assessment (24-hour recall) and estimation of caloric and protein needs. Medical records were reviewed 30 days after discharge. Seventy-three patients were evaluated on admission and 29 on day 7 of hospitalization. The prevalence of malnutrition was 47.7%. On admission, patients consumed 71.6 (SD 22.0)% of the prescribed dietary calories and 68.2 (SD 23.5)% of prescribed proteins. The death rate was 2.8% among patients who ate ≥75% and 17.9% among those who ate <75% (p = 0.040). No significant differences were observed between the intake of calories (p = 0.124) and protein (p = 0.126) on admission and on day 7 of hospitalization. Nutritional status was related to readmission rate, being 35.1% for malnourished vs. 8% for well-nourished (p = 0.014). Nutritional status and food intake were not related to the rest of the studied outcomes (length of stay and mechanical, metabolic or infectious complications). Intake did not decrease during hospitalization. There was an upward trend between reduced intake and mortality. Malnutrition was related to hospital readmission. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Efficacy of different monotherapies in second-line treatment for small cell lung cancer: a meta-analysis of randomized controlled trials

PubMed Central

Luo, Qiuping; Wang, Ziwei; Li, Shengjie; Zhou, Jianying

2015-01-01

Second-line chemotherapy has been proved to be effective on patients with relapsed or refractory small cell lung cancer (SCLC). Although topotecan has been approved by many countries for the monotherapy with an acknowledged efficacy, its efficacy of low response rate and short median survival time is disappointing. Considering the optimal regimen of second-line therapy is yet uncertain, we conducted this meta-analysis to provide theoretical basis for making clinical decisions. A comprehensive electronic search was performed to identify eligible studies. The ending points included response, overall survival (OS), and adverse events. Odds ratios and 95% confidence interval were calculated to compare the effects. Six trials with 1369 patients were included. With regard to response rate, only amrubicin showed a significant improvement compared with topotecan. Irinotecan and etoposide did not show any advantages. When targeted on OS, neither of these monotherapy regimens exhibited any advantage when compared to topotecan. When aimed at toxicity, amrubicin showed a better effect on reducing hematologic toxicity, but a worse outcome on increasing the nonhematologic toxicity, whereas others showed equal efficacy. There is no strong evidence that any advantage for second-line treatment of SCLC when compared with topotecan, except amrubicin. And amrubicin seems to be superior to topotecan in terms of response rates, with a lower toxicity than topotecan, which is of high value in clinical application, and may be the direction of second-line monotherapy in the future. PMID:26770633

A phase II clinical trial evaluating the use of two sequential, four-drug combination chemotherapy regimens in ambulatory bronchogenic adenocarcinoma patients.

PubMed

Broder, L E; Sridhar, K S; Selawry, O S; Charyulu, K N; Rao, R K; Saldana, M J; Lenz, C

1992-12-01

Forty-three ambulatory patients with locally advanced or metastatic bronchogenic adenocarcinoma were sequentially treated with two potentially mutually non-cross-resistant chemotherapy regimens. A new regimen, MVPF (mitomycin-c, vinblastine, procarbazine, and 5-fluorouracil), was given until progressive disease occurred. Then, a second regimen--MOCC (methotrexate, vincristine [Oncovin], cyclophosphamide, and CCNU)--was initiated. At further progression, regional disease patients received radiotherapy, whereas extensive disease patients received Phase II agents. Of the 43 patients entered on the study, 40 were evaluable. Three patients withdrew early due to poor tolerance of the regimen. The response rate for MVPF was 33% (12 of 40 PR, 1 of 40 CR) compared to a 4% (1 of 23 PR) response for MOCC (difference: p < or = .03), for a total response rate of 35%. Although there was an initial improvement in survival for responders (31.7 weeks) versus nonresponders (15.7 weeks) at the 75th percentile (p < or = .05), there was no significant difference in median survival. The hematologic toxicity was equivalent for both groups, whereas nonhematologic toxicity revealed a high incidence of nausea and vomiting in the MVPF group. It is concluded that this approach lent itself well to ambulatory care, and MVPF could be considered an alternative to cyclophosphamide-based regimens. However, the absence of a meaningful CR rate and lack of influence of response on median survival were factors limiting its effectiveness.

Physiological and lactation responses of Egyptian dairy Baladi goats to natural thermal stress under subtropical environmental conditions.

PubMed

El-Tarabany, Mahmoud S; El-Tarabany, Akram A; Atta, Mostafa A

2017-01-01

The objective of this study was to evaluate the impact of thermal stress on milk production and physiological traits of Baladi goats under subtropical Egyptian conditions. Sixty dairy Baladi goats were exposed to three different levels of temperature-humidity index (THI), including low (less than 70), moderate (over 70 and up to 80), and high levels (over 80). The influence of THI on the milk composition and physiological, hematological, and biochemical traits was investigated. Rectal temperature and respiration rate were significantly greater at the higher THI than at low and moderate THI (p = 0.016 and 0.002, respectively). Baladi goats had decreased daily milk yield in a rate of 27.3 and 19.3 % at high THI level, compared with low and moderate THI, respectively (p = 0.031). On the contrary, no significant differences have been reported in protein, fat, and total solids percentages at different THI levels. Total leucocyte count, serum glucose, and total protein were significantly reduced at high THI in comparison with low and moderate THI levels (p = 0.043, 0.001, and 0.001, respectively). However, dairy goats maintained relatively stable estimates for erythrocytes count, hemoglobin, serum triglycerides, cholesterol, catalase, total antioxidant capacity, and triiodothyronine at different THI levels. Our results indicate that dairy Baladi goats can tolerate THI levels up to 80; however, variable reduction in milk yield and few biochemical (serum total protein and glucose) and hematological (leucocytes count) parameters have been reported at a THI level higher than 80.

Genomic stability and physiological assessments of live offspring sired by a bull clone, Starbuck II.

PubMed

Ortegon, H; Betts, D H; Lin, L; Coppola, G; Perrault, S D; Blondin, P; King, W A

2007-01-01

It appears that overt phenotypic abnormalities observed in some domestic animal clones are not transmitted to their progeny. The current study monitored Holstein heifers sired by a bull clone, Starbuck II, from weaning to puberty. Genomic stability was assessed by telomere length status and chromosomal analysis. Growth parameters, blood profiles, physical exams and reproductive parameters were assessed for 12 months (and compared to age-matched control heifers). Progeny sired by the clone bull did not differ (P>0.05) in weight, length and height compared to controls. However, progeny had lower heart rates (HR) (P=0.009), respiratory rates (RR) (P=0.007) and body temperature (P=0.03). Hematological profiles were within normal ranges and did not differ (P>0.05) between both groups. External and internal genitalia were normal and both groups reached puberty at expected ages. Progeny had two or three ovarian follicular waves per estrous cycle and serum progesterone concentrations were similar (P=0.99) to controls. Telomere lengths of sperm and blood cells from Starbuck II were not different (P>0.05) than those of non-cloned cattle; telomere lengths of progeny were not different (P>0.05) from age-matched controls. In addition, progeny had normal karyotypes in peripheral blood leukocytes compared to controls (89.1% versus 86.3% diploid, respectively). In summary, heifers sired by a bull clone had normal chromosomal stability, growth, physical, hematological and reproductive parameters, compared to normal heifers. Furthermore, they had moderate stress responses to routine handling and restraint.

Hematological parameters and anaerobic threshold in Brazilian soccer players throughout a training program.

PubMed

Silva, A S R; Santhiago, V; Papoti, M; Gobatto, C A

2008-04-01

We assessed the responses of hematological parameters and their relationship to the anaerobic threshold of Brazilian soccer players during a training program. Twelve athletes were evaluated at the beginning (week 0, T1), in the middle (week 6, T2), and at the end (week 12, T3) of the soccer training program. On the first day at 7:30 am, before collecting the blood sample at rest for the determination of the hematological parameters, the athletes were conducted to the anthropometric evaluation. On the second day at 8:30 am, the athletes had their anaerobic threshold measured. Analysis of variance with Newman-Keuls'post hoc was used for statistical comparisons between the parameters measured during the soccer training program. Correlations between the parameters analyzed were determined using the Pearson's correlation coefficient. Erythrocytes concentration, hemoglobin, and hematocrit were significantly increased from T1 to T2. The specific soccer training program led to a rise in erythrocytes, hemoglobin, and hematocrit from T1 to T2. We assumed that these results occurred due to the plasma volume reduction and may be explained by the soccer training program characteristics. Furthermore, we did not observe any correlation between the anaerobic threshold and the hematological parameters.

BMC Blood Disorders becomes BMC Hematology: evolving along with the hematology field.

PubMed

Chap, Christna

2013-04-10

This Editorial marks the launch of BMC Hematology, formerly known as BMC Blood Disorders, within the BMC series of journals published by BioMed Central. The scope of BMC Hematology encompasses basic, experimental and clinical research related to hematology. In this Editorial we will discuss the rationale behind this relaunch and how, as an open access journal providing unrestricted and free access to scientific and scholarly work, BMC Hematology will help disseminate research in the hematology field in a freely-accessible manner.

Immunologic and hematologic responses in ponies with experimentally induced Strongylus vulgaris infection.

PubMed

Bailey, M; Martin, S C; Lloyd, S

1989-08-01

Immunologic and hematologic responses were examined in 4 ponies with experimentally induced Strongylus vulgaris infection and in 5 helminth-free ponies. Two ponies were inoculated with 200 larvae and 2 were inoculated with 700 larvae of S vulgaris and then were reinoculated with the same numbers of larvae 34 weeks later. Initial response of the ponies inoculated with S vulgaris was S vulgaris antigen-induced lymphocyte response that developed 1.5 to 3 weeks after inoculation and did not persist. Development of antigen-reactive lymphocytes was followed sequentially by a biphasic complement-fixing antibody response, then biphasic eosinophilia. Antibody titer to S vulgaris antigen was higher in ponies inoculated with 700 larvae, compared with that in ponies given 200 larvae of S vulgaris. Also, the second peak in antibody titer and in absolute number of eosinophils was observed earlier in ponies inoculated with 700 larvae, compared with ponies inoculated with 200 S vulgaris larvae, and subsided before or from about 24 weeks after inoculation. The prepatent period for S vulgaris infection was 24 to 25 weeks. After reinoculation with S vulgaris, a degree of increased lymphocyte responsiveness was apparent but, by 17 weeks after reinoculation, only the primary peak in the absolute number of eosinophils indicated an anamnestic response. Essentially, antibody was not detectable after reinoculation.

Genetic variation in IL28B (IFNL3) and response to interferon-alpha treatment in myeloproliferative neoplasms.

PubMed

Lindgren, Marie; Samuelsson, Jan; Nilsson, Lars; Knutsen, Håvar; Ghanima, Waleed; Westin, Johan; Johansson, Peter L; Andréasson, Björn

2018-05-01

In myeloproliferative neoplasms (MPN), interferon-alpha (IFN-α) is an effective treatment with disease-modifying properties but currently with no clear predictors of treatment outcome. Recent genomewide association studies in chronic hepatitis C have found a strong influence of genetic polymorphism near the IL28B (IFNL3) gene in response to IFN-α treatment. In this study, we sought to evaluate the prognostic impact of IL28B rs12979860, rs8099917, and rs12980275 on IFN-α treatment response in myeloproliferative neoplasms. We retrospectively evaluated 100 patients with MPN treated with IFN-α. The hematologic treatment response on IFN-α was compared between patients and correlated with host genetic variations in IL28B. The genotypes of IL28B were determined by allelic discrimination assays. The CC genotype of rs12979860 was found significantly associated with hematologic response in polycythemia vera (PV) with a complete response (CR) in 79% (CC) compared to 48% (non-CC), (P = .036). No association between the genotypes and treatment response on hydroxyurea was found. These results imply an effect of IL28B genotype on the outcome of IFN-α treatment in MPN. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Population specific biomarkers of human aging: a big data study using South Korean, Canadian and Eastern European patient populations.

PubMed

Mamoshina, Polina; Kochetov, Kirill; Putin, Evgeny; Cortese, Franco; Aliper, Alexander; Lee, Won-Suk; Ahn, Sung-Min; Uhn, Lee; Skjodt, Neil; Kovalchuk, Olga; Scheibye-Knudsen, Morten; Zhavoronkov, Alex

2018-01-11

Accurate and physiologically meaningful biomarkers for human aging are key to assessing anti-aging therapies. Given ethnic differences in health, diet, lifestyle, behaviour, environmental exposures and even average rate of biological aging, it stands to reason that aging clocks trained on datasets obtained from specific ethnic populations are more likely to account for these potential confounding factors, resulting in an enhanced capacity to predict chronological age and quantify biological age. Here we present a deep learning-based hematological aging clock modeled using the large combined dataset of Canadian, South Korean and Eastern European population blood samples that show increased predictive accuracy in individual populations compared to population-specific hematologic aging clocks. The performance of models was also evaluated on publicly-available samples of the American population from the National Health and Nutrition Examination Survey (NHANES). In addition, we explored the association between age predicted by both population-specific and combined hematological clocks and all-cause mortality. Overall, this study suggests a) the population-specificity of aging patterns and b) hematologic clocks predicts all-cause mortality. Proposed models added to the freely available Aging.AI system allowing improved ability to assess human aging. © The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America.

Hypergravity-Induced Changes in Hematological and Lymphocyte Function Parameters in a Mouse Model

NASA Technical Reports Server (NTRS)

Gridley, Daila S.; Miller, Glen M.; Nelson, Gregory A.; Pecaut, Michael J.

2003-01-01

The purpose of this study was to quantify hypergravity-induced changes in hematological and lymphocyte characteristics. Mice were subjected to 1, 2, and 3G and euthanized on days 1 , 4, 7, 10, and 21. The data show that increased gravitational force resulted in persistent hypothermia. Red blood cell (RBC) counts, hematocrit, and hemoglobin were reduced by day 21, whereas hemoglobin and RBC volume were low at most times of measurement. A transient increase was noted in platelet numbers in the 3G group. Fluctuations in spontaneous blastogenesis of lymphocytes were dependent upon centrifugation time and not gravity. Changes in splenocyte responses to T and B cell mitogens due to gravity were also noted. Cytokine production was primarily affected during the first week; IL-2, IL-4 and TNF-alpha were increased, whereas IFN-gamma was decreased. These findings indicate that altered gravity can influence both hematological and functional variables that may translate into serious health consequences.

THERAPY OF POLYCYTHEMIA VERA WITH RADIOYTTRIUM (Y-90)

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

Greenburg, J.; Sawitsky, A.; Dudley, H.C.

1962-01-01

BS>Nine patients with polycythemia vera were treated from 5-l7 months ago with a single intravenous injection of chelated radioactive yttrium (Y-90) in dosages ranging from 0.l0 to 0.25 mc/kg of body weight. An excellent response, both clinical and hematologic, was obtained in all the patients. This includes relief of symptoms, regression of organomegaly, and normalization of the hematologic picture. Two of these patients, treated l6 and 9 months ago, may possibly be going into relapse. The others are continuing in essentially complete remission. Toxicity was limtted to transient petechiosis and epistaxis, from which recovery was spontaneous. (auth)

Improvements and validation of the erythropoiesis control model for bed rest simulation

NASA Technical Reports Server (NTRS)

Leonard, J. I.

1977-01-01

The most significant improvement in the model is the explicit formulation of separate elements representing erythropoietin production and red cell production. Other modifications include bone marrow time-delays, capability to shift oxyhemoglobin affinity and an algorithm for entering experimental data as time-varying driving functions. An area of model development is suggested by applying the model to simulating onset, diagnosis and treatment of a hematologic disorder. Recommendations for further improvements in the model and suggestions for experimental application are also discussed. A detailed analysis of the hematologic response to bed rest including simulation of the recent Baylor Medical College bed rest studies is also presented.

Effects of carprofen on renal function and results of serum biochemical and hematologic analyses in anesthetized dogs that had low blood pressure during anesthesia.

PubMed

Boström, Ingrid M; Nyman, Görel C; Lord, Peter E; Häggström, Jens; Jones, Bernt E V; Bohlin, Henrik P

2002-05-01

To investigate effects of IV administered carprofen on indices of renal function and results of serum biochemical and hematologic analyses in dogs anesthetized with acepromazine-thiopentone-isoflurane that had low blood pressure during anesthesia. 6 healthy Beagles. A randomized crossover study was conducted, using the following treatments: saline (0.9% NaCl solution)-saline, saline-carprofen, and carprofen-saline. Saline (0.08 ml/kg) and carprofen (4 mg/kg) were administered IV. The first treatment was administered 30 minutes before induction of anesthesia and immediately before administration of acepromazine (0.1 mg/kg, IM). Anesthesia was induced with thiopentone (25 mg/ml, IV) and maintained with inspired isoflurane (2% in oxygen). The second treatment was administered 30 minutes after onset of inhalation anesthesia. Blood gases, circulation, and ventilation were monitored. Renal function was assessed by glomerular filtration rate (GFR), using scintigraphy, serum biochemical analyses, and urinalysis. Hematologic analysis was performed. Statistical analysis was conducted, using ANOVA or Friedman ANOVA. Values did not differ significantly among the 3 treatments. For all treatments, sedation and anesthesia caused changes in results of serum biochemical and hematologic analyses, a decrease in mean arterial blood pressure to 65 mm Hg, an increase of 115 pmol/L in angiotensin II concentration, and an increase of 100 seconds in time required to reach maximum activity counts during scintigraphy. Carprofen administered IV before or during anesthesia did not cause detectable significant adverse effects on renal function or results of serum biochemical and hematologic analyses in healthy Beagles with low blood pressure during anesthesia.

Second-line chemotherapy of disseminated malignant melanoma with cystemustine at 60 mg/m2: a phase II trial.

PubMed

Thivat, Emilie; Durando, Xavier; D'Incan, Michel; Cure, Hervé; Mouret-Reynier, Marie-Ange; Madelmont, Jean-Claude; Souteyrand, Pierre; Chollet, Philippe

2005-10-01

Nitrosoureas possess some anti-tumor activity as a single agent in metastatic melanoma (MM). In a phase II trial, we evaluated the anti-tumor effects of cystemustine chemotherapy, a new nitrosourea, as a second-line treatment. Patients were required to have histologic evidence of disseminated MM and had failed in first-line chemotherapy. Treatment comprised cystemustine given at a dose of 60 mg/m every 2 weeks by a 15-min infusion. From February 1997 to September 1999, 22 patients (median age 66 years) were enrolled and were assessable. Two complete responses, one partial response, three stable diseases and 16 progressions were observed, giving an overall response rate of 13.6%. Median duration of response was 10 months (range 4-63). Median survival of responders and non-responders was 11 and 4 months, respectively. However, hematological toxicity, particularly thrombopenia, was a limiting factor for one-third of patients. We conclude that cystemustine at 60 mg/m is active in patients who progressed after one line of chemotherapy in advanced disease, and offers the possibility of complete responses and long durations of these responses.

Oral Ezatiostat HCl (TLK199) and Myelodysplastic syndrome: a case report of sustained hematologic response following an abbreviated exposure.

PubMed

Quddus, Fahd; Clima, Jessica; Seedham, Helen; Sajjad, Ghulam; Galili, Naomi; Raza, Azra

2010-04-23

Treatment options for patients with lower risk non-del(5q) myelodysplastic syndromes (MDS) who fail erythroid stimulating agents are restricted to one of the hypomethylating drugs with an expected response rate of approximately 50%. Ezatiostat HCl, an agent with the potential for producing multi-lineage responses in this population is currently in clinical investigation phase. This case report describes a 77 year old male who received less than two cycles of therapy with ezatiostat HCl which had to be aborted due to intolerable side effects, but which produced a sustained normalization of all three blood counts. This trilineage response has now lasted for more than a year. Interestingly, the patient began with a del(5q) abnormality and responded briefly to lenalidomide. Upon relapse of the anemia, a bone marrow showed the disappearance of the del(5q) but the appearance of a new clonal abnormality t(2;3). Given that the patient had a complete cytogenetic response to a truncated exposure to lenalidomide followed by a trilineage response to an even briefer course of ezatiostat HCl suggests a potential role for ezatiostat HCl in del(5q) patients who relapse following lenalidomide.

Oral Ezatiostat HCl (TLK199) and Myelodysplastic syndrome: A case report of sustained hematologic response following an abbreviated exposure

PubMed Central

2010-01-01

Treatment options for patients with lower risk non-del(5q) myelodysplastic syndromes (MDS) who fail erythroid stimulating agents are restricted to one of the hypomethylating drugs with an expected response rate of ~50%. Ezatiostat HCl, an agent with the potential for producing multi-lineage responses in this population is currently in clinical investigation phase. This case report describes a 77 year old male who received less than two cycles of therapy with ezatiostat HCl which had to be aborted due to intolerable side effects, but which produced a sustained normalization of all three blood counts. This trilineage response has now lasted for more than a year. Interestingly, the patient began with a del(5q) abnormality and responded briefly to lenalidomide. Upon relapse of the anemia, a bone marrow showed the disappearance of the del(5q) but the appearance of a new clonal abnormality t(2;3). Given that the patient had a complete cytogenetic response to a truncated exposure to lenalidomide followed by a trilineage response to an even briefer course of ezatiostat HCl suggests a potential role for ezatiostat HCl in del(5q) patients who relapse following lenalidomide. PMID:20416051

Reduction of central line-associated bloodstream infections in a pediatric hematology/oncology population.

PubMed

Wilson, Matthew Z; Deeter, Deana; Rafferty, Colleen; Comito, Melanie M; Hollenbeak, Christopher S

2014-01-01

This study reports the results of an initiative to reduce central line-associated bloodstream infections (CLABSIs) among pediatric hematology/oncology patients, a population at increased risk for CLABSI. The study design was a pre-post comparison of a series of specific interventions over 40 months. Logistic regression was used to determine if the risk of developing CLABSI decreased in the postintervention period, after controlling for covariates. The overall CLABSI rate fell from 9 infections per 1000 line days at the beginning of the study to zero in a cohort of 291 patients encompassing 2107 admissions. Admissions during the intervention period had an 86% reduction in odds of developing a CLABSI, controlling for other factors. At the study team's institution, an initiative that standardized blood culturing techniques, lab draw times, line care techniques, and provided physician and nurse education was able to eliminate CLABSI among pediatric hematology/oncology patients. © 2013 by the American College of Medical Quality.

Long-term outcome and risk factors for uncontrolled seizures after a first seizure in children with hematological malignancies.

PubMed

Khan, Raja B; Morris, E Brannon; Pui, Ching-Hon; Hudson, Melissa M; Zhou, Yinmei; Cheng, Cheng; Ledet, Davonna S; Howard, Scott C

2014-06-01

Long-term outcomes of seizures that develop during treatment of childhood hematological malignancies have not been described. We analyzed seizure outcome in 62 children with leukemia or lymphoma treated at our institution. There was a median follow-up of 6.5 years since first seizure. Seizure etiology included intrathecal or systemic methotrexate in 24, leucoencephalopathy in 11, brain hemorrhage or thrombosis in 11, meningitis in 4, and no identifiable cause in 12. Seizures remained uncontrolled in 18, and risk factors for poor control included female sex (P = .02), no seizure control with first antiseizure drug (P = .08), and longer interval between cancer diagnosis and seizure onset (P = .09). Poor seizure control after initial antiseizure drug also predicted recurrent seizure after drug withdrawal (P = .04). In conclusion, seizures are controlled with medications in a majority of patients with hematological cancer. After a period without seizures, antiseizure drug withdrawal in appropriately selected patient has a high success rate. © The Author(s) 2013.

Typhoid fever with severe abdominal pain: diagnosis and clinical findings using abdomen ultrasonogram, hematology-cell analysis and the Widal test.

PubMed

Arjunan, Maripandi; Al-Salamah, Ali A

2010-10-04

A six-year-old boy with high-grade fever and abdominal pain in the epigastric region was examined with ultrasonogram of the abdomen. Hematology-cell analysis, serology (Widal test), urine analysis, and blood cultures were also performed. The ultrasonogram was helpful for the identification of multiple organ involvement with Salmonella typhi. The results revealed mild hepatosplenomegaly, minimal ascitis, and mesenteric lympoadenopathy. Hematological analysis showed a white blood count of 6,300 cells mL-1; a red blood cell count of 4.54 million/cu mm. The erythrocyte sedimentation rate (ESR) was 24 mm/1 hr; hemoglobin level of 11.5 g/dl; and a platelet count of 206,000 cells/mL. The patient's serum was agglutinated with lipopolysaccharide (TO), the titre value was 1:320 dilution, and flagellar antigen (TH) titre was 1:640. The patient was diagnosed with typhoid fever. Ceftriaxone was given intravenously for five days and the patient fully recovered.

Efficacy of β-Lactam/β-Lactamase Inhibitor Combinations for the Treatment of Bloodstream Infection Due to Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae in Hematological Patients with Neutropenia

PubMed Central

Royo-Cebrecos, Cristina; Abdala, Edson; Akova, Murat; Álvarez, Rocío; Maestro-de la Calle, Guillermo; Cano, Angela; Cervera, Carlos; Clemente, Wanessa T.; Martín-Dávila, Pilar; Freifeld, Alison; Gómez, Lucía; Gottlieb, Thomas; Gurguí, Mercè; Herrera, Fabián; Manzur, Adriana; Maschmeyer, Georg; Meije, Yolanda; Montejo, Miguel; Peghin, Maddalena; Rodríguez-Baño, Jesús; Ruiz-Camps, Isabel; Sukiennik, Teresa C.; Tebe, Cristian; Carratalà, Jordi

2017-01-01

ABSTRACT β-Lactam/β-lactamase inhibitors (BLBLIs) were compared to carbapenems in two cohorts of hematological neutropenic patients with extended-spectrum-β-lactamase (ESBL) bloodstream infection (BSI): the empirical therapy cohort (174 patients) and the definitive therapy cohort (251 patients). The 30-day case fatality rates and other secondary outcomes were similar in the two therapy groups of the two cohorts and also in the propensity-matched cohorts. BLBLIs might be carbapenem-sparing alternatives for the treatment of BSI due to ESBLs in these patients. PMID:28584145

Baseline hematology and clinical chemistry results from captive-raised trumpeter swans

USGS Publications Warehouse

Olsen, Glenn H.; Rininger, D.L.; Ets, M.K.; Sladen, William J. L.; Rees, Eileen C.; Earnst, Susan L.; Coulson, John C.

2002-01-01

Results from hematology and clinical chemistry tests are presented for healthy captive-raised Trumpeter Swans (Cygnus buccinator) to help establish baseline data. Blood samples were obtained from 14 cygnets between the ages of three to four and seven to eight months that were the subjects of a study to teach migration routes to swans. Males and females differed significantly in asparatate aminotransferase, alanine aminotransferase and total protein. Age categories differed significantly in hematocrit, white blood cell counts, alkaline phosphatase, aspar-rate aminotransferase, glucose, cholesterol and uric acid. There were no significant differences among age categories in values of alanine aminotransferase, calcium, triglycerides and total protein.

BMC Blood Disorders becomes BMC Hematology: evolving along with the hematology field

PubMed Central

2013-01-01

This Editorial marks the launch of BMC Hematology, formerly known as BMC Blood Disorders, within the BMC series of journals published by BioMed Central. The scope of BMC Hematology encompasses basic, experimental and clinical research related to hematology. In this Editorial we will discuss the rationale behind this relaunch and how, as an open access journal providing unrestricted and free access to scientific and scholarly work, BMC Hematology will help disseminate research in the hematology field in a freely-accessible manner. PMID:24499661

Bone marrow-on-a-chip replicates hematopoietic niche physiology in vitro.

PubMed

Torisawa, Yu-suke; Spina, Catherine S; Mammoto, Tadanori; Mammoto, Akiko; Weaver, James C; Tat, Tracy; Collins, James J; Ingber, Donald E

2014-06-01

Current in vitro hematopoiesis models fail to demonstrate the cellular diversity and complex functions of living bone marrow; hence, most translational studies relevant to the hematologic system are conducted in live animals. Here we describe a method for fabricating 'bone marrow-on-a-chip' that permits culture of living marrow with a functional hematopoietic niche in vitro by first engineering new bone in vivo, removing it whole and perfusing it with culture medium in a microfluidic device. The engineered bone marrow (eBM) retains hematopoietic stem and progenitor cells in normal in vivo-like proportions for at least 1 week in culture. eBM models organ-level marrow toxicity responses and protective effects of radiation countermeasure drugs, whereas conventional bone marrow culture methods do not. This biomimetic microdevice offers a new approach for analysis of drug responses and toxicities in bone marrow as well as for study of hematopoiesis and hematologic diseases in vitro.

Ipilimumab for Patients with Relapse after Allogeneic Transplantation

PubMed Central

Davids, Matthew S.; Kim, Haesook T.; Bachireddy, Pavan; Costello, Caitlin; Liguori, Rebecca; Savell, Alexandra; Lukez, Alexander P.; Avigan, David; Chen, Yi-Bin; McSweeney, Peter; LeBoeuf, Nicole R.; Rooney, Michael S.; Bowden, Michaela; Zhou, Chensheng W.; Granter, Scott R.; Hornick, Jason L.; Rodig, Scott J.; Hirakawa, Masahiro; Severgnini, Mariano; Hodi, F. Stephen; Wu, Catherine J.; Ho, Vincent T.; Cutler, Corey; Koreth, John; Alyea, Edwin P.; Antin, Joseph H.; Armand, Philippe; Streicher, Howard; Ball, Edward D.; Ritz, Jerome; Bashey, Asad; Soiffer, Robert J.

2016-01-01

BACKGROUND Loss of donor-mediated immune antitumor activity after allogeneic hematopoietic stem-cell transplantation (HSCT) permits relapse of hematologic cancers. We hypothesized that immune checkpoint blockade established by targeting cytotoxic T-lymphocyte–associated protein 4 with ipilimumab could restore antitumor reactivity through a graft-versus-tumor effect. METHODS We conducted a phase 1/1b multicenter, investigator-initiated study to determine the safety and efficacy of ipilimumab in patients with relapsed hematologic cancer after allogeneic HSCT. Patients received induction therapy with ipilimumab at a dose of 3 or 10 mg per kilogram of body weight every 3 weeks for a total of 4 doses, with additional doses every 12 weeks for up to 60 weeks in patients who had a clinical benefit. RESULTS A total of 28 patients were enrolled. Immune-related adverse events, including one death, were observed in 6 patients (21%), and graft-versus-host disease (GVHD) that precluded further administration of ipilimumab was observed in 4 patients (14%). No responses that met formal response criteria occurred in patients who received a dose of 3 mg per kilogram. Among 22 patients who received a dose of 10 mg per kilogram, 5 (23%) had a complete response, 2 (9%) had a partial response, and 6 (27%) had decreased tumor burden. Complete responses occurred in 4 patients with extramedullary acute myeloid leukemia and 1 patient with the myelodysplastic syndrome developing into acute myeloid leukemia. Four patients had a durable response for more than 1 year. Responses were associated with in situ infiltration of cytotoxic CD8+ T cells, decreased activation of regulatory T cells, and expansion of subpopulations of effector T cells in the blood. CONCLUSIONS Our early-phase data showed that administration of ipilimumab was feasible in patients with recurrent hematologic cancers after allogeneic HSCT, although immune-mediated toxic effects and GVHD occurred. Durable responses were observed in association with several histologic subtypes of these cancers, including extramedullary acute myeloid leukemia. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01822509.) PMID:27410923

Determinants of hematology-oncology trainees' postfellowship career pathways with a focus on nonmalignant hematology

PubMed Central

Jenkins, Sarah; Mikhael, Joseph; Gitlin, Scott D.

2018-01-01

Nonmalignant hematologic conditions are extremely prevalent and contribute significantly to the global burden of disease. The US health care system may soon face a shortage of specialists in nonmalignant hematology. We sought to identify factors that lead hematology-oncology fellows to pursue (or not to pursue) careers in nonmalignant hematology. Cross-sectional, web-based survey distributed to 149 graduates of a hematology-oncology fellowship program at a large academic medical center between 1998 and 2016. Eighty-six out of 149 graduates responded (57.7%); most (59 [68.6%]) practice at an academic medical center. Respondents spend a mean of 61% of their time in clinical practice, 23.7% conducting research, 5.2% in education, and 5.2% in administration. Those in clinical practice spend a mean of 52.1% of their time in solid tumor oncology, 37.5% in hematologic malignancies, and 10% in nonmalignant hematology; only 1 spent >50% of time practicing nonmalignant hematology. Factors most significantly affecting choice of patient population included clinical experience during fellowship and intellectual stimulation of the patient population/disease type. Factors that could have most significantly influenced a decision to spend more time in nonmalignant hematology included increased exposure/access to role models and mentors and opportunities for better career growth/advancement. Fellowship graduates spend >50% of their time in clinical practice, but almost none spend a significant amount of time practicing nonmalignant hematology. Given the growing number of patients with nonmalignant hematologic conditions and a possible future provider shortage, medical trainees should be encouraged to pursue careers in nonmalignant hematology. PMID:29463548

Hematological changes in nephritis in poultry induced by diets high in protein, high in calcium, containing urea, or deficient in vitamin A.

PubMed

Chandra, M; Singh, B; Singh, N; Ahuja, S P

1984-04-01

Nephritis was induced in 300, 18-day-old male Arbor Acre broiler chicks by feeding diets high (42.28%) in protein, high (3.27%) in calcium, containing urea (5%), or deficient in vitamin A. Various hematological parameters were studied at weekly intervals. Normocytic-normochromic anemia, characterized by a decrease in total erythrocyte counts, hemoglobin, packed cell volume, and an increase in erythrocyte sedimentation rate, was evident in the birds kept on diets high in protein, high in calcium, or deficient in vitamin A. Increased total erythrocytes, hemoglobin packed cell volume, and erythrocyte sedimentation rate was observed in birds fed urea. Differential leucocyte counts revealed lymphopenia, heterophilia and monocytosis in birds kept on diets high in protein, containing urea, or deficient in vitamin A. However, lymphocytosis, heteropenia , and monocytosis were recorded in birds fed the high calcium diet.

21 CFR 864.8625 - Hematology quality control mixture.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Hematology quality control mixture. 864.8625 Section 864.8625 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents § 864.8625 Hematology...

21 CFR 864.8625 - Hematology quality control mixture.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Hematology quality control mixture. 864.8625 Section 864.8625 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents § 864.8625 Hematology...

21 CFR 864.8625 - Hematology quality control mixture.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Hematology quality control mixture. 864.8625 Section 864.8625 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents § 864.8625 Hematology...

CPTAC Develops Fit-for-Purpose Multiplex Immuno-MRM Assay for Profiling the DNA Damage Response Pathway | Office of Cancer Clinical Proteomics Research

Cancer.gov

Ionizing radiation (IR) is a commonly employed cancer treatment that kills cancer cells by damaging their DNA. While the DNA damage response (DDR) pathway may be key to determining tumor responses, radiochemical damage due to IR can target the patients’ healthy dividing cells, leading to the formation of secondary hematologic and solid tumors after DNA-damaging therapy.

First-in-human response of BCL-2 inhibitor venetoclax in T-cell prolymphocytic leukemia.

PubMed

Boidol, Bernd; Kornauth, Christoph; van der Kouwe, Emiel; Prutsch, Nicole; Kazianka, Lukas; Gültekin, Sinan; Hoermann, Gregor; Mayerhoefer, Marius E; Hopfinger, Georg; Hauswirth, Alexander; Panny, Michael; Aretin, Marie-Bernadette; Hilgarth, Bernadette; Sperr, Wolfgang R; Valent, Peter; Simonitsch-Klupp, Ingrid; Moriggl, Richard; Merkel, Olaf; Kenner, Lukas; Jäger, Ulrich; Kubicek, Stefan; Staber, Philipp B

2017-12-07

T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive T-lymphoid malignancy usually refractory to current treatment strategies and associated with short overall survival. By applying next-generation functional testing of primary patient-derived lymphoma cells using a library of 106 US Food and Drug Administration (FDA)-approved anticancer drugs or compounds currently in clinical development, we set out to identify novel effective treatments for T-PLL patients. We found that the B-cell lymphoma 2 (BCL-2) inhibitor venetoclax (ABT-199) demonstrated the strongest T-PLL-specific response when comparing individual ex vivo drug response in 86 patients with refractory hematologic malignancies. Mechanistically, responses to venetoclax correlated with protein expression of BCL-2 but not with expression of the BCL-2 family members myeloid cell leukemia 1 (MCL-1) and BCL-XL in lymphoma cells. BCL-2 expression was inversely correlated with the expression of MCL-1. Based on the ex vivo responses, venetoclax treatment was commenced in 2 late-stage refractory T-PLL patients resulting in clinical responses. Our findings demonstrate first evidence of single-agent activity of venetoclax both ex vivo and in humans, offering a novel agent in T-PLL. © 2017 by The American Society of Hematology.

Phase II trial of irinotecan in patients with metastatic colorectal carcinoma.

PubMed

Pitot, H C; Wender, D B; O'Connell, M J; Schroeder, G; Goldberg, R M; Rubin, J; Mailliard, J A; Knost, J A; Ghosh, C; Kirschling, R J; Levitt, R; Windschitl, H E

1997-08-01

To evaluate the objective tumor response rate and toxicities of patients with metastatic colorectal carcinoma treated with irinotecan hydrochloride (CPT-11). A total of 121 patients with advanced colorectal carcinoma--90 with prior fluorouracil (5-FU) exposure and 31 chemotherapeutically naive patients--were enrolled between May 1993 and June 1994. Patients were treated with CPT-11 at 125 mg/m2 intravenously weekly for 4 weeks followed by a 2-week rest. Among 90 patients with prior 5-FU chemotherapy, 12 partial responses were observed (response rate, 13.3%; 95% confidence interval [CI], 7.1% to 22.1%). Among 31 chemotherapy-naive patients, eight had partial responses (response rate, 25.8%; 95% CI, 11.9% to 44.6%). The median response duration as measured from time of initial treatment for the two groups was 7.7 months and 7.6 months, respectively. The major adverse reactions were gastrointestinal and hematologic. The incidence of grade 3 or 4 diarrhea was 36.4%, while the overall incidence of grade 3 or 4 leukopenia was 21.5% of patients. Only four of 121 patients (3.3%) developed neutropenic fever (grade 4 neutropenia with > or = grade 2 fever). The incidence of grade 4 leukopenia was higher in patients with prior pelvic radiotherapy (chi2 test P = .04), while the incidence of grade 3 or 4 diarrhea demonstrated no association with previous pelvic irradiation. According to the study design, CPT-11 showed promising activity in chemotherapy-naive patients with advanced colorectal carcinoma and modest activity in patients with prior 5-FU exposure. The toxicity with this schedule appears manageable with appropriate dose modification for individual patient tolerance and an intensive loperamide regimen for the management of diarrhea. Care should be taken when treating patients with prior pelvic radiotherapy because of the increased risk of neutropenia.

Approval summary: azacitidine for treatment of myelodysplastic syndrome subtypes.

PubMed

Kaminskas, Edvardas; Farrell, Ann; Abraham, Sophia; Baird, Amy; Hsieh, Li-Shan; Lee, Shwu-Luan; Leighton, John K; Patel, Hasmukh; Rahman, Atiqur; Sridhara, Rajeshwara; Wang, Yong-Cheng; Pazdur, Richard

2005-05-15

This article summarizes data submitted to the U.S. Food and Drug Administration for marketing approval of azacitidine as injectable suspension (Vidaza, Pharmion Corporation, Boulder, CO) for treatment of patients with myelodysplastic syndrome. In one phase 3 controlled trial, 191 study subjects were randomized to treatment with azacitidine or to observation; an additional 120 patients were treated with azacitidine in two phase 2 single arm studies. The primary efficacy end point was the overall response rate, defined as complete or partial normalization of peripheral blood counts and bone marrow blast percentages for at least 4 weeks. In the controlled trial, the overall response rate was 15.7% in the azacitidine treatment group; there were no responders in the observation group (P < 0.0001). Response rates were similar in the two single arm studies. During response patients stopped being red cell or platelet transfusion dependent. Median duration of responses was at least 9 months. An additional 19% of azacitidine-treated patients had less than partial responses, most becoming transfusion independent. The most common adverse events attributed to azacitidine were gastrointestinal, hematologic, local (injection site), and constitutional. There were no azacitidine-related deaths. On May 19, 2004 the U.S. Food and Drug Administration approved azacitidine as injectable suspension for treatment of patients with the following myelodysplastic syndrome subtypes: refractory anemia or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia. Full prescribing information is available at http://www.fda.gov/cder/foi/label/2004/050794lbl.pdf. Azacitidine is the first agent approved for treatment of myelodysplastic syndrome.

Effect of cell phone exposure on physiologic and hematologic parameters of male medical students of Bijapur (Karnataka) with reference to serum lipid profile.

PubMed

Parkar, Matin A; Ahmed, Rishad; Abdullah, Bilal Bin; Patil, B S; Das, Kusal K

2010-01-01

The public awareness about cell phone safety increased greatly in the last few years as various reports of potential adverse health effects on humans exposed to radiations emitted from cellular phones were published. The aim of the study was to assess the effect of long term cell phone exposure on physiological and hematological parameters along with its impact on serum lipid profiles and a single call effect on heart rate, blood pressure and SpO2(%) of healthy male medical students. The students were divided into two groups, group I (n=22, age 20.63 +/- 1.17 yrs) comprising first year medical students who were never exposed to cell phones at the time of this study and group II (n=35, age 22.00 +/- 1.56 yrs) consists of final year (fourth year) male medical students who were using cell phone for more than four years before this study. The results showed no significant differences the groups in basal heart rate, systolic blood pressure, SpO2(%), or various hematologic parameters. Acute exposure (single call of cell phone with 900 MHz for 1 minute) in both groups showed a significant increase in peak heart rate in group II as compared with group I and a significant decrease in peak SpO2 (%) in group I as compared with group II. Serum total cholesterol, VLDL-cholesterol, and triglycerides concentration were significantly higher in group II (long term cell phone exposed) than in group I, suggesting a mild alteration of lipid profile among group II subjects.

[Systemic lupus erythematosus and pregnancy (effect of pre-conception hematologic disorders on fetal outcome)].

PubMed

Pajor, A; Pozsonyi, T; Nékám, K; Bakos, L; Haraszti, L; Paulin, F

1998-02-22

The aim of the study was to determine the fetal and neonatal outcomes of pregnancies conceived during the inactive phase of systemic lupus erythematosus (SLE). Fetal and neonatal outcomes in 75 pregnancies of 33 patients with SLE were analyzed. In 19 patients (57.6%) the SLE also had hematological autoimmune presentations prior to gestation, such as anemia, thrombopenia, garnulocytopenia, and antiphospholipid antibody and/or lupus anticoagulant (APA). Out of 75 pregnancies, 19 elective terminations were carried out because the disease was active or for non-medical reasons. The adverse fetal outcomes of those 56 pregnancies which occurred during the inactive phase were compared with those of the control patients. In SLE, the rates of spontaneous abortions (46.4%) and newborns with low (< 2500 gr) birthweight (36.7%) were found to increase roughly three times that of the controls and the perinatal fetal loss (16.7%) also increased significantly as compared with the control group (28.5 per thousand). APA noted at any time before pregnancy increased the low birthweight rate (75%) six fold and the perinatal loss (33.3%) more than ten fold but did not affect the rate of spontaneous abortions. Any kind of hemocytopenias without APA, noted before pregnancy did not worsen the fetal outcome in SLE. Neonatal lupus was diagnosed in 2 out of the 30 newborns. Our results suggest that among the hematologic manifestations of SLE presenting before pregnancy, APA can predict the high risks of low birthweight and perinatal fetal loss as opposed to hemocytopenias.

Safety evaluation of intravenously administered mono-thioated aptamer against E-selectin in mice

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

Kang, Shin-Ae; Tsolmon, Bilegtsaikhan; Mann, Aman P.

2015-08-15

The medical applications of aptamers have recently emerged. We developed an antagonistic thioaptamer (ESTA) against E-selectin. Previously, we showed that a single injection of ESTA at a dose of 100 μg inhibits breast cancer metastasis in mice through the functional blockade of E-selectin. In the present study, we evaluated the safety of different doses of intravenously administered ESTA in single-dose acute and repeat-dose subacute studies in ICR mice. Our data indicated that intravenous administration of up to 500 μg ESTA did not result in hematologic abnormality in either study. Additionally, intravenous injection of ESTA did not affect the levels ofmore » plasma cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, GM-CSF, IFN-γ, and TNF-α) or complement split products (C3a and C5a) in either study. However, repeated injections of ESTA slightly increased plasma ALT and AST activities, in accordance with the appearance of small necrotic areas in the liver. In conclusion, our data demonstrated that intravenous administration of ESTA does not cause overt hematologic, organs, and immunologic responses under the experimental conditions. - Highlights: • Intravenous administration of ESTA was well tolerated. • ESTA up to 500 μg does not cause hematologic, organs, and immunologic responses. • ESTA-mediated hepatic abnormality was considered minor.« less

The Co-Inheritance of Alpha-Thalassemia and Sickle Cell Anemia Is Associated with Better Hematological Indices and Lower Consultations Rate in Cameroonian Patients and Could Improve Their Survival

PubMed Central

Rumaney, Maryam Bibi; Ngo Bitoungui, Valentina Josiane; Vorster, Anna Alvera; Ramesar, Raj; Kengne, Andre Pascal; Ngogang, Jeanne; Wonkam, Ambroise

2014-01-01

Background Co-inheritance of α-thalassemia was reported to be associated with a delayed age of disease onset among Cameroonian Sickle Cell Anemia (SCA) patients. The present study aimed to explore the correlation between α-thalassemia, hematological indices, and clinical events in these patients. Methods and Findings We studied 161 Cameroonian SCA patients and 103 controls (59.1% HbAA) with median ages of 17.5 and 23 years. RFLP-PCR was used to confirm SCA genotype and to describe haplotypes in the HBB-like genes cluster. Multiplex Gap-PCR was performed to investigate the 3.7 kb α-globin gene deletions. SNaPshot PCR, capillary electrophoresis and cycle sequencing were used for the genotyping of 10 SNPs in BCL11A, HMIP1/2, OR51B5/6 and HBG loci, known to influence HbF levels. Generalised linear regression models adjusted for age, sex and SNPs genotypes was used to investigate effects of α-thalassemia on clinical and hematological indices. The median rate of vaso-occlusive painful crisis and hospitalisations was two and one per year, respectively. Stroke was reported in eight cases (7.4%). Benin haplotype was the most prevalent (66.3%; n = 208 chromosomes). Among patients, 37.3% (n = 60) had at least one 3.7 kb deletion, compared to 10.9% (n = 6) among HbAA controls (p<0.001). Among patients, the median RBC count increased with the number of 3.7 kb deletions [2.6, 3.0 and 3.4 million/dl, with no, one and two deletions (p = 0.01)]. The median MCV decreased with the number of 3.7 kb deletion [86, 80, and 68fl, with no, one and two deletions (p<0.0001)], as well as median WBC counts [13.2, 10.5 and 9.8×109/L (p<0.0001. The co-inheritance of α-thalassemia was associated with lower consultations rate (p = 0.038). Conclusion The co-inheritance of α-thalassemia and SCA is associated with improved hematological indices, and lower consultations rate in this group of patients. This could possibly improve their survival and explain the higher proportion of α-thalassemia among patients than controls. PMID:24978191

Bendamustine in Combination With Gemcitabine and Vinorelbine Is an Effective Regimen As Induction Chemotherapy Before Autologous Stem-Cell Transplantation for Relapsed or Refractory Hodgkin Lymphoma: Final Results of a Multicenter Phase II Study.

PubMed

Santoro, Armando; Mazza, Rita; Pulsoni, Alessandro; Re, Alessandro; Bonfichi, Maurizio; Zilioli, Vittorio Ruggero; Salvi, Flavia; Merli, Francesco; Anastasia, Antonella; Luminari, Stefano; Annechini, Giorgia; Gotti, Manuel; Peli, Annalisa; Liberati, Anna Marina; Di Renzo, Nicola; Castagna, Luca; Giordano, Laura; Carlo-Stella, Carmelo

2016-09-20

This multicenter, open-label, phase II study evaluated the combination of bendamustine, gemcitabine, and vinorelbine (BeGEV) as induction therapy before autologous stem-cell transplantation (ASCT) in patients with relapsed or refractory Hodgkin lymphoma (HL). Patients with HL who were refractory to or had relapsed after one previous chemotherapy line were eligible. The primary end point was complete response (CR) rate after four cycles of therapy. Secondary end points were: overall response rate, stem-cell mobilization activity, and toxicity. Progression-free and overall survival were also evaluated. In total, 59 patients were enrolled. After four cycles of therapy, 43 patients (73%) achieved CR, and six (10%) achieved partial response, for an overall response rate of 83%. The most common grade 3 to 4 nonhematologic toxicities included febrile neutropenia (n = 7) and infection (n = 4). Regarding hematologic toxicities, grade 3 to 4 thrombocytopenia and neutropenia were each experienced by eight patients (13.5%). CD34+ cells were successfully harvested in 55 of 57 evaluable patients, and 43 of 49 responding patients underwent ASCT. With a median follow-up of 29 months, the 2-year progression-free and overall survival rates for the total population were 62.2% and 77.6%, respectively. The same figures for patients undergoing autograft were 80.8% and 89.3%, respectively. This phase II study demonstrates that BeGEV is an effective salvage regimen able to induce CR in a high proportion of patients with relapsed or refractory HL before ASCT. These data provide a strong rationale for further development of the BeGEV regimen. © 2016 by American Society of Clinical Oncology.

Phase I study of 2'-3'-dideoxyinosine administered orally twice daily to patients with AIDS or AIDS-related complex and hematologic intolerance to zidovudine.

PubMed

Connolly, K J; Allan, J D; Fitch, H; Jackson-Pope, L; McLaren, C; Canetta, R; Groopman, J E

1991-11-01

To evaluate the safety and hematologic tolerance of 2'-3'-dideoxyinosine (didanosine, ddI) in subjects with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex and prior hematologic intolerance to zidovudine. A Phase I trial with two dose groups at a single-center, university-affiliated hospital ambulatory care center. Of 30 subjects enrolled, 21 had AIDS and nine had AIDS-related complex. All had CD4 lymphocyte counts less than 0.2 x 10(9)/L at entry. Didanosine was administered orally twice daily at a total daily dose of 750 mg or 1,500 mg for 12 weeks. Subjects who completed the 12-week study continued to receive ddI at the lower dose. All subjects were monitored for toxicity. Virologic and immunologic response markers were also measured. For the group as a whole, there was no significant decrease in mean hemoglobin level or leukocyte or platelet counts. The dose-limiting toxicity was peripheral neuropathy. Other significant toxicities included pancreatitis and hypocalcemia. Uric acid elevations were common but were without clinical consequence. A sustained decrease in serum p24 antigen of at least 50% was noted in 42% of subjects who were p24 antigen-positive at entry. The mean CD4 lymphocyte count showed an initial increase that was not sustained over the 12-week study. All subjects remained anergic to skin testing. Didanosine is well tolerated hematologically in some patients with prior significant hematologic intolerance to zidovudine. The toxicity profile for ddI differs from that of zidovudine and includes peripheral neuropathy and pancreatitis. Changes in CD4 lymphocyte number and HIV p24 antigen levels in some patients suggest antiviral activity of ddI in this population.

Profile and scientific production of the Brazilian Council for Scientific and Technological Development (CNPq) researchers in the field of Hematology/Oncology.

PubMed

Oliveira, Maria Christina Lopes Araujo; Martelli, Daniella Reis; Quirino, Isabel Gomes; Colosimo, Enrico Antônio; Silva, Ana Cristina Simões e; Martelli Júnior, Hercílio; Oliveira, Eduardo Araujo de

2014-01-01

several studies have examined the academic production of the researchers at the CNPq, in several areas of knowledge. The aim of this study was to evaluate the scientific production of researchers in Hematology/Oncology who hold scientific productivity grants from the Brazilian Council for Scientific and Technological Development. the Academic CVs of 28 researchers in Hematology/Oncology with active grants in the three-year period from 2006 to 2008 were included in the analysis. The variables of interest were: institution, researchers' time after doctorate, tutoring of undergraduate students, masters and PhD degree, scientific production and its impact. from a total of 411 researchers in Medicine, 28 (7%) were identified as being in the area of Hematology/Oncology. There was a slight predominance of males (53.6%) and grant holders in category 1. Three Brazilian states are responsible for approximately 90% of the researchers: São Paulo (21,75%), Rio de Janeiro (3,11%), and Minas Gerais (2, 7%). During their academic careers, the researchers published 2,655 articles, with a median of 87 articles per researcher (IQR = 52 to 122). 65 and 78% of this total were indexed on the Web of Science and Scopus databases, respectively. The researchers received 14,247 citations on the WoS database with a median of 385 citations per researcher. The average number of citations per article was 8.2. in this investigation, it was noted that researchers in the field of Hematology/Oncology have a relevant scientific output from the point of view of quantity and quality compared to other medical specialties.

Hematological and Biochemical Parameters in Elite Soccer Players During A Competitive Half Season

PubMed Central

Anđelković, Marija; Baralić, Ivana; Đorđević, Brižita; Stevuljević, Jelena Kotur; Radivojević, Nenad; Dikić, Nenad; Škodrić, Sanja Radojević; Stojković, Mirjana

2015-01-01

Summary Background The purpose of the present study was to report and discuss the hematological and biochemical behavior of elite soccer players, in order to get more insight in the physiological characteristics of these sportsmen and to provide trainers and sports doctors with useful indicators. Methods Nineteen male soccer players volunteered to participate in this study. We followed the young elite soccer players during a competitive half season. Venous blood samples were collected between 9:00 and 10:00 a.m. after an overnight fast (10 h) at baseline, after 45 and 90 days and hematological and biochemical parameters were measured. Results Hemoglobin and hematocrit levels were significantly reduced over the observational period (p<0.05), but erythrocyte count and iron levels remained unchanged. Bilirubin and ferritin levels significantly increased in response to regular soccer training (p<0.05). We observed a significant decrease in muscle enzyme plasma activity during the 90 days study period. ANOVA analysis revealed a significant increase in the leukocyte and neutrophil counts (p<0.05), in parallel with a significant decrease in the lymphocyte count (p<0.05) after the observational period of 90 days. Conclusions Elite soccer players are characterized by significant changes in biochemical and hematological parameters over the half season, which are linked to training workload, as well as adaptation induced by the soccer training. Although the values of the measured parameters fell within the reference range, regular monitoring of the biochemical and hematological parameters is fundamental for the identification of a healthy status and related optimal performances by sport doctors and trainers and selection of a correct workload by trainers. PMID:28356856

Oceans of Opportunity: Exploring Vertebrate Hematopoiesis in Zebrafish

PubMed Central

Carroll, Kelli J.; North, Trista E.

2015-01-01

Exploitation of the zebrafish model in hematology research has surged in recent years, becoming one of the most useful and tractable systems for understanding regulation of hematopoietic development, homeostasis, and malignancy. Despite the evolutionary distance between zebrafish and humans, remarkable genetic and phenotypic conservation in the hematopoietic system has enabled significant advancements in our understanding of blood stem and progenitor cell (HSPC) biology. The strengths of zebrafish in hematology research lie in the ability to perform real-time in vivo observations of hematopoietic stem, progenitor and effector cell emergence, expansion and function, as well as the ease with which novel genetic and chemical modifiers of specific hematopoietic processes or cell-types can be identified and characterized. Further, a myriad of transgenic lines have been developed including fluorescent reporter systems to aid in the visualization and quantification of specified cell types of interest and cell-lineage relationships, as well as effector lines that can be used to implement a wide range of experimental manipulations. As our understanding of the complex nature of HSPC biology during development, in response to infection or injury, or in the setting of hematological malignancy, continues to deepen, zebrafish will remain essential for exploring the spatio-temporal organization and integration of these fundamental processes, as well as the identification of efficacious small molecule modifiers of hematopoietic activity. In this review, we discuss the biology of the zebrafish hematopoietic system, including similarities and differences from mammals, and highlight important tools currently utilized in zebrafish embryos and adults to enhance our understanding of vertebrate hematology, with emphasis on findings that have impacted our understanding of the onset or treatment of human hematologic disorders and disease. PMID:24816275

Hematologic and plasma biochemical changes associated with fenbendazole administration in Hermann's tortoises (testudo hermanni).

PubMed

Neiffer, Donald L; Lydick, Dianna; Burks, Kyle; Doherty, Donna

2005-12-01

Toxicosis associated with benzimidazole anthelmintics has been reported with increasing frequency in zoologic collections. Clinical signs, clinicopathologic abnormalities, and gross and histologic lesions are primarily the result of damage to the gastrointestinal and hematopoietic systems. Profound leukopenia, especially granulocytopenia, is the most common and severe clinicopathologic change associated with benzimidazole administration. Death usually occurs from overwhelming systemic bacterial and/or fungal infections secondary to severe immunosuppression. In this 125-day study, six male Hermann's tortoises (Testudo hermanni) were treated orally with two 5-day courses of fenbendazole 2 wk apart at a dosage of 50 mg/kg. Serial blood samples were used to assess hematologic and plasma biochemical changes before, during, and following the treatment period. Although the tortoises remained healthy, blood sampling indicated an extended heteropenia with transient hypoglycemia, hyperuricemia, hyperphosphatemia, and equivocal hyperproteinemia/hyperglobulinemia, which were considered to be in response to fenbendazole administration. Changes in several other clinicopathologic parameters appeared to correlate with fenbendazole administration. The hematologic and biochemical changes seen in the healthy animals in this study should be considered when treating compromised tortoises with fenbendazole. Hematologic and plasma biochemical status of tortoises/reptiles should be determined before treatment and monitored during the treatment period. The risk of mortality of an individual from nematode infection should be assessed relative to the potential for metabolic alteration and secondary septicemia following damage to hematopoietic and gastrointestinal systems by fenbendazole.

Hematological parameters of human immunodeficiency virus positive pregnant women on antiretroviral therapy in Aminu Kano Teaching Hospital Kano, North Western Nigeria.

PubMed

Abdulqadir, Ibrahim; Ahmed, Sagir Gumel; Kuliya, Aisha Gwarzo; Tukur, Jamilu; Yusuf, Aminu Abba; Musa, Abubakar Umar

2018-01-01

Human immunodeficiency virus (HIV) scourge continues to affect young women within the reproductive age group and pregnancy is a recognized indication for the use antiretroviral (ARV) drugs among HIV-positive women. The aim is to determine the combined effect of pregnancy, HIV and ARV drugs on the hematological parameters of the pregnant women. This was a comparative cross-sectional study conducted among 70 each of HIV-positive and negative pregnant women. Bio-demographic and clinical data were extracted from the client folder and 4 ml of blood sample was obtained from each participant. Full blood count was generated using Swelab automatic hematology analyzer while reticulocyte count and erythrocyte sedimentation rate (ESR) were conducted manually. Data analysis was performed using SPSS version software 16 while P < 0.05 was considered statistically significant. Pregnant women with HIV had statistically significant lower hematocrit and white blood cell (WBC) and higher ESR than pregnant women without HIV ( P < 0.000). There was no statistically significant difference between the two groups in terms of platelet and reticulocyte ( P > 0.05). However, among HIV positive pregnant women, those with CD4 count <350/μL had statistically significant lower WBC and lymphocyte count than those with CD4 count ≥350/μL ( P < 0.05), whereas, those on zidovudine (AZT)-containing treatment had statistically significant lower hematocrit and higher mean cell volume than those on non-AZT-containing treatment ( P < 0.05), but there was no statistically significant difference in any of the hematological parameters ( P > 0.050) between women on first- and second-line ARV regimens. There is a significant difference in terms of hematological parameters between HIV-positive and HIV-negative pregnant women in this environment.

Efficacy and Safety of apatinib in patients with intermediate/advanced hepatocellular carcinoma: A prospective observation study.

PubMed

Yu, Wen-Chang; Zhang, Kong-Zhi; Chen, Shi-Guang; Liu, Wei-Fu

2018-01-01

This prospective study aimed to evaluate the efficacy and safety of apatinib in patients with intermediate/advanced hepatocellular carcinoma (HCC).The patients with intermediate/advanced HCC, who met predetermined inclusion and exclusion criteria, underwent oral treatment of apatinib 500 mg daily. The drug-related adverse effects were monitored by regular follow-up and workup including laboratory tests and imaging examinations. Tumor response was assessed by response evaluation criteria in solid tumor criteria. The time to tumor progression (TTP) and overall survival rate (OS) were calculated using the Kaplan-Meier method.A total of 31 patients were enrolled in the study from October 28, 2015 to December 28, 2016. The number of patients with intermediate and advanced HCC was 4 (12.90%) and 27 (87.10%), respectively. The mean tumor size was 9.47 ± 5.48 cm (range: 1.2-19 cm). Vascular invasion was seen in 14 patients (45.16%). A total of 21 (67.74%) patients exhibited extrahepatic metastases. On the basis of first follow-up computed tomography and magnetic resonance imaging at 6 weeks after treatment, 10 (32.26%), 15 (48.39%), and 6 (19.35%) of 31 patients achieved a partial response, stable disease, and progression of disease, respectively. Response rate and disease control rate were 32.26% and 80.65%, respectively. The median TTP was 4.8 months (95% confidence interval: 3.75-5.86 months). Furthermore, 6- and 12-month OS rates were 73.8% and 55.4%, respectively. Grade 3 thrombocytopenia (6.45%) and hypertension (48.39%) were the most common hematologic and nonhematologic toxicities. Grade 3 elevation of either serum total bilirubin or aminotransferase (6.45%) was observed as the top incidence among important indexes of liver function.Our preliminary findings suggest apatinib is a safe and effective therapy in intermediate/advanced HCC patients with high tumor response and survival rates. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Efficacy and Safety of apatinib in patients with intermediate/advanced hepatocellular carcinoma: A prospective observation study

PubMed Central

Yu, Wen-Chang; Zhang, Kong-Zhi; Chen, Shi-Guang; Liu, Wei-Fu

2018-01-01

Abstract This prospective study aimed to evaluate the efficacy and safety of apatinib in patients with intermediate/advanced hepatocellular carcinoma (HCC). The patients with intermediate/advanced HCC, who met predetermined inclusion and exclusion criteria, underwent oral treatment of apatinib 500 mg daily. The drug-related adverse effects were monitored by regular follow-up and workup including laboratory tests and imaging examinations. Tumor response was assessed by response evaluation criteria in solid tumor criteria. The time to tumor progression (TTP) and overall survival rate (OS) were calculated using the Kaplan–Meier method. A total of 31 patients were enrolled in the study from October 28, 2015 to December 28, 2016. The number of patients with intermediate and advanced HCC was 4 (12.90%) and 27 (87.10%), respectively. The mean tumor size was 9.47 ± 5.48 cm (range: 1.2–19 cm). Vascular invasion was seen in 14 patients (45.16%). A total of 21 (67.74%) patients exhibited extrahepatic metastases. On the basis of first follow-up computed tomography and magnetic resonance imaging at 6 weeks after treatment, 10 (32.26%), 15 (48.39%), and 6 (19.35%) of 31 patients achieved a partial response, stable disease, and progression of disease, respectively. Response rate and disease control rate were 32.26% and 80.65%, respectively. The median TTP was 4.8 months (95% confidence interval: 3.75–5.86 months). Furthermore, 6- and 12-month OS rates were 73.8% and 55.4%, respectively. Grade 3 thrombocytopenia (6.45%) and hypertension (48.39%) were the most common hematologic and nonhematologic toxicities. Grade 3 elevation of either serum total bilirubin or aminotransferase (6.45%) was observed as the top incidence among important indexes of liver function. Our preliminary findings suggest apatinib is a safe and effective therapy in intermediate/advanced HCC patients with high tumor response and survival rates. PMID:29505026

Eosinophilic pustular folliculitis associated with hematological disorders: A report of two cases and review of Japanese literature.

PubMed

Takamura, Saori; Teraki, Yuichi

2016-04-01

Eosinophilic pustular folliculitis (EPF) occurs in patients with hematological disorders. However, clinical information about hematological disorder-associated EPF is scarce. We report two cases of EPF associated with mantle cell lymphoma and reviewed the available published work on Japanese cases. We identified a total of 23 Japanese cases, including the two cases reported here, who had hematological disorder-associated EPF. Fourteen cases were associated with treatment for hematological malignancies (transplantation-related EPF) and nine cases were associated with hematological malignancies themselves (hematological malignancy-related EPF). Although the skin eruption was clinically indistinguishable between the two subtypes, transplantation-related EPF occurred on the face and trunk of young and middle-aged men and women, whereas hematological malignancy-related EPF occurred mostly on the face of older men. Peripheral blood eosinophilia was more frequently observed in transplantation-related EPF. These observations suggest variations among patients with EPF associated with hematological disorders. © 2015 Japanese Dermatological Association.

[Hematological and immunological parameters during Ebola virus passages in guinea-pigs].

PubMed

Dadaeva, A A; Sizikova, L P; Subbotina, E L; Chepurnov, A A

2006-01-01

The trend in hematological and immunological parameters during Ebola virus passages in guinea-pigs indicated that pathophysiological changes occurred just during the second passage and further became stronger. The increase of some parameters and their correlation with the occurrence of fatal outcomes allowed the authors to reveal the most significant changes as increased juvenile platelets, whole blood virus appearance, higher echinocytes, a rise in the pro mil of blast cells and megakaryocytes in the bone marrow, and decreased neutrophilic phagocytic activity. Viral acquisition of the properties of lethality to guinea-pigs depends on the fine mechanisms responsible for viral interaction with host cells, which may lead to viral genetic changes during passages.

EXPERIMENTAL USEFULNESS OF THE KANGAROO RAT

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

Haley, T.J.

1963-09-13

The kangaroo rat is readily tamed and has certain characteristics that make it unique and of interest in highly specialized research programs. Studies were conducted on its ability to exist on a dried diet with only a bare minimum of water and that obtained from succulent plants. Hematological studies indicate that the kangaroo rat exhibits a different hematological distribution of cells than the mouse or rat. The lymphocyte constitutes 81.4% of the total leokocytes. The hematocrit has a value of 46 to 48 in spite of the high degree of water conservation practiced by the animal. The response to ionizingmore » radiation of this species does not differ from that reported for the mouse or rat. Behavior studies indicate that the digging characteristics of the kangaroo rat are similar to those of the gerbil. Furthermore, the animal shows definite psychotic tendencies under the influence of psychotomimetics like LSD-25 and psilocybin. An evaluation of the physiological responses of isolated tissues from this animal as well as its responses to anesthetics is being undertaken to evaluate its further usefulness in the laboratory. (auth)« less

Hematological parameters in relation to age, sex and biochemical values for mute swans (Cygnus olor).

PubMed

Dolka, B; Włodarczyk, R; Zbikowski, A; Dolka, I; Szeleszczuk, P; Kluciński, W

2014-06-01

The knowledge of the correct morphological and biochemical parameters in mute swans is an important indicator of their health status, body condition, adaptation to habitat and useful diagnostic tools in veterinary practice and ecological research. The aim of the study was to obtain hematological parameters in relation to age, sex and serum biochemistry values in wild-living mute swans. We found the significant differences in the erythrocyte count, hematocrit, hemoglobin concentration and erythrocyte sedimentation rate in relation to age of mute swans. There were no differences in hematological values between males and females. The leukogram and H/L ratio did not vary by age and sex in swans. Among of biochemical parameters the slightly increased AST, ALP, CK, K, urea, decreased CHOL and TG values were recorded. As far as we know, this is the first study in which the morphometric parameters of blood cells in mute swans were presented. We found extremely low concentration of lead in blood (at subthreshold level). No blood parasites were found in blood smears. The analysis of body mass and biometric parameters revealed a significant differences dependent on age and sex. No differences in the scaled mass index were found. Our results represent a normal hematologic and blood chemistry values and age-sex related changes, as reference values for the mute swan.

Evaluation of 143 Cases of Immune Thrombocytopenic Purpura With Regards to Clinical Course and Response to Treatment

PubMed Central

Albayrak, Murat; Balcik, Ozlem Sahin; Aki, Sahika Zeynep; Gokmen, Ayla; Ceran, Funda; Yokus, Osman; Dagdas, Simten; Ayli, Meltem; Ozet, Gulsum

2010-01-01

Objective: Immune thrombocytopenic purpura (ITP) is also known as idiopathic thrombocytopenic purpura. Increased platelet destruction and insufficient platelet production are both responsible for its etiopathogenesis. ITP can be diagnosed after excluding other possible causes of thrombocytopenia. Materials and Methods: One hundred forty-three cases of chronic ITP that were monitored in a hematology clinic were retrospectively evaluated. All cases received first line treatment of 1 mg/kg/day prednisolone. Corticosteroid nonresponsive (CN) cases and corticosteroid-dependent (CD) cases underwent splenectomies. Results: The rate of CN/CD cases was found to be 53% (n=76). Sixty-six percent of these cases (n=50) underwent splenectomies. The ratio of non-responsive cases to relapse cases after splenectomy (SN/SR) was 30% (n=15). The total number of cases was 41, including those without splenectomy (n=26) and with SY/SR (n=15). Helicobacter pylori (Hp) eradication, immunosuppressive agents and danazol treatments were administered to patients (n=10, n=14 and n=4, respectively). Currently, 13 patients are being monitored without treatment. Fifteen patients who were non-responsive to Hp eradication treatment, immunosuppressive treatment or danazol treatment are still being monitored without any treatment. Conclusion: Optimal treatment is not available for splenectomy-resistant cases of ITP. The response rates for Hp eradication treatment, immunosuppressive treatments and anabolic agents are low. Therefore, larger studies with more patients are required using new agents, such as thrombopoietin (TPO) receptor agonists and anti-CD20 monoclonal antibodies. PMID:25610140

The efficacy and safety of pomalidomide in relapsed/refractory multiple myeloma in a "real-world" study: Polish Myeloma Group experience.

PubMed

Charlinski, Grzegorz; Grzasko, Norbert; Jurczyszyn, Artur; Janczarski, Mariusz; Szeremet, Agnieszka; Waszczuk-Gajda, Anna; Bernatowicz, Paweł; Swiderska, Alina; Guzicka-Kazimierczak, Renata; Lech-Maranda, Ewa; Szczepaniak, Andrzej; Wichary, Ryszard; Dmoszynska, Anna

2018-06-08

Patients with relapsed/refractory multiple myeloma (RRMM) have poor prognosis. Pomalidomide is an immunomodulatory compound that has demonstrated activity in MM patients with disease refractory to lanlidomide and bortezomib. Participants of clinical trials are highly selected populations; therefore, the aim of this study was to present observations from real practice that might provide important information for practitioners. We analyzed retrospectively 50 patients treated with pomalidomide in 12 Polish sites between 2014 and 2017. Median age was 63 years, median time since diagnosis 4.5 years and median number of prior regimens 4. The overall response rate was 39.1%. Median progression-free survival (PFS) and overall survival (OS) were 10.0 and 14.0 months, respectively. Previous treatment with immunomodulatory drugs, bortezomib or stem cell transplant had no impact on PFS and OS. Most frequent grade 3/4 treatment-emergent adverse events were hematologic (neutropenia 24.0%, thrombocytopenia 10.0%, anemia 8.0%). Most common grade 3/4 non-hematologic toxicities were respiratory tract infection (14.0%) and neuropathy (4.0%). This real-world data have confirmed that pomalidomide is an active drug in RRMM and support results of published clinical trials and other real-world studies. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Clinical outcomes of TS-1 chemotherapy for advanced and recurrent gastric cancer.

PubMed

Lee, Sung Ryol; Kim, Hyung Ook; Yoo, Chang Hak

2011-09-01

Titanium silicate (TS)-1 chemotherapy has been widely used against gastric cancer in Japan. The aim of the present study was to assess the efficacy and hematological safety of TS-1 as treatment for advanced and recurrent gastric cancer. From September 2006 to February 2011, 51 advanced or recurrent gastric cancers were treated with TS-1. One course of treatment consisted of 40, 50, or 60 mg/m(2) of TS-1 twice a day for 28 days, followed by withdrawal for two weeks. The primary end point was progression-free survival (PFS), and the secondary end point was overall survival (OS). The disease control rate was 39.2% (complete response, 0/51; partial response, 6/51; stable disease, 14/51; progressive disease, 23/51; not evaluable, 8/51). The median PFS was 4.0 months (95% confidence interval [CI], 2.2 to 5.7); the median PFS of the advanced group was 6.0 months (95% CI, 2.8 to 9.1), and the median PFS of the recurrent group was 3.0 months (95% CI, 1.8 to 4.1). The median OS was 11.0 months (95% CI, 6.3 to 15.6); the median OS of the advanced group was 10.0 months (95% CI, 4.9 to 15.0), and the median OS of the recurrent group was 14.0 months (95% CI, 4.1 to 23.8). Grade 3 or 4 hematological toxicity occurred in three patients (5.9%), anemia occurred in two patients (3.9%), and thrombocytopenia occurred in one patient (2%). TS-1 chemotherapy was safe and effective, with relatively long PFS and OS in patients with advanced and recurrent gastric cancers.

A multicenter phase II study of carboplatin in advanced ovarian carcinoma: final report.

PubMed

Kjorstad, K; Harris, A; Bertelsen, K; Slevin, M; Schultz, H; Hellman, K; Janssens, N; Martin, A; Canetta, R

1992-03-01

A phase II trial of single-agent carboplatin in advanced ovarian cancer was performed by 19 institutions from 10 European countries. A total of 260 patients were treated, with a median age of 55 (range: 20-79) years. Karnofsky performance status was 80-100 in about two-thirds of the patients. Prior therapy consisted of surgery only in 31 patients, irradiation in 9, chemotherapy without cisplatin in 45, and with cisplatin in 175. Carboplatin was administered as second-line therapy in about one-half and as third-line or more in one additional third of the study population. Initial dose was 400 mg/m2 in 90, 360 mg/m2 in 152, and 320 mg/m2 or less in 18 patients. A total of 971 courses (mean 3.7, median 2, range: 1-13) of therapy were administered. A total of 16 complete and 46 partial responses were observed in 226 evaluable patients, for an objective response rate of 27%. Efficacy was greater in chemotherapy-untreated patients (51% vs. 23%, p = 0.002). In cisplatin-pretreated patients activity was significantly higher in non-refractory patients (26% vs. 4%, p = 0.015). Myelosuppression was the most significant side effect. However, low hematologic counts seldom translated into clinically significant complications. Patients with impaired baseline creatinine clearance and poor performance status were at higher risk of developing severe myelosuppression during the initial course of treatment. Non hematologic side effects were rare and mild, except for emesis. Carboplatin has a definite role in the treatment of ovarian cancer, but almost complete cross-resistance with the parent compound was observed clinically.

Chronic myeloid leukemia patients in Tunisia: epidemiology and outcome in the imatinib era (a multicentric experience).

PubMed

Ben Lakhal, Raihane; Ghedira, Hela; Bellaaj, Hatem; Ben Youssef, Yosra; Menif, Samia; Manai, Zeineb; Bedoui, Manel; Lakhal, Amel; M'Sadek, Fehmi; Elloumi, Moez; Khélif, Abderrahmane; Ben Romdhane, Neila; Laatiri, Mohamed Adnène; Ben Othmen, Tarek; Meddeb, Balkis

2018-04-01

Data are limited in developing countries regarding the clinicopathologic features and response to therapy of chronic myeloid leukemia (CML) in the era of imatinib (IM). The objective of this study is to report on the clinicoepidemiologic features of CML in Tunisia, to evaluate the long-term outcome of patients in chronic (CP) or accelerated phase (AP) treated with IM 400 mg daily as frontline therapy, and to determine imatinib's efficacy and safety. From October 2002 to December 2014, 410 CML patients were treated with IM in six Tunisian departments of hematology. Response (hematologic, cytogenetic, and molecular responses) and outcome-overall survival (OS), event-free survival (EFS), and progression-free survival (PFS)-were evaluated. The following prognostic factors were analyzed for their impact on the European leukemia net (ELN) response, OS, EFS, and PFS at 5 years: age, sex, leukocyte count, Sokal score, European Treatment and Outcome Study (EUTOS) score, CML phase, time to starting IM, and impact of adverse events. The median age was 45 years (3-85 years). Two hundred ten (51.2%) patients were male. Splenomegaly was present in 322 of the 410 (79%). Additional cytogenetic abnormalities were encountered in 25 (6.3%) patients. At diagnosis, 379 (92.4%) patients were in CP, 31 (7.6%) were in AP. The Sokal risk was low in 87 (22.5%), intermediate in 138 (35.7%), and high in 164 patients (41.9%). The EUTOS risk was low in 217 (74%), and high in 77 (26%) patients. The rates of cumulative complete cytogenetic response (CCyR), major molecular response (MMR), and molecular response 4/5 log (MR4.5) in CP/AP-CML patients were 72, 68.4, and 46.4%, respectively. The median time to reach CCyR, MMR, and MR4.5 was 6 months (3-51), 18 months (3-72), and 24 months (3-100), respectively. According to the ELN criteria, optimal, suboptimal response, and failure were noted in 206 (51.8%), 61 (15.3%), and 125 (31.4%) patients, respectively. Five-year event-free survival (EFS), progression-free survival (PFS), and overall survival (OS) were 81, 90, and 90%, respectively. By multivariate analysis, AP, high EUTOS risk, and baseline WBC ≥ 150G/l remained independent predictive factors of non-optimal response to IM. The adverse events (AE) of IM were moderate and tolerable. With the caveats that the monitoring of the disease was not optimal, response rates were similar to those reported in previous studies. It is clear to us that improvements should be made in treatment of AP-CML and high Sokal risk group of CP-CML. The frontline use of second-generation tyrosine kinase inhibitor (TKI) is expected to improve the results of the first-line treatment of these high-risk Tunisian patients, but cost and accessibility of this therapy remain the problems in developing countries.

Concomitant chemoradiotherapy versus induction docetaxel, cisplatin and 5 fluorouracil (TPF) followed by concomitant chemoradiotherapy in locally advanced head and neck cancer: a phase II randomized study.

PubMed

Paccagnella, A; Ghi, M G; Loreggian, L; Buffoli, A; Koussis, H; Mione, C A; Bonetti, A; Campostrini, F; Gardani, G; Ardizzoia, A; Dondi, D; Guaraldi, M; Cavallo, R; Tomio, L; Gava, A

2010-07-01

Concomitant chemoradiotherapy (CT/RT) is the standard treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN). We evaluated the efficacy of induction docetaxel (Taxotere), cisplatin, and 5-fluorouracil (TPF) before CT/RT versus CT/RT alone. Patients with stage III-IVM0 SCCHN, Eastern Cooperative Oncology Group performance status of zero to one, were randomly assigned to receive CT/RT alone (arm A: two cycles of cisplatin 20 mg/m(2), days1-4, plus 5-fluorouracil 800 mg/m(2)/day 96 h continuous infusion, during weeks 1 and 6 of radiotherapy) or three cycles of TPF (arm B: docetaxel 75 mg/m(2) and cisplatin 80 mg/m(2), day 1, and 5-fluorouracil 800 mg/m(2)/day 96 h continuous infusion, every 3 weeks) followed by the same CT/RT. The primary end point was the rate of radiologic complete response (CR) at 6-8 weeks after the end of CT/RT. A total of 101 patients were randomly allocated to the study (51 arm A; 50 arm B). CR rates were 21.2% (arm A) versus 50% (arm B). Median progression-free survival and overall survival were, respectively, 19.7 and 33.3 months (arm A) and 30.4 and 39.6 months (arm B). Hematologic and non-hematologic toxic effects during CT/RT were similar in the two arms. Induction TPF followed by CT/RT was associated with higher radiologic CR in patients with locally advanced SCCHN with no negative impact on CT/RT feasibility.

Efficacy of combination chemotherapy using irinotecan and nedaplatin for patients with recurrent and refractory endometrial carcinomas: preliminary analysis and literature review.

PubMed

Miyamoto, Morikazu; Takano, Masashi; Kuwahara, Mika; Soyama, Hiroaki; Kato, Kento; Matuura, Hiroko; Sakamoto, Takahiro; Takasaki, Kazuki; Aoyama, Tadashi; Yoshikawa, Tomoyuki; Furuya, Kenichi

2018-01-01

We aimed to retrospectively evaluate the efficacy and toxicity of an irinotecan hydrochloride (CPT) and nedaplatin (N) combination therapy for recurrent and refractory endometrial carcinoma, administered based on UGT1A1 genotype. Between 2009 and 2017, 21 patients who received CPT-N therapy for recurrent endometrial carcinoma as second- or third-line chemotherapy at our hospital were identified. The CPT-N regimen included 40-70 mg/m 2 of CPT-11 on days 1, 8, and 15, and 50 mg/m 2 of nedaplatin on day 1, q4 weeks. The median patient age was 63 years. The number of prior chemotherapeutic regimens ranged from 1 to 2. Two patients had prior pelvic irradiation. The response rate [ratio of complete remission (CR) to partial remission (PR)] of CPT-N therapy was 3 of 21 (14.3%), and clinical benefit rate (CBR) [the combined percentages of CR, PR, and stable disease (SD)] was 9 of 21 (42.8%). Toxicities included grade 3 neutropenia [4 (19.0%) cases], grade 3 febrile neutropenia [2 (9.5%) cases], and grade 3 diarrhea [3 (14.3%) cases]; all resolved with conservative treatment. Patients with a wild-type UGT1A1 status received higher doses of CPT-11 (p = 0.048) and had similar RR and CBR compared to those with a UGT1A1*6 and *28 status. There were no significant differences in frequencies of hematological or non-hematological toxicities, regardless of UGT1A1 status. The CPT-N regimen for recurrent and refractory endometrial carcinoma had tolerable side effects and significant efficacy. This regimen is a viable treatment option for endometrial carcinoma.

Phase II trial of yttrium-90-DOTA-biotin pretargeted by NR-LU-10 antibody/streptavidin in patients with metastatic colon cancer

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

Knox, S J.; Goris, M L.; Tempero, M

A Phase II study of yttrium-90-tetra-azacyclododecanetetra-acetic acid-biotin (Y-90-DOTA-biotin) pretargeted by NR-LU-10 antibody/streptavidin (SA) was performed. The primary objectives of the study were to evaluate the efficacy and safety of this therapy in patients with metastatic colon cancer. Twenty-five patients were treated with a single dose of 110 mCi/m{sup 2} (mean administered dose, 106.5-10.3 mCi/m{sup 2}) of Y-90-DOTA-biotin. There were three components of the therapy. Patients first received NR-LU-10/SA on day 1. A clearing agent (biotin-galactose-human serum albumin) was administered 48 h after the NR-LU-10/SA to remove residual circulating unbound NR-LU-10/SA. Lastly, 24 h after administration of clearing agent, patients receivedmore » biotin-DOTA-labeled with 110 mCi/m{sup 2} Y-90. All three components of the therapy were administered i.v. Both hematological and nonhematological toxicities were observed. Diarrhea was the most frequent grade 4 nonhematological toxicity (16%; with 16% grade 3 diarrhea). Hematological toxicity was less severe with 8% grade 3 and 8% grade 4 neutropenia and 8% grade 3 and 16% grade 4 thrombocytopenia. The overall response rate was 8%. Two partial responders had freedom from progression of 16 weeks. Four patients (16%) had stable disease with freedom from progression of 10-20 weeks. Despite the relatively disappointing results of this study in terms of therapeutic efficacy and toxicity, proof of principle was obtained for the pretargeting approach. In addition, valuable new information was obtained about normal tissue tolerance to low-dose-rate irradiation that will help to provide useful guidelines for future study designs.« less

An assessment of hematological and biochemical responses in the tropical fish Epinephelus stoliczkae of Chabahar Bay and Gulf of Oman under chromium exposure: ecological and experimental tests.

PubMed

Sadeghi, Parvin; Savari, Ahmad; Movahedinia, Abdolali; Safahieh, Alireza; Azhdari, Danial

2014-05-01

The aim of this investigation was to evaluate the effect of chromium on hematological and biochemical parameters in Epaulet Grouper, Epinephelus stoliczkae of Chabahar Bay and Gulf of Oman by ecological and experimental tests. Spatial evaluation of ecological test results showed these parameters had significant difference among some sampling sites. Examination of hematological and biochemical profiles on Epaulet Grouper was performed after 0.5, 1, 7, 14, and 21 days of chromium exposure (3.6, 7.31 and 14.6 mg/L). Experimental test results of chromium induce indicated the significant decrease in MCV, MCH, neutrophils, basophils, plasma protein and significant increase in MCHC, lymphocytes, monocytes, eosinophils and a biphasic trend in Hb, Ht, RBC, WBC, and glucose (p < 0.05). Cellular and nuclear axis, cytoplasmic volume, cell and nuclear volume, and surface area were significantly different for ecological and experimental results (p < 0.05). It was concluded that these parameters are sensitive in monitoring the toxicity of chromium concentrations.

The Final (Oral Ebola) Vaccine Trial on Captive Chimpanzees?

PubMed Central

Walsh, Peter D.; Kurup, Drishya; Hasselschwert, Dana L.; Wirblich, Christoph; Goetzmann, Jason E.; Schnell, Matthias J.

2017-01-01

Could new oral vaccine technologies protect endangered wildlife against a rising tide of infectious disease? We used captive chimpanzees to test oral delivery of a rabies virus (RABV) vectored vaccine against Ebola virus (EBOV), a major threat to wild chimpanzees and gorillas. EBOV GP and RABV GP-specific antibody titers increased exponentially during the trial, with rates of increase for six orally vaccinated chimpanzees very similar to four intramuscularly vaccinated controls. Chimpanzee sera also showed robust neutralizing activity against RABV and pseudo-typed EBOV. Vaccination did not induce serious health complications. Blood chemistry, hematologic, and body mass correlates of psychological stress suggested that, although sedation induced acute stress, experimental housing conditions did not induce traumatic levels of chronic stress. Acute behavioral and physiological responses to sedation were strongly correlated with immune responses to vaccination. These results suggest that oral vaccination holds great promise as a tool for the conservation of apes and other endangered tropical wildlife. They also imply that vaccine and drug trials on other captive species need to better account for the effects of stress on immune response. PMID:28277549

AMBIENT COARSE PARTICULATE MATTER ASSOCIATED WITH HEMATOLOGIC FACTORS IN ADULT ASTHMATICS

EPA Science Inventory

Introduction: The elderly and those with cardiovascular disease are susceptible to particulate matter (PM) exposures. Asthmatics are thought to be primarily affected by PM via airway inflammation. We investigated whether factors in blood hemostasis change in response to fluctuat...

Adoptive T cell therapy: An overview of obstacles and opportunities.

PubMed

Baruch, Erez Nissim; Berg, Amy Lauren; Besser, Michal Judith; Schachter, Jacob; Markel, Gal

2017-06-01

The therapeutic potential of adoptive cell therapy (ACT) in cancer patients was first acknowledged 3 decades ago, but it was an esoteric approach at the time. In recent years, technological advancements have transformed ACT into a viable therapeutic option that can be curative in some patients. In fact, current ACT response rates are 80% to 90% for hematological malignancies and 30% for metastatic melanoma refractory to multiple lines of therapy. Although these results are encouraging, there is still much to be done to fulfill ACT's potential, specifically with regard to improving clinical efficacy, expanding clinical indications, reducing toxicity, and increasing production and cost-effectiveness. This review addresses the current major obstacles to ACT and presents potential solutions. Cancer 2017;123:2154-62. © 2017 American Cancer Society. © 2017 American Cancer Society.

Randomized, double-blind phase II study to compare nitroglycerin plus oral vinorelbine plus cisplatin with oral vinorelbine plus cisplatin alone in patients with stage IIIB/IV non-small cell lung cancer (NSCLC).

PubMed

Reinmuth, N; Meyer, A; Hartwigsen, D; Schaeper, C; Huebner, G; Skock-Lober, R; Bier, A; Gerecke, U; Held, C-P; Reck, M

2014-03-01

Adding nitroglycerin to the combination of vinorelbine plus cisplatin has been reported to improve the overall survival (OS) of Asian patients with stage IIIB/IV non-small cell lung cancer (NSCLC) probably due to better drug delivery based on changed vascular tonus. The main objective of our study was to evaluate the effect of adding nitroglycerin to vinorelbine and cisplatin in a Caucasian population. 66 chemonaïve patients with stage IIIB/IV NSCLC received oral vinorelbine (first cycle 60 mg/m(2), subsequent cycles: 80 mg/m(2) in the absence of any hematological toxicity ≥ grade 3 in cycle 1) once daily on days 1 and 8 of each cycle and cisplatin (80 mg/m(2) i.v.) on day 1 of each cycle (q3w). Nitroglycerin (arm A, n=34) or placebo patches (arm B, n=32) were administered once daily from day -3 to day 2 of each cycle and were removed about 12h after administration. One nitroglycerin patch contained 25mg nitroglycerin. Median age was 62.5 (33-82) years. In the overall population (n=66), the objective response rate (ORR) was 27.3% (all PR; 95%CI: 17.0-39.6), with a disease control rate (DCR) of 57.6% (95%CI: 44.8-69.7), a median time to progression (TTP) of 4.8 months (n=58; 95%CI: 3.4-5.9) and a median overall survival (OS) of 11.5 months (95%CI: 7.9-13.6). ORR and DCR were numerically higher in arm A than in arm B (35.3% vs. 18.8% and 61.8% vs. 53.1%, respectively), whereas TTP and OS were comparable. The main hematological and non-hematological toxicities grade ≥ 3 were moderate with no significant differences between the two treatment arms. Overall, oral vinorelbine plus cisplatin showed a high level of efficacy and adequate tolerability in first line treatment of NSCLC. Despite the low sample size per group the results seem to confirm the previous results reported in Asian patients. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

ATF4 induction through an atypical integrated stress response to ONC201 triggers p53-independent apoptosis in hematological malignancies

PubMed Central

Ishizawa, Jo; Kojima, Kensuke; Chachad, Dhruv; Ruvolo, Peter; Ruvolo, Vivian; Jacamo, Rodrigo O.; Borthakur, Gautam; Mu, Hong; Zeng, Zhihong; Tabe, Yoko; Allen, Joshua E.; Wang, Zhiqiang; Ma, Wencai; Lee, Hans C.; Orlowski, Robert; Sarbassov, Dos D.; Lorenzi, Philip L.; Huang, Xuelin; Neelapu, Sattva S.; McDonnell, Timothy; Miranda, Roberto N.; Wang, Michael; Kantarjian, Hagop; Konopleva, Marina; Davis, R. Eric.; Andreeff, Michael

2016-01-01

The clinical challenge posed by p53 abnormalities in hematological malignancies requires therapeutic strategies other than standard genotoxic chemotherapies. ONC201 is a first-in-class small molecule that activates p53-independent apoptosis, has a benign safety profile, and is in early clinical trials. We found that ONC201 caused p53-independent apoptosis and cell cycle arrest in cell lines and in mantle cell lymphoma (MCL) and acute myeloid leukemia (AML) samples from patients; these included samples from patients with genetic abnormalities associated with poor prognosis or cells that had developed resistance to the nongenotoxic agents ibrutinib and bortezomib. Moreover, ONC201 caused apoptosis in stem and progenitor AML cells and abrogated the engraftment of leukemic stem cells in mice while sparing normal bone marrow cells. ONC201 caused changes in gene expression similar to those caused by the unfolded protein response (UPR) and integrated stress responses (ISRs), which increase the translation of the transcription factor ATF4 through an increase in the phosphorylation of the translation initiation factor eIF2α. However, unlike the UPR and ISR, the increase in ATF4 abundance in ONC201-treated hematopoietic cells promoted apoptosis and did not depend on increased phosphorylation of eIF2α. ONC201 also inhibited mammalian target of rapamycin complex 1 (mTORC1) signaling, likely through ATF4-mediated induction of the mTORC1 inhibitor DDIT4. Overexpression of BCL-2 protected against ONC201-induced apoptosis, and the combination of ONC201 and the BCL-2 antagonist ABT-199 synergistically increased apoptosis. Thus, our results suggest that by inducing an atypical ISR and p53-independent apoptosis, ONC201 has clinical potential in hematological malignancies. PMID:26884599

Bleeding frequency and characteristics among hematologic malignancy inpatient rehabilitation patients with severe thrombocytopenia.

PubMed

Fu, Jack B; Tennison, Jegy M; Rutzen-Lopez, Isabel M; Silver, Julie K; Morishita, Shinichiro; Dibaj, Seyedeh S; Bruera, Eduardo

2018-03-28

To identify the frequency and characteristics of bleeding complications during acute inpatient rehabilitation of hematologic malignancy patients with severe thrombocytopenia. Retrospective descriptive analysis. Comprehensive cancer center acute inpatient rehabilitation unit. Consecutive hematologic malignancy patients with a platelet count of less than or equal to 20,000/microliter (μL) on the day of acute inpatient rehabilitation admission from 1/1/2005 through 8/31/2016. Medical records were retrospectively analyzed for demographic, laboratory, and medical data. Patients were rehabilitated using the institutional exercise guidelines for thrombocytopenic patients. Bleeding events noted in the medical record. Out of 135 acute inpatient rehabilitation admissions, 133 unique patients were analyzed with a total of 851 inpatient rehabilitation days. The mean platelet count was 14,000/μL on the day of admission and 22,000/μL over the course of the rehabilitation admission. There were 252 days of inpatient rehabilitation where patients had less than 10,000/μL platelets. A total of 97 bleeding events were documented in 77/135 (57%) admissions. Of the 97 bleeding events, 72 (74%), 14 (14%), and 11 (11%) were considered to be of low, medium, and high severity, respectively. There were 4/97 (4%) bleeding events that were highly likely attributable to physical activity but only 1/4 was considered high severity. Bleeding rates were .09, .08, .17, and .37 for > 20,000, 15-20,000, 10-15,000, and < 10,000/μL mean platelet counts respectively (p = .003). Forty-four percent of patients were transferred back to the primary acute care service with infection being the most common reason for transfer. This study is the first to examine exercise-related bleeding complications during acute inpatient rehabilitation in severely thrombocytopenic hematologic cancer patients. Bleeding rates increased with lower platelet counts. However, using the exercise guidelines for severely thrombocytopenic patients, the risk of severe exercise-related bleeding events was low.

Azacytidine in combination with tyrosine kinase inhibitors induced durable responses in patients with advanced phase chronic myelogenous leukemia.

PubMed

Ruggiu, Mathilde; Oberkampf, Florence; Ghez, David; Cony-Makhoul, Pascale; Beckeriche, Florence; Cano, Isabelle; Taksin, Anne L; Benbrahim, Omar; Ghez, Stéphanie; Farhat, Hassan; Rigaudeau, Sophie; de Gunzburg, Noémie; Lara, Diane; Terre, Christine; Raggueneau, Victoria; Garcia, Isabel; Spentchian, Marc; De Botton, Stéphane; Rousselot, Philippe

2017-11-28

Although the tyrosine kinase inhibitor (TKI) era has brought great improvement in outcome in chronic myelogenous leukemia (CML), prognosis of accelerated phase or myeloid blast crisis patients or of de novo Philadelphia chromosome-positive acute myeloid leukemia remains poor. We conducted a retrospective study on patients with advanced phase disease treated with a TKI and azacytidine. Sixteen patients were eligible. Median age was 64.9 years, the median number of previous therapies was 2.5 lines, and median follow-up was 23.1 months. Hematologic response (HR) rate was 81.3%. Median overall survival (OS), event free survival and relapse-free survival (RFS) were 31.5, 23.3, and 32.2 months, respectively. All except one patient were treated as out-patients after the first cycle. Five patients were bridged to allogenic hematopoietic stem cells transplant. The combination of a TKI and azacytidine is a safe and efficient regiment for patients with CML patients in advanced phases.

Thalidomide, clarithromycin, lenalidomide and dexamethasone therapy in newly diagnosed, symptomatic multiple myeloma.

PubMed

Mark, Tomer M; Bowman, Isaac A; Rossi, Adriana C; Shah, Manan; Rodriguez, Melissa; Quinn, Ryann; Pearse, Roger N; Zafar, Faiza; Pekle, Karen; Jayabalan, David; Ely, Scott; Coleman, Morton; Chen-Kiang, Selina; Niesvizky, Ruben

2014-12-01

We studied T-BiRD (thalidomide [Thalomid(®)], clarithromycin [Biaxin(®)], lenalidomide [Revlimid(®)] and dexamethasone) in symptomatic, newly diagnosed multiple myeloma. In 28-day cycles, patients received dexamethasone 40 mg/day on days 1, 8, 15, 22, clarithromycin 500 mg twice daily on days 1-28; lenalidomide 25 mg/day on days 1-21; and thalidomide 100 mg/day (50 mg/day on days 1-7 of cycle 1 only) on days 1-28. Twenty-six patients received a median of 6 cycles (range 0-41). Overall response rate (ORR) was 80% for the group and 100% in 11 patients who underwent autologous stem cell transplantation as part of first-line therapy. The 4-year overall survival rate was 74.9%, and the median progression-free survival was 35.6 months. Eight patients discontinued due to regimen toxicity. Grade 3 non hematologic toxicity affected 12 patients (46.2%). T-BiRD is a highly active regimen with potential toxicity limitations. ClinicalTrials.gov identifier: NCT00538733.

Multicenter analysis of treatment outcomes in adult patients with lymphoblastic lymphoma who received hyper-CVAD induction followed by hematopoietic stem cell transplantation.

PubMed

Jeong, Seong Hyun; Moon, Joon Ho; Kim, Jin Seok; Yang, Deok-Hwan; Park, Yong; Cho, Seok Goo; Kwak, Jae-Yong; Eom, Hyeon Seok; Won, Jong Ho; Hong, Jun Shik; Oh, Sung Yong; Lee, Ho Sup; Kim, Seok Jin

2015-04-01

The hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) regimen has been widely used for lymphoblastic lymphoma (LBL) as a primary treatment. However, there is few data about its treatment outcome in Asian patients. Thus, we conducted this study to evaluate the efficacy of hyper-CVAD induction and stem cell transplantation (SCT) consolidation in LBL patients. The treatment responses of 49 patients treated with the hyper-CVAD regimen were retrospectively analyzed in 13 institutions. Given 24 patients who responded to hyper-CVAD underwent consolidation treatment with SCT, overall survival (OS) and progression-free survival (PFS) of patients who received SCT were compared with patients who did not. The overall response rate was 79 %: 73 % (36/49) complete responses, 6 % (3/49) partial responses, and 4 % (2/49) induction deaths. The major limitation for the delivery of the planned hyper-CVAD cycles was hematological toxicity. Among 39 responders, 24 patients underwent autologous (n = 16) and allogeneic SCT (n = 8) consolidation. Their 3-year OS and PFS rates were 76 and 78 %, respectively, and there was no difference in survival outcomes between autologous and allogeneic SCT. However, 15 patients without SCT consolidation showed poorer PFS even though they all achieved complete response. Thus, only seven patients maintained their response at the time of analysis. In conclusion, the hyper-CVAD regimen is effective for remission induction in LBL, and SCT consolidation after hyper-CVAD induction produced better clinical outcomes than did continuation of hyper-CVAD.

Low usage rate of banked sibling cord blood units in hematopoietic stem cell transplantation for children with hematological malignancies: implications for directed cord blood banking policies.

PubMed

Goussetis, Evgenios; Peristeri, Ioulia; Kitra, Vasiliki; Papassavas, Andreas C; Theodosaki, Maria; Petrakou, Eftichia; Spiropoulos, Antonia; Paisiou, Anna; Soldatou, Alexandra; Stavropoulos-Giokas, Catherine; Graphakos, Stelios

2011-02-15

Directed sibling cord blood banking is indicated in women delivering healthy babies who already have a sibling with a disease that is potentially treatable with an allogeneic cord blood transplant. We evaluated the effectiveness of a national directed cord blood banking program in sibling HLA-identical stem cell transplantation for hematological malignancies and the factors influencing the usage rate of the stored cord blood units. Fifty families were enrolled from which, 48 cord blood units were successfully collected and 2 collections failed due to damaged cord/placenta at delivery. Among enrolled families 4 children needed transplantation; however, only one was successfully transplanted using the collected cord blood unit containing 2×10(7) nucleated cells/kg in conjunction with a small volume of bone marrow from the same HLA-identical donor. Two children received grafts from matched unrelated donors because their sibling cord blood was HLA-haploidentical, while the fourth one received bone marrow from his HLA-identical brother, since cord blood could not be collected due to damaged cord/placenta at delivery. With a median follow-up of 6 years (range, 2-12) for the 9 remaining HLA-matched cord blood units, none from the prospective recipients needed transplantation. The low utilization rate of sibling cord blood in the setting of hematopoietic stem cell transplantation for pediatric hematological malignant diseases necessitates the development of directed cord blood banking programs that limit long-term storage for banked cord blood units with low probability of usage such as non-HLA-identical or identical to patients who are in long-term complete remission. Copyright © 2010 Elsevier Inc. All rights reserved.

Efficacy of vincristine and etoposide with escalating cyclophosphamide in poor-prognosis pediatric brain tumors1

PubMed Central

Ziegler, David S.; Cohn, Richard J.; McCowage, Geoffrey; Alvaro, Frank; Oswald, Cecilia; Mrongovius, Robert; White, Les

2006-01-01

The objective of this study was to assess the efficacy of the VETOPEC regimen, a regimen of vincristine and etoposide with escalating doses of cyclophosphamide (CPA), in pediatric patients with high-risk brain tumors. Three consecutive studies by the Australia and New Zealand Children’s Cancer Study Group—VETOPEC I, Baby Brain 91, and VETOPEC II—have used a specific chemotherapy regimen of vincristine (VCR), etoposide (VP-16) and escalating CPA in patients with relapsed, refractory, or high-risk solid tumors. Patients in the VETOPEC II cohort were treated with very high dose CPA with peripheral blood stem cell (PBSC) rescue. We analyzed the subset of patients with high-risk brain tumors treated with these intensive VETOPEC-based protocols to assess the response, toxicity, and survival. We also assessed whether the use of very high dose chemotherapy with stem cell rescue improved the response rate or affected toxicity. Seventy-one brain tumor patients were treated with VETOPEC-based protocols. Of the 54 patients evaluable for tumor response, 17 had a complete response (CR) and 20 a partial response (PR) to treatment, which yielded an overall response rate of 69%. The CR + PR was 83% (19/23) for medulloblastomas, 56% (5/9) for primitive neuroectodermal tumors, 55% (6/11) for grade 3 and 4 astrocytomas, and 80% (6/8) for ependymomas. At a median follow-up of 36 months, overall survival for the entire cohort of 71 patients was 32%, with event-free survival of 13%. There were no toxic deaths within the PBSC-supported VETOPEC II cohort, despite higher CPA doses, compared with 7% among the non-PBSC patients. This regimen produces high response rates in a variety of very poor prognosis pediatric brain tumors. The maximum tolerated dose of CPA was not reached. Higher escalation in doses of CPA did not deliver a further improvement in response. With PBSC rescue in the VETOPEC II study, hematologic toxicity was no longer a limiting factor. The response rates observed support further development of this chemotherapy regimen. PMID:16443948

Phase II trial of cystemustine, a new nitrosourea, as treatment of high-grade brain tumors in adults.

PubMed

Roche, H; Cure, H; Adenis, A; Fargeot, P; Terret, C; Lentz, M A; Madelmont, J C; Fumoleau, P; Hanausk, A; Chollet, P

2000-09-01

This study included 39 patients (37 evaluable, of whom 30 patients with recurrent gliomas and 7 patients with gliomas untreated by radiotherapy); they were enrolled into a phase II trial using a new nitrosourea, cystemustine, administrated every 2 weeks at 60 mg/m2 as a 15 min-infusion. Pathology at inclusion was (WHO classification): 14 glioblastomas, 20 grade 3-4 astrocytomas and 3 grade 3 oligodendrogliomas. Four partial responses have been obtained, giving an overall response rate of 10.8%. Four additional patients had a partial response, which for various reasons was not confirmed 4 weeks later; 12 patients had a stable disease for at least 8 weeks, 15 patients had progressive disease. Of the 4 responses, 2 were with a grade 3 oligodendroglioma and 2 glioblastoma. Toxicity (WHO grading) was mainly hematological: leukopenia (16.2% grade 3-4), neutropenia (29.7% grade 3-4), thrombopenia (27% grade 3-4). No other toxicity greater than grade 2 was observed. In conclusion, cystemustine at 60 mg/m2 has moderate clinical activity in relapsing glioma. Our results warrant further investigation of this agent with an increased dose or modified scheme.

Bortezomib-Containing Regimens for the Treatment of Newly Diagnosed and Relapsed Amyloid Light Chain Amyloidosis: A Single-Center Experience.

PubMed

Jimenez-Zepeda, Victor H; Duggan, Peter; Neri, Paola; Bahlis, Nizar J

2016-06-01

The proteasome is an exciting target for the development of novel anticancer therapies. Recent evidence has suggested that bortezomib, a dipeptide boronate proteasome inhibitor, exhibits unprecedented single-agent activity in amyloid light chain (AL) amyloidosis. We performed a retrospective review of the use of bortezomib-containing regimens to assess the rapidity and quality of response at our institution. A total of 52 patients with documented newly diagnosed and relapsed AL amyloidosis treated with bortezomib-containing regimens were identified from our institutional database. After a median of 4 cycles (range, 1-22 cycles), a hematologic response was seen in 49 patients (94.2%), including a complete response in 15 (28.8%), a very good partial response in 25 (48.1%), and a partial response in 9 (17.3%). At 6 weeks, 37 patients had already achieved a partial response. An organ response at 6 months was documented in 31 patients (59.6%). With respect to the cardiac response, a > 30% decrease in N-terminal pro-hormone brain natriuretic peptide (NT-proBNP) was observed in 17 of 35 evaluable patients (48.6%; NT-proBNP > 650 ng/L) at a median of 6 months. Overall survival was shorter for the patients with NT-proBNP > 5000 ng/L and for those who achieved less than a very good partial response. Bortezomib is a safe and well-tolerated therapy for patients with AL amyloidosis with a rapid hematologic response and cardiac response, as assessed by the NT-proBNP level. Copyright © 2016 Elsevier Inc. All rights reserved.

42 CFR 493.851 - Standard; Hematology.

Code of Federal Regulations, 2014 CFR

2014-10-01

... acceptable responses for each analyte in each testing event is unsatisfactory analyte performance for the... testing event. (e)(1) For any unsatisfactory analyte or test performance or testing event for reasons... any unacceptable analyte or testing event score, remedial action must be taken and documented, and the...

42 CFR 493.851 - Standard; Hematology.

Code of Federal Regulations, 2013 CFR

2013-10-01

... acceptable responses for each analyte in each testing event is unsatisfactory analyte performance for the... testing event. (e)(1) For any unsatisfactory analyte or test performance or testing event for reasons... any unacceptable analyte or testing event score, remedial action must be taken and documented, and the...

42 CFR 493.851 - Standard; Hematology.

Code of Federal Regulations, 2012 CFR

2012-10-01

... acceptable responses for each analyte in each testing event is unsatisfactory analyte performance for the... testing event. (e)(1) For any unsatisfactory analyte or test performance or testing event for reasons... any unacceptable analyte or testing event score, remedial action must be taken and documented, and the...

C3 glomerulopathy associated with monoclonal Ig is a distinct subtype.

PubMed

Ravindran, Aishwarya; Fervenza, Fernando C; Smith, Richard J H; Sethi, Sanjeev

2018-05-02

Monoclonal immunoglobulins (MIg) may play a causal role in C3 glomerulopathy (C3G) by impairing regulation of the alternative pathway of complement. Ninety-five patients with C3G were tested for MIg of which 36 were positive. Their mean age at diagnosis was 60 years and among patient 50 years and older, 65.1% had a MIg. At presentation, median serum creatinine and proteinuria were 1.9 mg/dL and 3.0 g/24 hours. Hematuria was present in 32 (88.9%) patients. Twelve (34.3%) patients had low C3 levels. C3 nephritic factor was detected in 45.8% patients; pathogenic variants in complement protein genes were rare. Hematologic evaluation revealed monoclonal gammopathy of renal significance in 26 patients, multiple myeloma in five, smoldering multiple myeloma in two, and chronic lymphocytic leukemia, lymphoma, or type I cryoglobulin each in one patient. After a median follow-up of 43.6 months, the median serum creatinine and proteinuria were 1.4 mg/dL and 0.8g/24 hours. Nine patients developed ESRD. Sixteen patients received MIg-targeted treatment, 17 patients received non-targeted treatment while three patients were managed conservatively. Of the 16 patients receiving MIg-targeted treatment, ten achieved complete/very good/partial hematologic response. Of these, seven achieved a complete/partial/stable renal response. Five patients receiving targeted treatment did not achieve hematologic response, none had a renal response. Patients receiving targeted treatment were more likely to have multiple myeloma/smoldering multiple myeloma. Patients receiving non-targeted treatment were more likely to have monoclonal gammopathy of renal significance. Thus, C3G with MIg is seen in older patients, C3 nephritic factor is the most common autoantibody detected, and MIg-targeted treatment may result in remission and stabilization of kidney function in a subset of these patients. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Methotrexate vs Cyclosporin A as a single agent for graft-versus-host disease prophylaxis in pediatric patients with hematological malignancies undergoing allogeneic bone marrow transplantation from HLA-identical siblings: a single-center analysis in Japan.

PubMed

Koga, Y; Nagatoshi, Y; Kawano, Y; Okamura, J

2003-07-01

The efficacy of methotrexate (MTX) as a single graft-versus-host disease (GVHD) prophylaxis agent was compared to that of cyclosporin A (CSA) in 62 pediatric patients (median age: 8 years) with hematological malignancies who had undergone bone marrow transplantation (BMT) from HLA-identical sibling donors at National Kyushu Cancer Center since 1977. In all, 30 patients received MTX by intravenous bolus injection, with a dose of 15 mg/m(2) on day +1, followed by 10 mg/m(2) on days +3, +6, and +11, and then once a week until day +100. A total of 32 patients were treated with CSA, which was given intravenously in the early stages and orally thereafter until day +100, and then gradually tapered and stopped 6 months after BMT. There were no differences between the groups in terms of rates of hematopoietic recovery after BMT. The probabilities of acute GVHD (grades II-IV) and chronic GVHD were 29.6 vs 40.6% (P=0.294) and 19 vs 20% (MTX vs CSA), respectively. Relapse rates and event-free survival were identical. These results suggest that MTX and CSA were equally effective when given after BMT in Japanese pediatric patients with hematological malignancies. Since MTX was given over a shorter time than CSA, it might be more practical in the management of such patients.

[Nab-Paclitaxel plus Gemcitabine Hydrochloride in Patients with Metastatic or Recurrent Pancreatic Cancer - A Single Institution Experience].

PubMed

Takeda, Yutaka; Katsura, Yoshiteru; Ohmura, Yoshiaki; Sakamoto, Takuya; Akiyama, Yasuki; Kuwahara, Ryuichi; Morimoto, Yoshihiro; Ishida, Tomo; Oneda, Yasuo; Murakami, Kouhei; Naito, Atsushi; Kagawa, Yoshinori; Takeno, Atsushi; Kato, Takeshi; Tamura, Shigeyuki

2016-11-01

Pancreatic adenocarcinoma is one of the leading causes of cancer deaths in Japan.Albumin -bound paclitaxel (nab-paclitaxel)plus gemcitabine hydrochloride(GEM)combination chemotherapy provided significant improvements in the overall and progression-free survival in a phase III trial in Europe and America and a phase II trial in Japan.As a result, this combination therapy was approved for use in Japan. We evaluated the efficacy of nab-paclitaxel plus GEM with metastatic or recurrent pancreatic cancer.Between December 2014 and March 2016, 11 patients received nab-paclitaxel plus GEM as follows: nab-paclitaxel(125mg/m2 of body-surface area)followed by GEM(1,000mg/m2)on days 1, 8, and 15 every 4 weeks.The treatment was continued until disease progression, unacceptable adverse events, discontinuation as decided by the investigators, or patient refusal. The mean age was 65.6 years(range, 48-75 years), and 8 out of 11 patients were men.Ten patients had an Eastern Cooperative Oncology Group(ECOG)performance status(PS)of 0.Ten patients had metastatic disease.Only 4 patients had no prior therapy.The mean duration of treatment was 10.2 weeks(range, 2-41 weeks).The relative dose intensities of nab-paclitaxel and GEM were 90.6%(66.7-100%)and 87.5%(62.9-100%), respectively.The major Grade 3 or 4 hematological toxicities were leucopenia(54.5%), neutropenia(36.4%), anemia (27.3%), and thrombocytopenia(18.2%).The major grade 2 or 3 non-hematological toxicities were fatigue(45.6%), skin rash(27.3%), peripheral sensory neuropathy(9.1%), anorexia(9.1%), and stomatitis(9.1%).There were no treatmentrelated deaths.Interstitial lung disease was not observed.The 6 month progression-free and overall survival rate were 25.7% and 66.7%, respectively. The disease control rate was 90.9%(complete response, n=0; partial response, n=1; stable disease, n=9; progressive disease, n=1). Nab-paclitaxel plus GEM is well tolerated and associated with efficacy and improved survival outcomes.Nab -paclitaxel plus GEM can be the standard treatment for patients with metastatic pancreatic adenocarcinoma.

Tumor Lysis Syndrome in Chronic Lymphocytic Leukemia with Novel Targeted Agents.

PubMed

Cheson, Bruce D; Heitner Enschede, Sari; Cerri, Elisa; Desai, Monali; Potluri, Jalaja; Lamanna, Nicole; Tam, Constantine

2017-11-01

Tumor lysis syndrome (TLS) is an uncommon but potentially life-threatening complication associated with the treatment of some cancers. If left untreated, TLS may result in acute renal failure, cardiac dysrhythmia, neurologic complications, seizures, or death. Tumor lysis syndrome is most commonly observed in patients with hematologic malignancies with a high proliferation rate undergoing treatment with very effective therapies. In chronic lymphocytic leukemia (CLL), historically, TLS has been observed less often, owing to a low proliferation rate and slow response to chemotherapy. New targeted therapies have recently been approved in the treatment of CLL, including the oral kinase inhibitors, idelalisib and ibrutinib, and the B-cell lymphoma-2 protein inhibitor, venetoclax. Several others are also under development, and combination strategies of these agents are being explored. This review examines the diagnosis, prevention, and management of TLS and summarizes the TLS experience in CLL clinical trials with newer targeted agents. Overall, the risk of TLS is small, but the consequences may be fatal; therefore, patients should be monitored carefully. Therapies capable of eliciting rapid response and combination regimens are increasingly being evaluated for treatment of CLL, which may pose a higher risk of TLS. For optimal management, patients at risk for TLS require prophylaxis and close monitoring with appropriate tests and appropriate management to correct laboratory abnormalities, which allows for safe and effective disease control. Tumor lysis syndrome (TLS) is a potentially fatal condition observed with hematologic malignancies, caused by release of cellular components in the bloodstream from rapidly dying tumor cells. The frequency and severity of TLS is partly dependent upon the biology of the disease and type of therapy administered. Novel targeted agents highly effective at inducing rapid cell death in chronic lymphocytic leukemia (CLL) may pose a risk for TLS in patients with tumors characterized by rapid growth, high tumor burden, and/or high sensitivity to treatment. In this review, prevention strategies and management of patients with CLL who develop TLS are described. © 2017 The Authors The Oncologist published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

The European Hematology Association Roadmap for European Hematology Research: a consensus document.

PubMed

Engert, Andreas; Balduini, Carlo; Brand, Anneke; Coiffier, Bertrand; Cordonnier, Catherine; Döhner, Hartmut; de Wit, Thom Duyvené; Eichinger, Sabine; Fibbe, Willem; Green, Tony; de Haas, Fleur; Iolascon, Achille; Jaffredo, Thierry; Rodeghiero, Francesco; Salles, Gilles; Schuringa, Jan Jacob

2016-02-01

The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at €23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap.The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders.The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients. Copyright© Ferrata Storti Foundation.

The European Hematology Association Roadmap for European Hematology Research: a consensus document

PubMed Central

Engert, Andreas; Balduini, Carlo; Brand, Anneke; Coiffier, Bertrand; Cordonnier, Catherine; Döhner, Hartmut; de Wit, Thom Duyvené; Eichinger, Sabine; Fibbe, Willem; Green, Tony; de Haas, Fleur; Iolascon, Achille; Jaffredo, Thierry; Rodeghiero, Francesco; Salles, Gilles; Schuringa, Jan Jacob

2016-01-01

The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at €23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine ‘sections’ in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients. PMID:26819058

Hematology of healthy Florida manatees (Trichechus manatus).

PubMed

Harvey, John W; Harr, Kendal E; Murphy, David; Walsh, Michael T; Nolan, Elizabeth C; Bonde, Robert K; Pate, Melanie G; Deutsch, Charles J; Edwards, Holly H; Clapp, William L

2009-06-01

Hematologic analysis is an important tool in evaluating the general health status of free-ranging manatees and in the diagnosis and monitoring of rehabilitating animals. The purpose of this study was to evaluate diagnostically important hematologic analytes in healthy manatees (Trichechus manatus) and to assess variations with respect to location (free ranging vs captive), age class (small calves, large calves, subadults, and adults), and gender. Blood was collected from 55 free-ranging and 63 captive healthy manatees. Most analytes were measured using a CELL-DYN 3500R; automated reticulocytes were measured with an ADVIA 120. Standard manual methods were used for differential leukocyte counts, reticulocyte and Heinz body counts, and plasma protein and fibrinogen concentrations. Rouleaux, slight polychromasia, stomatocytosis, and low numbers of schistocytes and nucleated RBCs (NRBCs) were seen often in stained blood films. Manual reticulocyte counts were higher than automated reticulocyte counts. Heinz bodies were present in erythrocytes of most manatees. Compared with free-ranging manatees, captive animals had slightly lower MCV, MCH, and eosinophil counts and slightly higher heterophil and NRBC counts, and fibrinogen concentration. Total leukocyte, heterophil, and monocyte counts tended to be lower in adults than in younger animals. Small calves tended to have higher reticulocyte counts and NRBC counts than older animals. Hematologic findings were generally similar between captive and free-ranging manatees. Higher manual reticulocyte counts suggest the ADVIA detects only reticulocytes containing large amounts of RNA. Higher reticulocyte and NRBC counts in young calves probably reflect an increased rate of erythropoiesis compared with older animals.

Dacarbazine as single-agent therapy for relapsed lymphoma in dogs.

PubMed

Griessmayr, P C; Payne, S E; Winter, J E; Barber, L G; Shofer, F S

2009-01-01

Multidrug resistance is the most common cause of treatment failure in dogs with multicentric lymphoma. 5-(3,3-Dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) is an atypical alkylator used as standard treatment in human Hodgkin's lymphoma, and has been effective in combination treatment to treat resistant lymphoma in dogs. However, no data are available on the use of DTIC as a single agent in the treatment of relapsed canine lymphoma. Single-agent DTIC is effective and safe in treating dogs with lymphoma that relapsed or failed to respond to previous chemotherapy. Forty client-owned dogs with relapsed lymphoma. Dogs were eligible for the retrospective study if they had a histologically or cytologically confirmed diagnosis of lymphoma and had relapsed. Dogs received DTIC (800-1,000 mg/m(2) every 2-3 weeks as a 4-5-hour IV infusion) and were evaluated for response rate and duration. Hematologic and gastrointestinal toxicity was assessed. The overall response rate for dogs being treated with DTIC was 35% (14 dogs) with a median progression-free interval of 43 days. Thirteen dogs had a partial response and 1 dog had a complete response. Stable disease was achieved in 3 dogs. Mild gastrointestinal toxicity was reported in 3 dogs posttreatment. Thrombocytopenia was the principal toxicity observed 7-14 days after the treatment. Treatments were delayed because of thrombocytopenia. DTIC, when used alone, is effective in the treatment of dogs with relapsed lymphoma.

The role of radiotherapy in the management of POEMS syndrome.

PubMed

Suh, Yang-Gun; Kim, Young-Suk; Suh, Chang-Ok; Kim, Yu Ri; Cheong, June-Won; Kim, Jin Seok; Cho, Jaeho

2014-11-28

POEMS syndrome is a paraneoplastic syndrome caused by an underlying plasma cell proliferative disease. In this study, we examined the treatment outcomes and role of radiotherapy in the management of POEMS syndrome. In total, 33 patients diagnosed with POEMS syndrome were analyzed. These patients presented with osteosclerotic myeloma (OSM, n = 13), Castleman's disease (CD, n = 4), OSM with CD (n = 10), and vascular endothelial growth factor elevation without gross lesions (VEGFe, n = 6), respectively. The patients were treated by radiotherapy alone (n = 4), chemotherapy alone (n = 16), or a combination thereof (n = 9). The clinical response rates of radiotherapy, chemotherapy, and radiotherapy plus chemotherapy were 75%, 69%, and 89%, respectively. In addition, the hematologic response rates were 50%, 69%, and 71%, respectively. Among the six patients with limited multiple lesions who underwent radiotherapy, the clinical symptoms were improved in five patients after radiotherapy. The median progression-free survival (PFS) was 51 months, and the median overall survival (OS) was 65 months. In univariate analysis, the administration of chemotherapy was significantly associated with better PFS (p = 0.007) and OS (p = 0.020). In contrast, underlying VEGFe was a significant factor worsening PFS (p = 0.035) and OS (p = 0.008). Radiotherapy produces a reliable clinical response and is effective in improving POEMS-associated symptoms that are refractory to chemotherapy in selected patients with clustered or limited multiple lesions that can be covered by single radiation field.

Health Benefits of Animal Research: The Mouse in Biomedical Research.

ERIC Educational Resources Information Center

Jonas, Albert M.

1984-01-01

Traces the history of using mice for medical research and discusses the benefits of using these animals for studies in bacteriology, virology, genetics (considering X-linked genetic homologies between mice and humans), molecular biology, immunology, hematology, immune response disorders, oncology, radiobiology, pharmacology, behavior genetics,…

ENDOTHELIAL CELL DYSFUNCTION AND VASCULAR INFLAMMATION ARE ASSOCIATED WITH EXPOSURE TO FINE PARTICLES IN DIABETICS

EPA Science Inventory

Exposure to fme airborne particulate matter (PM2.5) has been shown to be responsible for cardiovascular and hematological effects, especially in older people with cardiovascular disease. Some epidemiology studies suggest that diabetics may be a particularly susceptible population...

Functional evaluation of circulating hematopoietic progenitors in Noonan syndrome

PubMed Central

TIMEUS, FABIO; CRESCENZIO, NICOLETTA; BALDASSARRE, GIUSEPPINA; DORIA, ALESSANDRA; VALLERO, STEFANO; FOGLIA, LUISELDA; PAGLIANO, SARA; ROSSI, CESARE; SILENGO, MARGHERITA CIRILLO; RAMENGHI, UGO; FAGIOLI, FRANCA; DI MONTEZEMOLO, LUCA CORDERO; FERRERO, GIOVANNI BATTISTA

2013-01-01

Noonan syndrome (NS) is an autosomal dominant disorder, characterized by short stature, multiple dysmorphisms and congenital heart defects. A myeloproliferative disorder (NS/MPD), resembling juvenile myelomonocytic leukemia (JMML), is occasionally diagnosed in infants with NS. In the present study, we performed a functional evaluation of the circulating hematopoietic progenitors in a series of NS, NS/MPD and JMML patients. The different functional patterns were compared with the aim to identify a possible NS subgroup worthy of stringent hematological follow-up for an increased risk of MPD development. We studied 27 NS and 5 JMML patients fulfilling EWOG-MDS criteria. The more frequent molecular defects observed in NS were mutations in the PTPN11 and SOS genes. The absolute count of monocytes, circulating CD34+ hematopoietic progenitors, their apoptotic rate and the number of circulating CFU-GMs cultured in the presence of decreasing concentrations or in the absence of granulocyte-macrophage colony-stimulating factor (GM-CSF) were evaluated. All JMML patients showed monocytosis >1,000/μl. Ten out of the 27 NS patients showed monocytosis >1,000/μl, which included the 3 NS/MPD patients. In JMML patients, circulating CD34+ cells were significantly increased (median, 109.8/μl; range, 44–232) with a low rate of apoptosis (median, 2.1%; range, 0.4–12.1%), and circulating CFU-GMs were hyper-responsive to GM-CSF. NS/MPD patients showed the same flow cytometric pattern as the JMML patients (median, CD34+ cells/μl, 205.7; range, 58–1374; median apoptotic rate, 1.4%; range, 0.2–2.4%) and their circulating CFU-GMs were hyper-responsive to GM-CSF. These functional alterations appeared 10 months before the typical clinical manifestations in 1 NS/MPD patient. In NS, the CD34+ absolute cell count and circulating CFU-GMs showed a normal pattern (median CD34+ cells/μl, 4.9; range, 1.3–17.5), whereas the CD34+ cell apoptotic rate was significantly decreased in comparison with the controls (median, 8.6%; range, 0–27.7% vs. median, 17.6%; range, 2.8–49.6%), suggesting an increased CD34+ cell survival. The functional evaluation of circulating hematopoietic progenitors showed specific patterns in NS and NS/MPD. These tests are a reliable integrative tool that, together with clinical data and other hematological parameters, could help detect NS patients with a high risk for a myeloproliferative evolution. PMID:23756559

Ruxolitinib is effective and safe in Japanese patients with hydroxyurea-resistant or hydroxyurea-intolerant polycythemia vera with splenomegaly.

PubMed

Kirito, Keita; Suzuki, Kenshi; Miyamura, Koichi; Takeuchi, Masahiro; Handa, Hiroshi; Okamoto, Shinichiro; Gadbaw, Brian; Yamauchi, Kyosuke; Amagasaki, Taro; Ito, Kazuo; Hino, Masayuki

2018-02-01

Ruxolitinib, a potent JAK1/JAK2 inhibitor, was found to be superior to the best available therapy (BAT) in controlling hematocrit, reducing splenomegaly, and improving symptoms in the phase 3 RESPONSE study of patients with polycythemia vera with splenomegaly who experienced an inadequate response to or adverse effects from hydroxyurea. We report findings from a subgroup analysis of Japanese patients in RESPONSE (n = 18). The composite response rate (hematocrit control and spleen response) was higher in patients receiving ruxolitinib (50.0%) than in those receiving BAT (8.3%). A total of 50.0% of patients randomized to ruxolitinib achieved a spleen response vs 8.3% of those receiving BAT; 100 and 33.3% of patients in the respective groups achieved hematocrit control, with mean hematocrit in ruxolitinib-treated patients remaining stable at < 45% throughout the study. Similarly, a higher proportion of ruxolitinib-treated patients achieved complete hematologic remission (33.3 vs 16.7%). Ruxolitinib also led to rapid improvements in pruritus. All responses with ruxolitinib were durable to week 80, and its safety profile was consistent with that in the overall study. These findings suggest that ruxolitinib is an effective and well-tolerated treatment option for Japanese patients with polycythemia vera with an inadequate response to or adverse effects from hydroxyurea.

Verification and quality control of routine hematology analyzers.

PubMed

Vis, J Y; Huisman, A

2016-05-01

Verification of hematology analyzers (automated blood cell counters) is mandatory before new hematology analyzers may be used in routine clinical care. The verification process consists of several items which comprise among others: precision, accuracy, comparability, carryover, background and linearity throughout the expected range of results. Yet, which standard should be met or which verification limit be used is at the discretion of the laboratory specialist. This paper offers practical guidance on verification and quality control of automated hematology analyzers and provides an expert opinion on the performance standard that should be met by the contemporary generation of hematology analyzers. Therefore (i) the state-of-the-art performance of hematology analyzers for complete blood count parameters is summarized, (ii) considerations, challenges, and pitfalls concerning the development of a verification plan are discussed, (iii) guidance is given regarding the establishment of reference intervals, and (iv) different methods on quality control of hematology analyzers are reviewed. © 2016 John Wiley & Sons Ltd.

Drug-Induced Hematologic Syndromes

PubMed Central

Mintzer, David M.; Billet, Shira N.; Chmielewski, Lauren

2009-01-01

Objective. Drugs can induce almost the entire spectrum of hematologic disorders, affecting white cells, red cells, platelets, and the coagulation system. This paper aims to emphasize the broad range of drug-induced hematological syndromes and to highlight some of the newer drugs and syndromes. Methods. Medline literature on drug-induced hematologic syndromes was reviewed. Most reports and reviews focus on individual drugs or cytopenias. Results. Drug-induced syndromes include hemolytic anemias, methemoglobinemia, red cell aplasia, sideroblastic anemia, megaloblastic anemia, polycythemia, aplastic anemia, leukocytosis, neutropenia, eosinophilia, immune thrombocytopenia, microangiopathic syndromes, hypercoagulability, hypoprothrombinemia, circulating anticoagulants, myelodysplasia, and acute leukemia. Some of the classic drugs known to cause hematologic abnormalities have been replaced by newer drugs, including biologics, accompanied by their own syndromes and unintended side effects. Conclusions. Drugs can induce toxicities spanning many hematologic syndromes, mediated by a variety of mechanisms. Physicians need to be alert to the potential for iatrogenic drug-induced hematologic complications. PMID:19960059

Palonosetron versus other 5-HT₃ receptor antagonists for prevention of chemotherapy-induced nausea and vomiting in patients with hematologic malignancies treated with emetogenic chemotherapy in a hospital outpatient setting in the United States.

PubMed

Craver, Chris; Gayle, Julie; Balu, Sanjeev; Buchner, Deborah

2011-01-01

This study evaluated the rate of uncontrolled chemotherapy-induced nausea and vomiting (CINV) after initiating antiemetic prophylaxis with palonosetron versus other 5-HT₃ receptor antagonists (RAs) in patients diagnosed with hematologic malignancies (lymphoma and leukemia) and receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC) in a hospital outpatient setting. Patients aged ≥ 18 years and diagnosed with hematologic malignancies initiating HEC or MEC and antiemetic prophylaxis with palonosetron (Group 1) and other 5-HT₃ RAs (Group 2) for the first time in a hospital outpatient setting between 4/1/2007 and 3/31/2009 were identified from the Premier Perspective Database. Within each cycle, CINV events were identified (in the hospital outpatient, inpatient, and emergency room settings) through ICD-9 codes for nausea, vomiting, and/or volume depletion (from each CT administration day 1 until the end of the CT cycle), or use of rescue medications (day 2 until the end of the CT cycle). Negative binomial distribution generalized linear multivariate regression model estimating the CINV event rate on CT, specific CT cycles, and cancer diagnosis (leukemia/lymphoma)-matched groups in the follow-up period (first of 8 cycles or 6 months) was developed. Of 971 identified patients, 211 initiated palonosetron (Group 1). Group 1 patients comprised of more females [50.2 vs. 41.4%; p = 0.0226], Whites [74.4 vs. 70.4%, and Hispanics [7.6 vs. 6.3%; all races p = 0.0105], received more HEC treatments [89.6 vs. 84.2%; all CT types p = 0.0129], and had more lymphoma diagnosed patients [89.6 vs. 76.3%; all cancer types p = 0.0033] at baseline. After controlling for differences in several demographic and clinical variables, the regression model predicted a 20.4% decrease in CINV event rate per CT cycle for Group 1 versus Group 2 patients. Study limitations include potential lack of generalizability, absence of data on certain confounders including alcohol consumption and prior history of motion sickness, potential underestimation of incidence of uncontrolled CINV, and inability to draw conclusions pertaining to cause and effect relationship. In this retrospective hospital study, patients with hematologic malignancies treated with HEC or MEC and initiated on antiemetic prophylaxis with palonosetron in the hospital outpatient setting were more likely to experience significantly lower CINV event rates (in the hospital outpatient, inpatient, and emergency room settings) versus patients initiated on other 5-HT₃ RAs.

225Ac-PSMA-617 for PSMA-Targeted α-Radiation Therapy of Metastatic Castration-Resistant Prostate Cancer.

PubMed

Kratochwil, Clemens; Bruchertseifer, Frank; Giesel, Frederik L; Weis, Mirjam; Verburg, Frederik A; Mottaghy, Felix; Kopka, Klaus; Apostolidis, Christos; Haberkorn, Uwe; Morgenstern, Alfred

2016-12-01

Prostate-specific membrane antigen (PSMA) is a promising target in prostate cancer. Recently, we started the first-in-human treatment with an α-radionuclide-labeled PSMA ligand. Although the case series is still ongoing, we here report in advance about two patients in highly challenging clinical situations who showed a complete response to 225 Ac-PSMA-617 therapy. 68 Ga-PSMA-11 PET/CT validated the presence of the PSMA-positive tumor phenotype. A 100-kBq activity of 225 Ac-PSMA-617 per kilogram of body weight was administered bimonthly. Prostate-specific antigen response and hematologic toxicity were measured at least every 4 wk. Restaging was performed with 68 Ga-PSMA-11 PET/CT. Both patients experienced a prostate-specific antigen decline to below the measurable level and showed a complete response on imaging. No relevant hematologic toxicity was observed. Xerostomia was the only mentionable clinical side effect. Targeted α-therapy with 225 Ac-PSMA-617, although still experimental, obviously has strong potential to significantly benefit advanced-stage prostate cancer patients. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

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

Guiney, M.J.; Liew, K.H.; Quong, G.G.

A retrospective study was performed to assess the effect of splenic irradiation (SI) on splenomegaly, splenic pain, anemia, and thrombocytopenia in patients with chronic lymphocytic leukemia. Twenty-two patients received 32 courses of SI. Of 31 courses of SI given for splenomegaly there were 19 responders (61%). Ten courses of SI were given for splenic pain resulting in partial relief of pain in 4 courses and complete relief in 4 courses. Only 4 of 16 courses given for anemia resulted in elevations of hemoglobin of 2 g/dL or more. Of the 14 courses of SI given for thrombocytopenia there were onlymore » 2 responses with platelet counts decreasing further in another 9 courses. The median duration of response was 14 months (range: 3-116 months). There was no dose-response relationship detected for SI in CLL. Treatment related toxicity was hematologic and secondary to leucopenia and thrombocytopenia. We recommend the use of small fraction sizes of 25 cGy to 50 cGy and close monitoring of hematological parameters. Splenic irradiation effectively palliates splenomegaly and reduces spleen size in CLL. It was of limited value in correcting anemia and thrombocytopenia in this patient population.« less

Donor Chimerism of B Cells and Nature Killer Cells Provides Useful Information to Predict Hematologic Relapse following Allogeneic Hematopoietic Stem Cell Transplantation.

PubMed

Jiang, Ying; Wan, Liping; Qin, Youwen; Wang, Xiaorui; Yan, Shike; Xie, Kuangcheng; Wang, Chun

2015-01-01

In this study we investigated the correlation between donor chimerism status and disease relapse following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The chimerism of Fluorescence-activated cell sorter (FACS) sorted CD3+T lymphocytes of 153 cases, CD56+CD16+NK lymphocytes of 153 cases and CD19+B lymphocytes of 31 cases with acute B lymphoblastic leukemia (B-ALL) was analyzed post-transplant utilizing polymerase chain reaction amplification of short tandem repeats (PCR-STR). A total of 33 patients (33/153, 21.6%) had recurrent disease. The positive predictive values of declining donor chimerism for hematologic and isolated extramedullary relapse were 58.8% and 10% (P=0.018, Chi-Square). The positive predictive values of declining donor chimerism in BMB, BMT, BMNK and PBB for hematologic relapse were 11.6%, 0%, 0% and 0% under close monitoring in patients with B-ALL. Only the donor chimerism in BMB significantly decreased in the group with hematologic relapse as compared with the group without hematologic relapse (P=0.00, Independent-samples T test) in patients with B-ALL. The median drop of donor chimerism in PBT, BMT, PBNK and BMNK were 0%, 0%, 5.9% and 2.8% one or two weeks prior to hematologic relapse in patients with non-B-ALL. The donor chimerism in PBNK significantly decreased prior to hematologic relapse in the group with hematologic relapse as compared with the group without hematologic relapse (P=0.022, Independent-samples T test).These data suggest donor chimerism of BMB can be used to predict the occurrence of hematologic relapse in patients with B-ALL. Donor chimerism decrease in PBNK was associated with a somewhat increased risk of hematologic relapse in patients with non-B-ALL. Therefore, our results reveal a more effective path to individually predict for hematologic relapse by dynamic monitoring different cell lineages in different disease.

Hemopoietic Response to Low Dose-Rates of Ionizing Radiation Shows Stem Cell Tolerance and Adaptation

PubMed Central

Fliedner, Theodor M.; Graessle, Dieter H.; Meineke, Viktor; Feinendegen, Ludwig E.

2012-01-01

Chronic exposure of mammals to low dose-rates of ionizing radiation affects proliferating cell systems as a function of both dose-rate and the total dose accumulated. The lower the dose-rate the higher needs to be the total dose for a deterministic effect, i.e., tissue reaction to appear. Stem cells provide for proliferating, maturing and functional cells. Stem cells usually are particularly radiosensitive and damage to them may propagate to cause failure of functional cells. The paper revisits 1) medical histories with emphasis on the hemopoietic system of the victims of ten accidental chronic radiation exposures, 2) published hematological findings of long-term chronically gamma-irradiated rodents, and 3) such findings in dogs chronically exposed in large life-span studies. The data are consistent with the hypothesis that hemopoietic stem and early progenitor cells have the capacity to tolerate and adapt to being repetitively hit by energy deposition events. The data are compatible with the “injured stem cell hypothesis”, stating that radiation–injured stem cells, depending on dose-rate, may continue to deliver clones of functional cells that maintain homeostasis of hemopoiesis throughout life. Further studies perhaps on separated hemopoietic stem cells may unravel the molecular-biology mechanisms causing radiation tolerance and adaptation. PMID:23304110

HEMATOLOGIC RESPONSES TO INHALATION OF CONCENTRATED AIR PARTICLES (CAPS) AND TRANSIENT MYOCARDIAL ISCHEMIA (MI). (R827353C008)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Protein Nutrition of Southern Plains Small Mammals: Immune Response to Variation in Maternal and Offspring Dietary Nitrogen

EPA Science Inventory

Maternal nutrition during pregnancy and postnatal offspring nutrition may influence offspring traits. We investigated the effects of maternal and postweaning offspring dietary nitrogen on immune function and hematology in two species of rodent: the hispid cotton rat (Sigmodon his...

Surveillance of healthcare associated infections in pediatric cancer patients between 2004 and 2009 in a public pediatric hospital in Mexico city, Mexico.

PubMed

Hernández Orozco, Hilda; Lucas Resendiz, Esperanza; Castañeda, Jose Luis; De Colsa, Agustin; Ramirez Mayans, Jaime; Johnson, Kyle M; Gonzalez, Napoleon; Caniza, Miguela A

2014-03-01

Pediatric oncology and hematology patients are at increased risk of developing healthcare associated infections (HAIs). We conducted a prospective surveillance study on children with cancer admitted to the pediatric hematology and oncology units at a public pediatric hospital in Mexico from January 2004 to December 2009. The incidence of HAIs and groups at greatest risk for HAIs were analyzed. The annual HAI incidence rate and incidence density were calculated. Risk factors such as site of infection, HAI types, and cancer diagnosis were studied. A total of 9420 patients participated, and 409 had HAIs (479 episodes). Annual HAI rates were 3.7 to 5.5 per 100 admissions and the incidence density was 5.75 to 6 HAIs per 1000 inpatient days annually. There were 272 (56.8%) bloodstream infections, 45 (9.4%) pneumonia cases, and 44 (9.2%) skin and soft tissue infections. Children with acute lymphoblastic leukemia had 37.2% and those with acute myeloid leukemia had 16.4% of the HAIs. A total of 11.5% of the HAIs were in children with osteosarcoma. The most common pathogens were Gram-negative bacteria. The HAI-associated mortality rate was 3.7%. Although the overall HAI rate is in line with published reports, the mortality rate was higher, suggesting the incorporation of more aggressive methods to treat infections at our hospital.

Acute empathy decline among resident physician trainees on a hematology-oncology ward: an exploratory analysis of house staff empathy, distress, and patient death exposure.

PubMed

McFarland, Daniel C; Malone, Adriana K; Roth, Andrew

2017-05-01

A reason for empathy decline during medical training has not been fully elucidated. Empathy may decrease acutely during an inpatient hematology-oncology rotation because of the acuity of death exposures. This study aimed to explore physician trainee empathy, distress, death exposures, and their attributed meaning for the trainee. Internal medicine interns and residents at a single academic center were evaluated before and after hematology-oncology ward rotations using Interpersonal Reactivity Index for empathy, previously cited reasons for empathy decline, Impact of Event Scale-Revised for distress, death exposures (no. of dying patients cared for) and attributed sense of meaning (yes/no) (post-rotation). Fifty-six trainees completed both pre-rotation and post-rotation questionnaires (58% response). Empathy averaged 58.9 (SD 12.0) before and 56.8 (SD 11.1) after the rotation (2.1 point decrease) (p = 0.018). Distress was elevated but did not change significantly during the rotation. Residents cared for 4.28 dying patients. Seventy-three percent reported that death was the most stressful event during the rotation, yet 68% reported that they derived a sense of meaning from caring for dying patients. Empathy and distress scales were positively correlated before the rotation (r = 0.277, p = 0.041) but not after (r = .059, p = 0.69). This study suggests that an acute drop in empathy can occur over several weeks in residents rotating through inpatient hematology-oncology, similar to empathy decline associated with years of training in other studies. Empathy decline may be associated with elevated distress and death exposures on the hematology-oncology ward and should be explored further in other medical training environments. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Effects of the polyunsaturated fatty acids, EPA and DHA, on hematological malignancies: a systematic review

PubMed Central

Moloudizargari, Milad; Mortaz, Esmaeil; Asghari, Mohammad Hossein; Adcock, Ian M.; Redegeld, Frank A.; Garssen, Johan

2018-01-01

Omega-3 polyunsaturated fatty acids (PUFAs) have well established anti-cancer properties. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are among this biologically active family of macromolecules for which various anti-cancer effects have been explained. These PUFAs have a high safety profile and can induce apoptosis and inhibit growth of cancer cells both in vitro and in vivo, following a partially selective manner. They also increase the efficacy of chemotherapeutic agents by increasing the sensitivity of different cell lines to specific anti-neoplastic drugs. Various mechanisms have been proposed for the anti-cancer effects of these omega-3 PUFAs; however, the exact mechanisms still remain unknown. While numerous studies have investigated the effects of DHA and EPA on solid tumors and the responsible mechanisms, there is no consensus regarding the effects and mechanisms of action of these two FAs in hematological malignancies. Here, we performed a systematic review of the beneficial effects of EPA and DHA on hematological cell lines as well as the findings of related in vivo studies and clinical trials. We summarize the key underlying mechanisms and the therapeutic potential of these PUFAs in the treatment of hematological cancers. Differential expression of apoptosis-regulating genes and Glutathione peroxidase 4 (Gp-x4), varying abilities of different cancerous and healthy cells to metabolize EPA into its more active metabolites and to uptake PUFAS are among the major factors that determine the sensitivity of cells to DHA and EPA. Considering the abundance of data on the safety of these FAs and their proven anti-cancer effects in hematological cell lines and the lack of related human studies, further research is warranted to find ways of exploiting the anticancer effects of DHA and EPA in clinical settings both in isolation and in combination with other therapeutic regimens. PMID:29545942

Effects of the polyunsaturated fatty acids, EPA and DHA, on hematological malignancies: a systematic review.

PubMed

Moloudizargari, Milad; Mortaz, Esmaeil; Asghari, Mohammad Hossein; Adcock, Ian M; Redegeld, Frank A; Garssen, Johan

2018-02-20

Omega-3 polyunsaturated fatty acids (PUFAs) have well established anti-cancer properties. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are among this biologically active family of macromolecules for which various anti-cancer effects have been explained. These PUFAs have a high safety profile and can induce apoptosis and inhibit growth of cancer cells both in vitro and in vivo , following a partially selective manner. They also increase the efficacy of chemotherapeutic agents by increasing the sensitivity of different cell lines to specific anti-neoplastic drugs. Various mechanisms have been proposed for the anti-cancer effects of these omega-3 PUFAs; however, the exact mechanisms still remain unknown. While numerous studies have investigated the effects of DHA and EPA on solid tumors and the responsible mechanisms, there is no consensus regarding the effects and mechanisms of action of these two FAs in hematological malignancies. Here, we performed a systematic review of the beneficial effects of EPA and DHA on hematological cell lines as well as the findings of related in vivo studies and clinical trials. We summarize the key underlying mechanisms and the therapeutic potential of these PUFAs in the treatment of hematological cancers. Differential expression of apoptosis-regulating genes and Glutathione peroxidase 4 (Gp-x4), varying abilities of different cancerous and healthy cells to metabolize EPA into its more active metabolites and to uptake PUFAS are among the major factors that determine the sensitivity of cells to DHA and EPA. Considering the abundance of data on the safety of these FAs and their proven anti-cancer effects in hematological cell lines and the lack of related human studies, further research is warranted to find ways of exploiting the anticancer effects of DHA and EPA in clinical settings both in isolation and in combination with other therapeutic regimens.

Imatinib mesylate in chronic myeloid leukemia: frontline treatment and long-term outcomes.

PubMed

Stagno, Fabio; Stella, Stefania; Spitaleri, Antonio; Pennisi, Maria Stella; Di Raimondo, Francesco; Vigneri, Paolo

2016-01-01

The tyrosine kinase inhibitor Imatinib Mesylate has dramatically improved the clinical outcome of chronic myeloid leukemia (CML) patients in the chronic phase of the disease, generating unprecedented rates of complete hematologic and cytogenetic responses and sustained reductions in BCR-ABL transcripts. Here, we present an overview on the efficacy and safety of Imatinib and describe the most important clinical studies employing this drug for the frontline treatment of chronic phase CML. We also discuss recent reports describing the long-term outcome of patients receiving Imatinib for their disease. The imminent availability of generic forms of Imatinib coupled with the approval of expensive second-generation tyrosine kinase inhibitors underlines an unmet need for early molecular parameters that may distinguish CML patients likely to benefit from the drug from those that should receive alternative forms of treatment.

Tissue Residues, Hematological and Biochemical Effects of Tilmicosin in Broiler Chicken

PubMed Central

Elsayed, Mossad; Elkomy, Ashraf; Morad, Mohamed

2014-01-01

The aim of this study was to determine the blood and tissue concentrations profile and effect of tilmicosin on some hematological and biochemical parameters in broiler chicken. Fifty clinically healthy Hubbard chickens were orally administered 25 mg/kg BW of tilmicosin once daily for 5 consecutive days. Tissue residues of tilmicosin in slaughtered healthy chicken could not be detected by microbiological assay in all tested tissues except in lung (at 96 hours) and liver and kidneys (at 72 hours) after last administration. Tilmicosin caused temporary decrease in the RBCs and WBCs counts and has no effect on hemoglobin (Hb) and packed cell volume concentration (PCV). Also, the effect of tilmicosin on some biochemical parameters was as follows: the concentrations of creatinine, uric acid, electrolytes (sodium, potassium, and calcium), glucose, AST, ALT, ALP, and HDL-cholesterol in the serum of treated chicken did not change in response to the repeated oral administration of tilmicosin. There were only a temporary significant decrease in total protein and albumin concentrations and a significant increase in cholesterol and triglycerides concentrations. Chicken must not be slaughtered before 4 days from the stopping of tilmicosin administration. Tilmicosin makes temporary changes on hematological and biochemical parameters in broiler chicken. PMID:24808972

Tissue residues, hematological and biochemical effects of tilmicosin in broiler chicken.

PubMed

Elsayed, Mossad; Elkomy, Ashraf; Aboubakr, Mohamed; Morad, Mohamed

2014-01-01

The aim of this study was to determine the blood and tissue concentrations profile and effect of tilmicosin on some hematological and biochemical parameters in broiler chicken. Fifty clinically healthy Hubbard chickens were orally administered 25 mg/kg BW of tilmicosin once daily for 5 consecutive days. Tissue residues of tilmicosin in slaughtered healthy chicken could not be detected by microbiological assay in all tested tissues except in lung (at 96 hours) and liver and kidneys (at 72 hours) after last administration. Tilmicosin caused temporary decrease in the RBCs and WBCs counts and has no effect on hemoglobin (Hb) and packed cell volume concentration (PCV). Also, the effect of tilmicosin on some biochemical parameters was as follows: the concentrations of creatinine, uric acid, electrolytes (sodium, potassium, and calcium), glucose, AST, ALT, ALP, and HDL-cholesterol in the serum of treated chicken did not change in response to the repeated oral administration of tilmicosin. There were only a temporary significant decrease in total protein and albumin concentrations and a significant increase in cholesterol and triglycerides concentrations. Chicken must not be slaughtered before 4 days from the stopping of tilmicosin administration. Tilmicosin makes temporary changes on hematological and biochemical parameters in broiler chicken.

Leukogram Profile and Clinical Status in vivax and falciparum Malaria Patients from Colombia

PubMed Central

Tobón-Castaño, Alberto; Mesa-Echeverry, Esteban; Miranda-Arboleda, Andrés Felipe

2015-01-01

Introduction. Hematological alterations are frequent in malaria patients; the relationship between alterations in white blood cell counts and clinical status in malaria is not well understood. In Colombia, with low endemicity and unstable transmission for malaria, with malaria vivax predominance, the hematologic profile in malaria patients is not well characterized. The aim of this study was to characterize the leukogram in malaria patients and to analyze its alterations in relation to the clinical status. Methods. 888 leukogram profiles of malaria patients from different Colombian regions were studied: 556 with P. falciparum infection (62.6%), 313 with P. vivax infection (35.2%), and 19 with mixed infection by these species (2.1%). Results. Leukocyte counts at diagnosis were within normal range in 79% of patients and 18% had leucopenia; the most frequent alteration was lymphopenia (54%) followed by monocytosis (11%); the differential granulocyte count in 298 patients revealed eosinophilia (15%) and high basophil counts (8%). Leukocytosis, eosinopenia, and neutrophilia were associated with clinical complications. The utility of changes in leukocyte counts as markers of severity should be explored in depth. A better understanding of these hematological parameters will allow their use in prompt diagnosis of malaria complications and monitoring treatment response. PMID:26664413

Unmet needs in the transition to adulthood: 18- to 30-year-old people with hemophilia.

PubMed

Quon, Doris; Reding, Mark; Guelcher, Chris; Peltier, Skye; Witkop, Michelle; Cutter, Susan; Buranahirun, Cathy; Molter, Don; Frey, Mary Jane; Forsyth, Angela; Tran, Duc Bobby; Curtis, Randall; Hiura, Grant; Levesque, Justin; de la Riva, Debbie; Compton, Matthew; Iyer, Neeraj N; Holot, Natalia; Cooper, David L

2015-12-01

Young adults with hemophilia face unique challenges during the transition to adulthood, including issues associated with switching from pediatric to adult hematology care, building mature interpersonal relationships, and establishing an independent career with an assurance of medical insurance coverage. A greater understanding of these challenges is essential for developing effective strategies to address the specific needs of this population. These challenges may be differentiated from those of older adults with hemophilia in large part because of more extensive childhood prophylaxis and safer factor products, resulting in fewer joint problems and lower rates of HIV and HCV infections. This analysis of the changing nature and unmet needs of today's young adults entering into adult hemophilia treatment centers, as well as potential strategies for optimally addressing these needs, was developed following roundtable discussions between patients, caregivers, hematologists, and other health care professionals participating in comprehensive care. Challenges identified among young adults with hemophilia include psychosocial issues related to maturity, personal responsibility, and increased independence, as well as concerns regarding when and with whom to share information about one's hemophilia, limited awareness of educational and financial resources, and a low perceived value of regular hematology care. The initiatives proposed herein highlight important opportunities for health care professionals at pediatric and adult hemophilia treatment centers, as well as national organizations, community groups, and career counselors, to address key unmet needs of this patient population. © 2015 Wiley Periodicals, Inc.

ω-3 Fatty Acids Reduce Chemotherapy-Induced Hematological Toxicity by Bone Marrow Stimulation in Mice.

PubMed

Murakami, Kohei; Miyata, Hiroshi; Miyazaki, Yasuhiro; Makino, Tomoki; Takahashi, Tsuyoshi; Kurokawa, Yukinori; Yamasaki, Makoto; Nakajima, Kiyokazu; Takiguchi, Shuji; Mori, Masaki; Doki, Yuichiro

2017-07-01

ω-3 Fatty acids exert several benefits during chemotherapy, such as preventing intestinal mucosal damage and improving response to chemotherapy. However, little is known about the effect of ω-3 fatty acids on chemotherapy-induced hematological toxicities. Mice that had consumed either an ω-3-rich or an ω-3-poor diet for 2 weeks were intraperitoneally administered cisplatin. The resultant changes in blood cell count, bone marrow cell count, and cytokine levels in bone marrow supernatant were analyzed. The effect of ω-3 fatty acids on human peripheral blood mononuclear cells (PBMCs) exposed to cisplatin was also examined. Although peripheral blood cell counts decreased after cisplatin treatment in both groups of mice, the decrease in white blood cell count was significantly lower in mice that consumed the ω-3-rich diet. The decrease in bone marrow cells after cisplatin treatment was also reduced in mice that consumed the ω-3-rich diet. Levels of stem cell factor (SCF) and fibroblast growth factor 1 (FGF-1) were significantly higher in bone marrow supernatants from mice that consumed the ω-3-rich diet. The rate of apoptosis in PBMCs (after exposure to cisplatin) cultured in medium containing ω-3 fatty acids was significantly lower than in PBMCs cultured in control medium. ω-3-Rich diets reduced chemotherapy-induced leukopenia in mice. This may be the result of increased numbers of bone marrow cells due to higher levels of SCF and FGF-1 in the bone marrow.

Hemoglobin Threshold for Blood Transfusion in a Pediatric Intensive Care Unit.

PubMed

Chegondi, Madhuradhar; Sasaki, Jun; Raszynski, André; Totapally, Balagangadhar R

2016-07-01

To evaluate the hemoglobin threshold for red cell transfusion in children admitted to a pediatric intensive care unit (PICU). Retrospective chart review study. Tertiary care PICU. Critically ill pediatric patients requiring blood transfusion. No intervention. We analyzed the charts of all children between 1 month and 21 years of age who received packed red blood cell (PRBC) transfusions during a 2-year period. The target patients were identified from our blood bank database. For analysis, the patients were subdivided into four groups: acute blood loss (postsurgically, trauma, or acute gastrointestinal bleeding from other causes), hematologic (hematologic malignancies, bone marrow suppression, hemolytic anemia, or sickle cell disease), unstable (FiO 2 > 0.6 and/or on inotropic support), and stable groups. We also compared the pre-transfusion hemoglobin threshold in all unstable patients with that of all stable patients. A total of 571 transfusion episodes in 284 patients were analyzed. 28% (n = 160) of transfusions were administered to patients in the acute blood loss group, 36% (n = 206) to hematologic patients, 17% (n = 99) to unstable patients, and 18% (n = 106) to stable patients. The mean pre-transfusion hemoglobin (± SD) in all children as well as in the acute blood loss, hematologic, unstable and stable groups was 7.3 ± 1.20, 7.83 ± 1.32, 6.97 ± 1.31, 7.96 ± 1.37, 7.31 ± 1.09 g/dl, respectively. The transfusion threshold for acute blood loss and unstable groups was higher compared to hematologic and stable groups (p < 0.001; ANOVA with multiple comparisons). The mean pre-transfusion hemoglobin threshold for stable and unstable patients among all groups was 7.3 ± 1.3 and 7.9 ± 1.3 (p < 0.0001), respectively. The observed mortality rate was higher among children who received transfusion compared to other children admitted to PICU. The hemoglobin threshold for transfusion varied according to clinical conditions. Overall, the hemoglobin threshold for transfusion was 7.3 ± 1.20 g/dl.

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

Mizumoto, Masashi; Department of Radiation Oncology, University of Tsukuba, Tsukuba, Ibaraki; Sugahara, Shinji

Purpose: To evaluate the efficacy and safety of hyperfractionated concomitant boost proton beam therapy (PBT) for patients with esophageal cancer. Methods and Materials: The study participants were 19 patients with esophageal cancer who were treated with hyperfractionated photon therapy and PBT between 1990 and 2007. The median total dose was 78 GyE (range, 70-83 GyE) over a median treatment period of 48 days (range, 38-53 days). Ten of the 19 patients were at clinical T Stage 3 or 4. Results: There were no cases in which treatment interruption was required because of radiation-induced esophagitis or hematologic toxicity. The overall 1-more » and 5-year actuarial survival rates for all 19 patients were 79.0% and 42.8%, respectively, and the median survival time was 31.5 months (95% limits: 16.7- 46.3 months). Of the 19 patients, 17 (89%) showed a complete response within 4 months after completing treatment and 2 (11%) showed a partial response, giving a response rate of 100% (19/19). The 1- and 5-year local control rates for all 19 patients were 93.8% and 84.4 %, respectively. Only 1 patient had late esophageal toxicity of Grade 3 at 6 months after hyperfractionated PBT. There were no other nonhematologic toxicities, including no cases of radiation pneumonia or cardiac failure of Grade 3 or higher. Conclusions: The results suggest that hyperfractionated PBT is safe and effective for patients with esophageal cancer. Further studies are needed to establish the appropriate role and treatment schedule for use of PBT for esophageal cancer.« less

Immunologic responses in corn snakes (Pantherophis guttatus) after experimentally induced infection with ferlaviruses.

PubMed

Neul, Annkatrin; Schrödl, Wieland; Marschang, Rachel E; Bjick, Tina; Truyen, Uwe; von Buttlar, Heiner; Pees, Michael

2017-04-01

OBJECTIVE To measure immunologic responses of snakes after experimentally induced infection with ferlaviruses. ANIMALS 42 adult corn snakes (Pantherophis guttatus) of both sexes. PROCEDURES Snakes were inoculated intratracheally with genogroup A (n = 12), B (12), or C (12) ferlavirus (infected groups) or cell-culture supernatant (6; control group) on day 0. Three snakes from each infected group were euthanized on days 4, 16, 28, and 49, and 3 snakes from the control group were euthanized on day 49. Blood samples were collected from live snakes on days -6 (baseline), 4, 16, 28, and 49. Hematologic tests were performed and humoral responses assessed via hemagglutination-inhibition assays and ELISAs. Following euthanasia, gross pathological and histologic evaluations and virus detection were performed. RESULTS Severity of clinical signs of and immunologic responses to ferlavirus infection differed among snake groups. Hematologic values, particularly WBC and monocyte counts, increased between days 4 and 16 after infection. A humoral response was identified between days 16 and 28. Serum IgM concentrations increased from baseline earlier than IgY concentrations, but the IgY relative increase was higher at the end of the study. The hemagglutination-inhibition assay revealed that the strongest reactions in all infected groups were against the strain with which they had been infected. Snakes infected with genogroup A ferlavirus had the strongest immune response, whereas those infected with genogroup B had the weakest responses. CONCLUSIONS AND CLINICAL RELEVANCE Results of this experimental study suggested that the ferlavirus strain with the highest virulence induced the weakest immune response in snakes.

Hematopoietic cell transplantation in Fanconi anemia: current evidence, challenges and recommendations.

PubMed

Ebens, Christen L; MacMillan, Margaret L; Wagner, John E

2017-01-01

Hematopoietic cell transplantation for Fanconi Anemia (FA) has improved dramatically over the past 40 years. With an enhanced understanding of the intrinsic DNA-repair defect and pathophysiology of hematopoietic failure and leukemogenesis, sequential changes to conditioning and graft engineering have significantly improved the expectation of survival after allogeneic hematopoietic cell transplantation (alloHCT) with incidence of graft failure decreased from 35% to <10% and acute graft-versus-host disease (GVHD) from >40% to <10%. Today, five-year overall survival exceeds 90% in younger FA patients with bone marrow failure but remains about 50% in those with hematologic malignancy. Areas covered: We review the evolution of alloHCT contributing to decreased rates of transplant related complications; highlight current challenges including poorer outcomes in cases of clonal hematologic disorders, alloHCT impact on endocrine function and intrinsic FA risk of epithelial malignancies; and describe investigational therapies for prevention and treatment of the hematologic manifestations of FA. Expert commentary: Current methods allow for excellent survival following alloHCT for FA associated BMF irrespective of donor hematopoietic cell source. Alternative curative approaches, such as gene therapy, are being explored to eliminate the risks of GVHD and minimize therapy-related adverse effects.

Menstrual management and reproductive concerns in adolescent and young adult women with underlying hematologic or oncologic disease.

PubMed

Quinn, Sheila M; Louis-Jacques, Jennifer

2016-08-01

Heavy menstrual bleeding is common among adolescent and young adult women, and can affect health-related quality of life. The cause of heavy menstrual bleeding is not uncommonly because of an underlying hematologic or oncologic disease process, which substantially influences the way patients are counseled and treated. Options for menstrual management are more numerous today than ever before and range from minimizing monthly blood loss to suppressing the cycle altogether. However, an underlying bleeding disorder or malignancy can introduce many nuances and limits in individual patient care, which this review highlights. Additionally, because survival rates for adolescent and young adult cancers are improving, more of these patients are planning for lives after their disease, which may include starting or adding to a family. Options for fertility preservation during cancer therapy regimens are solidifying and both primary practitioners and subspecialists should be aware of the possibilities. Patients with underlying hematologic or oncologic disease require management of menstrual bleeding, but also deserve a comprehensive evaluation and counseling regarding their individualized contraceptive needs and fertility preservation options during their reproductive years. This review employs the latest evidence from current literature to help guide clinicians caring for this unique demographic.

Three-generation reproduction toxicity study of genetically modified rice with insect resistant genes.

PubMed

Hu, Yichun; Zhuo, Qin; Gong, Zhaolong; Piao, Jianhua; Yang, Xiaoguang

2017-01-01

In the present work, we evaluated the three generation reproductive toxicity of the genetically modified rice with insectresistant cry1Ac and sck genes. 120 Sprague-Dawley (SD) rats were divided into three groups which were fed with genetically modified rice diet (GM group), parental control rice diet (PR group) and AIN-93 control diet (both used as negative control) respectively. Bodyweight, food consumption, reproductive data, hematological parameters, serum chemistry, relative organ weights and histopathology for each generation were examined respectively. All the hematology and serum chemistry parameters, organ/body weight indicators were within the normal range or no change to the adverse direction was observed, although several differences in hematology and serum chemistry parameters (WBC, BUN, LDH of male rat, PLT, PCT, MPV of female rats), reproductive data (rate of morphologically abnormal sperm) were observed between GM rice group and two control groups. No macroscopic or histological adverse effects were found or considered as treatment-related, either. Overall, the three generation study of genetically modified rice with cry1Ac and sck genes at a high level showed no unintended adverse effects on rats's reproductive system. Copyright © 2016. Published by Elsevier Ltd.

American Society of Pediatric Hematology/Oncology

MedlinePlus

... Learn More Explore career opportunities in pediatric hematology/oncology Visit the ASPHO Career Center. Learn More Join ... Privacy Policy » © The American Society of Pediatric Hematology/Oncology

Immunosuppressive therapy for patients with Down syndrome and idiopathic aplastic anemia.

PubMed

Suzuki, Kyogo; Muramatsu, Hideki; Okuno, Yusuke; Narita, Atsushi; Hama, Asahito; Takahashi, Yoshiyuki; Yoshida, Makoto; Horikoshi, Yasuo; Watanabe, Ken-Ichiro; Kudo, Kazuko; Kojima, Seiji

2016-07-01

Idiopathic aplastic anemia (AA) is a rare hematological complication of Down syndrome (DS). The safety and efficacy of immunosuppressive therapy (IST) in individuals with DS remain unknown. We used a standard regimen of IST, comprising antithymocyte globulin and cyclosporine A, to treat three children with DS and idiopathic acquired AA. Two patients achieved a hematological (complete or partial) response and became transfusion independent at the final follow-up. The third patient failed to respond to IST and underwent bone marrow transplantation from a human leukocyte antigen (HLA)-mismatched unrelated donor. None of the patients experienced severe or unexpected adverse events during IST. Our experience suggests that IST is a safe and reasonable treatment, even in individuals with DS who suffer from AA and lack an HLA-matched sibling donor.

Detection of malignancy in body fluids: a comparison of the hematology and cytology laboratories.

PubMed

Jerz, Jaclyn L; Donohue, Rachel E; Mody, Rayomond R; Schwartz, Mary R; Mody, Dina R; Zieske, Arthur W

2014-05-01

Body fluids submitted to the hematology laboratory for cell counts may also be examined for the presence of malignancy. Previous studies evaluating the hematology laboratory's performance at detecting malignancy in body fluids have reached conflicting conclusions. To investigate the hematology laboratory's ability to detect malignancy in body fluids by comparison with cytology. Retrospective analysis of 414 body fluid samples during an 18-month period, with introduction of new quality assurance measures after the first 210 cases. If no concurrent cytology was ordered, results were compared with recent previous and/or subsequent cytologic, histologic, or flow cytometric diagnoses. Of the initial 210 cases, the hematology laboratory detected 3 of 13 malignancies diagnosed by concurrent cytology (23% sensitivity), with no false-positives (100% specificity). Malignancy was not identified on retrospective review of the hematology slides in the 10 discrepant cases. After the initial study, educational sessions on morphology for the medical technologists and a more thorough hematology-cytology correlation policy were implemented. The subsequent 204 hematology laboratory cases had increased sensitivity for the detection of malignancy (60%; 6 of 10). Definitive features of malignancy were seen in only one discrepant hematology laboratory slide on retrospective review. This case had not been flagged for hematopathologist review. None of the discrepancies before or after implementation of the additional quality assurance measures impacted patient care. Body fluid processing by the hematology laboratory is not optimized for the detection of malignancy. Concurrent cytologic examination is critical for the detection of malignancy, and needs to be considered as cost-saving measures are increasingly implemented.

Concurrent chemoradiotherapy versus radiotherapy alone for locoregionally advanced nasopharyngeal carcinoma in the era of intensity-modulated radiotherapy: a meta-analysis.

PubMed

He, Yan; Guo, Tao; Guan, Hui; Wang, Jingjing; Sun, Yu; Peng, Xingchen

2018-01-01

In this study, we attempted to compare the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) with radiotherapy alone (RT) for locoregionally advanced nasopharyngeal carcinoma (LANPC) in the era of intensity-modulated radiotherapy (IMRT) by meta-analysis. We searched databases, and all randomized controlled trials meeting the inclusion criteria were utilized for a meta-analysis with RevMan 5.3 based on the Cochrane methodology. Fifteen studies were found suitable based on the inclusion criteria. CCRT not only significantly improved the overall response rate (risk ratio [RR]=0.53, 95% CI 0.43-0.66) and the complete response rate (RR=0.60, 95% CI 0.51-0.71) but also contributed to longer overall survival. The incidence of grade 3-4 adverse events from CCRT group increased in hematologic toxicity (RR 2.25, 95% CI 1.54-3.29), radiation-induced oral mucositis (RR 1.64, 95% CI 1.14-2.35), and radiodermatitis (RR 1.80, 95% CI 1.13-2.88). Compared with IMRT alone, CCRT provided survival benefit with acceptable toxicity in patients with LANPC. However, we need multicenter randomized controlled trials and long-term follow-up to evaluate the eventual efficacy and toxicity of concurrent chemotherapy plus IMRT.

Central Line Associated Blood Stream Infections in Pediatric Hematology/Oncology Patients With Different Types of Central Lines.

PubMed

Hord, Jeffrey D; Lawlor, John; Werner, Eric; Billett, Amy L; Bundy, David G; Winkle, Cindi; Gaur, Aditya H

2016-09-01

Central line associated bloodstream infections (CLABSIs) are a significant cause of morbidity and mortality in pediatric hematology/oncology (PHO) patients. Understanding the differences in CLABSI rates by central line (CL) type is important to inform clinical decisions. CLABSI, using similar definitions, noted with three commonly used CL types (totally implanted catheter [port], tunneled externalized catheter [TEC], peripherally inserted central catheter [PICC]) and CL-specific line days were prospectively tracked across 15 US PHO centers from May 2012 until April 2015 and CLABSI rates (CLABSI per 1,000 CL-specific line days) were calculated. Host and organism characterstics associated with the CLABSI events were analyzed. Over the course of 2.8 million line days, 1,113 CLABSI events (397 in inpatients and 716 in ambulatory patients) were noted. The inpatient CLABSI rate was higher than the ambulatory CLABSI rate for each of the CL types: 1.48 versus 0.16 for ports, 3.51 versus 1.38 for TECs, and 3.07 versus 1.16 for PICCs, respectively. TECs and PICCs were associated with higher CLABSI rates than ports, inpatient and ambulatory. We found that CLABSI rates were significantly higher for inpatients compared to ambulatory PHO patients for all CL types. Among ambulatory patients, TECs had the highest CLABSI rate and ports the lowest. Among inpatients, TECs and PICCs had higher CLABSI rates than ports but were not statistically different from one another. Cognizant that host and underlying disease attributes may contribute to these differences, these results can still inform CL choice in clinical practice. © 2016 Wiley Periodicals, Inc.

Iron, Hematological Parameters and Blood Plasma Lipid Profile in Vitamin D Supplemented and Non-Supplemented Young Soccer Players Subjected to High-Intensity Interval Training.

PubMed

Jastrzebska, Maria; Kaczmarczyk, Mariusz; Suárez, Arturo Diaz; Sánchez, Guillermo Felipe López; Jastrzebska, Joanna; Radziminski, Lukasz; Jastrzebski, Zbigniew

2017-01-01

Vitamin D deficiency has been associated with increased risk for cardiovascular disease and anemia. Vitamin D-related changes in lipid profile have been studied extensively but the relationship between vitamin D and lipid metabolism is not completely understood. As both vitamin D and intermittent training may potentially affect iron and lipid metabolism, the aim of the study was to evaluate whether a daily supplementation of vitamin D can modulate the response of hematological and lipid parameters to high-intensity interval training (HIIT) in soccer players. Thirty-six young elite junior soccer players were included in the placebo-controlled, double-blind study. Participants were non-randomly allocated into either a supplemented group (SG, n=20, HIIT and 5,000 IU of vitamin D daily) or placebo group (PG, n=16, HIIT and sunflower oil). Hematological parameters were ascertained before and after the 8-wk training. The change score (post- and pre-training difference) was calculated for each individual and the mean change score (MCS) was compared between SG and PG using the t test and analysis of covariance. There were no differences between SG and PG at baseline. The red and white cell count, hemoglobin, hematocrit, MCHC, ferritin, and HDL-cholesterol changed significantly over the 8-wk HIIT. However, no significant differences in MCS were observed between SG and PG for any variable. A daily vitamin D supplement did not have any impact on alteration in hematological or lipid parameters in young soccer players in the course of high-intensity interval training.

Phenotypic plasticity in blood–oxygen transport in highland and lowland deer mice

PubMed Central

Tufts, Danielle M.; Revsbech, Inge G.; Cheviron, Zachary A.; Weber, Roy E.; Fago, Angela; Storz, Jay F.

2013-01-01

SUMMARY In vertebrates living at high altitude, arterial hypoxemia may be ameliorated by reversible changes in the oxygen-carrying capacity of the blood (regulated by erythropoiesis) and/or changes in blood–oxygen affinity (regulated by allosteric effectors of hemoglobin function). These hematological traits often differ between taxa that are native to different elevational zones, but it is often unknown whether the observed physiological differences reflect fixed, genetically based differences or environmentally induced acclimatization responses (phenotypic plasticity). Here, we report measurements of hematological traits related to blood–O2 transport in populations of deer mice (Peromyscus maniculatus) that are native to high- and low-altitude environments. We conducted a common-garden breeding experiment to assess whether altitude-related physiological differences were attributable to developmental plasticity and/or physiological plasticity during adulthood. Under conditions prevailing in their native habitats, high-altitude deer mice from the Rocky Mountains exhibited a number of pronounced hematological differences relative to low-altitude conspecifics from the Great Plains: higher hemoglobin concentrations, higher hematocrits, higher erythrocytic concentrations of 2,3-diphosphoglycerate (an allosteric regulator of hemoglobin–oxygen affinity), lower mean corpuscular hemoglobin concentrations and smaller red blood cells. However, these differences disappeared after 6 weeks of acclimation to normoxia at low altitude. The measured traits were also indistinguishable between the F1 progeny of highland and lowland mice, indicating that there were no persistent differences in phenotype that could be attributed to developmental plasticity. These results indicate that the naturally occurring hematological differences between highland and lowland mice are environmentally induced and are largely attributable to physiological plasticity during adulthood. PMID:23239893

Management of iron deficiency anemia: a survey of pediatric hematology/oncology specialists.

PubMed

Powers, Jacquelyn M; McCavit, Timothy L; Buchanan, George R

2015-05-01

Iron deficiency anemia (IDA) is the most common hematologic condition in children and adolescents in the United States (US). No prior reports have described the management of IDA by a large cohort of pediatric hematology/oncology specialists. A 20-question electronic survey that solicited responses to two hypothetical cases of IDA was sent to active members of the American Society of Pediatric Hematology/Oncology (ASPHO) in the US. Of 1,217 recipients, 398 (32.7%) reported regularly treating IDA and completed the survey. In a toddler with nutritional IDA, 15% (N = 61) of respondents reported ordering no diagnostic test beyond a complete blood count. Otherwise, wide variability in laboratory testing was reported. For treatment, most respondents would prescribe ferrous sulfate (N = 335, 84%) dosed at 6 mg/kg/day (N = 248, 62%) divided twice daily (N = 272, 68%). The recommended duration of iron treatment after resolution of anemia and normalized serum ferritin varied widely from 0 to 3 months. For an adolescent with heavy menstrual bleeding and IDA, most respondents recommended ferrous sulfate (N = 327, 83%), with dosing based on the number of tablets daily. For IDA refractory to oral treatment, intravenous iron therapy was recommended most frequently, 48% (N = 188) using iron sucrose, 17% (N = 68) ferric gluconate, and 15% (N = 60) low molecular weight iron dextran. The approach to diagnosis and treatment of IDA in childhood was widely variable among responding ASPHO members. Given the lack of an evidence base to guide clinical decision making, further research investigating IDA management is needed. © 2015 Wiley Periodicals, Inc.

HIV-associated hematologic malignancies: Experience from a Tertiary Cancer Center in India.

PubMed

Reddy, Rakesh; Gogia, Ajay; Kumar, Lalit; Sharma, Atul; Bakhshi, Sameer; Sharma, Mehar C; Mallick, Saumyaranjan; Sahoo, Ranjit

2016-01-01

Data on HIV associated hematologic malignancies is sparse from India. This study attempts to analyze the spectrum and features of this disease at a tertiary cancer center in India. Retrospective study from case records of patients registered with a diagnosis of hematologic malignancy and HIV infection between January 2010 and June 2015. Thirteen cases of HIV associated hematologic malignancies were identified, six of them pediatric. HIV diagnosis was concurrent to diagnosis of cancer in 12 and preceded it in one of them. ECOG PS at presentation was >1 in all of them. All patients, except one, had B symptoms. Six of the patients had bulky disease and six are stage 4. Predominant extranodal disease was seen in 67% of them. NHL accounted for 10 of 13 patients and DLBCL-Germinal center was the most common subtype. Mean CD4+ cell count was 235/μL (range, 32-494). HAART could be given along with chemotherapy to 11 patients. Two-thirds of patients received standard doses of therapy. Chemo-toxicity required hospitalization in 58%. CR was achieved in 45% and 36% had progressive disease with first-line therapy. At the time of last follow up, 3 patients were alive with responsive disease, 2 in CR and 1 in PR. None of the pediatric patients were long time responders. These malignancies were of advanced stage and higher grade. Goal of therapy, in the HAART era, is curative. Pediatric patients had dismal outcome despite good chemotherapy and HAART. There is an urgent need to improve data collection for HIV related cancers in India.

Therapeutic efficacy and toxicity of bolus application of chemotherapy protocol in the treatment of metastatic colorectal cancer.

PubMed

Šišić, Ibrahim; Pojskić, Belma; Mekić Abazović, Alma; Kovčin, Vladimir

2015-08-01

To compare efficacy and toxicity of bolus application of chemotherapy protocol, oxaliplatin, fluorouracil (bolus), leucovorin (folfox) between two groups of patients in the therapy of metastatic colorectal carcinoma (mCRC). A total of 63 patients were treated for mCRC in the period January 2009 - January 2010 at the Department of Oncology of the Cantonal Hospital Zenica, Bosnia and Herzegovina (first group, 30 patients) and at the Department of Oncology of the Clinical Hospital Centre Bežanijska kosa in Belgrade, Serbia, in the period January 2005 - January 2006 (second group, 33 patients). The patients were treated according the same protocol, i.v. bolus infusion, but in different day intervals (D), 1, 8, 15/28 days or D1-D5/28 days, respectively. In all patients the following factors were analyzed: tumor response, overall survival (OS), progression free survival, hematological and non-hematological toxicity . Colon was the primary localization in almost two thirds of patients. There was no statistically significant difference between the groups according to the age, hematological and non-hematological toxicity, as well as in achieved OS. Progression free survival expressed in months was in average 5 months though with a large range between minimal and maximal survival time. Both groups have shown equivalent efficacy to applied chemotherapy protocols. Overall survival in the two groups matched data from the literature. Further research should confirm success of the combination of chemotherapy protocols and their combination with the biological therapy. Copyright© by the Medical Assotiation of Zenica-Doboj Canton.

Hematological Analysis of the Ascidian Botrylloides leachii (Savigny, 1816) During Whole-Body Regeneration.

PubMed

Blanchoud, Simon; Zondag, Lisa; Lamare, Miles D; Wilson, Megan J

2017-06-01

Whole-body regeneration (WBR)-the formation of an entire adult from only a small fragment of its own tissue-is extremely rare among chordates. Exceptionally, in the colonial ascidian Botrylloides leachii (Savigny, 1816) a fully functional adult is formed from their common vascular system after ablation of all adults from the colony in just 10 d, thanks to their high blastogenetic potential. While previous studies have identified key genetic markers and morphological changes, no study has yet focused on the hematological aspects of regeneration despite the major involvement of the remaining vascular system and the contained hemocytes in this process. To dissect this process, we analyzed colony blood flow patterns using time-lapse microscopy to obtain a quantitative description of the velocity, reversal pattern, and average distance traveled by hemocytes. We also observed that flows present during regeneration are powered by temporally and spatially synchronized contractions of the terminal ampullae. In addition, we revised previous studies of B. leachii hematology as well as asexual development using histological sectioning and compared the role played by hemocytes during WBR. We found that regeneration starts with a rapid healing response characterized by hemocyte aggregation and infiltration of immunocytes, followed by increased activity of hemoblasts, recruitment of macrophage-like cells for clearing the tissues of debris, and their subsequent disappearance from the circulation concomitant with the maturation of a single regenerated adult. Overall, we provide a detailed account of the hematological properties of regenerating B. leachii colonies, providing novel lines of inquiry toward the decipherment of regeneration in chordates.

Effect of substituting increasing levels of organic Zn for inorganic Zn on performance, hematological and serum biochemical constituents, antioxidant status and immune response in rat.

PubMed

Nagalakshmi, D; Sridhar, K; Swain, P S; Reddy, A G

2016-01-01

The effect of replacing dietary Zn supplemented from inorganic (ZnCO 3 ) source with organic Zn (Zn methionine; Zn-met) was investigated in 72 rats (98.42 ± 1.483 g) by randomly allotting to 4 diets (6 replicates/diet, 3 rats/replicate). Basal diet was prepared with purified ingredients without Zn. The control diet (AIN-76A) contained 12 ppm of Zn from ZnCO 3 (100-I). In the other diets ZnCO 3 was replaced with Zn-met at the rates of 50 (50I:50O), 75 (25I:75O) or 100% (100-O). Weekly body weight and daily feed intake were recorded for 14 weeks. Blood was collected by retro-orbital puncture on the 70th and 80th day to determine haematological and various serum biochemical constituents, and antioxidant enzyme activities in haemolysate, respectively. Rats were antigenically challenged with sheep RBC on day 73 to assess humoral immune response (HIR), and on day 95 for cell mediated immune response (CMIR) and rats were sacrificed at the end of rearing period to collect liver, muscle, pancreas and kidneys for Zn estimation and oxidative stress markers in liver. The data were analysed using completely randomized design. Weight gain and feed intake, hematological and serum biochemical constituents, Zn content in organs (except liver) were not influenced by replacing ZnCO 3 with Zn-met. Zinc concentrations in the serum and liver were higher (P<0.05) with 50% replacement of ZnCO 3 with Zn-met compared to 0 or 100% replacement. Lower (P<0.05) lipid peroxidation and higher (P<0.05) glutathione peroxidase and glutathione reductase activities were observed with 50 and 75% replacement of ZnCO 3 with Zn-met compared to 0 or 100% replacement. Protein carbonyls and reduced glutathione in liver were not affected, while TBARS decreased (P<0.05) with substituting Zn-met (50-100%) for ZnCO 3 . The HIR and CMIR increased with increasing Zn-met supplementation and the highest response was observed with 75-100% replacement of ZnCO 3 with Zn-met. It is concluded that replacement of 50 or 75% of ZnCO 3 with Zn-met increased antioxidant and immune response in rats with no effect on growth.

Marriage, employment, and health insurance in adult survivors of childhood cancer.

PubMed

Crom, Deborah B; Lensing, Shelly Y; Rai, Shesh N; Snider, Mark A; Cash, Darlene K; Hudson, Melissa M

2007-09-01

Adult survivors of childhood cancer are at risk for disease- and therapy-related morbidity, which can adversely impact marriage and employment status, the ability to obtain health insurance, and access to health care. Our aim was to identify factors associated with survivors' attainment of these outcomes. We surveyed 1,437 childhood cancer survivors who were >18 years old and >10 years past diagnosis. We compared our cohort's data to normative data in the Medical Expenditure Panel Survey and the U.S. Census Bureau's Current Population Surveys. Respondents were stratified by hematologic malignancies, central nervous system tumors, or other solid tumors and by whether they had received radiation therapy. Most respondents were survivors of hematologic malignancies (71%), white (91%), and working full-time (62%); 43% were married. Compared with age- and sex-adjusted national averages, only survivors of hematologic malignancies who received radiation were significantly less likely to be married (44 vs. 52%). Full-time employment among survivors was lower than national norms, except among survivors of hematologic malignancies who had not received radiation therapy. The rates of coverage of health insurance, especially public insurance, were higher in all diagnostic groups than in the general population. While difficulty obtaining health care was rarely reported, current unemployment and a lack of insurance were associated with difficulty in obtaining health care (P < 0.05 and P < 0.001, respectively). CONCLUSIONS/IMPLICATIONS FOR CANCER SURVIVORS: Subgroups of cancer survivors do experience long-term differences in functional outcomes that should be addressed early. Survivors who are unmarried, unemployed, and uninsured experience difficulty accessing health care needed to address long-term health concerns.

Hematology of healthy Florida manatees (Trichechus manatus)

USGS Publications Warehouse

Harvey, J.W.; Harr, K.E.; Murphy, D.; Walsh, M.T.; Nolan, E.C.; Bonde, R.K.; Pate, M.G.; Deutsch, C.J.; Edwards, H.H.; Clapp, W.L.

2009-01-01

Background: Hematologic analysis is an important tool in evaluating the general health status of free-ranging manatees and in the diagnosis and monitoring of rehabilitating animals. Objectives: The purpose of this study was to evaluate diagnostically important hematologic analytes in healthy manatees (Trichechus manatus) and to assess variations with respect to location (free ranging vs captive), age class (small calves, large calves, subadults, and adults), and gender. Methods: Blood was collected from 55 free-ranging and 63 captive healthy manatees. Most analytes were measured using a CELL-DYN 3500R; automated reticulocytes were measured with an ADVIA 120. Standard manual methods were used for differential leukocyte counts, reticulocyte and Heinz body counts, and plasma protein and fibrinogen concentrations. Results: Rouleaux, slight polychromasia, stomatocytosis, and low numbers of schistocytes and nucleated RBCs (NRBCs) were seen often in stained blood films. Manual reticulocyte counts were higher than automated reticulocyte counts. Heinz bodies were present in erythrocytes of most manatees. Compared with free-ranging manatees, captive animals had slightly lower MCV, MCH, and eosinophil counts and slightly higher heterophil and NRBC counts, and fibrinogen concentration. Total leukocyte, heterophil, and monocyte counts tended to be lower in adults than in younger animals. Small calves tended to have higher reticulocyte counts and NRBC counts than older animals. Conclusions: Hematologic findings were generally similar between captive and free-ranging manatees. Higher manual reticulocyte counts suggest the ADVIA detects only reticulocytes containing large amounts of RNA. Higher reticulocyte and NRBC counts in young calves probably reflect an increased rate of erythropoiesis compared with older animals. ?? 2009 American Society for Veterinary Clinical Pathology.

Toxic elements and associations with hematology, plasma biochemistry, and protein electrophoresis in nesting loggerhead sea turtles (Caretta caretta) from Casey Key, Florida.

PubMed

Perrault, Justin R; Stacy, Nicole I; Lehner, Andreas F; Poor, Savannah K; Buchweitz, John P; Walsh, Catherine J

2017-12-01

Toxic elements (arsenic, cadmium, lead, mercury, selenium, thallium) are a group of contaminants that are known to elicit developmental, reproductive, general health, and immune system effects in reptiles, even at low concentrations. Reptiles, including marine turtles, are susceptible to accumulation of toxic elements due to their long life span, low metabolic rate, and highly efficient conversion of prey into biomass. The objectives of this study were to (1) document concentrations of arsenic, cadmium, lead, mercury, selenium, and thallium in whole blood and keratin from nesting loggerhead sea turtles (Caretta caretta) from Casey Key, Florida and document correlations thereof and (2) correlate whole blood toxic element concentrations to various hematological and plasma biochemistry analytes. Baselines for various hematological and plasma analytes and toxic elements in whole blood and keratin (i.e., scute) in nesting loggerheads are documented. Various correlations between the toxic elements and hematological and plasma biochemistry analytes were identified; however, the most intriguing were negative correlations between arsenic, cadmium, lead, and selenium with and α- and γ-globulins. Although various extrinsic and intrinsic variables such as dietary and feeding changes in nesting loggerheads need to be considered, this finding may suggest a link to altered humoral immunity. This study documents a suite of health variables of nesting loggerheads in correlation to contaminants and identifies the potential of toxic elements to impact the overall health of nesting turtles, thus presenting important implications for the conservation and management of this species. Copyright © 2017 Elsevier Ltd. All rights reserved.

Changes of hematological and biochemical parameters and levels of pepsinogen, histamine and prostaglandins in dairy cows affected with left displacement of the abomasum.

PubMed

Al-Rawashdeh, O; Ismail, Z Bani; Talafha, A; Al-Momani, A

2017-03-28

The aims of this study were to determine the serum levels of pepsinogen, histamine, and prostaglandins F2α and E2 in lactating dairy cows affected with left displacement of the abomasum (LDA). In addition, the hematological and serum biochemical parameters were also determined in cows affected with LDA. A total of 52 adult lactating Holstein-Friesian cows affected with LDA and 30 normal cows (control) were used. In LDA cows, the average age, BCS and body weight were 4.9 ± 1.2 years, 2.5 ± 0.75, and 525 ± 150kg respectively. The average days-in-milk (DIM) in affected cows was 14 ± 6 with a range between 7 to 45 days. There were no significant differences in values of rectal temperature, heart rate and respiration rate between LDA cows and control. Rumen motility was significantly (p≤0.05) decreased in LDA cows. Cows affected with LDA had significantly (p≤0.05) increased glucose levels, and decreased levels of calcium and magnesium. There were significantly (p≤0.05) increased serum levels of pepsinogen and histamine in LDA cows while levels of prostaglandin E2 were significantly decreased in comparison to those in control cows. There were no significant changes in serum levels of prostaglandin F2α. In the hematology analyses, there were no significant changes in cows with LDA when compared to those in control cows. This study provides evidence of a possible role for pepsinogen, histamine and prostaglandin E2 in the etiopathophysiology of LDA in dairy cows.

Hematological profile and risk factors associated with pulmonary tuberculosis patients in Quetta, Pakistan.

PubMed Central

Shafee, Muhammad; Abbas, Ferhat; Ashraf, Muhammad; Alam Mengal, Mohammad; Kakar, Niamatullah; Ahmad, Zafar; Ali, Fawad

2014-01-01

Objectives: Tuberculosis (TB) is a chronic debilitating infectious disease affecting more than one third of the global population. This study was designed to investigate different peripheral blood parameters and risk factors in TB patients. Methods: A total of 600 (Male, 238 and Female, 362) aging 20-80 Years patients with clinical signs of prolonged cough, chest pain and fever, were evaluated for peripheral blood parameters using hematology analyzer. All the informations related to the disease were collected from the patients and recorded using predesigned questionnaire. Results: Erythrocytic Sedimentation Rate (ESR), Hemoglobin (Hb) and lymphocytes were markedly changed in both sexes. Hemoglobin was recorded lower than normal value in 55% and 53% of male and female population respectively. Total leukocyte count was also lower than normal values in 8% and 6% of male and female respectively. Similarly neutropenia was observed in 5% and 8% cases, while neutrophilia was recorded as 60% and 64% in male and female patients respectively. Lymphocytopenia was also observed in 59% and 43% patients in male and female respectively. Illiteracy, smoking habits, overcrowding and living in shared houses were the main associated risk factors contributing in the enhancement of the disease. Conclusion: The disease was present significantly more in females and was relatively higher in older patients. Different hematological parameters like Erythrocytic sedimentation Rate (ESR), platelets and leukocytes work as hallmark and help the clinicians in early diagnosis of the disease. Malnutrition, smoking tobacco, living in shared houses, illiteracy and poverty were the common risk factors contributing to the dissemination of the tuberculosis in the target area population. PMID:24639827

[Epidemiology of febrile neutropenia in patients with hematological disease-a prospective multicentre survey in China].

PubMed

Yan, C H; Xu, T; Zheng, X Y; Sun, J; Duan, X L; Gu, J L; Zhao, C L; Zhu, J; Wu, Y H; Wu, D P; Hu, J D; Huang, H; Jiang, M; Li, J; Hou, M; Wang, C; Shao, Z H; Liu, T; Hu, Y; Huang, X J

2016-03-01

To investigate the incidence, clinical and microbiological features of febrile, and risk factors during neutropenia periods in patients with hematological diseases. From October 20, 2014 to March 20, 2015, consecutive patients who had hematological diseases and developed neutropenia during hospitalization were enrolled in the prospective, multicenter and observational study. A total of 784 episodes of febrile occurred in 1 139 neutropenic patients with hematological diseases. The cumulative incidence of febrile was 81.9% at 21 days after neutropenia. Multivariate analysis suggested that central venous catheterization (P<0.001, HR=3.407, 95% CI 2.276-4.496), gastrointestinal mucositis (P<0.001, HR=10.548, 95% CI 3.245-28.576), previous exposure to broad-spectrum antibiotics within 90 days (P<0.001, HR=3.582, 95% CI 2.387-5.770) and duration of neutropenia >7 days (P<0.001,HR=4.194, 95% CI 2.572-5.618) were correlated with higher incidence of febrile during neutropenia. With the increase of the risk factors, the incidence of febrile increased gradually (35.4%, 69.2%, 86.1%, 95.6%, P<0.001). Of 784 febrile cases, 253 (32.3%) were unknown origin, 429 (54.7% )of clinical documented infections and 102(13.0%) of microbiological documented infections. The most common sites of infection were pulmonary (49.5%), upper respiratory (16.0%), crissum (9.8%), blood stream (7.7%). The most common pathogens were gram-negative bacteria (44.54%), followed by gram-positive bacteria (37.99% ) and fungi (17.47% ). There was no significant difference in mortality rates between cases with febrile and cases without febrile (9.2% vs 4.8%, P=0.099). Multivariate analysis also suggested that >40 years old (P=0.047, HR=5.000, 95% CI 0.853-28.013), hemodynamic instability (P=0.001, HR=13.185, 95% CI 2.983-54.915), prior colonization or infection by resistant pathogens (P=0.005, HR=28.734, 95% CI 2.921-313.744), blood stream infection (P=0.038, HR=9.715, 95% CI 1.110-81.969) and pulmonary infection (P=0.031, HR=25.905, 95% CI 1.381-507.006) were correlated with higher mortality rate in cases with febrile. Febrile was the common complication during neutropenia periods in patients with hematological disease. There was different distribution of organisms in different sites of infection. Moreove, the duration of neutropenia >7 days, central venous catheterization, gastrointestinal mucositis and previous exposure to broad-spectrum antibiotics within 90 days were the risk factors for the higher incidence of febrile.

Strategies for the Identification of T Cell–Recognized Tumor Antigens in Hematological Malignancies for Improved Graft-versus-Tumor Responses after Allogeneic Blood and Marrow Transplantation

PubMed Central

Zilberberg, Jenny; Feinman, Rena; Korngold, Robert

2015-01-01

Allogeneic blood and marrow transplantation (allo-BMT) is an effective immunotherapeutic treatment that can provide partial or complete remission for patients with hematological malignancies. Mature donor T cells in the donor inoculum play a central role in mediating graft-versus-tumor (GVT) responses by destroying residual tumor cells that persist after conditioning regimens. Alloreactivity towards minor histocompatibility antigens (miHA), which are varied tissue-related self-peptides presented in the context of major histocompatibility complex (MHC) molecules on recipient cells, some of which may be shared on tumor cells, is a dominant factor for the development of GVT. Potentially, GVT can also be directed to tumor-associated antigens or tumor-specific antigens that are more specific to the tumor cells themselves. The full exploitation of allo-BMT, however, is greatly limited by the development of graft-versus-host disease (GVHD), which is mediated by the donor T cell response against the miHA expressed in the recipient’s cells of the intestine, skin, and liver. Because of the significance of GVT and GVHD responses in determining the clinical outcome of patients, miHA and tumor antigens have been intensively studied, and one active immunotherapeutic approach to separate these two responses has been cancer vaccination after allo-BMT. The combination of these two strategies has an advantage over vaccination of the patient without allo-BMT because his or her immune system has already been exposed and rendered unresponsive to the tumor antigens. The conditioning for allo-BMT eliminates the patient’s existing immune system, including regulatory elements, and provides a more permissive environment for the newly developing donor immune compartment to selectively target the malignant cells. Utilizing recent technological advances, the identities of many human miHA and tumor antigenic peptides have been defined and are currently being evaluated in clinical and basic immunological studies for their ability to produce effective T cell responses. The first step towards this goal is the identification of targetable tumor antigens. In this review, we will highlight some of the technologies currently used to identify tumor antigens and anti-tumor T cell clones in hematological malignancies. PMID:25459643

Strategies for the identification of T cell-recognized tumor antigens in hematological malignancies for improved graft-versus-tumor responses after allogeneic blood and marrow transplantation.

PubMed

Zilberberg, Jenny; Feinman, Rena; Korngold, Robert

2015-06-01

Allogeneic blood and marrow transplantation (allo-BMT) is an effective immunotherapeutic treatment that can provide partial or complete remission for patients with hematological malignancies. Mature donor T cells in the donor inoculum play a central role in mediating graft-versus-tumor (GVT) responses by destroying residual tumor cells that persist after conditioning regimens. Alloreactivity towards minor histocompatibility antigens (miHA), which are varied tissue-related self-peptides presented in the context of major histocompatibility complex (MHC) molecules on recipient cells, some of which may be shared on tumor cells, is a dominant factor for the development of GVT. Potentially, GVT can also be directed to tumor-associated antigens or tumor-specific antigens that are more specific to the tumor cells themselves. The full exploitation of allo-BMT, however, is greatly limited by the development of graft-versus-host disease (GVHD), which is mediated by the donor T cell response against the miHA expressed in the recipient's cells of the intestine, skin, and liver. Because of the significance of GVT and GVHD responses in determining the clinical outcome of patients, miHA and tumor antigens have been intensively studied, and one active immunotherapeutic approach to separate these two responses has been cancer vaccination after allo-BMT. The combination of these two strategies has an advantage over vaccination of the patient without allo-BMT because his or her immune system has already been exposed and rendered unresponsive to the tumor antigens. The conditioning for allo-BMT eliminates the patient's existing immune system, including regulatory elements, and provides a more permissive environment for the newly developing donor immune compartment to selectively target the malignant cells. Utilizing recent technological advances, the identities of many human miHA and tumor antigenic peptides have been defined and are currently being evaluated in clinical and basic immunological studies for their ability to produce effective T cell responses. The first step towards this goal is the identification of targetable tumor antigens. In this review, we will highlight some of the technologies currently used to identify tumor antigens and anti-tumor T cell clones in hematological malignancies. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

The Coags Uncomplicated App: Fulfilling Educational Gaps Around Diagnosis and Laboratory Testing of Coagulation Disorders.

PubMed

Kessler, Craig; Peerschke, Ellinor I; Chitlur, Meera B; Kulkarni, Roshni; Holot, Natalia; Cooper, David L

2017-04-18

Patients with coagulation disorders may present to a variety of physician specialties; however, accurate and efficient diagnosis can be challenging for physicians not specialized in hematology, due to identified gaps in knowledge around appropriate laboratory assays and interpretation of test results. Coags Uncomplicated was developed to fill this unmet educational need by increasing practical knowledge of coagulation disorders among nonexpert physicians and other health care professionals (HCPs) in a point-of-care (POC) setting. The aim of this study was to assess patterns of use of the mobile app Coags Uncomplicated, a tool designed to support education regarding accurate and efficient diagnosis of bleeding disorders. App metrics were obtained by tracking registered user data. Additionally, a survey was distributed to registered users, to assess circumstances and frequency of use. The most common specialties of 7596 registered US users were hematology-oncology (n=1534, 20.19%), hematology (n=1014, 13.35%), and emergency medicine (n=1222, 16.09%); most identified as physicians (n=4082, 53.74%). Specialties accounting for the greatest numbers of screen views were hematology-oncology (99,390 views), hematology (47,808 views), emergency medicine (23,121 views), and internal medicine (22,586 views). The most common diagnostic endpoints reached were disseminated intravascular coagulation (DIC; 2713 times), liver disease effect (2108 times), and vitamin K deficiency (1584 times). Of 3424 users asked to take the survey, 262 responded (7.65%); most were physicians in direct clinical care (71%) and specialized in hematology-oncology (39%) or emergency medicine (21%). Most frequent use was reported by hematologists (69%, ≥6 times) and hematologists-oncologists (38%, ≥6 times). Most physicians (89.2%) reported using the app for patient-case-related education around appropriate use of laboratory tests in diagnostic evaluation. Physicians rated Lab Value Analyzer (mean 4.43) and Lab Test Algorithm (mean 4.46) tools highly on a 5-point "how helpful" scale and were likely to recommend the app to colleagues. App use among physicians and other HCPs is consistent with value as a POC educational tool, which may facilitate differential diagnoses and appropriate early consultation with hematologists. ©Craig Kessler, Ellinor I Peerschke, Meera B Chitlur, Roshni Kulkarni, Natalia Holot, David L Cooper. Originally published in JMIR Medical Education (http://mededu.jmir.org), 18.04.2017.

Associations of endothelial dysfunction with exposure to ambient fine particles in diabetic subjects: are the effects modified by patient characteristics?

EPA Science Inventory

Objective: Exposure to fme airborne particulate matter (PM2.5) has been shown to be responsible for cardiovascular and hematological effects, especially in older people with cardiovascular disease. Results of epidemiological studies suggest that subjects with diabetes may be a pa...

Utility of CRISPR/Cas9 systems in hematology research.

PubMed

Lucas, Daniel; O'Leary, Heather A; Ebert, Benjamin L; Cowan, Chad A; Tremblay, Cedric S

2017-10-01

Since the end of the 20th century, novel approaches have emerged to manipulate experimental models of hematological disorders so that they more accurately mirror what is observed in the clinical setting. Despite these technological advances, the characterization of crucial genes for benign or malignant hematological disorders remains challenging, given the dynamic nature of the hematopoietic system and the genetic heterogeneity of these disorders. To overcome this limitation, genome-editing technologies have been developed to manipulate the genome specifically via deletion, insertion, or modification of targeted loci. These technologies have progressed swiftly, allowing their common use to investigate genetic function in experimental hematology. Among them, homologous-recombination-mediated targeting technologies have facilitated the manipulation of specific loci by generating knock-out and knock-in models. Despite promoting significant advances in our understanding of the molecular mechanisms involved in hematology, these inefficient, time-consuming, and labor-intensive approaches did not permit the development of cellular or animal models, recapitulating the complexity of hematological disorders. On October 26, 2016, Drs. Ben Ebert and Chad Cowan shared their knowledge of and experience with the utilization of CRISPR for models of myeloid malignancy, disease, and novel therapeutics in an International Society for Experimental Hematology webinar titled "Utility of CRISPR/Cas9 Systems in Hematology Research." Here, we provide an overview of the topics they covered, including their insights into the novel applications of the technique and its strengths and limitations. Copyright © 2017 ISEH – Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

BEST-TEST2: assessment of hematology trainee knowledge of transfusion medicine.

PubMed

Lin, Yulia; Tinmouth, Alan; Mallick, Ranjeeta; Haspel, Richard L

2016-02-01

As transfusion is a common therapy and key component in every hematologist's practice, hematology training programs should dedicate significant time and effort to delivering high-quality transfusion medicine education to their trainees. The current state of hematology trainee knowledge of transfusion medicine is not known. A validated assessment tool developed by the Biomedical Excellence for Safer Transfusion (BEST) Collaborative was used to assess prior transfusion medicine education, attitudes, perceived ability, and transfusion medicine knowledge of hematology trainees. A total of 149 hematology trainees at 17 international sites were assessed. The overall mean exam score was 61.6% (standard deviation, 13.4%; range, 30%-100%) with no correlation in exam scores with postgraduate year or previous transfusion medicine education in medical school or internal medicine residency. However, better scores correlated with 3 or more hours of transfusion medicine education (p = 0.0003) and perceived higher-quality education during hematology training (p = 0.03). Hematology trainees at US sites, where hematology is often combined with oncology training, had statistically lower scores than trainees at non-US sites (56.2% vs. 67.4%; p < 0.0001). In terms of topic areas, although 93% of participants had obtained consent for transfusion, the lowest scores were on transfusion reaction-related questions. Given the overall poor performance, this study serves as an impetus for all hematology training programs to reevaluate the quality and quantity of transfusion medicine training and can assist in the development of targeted curricula. © 2015 AABB.

Palliative Short-Course Radiation Therapy in Rectal Cancer: A Phase 2 Study

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

Picardi, Vincenzo; Deodato, Francesco; Guido, Alessandra

2016-07-15

Purpose: The management of patients with symptomatic rectal cancer not amenable to curative treatment may be challenging. The aim of this phase 2 study was to evaluate the efficacy of short-course radiation therapy in patients with obstructing rectal cancer. Methods and Materials: Patients who were not candidates for surgical resection because of synchronous metastases, age, and/or comorbidities were considered eligible. The sample size was calculated based on the 2-stage design of Simon. Short-course radiation therapy was delivered with an isocentric 4-field box technique (total, 25 Gy; 5 fractions in 5 days). Chemotherapy was suspended during radiation treatment. Clinical outcome measures were symptomaticmore » response rate, toxicity, colostomy-free survival, and overall survival. Results: From October 2003 to November 2012, 18 patients (median age, 77.5 years) were enrolled. The median follow-up was 11.5 months (range, 3-36 months). Four weeks after treatment, a complete response (ie, complete symptom resolution) was observed in 38.9% of patients and a partial response in 50.0% cases, whereas 11.1% had no response. The rates of reduction or resolution of pain and bleeding were 87.5% and 100%, respectively. The 1-, 2-, and 3-year colostomy-free survival rates were 100%, 71.4%, and 47.6%, respectively (median, 30 months). The 1-, 2-, and 3-year cumulative overall survival rates were 85.2%, 53%, and 39.8%, respectively (median, 25 months). No patients stopped treatment because of gastrointestinal or genitourinary toxicities: 38.9% of patients had grade 1 to 2 toxicity, and 16.7% had grade 3 toxicity. Only 1 patient had hematologic grade 2 toxicity, and 2 patients had grade 2 skin toxicity. Conclusions: Short-course radiation therapy may represent a safe and effective alternative treatment option in patients with obstructing rectal cancer not eligible for curative treatment, allowing colostomy to be avoided in a substantial proportion of patients.« less

Paclitaxel, Ifosfamide, and Cisplatin Efficacy for First-Line Treatment of Patients With Intermediate- or Poor-Risk Germ Cell Tumors

PubMed Central

Hu, James; Dorff, Tanya B.; Lim, Kristina; Patil, Sujata; Woo, Kaitlin M.; Carousso, Maryann; Hughes, Amanda; Sheinfeld, Joel; Bains, Manjit; Daneshmand, Siamak; Ketchens, Charlene; Bajorin, Dean F.; Bosl, George J.; Quinn, David I.; Motzer, Robert J.

2016-01-01

Purpose Paclitaxel, ifosfamide, and cisplatin (TIP) achieved complete responses (CRs) in two thirds of patients with advanced germ cell tumors (GCTs) who relapsed after first-line chemotherapy with cisplatin and etoposide with or without bleomycin. We tested the efficacy of first-line TIP in patients with intermediate- or poor-risk disease. Patients and Methods In this prospective, multicenter, single-arm phase II trial, previously untreated patients with International Germ Cell Cancer Collaborative Group poor-risk or modified intermediate-risk GCTs received four cycles of TIP (paclitaxel 240 mg/m2 over 2 days, ifosfamide 6 g/m2 over 5 days with mesna support, and cisplatin 100 mg/m2 over 5 days) once every 3 weeks with granulocyte colony-stimulating factor support. The primary end point was the CR rate. Results Of the first 41 evaluable patients, 28 (68%) achieved a CR, meeting the primary efficacy end point. After additional accrual on an extension phase, total enrollment was 60 patients, including 40 (67%) with poor risk and 20 (33%) with intermediate risk. Thirty-eight (68%) of 56 evaluable patients achieved a CR and seven (13%) achieved partial responses with negative markers (PR-negative) for a favorable response rate of 80%. Five of seven achieving PR-negative status had seminoma and therefore did not undergo postchemotherapy resection of residual masses. Estimated 3-year progression-free survival and overall survival rates were 72% (poor risk, 63%; intermediate risk, 90%) and 91% (poor risk, 87%; intermediate risk, 100%), respectively. Grade 3 to 4 toxicities consisted primarily of reversible hematologic or electrolyte abnormalities, including neutropenic fever in 18%. Conclusion TIP demonstrated efficacy as first-line therapy for intermediate- and poor-risk GCTs with an acceptable safety profile. Given higher rates of favorable response, progression-free survival, and overall survival compared with prior first-line studies, TIP warrants further study in this population. PMID:27185842

Relationship of Ferritin to Symptom Ratings Children with Attention Deficit Hyperactivity Disorder: Effect of Comorbidity

ERIC Educational Resources Information Center

Oner, Pinar; Oner, Ozgur

2008-01-01

Our aim was to investigate the relation between behavioral symptoms and hematological variables which are related with iron deficiency and anemia, ferritin, hemoglobin, mean corpuscular volume (MCV), and reticulosite distribution width (RDW) in children and adolescents with pure Attention Deficit Hyperactivity Disorder (ADHD) or ADHD comorbid with…

Prolonged myelosuppression with clofarabine in the treatment of patients with relapsed or refractory, aggressive non-Hodgkin lymphoma

PubMed Central

BLUM, KRISTIE A.; HAMADANI, MEHDI; PHILLIPS, GARY S.; LOZANSKI, GERARD; JOHNSON, AMY J.; LUCAS, DAVID M.; SMITH, LISA L.; BAIOCCHI, ROBERT; LIN, THOMAS S.; PORCU, PIERLUIGI; DEVINE, STEVEN M.; BYRD, JOHN C.

2013-01-01

We evaluated the safety and efficacy of the purine nucleoside analogue, clofarabine, in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL). Six patients with DLBCL (n = 5) or MCL (n = 1) and a median age of 68 years were treated with 40 mg/m2 clofarabine IV over 2 h for 5 days, repeated every 28 days, for 1–2 cycles. The overall response rate was 50% (complete response = 1, complete response unconfirmed = 1, partial response = 1). Median progression-free survival was 3.5 months (range 1.5–10 months) and the median overall survival was 7.8 months (range 3–31 months). Grade 3–4 neutropenia and thrombocytopenia was universal, with a median of 34 (range 19–55) and 77 (range 0–275) days required for neutrophil and platelet recovery. Grade 3 non-hematologic toxicities included transaminitis, febrile neutropenia, non-neutropenic infections and orthostatic hypotension. Further accrual to the study was terminated due to prolonged Grade 3–4 myelosuppression and orthostatic hypotension in five of six patients. Clofarabine exhibits evidence of single agent activity in relapsed or refractory DLBCL. However, further study with novel administration schedules that maintain this efficacy and limit toxicity is warranted. PMID:19263294

Esophageal replacement by hydroxylated bacterial cellulose patch in a rabbit model.

PubMed

Zhu, Changlai; Liu, Fang; Qian, Wenbo; Wang, Yingjie; You, Qingsheng; Zhang, Tianyi; Li, Feng

2015-01-01

To repair esophageal defects by hydroxylated and kombucha-synthesized bacterial cellulose (HKBC) patch in a rabbit model. Semicircular esophageal defects 1 cm in length of the cervical esophagus were initially created in 18 Japanese big-ear rabbits and then repaired with HKBC patch grafts. The clinical outcomes including survival rate, weight change, food intake, and hematological and radiologic evaluation were observed. After X-ray evaluation, the rabbits were sacrificed sequentially at 1, 3, and 6 months for histopathologic analysis with light microscopy and scanning electron microscopy. Survival rate during the first month was 88.9% (n = 16). Two rabbits died from anastomotic leakage during the entire follow-up. Postoperatively, feeding function and body weight were gradually restored in the surviving animals. No hematological abnormalities were found, and no obvious anastomotic leakage, stenosis, or obstruction was observed under X-ray examination. The histopathologic results showed a progressive regeneration of the esophagus in the graft area, where the neo-esophagus tissue had characteristics similar to native esophageal tissue after 3 months of surgery. HKBC is beneficial for esophageal tissue regeneration and may be a promising material for esophageal reconstruction.

Mortality and hematology associated with the ingestion of one number four lead shot in black ducks, Anas rubripes

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

Pain, D.J.; Rattner, B.A.

The black duck (anas rubripes) is a dabbling duck endemic to North America. Since population surveys of this species began in the early 1950's, numbers have declined steadily at the rate of approximately 1.5% a year. In 1980 the North American population was estimated to be only 42% of that recorded in 1952. Several reasons have been suggested for this decline. One environmental contaminant that may be contributing to the decline is spent lead gunshot. The ingestion of gunshot by waterfowl is well documented and is thought to kill an estimated 1.6-3.8 million waterfowl each year in North America. Theremore » has been little research concerning the toxicity of lead gunshot to the black duck and the present significance of lead poisoning as a mortality factor in this species. This study reports the results of an experiment in which captive black ducks were dosed with one number four lead shot. Mortality rates and hematological effects are discussed in relation to lead toxicity.« less

ATF4 induction through an atypical integrated stress response to ONC201 triggers p53-independent apoptosis in hematological malignancies.

PubMed

Ishizawa, Jo; Kojima, Kensuke; Chachad, Dhruv; Ruvolo, Peter; Ruvolo, Vivian; Jacamo, Rodrigo O; Borthakur, Gautam; Mu, Hong; Zeng, Zhihong; Tabe, Yoko; Allen, Joshua E; Wang, Zhiqiang; Ma, Wencai; Lee, Hans C; Orlowski, Robert; Sarbassov, Dos D; Lorenzi, Philip L; Huang, Xuelin; Neelapu, Sattva S; McDonnell, Timothy; Miranda, Roberto N; Wang, Michael; Kantarjian, Hagop; Konopleva, Marina; Davis, R Eric; Andreeff, Michael

2016-02-16

The clinical challenge posed by p53 abnormalities in hematological malignancies requires therapeutic strategies other than standard genotoxic chemotherapies. ONC201 is a first-in-class small molecule that activates p53-independent apoptosis, has a benign safety profile, and is in early clinical trials. We found that ONC201 caused p53-independent apoptosis and cell cycle arrest in cell lines and in mantle cell lymphoma (MCL) and acute myeloid leukemia (AML) samples from patients; these included samples from patients with genetic abnormalities associated with poor prognosis or cells that had developed resistance to the nongenotoxic agents ibrutinib and bortezomib. Moreover, ONC201 caused apoptosis in stem and progenitor AML cells and abrogated the engraftment of leukemic stem cells in mice while sparing normal bone marrow cells. ONC201 caused changes in gene expression similar to those caused by the unfolded protein response (UPR) and integrated stress responses (ISRs), which increase the translation of the transcription factor ATF4 through an increase in the phosphorylation of the translation initiation factor eIF2α. However, unlike the UPR and ISR, the increase in ATF4 abundance in ONC201-treated hematopoietic cells promoted apoptosis and did not depend on increased phosphorylation of eIF2α. ONC201 also inhibited mammalian target of rapamycin complex 1 (mTORC1) signaling, likely through ATF4-mediated induction of the mTORC1 inhibitor DDIT4. Overexpression of BCL-2 protected against ONC201-induced apoptosis, and the combination of ONC201 and the BCL-2 antagonist ABT-199 synergistically increased apoptosis. Thus, our results suggest that by inducing an atypical ISR and p53-independent apoptosis, ONC201 has clinical potential in hematological malignancies. Copyright © 2016, American Association for the Advancement of Science.

Metastatic Bone Pain Palliation using (177)Lu-Ethylenediaminetetramethylene Phosphonic Acid.

PubMed

Alavi, Mehrosadat; Omidvari, Shapour; Mehdizadeh, Alireza; Jalilian, Amir R; Bahrami-Samani, Ali

2015-01-01

(177)Lu-ethylenediaminetetramethylene phosphonic acid (EDTMP) is presently suggested as an excellent bone seeking radionuclide for developing metastatic bone pain (MBP) palliation agent owing to its suitable nuclear decay characteristics. To find the exact dosage and its efficiency, this clinical study was performed on the human being, using (177)Lu-EDTMP for MBP palliation. (177)Lu-EDTMP was prepared by Iran, atomic energy organization. Thirty consecutive patients with determined tumors, incontrollable MBP, and positive bone scan at 4 weeks before the beginning of the study participated in this study in the nuclear medicine ward. (177)Lu-EDTMP in the form of sterile slow IV injection was administered with a dose of 29.6 MBq/kg. Short form of brief pain inventory questionnaire was used to evaluate the efficiency of the intervention. Questionnaires were filled out by an expert nuclear physician every 2 weeks while the cell blood count was also checked every 2 weeks up to 12 weeks for evaluation of bone marrow suppression and hematological toxicity. Furthermore, whole body scan was done at days 1, 3, and 7. Twenty-five patients showed a significant pain relief since 2 weeks after the injection, and continued until the end of the follow up period (12 weeks). There were no significant early complications such as bone marrow suppression, hematological toxicity, and no systemic adverse effects. No complication was observed in renal function. Twenty one patients showed flare phenomenon that was started after the 12.2 ± 1.78 h lasting for 38.4 ± 23.08. Sixteen patients (53%) were completely treated; nine patients (30%) showed a partial response, and five patients (17%) had no response to treatment. Total response to treatment was achieved in 25 patients (83%). At the end of the evaluation, no bone marrow suppression or hematologic toxicity was observed. (177)Lu-EDTMP has shown suitable physical and biological properties with good results in long term bone pain relief for patients with bone metastasis.

Metastatic Bone Pain Palliation using 177Lu-Ethylenediaminetetramethylene Phosphonic Acid

PubMed Central

Alavi, Mehrosadat; Omidvari, Shapour; Mehdizadeh, Alireza; Jalilian, Amir R.; Bahrami-Samani, Ali

2015-01-01

177Lu-ethylenediaminetetramethylene phosphonic acid (EDTMP) is presently suggested as an excellent bone seeking radionuclide for developing metastatic bone pain (MBP) palliation agent owing to its suitable nuclear decay characteristics. To find the exact dosage and its efficiency, this clinical study was performed on the human being, using 177Lu-EDTMP for MBP palliation. 177Lu-EDTMP was prepared by Iran, atomic energy organization. Thirty consecutive patients with determined tumors, incontrollable MBP, and positive bone scan at 4 weeks before the beginning of the study participated in this study in the nuclear medicine ward. 177Lu-EDTMP in the form of sterile slow IV injection was administered with a dose of 29.6 MBq/kg. Short form of brief pain inventory questionnaire was used to evaluate the efficiency of the intervention. Questionnaires were filled out by an expert nuclear physician every 2 weeks while the cell blood count was also checked every 2 weeks up to 12 weeks for evaluation of bone marrow suppression and hematological toxicity. Furthermore, whole body scan was done at days 1, 3, and 7. Twenty-five patients showed a significant pain relief since 2 weeks after the injection, and continued until the end of the follow up period (12 weeks). There were no significant early complications such as bone marrow suppression, hematological toxicity, and no systemic adverse effects. No complication was observed in renal function. Twenty one patients showed flare phenomenon that was started after the 12.2 ± 1.78 h lasting for 38.4 ± 23.08. Sixteen patients (53%) were completely treated; nine patients (30%) showed a partial response, and five patients (17%) had no response to treatment. Total response to treatment was achieved in 25 patients (83%). At the end of the evaluation, no bone marrow suppression or hematologic toxicity was observed. 177Lu-EDTMP has shown suitable physical and biological properties with good results in long term bone pain relief for patients with bone metastasis. PMID:26097421

Effects of feed-borne Fusarium mycotoxins on hematology and immunology of turkeys.

PubMed

Chowdhury, S R; Smith, T K; Boermans, H J; Woodward, B

2005-11-01

Feeding grains naturally-contaminated with Fusarium mycotoxins has been shown to alter the metabolism and performance of turkeys. The objectives of the current experiment were to examine the effects of feeding turkeys with grains naturally contaminated with Fusarium mycotoxins on their hematology and immunological indices (including functions), and the possible protective effect of feeding a polymeric glucomannan mycotoxin adsorbent (GMA). Two hundred twenty-five 1-d-old male turkey poults were fed corn, wheat, and soybean meal-based starter (0 to 3 wk), grower (4 to 6 wk), developer (7 to 9 wk), and finisher (10 to 12 wk) diets formulated with uncontaminated grains, contaminated grains, or contaminated grains with 0.2% GMA. The chronic consumption of Fusarium mycotoxins caused minor and transient changes in hematocrit (0.33 L/L) and hemoglobin (10(6) g/L) concentrations as well as in blood basophil (0.13 x 10(9)/L) and monocyte counts (3.42 x 10(9)/L) compared with controls. Supplementation of the contaminated diet with GMA prevented these effects on blood cell counts. Biliary IgA concentrations were significantly increased (4.45-fold) when birds were fed contaminated grains compared with controls, but serum IgA concentrations were not affected. Contact hypersensitivity to dinitrochlorobenzene, which is a CD8+ T-cell-mediated delayed-type hypersensitivity response, was decreased (48%) by feed-borne mycotoxins compared with the control. By contrast, the primary and secondary antibody response to sheep red blood cells, a CD4+ T-cell-mediated response, was not affected. It was concluded that chronic consumption of grains naturally contaminated with Fusarium mycotoxins exerts only minor adverse effects on the hematology and some immunological indices of turkeys. Consumption of grains naturally contaminated with Fusarium mycotoxins may, however, increase the susceptibility of turkeys to infectious agents against which CD8+ T cells play a major role in defense.

Mixed-phenotype large granular lymphocytic leukemia (LGLL): a rare subtype in the LGLL Spectrum.

PubMed

Neff, Jadee L; Rangan, Aruna; Jevremovic, Dragan; Nguyen, Phuong L; Chiu, April; Go, Ronald S; Chen, Dong; Morice, William G; Shi, Min

2018-06-24

Large granular lymphocytic leukemia (LGLL) is a chronic proliferation of cytotoxic lymphocytes in which over 70% of patients develop cytopenia(s) requiring therapy. LGLL includes T-cell LGLL (T-LGLL) and chronic lymphoproliferative disorder of NK-cells (CLPD-NK). The neoplastic cells in LGLL usually exhibit a single immunophenotype in a patient, with CD8-positive/αβ T-cell type being the most common, followed by NK-cell, γδ T-cell, and CD4-positive/αβ T-cell types. We investigated a total of 220 LGLL cases and identified 12 mixed-phenotype LGLLs (5%): 7 cases with coexistent αβ T-cell and NK-cell clones and 5 with coexistent αβ and γδ T-cell clones. With a median follow-up of 48months, the clinicopathologic characteristics of these patients appeared similar to those of typical LGLL patients. Treatment was instituted in 9 patients and 5 patients (55%) attained complete hematologic response (CR) or partial response (PR). The therapeutic response rate of this cohort is comparable to the reported overall response rate of 40-60% in typical LGLL patients. Three patients who did not receive any treatment had progressive or persistent cytopenias. Interestingly, inverted proportions of two clones at disease recurrence were identified in 4 patients (36%) and stable clonal proportions in 7 patients (64%). Mixed-phenotype LGLL is rare, and this study underscores the importance of recognizing this rare type of LGLL in patients who may benefit from LGLL treatment. Copyright © 2018. Published by Elsevier Inc.

Sex-specific differences in cardiac control and hematology of sockeye salmon (Oncorhynchus nerka) approaching their spawning grounds.

PubMed

Sandblom, Erik; Clark, Timothy D; Hinch, Scott G; Farrell, Anthony P

2009-10-01

Some male salmonids (e.g., rainbow trout) display profound cardiovascular adjustments during sexual maturation, including cardiac growth and hypertension, and tachycardia has been observed in free-ranging male salmonids near their spawning grounds. In the present study, we investigated cardiac control, dorsal aortic blood pressure, cardiac morphometrics, and hematological variables in wild, sexually maturing sockeye salmon (Oncorhynchus nerka) with a particular aim to decipher any sex-specific differences. Routine heart rate (f(H)) was significantly higher in females (52 vs. 43 beats/min), which was due to significantly lower cholinergic tone (28 vs. 46%), because there were no differences in adrenergic tone or intrinsic heart rate between sexes. No differences in blood pressure were observed despite males possessing an 11% greater relative ventricular mass. Concomitant with higher routine heart rates, female sockeye had significantly higher levels of cortisol, testosterone, and 17beta-estradiol, whereas the level of 11-ketotestosterone was higher in males. There were no differences in hematocrit or hemoglobin concentration between the sexes. The findings of this study highlight the importance of considering sex as a variable in research fields such as conservation biology and when modeling the consequences of local and global climate change. Indeed, this study helps to provide a mechanistic basis for the significantly higher rates of female mortality observed in previous studies of wild-caught sockeye salmon.

Specialized physiological studies in support of manned space flight

NASA Technical Reports Server (NTRS)

Luft, U. C.; Loeppky, J. A.; Venters, M. D.; Kobayashi, Y.

1978-01-01

The effects of a diuretic (Lasix) induced dehydration on the cardiovascular and hematological responses to lower body negative pressure (LBNP) were analyzed and compared to previous observations on dehydration following exercise in the heat. During LBNP runs the subjects were monitored for changes in blood volume, heart rate, blood pressure, and variations in the volume of the left calf. It was concluded that Lasix dehydration produced a depletion of the body electrolytes at the expense of both the plasma and extravascular compartments. Striking differences were found between those subjects who were physically active (Runners: R) and those who did not engage in any regular physical activity (Non-runners: NR). Tolerance to LBNP (Torr x min) was significantly lower in the R's than the NR's before and after dehydration, however the R's lost more of their tolerance after dehydration with Lasix than after exercise in the heat for about the same fluid loss. The opposite was true for the NR's. Two factors appear to be responsible for the lower LBNP tolerance in R's: parasympathetic inhibition of cardiac activity during LBNP and a greater propensity to pool blood in the lower extremities.

Doxorubicin and ifosfamide combination chemotherapy in previously treated acute leukemia in adults: a Southwest Oncology Group pilot study.

PubMed

Ryan, D H; Bickers, J N; Vial, R H; Hussein, K; Bottomley, R; Hewlett, J S; Wilson, H E; Stuckey, W J

1980-01-01

The Southwest Oncology Group did a limited institutional pilot study of the combination of doxorubicin and ifosfamide in the treatment of previously treated adult patients with acute leukemia. Thirty-four patients received one or two courses of the combination. All patients had received prior chemotherapy and 32 had received prior anthracycline chemotherapy. Three patients died before their responses could be fully evaluated. Fourteen patients achieved complete remission (41%) and one patient achieved partial remission. The complete remission rate was 27% for patients with acute myeloblastic leukemia (myelomonoblastic leukemia, monoblastic leukemia, and erythroleukemia) and 89% for patients with acute lymphocytic and undifferentiated leukemia (ALL). Toxic effects included severe hematologic reactions in 33 of 34 patients, hematuria in six patients, altered sensorium in one patient, and congestive heart failure in one patient. The safety of the combination was established and toxic side effects of this therapy were tolerable. The 89% complete remission rate for previously treated patients with ALL suggests that the combination of doxorubicin and ifosfamide may be particularly effective in ALL.

NF-κB in Hematological Malignancies

PubMed Central

Imbert, Véronique; Peyron, Jean-François

2017-01-01

NF-κB (Nuclear Factor Κ-light-chain-enhancer of activated B cells) transcription factors are critical regulators of immunity, stress response, apoptosis, and differentiation. Molecular defects promoting the constitutive activation of canonical and non-canonical NF-κB signaling pathways contribute to many diseases, including cancer, diabetes, chronic inflammation, and autoimmunity. In the present review, we focus our attention on the mechanisms of NF-κB deregulation in hematological malignancies. Key positive regulators of NF-κB signaling can act as oncogenes that are often prone to chromosomal translocation, amplifications, or activating mutations. Negative regulators of NF-κB have tumor suppressor functions, and are frequently inactivated either by genomic deletions or point mutations. NF-κB activation in tumoral cells is also driven by the microenvironment or chronic signaling that does not rely on genetic alterations. PMID:28561798

One-Unit versus Two-Unit Cord-Blood Transplantation for Hematologic Cancers

PubMed Central

Wagner, John E.; Eapen, Mary; Carter, Shelly; Wang, Yanli; Schultz, Kirk R.; Wall, Donna A.; Bunin, Nancy; Delaney, Colleen; Haut, Paul; Margolis, David; Peres, Edward; Verneris, Michael R.; Walters, Mark; Horowitz, Mary M.; Kurtzberg, Joanne

2014-01-01

BACKGROUND Umbilical-cord blood has been used as the source of hematopoietic stem cells in an estimated 30,000 transplants. The limited number of hematopoietic cells in a single cord-blood unit prevents its use in recipients with larger body mass and results in delayed hematopoietic recovery and higher mortality. Therefore, we hypothesized that the greater numbers of hematopoietic cells in two units of cord blood would be associated with improved outcomes after transplantation. METHODS Between December 1, 2006, and February 24, 2012, a total of 224 patients 1 to 21 years of age with hematologic cancer were randomly assigned to undergo double-unit (111 patients) or single-unit (113 patients) cord-blood transplantation after a uniform myeloablative conditioning regimen and immunoprophylaxis for graft-versus-host disease (GVHD). The primary end point was 1-year overall survival. RESULTS Treatment groups were matched for age, sex, self-reported race (white vs. nonwhite), performance status, degree of donor–recipient HLA matching, and disease type and status at transplantation. The 1-year overall survival rate was 65% (95% confidence interval [CI], 56 to 74) and 73% (95% CI, 63 to 80) among recipients of double and single cord-blood units, respectively (P = 0.17). Similar outcomes in the two groups were also observed with respect to the rates of disease-free survival, neutrophil recovery, transplantation-related death, relapse, infections, immunologic reconstitution, and grade II–IV acute GVHD. However, improved platelet recovery and lower incidences of grade III and IV acute and extensive chronic GVHD were observed among recipients of a single cord-blood unit. CONCLUSIONS We found that among children and adolescents with hematologic cancer, survival rates were similar after single-unit and double-unit cord-blood transplantation; however, a single-unit cord-blood transplant was associated with better platelet recovery and a lower risk of GVHD. PMID:25354103

One-unit versus two-unit cord-blood transplantation for hematologic cancers.

PubMed

Wagner, John E; Eapen, Mary; Carter, Shelly; Wang, Yanli; Schultz, Kirk R; Wall, Donna A; Bunin, Nancy; Delaney, Colleen; Haut, Paul; Margolis, David; Peres, Edward; Verneris, Michael R; Walters, Mark; Horowitz, Mary M; Kurtzberg, Joanne

2014-10-30

Umbilical-cord blood has been used as the source of hematopoietic stem cells in an estimated 30,000 transplants. The limited number of hematopoietic cells in a single cord-blood unit prevents its use in recipients with larger body mass and results in delayed hematopoietic recovery and higher mortality. Therefore, we hypothesized that the greater numbers of hematopoietic cells in two units of cord blood would be associated with improved outcomes after transplantation. Between December 1, 2006, and February 24, 2012, a total of 224 patients 1 to 21 years of age with hematologic cancer were randomly assigned to undergo double-unit (111 patients) or single-unit (113 patients) cord-blood transplantation after a uniform myeloablative conditioning regimen and immunoprophylaxis for graft-versus-host disease (GVHD). The primary end point was 1-year overall survival. Treatment groups were matched for age, sex, self-reported race (white vs. nonwhite), performance status, degree of donor-recipient HLA matching, and disease type and status at transplantation. The 1-year overall survival rate was 65% (95% confidence interval [CI], 56 to 74) and 73% (95% CI, 63 to 80) among recipients of double and single cord-blood units, respectively (P=0.17). Similar outcomes in the two groups were also observed with respect to the rates of disease-free survival, neutrophil recovery, transplantation-related death, relapse, infections, immunologic reconstitution, and grade II-IV acute GVHD. However, improved platelet recovery and lower incidences of grade III and IV acute and extensive chronic GVHD were observed among recipients of a single cord-blood unit. We found that among children and adolescents with hematologic cancer, survival rates were similar after single-unit and double-unit cord-blood transplantation; however, a single-unit cord-blood transplant was associated with better platelet recovery and a lower risk of GVHD. (Funded by the National Heart, Lung, and Blood Institute and the National Cancer Institute; ClinicalTrials.gov number, NCT00412360.).

Sequential chemoimmunotherapy of fludarabine, mitoxantrone, and cyclophosphamide induction followed by alemtuzumab consolidation is effective in T-cell prolymphocytic leukemia.

PubMed

Hopfinger, Georg; Busch, Raymonde; Pflug, Natali; Weit, Nicole; Westermann, Anne; Fink, Anna-Maria; Cramer, Paula; Reinart, Nina; Winkler, Dirk; Fingerle-Rowson, Günter; Stilgenbauer, Stephan; Döhner, Hartmut; Kandler, Gabriele; Eichhorst, Barbara; Hallek, Michael; Herling, Marco

2013-06-15

Scarce systematic trial data have prevented uniform therapeutic guidelines for T-cell prolymphocytic leukemia (T-PLL). A central need in this historically refractory tumor is the controlled evaluation of multiagent chemotherapy and its combination with the currently most active single agent, alemtuzumab. This prospective multicenter phase 2 trial assessed response, survival, and toxicity of a novel regimen in previously treated (n = 9) and treatment-naive (n = 16) patients with T-PLL. Induction by fludarabine, mitoxantrone, and cyclophosphamide (FMC), for up to 4 cycles, was followed by alemtuzumab (A) consolidation, up to 12 weeks. Of the 25 patients treated with FMC, 21 subsequently received alemtuzumab. Overall response rate to FMC was 68%, comprising 6 complete remissions (all bone-marrow confirmed) and 11 partial remissions. Alemtuzumab consolidation increased the intent-to-treat overall response rate to 92% (12 complete remissions; 11 partial remissions). Median overall survival after FMC-A was 17.1 months and median progression-free survival was 11.9 months. Progression-free survival tended to be shorter for patients with high-level T-cell leukemia 1 oncoprotein expression. Hematologic toxicities were the most frequent grade 3/4 side effects under FMC-A. Exclusively in the 21 alemtuzumab-consolidated patients, 13 cytomegalovirus reactivations were observed; 9 of these 13 represented a clinically relevant infection. FMC-A is a safe and efficient protocol in T-PLL, which compares favorably to published data. Copyright © 2013 American Cancer Society.

[Phase II study of YNK01 (1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate) on hematological malignancies].

PubMed

Tatsumi, N; Yamada, K; Ohshima, T; Nakamura, T; Ohno, R; Masaoka, T; Kimura, I; Kimura, K

1990-12-01

Phase II study of YNK01 (1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate), a derivative of cytosine arabinoside, on hematological malignancies was conducted by multi-institutional cooperative group. YNK01 was administered orally at dose of 100-300 mg/body/day for more than 2 weeks. The number of registered and evaluated patients were 211 and 156, respectively. Of 23 patients with acute myelogeneous leukemia (AML), 2 complete response (CR), one partial response (PR) were observed (CR + PR: 13.0%). Hypoplastic leukemia (1/4: 25%), acute unclassified leukemia (1/1: 100%). Of 45 patients with MDS, 2CRs, 6 good response (GR) and 5PRs were observed (CR + PR: 28.9%). AML developing after a prior history of MDS (5/17: 29.4%), CML-BC (2/9: 22.2%). Of 19 patients with CML, 9 achieved CR, 3 achieved PR (63.2%). Of 11 patients with polycythemia vera, 4 achieved CR, 5 achieved PR (81.8%). Of 6 patients with essential thrombocytosis, 2 achieved CR, one achieved PR (50%). The major adverse effects included gastrointestinal toxicities such as nausea, vomiting, anorexia, diarrhea, and elevation of GOT and GPT which were tolerable and reversible. This study indicates that YNK01 is a useful agent against acute leukemia and MDS, especially RAEB, RAEB in T, CMMoL.

Sex differences in the toxicity of polyethylene glycol-coated gold nanoparticles in mice

PubMed Central

Chen, Jie; Wang, Hao; Long, Wei; Shen, Xiu; Wu, Di; Song, Sha-Sha; Sun, Yuan-Ming; Liu, Pei-Xun; Fan, Saijun; Fan, Feiyue; Zhang, Xiao-Dong

2013-01-01

Gold nanoparticles have received wide interest in disease diagnosis and therapy, but one of the important issues is their toxicological effects in vivo. Sex differences in the toxicity of gold nanoparticles are not clear. In this work, body weight, organ weight, hematology, and biochemistry were used to evaluate sex differences in immune response and liver and kidney damage. Pathology was used to observe the general toxicity of reproductive organs. The immune response was influenced significantly in female mice, with obvious changes in spleen and thymus index. Hematology results showed that male mice treated with 22.5 nm gold nanoparticles received more significant infection and inflammation than female mice. Meanwhile, the biochemistry results showed that 4.4 and 22.5 nm gold nanoparticles caused more significant liver damage in male mice than female mice, while 22.5, 29.3, and 36.1 nm gold nanoparticles caused more significant kidney damage in female mice than male mice. No significant toxicological response was found in the reproductive system for female or male mice. It was found that gold nanoparticles caused more serious liver toxicity and infection in male mice than female mice. These findings indicated that sex differences may be one of the important elements for in vivo toxicity of gold nanoparticles. PMID:23861586

Different hematologic responses to hypoxia in Sherpas and Quechua Indians.

PubMed

Winslow, R M; Chapman, K W; Gibson, C C; Samaja, M; Monge, C C; Goldwasser, E; Sherpa, M; Blume, F D; Santolaya, R

1989-04-01

Previous studies of the erythropoietic response to hypoxia in high-altitude natives suggest that the hematocrit and hemoglobin values in Himalayan natives (Sherpas) are lower than expected for the altitude, perhaps because of a genetic adaptation. However, differences in sampling techniques and experimental methods make comparisons difficult. Our studies were carried out to compare the erythropoietic response with the same altitude in age-matched natives of the Himalayas and Andes by the same experimental techniques. Healthy male subjects were selected in Ollagüe, Chile (n = 29, 27.3 +/- 5.9 yr) and in Khunde, Nepal (n = 30, 24.7 +/- 3.8 yr). Both of these villages are located at 3,700 m above sea level. Hematologic measurements confirmed lower hematocrit values in Nepal (48.4 +/- 4.5%) than in Chile (52.2 +/- 4.6%) (P less than 0.003). When subjects were matched for hematocrit, erythropoietin concentrations in Chile were higher than in Nepal (P less than 0.01). Detailed measurements of blood O2 affinity in Nepal showed no differences in shape or position of the O2 equilibrium curve between Sherpas and Western sojourners. Our results indicate that although Quechua Indians have higher hematocrits than Sherpas living at the same altitude, nevertheless they may be functionally anemic.

VB-CHEP chemotherapy regimen for aggressive non-Hodgkin's lymphomas.

PubMed

Yalçin, S; Kars, A; Ozişik, Y; Tekuzman, G; Ozyilkan, O; Celik, I; Barişta, I; Güllü, I; Güler, N; Baltali, E; Firat, D

1998-10-01

Despite intensive search for the optimal combination chemotherapy for aggressive non-Hodgkin's lymphoma (NHL), the CHOP (cyclophosphamide, adriamycin, vincristine and prednisolone) regimen is still the standard therapy. We investigated the clinical efficacy of a new combination regimen consisting of vincristine, bleomycin-cyclophosphamide, adriamycin, etoposide and prednisolone (VB-CHEP) in patients with aggressive NHL. A total of 29 patients with aggressive NHL was enrolled into the protocol. Eight patients were consolidated with cisplatin and cytarabine and 5 patients received radiotherapy for bulky disease. Objective response was achieved in 82.8% of the patients. Complete remission (CR) and partial remission rates were 72.4%, and 10.3%, respectively. CR rate was significantly lower in patients with advanced stage, extranodal disease and bone marrow involvement. Median follow-up time is 34+ months; 17 patients are disease-free while 12 died and only 2 patients with CR have relapsed so far. Median response duration is 29+ months and the median survival is 48+ months. The survival rate is 69% in the first year and 66% in the second year. A total of 152 cycles were evaluated for toxicity. Major hematological toxicity was myelosuppression and neutropenia, detected in 50.65%, was mostly grades 1-2. Neutropenic fever occurred in only 11 cycles. The side effects of the consolidation therapy were also acceptable. We conclude that the VB-CHEP regimen with consolidation therapy for high-risk patients may be an effective treatment for advanced stage aggressive NHL.

Present status and perspective of laboratory hematology in Japan: On the standardization of blood cell morphology including myelodysplasia: On behalf of the Japanese Society for Laboratory Hematology.

PubMed

Tohyama, K

2018-05-01

The Japanese Society for Laboratory Hematology (JSLH) was launched in 2000 and has been developed by a mutual collaboration of hematologists, medical technologists, and the companies involved in hematological laboratory testing. The aim of JSLH is the progress and development of laboratory hematology by academic conferences, periodic publication of academic journal, training and education (in the meeting, the journal, or the website), promotion of the standardization of laboratory hematology, and certification of the laboratory hematology specialists. Among 3 specialized committees organized for the standardization of laboratory hematology, the standardization committee on blood cell morphology has been dealing with the various projects on peripheral/bone marrow blood cells and normal/abnormal morphology. Another independent organization, the Japanese National Research Group on idiopathic bone marrow failure syndromes (BMF), has raised the importance of the dysplasia of myelodysplastic syndromes (MDS) and has been conducting the prospective registration, central review, and follow-up study of MDS. This group recently proposed the grading system for diagnostic accuracy of MDS, and the detailed procedure of morphological diagnosis of MDS is presented in the specialized color atlas with typical photographs of various dysplasia. JSLH has also approved the grading system for diagnostic accuracy of MDS and adopted this standardized diagnostic system to the educational item for certification of the laboratory hematology specialists, aiming at a nationwidely expanding morphological evaluation of myelodysplasia. Further and significant progress in the standardization of blood cell morphology will be expected in Japan through the activity of JSLH. © 2018 John Wiley & Sons Ltd.

Improved Outcomes After Autologous Hematopoietic Cell Transplantation for Light Chain Amyloidosis: A Center for International Blood and Marrow Transplant Research Study

PubMed Central

D'Souza, Anita; Dispenzieri, Angela; Wirk, Baldeep; Zhang, Mei-Jie; Huang, Jiaxing; Gertz, Morie A.; Kyle, Robert A.; Kumar, Shaji; Comenzo, Raymond L.; Peter Gale, Robert; Lazarus, Hillard M.; Savani, Bipin N.; Cornell, Robert F.; Weiss, Brendan M.; Vogl, Dan T.; Freytes, César O.; Scott, Emma C.; Landau, Heather J.; Moreb, Jan S.; Costa, Luciano J.; Ramanathan, Muthalagu; Callander, Natalie S.; Kamble, Rammurti T.; Olsson, Richard F.; Ganguly, Siddhartha; Nishihori, Taiga; Kindwall-Keller, Tamila L.; Wood, William A.; Mark, Tomer M.; Hari, Parameswaran

2015-01-01

Purpose Autologous hematopoietic cell transplantation, or autotransplantation, is effective in light-chain amyloidosis (AL), but it is associated with a high risk of early mortality (EM). In a multicenter randomized comparison against oral chemotherapy, autotransplantation was associated with 24% EM. We analyzed trends in outcomes after autologous hematopoietic cell transplantation for AL in North America. Patients and Methods Between 1995 and 2012, 1,536 patients with AL who underwent autotransplantation at 134 centers were identified in the Center for International Blood and Marrow Transplant Research database. EM and overall survival (OS) were analyzed in three time cohorts: 1995 to 2000 (n = 140), 2001 to 2006 (n = 596), and 2007 to 2012 (n = 800). Hematologic and renal responses and factors associated with EM, relapse and/or progression, progression-free survival and OS were analyzed in more recent subgroups from 2001 to 2006 (n = 197) and from 2007 to 2012 (n = 157). Results Mortality at 30 and 100 days progressively declined over successive time periods from 11% and 20%, respectively, in 1995 to 2000 to 5% and 11%, respectively, in 2001 to 2006, and to 3% and 5%, respectively, in 2007 to 2012. Correspondingly, 5-year OS improved from 55% in 1995 to 2000 to 61% in 2001 to 2006 and to 77% in 2007 to 2012. Hematologic response to transplantation improved in the latest cohort. Renal response rate was 32%. Centers performing more than four AL transplantations per year had superior survival outcomes. In the multivariable analysis, cardiac AL was associated with high EM and inferior progression-free survival and OS. Autotransplantation in 2007 to 2012 and use of higher dosages of melphalan were associated with a lowered relapse risk. A Karnofsky score less than 80 and creatinine levels 2 mg/m2 or greater were associated with worsened OS. Conclusion Post-transplantation survival in AL has improved, with a dramatic reduction in early post-transplantation mortality and excellent 5-year survival. The risk-benefit ratio for autotransplantation has changed, and randomized comparison with nontransplantation approaches is again warranted. PMID:26371138

Progression-Free Survival Among Patients With Well-Differentiated or Dedifferentiated Liposarcoma Treated With CDK4 Inhibitor Palbociclib: A Phase 2 Clinical Trial.

PubMed

Dickson, Mark A; Schwartz, Gary K; Keohan, Mary Louise; D'Angelo, Sandra P; Gounder, Mrinal M; Chi, Ping; Antonescu, Cristina R; Landa, Jonathan; Qin, Li-Xuan; Crago, Aimee M; Singer, Samuel; Koff, Andrew; Tap, William D

2016-07-01

More than 90% of well-differentiated or dedifferentiated liposarcomas (WD/DDLS) have CDK4 amplification. The selective CDK4 and CDK6 inhibitor palbociclib inhibits growth and induces senescence in liposarcoma cell lines and xenografts. Our prior phase 2 study demonstrated that treatment with palbociclib (200 mg daily for 14 days every 21 days) resulted in clinical benefit in WD/DDLS but moderate hematologic toxic effects. It is important to understand whether palbociclib at a new dose and schedule-125 mg daily for 21 days every 28 days-results in clinical benefit and manageable toxic effects. To determine the progression-free survival (PFS) at 12 weeks of patients with WD/DDLS treated with palbociclib (PD0332991). In this phase 2, nonrandomized, open-label clinical trial conducted at the Memorial Sloan Kettering Cancer Center, 60 patients 18 years and older with advanced WD/DDLS and measurable disease by RECIST 1.1 were enrolled from December 2011 to January 2014 and followed to March 2015. Patients received oral palbociclib at 125 mg daily for 21 days in 28-day cycles. Primary end point was PFS. Secondary end points included response rate and toxic effects. Overall, 30 patients were enrolled in the initial cohort and 30 more in an expansion cohort. Median (range) age was 61.5 (35-87) years; 31 patients (52%) were male; median (range) Eastern Cooperative Oncology Group score was 0 (0-1). Progression-free survival at 12 weeks was 57.2% (2-sided 95% CI, 42.4%-68.8%), and the median PFS was 17.9 weeks (2-sided 95% CI, 11.9-24.0 weeks). There was 1 complete response. Toxic effects were primarily hematologic and included neutropenia (grade 3, n = 20 [33%]; grade 4, n = 2 [3%]) but no neutropenic fever. In patients with advanced WD/DDLS, treatment with palbociclib was associated with a favorable PFS and occasional tumor response. This dose and schedule appears active and may have less toxic effects than 200 mg for 14 days. clinicaltrials.gov Identifier: NCT01209598.

EXPOSURE TO CONCENTRATED AMBIENT AIR PARTICLES ALTERS HEMATOLOGIC INDICES IN HUMANS

EPA Science Inventory

Descriptions of changes in hematological indices have contested the premise that the biological effects of suspended particulate matter (PM) are restricted to the lung. Employing approximately 40 hematologic parameters reflecting blood cells, chemistries, mediators, and coagulati...

Comparative veterinary hematology: a bird's eye view.

PubMed

Jensen, E C

1981-12-01

A comparative look at veterinary hematology in the class Mammalia is presented to acquaint the medical technologist with a new dimension in clinical pathology. Aspects of clinical hematology, such as erythrocyte and leukocyte morphologies, dynamics, and diseases, are discussed.

[Malaria and hematological aspects among residents to be impacted by reservoirs for the Santo Antônio and Jirau Hydroelectric Power Stations, Rondônia State, Brazil].

PubMed

Katsuragawa, Tony Hiroshi; Cunha, Roberto Penna de Almeida; de Souza, Daniele Cristina Apoluceno; Gil, Luiz Herman Soares; Cruz, Rafael Bastos; Silva, Alexandre de Almeida E; Tada, Mauro Shugiro; da Silva, Luiz Hildebrando Pereira

2009-07-01

In Rondônia State, Brazil, two new hydroelectric plants, Santo Antônio and Jirau, are scheduled for construction on the Madeira River, upriver from the State capital, Porto Velho. The current study analyzes malaria prevalence before the construction and provides information on the possible impacts of malaria burden related to the influx of thousands of persons attracted by direct and indirect employment opportunities. According to the findings, malaria is present throughout the region, with varying prevalence rates. The existence of potential asymptomatic malaria carriers among the local population may be epidemiologically relevant and should be considered in the malaria control programs organized by public authorities and companies responsible for building the power plants, aimed at early diagnosis and treatment, vector control, water supply, and infrastructure in the urban areas.

Synthesis and in vitro evaluation of methotrexate conjugated O, N-carboxymethyl chitosan via peptidyl spacers

NASA Astrophysics Data System (ADS)

Li, Dan; Lu, Bo; Zhang, Hong; Huang, Zhijun; Xu, Peihu; Zheng, Hua; Yin, Yihua; Xu, Haixing; Liu, Xia; Lou, Yiceng; Zhang, Xueqiong; Xiong, Fuliang

2014-09-01

The use of methotrexate (MTX), an anticancer drug for the treatment of hematologic malignancies, has been limited in the clinical application due to its poor water solubility, high clearance rate, and lack of target specificity. To solve these problems, O, N-carboxymethyl chitosan-dipeptide-MTX conjugates have been synthesized and characterized by fourier transform infrared radiation spectroscopy and proton nuclear magnetic resonance (1H NMR). All polymeric conjugates showed satisfactory water solubility. The results of the study revealed that drug release and toxicity were affected by employing polymeric conjugation strategy and dipeptide spacers [glycylglycine (Gly-Gly), glycyl- l-phenylalanine (Gly-Phe), glycyl- l-tyrosine (Gly-Tyr)]. It has been found that drugs could be effectively loaded and released when polymeric prodrugs were combined with a dipeptide spacer. In conclusion, O, N-CMCS-dipeptide-MTX polymeric prodrugs could potentially be used as responsive drug delivery systems.

Plastics and cardiovascular health: phthalates may disrupt heart rate variability and cardiovascular reactivity.

PubMed

Jaimes, Rafael; Swiercz, Adam; Sherman, Meredith; Muselimyan, Narine; Marvar, Paul J; Posnack, Nikki Gillum

2017-11-01

Plastics have revolutionized medical device technology, transformed hematological care, and facilitated modern cardiology procedures. Despite these advances, studies have shown that phthalate chemicals migrate out of plastic products and that these chemicals are bioactive. Recent epidemiological and research studies have suggested that phthalate exposure adversely affects cardiovascular function. Our objective was to assess the safety and biocompatibility of phthalate chemicals and resolve the impact on cardiovascular and autonomic physiology. Adult mice were implanted with radiofrequency transmitters to monitor heart rate variability, blood pressure, and autonomic regulation in response to di-2-ethylhexyl-phthalate (DEHP) exposure. DEHP-treated animals displayed a decrease in heart rate variability (-17% SD of normal beat-to-beat intervals and -36% high-frequency power) and an exaggerated mean arterial pressure response to ganglionic blockade (31.5% via chlorisondamine). In response to a conditioned stressor, DEHP-treated animals displayed enhanced cardiovascular reactivity (-56% SD major axis Poincarè plot) and prolonged blood pressure recovery. Alterations in cardiac gene expression of endothelin-1, angiotensin-converting enzyme, and nitric oxide synthase may partly explain these cardiovascular alterations. This is the first study to show an association between phthalate chemicals that are used in medical devices with alterations in autonomic regulation, heart rate variability, and cardiovascular reactivity. Because changes in autonomic balance often precede clinical manifestations of hypertension, atherosclerosis, and conduction abnormalities, future studies are warranted to assess the downstream impact of plastic chemical exposure on end-organ function in sensitive patient populations. This study also highlights the importance of adopting safer biomaterials, chemicals, and/or surface coatings for use in medical devices. NEW & NOTEWORTHY Phthalates are widely used in the manufacturing of consumer and medical products. In the present study, di-2-ethylhexyl-phthalate exposure was associated with alterations in heart rate variability and cardiovascular reactivity. This highlights the importance of investigating the impact of phthalates on health and identifying suitable alternatives for medical device manufacturing. Copyright © 2017 the American Physiological Society.

Promising outcomes of definitive chemoradiation and cetuximab for patients with esophageal squamous cell carcinoma.

PubMed

Chen, Yongshun; Wu, Xiaoyuan; Bu, Shanshan; He, Chunyu; Wang, Wen; Liu, Jinsong; Guo, Wei; Tan, Bo; Wang, Yanxia; Wang, Jianhua

2012-11-01

This study investigated cetuximab added to definitive concurrent chemoradiation for esophageal squamous cell carcinoma (ESCC). Previously untreated patients with stage II-IVa ESCC received cetuximab (400 mg/m(2) per week in week 1, then 250 mg/m(2) per week during weeks 2-8), paclitaxel (45 mg/m(2) per week) and cisplatin (20 mg/m(2) per week) in weeks 2-8 with 59.4 Gy radiotherapy. Epidermal growth factor receptor (EGFR) status in tumor specimens was assessed. Thirty-one patients were enrolled and evaluated for toxicity. Of the 29 patients assessable for a response, 20 (69.0%) had a clinical complete response (CR). Over a median follow up of 23.6 months, disease progression was observed in seven patients. The 1- and 2-year progression-free survival (PFS) rates were 85.5% and 75.1%, respectively. The PFS was shorter for patients with lymphatic metastatic disease than for those with locally confined tumor; the 1-year PFS rates were 78.7% and 92.3%, respectively (P = 0.038). Sixteen (55.2%) patients were immunohistochemically positive for EGFR. The patients with EGFR-expressing tumor had a CR rate of 75.0% compared with 61.5% in those with negative EGFR expression (P = 0.024). The PFS for patients with EGFR-expressing tumor was longer compared with the PFS of patients with negative EGFR (P = 0.133). The patients with prominent cetuximab-induced rash (≥grade 2) had a better CR rate and PFS than those with no or grade 1 rash (P < 0.05). The rates of grades 3/4 esophagitis, hematological and dermatological toxicities were 9.7%, 29.0% and 16.1%, respectively. The regimen of definitive chemoradiation plus cetuximab achieved good clinical response and has an acceptable safety profile in Chinese ESCC patients. © 2012 Japanese Cancer Association.

Babesia canis vogeli, Ehrlichia canis, and Anaplasma platys infection in a dog.

PubMed

Al Izzi, Salah; Martin, Donald S; Chan, Roxanne Y Y; Leutenegger, Christian M

2013-12-01

A 12-month-old male neutered mixed breed dog was presented with a history of diarrhea, lethargy, emaciation, polydypsia, and sniffling. Physical examination findings included pale mucous membranes, increased heart and respiratory rates, and normal rectal temperature (38°C). Hematologic abnormalities included anemia and thrombocytopenia. Biochemical abnormalities included hypoalbuminemia, hyperbilirubinemia, and elevated ALP and ALT activities. A SNAP 4Dx test result was positive for Ehrlichia canis. Babesia canis vogeli organisms were found in the peripheral blood films, while morulae of E canis were not seen. Real-time polymerase chain reaction testing confirmed the presence of both B c vogeli and E canis organisms, and also was positive for Anaplasma platys infection. The dog recovered following treatment with doxycycline and imidocarb dipropionate, with normal hematology and biochemical profiles. © 2013 American Society for Veterinary Clinical Pathology.

Hematologic problems in pediatric patients.

PubMed

Cahill, M

1996-02-01

To provide a review of the common hematologic disorders of childhood: iron deficiency anemia, aplastic anemia, sickle cell disease, and hemophilia. Review articles and book chapters pertaining to the care and treatment of children with hematologic disorders. These common hematologic disorders of childhood have the potential to cause not only acute illness but chronic medical problems, particularly in the growing child. Anticipating and preventing the long-term effects of the illness and treatment are the primary goals of care. Nursing assessment, patient education, and long-term follow-up are major factors in the care of children with hematologic disorders. Nurse-managed comprehensive care clinics have provided successful programs directed at acute care and maintenance care for these children and their families.

PD-1 expression and clinical PD-1 blockade in B-cell lymphomas.

PubMed

Xu-Monette, Zijun Y; Zhou, Jianfeng; Young, Ken H

2018-01-04

Programmed cell death protein 1 (PD-1) blockade targeting the PD-1 immune checkpoint has demonstrated unprecedented clinical efficacy in the treatment of advanced cancers including hematologic malignancies. This article reviews the landscape of PD-1/programmed death-ligand 1 (PD-L1) expression and current PD-1 blockade immunotherapy trials in B-cell lymphomas. Most notably, in relapsed/refractory classical Hodgkin lymphoma, which frequently has increased PD-1 + tumor-infiltrating T cells, 9p24.1 genetic alteration, and high PD-L1 expression, anti-PD-1 monotherapy has demonstrated remarkable objective response rates (ORRs) of 65% to 87% and durable disease control in phase 1/2 clinical trials. The median duration of response was 16 months in a phase 2 trial. PD-1 blockade has also shown promise in a phase 1 trial of nivolumab in relapsed/refractory B-cell non-Hodgkin lymphomas, including follicular lymphoma, which often displays abundant PD-1 expression on intratumoral T cells, and diffuse large B-cell lymphoma, which variably expresses PD-1 and PD-L1. In primary mediastinal large B-cell lymphoma, which frequently has 9p24.1 alterations, the ORR was 35% in a phase 2 trial of pembrolizumab. In contrast, the ORR with pembrolizumab was 0% in relapsed chronic lymphocytic leukemia (CLL) and 44% in CLL with Richter transformation in a phase 2 trial. T cells from CLL patients have elevated PD-1 expression; CLL PD-1 + T cells can exhibit a pseudo-exhaustion or a replicative senescence phenotype. PD-1 expression was also found in marginal zone lymphoma but not in mantle cell lymphoma, although currently anti-PD-1 clinical trial data are not available. Mechanisms and predictive biomarkers for PD-1 blockade immunotherapy, treatment-related adverse events, hyperprogression, and combination therapies are discussed in the context of B-cell lymphomas. © 2018 by The American Society of Hematology.

Treatment of ovarian cancer with surgery, short-course chemotherapy and whole abdominal radiation.

PubMed

Buser, K; Bacchi, M; Goldhirsch, A; Greiner, R; Diener, P; Sessa, C; Jungi, W F; Forni, M; Leyvraz, S; Engeler, V

1996-01-01

The primary aim was to induce a high number of pCR in early (FIGO IC, IIB + C) - and advanced (FIGO III-IV) - stage ovarian cancer with a surgery plus 4 cycles of cisplatin and melphalan (PAMP) regimen. The second objective was to prevent relapse with WAR in patients in remission after chemotherapy. 218 eligible patients were treated after staging laparotomy with cisplatin 80 mg/sqm i.v. on day 1 and melphalan 12 mg/sqm i.v. on day 2 q 4 weeks. Response was verified by second-look laparotomy. WAR was carried out with the open field technique on a linear accelerator (daily dose: 1.3 Gy, total dose: 29.9 Gy) in patients with pathological or clinical CR or pathological PR with microscopical residual disease. 146/218 patients (67%, 95% CI: 61%-73%) responded to PAMP: 56 (26%) achieved pCR, 24 (11%), cCR, 56 (26%) pPR and 10 (5%) cPR (c = clinical, p = pathological). Multivariate analyses revealed that in advanced stages (92 cases in remission), the achievement of pCR was the most important factor for longer time to failure (TTF) and survival. Only 51/118 (43%) patients in remission received WAR. Early-stage patients <= 55 years were more likely to have WAR than patients older than 55 years (77% vs. 23%; p = 0.02). Advanced-stage patients with cCR were less likely to be irradiated than patients with pCR or pPR (10% vs. 51%; p = 0.003). Toxicity of PAMP was acceptable with 10% of WHO grade 4 hematologic toxicity. Acute hematological toxicity of WAR caused interruption (33%) or incompleteness (33%) of irradiation in the majority of patients. PAMP is an effective treatment for advanced ovarian cancer with a 67% response rate after 4 cycles. For the majority of patients in remission, WAR as a consolidation treatment was hardly feasible. For these patients new treatment modalities to consolidate remission are needed.

The clinical and molecular diversity of mast cell leukemia with or without associated hematologic neoplasm

PubMed Central

Jawhar, Mohamad; Schwaab, Juliana; Meggendorfer, Manja; Naumann, Nicole; Horny, Hans-Peter; Sotlar, Karl; Haferlach, Torsten; Schmitt, Karla; Fabarius, Alice; Valent, Peter; Hofmann, Wolf-Karsten; Cross, Nicholas C.P.; Metzgeroth, Georgia; Reiter, Andreas

2017-01-01

Mast cell leukemia is a rare variant of advanced systemic mastocytosis characterized by at least 20% of mast cells in a bone marrow smear. We evaluated clinical and molecular characteristics of 28 patients with (n=20, 71%) or without an associated hematologic neoplasm. De novo mast cell leukemia was diagnosed in 16 of 28 (57%) patients and secondary mast cell leukemia evolving from other advanced systemic mastocytosis subtypes in 12 of 28 (43%) patients, of which 7 patients progressed while on cytoreductive treatment. Median bone marrow mast cell infiltration was 65% and median serum tryptase was 520 μg/L. C-findings were identified in 26 of 28 (93%) patients. Mutations in KIT (D816V, n=19; D816H/Y, n=5; F522C, n=1) were detected in 25 of 28 (89%) patients and prognostically relevant additional mutations in SRSF2, ASXL1 or RUNX1 (S/A/Rpos) in 13 of 25 (52%) patients. Overall response rate in 18 treatment-naïve patients was 5 of 12 (42%) on midostaurin and 1 of 6 (17%) on cladribine, and after switch 1 of 4 (25%) on midostaurin and 0 of 3 on cladribine, respectively. S/A/Rpos adversely affected response to treatment and progression to secondary mast cell leukemia (n=6) or acute myeloid leukemia (n=3) while on treatment (P<0.05). The median overall survival from mast cell leukemia diagnosis was 17 months as compared to 44 months in a control group of 124 patients with advanced systemic mastocytosis but without mast cell leukemia (P=0.03). In multivariate analyses, S/A/Rpos remained the only independent poor prognostic variable predicting overall survival (P=0.007). In conclusion, the molecular signature should be determined in all patients with mast cell leukemia because of its significant clinical and prognostic relevance. PMID:28255023

Treosulfan in the Treatment of Advanced Ovarian Cancer - Results of a German Multicenter Non-interventional Study.

PubMed

Chekerov, Radoslav; Kaltenecker, Gabriele; Reichert, Dietmar; Göhler, Thomas; Klare, Peter; Oskay-Özcelik, Gülten; Sauer, Uwe; Wischnik, Arthur; Vehling-Kaiser, Ursula; Becker, Martin; Hutzschenreuter, Ulrich; Ammon, Andreas; Heidrich-Lorsbach, Elke; Sehouli, Jalid

2015-12-01

Data on routine systemic treatment of patients with ovarian cancer are currently available only to a limited degree. The alkylating agent treosulfan is approved in oral (p.o.) and intravenous (i.v.) form for the treatment of ovarian carcinoma. The present non-interventional study analyzed the clinical use of treosulfan in Germany, evaluating the mode of application, toxicity, and response and survival rate. Two hundred and forty-eight ovarian cancer patients in 57 Centers, who received treosulfan mainly either i.v. (5,000-8,000 mg/m(2) d1, q21d or q28d) or p.o. (400-600 mg/m(2) d1-14 or 21, q28d) for at least one therapy cycle were evaluable and were included in the study. With a median age of 70 years (range=36-92 years), predominantly elderly patients received treosulfan treatment. Most participants presented serous histology (131, 52.8%) and advanced-stage FIGO III (122, 49%) or IV (55, 22%) disease. Median ECOG status was 1 (range=0-2), whereas cardiac co-morbidity was common (31%). Treosulfan was usually administered as second- (26%), third- (21%) or fourth-line (17%) therapy. Two hundred and one patients received i.v. and 47 p.o. The most common reason for dose modifications was due to hematological toxicity (46%). The main reason for a therapy discontinuation was progressive disease (38.5%). Response was observed in 25.8% of participants, disease stabilization in 28.6 % and progress in 45.6%. The median progression-free and overall survival was 196 and 405 days, respectively. In predominantly elderly and heavily pre-treated patients with recurrent ovarian cancer, treosulfan featured a clinical relevant efficacy and well-manageable, mostly hematological, toxicity, which resulted in a positive therapeutic index. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Challenges to laboratory hematology practice: Egypt perspective.

PubMed

Rizk, S H

2018-05-01

Laboratory hematology is an integral part of all clinical laboratories along the extensive healthcare facilities in Egypt. The aim of this review is to portrait the laboratory hematology practice in Egypt including its unique socioeconomic background, blood disease pattern, education and training, regulatory oversight, and the related challenges. Current practice varies widely between different parts of the healthcare system in terms of the range of tests, applied techniques, workforce experience, and quality of service. The national transfusion service (NBTS) in Egypt has been recently upgraded and standardized according to the World Health Organization (WHO) guidelines. Formal postgraduate education roughly follows the British system. Laboratory hematology specialization is achieved through 2-3 years masters' degree followed by 2-4 years doctorate degree in clinical pathology with training and research in hematology. Improvement of laboratory hematology education is recently undergoing a reform as a part of the modernization of higher education policy and following the standards developed by the National Quality Assurance and Accreditation Agency (NQAAA). Accreditation of medical laboratories is recently progressing with the development of the "Egyptian Accreditation Council" (EGAC) as the sole accreditation body system and training of assessors. Current laboratory system has many challenges, some are related to the inadequate system performance, and others are unique to laboratory hematology issues. The rapid technological advances and therapeutic innovations in hematology practice call for an adapting laboratory system with continuous upgrading. © 2018 John Wiley & Sons Ltd.

A stapled BIM peptide overcomes apoptotic resistance in hematologic cancers

PubMed Central

LaBelle, James L.; Katz, Samuel G.; Bird, Gregory H.; Gavathiotis, Evripidis; Stewart, Michelle L.; Lawrence, Chelsea; Fisher, Jill K.; Godes, Marina; Pitter, Kenneth; Kung, Andrew L.; Walensky, Loren D.

2012-01-01

Cancer cells subvert the natural balance between cellular life and death, achieving immortality through pathologic enforcement of survival pathways and blockade of cell death mechanisms. Pro-apoptotic BCL-2 family proteins are frequently disarmed in relapsed and refractory cancer through genetic deletion or interaction-based neutralization by overexpressed antiapoptotic proteins, resulting in resistance to chemotherapy and radiation treatments. New pharmacologic strategies are urgently needed to overcome these formidable apoptotic blockades. We harnessed the natural killing activity of BCL-2–interacting mediator of cell death (BIM), which contains one of the most potent BH3 death domains of the BCL-2 protein family, to restore BH3-dependent cell death in resistant hematologic cancers. A hydrocarbon-stapled peptide modeled after the BIM BH3 helix broadly targeted BCL-2 family proteins with high affinity, blocked inhibitory antiapoptotic interactions, directly triggered proapoptotic activity, and induced dose-responsive and BH3 sequence–specific cell death of hematologic cancer cells. The therapeutic potential of stapled BIM BH3 was highlighted by the selective activation of cell death in the aberrant lymphoid infiltrates of mice reconstituted with BIM-deficient bone marrow and in a human AML xenograft model. Thus, we found that broad and multimodal targeting of the BCL-2 family pathway can overcome pathologic barriers to cell death. PMID:22622039

Temporal and spatial bioassessment of ecological risk of Amazonian Itchyofauna associated to Hg exposure

NASA Astrophysics Data System (ADS)

Castilhos, Z. C.; Almonsy, N.; Souto, P. S.; Pereira da Silva, L. C. C.; Bidone, E. D.

2003-05-01

In Amazon artisan gold mining, mercury (Hg) is released to environment during its use to amalgamate the fine particles of gold. Once mercury entries in aquatic ecosystems, it might be methylated to methylmercury (MeHg). The objectives of this work were: (i) to establish and compare the dose-response relationship for Hg accumulation by Tucunaré for a contaminated and a background area; (ii) to test the DRAC methodology to proceed field sampling of fish; (iii) to conduct a temporal analysis of magnitude of mercury contamination in fish during the last decade by using DRAC methodology and (v) to investigate the relationship between hematological parameters (erythrocytes, hematocrit, leukocytes and mean corpuscular volume) and Hg exposure in fish.. Close to 100 Tucunarés were caught in the Tapajós River region. The results showed significant differences in hematological parameters and Hg concentration considering contaminated and background areas and the temporal assessment suggest increase the Hg bio-availability during last decade in Tapajos River Region. One could suggest that those hematological parameters might be used as physiological biomarkers of Hg exposure in ecological risk assessment process and that Hg used by or remaining from gold mining “garimpos” might be continuous bio-available to Amazonian biota.

Role of Non Receptor Tyrosine Kinases in Hematological Malignances and its Targeting by Natural Products.

PubMed

Siveen, Kodappully S; Prabhu, Kirti S; Achkar, Iman W; Kuttikrishnan, Shilpa; Shyam, Sunitha; Khan, Abdul Q; Merhi, Maysaloun; Dermime, Said; Uddin, Shahab

2018-02-19

Tyrosine kinases belong to a family of enzymes that mediate the movement of the phosphate group to tyrosine residues of target protein, thus transmitting signals from the cell surface to cytoplasmic proteins and the nucleus to regulate physiological processes. Non-receptor tyrosine kinases (NRTK) are a sub-group of tyrosine kinases, which can relay intracellular signals originating from extracellular receptor. NRTKs can regulate a huge array of cellular functions such as cell survival, division/propagation and adhesion, gene expression, immune response, etc. NRTKs exhibit considerable variability in their structural make up, having a shared kinase domain and commonly possessing many other domains such as SH2, SH3 which are protein-protein interacting domains. Recent studies show that NRTKs are mutated in several hematological malignancies, including lymphomas, leukemias and myelomas, leading to aberrant activation. It can be due to point mutations which are intragenic changes or by fusion of genes leading to chromosome translocation. Mutations that lead to constitutive kinase activity result in the formation of oncogenes, such as Abl, Fes, Src, etc. Therefore, specific kinase inhibitors have been sought after to target mutated kinases. A number of compounds have since been discovered, which have shown to inhibit the activity of NRTKs, which are remarkably well tolerated. This review covers the role of various NRTKs in the development of hematological cancers, including their deregulation, genetic alterations, aberrant activation and associated mutations. In addition, it also looks at the recent advances in the development of novel natural compounds that can target NRTKs and perhaps in combination with other forms of therapy can show great promise for the treatment of hematological malignancies.

Effect of recombinant human granulocyte colony-stimulating factor on combination therapy with aztreonam and clindamycin for infections in neutropenic patients with hematologic diseases.

PubMed

Toyama, K; Yaguchi, M; Mizoguchi, H; Masuda, M; Urabe, A; Ikeda, Y; Aoki, I; Shinbo, T; Togawa, A; Hirashima, K; Miura, Y; Hirose, S; Tsuruoka, N; Omine, M; Kamakura, M; Saito, T; Arimori, S; Aoki, N; Kuraishi, Y; Hirai, H; Asano, S; Mori, M; Shirai, T; Muto, Y; Takaku, F

1996-12-01

The present multicenter study was performed to evaluate the effect of recombinant human granulocyte-colony stimulating factor (rhG-CSF) on combination therapy using aztreonam (AZT) and clindamycin (CLDM) to treat severe infection in neutropenic patients with hematologic diseases. Forty-three neutropenic patients with infections (rhG-CSF group) were treated with AZT (2 g) and CLDM (600 mg) 2-3 times daily as well as rhG-CSF (Lenograstim or Filgrastim: 2-5 mu/kg/day). The clinical efficacy of this regimen was compared to that obtained in 44 febrile neutropenic patients, with hematologic diseases, who received only AZT and CLDM in a previous study (historical control group). The overall efficacy rate was 69.8% (30/43) in the rhG-CSF group and 65.9% (29/44) in the historical control group. Although the neutrophil count was significantly increased and C-reactive protein tended to be lower in the rhG-CSF group, the daily maximum body temperature profiles of the 2 groups were nearly the same. These results suggest that rhG-CSF is of little benefit in the treatment of single infectious episodes in neutropenic patients, and that appropriate antibiotic therapy is more important.

Comparable post-relapse outcomes between haploidentical and matched related donor allogeneic stem cell transplantation.

PubMed

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

2017-03-01

We investigated the impact of donor type on post-relapse survival (PRS) in 85 patients with hematological relapse after their first allogeneic hematological stem cell transplantation (allo-HSCT) for hematological malignancy. The median follow-up was 64 months among survivors. Both 3-year overall survival and 3-year PRS were similar in haploidentical donor (HID) and matched sibling donor (MRD) transplantation (13.0%±4.7% vs 19.4%±7.1%, P=0.913 and 7.7±3.9% vs 9.7±5.3%, P= 0.667). Higher rates of post-relapse grade II-IV and III-IV acute GvHD (aGvHD) were observed in HID transplantation patients. A higher cumulative incidence of post-relapse extensive chronic GvHD was also observed for HID transplantation patients. Multivariate analyses confirmed that treatment including donor lymphocyte infusion (DLI), late relapse >1 year, and in first CR at transplantation were associated with superior PRS (P=0.012, hazard ratio (HR)=0.527 (0.320-0.866)); P=0.033, HR=0.534 (0.300-0.952) and P=0.046, HR=0.630 (0.400-0.992). The data suggest that post-relapse outcomes are comparable in HID and MRD transplantation, and that DLI is safe for relapsed patients after haploidentical transplantation.

BLOOD CHEMISTRY AND HEMATOLOGY VALUES IN HEALTHY AND REHABILITATED ROUGH-TOOTHED DOLPHINS ( STENO BREDANENSIS).

PubMed

Manire, Charles A; Reiber, C Melanie; Gaspar, Cécile; Rhinehart, Howard L; Byrd, Lynne; Sweeney, Jay; West, Kristi L

2018-01-01

Rehabilitation efforts for live stranded marine mammals are guided by diagnostic measures of blood chemistry and hematology parameters obtained from each individual undergoing treatment. Despite the widespread use of blood parameters, reference values are not available in the literature from healthy rough-toothed dolphins ( Steno bredanensis) with which to infer the health status of an animal. We examined serum or plasma chemistry and hematology data from 17 rough-toothed dolphins either housed at Dolphin Quest French Polynesia or during their rehabilitation at the Dolphin and Whale Hospital in Sarasota, Florida, US between 1994 and 2005. Blood parameters were compared among healthy animals, rehabilitation animals that were eventually released, and rehabilitation animals that died. This study indicated significant differences in many blood parameters for the poorly known rough-toothed dolphin that are likely to vary between healthy and sick animals. These included aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, bicarbonate, and globulins, which were greater in sick dolphins, and alkaline phosphatase and total protein which were greater in healthy individuals. Total white blood cell counts were lower in healthy animals as were the absolute numbers of neutrophils, monocytes, and eosinophils. Analysis of first blood sample levels for glucose, sodium, and erythrocyte sedimentation rate may have value for triage and prognostic evaluation.

Imatinib mesylate, the first molecularly targeted gene suppressor.

PubMed

Pindolia, Vanita K; Zarowitz, Barbara J

2002-10-01

To review the pharmacology, pharmacokinetics, efficacy, safety, and drug-drug and drug-food interactions of imatinib and the economic considerations of imatinib in the treatment of chronic myeloid leukemia (CML). Literature accessed through MEDLINE (January 1970-January 2002), abstracts from the 2001 annual meetings of the American Society of Clinical Oncology and the American Society of Hematology, imatinib product labeling, and additional studies or abstracts identified from the bibliographies of the reviewed literature were used to compile data. Key search terms were allogeneic bone marrow transplant and stem cell transplant, chronic myeloid leukemia, imatinib, interferon, Gleevec, leukemia, gastrointestinal stromal tumors, STI-571, and tyrosine kinase inhibitors. Imatinib is a distinctively characteristic drug targeted toward inhibition of tyrosine kinase activity. Imatinib is indicated for the treatment of patients with CML who failed interferon (IFN)-alpha therapy and for the treatment of patients with gastrointestinal stromal tumors (GISTs) expressing the tyrosine kinase receptor c-kit. Imatinib produces positive short-term hematologic and cytogenetic responses in patients with CML; short-term positive objective responses have been shown for patients with GISTs. To our knowledge, there are no controlled trials demonstrating long-term safety, improvement in disease-related symptoms, or increased survival with imatinib. Serious adverse effects requiring dosage decreases and/or therapy termination are edema, hepatotoxicity, and hematologic toxicity. Imatinib also has been found to inhibit tyrosine kinases involved in the growth of other malignancies. The role of imatinib in tumors that express a tyrosine kinase is constantly evolving with new research results. Imatinib therapy should be limited to patients whose tumor growth is related to a genetically defective tyrosine kinase. In cases of CML, imatinib should be further limited to patients who have tried and failed IFN-alpha therapy or who are not candidates for an allogeneic stem cell transplant.

Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia.

PubMed

Byrd, John C; Furman, Richard R; Coutre, Steven E; Flinn, Ian W; Burger, Jan A; Blum, Kristie A; Grant, Barbara; Sharman, Jeff P; Coleman, Morton; Wierda, William G; Jones, Jeffrey A; Zhao, Weiqiang; Heerema, Nyla A; Johnson, Amy J; Sukbuntherng, Juthamas; Chang, Betty Y; Clow, Fong; Hedrick, Eric; Buggy, Joseph J; James, Danelle F; O'Brien, Susan

2013-07-04

The treatment of relapsed chronic lymphocytic leukemia (CLL) has resulted in few durable remissions. Bruton's tyrosine kinase (BTK), an essential component of B-cell-receptor signaling, mediates interactions with the tumor microenvironment and promotes the survival and proliferation of CLL cells. We conducted a phase 1b-2 multicenter study to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of ibrutinib (PCI-32765), a first-in-class, oral covalent inhibitor of BTK designed for treatment of B-cell cancers, in patients with relapsed or refractory CLL or small lymphocytic lymphoma. A total of 85 patients, the majority of whom were considered to have high-risk disease, received ibrutinib orally once daily; 51 received 420 mg, and 34 received 840 mg. Toxic effects were predominantly grade 1 or 2 and included transient diarrhea, fatigue, and upper respiratory tract infection; thus, patients could receive extended treatment with minimal hematologic toxic effects. The overall response rate was the same in the group that received 420 mg and the group that received 840 mg (71%), and an additional 20% and 15% of patients in the respective groups had a partial response with lymphocytosis. The response was independent of clinical and genomic risk factors present before treatment, including advanced-stage disease, the number of previous therapies, and the 17p13.1 deletion. At 26 months, the estimated progression-free survival rate was 75% and the rate of overall survival was 83%. Ibrutinib was associated with a high frequency of durable remissions in patients with relapsed or refractory CLL and small lymphocytic lymphoma, including patients with high-risk genetic lesions. (Funded by Pharmacyclics and others; ClinicalTrials.gov number, NCT01105247.).

Targeting BTK with Ibrutinib in Relapsed Chronic Lymphocytic Leukemia

PubMed Central

Byrd, John C.; Furman, Richard R.; Coutre, Steven E.; Flinn, Ian W.; Burger, Jan A.; Blum, Kristie A.; Grant, Barbara; Sharman, Jeff P.; Coleman, Morton; Wierda, William G.; Jones, Jeffrey A.; Zhao, Weiqiang; Heerema, Nyla A.; Johnson, Amy J.; Sukbuntherng, Juthamas; Chang, Betty Y.; Clow, Fong; Hedrick, Eric; Buggy, Joseph J.; James, Danelle F.; O'Brien, Susan

2013-01-01

BACKGROUND The treatment of relapsed chronic lymphocytic leukemia (CLL) has resulted in few durable remissions. Bruton's tyrosine kinase (BTK), an essential component of B-cell–receptor signaling, mediates interactions with the tumor microenvironment and promotes the survival and proliferation of CLL cells. METHODS We conducted a phase 1b–2 multicenter study to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of ibrutinib (PCI-32765), a first-in-class, oral covalent inhibitor of BTK designed for treatment of B-cell cancers, in patients with relapsed or refractory CLL or small lymphocytic lymphoma. A total of 85 patients, the majority of whom were considered to have high-risk disease, received ibrutinib orally once daily; 51 received 420 mg, and 34 received 840 mg. RESULTS Toxic effects were predominantly grade 1 or 2 and included transient diarrhea, fatigue, and upper respiratory tract infection; thus, patients could receive extended treatment with minimal hematologic toxic effects. The overall response rate was the same in the group that received 420 mg and the group that received 840 mg (71%), and an additional 20% and 15% of patients in the respective groups had a partial response with lymphocytosis. The response was independent of clinical and genomic risk factors present before treatment, including advanced-stage disease, the number of previous therapies, and the 17p13.1 deletion. At 26 months, the estimated progression-free survival rate was 75% and the rate of overall survival was 83%. CONCLUSIONS Ibrutinib was associated with a high frequency of durable remissions in patients with relapsed or refractory CLL and small lymphocytic lymphoma, including patients with high-risk genetic lesions. (Funded by Pharmacyclics and others; ClinicalTrials.gov number, NCT01105247.) PMID:23782158

Randomized phase II study of sequential carboplatin plus paclitaxel and gefitinib in chemotherapy-naïve patients with advanced or metastatic non-small-cell lung cancer: Long-term follow-up results.

PubMed

Kubo, Emi; Yamamoto, Noboru; Nokihara, Hiroshi; Fujiwara, Yutaka; Horinouchi, Hidehito; Kanda, Shintaro; Goto, Yasushi; Ohe, Yuichiro

2017-01-01

The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib was initially approved in Japan in 2002 for the treatment of advanced or metastatic non-small-cell lung cancer (NSCLC); however, the optimal order of conventional cytotoxic chemotherapy (carboplatin and paclitaxel) and gefitinib administration has not been determined. We conducted a randomized phase II study of carboplatin and paclitaxel followed by gefitinib vs. gefitinib followed by carboplatin and paclitaxel to select a candidate for further development in a phase III study of chemotherapy-naïve patients with advanced or metastatic NSCLC, regardless of their EGFR mutation status. A total of 97 patients meeting this description were randomly assigned to arm A (carboplatin and paclitaxel followed by gefitinib; n=49) or B (gefitinib followed by carboplatin and paclitaxel; n=48) from June, 2003 to October, 2005. Carboplatin and paclitaxel were administered in 4 cycles every 3 weeks; gefitinib was continued until disease progression or development of unacceptable toxicity. The primary endpoint was overall survival; the secondary endpoints were response rate and adverse event prevalence. The median overall follow-up was 65.1 months (range, 28.7-75.1 months). The major toxicities were hematological (carboplatin and paclitaxel) or skin rash, diarrhea and hepatic dysfunction (gefitinib). Interstitial lung disease was observed in 1 patient from each arm. In arms A and B, the carboplatin and paclitaxel response rate, gefitinib response rate, and median survival durations were 34.8 and 26.5%, 33.3 and 35.7%, and 18.8 and 17.2 months, respectively. Arm A was selected for a subsequent phase III study.

RANDOMIZED TRIAL OF PEGYLATED LIPOSOMAL DOXORUBICIN (PLD) PLUS CARBOPLATIN VERSUS CARBOPLATIN IN PLATINUM-SENSITIVE (PS) PATIENTS WITH RECURRENT EPITHELIAL OVARIAN OR PERITONEAL CARCINOMA AFTER FAILURE OF INITIAL PLATINUM-BASED CHEMOTHERAPY (SOUTH WEST ONCOLOGY GROUP PROTOCOL S0200)

PubMed Central

Alberts, David S.; Liu, P. Y.; Wilczynski, Sharon P.; Clouser, Mary C.; Lopez, Ana Maria; Michelin, David P.; Lanzotti, Victor J.; Markman, Maurie

2008-01-01

Objective Because debate continues over the role of combination, platinum-based chemotherapy for platinum sensitive (PS), recurrent ovarian cancer (OC), we compared overall survival (OS), progression-free survival (PFS), confirmed complete response rate and time to treatment failure in this population. Methods Patients with recurrent stage III or IV OC, a progression-free and platinum-free interval of 6- 24 months after first-line platinum-based chemotherapy and up to 12 courses of a non-platinum containing consolidation treatment were eligible. Patients were randomized to IV pegylated liposomal doxorubicin (PLD) (30 mg/m2) plus IV carboplatin (AUC=5 mg/mL × min) once every 4 weeks (PLD arm) or IV carboplatin alone (AUC=5mg/mL × min) once every 4 weeks. Results The PLD arm enrolled 31 patients and the carboplatin alone arm 30 for a total of 61 patients out of 900 planned. Response rates were 67% for the PLD arm and 32% for the carboplatin only arm (Fisher’s exact p=0.02). The estimated median PFS was 12 and 8 months for PLD versus carboplatin alone. The estimated median OS on the PLD arm was 26 months and 18 months on the carboplatin only arm (p=0.02). Twenty-six percent of the patients on the PLD arm reported grade 4 toxicities, all hematological in nature. Conclusion This study was closed early because of slow patient accrual. The response rate, median PFS and OS results are intriguing. These data suggest that there may be an advantage to the PLD plus carboplatin combination treatment in patients with PS, recurrent OC. The regimen should be further tested. PMID:17949799

A phase 3 randomized placebo-controlled trial of darbepoetin alfa in patients with anemia and lower-risk myelodysplastic syndromes.

PubMed

Platzbecker, U; Symeonidis, A; Oliva, E N; Goede, J S; Delforge, M; Mayer, J; Slama, B; Badre, S; Gasal, E; Mehta, B; Franklin, J

2017-09-01

The use of darbepoetin alfa to treat anemia in patients with lower-risk myelodysplastic syndromes (MDS) was evaluated in a phase 3 trial. Eligible patients had low/intermediate-1 risk MDS, hemoglobin ⩽10 g/dl, low transfusion burden and serum erythropoietin (EPO) ⩽500 mU/ml. Patients were randomized 2:1 to receive 24 weeks of subcutaneous darbepoetin alfa 500 μg or placebo every 3 weeks (Q3W), followed by 48 weeks of open-label darbepoetin alfa. A total of 147 patients were randomized, with median hemoglobin of 9.3 (Q1:8.8, Q3:9.7) g/dl and median baseline serum EPO of 69 (Q1:36, Q3:158) mU/ml. Transfusion incidence from weeks 5-24 was significantly lower with darbepoetin alfa versus placebo (36.1% (35/97) versus 59.2% (29/49), P=0.008) and erythroid response rates increased significantly with darbepoetin alfa (14.7% (11/75 evaluable) versus 0% (0/35 evaluable), P=0.016). In the 48-week open-label period, dose frequency increased from Q3W to Q2W in 81% (102/126) of patients; this was associated with a higher hematologic improvement-erythroid response rate (34.7% (34/98)). Safety results were consistent with a previous darbepoetin alfa phase 2 MDS trial. In conclusion, 24 weeks of darbepoetin alfa Q3W significantly reduced transfusions and increased rates of erythroid response with no new safety signals in lower-risk MDS (registered as EudraCT#2009-016522-14 and NCT#01362140).

Increased mortality in hematological malignancy patients with acute respiratory failure from undetermined etiology: a Groupe de Recherche en Réanimation Respiratoire en Onco-Hématologique (Grrr-OH) study.

PubMed

Contejean, Adrien; Lemiale, Virginie; Resche-Rigon, Matthieu; Mokart, Djamel; Pène, Frédéric; Kouatchet, Achille; Mayaux, Julien; Vincent, François; Nyunga, Martine; Bruneel, Fabrice; Rabbat, Antoine; Perez, Pierre; Meert, Anne-Pascale; Benoit, Dominique; Hamidfar, Rebecca; Darmon, Michael; Jourdain, Mercé; Renault, Anne; Schlemmer, Benoît; Azoulay, Elie

2016-12-01

Acute respiratory failure (ARF) is the most frequent complication in patients with hematological malignancies and is associated with high morbidity and mortality. ARF etiologies are numerous, and despite extensive diagnostic workflow, some patients remain with undetermined ARF etiology. This is a post-hoc study of a prospective multicenter cohort performed on 1011 critically ill hematological patients. Relationship between ARF etiology and hospital mortality was assessed using a multivariable regression model adjusting for confounders. This study included 604 patients with ARF. All patients underwent noninvasive diagnostic tests, and a bronchoscopy and bronchoalveolar lavage (BAL) was performed in 155 (25.6%). Definite diagnoses were classified into four exclusive etiological categories: pneumonia (44.4%), non-infectious diagnoses (32.6%), opportunistic infection (10.1%) and undetermined (12.9%), with corresponding hospital mortality rates of 40, 35, 55 and 59%, respectively. Overall hospital mortality was 42%. By multivariable analysis, factors associated with hospital mortality were invasive pulmonary aspergillosis (OR 7.57 (95% CI 3.06-21.62); p < 0.005), use of invasive mechanical ventilation (OR 1.65 (95% CI 1.07-2.55); p = 0.02), a SOFA score >7 (OR 3.32 (95% CI 2.15-5.15); p < 0.005) and an undetermined ARF etiology (OR 2.92 (95% CI 1.71-5.07); p < 0.005). In patients with hematological malignancies and ARF, up to 13% remain with undetermined ARF etiology despite comprehensive diagnostic workup. Undetermined ARF etiology is independently associated with hospital mortality. Studies to guide second-line diagnostic strategies are warranted. ClinicalTrials.Gov NCT01172132.

Hematology, cytochemistry and ultrastructure of blood cells in fishing cat (Felis viverrina).

PubMed

Prihirunkit, Kreangsak; Salakij, Chaleow; Apibal, Suntaree; Narkkong, Nual Anong

2007-06-01

Hematological, cytochemical and ultrastructural features of blood cells in fishing cat (Felis viverrina) were evaluated using complete blood cell counts with routine and cytochemical blood stains, and scanning and transmission electron microscopy. No statistically significant difference was found in different genders of this animal. Unique features of blood cells in this animal were identified in hematological, cytochemical and ultrastructural studies. This study contributes to broaden hematological resources in wildlife animals and provides a guideline for identification of blood cells in the fishing cat.

Phase II Study of Neoadjuvant Anthracycline-Based Regimens Combined With Nanoparticle Albumin-Bound Paclitaxel and Trastuzumab for Human Epidermal Growth Factor Receptor 2-Positive Operable Breast Cancer.

PubMed

Tanaka, Satoru; Iwamoto, Mitsuhiko; Kimura, Kosei; Matsunami, Nobuki; Morishima, Hirotaka; Yoshidome, Katsuhide; Nomura, Takashi; Morimoto, Takashi; Yamamoto, Daigo; Tsubota, Yu; Kobayashi, Toshihiro; Uchiyama, Kazuhisa

2015-06-01

We treated patients with operable human epidermal growth factor receptor 2-positive breast cancer with neoadjuvant anthracycline regimens followed by nanoparticle albumin-bound paclitaxel plus trastuzumab. Of the 44 patients, 49% achieved a pathologic complete response (pCR). The pCR rate was 36% and 71% in the patients with estrogen receptor-positive and -negative cancer, respectively. Neoadjuvant therapy using this combination appears to be effective and safe. Introduction: Neoadjuvant chemotherapy plus trastuzumab. Neoadjuvant chemotherapy plus trastuzumab results in a 30% to 50% pathologic complete response (pCR) rate in human epidermal growth factor receptor 2 (HER2)-positive breast cancer and has been associated with improved therapeutic outcomes. Thus, the pCR rate can be useful in evaluating novel agents in this patient population. Nanoparticle albumin-bound (nab)-paclitaxel (PTX) can reduce the toxicity of PTX while maintaining its efficacy. The present study evaluated the activity and safety of nab-PTX as a neoadjuvant treatment of HER2(+) breast cancer. We treated patients with stage I to IIIA breast cancer using neoadjuvant epirubicin/cyclophosphamide (EC) or 5-fluorouracil/epirubicin/cyclophosphamide every 3 weeks (q3w) for 4 cycles, followed by nab-PTX (260 mg/m(2)) plus trastuzumab q3w for 4 cycles. The primary endpoint was the pCR rate. The secondary endpoints included the clinical response rate, disease-free survival, pathologic response rate (defined as pCR or minimal residual invasive disease only in the breast), breast-conserving surgery rate, and safety. Forty-six patients were enrolled. One patient met the exclusion criteria because of the coexistence of another malignant disease; therefore, we evaluated 45 patients in the entire study. One patient experienced rapid disease progression during EC therapy, leaving 44 patients evaluable for nab-PTX treatment. Of the 45 patients, 49% achieved a pCR. The pCR rate was 36% and 71% in those with estrogen receptor-positive and -negative cancer, respectively. Of all the study treatments, the most frequent reason for delay or dose reduction was hematologic toxicity; only 1 patient required a dose reduction for nab-PTX because of peripheral neuropathy. Neoadjuvant therapy using this combination appears to be effective and safe. Copyright © 2015 Elsevier Inc. All rights reserved.

Elevated risks for amyotrophic lateral sclerosis and blood disorders in Ashkenazi schizophrenic pedigrees suggest new candidate genes in schizophrenia

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

Goodman, A.B.

1994-09-15

Among relatives of Ashkenazi schizophrenic probands the rate of amyotrophic lateral sclerosis was 3/1,000, compared to expected population rates of approximately 2/100,000. Relative risk of bleeding disorders, including hematologic cancers, was increased more than three-fold compared to controls. Co-occurrence of motor neuron disease and blood dyscrasias, accompanied by psychosis, has long been recognized. A virally-mediated autoimmune pathogenesis has been proposed. However, the familial co-occurrence of these three disease entities raises the possibility that the disease constellation be considered as a manifestation of a common underlying genetic defect. Such expansion of the spectrum of affectation might enhance the power of bothmore » candidate gene and linkage studies. Based on these findings, the loci suggested as candidate regions in schizophrenia include a potential hot spot on chromosome 21q21-q22, involving the superoxide dismutase and amyloid precursor protein genes. Alternatively, genes on other chromosomes involved in the expression, transcription, or regulation of these genes, or associated with the illnesses of high frequency in these pedigrees are suggested. Candidates include the choroid plexus transport protein, transthyretin at 18q11.2-q12.1; the t(14;18)(q22;21) characterizing B-cell lymphoma-2, the most common form of hematologic cancer; and the 14q24 locus of early onset Alzheimer`s disease, c-Fos, transforming growth factor beta 3, and heat shock protein A2. Expression of hematologic cancers and the suggested candidate genes are known to involve retinoid pathways, and retinoid disregulation has been proposed as a cause of schizophrenia. 67 refs., 2 figs., 1 tab.« less

Laparoscopic splenectomy in pediatric age: long-term follow-up.

PubMed

Ates, Ufuk; Tastekin, Nil Y; Gollu, Gulnur; Ergun, Ergun; Yagmurlu, Aydin

2017-12-01

In the last century, with the advancement of the diagnostic procedures, hematologic disorders in pediatric age group have been increased dramatically. In parallel with this increase, splenectomy procedures have also been popularized with different techniques and surgical outcomes. Laparoscopic splenectomy (LS) in the pediatric age group is generally accepted as a technically demanding procedure, which needs experience. The purpose of this study is to present the long-term follow-up results of a case series of children who underwent LS for a variety of hematologic disorders, evaluate possible complications and outcomes. All patients who were admitted to the clinic and who were scheduled for LS from 2005 to 2016 were considered for this study. The study parameters were grouped in four categories including socio-demographic data, preoperative evaluation, clinical follow-up and complications. There were 24 male (48.9%) and 25 (51.1%) female patients. The median age and body weight for the study group was 12 years and 35 kg. Most common indications for LS were thalassemia (13; 26.5%) and hereditary spherocytosis (12; 24.4%). As a technical standpoint, 2 patients (4%) underwent singleport LS surgery. The mean time for LS surgeries was found as 80 minutes. The total intraoperative complication rate was 4% (2/57). The mean time for hospital stay was 5 days. Mean follow-up period was 6.4 years (range: 6 months-16 years). There was no long-term complication. Bilirubin levels and need for blood transfusion significantly decreased in the long term follow-up period (p <0.05). LS is a powerful tool in the hands of an experienced surgeon. It's a safe and effective procedure in children with hematologic disorders resulting in shorter length of stay and lower complication rates. Sociedad Argentina de Pediatría

Early career mentoring through the American Society of Pediatric Hematology/Oncology: Lessons learned from a pilot program.

PubMed

Badawy, Sherif M; Black, Vandy; Meier, Emily R; Myers, Kasiani C; Pinkney, Kerice; Hastings, Caroline; Hilden, Joanne M; Zweidler-McKay, Patrick; Stork, Linda C; Johnson, Theodore S; Vaiselbuh, Sarah R

2017-03-01

Effective networking and mentorship are critical determinants of career satisfaction and success in academic medicine. The American Society of Pediatric Hematology/Oncology (ASPHO) mentoring program was developed to support Early Career (EC) members. Herein, the authors report on the initial 2-year outcomes of this novel program. Mentees selected mentors with expertise in different subspecialties within the field from mentor profiles at the ASPHO Web site. Of 23 enrolled pairs, 19 mentors and 16 mentees completed electronic program feedback evaluations. The authors analyzed data collected between February 2013 and December 2014. The authors used descriptive statistics for categorical data and thematic analysis for qualitative data. The overall response rate was 76% (35/46). At the initiation of the relationship, career development and research planning were the most commonly identified goals for both mentors and mentees. Participants communicated by phone, e-mail, or met in-person at ASPHO annual meetings. Most mentor-mentee pairs were satisfied with the mentoring relationship, considered it a rewarding experience that justified their time and effort, achieved their goals in a timely manner with objective work products, and planned to continue the relationship. However, time constraints and infrequent communications remained a challenge. Participation in the ASPHO mentoring program suggests a clear benefit to a broad spectrum of ASPHO EC members with diverse personal and professional development needs. Efforts to expand the mentoring program are ongoing and focused on increasing enrollment of mentors to cover a wider diversity of career tracks/subspecialties and evaluating career and academic outcomes more objectively. © 2016 Wiley Periodicals, Inc.

Venetoclax for patients with chronic lymphocytic leukemia who progressed during or after idelalisib therapy.

PubMed

Coutre, Steven; Choi, Michael; Furman, Richard R; Eradat, Herbert; Heffner, Leonard; Jones, Jeffrey A; Chyla, Brenda; Zhou, Lang; Agarwal, Suresh; Waskiewicz, Tina; Verdugo, Maria; Humerickhouse, Rod A; Potluri, Jalaja; Wierda, William G; Davids, Matthew S

2018-04-12

B-cell receptor pathway inhibitors (BCRis) have transformed treatment of chronic lymphocytic leukemia (CLL); however, the efficacy of therapies for patients whose disease is refractory to/relapses after (R/R) BCRis is unknown. Venetoclax is a selective, orally bioavailable BCL-2 inhibitor with activity in patients with CLL, including those who are heavily pretreated or have 17p deletion. This phase 2 study prospectively evaluated venetoclax in patients with R/R CLL after ibrutinib or idelalisib; here we report on patients who received idelalisib as the last BCRi before enrollment. Venetoclax was initiated at 20 mg daily, followed by intrapatient ramp-up to 400 mg daily. Primary objectives included efficacy (objective response rate [ORR]) and safety of venetoclax. The study enrolled 36 patients who previously received idelalisib (ORR, 67% [24/36]); 2 patients achieved complete remission, and 1 had complete remission with incomplete bone marrow recovery. Median progression-free survival (PFS) has not yet been reached; estimated 12-month PFS was 79%. The most common adverse events (AEs; all grades) were neutropenia (56%), diarrhea (42%), upper respiratory tract infection (39%), thrombocytopenia (36%), nausea (31%), fatigue (28%), cough (22%), rash (22%), and anemia (22%). Grade 3 or 4 AEs were primarily hematologic (neutropenia [50%], thrombocytopenia [25%], and anemia [17%]). No patients experienced tumor lysis syndrome. Venetoclax demonstrated promising clinical activity and favorable tolerability in patients with CLL whose disease progressed during or after idelalisib therapy. This trial was registered at www.clinicaltrials.gov as #NCT02141282. © 2018 by The American Society of Hematology.

Early career mentoring through the American Society of Pediatric Hematology/Oncology: Lessons learned from a pilot program

PubMed Central

Badawy, Sherif M.; Black, Vandy; Meier, Emily R.; Myers, Kasiani C.; Pinkney, Kerice; Hastings, Caroline; Hilden, Joanne M.; Zweidler-McKay, Patrick; Stork, Linda C.; Johnson, Theodore S.; Vaiselbuh, Sarah R.

2017-01-01

Background Effective networking and mentorship are critical determinants of career satisfaction and success in academic medicine. The American Society of Pediatric Hematology/Oncology (ASPHO) mentoring program was developed to support Early Career (EC) members. Herein, the authors report on the initial 2-year outcomes of this novel program. Procedure Mentees selected mentors with expertise in different subspecialties within the field from mentor profiles at the ASPHO Web site. Of 23 enrolled pairs, 19 mentors and 16 mentees completed electronic program feedback evaluations. The authors analyzed data collected between February 2013 and December 2014. The authors used descriptive statistics for categorical data and thematic analysis for qualitative data. Results The overall response rate was 76% (35/46). At the initiation of the relationship, career development and research planning were the most commonly identified goals for both mentors and mentees. Participants communicated by phone, e-mail, or met in-person at ASPHO annual meetings. Most mentor–mentee pairs were satisfied with the mentoring relationship, considered it a rewarding experience that justified their time and effort, achieved their goals in a timely manner with objective work products, and planned to continue the relationship. However, time constraints and infrequent communications remained a challenge. Conclusions Participation in the ASPHO mentoring program suggests a clear benefit to a broad spectrum of ASPHO EC members with diverse personal and professional development needs. Efforts to expand the mentoring program are ongoing and focused on increasing enrollment of mentors to cover a wider diversity of career tracks/subspecialties and evaluating career and academic outcomes more objectively. PMID:27616578

Characteristics of culture-positive invasive pulmonary aspergillosis in patients with hematologic diseases: Comparison between Aspergillus fumigatus and non-fumigatus Aspergillus species.

PubMed

Cho, Sung-Yeon; Lee, Dong-Gun; Choi, Jae-Ki; Lee, Hyo-Jin; Kim, Si-Hyun; Park, Sun Hee; Choi, Su-Mi; Choi, Jung-Hyun; Yoo, Jin-Hong; Park, Yeon-Joon; Lee, Jong-Wook

2017-12-01

While the epidemiology and clinical differences of various Candida spp. has been relatively well-identified, data regarding invasive aspergillosis (IA) caused by different Aspergillus spp. are insufficient.We aimed to determine the epidemiology of culture-positive invasive pulmonary aspergillosis (IPA) and to compare the characteristics and outcomes of Aspergillus fumigatus IPA with those of non-fumigatus IPA in patients with hematologic diseases. All consecutive cases of IPA from 2011 to 2015 were reviewed retrospectively.There were 430 proven/probable IPA and 76 culture-positive proven/probable IPA. Excluding cases of multiple species of fungi or cases having difficulties in species-level identification, 41 A fumigatus and 22 non-fumigatus IPA (Aspergillus flavus [n = 11], Aspergillus niger [n = 6], and Aspergillus terreus [n = 5]) were compared. There were no significant differences in baseline characteristics between the 2 groups. However, disseminated IA was more common in non-fumigatus IPA (2.4% vs 18.2%; P = .046). Paranasal sinus (PNS) involvement was more common in non-fumigatus IPA. There was a trend towards higher peak serum galactomannan values in non-fumigatus IPA than in A fumigatus IPA group (median 1.33 [interquartile 0.98-3.29] vs 0.97 [0.66-1.97]; P = .084). Clinical response and mortality did not differ between groups.The culture-positive rate of proven/probable IPA was 17.7%, of which non-fumigatus Aspergillus accounted for about one-third. Disseminated IA, especially involving the PNS, was more frequent in non-fumigatus IPA than in A fumigatus IPA.

Multiscale modelling of Flow-Induced Blood Cell Damage

NASA Astrophysics Data System (ADS)

Liu, Yaling; Sohrabi, Salman

2017-11-01

We study red blood cell (RBC) damage and hemolysis at cellular level. Under high shear rates, pores form on RBC membranes through which hemoglobin (Hb) leaks out and increases free Hb content of plasma leading to hemolysis. By coupling lattice Boltzmann and spring connected network models through immersed boundary method, we estimate hemolysis of a single RBC under various shear rates. The developed cellular damage model can be used as a predictive tool for hydrodynamic and hematologic design optimization of blood-wetting medical devices.

CUDC-907 in relapsed/refractory diffuse large B-cell lymphoma, including patients with MYC-alterations: results from an expanded phase I trial.

PubMed

Oki, Yasuhiro; Kelly, Kevin R; Flinn, Ian; Patel, Manish R; Gharavi, Robert; Ma, Anna; Parker, Jefferson; Hafeez, Amir; Tuck, David; Younes, Anas

2017-11-01

CUDC-907 is a first-in-class, oral small molecule inhibitor of both HDAC (class I and II) and PI3K (class Iα, β, and δ) enzymes, with demonstrated anti-tumor activity in multiple pre-clinical models, including MYC-driven ones. In this report, we present the safety and preliminary activity results of CUDC-907, with and without rituximab, in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), with a particular focus on those with MYC-altered disease. Thirty-seven DLBCL patients were enrolled, 14 with confirmed MYC-altered disease. Twenty-five patients received monotherapy treatment, and 12 received the combination of CUDC-907 with rituximab. CUDC-907 monotherapy and combination demonstrated similar safety profiles consisting primarily of Grade 1/2 hematologic and gastrointestinal events. The most frequently reported Grade ≥3 treatment-related events were thrombocytopenia, neutropenia, diarrhea, fatigue, and anemia. Eleven responses (5 complete responses and 6 partial responses) were reported, for a response rate of 37% (11 out of 30) in evaluable patients [30% (11 out of 37) including all patients]. The objective response rate in evaluable MYC-altered DLBCL patients was 64% (7 out of 11; 4 complete responses and 3 partial responses), while it was 29% (2 out of 7) in MYC unaltered, and 17% (2 out of 12) in those with unknown MYC status. Median duration of response was 11.2 months overall; 13.6 months in MYC-altered patients, 6.0 months in MYC unaltered, and 7.8 months in those with MYC status unknown. The tolerable safety profile and encouraging evidence of durable anti-tumor activity, particularly in MYC-altered patients, support the continued development of CUDC-907 in these populations of high unmet need. ( clinicaltrials.gov identifier: 01742988 ). Copyright© Ferrata Storti Foundation.

78 FR 54487 - Abbott Laboratories; Diagnostic-Hematology; Including On-Site Leased Workers From Manpower...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-04

... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-82,379] Abbott Laboratories... February 22, 2013, applicable to workers of Abbott Laboratories, Diagnostic--Hematology division, including... Clara, California location of Abbott Laboratories, Diagnostic--Hematology Division. The Department has...

Hematologic abnormalities associated with Simian Immunodeficieny Virus (SIV) Infection mimic those in HIV infection

PubMed Central

Gill, Amy F.; Ahsan, Muhammad H.; Lackner, Andrew A.; Veazey, Ronald S.

2012-01-01

Studies of hematologic abnormalities in HIV infected patients are confounded by a multitude of factors. A retrospective data analysis of SIV infected Rhesus macaques (RM) of Indian origin was performed to determine the prevalence of hematologic abnormalities free of these confounds. Hematologic data from rhesus macaques inoculated with SIV and without antiviral therapy were examined pre-inoculation, and throughout infection and the development of AIDS. Anemia, thrombocytopenia, lymphopenia, eosinophilia, and neutropenia all increased in prevalence with SIV infection. Significant increases in prevalence for both neutropenia and neutrophilia were also detected in SIV-infected macaques. SIV-infected macaques also had lower lymphocyte counts and increased prevalence of lymphopenia compared to non-infected subjects. The prevalence of eosinophilia was significantly increased during SIV infection. Concordance of hematologic abnormalities during SIV infection of macaques with similar changes in HIV infection of humans suggest that, like in HIV infection, hematologic abnormalities are major complications of SIV infection. PMID:22620272

Hematologic abnormalities associated with simian immunodeficieny virus (SIV) infection mimic those in HIV infection.

PubMed

Gill, Amy F; Ahsan, Muhammad H; Lackner, Andrew A; Veazey, Ronald S

2012-06-01

Studies of hematologic abnormalities in HIV-infected patients are confounded by a multitude of factors. A retrospective data analysis of simian immunodeficieny virus (SIV)-infected rhesus macaques (RM) of Indian origin was performed to determine the prevalence of hematologic abnormalities free of these confounds. Hematologic data from RM inoculated with SIV and without antiviral therapy were examined pre-inoculation, and throughout infection and the development of AIDS. Anemia, thrombocytopenia, lymphopenia, eosinophilia, and neutropenia all increased in prevalence with SIV infection. Significant increases in prevalence for both neutropenia and neutrophilia were also detected in SIV-infected macaques. SIV-infected macaques also had lower lymphocyte counts and increased prevalence of lymphopenia compared with non-infected subjects. The prevalence of eosinophilia was significantly increased during SIV infection. Concordance of hematologic abnormalities during SIV infection of macaques with similar changes in HIV infection of humans suggests that, like in HIV infection, hematologic abnormalities are major complications of SIV infection. © 2012 John Wiley & Sons A/S.

Venetoclax and low-dose cytarabine induced complete remission in a patient with high-risk acute myeloid leukemia: a case report.

PubMed

Liu, Bingshan; Narurkar, Roshni; Hanmantgad, Madhura; Zafar, Wahib; Song, Yongping; Liu, Delong

2018-05-21

Conventional combination therapies have not resulted in considerable progress in the treatment of acute myeloid leukemia (AML). Elderly patients with AML and poor risk factors have grave prognosis. Midostaurin has been recently approved for the treatment of FLT-3-mutated AML. Venetoclax, a BCL-2 inhibitor, has been approved for the treatment of relapsed and/or refractory chronic lymphoid leukemia. Clinical trials on applying venetoclax in combination with cytarabine and other agents to treat various hematological malignancies are currently underway. Here, we present a case of a male patient with poor performance status and who developed AML following allogeneic hematopoietic stem cell transplant for high-risk myelodysplasia. The patient with high risk AML achieved complete response to the combined treatment regimen of low-dose cytarabine and venetoclax. Furthermore, we reviewed current clinical trials on the use of venetoclax for hematological malignancies.

First report of changes in leukocyte morphology in response to inflammatory conditions in Asian and African elephants (Elephas maximus and Loxodonta africana).

PubMed

Stacy, Nicole I; Isaza, Ramiro; Wiedner, Ellen

2017-01-01

Although the hematology of healthy elephants has been well-described, published information on hematological changes during disease is limited. The objective of this study was to describe qualitative morphological changes in the leukocytes of Asian and African elephants (Elephas maximus and Loxodonta africana) diagnosed with a variety of inflammatory conditions. Twenty-five of 27 elephants had morphological changes in their leukocytes, although only 16 of these had a concurrent inflammatory leukogram. Morphological changes included heterophil left-shifting with or without concurrent dysgranulopoiesis, toxicity, or hypersegmentation, reactive lymphocytes, plasma cells, and/or vacuolated monocytes. Although the observed leukocyte morphological changes are non-specific, their early recognition upon blood film evaluation may provide important, clinically-relevant information, particularly if the leukogram is normal. This case series is the first description of qualitative morphological changes in the leukocytes of elephants in association with inflammation.

Myelofibrosis and acquired hemophilia A: a case report.

PubMed

Wrobel, Marie; Comio, Emilie; Gay, Valerie; Baroudi, Noureddine; Meyer, Pascal; Chuniaud-Louche, Christine; Hacini, Maya; Pica, Gian Matteo

2016-05-07

Myelofibrosis and acquired hemophilia A is a rare association. To the best of our knowledge only one case of myelofibrosis and acquired hemophilia A has been previously described. A 66-year-old Caucasian man diagnosed with myelofibrosis evolving in acute myeloid leukemia was referred to us for postoperative bleeding. Hemostatic studies showed prolonged activated partial thromboplastin time, decreased factor VIII coagulation, and a high factor VIII inhibitor titer; these findings led to a diagnosis of acquired hemophilia A for which he was treated with methylprednisolone and recombinant activated factor VII on admission. Due to a lack of response he was subsequently treated with rituximab combined with activated prothrombin complex concentrates. Furthermore, he received azacytidine to treat the underlying hematological malignancies. Immunosuppressive rituximab therapy resolved acquired hemophilia A with marked efficacy. Rapid and accurate diagnosis, effective hemostatic therapy, and timely treatment for underlying disease are important in the management of acquired hemophilia A secondary to hematological malignancy.

First report of changes in leukocyte morphology in response to inflammatory conditions in Asian and African elephants (Elephas maximus and Loxodonta africana)

PubMed Central

Isaza, Ramiro; Wiedner, Ellen

2017-01-01

Although the hematology of healthy elephants has been well-described, published information on hematological changes during disease is limited. The objective of this study was to describe qualitative morphological changes in the leukocytes of Asian and African elephants (Elephas maximus and Loxodonta africana) diagnosed with a variety of inflammatory conditions. Twenty-five of 27 elephants had morphological changes in their leukocytes, although only 16 of these had a concurrent inflammatory leukogram. Morphological changes included heterophil left-shifting with or without concurrent dysgranulopoiesis, toxicity, or hypersegmentation, reactive lymphocytes, plasma cells, and/or vacuolated monocytes. Although the observed leukocyte morphological changes are non-specific, their early recognition upon blood film evaluation may provide important, clinically-relevant information, particularly if the leukogram is normal. This case series is the first description of qualitative morphological changes in the leukocytes of elephants in association with inflammation. PMID:28934325

Interferon-α Based Individualized Treatment of a High Risk Chronic Myelogenous Leukemia Patient Harboring T315I Mutation.

PubMed

Zeng, Yunxin; Zhang, Jingwen; Li, Xiaoqing; Zhang, Ling; Liu, Jiajun

2018-06-01

T315I mutation is the most common BCR-ABL mutation and confers resistance to all the first and second generation BCR-ABL tyrosine kinases, including nilotinib and dasatinib. We report a high risk chronic myelogenous leukemia (CML) patient harboring the T315I mutation treated by Interferon-α (INF-α) solo and subsequently combined with dasatinib. Hematological investigation, bone marrow cytology inspection, chromosomal analysis (G-banding), and real-time quantitative polymerase chain reaction (RQ-PCR) were performed on a 47-year-old male patient. After 8 months IFN-α monotherapy, the patient lost the T315I mutation but acquired a new F359V mutation. After 2 months on dasatinib and INF-α treatment, the patient achieved complete hematologic response (CHR). IFN-α based combination therapy could be a viable treatment option for CML patients harboring T315I BCR-ABL mutation.

Hematology and plasma chemistry reference intervals for cultured tilapia (Oreochromis hybrid).

PubMed

Hrubec, Terry C.; Cardinale, Jenifer L.; Smith, Stephen A.

2000-01-01

Tilapia are a commonly aquacultured fish yet little is known about their normal physiology and response to disease. In this study we determined the results of complete hematologic (n=40) and plasma biochemical profiles (n=63) in production tilapia (Oreochromis hybrids). The fish were raised in recirculating systems with a high stocking density (120 g/L), and were in the middle of a 15-month production cycle. Blood was analyzed using standard techniques, and reference intervals were determined using nonparametric methods. Non-production tilapia (n=15) from low-density tanks (4 g/L) also were sampled; the clinical chemistry results were compared to reference intervals from the fish raised in high-density tanks. Differences were noted in plasma protein, calcium and phosphorus concentrations, such that reference intervals for high-density production tilapia were not applicable to fish raised under different environmental and management conditions.

Outcomes with single agent LIPO-DOX in platinum-resistant ovarian and fallopian tube cancers and primary peritoneal adenocarcinoma - Chiang Mai University Hospital experience.

PubMed

Suprasert, Prapaporn; Manopunya, Manatsawee; Cheewakriangkrai, Chalong

2014-01-01

Single pegylated liposomal doxorubicin (PLD) is commonly used as a salvage treatment in platinum-resistant ovarian cancer, fallopian tube cancer and primary peritoneal adenocarcinoma (PPA) with a satisfactory outcome. However, the data for second generation PLD administered in this setting are still limited. We conducted a retrospective study to evaluate the outcome of patients who received single-agent second generation PLD (LIPO-DOX) after the development of clinical platinum resistance. The study period was between March 2008 and March 2013. LIPO-DOX was administered intravenously 40 mg/m2 every 28 days until disease progression, but for not more than six cycles. The response rate was evaluated using the Gynecologic Cancer Intergroup (GCIG) criteria while the toxicity was evaluated according to WHO criteria. Twenty-nine patients met the inclusion criteria in the study period with an overall response rate of 13.8%. The median progression free survival and overall survival were three and eleven months, respectively. With the total of 96 cycles of chemotherapy, the patients developed grades 3 and 4 hematologic toxicity as follows: anemia, 0%, leukopenia, 9.6%, neutropenia, 32.3% and thrombocytopenia, 0%. In conclusion, the single agent second generation PLD demonstrated modest efficacy in patients with platinum-resistant ovarian cancer, fallopian tube cancer and PPA without serious toxicity.

Chlorambucil plus Rituximab as Front-Line Therapy in Elderly/Unfit Patients Affected by B-Cell Chronic Lymphocytic Leukemia: Results of a Single-Centre Experience

PubMed Central

Laurenti, Luca; Vannata, Barbara; Innocenti, Idanna; Autore, Francesco; Santini, Francesco; Piccirillo, Nicola; Za, Tommaso; Bellesi, Silvia; Marietti, Sara; Sica, Simona; Efremov, Dimitar G.; Leone, Giuseppe

2013-01-01

The current standard first line therapy for fit patients with B-CLL/SLL is based on combination of fludarabine-cyclophosphamide and rituximab. However, elderly patients or patients with comorbidities poorly tolerate purine analogue-based chemotherapy and they are often treated with Chlorambucil (Chl) only. However, complete response (CR) and overall response (OR) rates with Chl are relatively low. We now investigated whether the addition of Rituximab to Chl will improve the efficacy without impairing the tolerability in elderly and unfit patients. We included in our study 27 elderly or unfit patients that had not received prior therapy. All patients were treated with Chl (1mg/Kg per 28-day cycle for 8 cycles) plus Rituximab (375 mg/m2 for the first course and 500 mg/m2 for subsequent cycles until the 6th cycle). We obtained an OR rate of 74%. The most frequent adverse effect was grade 3–4 neutropenia, which occurred in 18.5% of the patients. Infections or grade 3–4 extra-hematological side effects were not recorded. None of the patients required reduction of dose, delay of therapy or hospitalization. Overall, these data suggest that Chl-R is an effective and well tolerated regimen in elderly/unfit patients with CLL. PMID:23667729

21 CFR 864.8625 - Hematology quality control mixture.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Hematology quality control mixture. 864.8625 Section 864.8625 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... quality control mixture. (a) Identification. A hematology quality control mixture is a device used to...

Hematology, cytochemistry and ultrastructure of blood cells in fishing cat (Felis viverrina)

PubMed Central

Salakij, Chaleow; Apibal, Suntaree; Narkkong, Nual-Anong

2007-01-01

Hematological, cytochemical and ultrastructural features of blood cells in fishing cat (Felis viverrina) were evaluated using complete blood cell counts with routine and cytochemical blood stains, and scanning and transmission electron microscopy. No statistically significant difference was found in different genders of this animal. Unique features of blood cells in this animal were identified in hematological, cytochemical and ultrastructural studies. This study contributes to broaden hematological resources in wildlife animals and provides a guideline for identification of blood cells in the fishing cat. PMID:17519570

Measuring symptoms as a critical component of drug development and evaluation in hematological diseases

PubMed Central

Williams, Loretta A; Yucel, Emre; Cortes, Jorge E; Cleeland, Charles S

2014-01-01

With the rapid development of new therapies for patients with hematological malignancies, there is an increasing need for patient report of symptom status during all phases of drug testing. The patient’s perspective on new treatments reflects treatment tolerability as well as symptom benefit, and may assist patients and clinicians in choosing treatments. Inclusion of patient-reported outcomes, more common in solid-tumor than hematological trials, provides early information about symptoms to guide decisions about appropriate dosing and supportive care needs. We provide a historical overview of the use of patient-reported outcomes and symptom assessment in solid-tumor and hematological drug development, and offer recommendations about methodological issues in the monitoring of symptoms in the drug development process in hematological clinical trials. PMID:24910769

Weekly Versus Triweekly Cisplatin-Based Chemotherapy Concurrent With Radiotherapy in the Treatment of Cervical Cancer: A Meta-Analysis.

PubMed

Chen, Xingxing; Zou, Haizhou; Li, Huifang; Lin, Ruifang; Su, Meng; Zhang, Wenyi; Zhou, Yongqiang; Zhang, Ping; Hou, Meng; Deng, Xia; Zou, Changlin

2017-02-01

The aim of this study was to evaluate toxicity, compliance, recurrence and the survival of weekly and triweekly cisplatin-based concomitant chemoradiation in treatment of cervical cancer. The databases were searched from 1995 until 2015 to identify eligible studies on weekly versus triweekly cisplatin chemoradiotherapy. The data were analyzed by RevMan 5.3 software. A total of 5 randomized controlled trials were included in this review. Weekly cisplatin regimen significantly reduced the incidence of Hematologic toxicity. However, there was no significantly different between the 2 arms in compliance, recurrence and the survival rate (all P >0.05). Weekly cisplatin regimen had the similar therapeutic effect as the triweekly cisplatin regimen but with less hematologic toxicity. Therefore, we recommend the weekly cisplatin 30 to 40 mg/m chemoradiotherapy as the strong candidate for the optimal cisplatin dose and dosing schedule in the treatment of locally advanced cervical cancer.

Influenza vaccination responses in human systemic lupus erythematosus: impact of clinical and demographic features

PubMed Central

Crowe, Sherry R.; Merrill, Joan T.; Vista, Evan S.; Dedeke, Amy B.; Thompson, David M.; Stewart, Scott; Guthridge, Joel M.; Niewold, Timothy B.; Franek, Beverly S.; Air, Gillian M.; Thompson, Linda F.; James, Judith A.

2011-01-01

Objective Vaccination against common pathogens, such as influenza, is recommended for SLE patients to decrease infections and improve health. However, most vaccination response reports are limited to evaluation of SLE patients with quiescent disease. This study focuses on understanding the clinical, serological, therapeutic, and demographic factors which influence the response to influenza vaccination in patients with a range of disease activities. Methods Blood specimens and disease activity information were collected from seventy-two SLE patients at baseline and 2, 6 and 12 weeks after influenza vaccination. Influenza-specific antibody responses were assessed for antibody concentration (Bmax), relative affinity (Ka), and hemagglutination inhibition (HAI). Using a cumulative score, the subjects were evenly divided into high and low responders. Autoantibody levels were evaluated at each time-point by immunofluorescence and standard ELISAs. Results Low responders to the vaccine were more likely to have hematologic criteria (p=0.009), exhibit more ACR criteria (p=0.05), and be on concurrent prednisone treatment (p=0.04). Interestingly, European American patients were more likely to be low responders than African Americans (p = 0.03). Following vaccination, low responders were more likely to experience disease flares (p=0.01) and to have increased ANA titers (p = 0.04). Baseline serum interferon alpha activity was significantly higher in patients that experienced a flare after vaccination compared to a matched group of patients that did not flare (p= 0.04). Conclusions Ancestral background, prednisone treatment, hematological criteria and evidence of increased disease flares were associated with low antibody responses to influenza vaccination in SLE patients. PMID:21598235

Predicted Hematologic and Plasma Volume Responses Following Rapid Ascent to Progressive Altitudes

DTIC Science & Technology

2014-06-01

of these changes, and define baseline demographics and physiologic descriptors that are important in predicting these changes. The overall impact of... physiologic descriptors that are important in predicting these changes. Using general linear mixed models and a comprehensive relational database...accomplished using a comprehensive relational database containing individual ascent profiles, demographics, and physiologic subject descriptors as well as

Dose and dose rate effects of whole-body gamma-irradiation: II. Hematological variables and cytokines

NASA Technical Reports Server (NTRS)

Gridley, D. S.; Pecaut, M. J.; Miller, G. M.; Moyers, M. F.; Nelson, G. A.

2001-01-01

The goal of part II of this study was to evaluate the effects of gamma-radiation on circulating blood cells, functional characteristics of splenocytes, and cytokine expression after whole-body irradiation at varying total doses and at low- and high-dose-rates (LDR, HDR). Young adult C57BL/6 mice (n = 75) were irradiated with either 1 cGy/min or 80 cGy/min photons from a 60Co source to cumulative doses of 0.5, 1.5, and 3.0 Gy. The animals were euthanized at 4 days post-exposure for in vitro assays. Significant dose- (but not dose-rate-) dependent decreases were observed in erythrocyte and blood leukocyte counts, hemoglobin, hematocrit, lipopolysaccharide (LPS)-induced 3H-thymidine incorporation, and interleukin-2 (IL-2) secretion by activated spleen cells when compared to sham-irradiated controls (p < 0.05). Basal proliferation of leukocytes in the blood and spleen increased significantly with increasing dose (p < 0.05). Significant dose rate effects were observed only in thrombocyte counts. Plasma levels of transforming growth factor-beta 1 (TGF-beta 1) and splenocyte secretion of tumor necrosis factor-alpha (TNF-alpha) were not affected by either the dose or dose rate of radiation. The data demonstrate that the responses of blood and spleen were largely dependent upon the total dose of radiation employed and that an 80-fold difference in the dose rate was not a significant factor in the great majority of measurements.

Inpatient rehabilitation improved functional status in asthenic patients with solid and hematologic malignancies.

PubMed

Guo, Ying; Shin, Ki Y; Hainley, Susan; Bruera, Eduardo; Palmer, J Lynn

2011-04-01

The aim of this study was to compare functional outcomes in asthenic patients with hematologic malignancies with those of asthenic patients with solid tumors after inpatient rehabilitation. We hypothesized that asthenic patients with hematologic malignancies are less likely than patients with solid tumors to make functional improvement after rehabilitation. The records of 60 asthenic cancer patients (30 consecutive patients with solid tumors and 30 consecutive patients with hematologic malignancies) who underwent inpatient rehabilitation at a comprehensive cancer center between October 2005 and October 2007 were retrospectively reviewed. Patients with focal neurologic deficits were excluded. All patients admitted to the inpatient rehabilitation unit received 3 hrs of more of therapy per weekday. The main outcomes included total, motor, and cognitive Functional Independence Measure (FIM) scores, hospital and rehabilitation length of stay, and FIM efficiency. The mean total FIM score significantly improved in patients with solid tumors (mean, 15; range, -6 to 38) and in patients with hematologic malignancies (mean, 17; range, -3 to 27); however, between-group differences in FIM scores were not significant (P = 0.31). The solid tumor patients were significantly older than the hematologic malignancy patients (71 ± 11 vs. 64 ± 12 yrs; P = 0.02), but the mean rehabilitation lengths of stay were the same for each group (9.5 days; P = 0.82). The mean FIM efficiency in the hematologic malignancy group was higher than that of the solid tumor group (1.9 vs.1.4; P = 0.049). Asthenic patients with solid tumors or hematologic malignancies could benefit from inpatient rehabilitation and make significant functional gain.

Safety of long-term feeding of dl-alpha-lipoic acid and its effect on reduced glutathione:oxidized glutathione ratios in beagles.

PubMed

Zicker, Steven C; Hagen, Tory M; Joisher, Neha; Golder, Christina; Joshi, Dinesh K; Miller, E Phillip

2002-01-01

Alpha-lipoic acid is touted as a powerful antioxidant and possibly a conditionally essential nutrient in older mammals. The safety and efficacy of dl-alpha-lipoic acid was evaluated in 30 adult beagles that were evenly randomized into five groups, each of which was fed one of five different foods with varying inclusion rates of dl-alpha-lipoic acid (0, 150, 1500, 3000, and 4500 ppm). All dogs were fed their respective portion of food daily as their sole source of nutrition for 6 months. Evaluations included general health, body weight, food intake, hematologic and serum biochemical parameters, and glutathione:oxidized glutathione (GSH:GSSG) ratios in lymphocytes. No signs of toxicity were observed at any except the highest level of dl-alpha-lipoic acid inclusion, and no consistent abnormalities were noted in hematologic or biochemical measures at any level. There was a significant overall effect (P< .05) of food on the difference of GSH:GSSG ratio between Day 84 and Day 0. All inclusions of dl-alpha-lipoic acid increased the ratio of GSH:GSSG with the largest numeric improvement occurring at the lowest inclusion rate (150 ppm).

A multicenter phase 2 study of empirical low-dose liposomal amphotericin B in patients with refractory febrile neutropenia.

PubMed

Miyao, Kotaro; Sawa, Masashi; Kurata, Mio; Suzuki, Ritsuro; Sakemura, Reona; Sakai, Toshiyasu; Kato, Tomonori; Sahashi, Satomi; Tsushita, Natsuko; Ozawa, Yukiyasu; Tsuzuki, Motohiro; Kohno, Akio; Adachi, Tatsuya; Watanabe, Keisuke; Ohbayashi, Kaneyuki; Inagaki, Yuichiro; Atsuta, Yoshiko; Emi, Nobuhiko

2017-01-01

Invasive fungal infection (IFI) is a major life-threatening problem encountered by patients with hematological malignancies receiving intensive chemotherapy. Empirical antifungal agents are therefore important. Despite the availability of antifungal agents for such situations, the optimal agents and administration methods remain unclear. We conducted a prospective phase 2 study of empirical 1 mg/kg/day liposomal amphotericin B (L-AMB) in 80 patients receiving intensive chemotherapy for hematological malignancies. All enrolled patients were high-risk and had recurrent prolonged febrile neutropenia despite having received broad-spectrum antibacterial therapy for at least 72 hours. Fifty-three patients (66.3 %) achieved the primary endpoint of successful treatment, thus exceeding the predefined threshold success rate. No patients developed IFI. The treatment completion rate was 73.8 %, and only two cases ceased treatment because of adverse events. The most frequent events were reversible electrolyte abnormalities. We consider low-dose L-AMB to provide comparable efficacy and improved safety and cost-effectiveness when compared with other empirical antifungal therapies. Additional large-scale randomized studies are needed to determine the clinical usefulness of L-AMB relative to other empirical antifungal therapies.

Comparison of intermediate-dose methotrexate with cranial irradiation for the post-induction treatment of acute lymphocytic leukemia in children

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

Freeman, A.I.; Weinberg, V.; Brecher, M.L.

1983-03-03

The authors compared two regimens with respect to their ability to prolong disease-free survival in 506 children and adolescents with acute lymphocytic leukemia. All responders to induction therapy were randomized to treatment with 2400 rad of cranial irradiation plus intrathecal methotrexate or to treatment with intermediate-dose methotrexate plus intrathecal methotrexate, as prophylaxis for involvement of the central nervous system and other sanctuary areas. Complete responders were stratified into either standard-risk or increased-risk groups on the basis of age and white-cell count at presentation. Among patients with standard risk, hematologic relapses occurred in 9 of 117 given methotrexate and 24 ofmore » 120 given irradiation. The rate of central-nervous-system relapse was higher in the methotrexate group (23 of 117) than in the irradiation group. Among patients with increased risk, radiation offered greater protection to the central nervous system than methotrexate; there was no difference in the rate of hematologic relapse. Methotrexate offered better protection against systemic relapse in standard-risk patients and better protection against testicular relapse overall, but it offered less protection against relapses in the central nervous system than cranial irradiation.« less

21 CFR 864.9285 - Automated cell-washing centrifuge for immuno-hematology.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Automated cell-washing centrifuge for immuno... Establishments That Manufacture Blood and Blood Products § 864.9285 Automated cell-washing centrifuge for immuno-hematology. (a) Identification. An automated cell-washing centrifuge for immuno-hematology is a device used...

21 CFR 864.9285 - Automated cell-washing centrifuge for immuno-hematology.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Automated cell-washing centrifuge for immuno... Establishments That Manufacture Blood and Blood Products § 864.9285 Automated cell-washing centrifuge for immuno-hematology. (a) Identification. An automated cell-washing centrifuge for immuno-hematology is a device used...

21 CFR 864.9285 - Automated cell-washing centrifuge for immuno-hematology.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Automated cell-washing centrifuge for immuno... Establishments That Manufacture Blood and Blood Products § 864.9285 Automated cell-washing centrifuge for immuno-hematology. (a) Identification. An automated cell-washing centrifuge for immuno-hematology is a device used...

21 CFR 864.9285 - Automated cell-washing centrifuge for immuno-hematology.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Automated cell-washing centrifuge for immuno... Establishments That Manufacture Blood and Blood Products § 864.9285 Automated cell-washing centrifuge for immuno-hematology. (a) Identification. An automated cell-washing centrifuge for immuno-hematology is a device used...

21 CFR 864.9285 - Automated cell-washing centrifuge for immuno-hematology.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Automated cell-washing centrifuge for immuno... Establishments That Manufacture Blood and Blood Products § 864.9285 Automated cell-washing centrifuge for immuno-hematology. (a) Identification. An automated cell-washing centrifuge for immuno-hematology is a device used...

Striking hematological abnormalities in patients with microcephalic osteodysplastic primordial dwarfism type II (MOPD II): a potential role of pericentrin in hematopoiesis.

PubMed

Unal, Sule; Alanay, Yasemin; Cetin, Mualla; Boduroglu, Koray; Utine, Eda; Cormier-Daire, Valerie; Huber, Celine; Ozsurekci, Yasemin; Kilic, Esra; Simsek Kiper, Ozlem Pelin; Gumruk, Fatma

2014-02-01

Microcephalic osteodysplastic primordial dwarfism type II (MOPD II) is a rare primordial dwarfism that is similar to Seckel syndrome. Seckel syndrome is known to be associated with various hematological abnormalities; however, hematological findings in MOPD II patients have not been previously reported. The present study aimed to describe the hematological findings in a series of eight patients with MOPD II from a single center. The study included eight patients with MOPD II that were analyzed via molecular testing, and physical and laboratory examinations. Molecular testing showed that seven of the eight patients had pericentrin (PCNT) gene mutations. Hematological evaluation showed that 7 (87.5%) patients had thrombocytosis, 6 (75%) had leukocytosis, 5 (62.5%) had both leukocytosis and thrombocytosis, and 2 (25%) had anemia. We report leukocytosis and thrombocytosis as a common hematologic abnormality in patients with MOPD II. The present findings may improve our understanding of the potential function of the PCNT gene in hematopoietic cell proliferation and differentiation. © 2013 Wiley Periodicals, Inc.

[History of chronic myeloid leukemia: a paradigm in the treatment of cancer].

PubMed

Gonon-Demoulian, R; Goldman, J M; Nicolini, F E

2014-01-01

During two centuries, advances in medicine and medical research have helped to understand the pathophysiology of chronic myelogenous leukemia (CML). This hematologic malignancy is a unique model of oncogenesis where a single molecular hit, causing cell proliferation and survival, was identified. The chromosomal abnormality first highlighted by P. Nowell and D. Hungerford in 1960, and characterized as the reciprocal translocation t(9;22)(q34;q11), the Philadelphia chromosome, discovered in leukemic cells, by J. Rowley in 1973. At the end of the 20th century, the contribution of molecular biology techniques was crucial by the discovery of the BCR-ABL1 hybrid oncogene derived from the t(9;22), responsible for the translation of an aberrant protein tyrosine kinase. This BCR-ABL1 kinase deregulates signaling pathways that control normal cell cycle and survival in primitive hematopoietic cells and is thus responsible for malignant cell accumulation observed in CML. It was then only necessary to develop a targeted treatment adapted to this molecular hit. Recently, tyrosine kinase inhibitors, by their specific inhibitory activity of BCR-ABL, have revolutionized the treatment of CML, allowing rates of haematological, cytogenetic and molecular responses never seen to date, and has significantly improved the overall survival and the quality of life of patients.

Progress in the development of a transcutaneously powered axial flow blood pump ventricular assist system.

PubMed

Parnis, S M; Conger, J L; Fuqua, J M; Jarvik, R K; Inman, R W; Tamez, D; Macris, M P; Moore, S; Jacobs, G; Sweeney, M J; Frazier, O H

1997-01-01

Development of the Jarvik 2000 intraventricular assist system for long-term support is ongoing. The system integrates the Jarvik 2000 axial flow blood pump with a microprocessor based automatic motor controller to provide response to physiologic demands. Nine devices have been evaluated in vivo (six completed, three ongoing) with durations in excess of 26 weeks. Instrumented experiments include implanted transit-time ultrasonic flow probes and dual micromanometer LV/AoP catheters. Treadmill exercise and heart pacing studies are performed to evaluate control system response to increased heart rates. Pharmacologically induced cardiac dysfunction studies are performed in awake and anesthetized calves to demonstrate control response to simulated heart failure conditions. No deleterious effects or events were encountered during any physiologic studies. No hematologic, renal, hepatic, or pulmonary complications have been encountered in any study. Plasma free hemoglobin levels of 7.0 +/- 5.1 mg/dl demonstrate no device related hemolysis throughout the duration of all studies. Pathologic analysis at explant showed no evidence of thromboembolic events. All pump surfaces were free of thrombus except for a minimal ring of fibrin, (approximately 1 mm) on the inflow bearing. Future developments for permanent implantation will include implanted physiologic control systems, implanted batteries, and transcutaneous energy and data transmission systems.

High expression of ID family and IGJ genes signature as predictor of low induction treatment response and worst survival in adult Hispanic patients with B-acute lymphoblastic leukemia.

PubMed

Cruz-Rodriguez, Nataly; Combita, Alba L; Enciso, Leonardo J; Quijano, Sandra M; Pinzon, Paula L; Lozano, Olga C; Castillo, Juan S; Li, Li; Bareño, Jose; Cardozo, Claudia; Solano, Julio; Herrera, Maria V; Cudris, Jennifer; Zabaleta, Jovanny

2016-04-05

B-Acute lymphoblastic leukemia (B-ALL) represents a hematologic malignancy with poor clinical outcome and low survival rates in adult patients. Remission rates in Hispanic population are almost 30% lower and Overall Survival (OS) nearly two years inferior than those reported in other ethnic groups. Only 61% of Colombian adult patients with ALL achieve complete remission (CR), median overall survival is 11.3 months and event-free survival (EFS) is 7.34 months. Identification of prognostic factors is crucial for the application of proper treatment strategies and subsequently for successful outcome. Our goal was to identify a gene expression signature that might correlate with response to therapy and evaluate the utility of these as prognostic tool in hispanic patients. We included 43 adult patients newly diagnosed with B-ALL. We used microarray analysis in order to identify genes that distinguish poor from good response to treatment using differential gene expression analysis. The expression profile was validated by real-time PCR (RT-PCT). We identified 442 differentially expressed genes between responders and non-responders to induction treatment. Hierarchical analysis according to the expression of a 7-gene signature revealed 2 subsets of patients that differed in their clinical characteristics and outcome. Our study suggests that response to induction treatment and clinical outcome of Hispanic patients can be predicted from the onset of the disease and that gene expression profiles can be used to stratify patient risk adequately and accurately. The present study represents the first that shows the gene expression profiling of B-ALL Colombian adults and its relevance for stratification in the early course of disease.

Ruxolitinib vs best available therapy for ET intolerant or resistant to hydroxycarbamide.

PubMed

Harrison, Claire N; Mead, Adam J; Panchal, Anesh; Fox, Sonia; Yap, Christina; Gbandi, Emmanouela; Houlton, Aimee; Alimam, Samah; Ewing, Joanne; Wood, Marion; Chen, Frederick; Coppell, Jason; Panoskaltsis, Nicki; Knapper, Steven; Ali, Sahra; Hamblin, Angela; Scherber, Robyn; Dueck, Amylou C; Cross, Nicholas C P; Mesa, Ruben; McMullin, Mary Frances

2017-10-26

Treatments for high-risk essential thrombocythemia (ET) address thrombocytosis, disease-related symptoms, as well as risks of thrombosis, hemorrhage, transformation to myelofibrosis, and leukemia. Patients resistant/intolerant to hydroxycarbamide (HC) have a poor outlook. MAJIC (ISRCTN61925716) is a randomized phase 2 trial of ruxolitinib (JAK1/2 inhibitor) vs best available therapy (BAT) in ET and polycythemia vera patients resistant or intolerant to HC. Here, findings of MAJIC-ET are reported, where the modified intention-to-treat population included 58 and 52 patients randomized to receive ruxolitinib or BAT, respectively. There was no evidence of improvement in complete response within 1 year reported in 27 (46.6%) patients treated with ruxolitinib vs 23 (44.2%) with BAT ( P = .40). At 2 years, rates of thrombosis, hemorrhage, and transformation were not significantly different; however, some disease-related symptoms improved in patients receiving ruxolitinib relative to BAT. Molecular responses were uncommon; there were 2 complete molecular responses (CMR) and 1 partial molecular response in CALR- positive ruxolitinib-treated patients. Transformation to myelofibrosis occurred in 1 CMR patient, presumably because of the emergence of a different clone, raising questions about the relevance of CMR in ET patients. Grade 3 and 4 anemia occurred in 19% and 0% of ruxolitinib vs 0% (both grades) in the BAT arm, and grade 3 and 4 thrombocytopenia in 5.2% and 1.7% of ruxolitinib vs 0% (both grades) of BAT-treated patients. Rates of discontinuation or treatment switching did not differ between the 2 trial arms. The MAJIC-ET trial suggests that ruxolitinib is not superior to current second-line treatments for ET. This trial was registered at www.isrctn.com as #ISRCTN61925716. © 2017 by The American Society of Hematology.

Frontline rituximab, cyclophosphamide, doxorubicin, and prednisone with bortezomib (VR-CAP) or vincristine (R-CHOP) for non-GCB DLBCL.

PubMed

Offner, Fritz; Samoilova, Olga; Osmanov, Evgenii; Eom, Hyeon-Seok; Topp, Max S; Raposo, João; Pavlov, Viacheslav; Ricci, Deborah; Chaturvedi, Shalini; Zhu, Eugene; van de Velde, Helgi; Enny, Christopher; Rizo, Aleksandra; Ferhanoglu, Burhan

2015-10-15

This phase 2 study evaluated whether substituting bortezomib for vincristine in frontline rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy could improve efficacy in non-germinal center B-cell-like diffuse large B-cell lymphoma (non-GCB DLBCL), centrally confirmed by immunohistochemistry (Hans method). In total, 164 patients were randomized 1:1 to receive six 21-day cycles of rituximab 375 mg/m(2), cyclophosphamide 750 mg/m(2), and doxorubicin 50 mg/m(2), all IV day 1, prednisone 100 mg/m(2) orally days 1-5, plus either bortezomib 1.3 mg/m(2) IV days 1, 4, 8, 11 (rituximab, cyclophosphamide, doxorubicin, and prednisone with bortezomib [VR-CAP]; n = 84) or vincristine 1.4 mg/m(2) (maximum 2 mg) IV day 1 (R-CHOP; n = 80). There were no significant differences between VR-CAP and R-CHOP in complete response rate (64.5%, 66.2%; odds ratio [OR], 0.91; P = .80), overall response rate (93.4%, 98.6%; OR, 0.21; P = .11), progression-free survival (hazard ratio [HR], 1.12; P = .76), or overall survival (HR, 0.89; P = .75). Rates of grade ≥3 adverse events (AEs; 88%, 89%), serious AEs (38%, 34%), discontinuations due to AEs (7%, 3%), and deaths due to AEs (2%, 5%) were similar with VR-CAP and R-CHOP. Grade ≥3 peripheral neuropathy rates were 6% and 3%, respectively. VR-CAP did not improve efficacy vs R-CHOP in non-GCB DLBCL. This trial was registered at www.clinicaltrials.gov as #NCT01040871. © 2015 by The American Society of Hematology.

Combined systemic and intraventricular chemotherapy in primary CNS lymphoma: a pilot study

PubMed Central

Schlegel, U; Pels, H; Glasmacher, A; Kleinschmidt, R; Schmidt-Wolf, I; Helmstaedter, C; Fliessbach, K; Deckert, M; Van Roost, D; Fimmers, R; Bode, U; Klockgether, T

2001-01-01

The objective was to evaluate response rate, response duration, and toxicity after systemic and intraventricular chemotherapy in primary CNS lymphoma (PCNSL).
 From September 1995 to September 1998, 20 consecutive patients with PCNSL (median age 64, range 27 to 71 years) were enrolled in a pilot study evaluating chemotherapy without radiotherapy. A high dose methotrexate (MTX) (cycles 1, 2, 4, 5) and cytarabine (ara-C) (cycles 3, 6) based systemic therapy (including dexamethasone, vinca alkaloids, ifosfamide, and cyclophosphamide) was combined with intraventricular MTX, prednisolone, and ara-C.
 Complete response was achieved in 11 and partial remission in two patients; in one response could not be determined. Four patients showed progressive disease and two (70, 71 years) died from treatment related complications. Observation time was 2 to 59 months (median 31.5 months). Kaplan-Meier estimate for median time to treatment failure (TTF) was 20.5 months, and for median survival 54 months. Systemic toxicity was mainly hematological. Ommaya reservoir infection occurred in four patients and acute transient MTX induced encephalopathy in two (subacute in another). Cognitive dysfunction possibly due to treatment was seen in only one patient after relapse and after a total of 12 cycles (six at relapse).
 In conclusion, primary chemotherapy based on high dose MTX and ara-C is highly efficient in PCNSL. Toxicity is manageable in patients younger than 70years.

 PMID:11413277

Outcome of Frontline Treatment with "Generic" Imatinib In Adult Patients with Chronic Myeloid Leukemia in Algerian Population: A Multicenter Study.

PubMed

Entasoltan, B; Bekadja, M A; Touhami, H; Mehalhal, N; Zouaoui, Z; Mesli, N; Talbi, M; Bachiri, A; Michallet, M

2017-01-01

In a developing country like Algeria, such expensive therapy is not available. Alternative approaches are needed to help these adult. In Algeria 'imatib' (CIPLA-India) was introduced in 2006; but no study has been published yet in the North Africa region regarding response and outcome of this copy in CML patients. The goal of this multicenter study is to characterize newly adult CML in the western region of Algeria and to assess the effectiveness and safety of imatib (IM, copy) as frontline therapy for patients with CML. The study was carried out in 7 hematology centers in the western Algeria. Patients, who were diagnosed to be suffering from CML between January 1st, 2007 and December 31st, 2014 were selected for data analysis. All patients received a copy preparation, consisting of the alpha crystal form of imatinib, (IM, copy) at an oral dose of 400 mg daily and monitored for tolerance and side effects while on therapy. Between January 2007 and December 2014, 355 patients with CML were treated with imatib (Copy). The median follow- up of the study was 46 months (range: 13-107 months). Complete hematological response (CHR) was seen in 83% of patients within 3 months. According to the Sokal score, 72% patients with low, 78% with intermediate and 69% with high risk disease achieved a CHR in 3 months (p=0.26) and according to the EUTOS score, 81% of patients with low and 70% with high risk disease achieved a CHR in 3 months (p=0.08). The major molecular response (MMR) at six months (M6), M9, M12, M18 and M24 was 21%, 38%, 35%, 51% and 67% respectively and 34% of patients achieved a complete molecular response (CMR). The projected 5-year overall survival (OS) rate was 83%. Side effects of imatib (copy) in this study were similar to those reported previously for the entire imatinib mesylate treatment study and only 8% of patients were intolerant to imatib (copy) and treated with a second generation of BCR-ABL inhibitor. This study reflects real world experience treating patients with CML in a developing country and thus sheds light on differences in this population compared to Western countries. In conclusion, imatib (copy) is effective and safe in treating patients with CML in chronic phase and proves to have a durable outcome. To our knowledge this is the first study reporting the response to imatib (copy) in an Algerian population.

Successful treatment of refractory anemia with a combination regimen containing recombinant human erythropoietin, low-dose methylprednisolone and nandrolone.

PubMed

Tsiara, S N; Chaidos, A; Gouva, M; Christou, L; Panteli, K; Kapsali, E; Bourantas, K L

2004-03-01

Myelodysplastic syndromes (MDS) are a heterogenous group of hematological clonal malignancies. Patients belonging to the refractory anemia (RA) subtype are usually treated with recombinant human erythropoietin (EPO). Not all patients respond to EPO administration and they are strictly dependent on supportive therapy with red cell blood (RBC) transfusions. The aim of this study was to investigate the efficacy of an alternative combination regimen containing EPO, low-dose methylprednisolone and nandrolone decanoate, in patients with RA unresponsive to EPO administration alone. Ten patients, 4 women and 6 men, median age: 70 years (range: 55-78 years) with refractory anemia unresponsive to EPO administration and RBC transfusion-dependent were included in the study. Median hematological data at baseline were Hb: 8.7 g/dl, (range 6.2-9.8), WBC: 3.35x10(9)/l (range 2.1-4), PLT: 82.5x10(9)/l (range 59-110). EPO 150 U/Kg three times/week subcutaneously, low-dose methylprednisolone 8 mg/day orally and nandrolone decanoate (Decadurabolin) 50 mg two-times/week intramuscularly were administered. As complete response (CR) to treatment was considered the normalization of the peripheral blood and bone marrow smears and biopsy. As partial response (PR) was considered increase in Hb level > or = 2 g/dl, or up to 10 g/dl and discontinuation of RBC transfusions. The response to therapy was evaluated on the 4th week after the initiation of the combination treatment. Bone marrow smear evaluation was carried out at baseline and every six months afterwards. After a 4-week treatment all patients achieved PR and discontinued RBC transfusions. Median and range hematological values on the 4th week after treatment initiation were Hb: 11.2 g/dl, (range: 9.8-12.8), WBC: 4.4x10(9)/l (3.5-6.6), PLT: 130x10(9)/l (95-160). The increase observed in hematological values was significant (p = 0.0001, 0.0004 and < 0.0001, respectively, for Hb, WBC and PLT counts). Treatment was well tolerated. Furthermore, two women, on treatment with the combination regimen, achieved CR one after six months and the second after 12 months. They are alive after 5 years from initiation of the combination treatment. After a median period of 18 months (range 12 to 20 months) in PR three men developed acute leukemia; they received intensive antileukemic chemotherapy without any response and died during the phase of pancytopenia. Three other men achieved CR, one after 6 and two after 12 months of therapy and they are on regular follow-up. Two women after 10 and 14 months in PR developed acute leukemia and died. In conclusion, combination therapy with EPO, nandrolone decanoate and low-dose methylprednisolone may be effective as an alternative treatment for RBC transfusion-dependent patients with RA unresponsive to EPO administration alone.

Low rates of antibiotic resistance and infectious mortality in a cohort of high-risk hematology patients: A single center, retrospective analysis of blood stream infection

PubMed Central

Conn, Jason R.; Catchpoole, Elizabeth M.; Runnegar, Naomi; Mapp, Sally J.

2017-01-01

Febrile neutropenia (FN) is a medical emergency and can represent a life-threatening complication for hematology patients treated with intensive chemotherapy regimens. In clinical practice, the diagnostic yield of blood cultures and other investigations which aim to identify a causative organism or site of infection is low. We have retrospectively examined all blood cultures collected in a “real world” cohort of patients receiving chemotherapy for acute leukemia and patients with aggressive lymphoma treated with Hyper-CVAD/MTX-cytarabine, at a single tertiary center over a five-year period. In this cohort, the 30-day mortality following confirmed blood stream infection (BSI) was 5.9%, which is lower than most reports in the recent literature. We compared the blood culture results of inpatients undergoing induction chemotherapy and outpatients presenting with fevers and found a significantly higher rate of proven BSI in the outpatient group. In all settings, gram-negative organisms were most common. The rate of resistance to first-line empiric antibiotics among pathogenic isolates was 11.6% in the whole cohort, independent of blood culture circumstances. There was a trend to higher resistance rates among inpatients undergoing induction chemotherapy compared to patients presenting to the emergency department (17.4% vs 7.5%) but this did not reach statistical significance. We also report low rates of ciprofloxacin resistance (5% of isolates), in a center where universal fluoroquinolone prophylaxis is not employed. Our low resistance and mortality rates support our current therapeutic strategies, however presence of resistant organisms across the spectrum of indications for BC collection highlights the importance of surveilling local patterns, escalating antimicrobial therapy in the deteriorating patient, and considering advanced techniques for the rapid identification of resistance in this patient population. PMID:28542412

‘Trained immunity’: consequences for lymphoid malignancies

PubMed Central

Stevens, Wendy B.C.; Netea, Mihai G.; Kater, Arnon P.; van der Velden, Walter J.F.M.

2016-01-01

In hematological malignancies complex interactions exist between the immune system, microorganisms and malignant cells. On one hand, microorganisms can induce cancer, as illustrated by specific infection-induced lymphoproliferative diseases such as Helicobacter pylori-associated gastric mucosa-associated lymphoid tissue lymphoma. On the other hand, malignant cells create an immunosuppressive environment for their own benefit, but this also results in an increased risk of infections. Disrupted innate immunity contributes to the neoplastic transformation of blood cells by several mechanisms, including the uncontrolled clearance of microbial and autoantigens resulting in chronic immune stimulation and proliferation, chronic inflammation, and defective immune surveillance and anti-cancer immunity. Restoring dysfunction or enhancing responsiveness of the innate immune system might therefore represent a new angle for the prevention and treatment of hematological malignancies, in particular lymphoid malignancies and associated infections. Recently, it has been shown that cells of the innate immune system, such as monocytes/macrophages and natural killer cells, harbor features of immunological memory and display enhanced functionality long-term after stimulation with certain microorganisms and vaccines. These functional changes rely on epigenetic reprogramming and have been termed ‘trained immunity’. In this review the concept of ‘trained immunity’ is discussed in the setting of lymphoid malignancies. Amelioration of infectious complications and hematological disease progression can be envisioned to result from the induction of trained immunity, but future studies are required to prove this exciting new hypothesis. PMID:27903713

Effects of waterborne nitrite on hematological parameters and stress indicators in olive flounders, Paralichthys olivaceus, raised in bio-floc and seawater.

PubMed

Kim, Jun-Hwan; Kim, Jin-Young; Lim, Lok-Ji; Kim, Su Kyoung; Choi, Hye Sung; Hur, Young Baek

2018-06-11

Juvenile olive flounders, Paralichthys olivaceus (mean weight 2.69 ± 0.31 g), were raised in bio-floc and seawater for six months, these P. olivaceus (mean weight 280.1 ± 10.5 g, mean length 28.37 ± 2.3 cm) were exposed to different concentrations of waterborne nitrite (0, 25, 50, 100, and 200 mg NO 2 - /L) for 7 days. None of the P. olivaceus individuals exposed to bio-floc and seawater containing waterborne nitrite concentrations of 200 mg/L for 7 days survived. Hematological parameters (hemoglobin and hematocrit) were significantly reduced by nitrite exposure. Regarding plasma components, the concentrations of glucose, glutamic oxalate transaminase (GOT), and glutamic pyruvate transaminase (GPT) increased significantly in response to nitrite exposure, whereas cholesterol concentrations significantly decreased. Stress indicators, including concentrations of plasma glucose, cortisol, and liver and gill concentrations of heat shock protein 70 (HSP70) were significantly increased by nitrite exposure. The results of the study indicate that nitrite exposure affected the hematological parameters and stress indicators of P. olivaceus raised in bio-floc and seawater, and these changes were more prominent in the P. olivaceus raised in seawater than those raised in bio-floc. Copyright © 2018 Elsevier Ltd. All rights reserved.

Evaluation of the automated hematology analyzer ADVIA® 120 for cerebrospinal fluid analysis and usage of unique hemolysis reagent.

PubMed

Tanada, H; Ikemoto, T; Masutani, R; Tanaka, H; Takubo, T

2014-02-01

In this study, we evaluated the performance of the ADVIA 120 hematology system for cerebrospinal fluid (CSF) assay. Cell counts and leukocyte differentials in CSF were examined with the ADVIA 120 hematology system, while simultaneously confirming an effective hemolysis agent for automated CSF cell counts. The detection limits of both white blood cell (WBC) counts and red blood cell (RBC) counts on the measurement of CSF cell counts by the ADVIA 120 hematology system were superior at 2 cells/μL (10(-6) L). The WBC count was linear up to 9.850 cells/μL, and the RBC count was linear up to approximately 20 000 cells/μL. The intrarun reproducibility indicated good precision. The leukocyte differential of CSF cells, performed by the ADVIA120 hematology system, showed good correlation with the microscopic procedure. The VersaLyse hemolysis solution efficiently lysed the samples without interfering with cell counts and leukocyte differential, even in a sample that included approximately 50 000/μL RBC. These data show the ADVIA 120 hematology system correctly measured the WBC count and leukocyte differential in CSF. The VersaLyse hemolysis solution is considered to be optimal for hemolysis treatment of CSF when measuring cell counts and differentials by the ADVIA 120 hematology system. © 2013 John Wiley & Sons Ltd.

Hematology, Serum Chemistry, and Early Hematologic Changes in Free-Ranging South American Fur Seals ( Arctocephalus australis ) at Guafo Island, Chilean Patagonia.

PubMed

Seguel, Mauricio; Muñoz, Francisco; Keenan, Alessandra; Perez-Venegas, Diego J; DeRango, Eugene; Paves, Hector; Gottdenker, Nicole; Müller, Ananda

2016-07-01

The establishment of clinical pathology baseline data is critical to evaluate temporal and spatial changes in marine mammal groups. Despite increased availability of studies on hematology and biochemistry of marine mammals, reference ranges are lacking for many populations, especially among fur seal species. During the austral summers of 2014 and 2015, we evaluated basic hematologic and biochemical parameters in clinically healthy, physically restrained South American fur seal ( Arctocephalus australis ) lactating females and 2-mo-old pups. We also assessed the temporal variation of hematology parameters on the pups during their first 2 mo of life. Reference ranges of lactating females were similar to those previously reported in other fur seal species. In the case of pups, reference ranges are similar to values previously reported in sea lion species. As expected, most biochemical and hematologic values differ significantly between adult females and pups. As in other otariids, South American fur seals pups are born with higher values of total red blood cells, hemoglobin, and packed cell volume, and lower numbers of total leukocytes, neutrophils, lymphocytes, and eosinophils. To the best of our knowledge, data on hematology reference values for South American fur seals has not been previously reported and is useful for continued health monitoring of this species, as well as for comparisons with other otariid groups.

Success rate and risk factors for failure of empirical antifungal therapy with itraconazole in patients with hematological malignancies: a multicenter, prospective, open-label, observational study in Korea.

PubMed

Kim, Soo-Jeong; Cheong, June-Won; Min, Yoo Hong; Choi, Young Jin; Lee, Dong-Gun; Lee, Je-Hwan; Yang, Deok-Hwan; Lee, Sang Min; Kim, Sung-Hyun; Kim, Yang Soo; Kwak, Jae-Yong; Park, Jinny; Kim, Jin Young; Kim, Hoon-Gu; Kim, Byung Soo; Ryoo, Hun-Mo; Jang, Jun Ho; Kim, Min Kyoung; Kang, Hye Jin; Cho, In Sung; Mun, Yeung Chul; Jo, Deog-Yeon; Kim, Ho Young; Park, Byeong-Bae; Kim, Jin Seok

2014-01-01

We assessed the success rate of empirical antifungal therapy with itraconazole and evaluated risk factors for predicting the failure of empirical antifungal therapy. A multicenter, prospective, observational study was performed in patients with hematological malignancies who had neutropenic fever and received empirical antifungal therapy with itraconazole at 22 centers. A total of 391 patients who had abnormal findings on chest imaging tests (31.0%) or a positive result of enzyme immunoassay for serum galactomannan (17.6%) showed a 56.5% overall success rate. Positive galactomannan tests before the initiation of the empirical antifungal therapy (P=0.026, hazard ratio [HR], 2.28; 95% confidence interval [CI], 1.10-4.69) and abnormal findings on the chest imaging tests before initiation of the empirical antifungal therapy (P=0.022, HR, 2.03; 95% CI, 1.11-3.71) were significantly associated with poor outcomes for the empirical antifungal therapy. Eight patients (2.0%) had premature discontinuation of itraconazole therapy due to toxicity. It is suggested that positive galactomannan tests and abnormal findings on the chest imaging tests at the time of initiation of the empirical antifungal therapy are risk factors for predicting the failure of the empirical antifungal therapy with itraconazole. (Clinical Trial Registration on National Cancer Institute website, NCT01060462).

Blastic plasmacytoid dendritic cell neoplasm: update on molecular biology, diagnosis, and therapy.

PubMed

Riaz, Wasif; Zhang, Ling; Horna, Pedro; Sokol, Lubomir

2014-10-01

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with an aggressive clinical course. Most patients with BPDCN have skin lesions and simultaneous involvement of the peripheral blood, bone marrow, and lymph nodes. A search of PubMed and Medline was conducted for English-written articles relating to BPDCN, CD4(+)CD56(+) hematodermic neoplasm, and blastic natural killer cell lymphoma. Data regarding diagnosis, prognosis, and treatment were analyzed. BPDCN is derived from precursor plasmacytoid dendritic cells. The diagnosis of BPDCN is based on the characteristic cytology and immunophenotype of malignant cells coexpressing CD4, CD56, CD123, blood dendritic cell antigens 2 and 4, and CD2AP markers. Multiple chromosomal abnormalities and gene mutations previously reported in patients with myeloid and selected lymphoid neoplasms were identified in approximately 60% of patients with BPDCN. Prospectively controlled studies to guide treatment decisions are lacking. The overall response rate with aggressive acute lymphoblastic leukemia-type induction regimens was as high as 90%, but the durability of response was short. Median survival rates ranged between 12 and 16 months. Patients with relapsed disease may respond to L-asparaginase-containing regimens. Allogeneic hematopoietic stem cell transplantation, particularly when performed during the first remission, may produce durable remissions in selected adults. BPDCN is a rare aggressive disease that typically affects elderly patients. The most commonly affected nonhematopoietic organ is the skin. Although BPDCN is initially sensitive to conventional chemotherapy regimens, this response is relatively short and long-term prognosis is poor. In the near future, novel targeted therapies may improve outcomes for patients with BPDCN.

Biomarkers of Type II Synthetic Pyrethroid Pesticides in Freshwater Fish

PubMed Central

2014-01-01

Type II synthetic pyrethroids contain an alpha-cyano group which renders them more neurotoxic than their noncyano type I counterparts. A wide array of biomarkers have been employed to delineate the toxic responses of freshwater fish to various type II synthetic pyrethroids. These include hematological, enzymatic, cytological, genetic, omic and other types of biomarkers. This review puts together the applications of different biomarkers in freshwater fish species in response to the toxicity of the major type II pyrethroid pesticides and assesses their present status, while speculating on the possible future directions. PMID:24868555

Hematology and immunology studies

NASA Technical Reports Server (NTRS)

Kimzey, S. L.

1977-01-01

A coordinated series of experiments were conducted to evaluate immunologic and hemotologic system responses of Skylab crewmen to prolonged space flights. A reduced PHA responsiveness was observed on recovery, together with a reduced number of T-cells, with both values returning to normal 3 to 5 days postflight. Subnormal red cell count, hemoglobin concentration, and hematocrit values also returned gradually to preflight limits. Most pronounced changes were found in the shape of red blood cells during extended space missions with a rapid reversal of these changes upon reentry into a normal gravitational environment.

Biomarkers of type II synthetic pyrethroid pesticides in freshwater fish.

PubMed

Kaviraj, Anilava; Gupta, Abhik

2014-01-01

Type II synthetic pyrethroids contain an alpha-cyano group which renders them more neurotoxic than their noncyano type I counterparts. A wide array of biomarkers have been employed to delineate the toxic responses of freshwater fish to various type II synthetic pyrethroids. These include hematological, enzymatic, cytological, genetic, omic and other types of biomarkers. This review puts together the applications of different biomarkers in freshwater fish species in response to the toxicity of the major type II pyrethroid pesticides and assesses their present status, while speculating on the possible future directions.

Seasonal variation in hematology and blood plasma chemistry values of the timber rattlesnake (Crotalus horridus).

PubMed

LaGrange, Seth M; Kimble, Steven J A; MacGowan, Brian J; Williams, Rod N

2014-10-01

Hematology, biochemical analyses, and body condition indices are useful tools for describing animal health, especially when making management decisions for species of conservation concern. We report hematologic, biochemical, and body condition index data for 13 free-ranging timber rattlesnakes (Crotalus horridus) sampled repeatedly over an active season in Indiana, USA.

Single-unit umbilical cord blood transplantation from unrelated donors in patients with hematological malignancy using busulfan, thiotepa, fludarabine and ATG as myeloablative conditioning regimen.

PubMed

Sanz, J; Boluda, J C H; Martín, C; González, M; Ferrá, C; Serrano, D; de Heredia, C D; Barrenetxea, C; Martinez, A M; Solano, C; Sanz, M A; Sanz, G F

2012-10-01

Attempts to optimize outcomes in cord blood transplantation (CBT) by using new conditioning regimens and standardization of cord blood unit selection are warranted. In all, 88 patients (18 children and 70 adults) with hematological malignancy from nine Spanish institutions underwent a single-unit CBT after an i.v. BU-based myeloablative conditioning regimen. All evaluable patients except one engrafted. The overall cumulative incidence (CI) of myeloid engraftment was 94% at a median time of 19 days. In multivariate analysis, nonadvanced disease stage was the only factor with a favorable impact on myeloid engraftment. The CI of acute GVHD grades II-IV and chronic extensive GVHD were 24% each. The CI of nonrelapse mortality at 100 days, 180 days and 5 years was 14, 23 and 44%, respectively. The 5-year CI of relapse was 18%, whereas disease-free survival (DFS) was 46%, 39% and 11% for patients transplanted in early, intermediate and advanced stages of the disease, respectively. Our study shows high rates of engraftment with fast neutrophil recovery in patients undergoing single-unit CBT using a BU-based conditioning regimen. Long-term DFS can be achieved in a substantial number of patients with high-risk hematological malignancies, particularly when transplanted in an early stage of the disease.

Radiological, histological, and hematological evaluation of hydroxyapatite-coated resorbable magnesium alloy screws placed in rabbit tibia.

PubMed

Lim, Ho-Kyung; Byun, Soo-Hwan; Lee, Jin-Yong; Lee, Jung-Woo; Kim, Sae-Mi; Lee, Sung-Mi; Kim, Hyoun-Ee; Lee, Jong-Ho

2017-08-01

Titanium (Ti) screw has excellent mechanical property, and osseointegration capacity. However, they require surgery for removal. In contrast, polymer screws are resorbable, but they have poor mechanical properties. In this research, magnesium alloy screws (WE43: Mg-Y-Nd-Zr) that have advantages of titanium and polymer were manufactured. In addition, to increase biocompatibility and control degradation rate, the Mg alloy was coated with hydroxyapatite (HA). Torsion test and corrosion test were performed in vitro. For clinical, radiological and histological evaluation, on the eight rabbits, two HA-coated screws were installed in left tibia, and two noncoated screws were installed in right tibia. Each four rabbits were sacrificed 6 and 12 weeks postoperatively. For hematological evaluation, the same type of screws were installed on both legs. Complete blood count (CBC), Mg 2+ concentrate were sampled from the ear central artery on the operation day for a control point, and at 1, 2, 4, 6, 8, and 12 weeks. Mg alloy screws have no differences of biocompatibility according to the HA coating. However, resorption of screw was slower in case of the HA coating. The hematological problem related releasing of Mg was not found. The results suggest that Mg alloy screws have feasibility for clinical application. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1636-1644, 2017. © 2016 Wiley Periodicals, Inc.

Performance evaluation of Samsung LABGEO(HC10) Hematology Analyzer.

PubMed

Park, Il Joong; Ahn, Sunhyun; Kim, Young In; Kang, Seon Joo; Cho, Sung Ran

2014-08-01

The Samsung LABGEO(HC10) Hematology Analyzer (LABGEO(HC10)) is a recently developed automated hematology analyzer that uses impedance technologies. The analyzer provides 18 parameters including 3-part differential at a maximum rate of 80 samples per hour. To evaluate the performance of the LABGEO(HC10). We evaluated precision, linearity, carryover, and relationship for complete blood cell count parameters between the LABGEO(HC10) and the LH780 (Beckman Coulter Inc) in a university hospital in Korea according to the Clinical and Laboratory Standards Institute guidelines. Sample stability and differences due to the anticoagulant used (K₂EDTA versus K₃EDTA) were also evaluated. The LABGEO(HC10) showed linearity over a wide range and minimal carryover (<1%) for white blood cell, hemoglobin, red blood cell, and platelet parameters. Correlation between the LABGEO(HC10) and the LH780 was good for all complete blood cell count parameters (R > 0.92) except for mean corpuscular hemoglobin concentration. The bias estimated was acceptable for all parameters investigated except for monocyte count. Most parameters were stable until 24 hours both at room temperature and at 4°C. The difference by anticoagulant type was statistically insignificant for all parameters except for a few red cell parameters. The accurate results achievable and simplicity of operation make the unit recommendable for small to medium-sized laboratories.

Non-alcoholic fatty liver disease fibrosis score predicts hematological toxicity of chemotherapy including irinotecan for colorectal cancer.

PubMed

Yahagi, Masashi; Tsuruta, Masashi; Hasegawa, Hirotoshi; Okabayashi, Koji; Kitagawa, Yuko

2017-04-01

Liver dysfunction that may affect drug metabolism is a major concern in patients treated with chemotherapy. Thus, assessment of the degree of liver dysfunction is crucial for predicting the adverse events of chemotherapy. The non-alcoholic fatty liver disease fibrosis score (NFS) is a non-invasive clinical scoring system constructed from routine clinical and laboratory variables. The aim of this study was to evaluate whether NFS was useful for predicting the adverse events of chemotherapy including irinotecan (CPT-11) for colorectal cancer. Between January, 2007 and May, 2013, a total of 87 patients with unresectable/recurrent colorectal cancer who received first-line chemotherapy including CPT-11 were reviewed. Demographic variables, including pretreatment NFS, were retrospectively collected from medical records. The primary outcome was the association between pretreatment NFS and adverse events, such as hematological and non-hematological toxicity, of chemotherapy including CPT-11. The median pretreatment NFS was 1.302 (range, 5.158-2.620). Pretreatment NFS was an independent risk factor for hematological toxicity in a multivariate analysis (coefficient=0.932, 95% CI: 0.083-1.781; P=0.031). Receiver operating characteristic curve analysis identified 0.347 as the optimal cut-off value associated with hematological toxicity. Using this cut-off, high NFS was found to be a significant risk factor for hematological toxicity (coefficient=2.019, 95% CI: 0.239-3.798, P=0.026), but not for non-hematological toxicity (P=0.546). Therefore, based on these results, NFS appears to be a significant predictor of hematological adverse events in chemotherapy including CPT-11 for colorectal cancer and it is a non-invasive, useful tool that may be used for determining regimens or doses of chemotherapy including CPT-11.

Proceedings from the 1st Insights in Hematology Symposium, Cluj-Napoca, Romania March 11-12, 2016.

PubMed

Bojan, Anca; Berindan-Neagoe, Ioana; Ciurea, S; Dima, Delia; Fuji, Shigeo; Ghiaur, G; Grewal, Ravnit; Mccormack, Emmet; Tanase, Alina; Trifa, A; Tomuleasa, Ciprian

2016-09-01

In the March 2016 issue of the Lancet Haematology, the editorial office published a paper stating the roadmap for European research in hematology, based on the European Hematology Association (EHA) consensus document that outlines the directions in hematology for the following years across the continent. The meeting entitled "Insights in hematology" is organized a support for the initiative of a roadmap for European hematologists regarding research, may it be basic research or clinical research, but this consensus should not be focused mainly on European institutions, but rather form the backbone of global research between Europe and the United States, Japan or any other country. This will allow Europeans to learn as well as to share their experience with the rest of the scientific and medical community. And the Cluj-Napoca meeting should be followed by other such meetings all across the EU.

Immune thrombocytopenia: No longer ‘idiopathic’

PubMed Central

McCRAE, KEITH

2012-01-01

Immune thrombocytopenia (ITP) is a common hematologic disorder. Its pathogenesis involves both accelerated platelet destruction and impaired platelet production. First-line agents are usually effective initially but do not provide long-term responses. Splenectomy remains an effective long-term therapy, as does rituximab (Rituxan) in a subset of patients. Thrombopoietic agents offer a new alternative, although their place in the overall management of ITP remains uncertain. PMID:21632906

Hematology Expert System (HES) For Tonsillectomy/Adenoidectomy Patients

NASA Astrophysics Data System (ADS)

Pizzi, Nicolino J.; Kapoor, Sandhya; Gerrard, Jon M.

1989-03-01

The purpose of this expert system is to assess a predisposition to bleeding in a patient undergoing a tonsillectomy and/or adenoidectomy as may occur with patients who have certain blood conditions such as hemophilia and von Willebrand's disease. This goal is achieved by establishing a correlation between the patients' responses to a medical questionnaire and the relative quantities of blood lost during the operation.

Efficacy and Biological Correlates of Response in a Phase II Study of Venetoclax Monotherapy in Patients with Acute Myelogenous Leukemia.

PubMed

Konopleva, Marina; Pollyea, Daniel A; Potluri, Jalaja; Chyla, Brenda; Hogdal, Leah; Busman, Todd; McKeegan, Evelyn; Salem, Ahmed Hamed; Zhu, Ming; Ricker, Justin L; Blum, William; DiNardo, Courtney D; Kadia, Tapan; Dunbar, Martin; Kirby, Rachel; Falotico, Nancy; Leverson, Joel; Humerickhouse, Rod; Mabry, Mack; Stone, Richard; Kantarjian, Hagop; Letai, Anthony

2016-10-01

We present a phase II, single-arm study evaluating 800 mg daily venetoclax, a highly selective, oral small-molecule B-cell leukemia/lymphoma-2 (BCL2) inhibitor in patients with high-risk relapsed/refractory acute myelogenous leukemia (AML) or unfit for intensive chemotherapy. Responses were evaluated following revised International Working Group (IWG) criteria. The overall response rate was 19%; an additional 19% of patients demonstrated antileukemic activity not meeting IWG criteria (partial bone marrow response and incomplete hematologic recovery). Twelve (38%) patients had isocitrate dehydrogenase 1/2 mutations, of whom 4 (33%) achieved complete response or complete response with incomplete blood count recovery. Six (19%) patients had BCL2-sensitive protein index at screening, which correlated with time on study. BH3 profiling was consistent with on-target BCL2 inhibition and identified potential resistance mechanisms. Common adverse events included nausea, diarrhea and vomiting (all grades), and febrile neutropenia and hypokalemia (grade 3/4). Venetoclax demonstrated activity and acceptable tolerability in patients with AML and adverse features. Venetoclax monotherapy demonstrated clinical activity in patients with AML (relapsed/refractory or unfit for intensive chemotherapy) with a tolerable safety profile in this phase II study. Predictive markers of response consistent with BCL2 dependence were identified. Clinical and preclinical findings provide a compelling rationale to evaluate venetoclax combined with other agents in AML. Cancer Discov; 6(10); 1106-17. ©2016 AACRSee related commentary by Pullarkat and Newman, p. 1082This article is highlighted in the In This Issue feature, p. 1069. ©2016 American Association for Cancer Research.

[{sup 18}F]FDG-PET Standard Uptake Value as a Metabolic Predictor of Bone Marrow Response to Radiation: Impact on Acute and Late Hematological Toxicity in Cervical Cancer Patients Treated With Chemoradiation Therapy

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

Elicin, Olgun; Callaway, Sharon; Prior, John O.

2014-12-01

Purpose: To quantify the relationship between bone marrow (BM) response to radiation and radiation dose by using {sup 18}F-labeled fluorodeoxyglucose positron emission tomography [{sup 18}F]FDG-PET standard uptake values (SUV) and to correlate these findings with hematological toxicity (HT) in cervical cancer (CC) patients treated with chemoradiation therapy (CRT). Methods and Materials: Seventeen women with a diagnosis of CC were treated with standard doses of CRT. All patients underwent pre- and post-therapy [{sup 18}F]FDG-PET/computed tomography (CT). Hemograms were obtained before and during treatment and 3 months after treatment and at last follow-up. Pelvic bone was autosegmented as total bone marrow (BM{sub TOT}).more » Active bone marrow (BM{sub ACT}) was contoured based on SUV greater than the mean SUV of BM{sub TOT}. The volumes (V) of each region receiving 10, 20, 30, and 40 Gy (V{sub 10}, V{sub 20}, V{sub 30}, and V{sub 40}, respectively) were calculated. Metabolic volume histograms and voxel SUV map response graphs were created. Relative changes in SUV before and after therapy were calculated by separating SUV voxels into radiation therapy dose ranges of 5 Gy. The relationships among SUV decrease, radiation dose, and HT were investigated using multiple regression models. Results: Mean relative pre-post-therapy SUV reductions in BM{sub TOT} and BM{sub ACT} were 27% and 38%, respectively. BM{sub ACT} volume was significantly reduced after treatment (from 651.5 to 231.6 cm{sup 3}, respectively; P<.0001). BM{sub ACT} V{sub 30} was significantly correlated with a reduction in BM{sub ACT} SUV (R{sup 2}, 0.14; P<.001). The reduction in BM{sub ACT} SUV significantly correlated with reduction in white blood cells (WBCs) at 3 months post-treatment (R{sup 2}, 0.27; P=.04) and at last follow-up (R{sup 2}, 0.25; P=.04). Different dosimetric parameters of BM{sub TOT} and BM{sub ACT} correlated with long-term hematological outcome. Conclusions: The volumes of BM{sub TOT} and BM{sub ACT} that are exposed to even relatively low doses of radiation are associated with a decrease in WBC counts following CRT. The loss in proliferative BM SUV uptake translates into low WBC nadirs after treatment. These results suggest the potential of intensity modulated radiation therapy to spare BM{sub TOT} to reduce long-term hematological toxicity.« less

Treatment with DAV for advanced-stage hemangiosarcoma in dogs.

PubMed

Dervisis, Nikolaos G; Dominguez, Pedro A; Newman, Rebecca G; Cadile, Casey D; Kitchell, Barbara E

2011-01-01

Hemangiosarcoma (HSA) is an aggressive disease that is fairly common in the dog. The authors evaluated a doxorubicin, dacarbazine, and vincristine (DAV) combination protocol in dogs with nonresectable stage II and stage III HSA. Twenty-four dogs were enrolled in this prospective, phase 2 study. Doxorubicin and dacarbazine were administered on day 1 while vincristine was administered on days 8 and 15. The protocol was repeated every 21 days for a maximum of six cycles or until disease progression. Toxicity and efficacy were assessed by clinical and laboratory evaluation and by questionnaires completed by the owners. Of the 24 included dogs, 19 were evaluable for response. The response rate (including five complete responses and four partial responses) was 47.4%. Median time to tumor progression was 101 days and median overall survival was 125 days. Significant toxicities were noted, including 41 high-grade hematologic and 12 high-grade gastrointestinal toxic events. Five dogs discontinued treatment due to chemotherapy-related toxicities, but no treatment-related deaths occurred. Multivariate analysis identified patient age (relative risk [RR], 2.3, P=0.049) to be negatively associated with time to progression whereas dacarbazine dose reductions (RR, 0.06, P=0.031) were positively associated with time to progression. Dacarbazine dose reduction was the sole factor positively associated with overall survival (RR, 0.28, P=0.015). In conclusion, the DAV combination appears to offer clinical responses and may prolong survival in dogs with advanced-stage HSA.

Management strategies in pancreatic cancer.

PubMed

Campen, Christopher J; Dragovich, Tomislav; Baker, Amanda F

2011-04-01

Current first-line and adjuvant chemotherapeutic strategies for management of patients with pancreatic cancer are reviewed. Pancreatic adenocarcinoma is the 10th most prevalent cancer and the fourth most common cause of cancer deaths in the United States. More than 80% of patients with pancreatic cancer are diagnosed with locally advanced or metastatic disease and are not candidates for surgery; these patients often require multimodal treatment. The most widely used chemotherapy for such patients, as well as patients requiring adjuvant therapy after surgery, is gemcitabine or gemcitabine-based chemotherapy. All current chemotherapies for pancreatic cancer are associated with dose-limiting hematologic toxicity and other adverse effects that require ongoing monitoring and dosage adjustment to balance the benefits and risks of treatment. Pharmacists can play an important role in monitoring and providing drug information and guidance to patients and oncologists. Current investigational strategies include efforts to improve chemotherapy response rates and outcomes through modulation of cell signaling pathways and use of nanotechnology to improve drug delivery. Current management of pancreatic cancer is multifaceted, involving anticancer therapy, supportive care, and toxicity management. Standard systemic therapy with gemcitabine as a single agent or in combination with other cytotoxic agents provides modest benefits in terms of response and symptom control.

Mutual Benefit for Foreign Medical Students and Chinese Postgraduates: A Mixed Team-Based Learning Method Overcomes Communication Problems in Hematology Clerkship

ERIC Educational Resources Information Center

Chen, Xianling; Chen, Buyuan; Li, Xiaofan; Song, Qingxiao; Chen, Yuanzhong

2017-01-01

Hematology is difficult for students to learn. A beneficial education method for hematology clerkship training is required to help students develop clinical skills. Foreign medical students often encounter communication issues in China. To address this issue, Chinese post-graduates from our institute are willing to assist with educating foreign…

A report of three cases of untreated Graves' disease associated with pancytopenia in Malaysia.

PubMed

Rafhati, Abdullah Noor; See, Chee Keong; Hoo, Fan Kee; Badrulnizam, Long Bidin Mohamed

2014-01-01

Generally, clinical presentations of Graves' disease range from asymptomatic disease to overt symptomatic hyperthyroidism with heat intolerance, tremor, palpitation, weight loss, and increased appetite. However, atypical presentation of Graves' disease with hematological system involvement, notably pancytopenia, is distinctly uncommon. Hereby, we present and discuss a series of three untreated cases of Graves' disease clinically presented with pancytopenia and the hematological abnormalities that responded well to anti-thyroid treatment. With resolution of the thyrotoxic state, the hematological parameters improved simultaneously. Thus, it is crucial that anti-thyroid treatment be considered in patients with Graves' disease and pancytopenia after a thorough hematological evaluation.

Reference values of clinical chemistry and hematology parameters in rhesus monkeys (Macaca mulatta).

PubMed

Chen, Younan; Qin, Shengfang; Ding, Yang; Wei, Lingling; Zhang, Jie; Li, Hongxia; Bu, Hong; Lu, Yanrong; Cheng, Jingqiu

2009-01-01

Rhesus monkey models are valuable to the studies of human biology. Reference values for clinical chemistry and hematology parameters of rhesus monkeys are required for proper data interpretation. Whole blood was collected from 36 healthy Chinese rhesus monkeys (Macaca mulatta) of either sex, 3 to 5 yr old. Routine chemistry and hematology parameters, and some special coagulation parameters including thromboelastograph and activities of coagulation factors were tested. We presented here the baseline values of clinical chemistry and hematology parameters in normal Chinese rhesus monkeys. These data may provide valuable information for veterinarians and investigators using rhesus monkeys in experimental studies.

Nutritional status among pediatric cancer patients: a comparison between hematological malignancies and solid tumors.

PubMed

Tah, Pei Chien; Nik Shanita, Safii; Poh, Bee Koon

2012-10-01

This study aimed to compare the nutritional status of pediatric patients with hematological malignancies and solid tumors. A total of 74 pediatric cancer patients were assessed for anthropometric status, biochemical profiles, and dietary intake. The prevalence of undernutrition was higher among patients with solid tumors as reflected in their lower dietary intakes of energy and nutrients compared with patients with hematological malignancies. Adequate dietary intake is important for pediatric cancer patients, but nurses need to pay more attention to the diets of patients with solid tumors as compared with those with hematological malignancies. © 2012, Wiley Periodicals, Inc.

Seasonal variations in red deer (Cervus elaphus) hematology related to antler growth and biometrics measurements.

PubMed

Gaspar-López, Enrique; Landete-Castillejos, Tomás; Estevez, Jose Antonio; Ceacero, Francisco; Gallego, Laureano; García, Andrés Jose

2011-04-01

The aim of the study was to relate seasonal hematology changes with the rest of physiological variations suffered by red deer, such as antler and biometrics cycle, and to assess the relationship between hematology and the effort performed in antler development. Blood samples were taken from 21 male red deer every 4 weeks during 18 months. Samples were analyzed for the main hematological parameters. Simultaneously, biometrics measurements were taken, such as antler length, body weight, body condition score, testicular diameter (TD), and thoracic and neck girth. All the blood cell types (erythrocytes, leukocytes, and platelets) showed seasonal variations, increasing as antler cleaning approached, as did hematocrit and hemoglobin. The final size of antlers was negatively related to leukocyte count, nonlymphoid leukocyte count, red cell distribution width, mean corpuscular hemoglobin, mean platelet volume, and TD, whereas it was positively related to body condition during antler growth. Huge seasonal variations in some hematological values have been found to be related to changes in antler and biometrics measurements. Since these variations are even greater than the caused by deer handling, they should be taken into account when evaluating hematology in deer populations. Copyright © 2011 Wiley-Liss, Inc., A Wiley Company.

Canine and feline hematology reference values for the ADVIA 120 hematology system.

PubMed

Moritz, Andreas; Fickenscher, Yvonne; Meyer, Karin; Failing, Klaus; Weiss, Douglas J

2004-01-01

The ADVIA 120 is a laser-based hematology analyzer with software applications for animal species. Accurate reference values would be useful for the assessment of new hematologic parameters and for interlaboratory comparisons. The goal of this study was to establish reference intervals for CBC results and new parameters for RBC morphology, reticulocytes, and platelets in healthy dogs and cats using the ADVIA 120 hematology system. The ADVIA 120, with multispecies software (version 1.107-MS), was used to analyze whole blood samples from clinically healthy dogs (n=46) and cats (n=61). Data distribution was determined and reference intervals were calculated as 2.5 to 97.5 percentiles and 25 to 75 percentiles. Most data showed Gaussian or log-normal distribution. The numbers of RBCs falling outside the normocytic-normochromic range were slightly higher in cats than in dogs. Both dogs and cats had reticulocytes with low, medium, and high absorbance. Mean numbers of large platelets and platelet clumps were higher in cats compared with dogs. Reference intervals obtained on the ADVIA 120 provide valuable baseline information for assessing new hematologic parameters and for interlaboratory comparisons. Differences compared with previously published reference values can be attributed largely to differences in methodology.

Antimicrobial resistance patterns, clinical features, and risk factors for septic shock and death of nosocomial E coli bacteremia in adult patients with hematological disease: A monocenter retrospective study in China.

PubMed

Ma, Jie; Li, Ning; Liu, Yajie; Wang, Chong; Liu, Xiaoyan; Chen, Shengmei; Xie, Xinsheng; Gan, Silin; Wang, Meng; Cao, Weijie; Wang, Fang; Liu, Yanfan; Wan, Dingming; Sun, Ling; Sun, Hui

2017-05-01

The aim of this retrospective analysis was to evaluate the antimicrobial resistance, clinical features, and risk factors for septic shock and death of nosocomial E coli bacteremia in adult patients in a single hematological center in China. A retrospective case-control study of 157 adult hematological patients with 168 episodes of E coli bacteremia was initiated from April 2012 to July 2015. Antimicrobial susceptibility as well as antimicrobial co-resistance rates were analyzed. Clinical features and outcomes were also studied. In addition, risk factors for septic shock and death were investigated. Among the 553 positive blood isolates during the study period, the prevalence of E coli was 33.3% and ESBL production strains represented 61.9% of those examined. In all the E coli strains isolated, 85.6% were multidrug-resistance (MDR), 2.4% were extensive drug resistance (XDR), and 6.0% were resistant to carbapenems. More MDR phenotype was noted in ESBL-EC strains (98.6% vs 62.8%, P<.001) and isolates from neutropenic patients (98.6% vs 62.8%, P < .001). In the antimicrobial susceptibility test, carbapenems and amikacin exhibited not only higher in vitro activity against E coli (94.0% and 92.0%, respectively), but lower co-resistance rates to other antibiotics. Carbapenem resistant strains retained full sensitivity to tigecycline and 60% to amikacin. Piperacillin/tazobatam was the third sensitive drug to both ESBL-EC (77.1%) and non-ESBL-EC (86.0%). In our series, 81.6% episodes received appropriate initial antibiotic treatment and no significant decrease in it was found in bacteremia due to ESBL E coli and patients with neutropenia, septic shock. Septic shock was noted in 15.5% patients and the overall 30-day mortality rate was 21.7%. Multivariate analysis revealed that induction chemotherapy (OR 2.126; 95% CI 1.624-11.332; P = .003) and polymicrobial infection (OR 3.628; 95% CI 1.065-21.219; P = .041) were risk factors for septic shock, whereas male (OR 2.223; 95% CI 1.132-12.022; P < .01) and septic shock (OR 52.359; 95% CI 19.951-292.690; P = .030) were risk factors for death.In the hematology department, ESBL-producing and MDR are widely prevalent in E coli bacteremia which is still a major life-threatening problem, especially for patients with septic shock. For empirical antimicrobial therapy, combination based on aminoglycoside, especially amikacin, will be helpful to increase the antimicrobial coverage against ESBL-EC while combining tigecycline with aminoglycoside should be considered for seriously carbapenem-resistant infectious patients.

Post-Transplant Cyclophosphamide and Tacrolimus-Mycophenolate Mofetil Combination Prevents Graft-versus-Host Disease in Allogeneic Peripheral Blood Hematopoietic Cell Transplantation from HLA-Matched Donors.

PubMed

Carnevale-Schianca, Fabrizio; Caravelli, Daniela; Gallo, Susanna; Coha, Valentina; D'Ambrosio, Lorenzo; Vassallo, Elena; Fizzotti, Marco; Nesi, Francesca; Gioeni, Luisa; Berger, Massimo; Polo, Alessandra; Gammaitoni, Loretta; Becco, Paolo; Giraudo, Lidia; Mangioni, Monica; Sangiolo, Dario; Grignani, Giovanni; Rota-Scalabrini, Delia; Sottile, Antonino; Fagioli, Franca; Aglietta, Massimo

2017-03-01

Allogeneic hematopoietic cell transplant (HCT) remains the only curative therapy for many hematologic malignancies but it is limited by high nonrelapse mortality (NRM), primarily from unpredictable control of graft-versus-host disease (GVHD). Recently, post-transplant cyclophosphamide demonstrated improved GVHD control in allogeneic bone marrow HCT. Here we explore cyclophosphamide in allogeneic peripheral blood stem cell transplantation (alloPBSCT). Patients with high-risk hematologic malignancies received alloPBSCT from HLA-matched unrelated/related donors. GVHD prophylaxis included combination post-HCT cyclophosphamide 50 mg/kg (days +3 and +4) and tacrolimus/mofetil mycophenolate (T/MMF) (day +5 forward). The primary objective was the cumulative incidence of acute and chronic GVHD. Between March 2011 and May 2015, 35 consecutive patients received the proposed regimen. MMF was stopped in all patients at day +28; the median discontinuation of tacrolimus was day +113. Acute and chronic GVHD cumulative incidences were 17% and 7%, respectively, with no grade IV GVHD events, only 2 patients requiring chronic GVHD immunosuppression control, and no deaths from GVHD. Two-year NRM, overall survival, event-free survival, and chronic GVHD event-free survival rates were 3%, 77%, 54%, and 49%, respectively. The graft-versus-tumor effect was maintained as 5 of 15 patients (33%) who received HCT with evidence of disease experienced further disease response. A post-transplant cyclophosphamide + T/MMF combination strategy effectively prevented acute and chronic GVHD after alloPBSCT from HLA-matched donors and achieved an unprecedented low NRM without losing efficacy in disease control or impaired development of the graft-versus-tumor effect. This trial is registered at clinicaltrials.gov as NCT02300571. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Resilience of internal medicine house staff and its association with distress and empathy in an oncology setting.

PubMed

McFarland, Daniel C; Roth, Andrew

2017-10-01

Resilience is a beneficial trait for resident physicians who are exposed to adversity through their work with patients. Inpatient hematology-oncology produces vicarious trauma for physicians in training. Physician distress and empathy influence patient care and may be associated with respectively lower and greater levels of resilience. We collected measures of resilience (Connor-Davidson Resilience Scale), distress (Impact of Events Scale - Revised), and rotation-specific information (e.g., number of death encounters, death stress, and meaning) at the end of a routine hematology-oncology ward rotation. Empathy (Interpersonal Reactivity Index) was measured both before and after the rotation. Fifty-six out of 96 residents completed the study with an overall response rate of 58%. Resilience was negatively correlated with distress (r = -0.306, p = 0.023) but not with empathy (r = 0.172, p = 0.204) and nor with change in empathy over the course of the rotation (r = -0.122, p = 0.374). When separated by sex, male resilience was negatively correlated with distress (r = -0.389, p = 0.04), but female resilience was not. Resident distress levels were in a clinically significant (76%) or posttraumatic stress disorder range (17%), and resident empathy decreased during the rotation (p = 0.018). Resilience levels were similar in those who reported that death events were the most stressful experiences of the rotation and those who derived a sense of meaning from working with dying patients. Resident physicians experienced clinically relevant distress and a decrease in empathy. Resilient resident physicians were less likely to experience distress. This study provides evidence for the salutary effects of resilience on physician distress. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

The effects of combination of Eurycoma longifolia Jack ethanolic extract and doxorubicine on hematological profile in rats given by 7,12-dimethylbenz(a)anthracene

NASA Astrophysics Data System (ADS)

Nurani, L. H.; Mursyidi, A.; Widyarini, S.; Rohman, A.

2017-11-01

Doxorubicin (Dox) is known as anticancer drug commonly used for cancer treatment. Eurycoma longifolia Jack or Pasakbumi was reported to have chemopreventive effect. In cancer patients, there are some dysfunctions of blood parameter, therefore some hematologic tests are needed to monitor cancer patients. In this study, the effects of combination of ethanolic extract of E. longifolia Jack (EEE) and Dox on hematologic profiles were investigated in rats injected by DMBA. Rats were divided into eight groups. Group I was normal group; Group II, rats were treated with extract dose 100 mg/kgbw; Groups III, IV, V, VI, VII and VIII, rats were treated with Dox, DMBA, DMBA+Dox, DMBA+EEE, DMBA+Dox +EEE, and Dox+EEE, respectively. DMBA administration orally was conducted twice a week for 5 weeks. At 16th week of treatments, bloods were taken from orbitalis sinus for hematologicals profile (levels of Hb, erytrocyte, hematocrite, leukocyte, MCV, MCH, and differencial leucocyte count) measurements. These data were analyzed by one way ANOVA followed by LSD test. DMBA administration significantly decreased the hematological profiles compared to the normal group, except in lymphocyte level. Rats treated with extract and extract+Dox were able to increase the hematological profile compared to rats given by DMBA only. Based on these findings it can be concluded that the combination of EEE and Dox potentially increase hematological profile of rats given by DMBA.

B-Cell Hematologic Malignancy Vaccination Registry

ClinicalTrials.gov

2017-12-29

Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; Waldenstrom Macroglobulinemia; Lymphocytosis; Lymphoma, Non-Hodgkin; B-Cell Chronic Lymphocytic Leukemia; Hematological Malignancies

Distant testing in laboratory hematology and flow cytometry--the Indian experience.

PubMed

Das Gupta, Amar

2012-06-01

Outsourcing or sending out of patients' samples to other laboratories for hematologic investigations is a common practice these days. Preanalytic variables that alter cellular parameters and levels of analytes in transit and on storage can significantly and adversely affect interpretation of test results in hematology. Awareness of these changes is necessary to avoid misinterpretation of results that in turn could influence medical management decisions.

Late hematologic toxicity following treatment of rattlesnake envenomation with crotalidae polyvalent immune Fab antivenom.

PubMed

Ruha, Anne-Michelle; Curry, Steven C; Albrecht, Clay; Riley, Brad; Pizon, Anthony

2011-01-01

North American rattlesnake envenomations commonly produce defibrination, coagulopathy and/or thrombocytopenia, which may be reversed following treatment with Crotalidae Polyvalent Immune Fab Ovine (FabAV). Despite initial resolution with FabAV, late onset or recurrence of venom-induced hematologic effects may occur. Time at which onset of late hematotoxicity may first be detected is unknown. The purpose of this study was to identify the incidence and time of onset of recurrent or new late hypofibrinogenemia, coagulopathy, or thrombocytopenia in a cohort of rattlesnake envenomation patients seen in outpatient follow-up after treatment with FabAV, and to report hematologic outcomes in these patients. Review of 66 charts of patients with rattlesnake envenomation who were treated with FabAV, and subsequently had outpatient follow-up evaluation at least 48 h after last FabAV, was performed. Demographic information, rattlesnake and bite characteristics, dose and timing of antivenom administration, adverse events, in-patient laboratory values, length of hospital stay, and follow-up laboratory values were collected. The primary outcome parameters were recurrent or delayed onset coagulopathy, hypofibrinogenemia, or thrombocytopenia identified no sooner than 48 h after last dose of FabAV. Prior to control of the envenomation with FabAV, 42 patients (63.6%) experienced hematologic toxicity. At follow-up, 21 patients (32%) were found to have late coagulopathy, hypofibrinogenemia, or thrombocytopenia. Of twenty-three patients (35%) with more than one follow-up visit, fifteen had normal laboratory findings at the first follow-up visit. Five of these 15 patients (8% of total study group; 33% of this subgroup) with normal hematologic studies at first follow-up exhibited late hematologic toxicity at second follow-up. Severe late hematologic toxicity developed in five of 66 (8%) patients. One patient was retreated with FabAV for late severe thrombocytopenia. Recurrent and delayed onset of hematologic toxicity in rattlesnake envenomation victims treated with FabAV is common. Follow-up more than three days after treatment is necessary to detect all cases of late hematologic toxicity. Copyright © 2010 Elsevier Ltd. All rights reserved.

Co-Infection and Wild Animal Health: Effects of Trypanosomatids and Gastrointestinal Parasites on Coatis of the Brazilian Pantanal.

PubMed

Olifiers, Natalie; Jansen, Ana Maria; Herrera, Heitor Miraglia; Bianchi, Rita de Cassia; D'Andrea, Paulo Sergio; Mourão, Guilherme de Miranda; Gompper, Matthew Edzart

2015-01-01

Wild animals are infected by diverse parasites, but how they influence host health is poorly understood. We examined the relationship of trypanosomatids and gastrointestinal parasites with health of wild brown-nosed coatis (Nasua nasua) from the Brazilian Pantanal. We used coati body condition and hematological parameters as response variables in linear models that were compared using an information theoretic approach. Predictors were high/low parasitemias by Trypanosoma cruzi and T. evansi, and indices representing the abundance of distinct groups of gastrointestinal parasites. We also analyzed how host health changed with host sex and reproductive seasonality. Hemoparasites was best related to coati body condition and hematological indices, whereas abundance of gastrointestinal parasites was relatively less associated with coati health. Additionally, some associations were best predicted by models that incorporated reproductive seasonality and host sex. Overall, we observed a lower health condition during the breeding season, when coatis are under reproductive stress and may be less able to handle infection. In addition, females seem to handle infection better than males. Body condition was lower in coatis with high parasitemias of T. evansi, especially during the reproductive season. Total red blood cell counts, packed cell volume, platelets and eosinophils were also lower in animals with high T. evansi parasitemias. Total white blood cell counts and mature neutrophils were lower in animals with high parasitemias for both Trypanosoma species, with neutrophils decreasing mainly during the reproductive season. Overall, decreases in hematological parameters of females with T. evansi high parasitemias were less evident. For T. cruzi, monocytes decreased in individuals with high parasitemias. High abundances of microfilariae in the bloodstream, and cestode eggs and coccidian oocysts in feces were also associated with coati blood parameters. This study shows the potential value of examining hematological parameters as an approach to better understand the ecological relevance of parasite-host interactions.

Co-Infection and Wild Animal Health: Effects of Trypanosomatids and Gastrointestinal Parasites on Coatis of the Brazilian Pantanal

PubMed Central

Olifiers, Natalie; Jansen, Ana Maria; Herrera, Heitor Miraglia; Bianchi, Rita de Cassia; D’Andrea, Paulo Sergio; Mourão, Guilherme de Miranda; Gompper, Matthew Edzart

2015-01-01

Wild animals are infected by diverse parasites, but how they influence host health is poorly understood. We examined the relationship of trypanosomatids and gastrointestinal parasites with health of wild brown-nosed coatis (Nasua nasua) from the Brazilian Pantanal. We used coati body condition and hematological parameters as response variables in linear models that were compared using an information theoretic approach. Predictors were high/low parasitemias by Trypanosoma cruzi and T. evansi, and indices representing the abundance of distinct groups of gastrointestinal parasites. We also analyzed how host health changed with host sex and reproductive seasonality. Hemoparasites was best related to coati body condition and hematological indices, whereas abundance of gastrointestinal parasites was relatively less associated with coati health. Additionally, some associations were best predicted by models that incorporated reproductive seasonality and host sex. Overall, we observed a lower health condition during the breeding season, when coatis are under reproductive stress and may be less able to handle infection. In addition, females seem to handle infection better than males. Body condition was lower in coatis with high parasitemias of T. evansi, especially during the reproductive season. Total red blood cell counts, packed cell volume, platelets and eosinophils were also lower in animals with high T. evansi parasitemias. Total white blood cell counts and mature neutrophils were lower in animals with high parasitemias for both Trypanosoma species, with neutrophils decreasing mainly during the reproductive season. Overall, decreases in hematological parameters of females with T. evansi high parasitemias were less evident. For T. cruzi, monocytes decreased in individuals with high parasitemias. High abundances of microfilariae in the bloodstream, and cestode eggs and coccidian oocysts in feces were also associated with coati blood parameters. This study shows the potential value of examining hematological parameters as an approach to better understand the ecological relevance of parasite-host interactions. PMID:26657699

A Prospective, Holistic, Multicenter Approach to Tracking and Understanding Bloodstream Infections in Pediatric Hematology-Oncology Patients.

PubMed

Gaur, Aditya H; Bundy, David G; Werner, Eric J; Hord, Jeffrey D; Miller, Marlene R; Tang, Li; Lawlor, John P; Billett, Amy L

2017-06-01

OBJECTIVE To assess the burden of bloodstream infections (BSIs) among pediatric hematology-oncology (PHO) inpatients, to propose a comprehensive, all-BSI tracking approach, and to discuss how such an approach helps better inform within-center and across-center differences in CLABSI rate DESIGN Prospective cohort study SETTING US multicenter, quality-improvement, BSI prevention network PARTICIPANTS PHO centers across the United States who agreed to follow a standardized central-line-maintenance care bundle and track all BSI events and central-line days every month. METHODS Infections were categorized as CLABSI (stratified by mucosal barrier injury-related, laboratory-confirmed BSI [MBI-LCBI] versus non-MBI-LCBI) and secondary BSI, using National Healthcare Safety Network (NHSN) definitions. Single positive blood cultures (SPBCs) with NHSN defined common commensals were also tracked. RESULTS Between 2013 and 2015, 34 PHO centers reported 1,110 BSIs. Among them, 708 (63.8%) were CLABSIs, 170 (15.3%) were secondary BSIs, and 232 (20.9%) were SPBCs. Most SPBCs (75%) occurred in patients with profound neutropenia; 22% of SPBCs were viridans group streptococci. Among the CLABSIs, 51% were MBI-LCBI. Excluding SPBCs, CLABSI rates were higher (88% vs 77%) and secondary BSI rates were lower (12% vs 23%) after the NHSN updated the definition of secondary BSI (P<.001). Preliminary analyses showed across-center differences in CLABSI versus secondary BSI and between SPBC and CLABSI versus non-CLABSI rates. CONCLUSIONS Tracking all BSIs, not just CLABSIs in PHO patients, is a patient-centered, clinically relevant approach that could help better assess across-center and within-center differences in infection rates, including CLABSI. This approach enables informed decision making by healthcare providers, payors, and the public. Infect Control Hosp Epidemiol 2017;38:690-696.

Blood lactate levels in 31 female dogs with pyometra

PubMed Central

Hagman, Ragnvi; Reezigt, Bert Jan; Bergström Ledin, Hanna; Karlstam, Erika

2009-01-01

Background Canine pyometra is a life-threatening disease common in countries where spaying of dogs is not routinely performed. The disease is associated with endotoxemia, sepsis, systemic inflammatory response syndrome (SIRS) and a 3–4% mortality rate. Blood lactate analysis is clinically valuable in predicting prognosis and survival, evaluating tissue perfusion and treatment response in human and veterinary critical care settings. The aims of the present study were to investigate 1) the blood lactate levels of female dogs with pyometra by a hand-held analyser and 2) if these levels are related with the clinical status or other biochemical or hematological disorders. Methods In total 31 female dogs with pyometra admitted for surgical ovariohysterectomy and 16 healthy female control dogs were included in the present study. A complete physical examination including SIRS-status determination was performed. Blood samples for lactate concentrations, hematological and biochemical parameters, acid-base and blood gas analysis and other laboratory parameters were collected and subsequently analysed. The diagnosis pyometra was verified with histopathological examination of the uterus and ovaries. Increased hospitalisation length and presence of SIRS were used as indicators of outcome. Results In the pyometra group the median blood lactate level was 1,6 mmol l-1 (range <0.8–2.7 mmol l-1). In the control group the median lactate level was 1,2 mmol l-1 (range <0.8–2.1 mmol l-1). Of the 31 bitches 19 (61%) fulfilled 2 or more criteria for SIRS at inclusion, 10 bitches (32%) fulfilled 3 of the SIRS criteria whereas none accomplished more than 3 criteria. Lactate levels did not differ significantly between the pyometra and control group, or between the SIRS positive and SIRS negative dogs with pyometra. Increased lactate concentration (>2.5 mmol l-1) was demonstrated in one female dog with pyometra (3%), and was not associated with longer hospitalisation or presence of SIRS. Lactate measurement was not indicative of peritonitis. None of the bitches died during or within two months of the hospital stay. The measurements of temperature, heart rate, respiratory rate, percentage bandforms of neutrophilic granulocytes, α2-globulins, creatinin, pvCO2, TCO2 and base excess showed significant differences between the SIRS positive and the SIRS negative pyometra cases. Conclusion Increased blood lactate concentrations were demonstrated in 3% (1/31), and SIRS was present in 61% (19/31) of the female dogs with pyometra. Preoperative lactate levels were not related with presence of SIRS or prolonged hospitalisation. Lactate measurement was not indicative of peritonitis. The value of a single and repeated lactate analysis in more severely affected cases remains to be determined. PMID:19134167

Bronchoscopic diagnosis of pulmonary infiltrates in granulocytopenic patients with hematologic malignancies: BAL versus PSB and PBAL.

PubMed

Boersma, Wim G; Erjavec, Zoran; van der Werf, Tjip S; de Vries-Hosper, Hilly G; Gouw, Annette S H; Manson, Willem L

2007-02-01

Treatment of patients with hematologic malignancies is often complicated by severe respiratory infections. Bronchoscopy is generally to be used as a diagnostic tool in order to find a causative pathogen. In a prospective study the combination of protected specimen brush (PSB) and protected bronchoalveolar lavage (PBAL) was compared with bronchoalveolar lavage (BAL) for evaluated feasibility and diagnostic yield in granulocytopenic patients with hematologic malignancies and pulmonary infiltrates. All specimens from 63 bronchoscopic procedures (35 BAL and 28 PSB-PBAL) were investigated by cytological examination and various microbiological tests. If clinically relevant and feasible, based on the clinical condition and/or the presence of thrombocytopenia, lung tissue samples were obtained. The majority of the 58 included patients were diagnosed as having acute myeloid leukaemia and developed a severe neutropenia (BAL-group: 27 days; PSB-PBAL group: 30 days). Microbiological and cytological examination of 63 bronchoscopic procedures (35 BAL and 28 PSB-PBAL) yielded causative pathogens in 9 (26%) patients of the BAL-group and 8 (29%) patients of the PSB-PBAL group (PSB and PBAL 4 each). Aspergillus fumigatus was the pathogen most frequently (13%) detected. Using all available examinations including the results of autopsy, a presumptive diagnosis was established in 43% of the patients in the BAL group and 57% of those in the PSB-PBAL group; in these cases microbial aetiology was correctly identified in 67% and 57%, respectively. The complication rate was of these procedures were low, and none of the patients experienced serious complications due to the invasive techniques. Our results showed that modern bronchoscopic techniques such as PSB and PBAL did not yield better diagnostic results compared to BAL in granulocytopenic patients with hematologic malignancies and pulmonary infiltrates. In approximately half of the cases a presumptive diagnosis was made by bronchoscopic procedures.

The effect of enriched chicory inulin on liver enzymes, calcium homeostasis and hematological parameters in patients with type 2 diabetes mellitus: A randomized placebo-controlled trial.

PubMed

Farhangi, Mahdieh Abbasalizad; Javid, Ahmad Zare; Dehghan, Parvin

2016-08-01

Type 2 diabetic mellitus (T2DM) as one of the main causes of morbidity and mortality is associated with immune system disturbances and metabolic abnormalities. In the current study we aimed to evaluate the effects of enriched chicory inulin supplementation on liver enzymes, serum calcium and phosphorous concentrations and hematological parameters in patients with T2DM. Forty-six diabetic females patients were randomly allocated into intervention (n=27) and control (n=22) groups. Subjects in the intervention group received a daily dose of 10g of chicory and subjects in control group received a placebo for two months. Anthropometric variables, glucose homeostasis, hematological parameters and metabolic indices including serum alanine aminotransfersae (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), calcium and phosphorous as well as creatinine concentrations, glomerular filtration rate (GFR) and blood pressure were assessed at the beginning and end of the trial. Significant reductions in fasting serum glucose (FSG), Hb A1C, AST and ALP concentrations were observed in chicory-treated group. Systolic and diastolic blood pressures were also reduced in chicory-treated group. Serum calcium significantly increased after chicory supplementation but no change in placebo treated group has been occurred (P=0.014). Supplementation with enriched chicory for two months significantly reduced hematocrit and mean corpuscular volume (MCV) values (P<0.05). Changes in serum insulin, creatinine and GFR were not significant. The present study showed beneficial effects of oligofructose-enriched chicory on the improvement of the glucose and calcium homeostasis, liver function tests, blood pressure and reduction in hematologic risk factors of diabetes in female patients with T2DM. Further studies in both genders are needed to generalize these findings to total population. Copyright © 2016 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Physiologic and biochemical effects of electroacupuncture combined with intramuscular administration of dexmedetomidine to provide analgesia in goats.

PubMed

Shah, Zahir; Hu, Man L; Qiu, Zheng Y; Zhou, Fei Y; Zeng, Jie; Wan, Juan; Wang, Shao W; Zhang, Wei; Ding, Ming X

2016-03-01

To investigate physiologic and biochemical effects of electroacupuncture and dexmedetomidine administration to goats. 30 healthy adult goats. Goats were allotted to 5 groups (6 goats/group) and received electroacupuncture, dexmedetomidine (5 or 20 μg/kg, IM), electroacupuncture plus dexmedetomidine (5 μg/kg, IM), or saline (0.9% NaCl) solution (IM [control treatment]). Pain threshold, cardiorespiratory effects, rectal temperature, and hematologic and biochemical variables were assessed. Dexmedetomidine (20 μg/kg) increased pain threshold and decreased heart rate, respiratory rate, and rectal temperature. Pain threshold of goats receiving electroacupuncture plus dexmedetomidine (5 μg/kg) was higher than that of goats receiving electroacupuncture or of goats receiving dexmedetomidine at 5 μg/kg at 30 minutes, but did not differ from that of goats receiving dexmedetomidine at 20 μg/kg. Compared with goats administered dexmedetomidine at 20 μg/kg, goats receiving electroacupuncture plus dexmedetomidine at 5 μg/kg had a higher heart rate from 30 to 60 minutes and a higher respiratory rate from 5 to 60 minutes. Electroacupuncture plus dexmedetomidine (5 μg/kg) did not affect rectal temperature. Serum glucose concentrations of goats receiving electroacupuncture plus dexmedetomidine (5 μg/kg) were higher than for goats receiving dexmedetomidine at 5 μg/kg at 30 minutes but not for goats receiving dexmedetomidine at 20 μg/kg. Creatinine and BUN concentrations, alanine or aspartate aminotransferase activities, and hematologic variables of treated goats did not change. Electroacupuncture in combination with a low dose of dexmedetomidine (5 μg/kg, IM) administered to goats provided antinociception.

Microorganisms isolated from cultures and infection focus and antibiotic treatments in febrile neutropenic children from Şanlıurfa, Turkey.

PubMed

Özdemir, Z Canan; Koç, Ahmet; Ayçiçek, Ali

2016-01-01

Chemotherapy induced febrile neutropenia predisposes patients to life threatening infections. We aimed to determine the causative microorganisms, infection focus and antibiotic treatment success in febrile neutropenic children with leukemia. A total of 136 febrile neutropenic episodes in 48 leukemic children were reviewed retrospectively from records. Among 136 febrile neutropenic episodes, 68 (50%) episodes were microbiologically documented. Methicillin sensitive coagulase (-) Staphylococcus aureus were the most common isolates from hemoculture (20.5%). The most frequently documented infection focus was mucositis (31.9%). Ceftazidime plus amikacin was the most commonly used antimicrobial treatment for the empirical therapy (52.9%). The overall response rates were 70.5%, 86.9%, and 66.6% of first line, second line and third line therapies, respectively. The spectrum of isolates among febrile neutropenic children in our hematology clinic appears to be gram positive pathogens which are the most common agents. Therefore the, documentation of the flora in each unit could help to decide appropriate empirical therapy which is life saving.