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Sample records for autologous peripheral stem

  1. Biosimilar Filgrastim in Autologous Peripheral Blood Hematopoietic Stem Cell Mobilization and Post-Transplant Hematologic Recovery.

    PubMed

    Marchesi, Francesco; Mengarelli, Andrea

    2016-01-01

    To date, two kinds of Granulocyte Colony-Stimulating Factors (G-CSF) have been approved for autologous peripheral blood hematopoietic stem cell (PBSCs) mobilization and posttransplant hematologic recovery after high-dose chemotherapy: filgrastim (originator and biosimilar) and lenograstim. Biosimilar filgrastim has been approved on the basis of comparable efficacy and safety in clinical studies where it has been used as chemotherapy-induced febrile neutropenia prophylaxis, but no specific pre-registration studies have been published in the transplant setting. Hence, there is still general skepticism about the role of biosimilar G-CSFs in this setting of patients. This review of biochemical, pre-clinical and clinical data suggests significant comparability of biosimilar filgrastim with both originator filgrastim and lenograstim in autologous PBSCs mobilization and post-autograft hematologic recovery.

  2. High-dose chemotherapy and autologous peripheral blood stem cell transplantation in patients with multiple myeloma and renal insufficiency.

    PubMed

    Ballester, O F; Tummala, R; Janssen, W E; Fields, K K; Hiemenz, J W; Goldstein, S C; Perkins, J B; Sullivan, D M; Rosen, R; Sackstein, R; Zorsky, P; Saez, R; Elfenbein, G J

    1997-10-01

    Six patients with multiple myeloma and chronic renal insufficiency (serum creatinine >3.0 mg/dl), including four on dialysis, received high-dose busulfan and cyclophosphamide (BUCY) followed by autologous peripheral stem cell transplantation. Peripheral blood stem cells were collected after priming with cyclophosphamide, etoposide and G-CSF. Patterns of engraftment and toxicities were not apparently different from those seen in myeloma patients with normal renal function. There was one toxicity-related death, resulting from a massive spontaneous subdural hematoma. One patient died of disease progression 6 months after transplant, while the remaining four patients are alive and free of myeloma progression 6 to 39 months after high-dose therapy. Two of these patients have remained in complete remission for 28 and 39 months. Our experience suggests that high-dose therapy with BUCY and autologous peripheral blood stem cell rescue is feasible in patients with multiple myeloma and renal failure.

  3. Biosimilar G-CSF based mobilization of peripheral blood hematopoietic stem cells for autologous and allogeneic stem cell transplantation.

    PubMed

    Schmitt, Michael; Publicover, Amy; Orchard, Kim H; Görlach, Matthias; Wang, Lei; Schmitt, Anita; Mani, Jiju; Tsirigotis, Panagiotis; Kuriakose, Reeba; Nagler, Arnon

    2014-01-01

    The use of granulocyte colony stimulating factor (G-CSF) biosimilars for peripheral blood hematopoietic stem cell (PBSC) mobilization has stimulated an ongoing debate regarding their efficacy and safety. However, the use of biosimilar G-CSF was approved by the European Medicines Agency (EMA) for all the registered indications of the originator G-CSF (Neupogen (®) ) including mobilization of stem cells. Here, we performed a comprehensive review of published reports on the use of biosimilar G-CSF covering patients with hematological malignancies as well as healthy donors that underwent stem cell mobilization at multiple centers using site-specific non-randomized regimens with a biosimilar G-CSF in the autologous and allogeneic setting. A total of 904 patients mostly with hematological malignancies as well as healthy donors underwent successful autologous or allogeneic stem cell mobilization, respectively, using a biosimilar G-CSF (520 with Ratiograstim®/Tevagrastim, 384 with Zarzio®). The indication for stem cell mobilization in hematology patients included 326 patients with multiple myeloma, 273 with Non-Hodgkin's lymphoma (NHL), 79 with Hodgkin's lymphoma (HL), and other disease. 156 sibling or volunteer unrelated donors were mobilized using biosimilar G-CSF. Mobilization resulted in good mobilization of CD34+ stem cells with side effects similar to originator G-CSF. Post transplantation engraftment did not significantly differ from results previously documented with the originator G-CSF. The side effects experienced by the patients or donors mobilized by biosimilar G-CSF were minimal and were comparable to those of originator G-CSF. In summary, the efficacy of biosimilar G-CSFs in terms of PBSC yield as well as their toxicity profile are equivalent to historical data with the reference G-CSF.

  4. Epstein-Barr virus-associated lymphoproliferative disorder developed following autologous peripheral blood stem cell transplantation for relapsing Hodgkin's lymphoma.

    PubMed

    Izumiya, Sakura; Ishida, Mitsuaki; Hodohara, Keiko; Yoshida, Takashi; Okabe, Hidetoshi

    2012-06-01

    Post-transplant lymphoproliferative disorders (PTLDs) are lymphoid or plasmacytic proliferations that develop as a consequence of immunosuppression in a recipient of a solid organ, bone marrow or stem cell allograft. The development of PTLDs is usually associated with Epstein-Barr virus (EBV) and the disorder is also termed EBV-associated lymphoproliferative disorder (LPD). The development of PTLD is a rare complication in autologous bone marrow/peripheral blood stem cell transplantation. In the present study, we report a case of EBV-associated LPD which developed following autologous peripheral blood stem cell transplantation for relapsing Hodgkin's lymphoma. A 51-year-old male presented with swelling of the left cervical lymph nodes. A biopsy revealed nodular sclerosis classical Hodgkin's lymphoma. Following four courses of ABVd (adriamycin, bleomycin, vinblastine, dacarbazine) therapy, the Hodgkin's lymphoma relapsed. CHASE (cyclophosphamide, etoposide, cytarabine, dexamethasone) therapy and autologous peripheral blood stem cell transplantation were performed. In the 128 days following the transplantation, lymph node swelling was noted and a biopsy specimen demonstrated EBV-associated LPD. The serum copy number of EBV-DNA was 2.7×10(3) copies/ml. The occurrence of EBV-associated LPD may be on the rise due to the increased number of patients undergoing immunosuppression therapy. The measurement of the serum EBV-DNA copy number and the detection of EBV-infected atypical lymphocytes using in situ hybridization are significant in establishing an early accurate diagnosis and initiating the correct treatment for EBV-associated LPD in patients with immunosuppression.

  5. Conditioning with targeted busulfan for autologous peripheral blood stem cells transplantation for acute myelogenous leukemia in an XYY male.

    PubMed

    Sada, Eriko; Henzan, Hideho; Ohtani, Ryoko; Takase, Ken; Miyamoto, Toshihiro; Fukuda, Takahiro; Nagafuji, Koji; Yamauchi, Keita; Takamatsu, Yasushi; Inaba, Shoichi; Harada, Mine

    2005-01-01

    We report herein a 19-year-old Japanese male with XYY syndrome who developed acute myelogenous leukemia. During three courses of cytotoxic chemotherapy, he suffered repeated hepatic and renal insufficiencies, possibly related to latent dysfunction from the XYY syndrome. The patient was treated with granulocyte colony-stimulating factor combined with etoposide, cytarabine, and busulfan (the latter adjusted to a targeting dose) followed by autologous peripheral blood stem cell transplantation. He had no severe regimen-related toxicities and is now free of leukemia.

  6. Autologous peripheral blood stem cell harvest: Collection efficiency and factors affecting it

    PubMed Central

    Tiwari, Aseem K.; Pandey, Prashant; Subbaraman, Harini; Bhargava, Rahul; Rawat, Ganesh; Madiraju, Shivani; Raina, Vimarsh; Bhargava, Richa

    2016-01-01

    Background: Harvest of hematopoietic progenitor cells via leukapheresis is being used increasingly for transplants in India. Adequate yield of cells per kilogram body weight of recipient is required for successful engraftment. Collection efficiency (CE) is an objective quality parameter used to assess the quality of leukapheresis program. In this study, we calculated the CE of the ComTec cell separator (Fresenius Kabi, Germany) using two different formulae (CE1 and CE2) and analyzed various patient and procedural factors, which may affect it. Materials and Methods: One hundred and one consecutive procedures in 77 autologous donors carried out over 3 years period were retrospectively reviewed. Various characteristics like gender, age, weight, disease status, hematocrit, preprocedure total leukocyte count, preprocedure CD34 positive (CD34+) cells count, preprocedure absolute CD34+ cell count and processed apheresis volume effect on CE were compared. CE for each procedure was calculated using two different formulae, and results were compared using statistical correlation and regression analysis. Results: The mean CE1 and CE2 was 41.2 and 49.1, respectively. CE2 appeared to be more accurate indicator of overall CE as it considered the impact of continued mobilization of stem cells during apheresis procedure, itself. Of all the factors affecting CE, preprocedure absolute CD34+ was the only independent factor affecting CE. Conclusion: The only factor affecting CE was preprocedure absolute CD34+ cells. Though the mean CE2 was higher than CE1, it was not statistically significant. PMID:27011680

  7. Recovery of mucosal-associated invariant T cells after myeloablative chemotherapy and autologous peripheral blood stem cell transplantation.

    PubMed

    Novak, Jan; Dobrovolny, Jan; Brozova, Jitka; Novakova, Lucie; Kozak, Tomas

    2016-11-01

    Immune reconstitution after high-dose chemotherapy and stem cell transplantation plays a key role in restoring immunocompetence including defense against infection, immune regulation, and onco-immune surveillance. In this work, we examined the recovery of mucosal-associated invariant T (MAIT) cells, recently discovered innate-like T cells, after various types of myeloablative chemotherapy and autologous peripheral blood stem cell transplantation in 29 patients. We show that MAIT cells are relatively resistant to myeloablative conditioning. The median amount of MAIT cells rises to 43 % around day +30 and is sustained through further measurements on days +60 and +100. Moreover, MAIT cell recovery reaches 100 % of pre-treatment values in 33 % of patients already by day +60. The only factor affecting recovery of MAIT cells is age, younger age being associated with earlier MAIT cell recovery. The pre-treatment quantity of MAIT cells carries a prognostic impact on the early post-transplantation course. Patients with high levels of MAIT cells pre-treatment have significantly lower peak CRP levels (79.45 vs. 150 mg/L) post-treatment, reflecting a clinical trend of less severe infectious complications (less febrile days and less days on intravenous antibiotics). Altogether these data suggest that a high proportion of MAIT cells survive myeloablative chemotherapy and maintain their capacity to fight against infections probably on mucosal surfaces.

  8. Autologous Peripheral Blood Stem Cell Transplantation Improves Portal Hemodynamics in Patients with Hepatitis B Virus-related Decompensated Cirrhosis

    PubMed Central

    Deng, Qinzhi; Cai, Ting; Zhang, Shun; Hu, Airong; Zhang, Xingfen; Wang, Yinyin; Huang, Jianrong

    2015-01-01

    Background: Chronic hepatitis B virus (HBV) infection may eventually lead to decompensated liver cirrhosis, which is a terminal illness. Objectives: The aim of this study was to investigate the therapeutic efficacy of autologous peripheral blood stem cell (APBSC) transplantation to improve portal vein hemodynamics in patients with HBV-related decompensated cirrhosis. Patients and Methods: This prospective study included 68 hospitalized patients who were diagnosed with HBV-related decompensated cirrhosis. These patients were divided into two groups: the transplantation group included 33 patients, while the control group included 35. Both groups received conventional medical treatment simultaneously, and APBSC transplantation was performed on the patients in the transplantation group. We evaluated the effects of APBSC transplantation on postoperative liver function using the following indices: total bilirubin, serum prothrombin and albumin, spleen size, and portal vein hemodynamics. Postoperatively, all of the patients were followed up at 24, 36, and 48 weeks. Results: The transplantation group had no serious reactions. Compared with the control group, albumin and prothrombin activity in the transplantation group was significantly improved at 24, 36, and 48 weeks after the procedure, and spleen length and portal vein diameter were substantially reduced at 48 weeks. The velocity of peak portal vein blood flow and mean maximum portal vein blood flow were greatly increased in the APBSC transplantation group at 36 and 48 weeks, respectively; however, there was also decreased portal vein diameter, which reduced portal vein pressure in patients with HBV-related decompensated cirrhosis. Conclusions: APBSC transplantation greatly benefits HBV-linked decompensated cirrhosis patients and should be recommended in clinical practice. PMID:26977164

  9. Ifosfamide, Cisplatin or Carboplatin, and Etoposide (ICE)-based Chemotherapy for Mobilization of Autologous Peripheral Blood Stem Cells in Patients with Lymphomas

    PubMed Central

    Zhou, Ping; Liu, Peng; Zhou, Sheng-Yu; He, Xiao-Hui; Han, Xiao-Hong; Qin, Yan; Yang, Sheng; Zhang, Chang-Gong; Gui, Lin; Yao, Jia-Rui; Zhao, Li-Ya; Zhang, Shu-Xiang; Sun, Yan; Shi, Yuan-Kai

    2015-01-01

    Background: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a promising approach for lymphomas. This study aimed to evaluate the effect of ifosfamide, cisplatin or carboplatin, and etoposide (ICE)-based regimen as a mobilization regimen on relapsed, refractory, or high-risk aggressive lymphoma. Methods: From June 2001 to May 2013, patients with lymphomas who mobilized by ICE-based regimen for ASCT were analyzed in this retrospective study. The results of the autologous peripheral blood stem cells collection, toxicity, engraftment after ICE-based mobilization regimen were analyzed in this study. Furthermore, risk factors for overall survival (OS) and progression free survival (PFS) were evaluated by univariate analysis. Results: The stem cells were mobilized using ICE-based regimen plus rituximab or ICE-based regimen alone in 12 patients and 54 patients, respectively. The results of stem cell mobilization were excellent. Ninety-seven percentages of the patients had the stem cell collection of at least 2.0 × 106 CD34+ cells/kg and 68% had at least 5 × 106 CD34+ cells/kg. Fifty-eight percentage of the patients experienced Grade 4 neutropenia, 20% developed febrile neutropenia, and only 12% had Grade 4 thrombocytopenia. At a median follow-up of 63.8 months, the 5-year PFS and OS were 64.4% and 75.3%, respectively. Conclusion: ICE is a powerful regimen for stem cell mobilization in patients with lymphomas. PMID:26365969

  10. Repair of large full-thickness cartilage defect by activating endogenous peripheral blood stem cells and autologous periosteum flap transplantation combined with patellofemoral realignment.

    PubMed

    Fu, Wei-Li; Ao, Ying-Fang; Ke, Xiao-Yan; Zheng, Zhuo-Zhao; Gong, Xi; Jiang, Dong; Yu, Jia-Kuo

    2014-03-01

    Minimal-invasive procedure and one-step surgery offer autologous mesenchymal stem cells derived from peripheral blood (PB-MSCs) a promising prospective in the field of cartilage regeneration. We report a case of a 19-year-old male athlete of kickboxing with ICRS grade IV chondral lesions at the 60° region of lateral femoral trochlea, which was repaired by activating endogenous PB-MSCs plus autologous periosteum flap transplantation combined with correcting the patellofemoral malalignment. After a 7.5 year follow-up, the result showed that the patient returned to competitive kickboxing. Second-look under arthroscopy showed a smooth surface at 8 months postoperation. The IKDC 2000 subjective score, Lysholm score and Tegner score were 95, 98 and 9 respectively at the final follow up. CT and MRI evaluations showed a significant improvement compared with those of pre-operation.

  11. Persistent complete remission of acute leukemic-phase CCR4-positive gamma-delta peripheral T-cell lymphoma by autologous stem cell transplantation with mogamulizumab.

    PubMed

    Furukawa, Miki; Ikeda, Kazuhiko; Ohkawara, Hiroshi; Saito, Shunichi; Takahashi, Hiroshi; Ueda, Koki; Matsumoto, Hayato; Hashimoto, Yuko; Ohto, Hitoshi; Ogawa, Kazuei; Takeishi, Yasuchika

    2015-10-01

    Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), frequently shows a poor outcome. Especially, expressions of CC chemokine receptor 4 (CCR4) and γδ T-cell receptor (TCR) are associated with worse prognosis in PTCL-NOS. We here report successful treatment with autologous peripheral blood stem cell transplantation (auto-PBSCT) combined with anti-CCR4 antibody mogamulizumab for a very rare case of CCR4+γδTCR+ PTCL-NOS that coexisted with Hodgkin's lymphoma. PTCL-NOS in this patient progressed to leukemic phase, whereas Hodgkin's lymphoma disappeared with standard chemotherapies within 4 years of the initial diagnosis. Leukemic-phase PTCL-NOS was refractory to several chemotherapies. However, auto-PBSCT following high-dose chemotherapy combined with pre- and post-transplant mogamulizumab, which is a humanized monoclonal antibody to CCR4, provided persistent complete remission of PTCL-NOS, despite residual γδTCR+ in the transplanted stem cell product, suggesting a purging effect of mogamulizumab. At 15 months after transplantation, we also found markedly fewer effector regulatory T cells, which may have contributed to prolonged remission. This case suggests that autologous stem cell transplantation combined with mogamulizumab may have a potential to cure T-cell neoplasms that express CCR4 including leukemic-phase PTCL-NOS.

  12. Phase I-II study of high-dose busulfan and cyclophosphamide followed by autologous peripheral blood stem cell transplantation for hematological malignancies: toxicities and hematopoietic recovery.

    PubMed

    Ballester, O F; Agaliotis, D P; Hiemenz, J W; Janssen, W E; Fields, K K; Zorksy, P E; Goldstein, S C; Perkins, J B; Elfenbein, G J

    1996-07-01

    In a phase I-II study, we evaluated toxicities, tolerability, pace of engraftment, and tumor responses to high-dose bulsulfan and cyclophosphamide followed by autologous peripheral blood stem cell transplantation in patients with hematological malignancies. We treated 51 patients with various hematological malignancies involving the bone marrow with busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) followed by reinfusion of autologous peripheral blood stem cells. Stem cells were previously collected during hematopoietic recovery after cyclophosphamide (100 mg/kg) and etoposide (600 mg/m2) followed by G-CSF (5 micrograms/kg/day). Neutrophil recovery (>0.5 x 10(9)/I) was rapid in the majority of patients (median 10 days after transplant, range 7-91 days), resulting in a low number of days with severe neutropenia (median 7 days, range 5-85 days) and with fever (median 5 days, range 1-13 days). Platelet recovery, however, was delayed in 60% of patients. There was one acute transplant-related death (2%). Four patients died of late, presumed infections, pulmonary complications (interstitial pneumonia). Tumor responses were documented in a significant proportion of these patients with high-risk hematological malignancies. We conclude that peripheral blood stem cell transplantation results in rapid recovery of neutrophils but variable recovery of platelets after high-dose busulfan and cyclophosphamide, when stem cells are harvested following priming with cyclophosphamide/etoposide and G-CSF. The regimen is well-tolerated with limited non-hematological toxicities and transplant-related mortality. While significant tumor responses were documented in this trial, the ultimate efficacy of the regimen needs to be further defined.

  13. [White blood cell lysis syndrome after autologous peripheral blood stem cell transplantation in the treatment of renal AL amyloidosis. Case report].

    PubMed

    Gatica, Antonio; Bertin, Pablo; Tagle, Rodrigo

    2006-06-01

    The treatment of AL amyloidosis was not successful until the advent of myeloablative chemotherapy consisting of high-dose intravenous melphalan followed by autologous peripheral blood stem cell transplantation. This new treatment has achieved better survival rates and, remarkably, it has obtained complete remission. Among patients with renal involvement, achievement of a complete hematological response was associated with a 50% reduction in proteinuria and stable creatinine clearance in more than 2/3 of patients. Despite of these excellent results, this new therapy is associated with significant toxicity, including the development of acute renal failure due to white blood cell lysis syndrome. We report a 59 year-old female with a nephrotic syndrome due to primary amyloidosis successfully treated autologous stem cell transplantation who developed acute renal failure caused by white blood cell lysis syndrome. The patient required treatment with granulocytic colony stimulating factor and intermittent hemofiltration and was discharged 23 days after melphalan administration with a satisfactory renal function and white blood cell count. After one year of follow up, she maintains a good glomerular filtration rate, a proteinuria of less than, 1 g/day and normal hematological values.

  14. [T-cell large granular lymphocyte leukemia after autologous peripheral blood stem cell transplantation for malignant lymphoma-report of three cases and a review of the literature].

    PubMed

    Kuroda, Hiroyuki; Sakurai, Tamaki; Yamada, Michiko; Abe, Tomoyuki; Fujii, Shigeyuki; Maeda, Masahiro; Kohda, Kyuhei; Hirayama, Yasuo; Jyomen, Wataru; Uemura, Naoki; Ono, Michihiro; Fujimi, Yuko; Iyama, Satoshi; Sato, Tsutomu; Kato, Junji

    2011-10-01

    There have been only three reports in the literature of T-cell large granular lymphocyte (T-LGL) leukemia occurring after autologous peripheral stem cell transplantation (APBSCT). We describe 3 patients in whom a transient monoclonal T-LGL developed after APBSCT for malignant lymphoma. Case 1: A 58-year-old man with peripheral T-cell lymphoma in second complete remission (CR) who underwent APBSCT. Case 2: A 51-year-old man with follicular lymphoma in second CR who underwent APBSCT. Case 3: A 65-year-old man with diffuse large B-cell lymphoma in second CR who underwent tandem APBSCT. One month after transplant, fever followed by the proliferation of CD8+/CD57+ T-LGL in peripheral blood occurred in all three cases. Because clonal rearrangements of the T-cell receptor were detected in peripheral blood samples, T-LGL leukemia was diagnosed. The first patient had episodes of Epstein-Barr virus viremia. The other patients suffered from cytomegalovirus colitis after APBSCT. These data show that T-LGL leukemia can occur after viral infection followed by APBSCT.

  15. Addition of plerixafor to mobilization regimens in autologous peripheral blood stem cell transplants does not affect the correlation of preharvest hematopoietic precursor cell enumeration with first-harvest CD34+ stem cell yield.

    PubMed

    Villa, Carlos H; Shore, Tsiporah; Van Besien, Koen; Cushing, Melissa

    2012-12-01

    The CXCR4 antagonist plerixafor is increasingly used in the mobilization regimens for autologous peripheral blood stem cell (PBSC) transplantation. This agent may mobilize a different subset of the stem cell population than traditional regimens, such as growth factors (with and without chemotherapy). Thus, it is important to determine whether plerixafor has an effect on the utility of measurements used to predict the yield of CD34(+) cells, usually either preharvest peripheral blood CD34(+) enumeration by flow cytometry or hematopoietic precursor cell (HPC) enumeration by automated hematology analysis. Although HPC enumeration has a weaker correlation with first-harvest CD34(+) cell yield, this parameter still plays an important role in the timing of apheresis procedures for autologous PBSC transplantation because of its technical simplicity and low cost. In the present study, we retrospectively examined the correlation of HPC measurements with CD34(+) cell yields in patients with multiple myeloma and lymphoma undergoing autologous PBSC transplantation, and investigated how the mobilization regimen affected these results. We found that the correlation coefficients ranged from 0.5877 to 0.7668 and were not significantly impacted by differences in diagnosis or inclusion of plerixafor in the mobilization regimen. The predictive ability of HPC enumeration for various target yields was also examined, and receiver-operating characteristic curves were generated. An HPC cutoff of 20 should result in adequate initial CD34(+) cell yields (>2.5 × 10(6) cell/kg) in >80% of autologous donors with or without plerixafor. This study confirms the utility of HPC enumeration in prediction of adequate initial cell yields, and demonstrates that this utility is maintained regardless of whether or not plerixafor is included in the mobilization regimen.

  16. Autologous peripheral blood stem cell transplantation in children with refractory or relapsed lymphoma: results of Children's Oncology Group study A5962.

    PubMed

    Harris, Richard E; Termuhlen, Amanda M; Smith, Lynette M; Lynch, James; Henry, Michael M; Perkins, Sherrie L; Gross, Thomas G; Warkentin, Phyllis; Vlachos, Adrianna; Harrison, Lauren; Cairo, Mitchell S

    2011-02-01

    This prospective study was designed to determine the safety and efficacy of cyclophosphamide, BCNU, and etoposide (CBV) conditioning and autologous peripheral blood stem cell transplant (PBSCT) in children with relapsed or refractory Hodgkin and non-Hodgkin lymphoma (HL and NHL). Patients achieving complete remission (CR) or partial remission (PR) after 2 to 4 courses of reinduction underwent a granulocyte-colony stimulating factor (G-CSF) mobilized PBSC apheresis with a target collection dose of 5 × 10⁶ CD34(+)/kg. Those eligible to proceed received autologous PBSCT after CBV (7200 mg/m², 450-300 mg/m², 2400 mg/m²). Forty-three of 69 patients (30/39 HL, 13/30 NHL) achieved a CR/PR after reinduction. Thirty-eight patients (28 HL, 10 NHL) underwent PBSCT. All initial 6 patients who received BCNU at 450 mg/m² experienced grade III or IV pulmonary toxicity compared to none of the subsequent 32 receiving 300 mg/m² (P < .0001). The probability of overall survival (OS) at 3 years for all patients is 51% and for transplanted patients is 64%. The 3-year event-free survival (EFS) is 38% (45% for HL; 30% NHL). The 3-year EFS in transplanted patients is 66% (65% HL; 70% NHL). Initial duration of remission of ≥12 versus <12 months was associated with a significant increase in OS (3 years OS 70% versus 34%) (P = .003). BCNU at 300 mg/m(2) in a CBV regimen prior to PBSCT is well tolerated in relapsed or refractory pediatric lymphoma patients. A short duration (<12 months) of initial remission is associated with a poorer prognosis. Last, a high percentage of patients achieving a CR/PR after reinduction therapy can be salvaged with CBV and autologlous PBSCT.

  17. An algorithm for utilizing peripheral blood CD34 count as a predictor of the need for plerixafor in autologous stem cell mobilization--cost-effectiveness analysis.

    PubMed

    Abusin, Ghada A; Abu-Arja, Rolla F; Gingrich, Roger D; Silverman, Margarida D; Zamba, Gideon K D; Schlueter, Annette J

    2013-08-01

    Certain patients who receive granulocyte colony-stimulating factor (GCSF) for autologous hematopoietic stem cell (AHSC) collection fail to mobilize well enough to proceed with transplant. When plerixafor is used with GCSF, the likelihood of achieving the CD34⁺ stem cell target in fewer collections is higher; plerixafor use in all patients is unlikely to be cost-effective. This study retrospectively evaluated the effectiveness of utilizing a peripheral blood CD34⁺ stem cell count (PBCD34) ≤8/µL on day 4 of GCSF-based AHSC mobilization as a threshold for plerixafor administration, and compared the efficacy of collection and cost analysis using historical controls. All patients in the study cohort reached their CD34⁺ targets in ≤3 collections. Significantly more patients who received plerixafor + GCSF versus GCSF alone reached their CD34⁺ target in one collection (P = 0.045); however, there were no significant differences in the number of collections or in cumulative product yields. The historical cohort had 10.3% mobilization failures; the number of collections per patient needed to reach the target was significantly higher in the historical cohort versus study cohort (P = 0.001) as was the number of patients requiring more than one collection to reach their target (P = 0.023). However, the average cost per patient was also significantly higher in the study cohort (P = 0.025). Further refinement of the algorithm may reduce the difference in cost between the two mobilization strategies.

  18. Cryptococcal meningitis post autologous stem cell transplantation.

    PubMed

    Chaaban, S; Wheat, L J; Assi, M

    2014-06-01

    Disseminated Cryptococcus disease occurs in patients with defective T-cell immunity. Cryptococcal meningitis following autologous stem cell transplant (SCT) has been described previously in only 1 patient, 4 months post SCT and while off antifungal prophylaxis. We present a unique case of Cryptococcus meningitis pre-engraftment after autologous SCT, while the patient was receiving fluconazole prophylaxis. A 41-year-old man with non-Hodgkin's lymphoma underwent autologous SCT. Post-transplant prophylaxis consisted of fluconazole 400 mg daily, levofloxacin 500 mg daily, and acyclovir 800 mg twice daily. On day 9 post transplant, he developed fever and headache. Peripheral white blood cell count (WBC) was 700/μL. Magnetic resonance imaging of the brain showed lesions consistent with meningoencephalitis. Cerebrospinal fluid (CSF) analysis revealed a WBC of 39 with 77% lymphocytes, protein 63, glucose 38, CSF pressure 20.5 cmH2 O, and a positive cryptococcal antigen. CSF culture confirmed Cryptococcus neoformans. The patient was treated with liposomal amphotericin B 5 mg/kg intravenously daily, and flucytosine 37.5 mg/kg orally every 6 h. He was switched to fluconazole 400 mg daily after 3 weeks of amphotericin therapy, with sterilization of the CSF with negative CSFCryptococcus antigen and negative CSF culture. Review of the literature revealed 9 cases of cryptococcal disease in recipients of SCT. Median time of onset was 64 days post transplant. Only 3 meningitis cases were described; 2 of them after allogeneic SCT. Fungal prophylaxis with fluconazole post autologous SCT is recommended at least through engraftment, and for up to 100 days in high-risk patients. A high index of suspicion is needed to diagnose and treat opportunistic infections, especially in the face of immunosuppression and despite adequate prophylaxis. Infection is usually fatal without treatment, thus prompt diagnosis and therapy might be life saving.

  19. High-dose therapy and autologous peripheral blood stem cell transplantation in multiple myeloma: up-front or rescue treatment? Results of a multicenter sequential randomized clinical trial.

    PubMed

    Fermand, J P; Ravaud, P; Chevret, S; Divine, M; Leblond, V; Belanger, C; Macro, M; Pertuiset, E; Dreyfus, F; Mariette, X; Boccacio, C; Brouet, J C

    1998-11-01

    Results to date indicate that high-dose therapy (HDT) with autologous stem cell support improves survival of patients with symptomatic multiple myeloma (MM). We performed a multicenter, sequential, randomized trial designed to assess the optimal timing of HDT and autotransplantation. Among 202 enrolled patients who were up to 56 years old, 185 were randomly assigned to receive HDT and peripheral blood stem cell (PBSC) autotransplantation (early HDT group, n = 91) or a conventional-dose chemotherapy (CCT) regimen (late HDT group, n = 94). In the late HDT group, HDT and transplantation were performed as rescue treament, in case of primary resistance to CCT or at relapse in responders. PBSC were collected before randomization, after mobilization by chemotherapy, and, in the two groups, HDT was preceded by three or four treatments with vincristine, doxorubicin, and methylprednisolone. Data were analyzed on an intent-to-treat basis using a sequential design. Within a median follow-up of 58 months, estimated median overall survival (OS) was 64.6 months in the early HDT group and 64 months in the late group. Survival curves were not different (P = .92, log-rank test). Median event-free survival (EFS) was 39 months in the early HDT group whereas median time between randomization and CCT failure was 13 months in the late group. Average time without symptoms, treatment, and treatment toxicity (TWiSTT) were 27.8 months (95% confidence interval [CI]; range, 23.8 to 31.8) and 22.3 months (range, 16.0 to 28.6) in the two groups, respectively. HDT with PBSC transplantation obtained a median OS exceeding 5 years in young patients with symptomatic MM, whether performed early, as first-line therapy, or late, as rescue treatment. Early HDT may be preferred because it is associated with a shorter period of chemotherapy.

  20. Persistent seropositivity for yellow fever in a previously vaccinated autologous hematopoietic stem cell transplantation recipient.

    PubMed

    Hayakawa, Kayoko; Takasaki, Tomohiko; Tsunemine, Hiroko; Kanagawa, Shuzo; Kutsuna, Satoshi; Takeshita, Nozomi; Mawatari, Momoko; Fujiya, Yoshihiro; Yamamoto, Kei; Ohmagari, Norio; Kato, Yasuyuki

    2015-08-01

    The duration of a protective level of yellow fever antibodies after autologous hematopoietic stem cell transplantation in a previously vaccinated person is unclear. The case of a patient who had previously been vaccinated for yellow fever and who remained seropositive for 22 months after autologous peripheral blood stem cell transplantation for malignant lymphoma is described herein.

  1. Total Body Irradiation Compared With BEAM: Long-Term Outcomes of Peripheral Blood Autologous Stem Cell Transplantation for Non-Hodgkin's Lymphoma

    SciTech Connect

    Liu, Hong-Wei; Seftel, Matthew D.; Rubinger, Morel; Szwajcer, David; Demers, Alain

    2010-10-01

    Purpose: The optimal preparative regimen for non-Hodgkin's lymphoma patients undergoing autologous peripheral blood stem cell transplantation (PBSCT) is unknown. We compared a total body irradiation (TBI)-based regimen with a chemotherapy-alone regimen. Methods and Materials: A retrospective cohort study was performed at a Canadian cancer center. The TBI regimen consisted of cyclophosphamide, etoposide, and TBI 12 Gy in six fractions (CY/E/TBI). The chemotherapy-alone regimen consisted of carmustine, etoposide, cytarabine, and melphalan (BEAM). We compared the acute and long-term toxicities, disease relapse-free survival, and overall survival (OS). Results: Of 73 patients, 26 received CY/E/TBI and 47 received BEAM. The median follow-up for the CY/E/TBI group was 12.0 years and for the BEAM group was 7.3 years. After PBSCT, no differences in acute toxicity were seen between the two groups. The 5-year disease relapse-free survival rate was 50.0% and 50.7% in the CY/E/TBI and BEAM groups, respectively (p = .808). The 5-year OS rate was 53.9% and 63.8% for the CY/E/TBI and BEAM groups, respectivey (p = .492). The univariate analysis results indicated that patients with Stage IV, with chemotherapy-resistant disease, and who had received PBSCT before 2000 had inferior OS. A three-way categorical analysis revealed that transplantation before 2000, rather than the conditioning regimen, was a more important predictive factor of long-term outcome (p = .034). Conclusion: A 12-Gy TBI-based conditioning regimen for PBSCT for non-Hodgkin's lymphoma resulted in disease relapse-free survival and OS similar to that after BEAM. PBSCT before 2000, and not the conditioning regimen, was an important predictor of long-term outcomes. TBI was not associated with more acute toxicity or pneumonitis. We found no indication that the TBI regimen was inferior or superior to BEAM.

  2. Late-onset hepatic veno-occlusive disease post autologous peripheral stem cell transplantation successfully treated with oral defibrotide.

    PubMed

    Shah, Mithun S; Jeevangi, Nandish Kumar S; Joshi, Amit; Khattry, Navin

    2009-01-01

    Hepatic veno-occlusive disease (VOD) remains one of the commonest and most serious complications after myeloablative hematopoietic stem cell transplantation (HSCT). Clinical diagnosis of hepatic VOD is based on the finding of the triad of painful hepatomegaly, hyperbilirubinemia, and unexplained fluid retention occurring within 21 days of the transplant. However, the uncommon clinical entity of late-onset VOD can occur even beyond 20 days and should be considered in the differential diagnosis of any liver disease of more than 3 weeks' duration. While mild cases usually resolve spontaneously, severe VOD is associated with a grim prognosis. Defibrotide, a polydisperse mixture of single-stranded oligonucleotide with antithrombotic and fibrinolytic effects on microvascular endothelium, has emerged as an effective and safe therapy for patients with severe VOD. We describe a patient who presented 55 days post transplant with clinical features suggestive of VOD. Upon treatment with oral defibrotide, he showed complete resolution of the VOD.

  3. High-dose chemotherapy with autologous peripheral blood stem cell transplantation for choriocarcinoma: A case report and literature review

    PubMed Central

    Yamamoto, Eiko; Niimi, Kaoru; Fujikake, Kayo; Nishida, Tetsuya; Murata, Makoto; Mitsuma, Ayako; Ando, Yuichi; Kikkawa, Fumitaka

    2016-01-01

    Choriocarcinoma is a malignant gestational trophoblastic neoplasia (GTN) and one of the curable types of gynecological cancer. However, 10% of choriocarcinoma patients have a poor prognosis, particularly when they have metastasis, apart from pulmonary metastasis, or do not go into remission by the second chemotherapeutic regimen. We herein present the case of a 36-year-old patient who had choriocarcinoma with metastases to the lungs, liver and kidneys. The 5th and 6th regimens with cisplatin for choriocarcinoma failed and the patient developed brain metastases. She was then treated with four cycles of high-dose ifosfamide, carboplatin and etoposide (ICE) with blood progenitor cell support after confirming the effectiveness of ICE at normal doses. The serum human chorionic gonadotropin (hCG) level was 140,009 mIU/ml at the start of high-dose ICE and the patient tolerated this regimen well. However, the beneficial effect was decreasing with each successive course of treatment, with the lowest level of hCG at 103 mIU/ml after the fourth course. The patient did not achieve complete remission and succumbed to the disease 4 months after the last chemotherapy. The findings of the present case and a review of the related literature suggest that high-dose ICE with stem cell rescue may be considered as a viable treatment option for a multi-drug resistant choriocarcinoma or GTN. PMID:27900108

  4. Peripheral blood stem cell mobilization failure.

    PubMed

    Kurnaz, Fatih; Kaynar, Leylagül

    2015-08-01

    Autologous hematopoietic stem cell transplantation (HSCT) is an important and often life saving treatment for many hematological malignancies and selected solid tumors. To rescue hematopoiesis after high-dose chemotherapy in autologous HSCT depends on maintaining sufficient stem cells. Hematopoietic stem cells and progenitor cells expressing CD34 in the BM are mobilized into the circulation with granulocyte-colony stimulating factor ± chemotherapy prior to autologous HSCT. One of the most important factors for success of autologous HSCT is hematopoietic stem cell (HSC) count. Minimum threshold for the engraftment of hematopoietic cells is accepted as 2 × 10(6) CD34 + cells/kg especially for platelet engraftment. Below this level it is defined as stem cell mobilization failure. There are several factors affecting stem cell mobilization: prior chemotherapy (such as fludarabine, melphalan, lenalidomide) and radiotherapy, age, type of disease, bone marrow cellularity. We tried to summarize the reasons of peripheral stem cell mobilization failure.

  5. Clinical experience with plerixafor as a mobilization regimen for autologous peripheral blood stem cell transplantation in patients with refractory germ cell tumors.

    PubMed

    García-Escobar, Ignacio; Parrilla, Lucía; Ortega, Laura Montejano; Castellanos, Daniel; Pallarés, María Ángeles Montalbán; Cortés-Funés, Hernán

    2014-11-01

    The purpose of this study was to report our experience with administration of plerixafor for the mobilization of hematopoietic stem cells (HSCs) in patients with refractory or recurrent germ cell tumors who were candidates for salvage therapy with high-dose chemotherapy and HSC transplantation and for whom mobilization of HSCs had not been achieved by standard therapies. This retrospective and observational study selected patients who were eligible for autologous HSC transplantation (AHSCT) and received plerixafor after failure of HSC mobilization by granulocyte colony-stimulating factor (G-CSF). A total of 5 patients (4 male and 1 female), aged 19-41 years (mean age, 29.6 years) were initially selected. Four patients (80%) achieved an adequate HSC mobilization with plerixafor and subsequently received high-dose chemotherapy followed by HSC transplantation. In these patients, the number of CD34(+) cells collected following plerixafor mobilization was 1.8×10(6)-10.3×10(6) cells/kg, with a peak CD34(+) cell count of 7.0-32.0 cells/μl. Following HSC infusion, these 4 patients achieved a neutrophil count of >0.5×10(3)/mm(3) and a platelet count of >20,000/μl between days 10 and 14. Therefore, patients with high-risk germ cell tumors eligible for AHSCT who are refractory to mobilization by G-CSF, may benefit from the use of plerixafor, possibly to the same extent as patients with lymphoma and multiple myeloma.

  6. Dose-intensified bendamustine followed by autologous peripheral blood stem cell support in relapsed and refractory multiple myeloma with impaired bone marrow function.

    PubMed

    Breitkreutz, Iris; Becker, Natalia; Benner, Axel; Kosely, Florentina; Heining, Christoph; Hillengass, Jens; Egerer, Gerlinde; Ho, Anthony D; Goldschmidt, Hartmut; Raab, Marc S

    2016-12-01

    Therapeutic options in heavily pretreated relapsed/refractory multiple myeloma patients are often very limited because of impaired bone marrow function. Bendamustine is effective in multiple myeloma and has a favourable toxicity profile. We hypothesized that dose-intensified bendamustine (180 mg/m(2) , day 1 and 2) followed by autologous blood stem cell support (ASCS) would improve bone marrow function with low post-transplant toxicity in patients with severely impaired haematopoiesis. We analyzed 28 consecutive myeloma patients, with a median of three prior lines of therapy (range 2-7), who had relapsed from the last treatment with very limited bone marrow function and were therefore ineligible for conventional chemotherapy, novel agents or trial enrolment. Dose-intensified bendamustine with ASCS improved haematopoiesis as reflected by increased platelet counts (median 40/nl vs 94/nl, p = 0.0004) and white blood cell counts (3.0/nl vs 4.8/nl, p = 0.02) at day +100. The median time until engraftment of platelets (>50/nl) was 11 days (0-24 days) and of white cell counts (>1.0/nl) 0 days (0-24 days). At least, a minimal response was achieved in 36% of patients. The disease stabilization rate was 50% while the median progression-free survival rate was limited to 2.14 months. Most importantly, patients were once again eligible for alternative treatments including enrolment into clinical trials. We conclude that dose-intensified bendamustine followed by ASCS is safe and feasible for multiple myeloma patients with very limited bone marrow reserve. Copyright © 2015 John Wiley & Sons, Ltd.

  7. Clinical experience with plerixafor as a mobilization regimen for autologous peripheral blood stem cell transplantation in patients with refractory germ cell tumors

    PubMed Central

    GARCÍA-ESCOBAR, IGNACIO; PARRILLA, LUCÍA; ORTEGA, LAURA MONTEJANO; CASTELLANOS, DANIEL; PALLARÉS, MARÍA ÁNGELES MONTALBÁN; CORTÉS-FUNÉS, HERNÁN

    2014-01-01

    The purpose of this study was to report our experience with administration of plerixafor for the mobilization of hematopoietic stem cells (HSCs) in patients with refractory or recurrent germ cell tumors who were candidates for salvage therapy with high-dose chemotherapy and HSC transplantation and for whom mobilization of HSCs had not been achieved by standard therapies. This retrospective and observational study selected patients who were eligible for autologous HSC transplantation (AHSCT) and received plerixafor after failure of HSC mobilization by granulocyte colony-stimulating factor (G-CSF). A total of 5 patients (4 male and 1 female), aged 19–41 years (mean age, 29.6 years) were initially selected. Four patients (80%) achieved an adequate HSC mobilization with plerixafor and subsequently received high-dose chemotherapy followed by HSC transplantation. In these patients, the number of CD34+ cells collected following plerixafor mobilization was 1.8×106–10.3×106 cells/kg, with a peak CD34+ cell count of 7.0–32.0 cells/μl. Following HSC infusion, these 4 patients achieved a neutrophil count of >0.5×103/mm3 and a platelet count of >20,000/μl between days 10 and 14. Therefore, patients with high-risk germ cell tumors eligible for AHSCT who are refractory to mobilization by G-CSF, may benefit from the use of plerixafor, possibly to the same extent as patients with lymphoma and multiple myeloma. PMID:25279175

  8. Autologous hematopoietic stem cell transplantation in lymphoma patients is associated with a decrease in the double strand break repair capacity of peripheral blood lymphocytes

    PubMed Central

    Lacoste, Sandrine; Bhatia, Smita; Chen, Yanjun; Bhatia, Ravi; O’Connor, Timothy R.

    2017-01-01

    Patients who undergo autologous hematopoietic stem cell transplantation (aHCT) for treatment of a relapsed or refractory lymphoma are at risk of developing therapy related- myelodysplasia/acute myeloid leukemia (t-MDS/AML). Part of the risk likely resides in inherent interindividual differences in their DNA repair capacity (DRC), which is thought to influence the effect chemotherapeutic treatments have on the patient’s stem cells prior to aHCT. Measuring DRC involves identifying small differences in repair proficiency among individuals. Initially, we investigated the cell model in healthy individuals (primary lymphocytes and/or lymphoblastoid cell lines) that would be appropriate to measure genetically determined DRC using host-cell reactivation assays. We present evidence that interindividual differences in DRC double-strand break repair (by non-homologous end-joining [NHEJ] or single-strand annealing [SSA]) are better preserved in non-induced primary lymphocytes. In contrast, lymphocytes induced to proliferate are required to assay base excision (BER) or nucleotide excision repair (NER). We established that both NHEJ and SSA DRCs in lymphocytes of healthy individuals were inversely correlated with the age of the donor, indicating that DSB repair in lymphocytes is likely not a constant feature but rather something that decreases with age (~0.37% NHEJ DRC/year). To investigate the predictive value of pre-aHCT DRC on outcome in patients, we then applied the optimized assays to the analysis of primary lymphocytes from lymphoma patients and found that individuals who later developed t-MDS/AML (cases) were indistinguishable in their DRC from controls who never developed t-MDS/AML. However, when DRC was investigated shortly after aHCT in the same individuals (21.6 months later on average), aHCT patients (both cases and controls) showed a significant decrease in DSB repair measurements. The average decrease of 6.9% in NHEJ DRC observed among aHCT patients was much

  9. First-line therapy of peripheral T-cell lymphoma: extension and long-term follow-up of a study investigating the role of autologous stem cell transplantation

    PubMed Central

    Wilhelm, M; Smetak, M; Reimer, P; Geissinger, E; Ruediger, T; Metzner, B; Schmitz, N; Engert, A; Schaefer-Eckart, K; Birkmann, J

    2016-01-01

    Current guidelines recommend consolidation with autologous stem cell transplantation (autoSCT) after induction chemotherapy for most patients with peripheral T-cell lymphoma (PTCL). This assumption is based on five prospective phase II studies, three of which included <50 patients with limited follow-up. Here we present the final analysis of the prospective German study. The treatment regimen consisted of four to six cycles of CHOP chemotherapy followed by mobilizing therapy and stem cell collection. Patients in complete remission (CR) or partial remission (PR) underwent myeloablative chemo(radio)therapy and autoSCT. From January 2001 to July 2010, 111 patients were enrolled in the study. The main subgroups were PTCL not specified (n=42) and angioimmunoblastic T-cell lymphoma (n=37). Seventy-five (68%) of the 111 patients received transplantation. The main reason for not receiving autoSCT was progressive disease. In an intent-to-treat analysis, the complete response rate after myeloablative therapy was 59%. The estimated 5-year overall survival, disease-free survival and progression-free survival rates were 44%, 54% and 39%, respectively. The results of this study confirm that upfront autoSCT can result in long-term remissions in patients with all major subtypes of PTCL and therefore should be part of first-line therapy whenever possible. PMID:27471868

  10. Autologous stem cell transplantation for systemic sclerosis.

    PubMed

    Farge, Dominique; Nash, Richard; Laar, Jacob M

    2008-12-01

    Systemic sclerosis (SSc) is a generalised autoimmune disease, of yet unknown origin, with two major clinical subsets: the limited (lcSSc) and the diffuse cutaneous (dcSSc) forms, which can be distinguished by the extent of skin involvement, the autoantibody profile and the pattern of organ involvement. With an incidence of 1/10(5), SSc affects around 250,000 people in Europe and is responsible for significant morbidity with a 5-year mortality rate of at least 30% of all patients. In patients with rapidly progressive dcSSc, the 5-year mortality is estimated to be 40-50%. Hematopoietic stem cell transplantation (HSCT), mostly autologous but also allogeneic in some specific cases, has been employed worldwide since 1996 as a new therapeutic strategy in patients with a poor prognosis. In 2007, 150 HSCT procedures have been reported in the EBMT data base. We review herein both the short and the long-term reports from the various European and North American phase I-II studies, which have shown that autologous HSCT in selected patients with severe dcSSc results in sustained improvement of skin thickening and stabilisation of organ function up to seven years after transplantation. Based on these promising results, ongoing phase III trials have been designed in parallel, both in Europe (ASTIS) and in North America (SCOTT) aiming to analyse the respective benefits from autologous HSCT respectively without or with high dose irradiation. This review reports the current data concerning the effects of HSCT on survival, skin, and major organ function in patients with severe dcSSc.

  11. How to manage poor mobilizers for high dose chemotherapy and autologous stem cell transplantation?

    PubMed

    Ataca Atilla, Pinar; Bakanay Ozturk, Sule Mine; Demirer, Taner

    2016-12-26

    Today, peripheral blood stem cells are the preferred source of stem cells over bone marrow. Therefore, mobilization plays a crutial role in successful autologous stem cell transplantation. Poor mobilization is generally defined as failure to achieve the target level of at least 2×10(6) CD34(+) cells/kg body weight. There are several strategies to overcome poor mobilization: 1) Larger volume Leukapheresis (LVL) 2) Re-mobilization 3) Plerixafor 4) CM+Plerixafor (P)+G-CSF and 5) Bone Marrow Harvest. In this review, the definitions of successful and poor mobilization are discussed. Management strategies for poor mobilization are defined. The recent research on new agents are included.

  12. Necrobiotic xanthogranuloma successfully treated with autologous stem cell transplantation.

    PubMed

    Goede, Jeroen S; Misselwitz, Benjamin; Taverna, Christian; Schanz, Urs; Dispenzieri, Angela; Hummel, Yvonne; Trüeb, Ralph M; Fehr, Jörg

    2007-04-01

    Paraproteinemia can be complicated by necrobiotic xanthogranuloma. Therapeutic options for this progressive disease are limited, and there is no agreement on a single best strategy. We report the case of a patient with a massive periorbital infiltration narrowing the palpebral fissure and blinding the patient. Conventional myeloma therapy had only limited benefit in our patient. However, he was successfully treated with high-dose chemotherapy followed by autologous stem cell transplantation, rendering the patient free of symptoms. This is the first report of autologous stem cell transplantation in a patient with necrobiotic xanthogranuloma.

  13. Autologous stem cell transplantation versus alternative allogeneic donor transplants in adult acute leukemias.

    PubMed

    Claude Gorin, Norbert

    2016-04-01

    The availability of alternative sources of stem cells including most recently T-replete haploidentical marrow or peripheral blood, and the increasing use of reduced-intensity conditioning (RIC), renders feasible an allogeneic transplant to almost all patients with acute leukemia up to 70 years of age. Autologous stem cell transplantation (ASCT) for consolidation of complete remission (CR), however, offers in some circumstances an alternative option. Although associated with a higher relapse rate, autologous transplant benefits from a lower non-relapse mortality, the absence of graft-versus-host disease (GVHD), and a better quality of life for long-term survivors. The recent use of intravenous busulfan (IVBU) with high-dose melphalan, better monitoring of minimal residual disease (MRD), and maintenance therapy post autografting bring new interest. Few retrospective studies compared the outcome following alternative donor versus autologous transplants for remission consolidation. Genoidentical and phenoidentical allogeneic stem cell transplantations are undisputed gold standards, but there are no data showing the superiority of alternative allogeneic donor over autologous transplantation, at the time of undetectable MRD, in patients with good- and intermediate-1 risk acute myelocytic leukemia (AML) in first complete remission (CR1), acute promyelocytic leukemia in second complete remission (CR2), and Philadelphia chromosome-positive (Ph(+)) acute lymphocytic leukemia (ALL).

  14. Autologous hematopoietic stem cell transplantation for systemic sclerosis.

    PubMed

    Milanetti, Francesca; Bucha, Jurate; Testori, Alessandro; Burt, Richard K

    2011-03-01

    Systemic sclerosis is a rare disorder manifesting as skin and internal organ fibrosis, a diffuse vasculopathy, inflammation, and features of autoimmunity. Patients with diffuse cutaneous disease or internal organ involvement have a poor prognosis with high mortality. To date no therapy has been shown to reverse the natural course of the disease. Immune suppressive drugs are commonly utilized to treat patients, but randomized trials have generally failed to demonstrate any long-term benefit. In phase I/II trials, autologous hematopoietic stem cell transplantation (HSCT) has demonstrated impressive reversal of skin fibrosis, improved functionality and quality of life, and stabilization of internal organ function, but initial studies were complicated by significant treatment-related mortality. Treatment-related mortality was reduced by better pre-transplant evaluation to exclude patients with compromised cardiac function and by treating patients earlier in disease, allowing selected patients the option of autologous HSCT treatment. There are currently three ongoing randomized trials of autologous HSCT for systemic sclerosis: ASSIST (American Systemic Sclerosis Immune Suppression versus Transplant), SCOT (scleroderma cyclophosphamide versus Transplant), and ASTIS (Autologous Stem cell Transplantation International Scleroderma). The results from these trials should clarify the role of autologous HSCT in the currently limited therapeutic arsenal of severe systemic sclerosis.

  15. Mobilization of peripheral blood stem cells.

    PubMed

    Arslan, Onder; Moog, Rainer

    2007-10-01

    The use of peripheral blood stem cells (PBSC) as a source of hematopoietic stem cells is steadily increasing and has nearly supplanted bone marrow transplantation. The present article reviews mobilization of PBSC as well as the side effects. Under steady state conditions less than 0.05% of the white blood cells (WBC) are CD34+ cells. Chemotherapy results in a 5-15-fold increase of PBSC. Combining chemotherapy and growth factors increases CD34+ cells up to 6% of WBC. In the allogeneic setting, granulocyte-colony stimulating factor (G-CSF) is used alone for PBSC mobilization. Several factors affect the mobilization of PBSC: age, gender, type of growth factor, dose of the growth factor and in the autologous setting, the patient's diagnosis, chemotherapy regimen and number of previous chemotherapy cycles or radiation. Muscle and bone pain are frequent adverse events in allogeneic stem cell mobilization but are usually tolerated with the use of analgesics. Spleen enlargement followed by rupture is a serious complication in allogeneic donors. Large volume apheresis (LVL) with a processed volume of more than 4-fold of the patient's blood volume can be used to increase the CD34+ yield in patients with low CD34+ pre-counts, resulting in higher yields of CD34+ cells for transplantation. Processing of more blood in LVL is achieved by an increase of the blood flow rate and an altered anticoagulation regimen with the occurrence of more citrate reactions.

  16. Twenty-five years of peripheral blood stem cell transplantation.

    PubMed

    Körbling, Martin; Freireich, Emil J

    2011-06-16

    Peripheral blood stem cell transplantation (PBSCT) is the most common transplantation procedure performed in medicine. Its clinical introduction in 1986 replaced BM as a stem-cell source to approximately 100% in the autologous and to approximately 75% in the allogeneic transplantation setting. This historical overview provides a brief insight into the discovery of circulating hematopoietic stem cells in the early 1960s, the development of apheresis technology, the discovery of hematopoietic growth factors and small molecule CXCR4 antagonist for stem- cell mobilization, and in vivo experimental transplantation studies that eventually led to clinical PBSCT. Also mentioned are the controversies surrounding the engraftment potential of circulating stem cells before acceptance as a clinical modality. Clinical trials comparing the outcome of PBSCT with BM transplantation, registry data analyses, and the role of the National Marrow Donor Program (NMDP) in promoting unrelated blood stem-cell donation are addressed.

  17. Treatment of Oral Mucositis in Hematologic Patients Undergoing Autologous or Allogeneic Transplantation of Peripheral Blood Stem Cells: a Prospective, Randomized Study with a Mouthwash Containing Camelia Sinensis Leaf Extract

    PubMed Central

    Carulli, Giovanni; Rocco, Melania; Panichi, Alessia; Chios, Chiara Feira; Ciurli, Ester; Mannucci, Chiara; Sordi, Elisabetta; Caracciolo, Francesco; Papineschi, Federico; Benedetti, Edoardo; Petrini, Mario

    2013-01-01

    Oral mucositis is an important side effect of hematopoietic stem cell transplantation (HCST), mainly due to toxicity of conditioning regimens. It produces significant pain and morbidity. The present study reports a prospective, randomized, non-blinded study testing the efficacy of a new mouthwash, called Baxidil Onco® (Sanitas Farmaceutici Srl, Tortona, Italy) in 60 hematologic patients undergoing HCST (28 autologous, 32 allogeneic). Baxidil Onco®, used three times a day from Day -1 to Day +30, in addition to standard prophylactic schedules, was administered to 14 patients undergoing autologous and 14 patients undergoing allogeneic HCST. The remaining 32 patients (14 autologous and 18 HCST) were treated only with standard prophylactic schedules and served as control. In our study, the overall incidence of oral mucositis, measured according to the World Health Organization 0-4 scale, was 50% in the Baxidl Onco® group versus 82% in the control group (P=0.022). In addition, a significant reduction in scale 2-4 oral mucositis was observed in the Baxidil Onco® group (25% vs 56.2%; P=0.0029). The results obtained indicate that incidence, severity and duration of oral mucositis induced by conditioning regimens for HCST can be significantly reduced by oral rinsing with Baxidil Onco®, in addition to the standard prophylaxis scheme. Since Camelia Sinensin extract, which is used to produce green tea, is the main agent in this mouthwash, we hypothesize that the anti-oxidative properties of polyphenolic compounds of tea might exert protective effects on oral mucosa. PMID:23888242

  18. [Therapeutic intensification and autologous stem cell transplantation in autoimmune diseases].

    PubMed

    Marjanovic, Z; Gerber, I; Toledano, C; Hen-Solal, J; Damade, R; de Saint-Cyr, I; Sarrot-Reynauld, F; Ilié, D; Daneshpouy, M; Mounier, N; Ruivard, M; Tyndall, C; Vidal, E; Quere, I; Durand, J-M; Constans, J; Farge, D

    2005-02-26

    THE PATHOPHYSIOLOGY of most autoimmune diseases is often poorly understood. EXPERIMENTAL CONSIDERATIONS and clinical experience suggest that high doses immunoablation followed by stem cell transplantation is a therapeutic option to consider for certain severe autoimmune disorders. THE CONCEPT OF RESTORING NORMAL IMMUNE REACTIVITY must in part br true since current results of 466 transplants (445 autologous, 21 allogeneic) patients suffering from various autoimmune diseases show a beneficial outcome in approximately 2/3 of the patients. TO IMPROVE THE EFFICACY AND SAFETY OF SUCH AN AGGRESSIVE PROCEDURE in patients with potentially affected vital organs by the underlying autoimmune disease, it is especially important to follow international consensus guidelines and to centrally collect clinical data for in depth analysis in the EBMT International Stem Cell Project for Autoimmune Disease in Basel, Switzerland. PHASE III STUDIES ARE RUNNING FOR SYSTEMIC SCLEROSIS (Astis, Autologous Stem cell Transplantation International Rheumatoid Arthritis Trial) started in 2003. A STUDY PROJECT IS PLANNED FOR MULTIPLE SCLEROSIS (Astims, Autologous Stem cell Transplantation International Multiple Sclerosis).

  19. Busulfan and melphalan as consolidation therapy with autologous peripheral blood stem cell transplantation following Children's Oncology Group (COG) induction platform for high-risk neuroblastoma: early results from a single institution.

    PubMed

    Soni, Sandeep; Pai, Vinita; Gross, Thomas G; Ranalli, Mark

    2014-03-01

    Bu-Mel as preparative therapy prior to autologous stem cell rescue was recently shown to be superior to the conventional CEM regimen for HR NBL in Europe. There are no data available on the feasibility and toxicity of Bu-Mel as consolidation therapy following the COG-type induction regimens used in North America. We report early complications and outcomes of patients with HR NBL who received Bu-Mel for consolidation following COG-based induction. Retrospective analysis of all patients who had received Bu-Mel as preparative regimen prior to stem cell rescue for HR NBL was carried out. Toxicity, outcomes, and any delays to receiving radiation or anti-GD2 antibody therapy were analyzed. Six patients undergoing PBSCT had received Bu-Mel. The treatment was well tolerated. Mucositis was the main toxicity; three patients had developed neutropenia fever and none developed pulmonary toxicity. One patient had developed moderate SOS that responded to conservative management. All patients were able to receive and tolerate post-transplant local radiotherapy and ch.14.18 anti-GD2 antibody therapy without any delays. All patients are alive with no disease recurrence. The Bu-Mel regimen is well tolerated and is feasible post-COG-type induction platform.

  20. Autologous Stem Cells Transplantation in Egyptian Patients with Liver Cirrhosis on Top of Hepatitis C Virus

    PubMed Central

    Al Tayeb, Hoda; El Dorry, Ahmed; Amer, Nehad; Mowafy, Nadia; Zimaity, Maha; Bayoumy, Essam; Saleh, Shereen A.

    2015-01-01

    Background and Objectives Use of pluripotent stem cells is an ideal solution for liver insufficiencies. This work aims is to evaluate the safety and feasibility of autologous stem cells transplantation (SCT) in Egyptian patients of liver cirrhosis on top of hepatitis C virus (HCV). Subjects and Results 20 patients with HCV induced liver cirrhosis were divided into 2 groups. Group I: included 10 patients with liver cirrhosis Child score ≥9, for whom autologous stem cell transplantation was done using granulocyte colony stimulating factor (G-CSF) for stem cells mobilization. Separation and collection of the peripheral blood stem cells was done by leukapheresis. G-CSF mobilized peripheral blood mononuclear cells (G-CSF PB-MNCs) were counted by flow cytometry. Stem cell injection into the hepatic artery was done. Group II: included 10 patients with HCV induced liver cirrhosis as a control group. Follow up and comparison between both groups were done over a follow up period of 6 months. The procedure was well tolerated. Mobilization was successful and the total number of G-CSF PB-MNCs in the harvests ranged from 25×106 to 191×106. There was improvement in the quality of life, serum albumin, total bilirubin, liver enzymes and the Child-Pugh score of group I over the first two-three months after the procedure. Conclusion SCT in HCV induced liver cirrhosis is a safe procedure. It can improve the quality of life and hepatic functions transiently with no effect on the life expectancy or the fate of the liver cirrhosis. PMID:26634069

  1. Sustained telomere erosion due to increased stem cell turnover during triple autologous hematopoietic stem cell transplantation.

    PubMed

    Widmann, Thomas; Kneer, Harald; König, Jochem; Herrmann, Markus; Pfreundschuh, Michael

    2008-01-01

    Telomeres cap chromosomal ends and are shortened throughout a lifetime. Additional telomere erosion has been documented during conventional chemotherapy or hematopoietic stem cell transplantation. Previous studies of stem cell transplantation reported variable amounts of telomere shortening with inconsistent results regarding the persistence of telomere shortening. Here we have prospectively studied telomere length and proliferation kinetics of hematopoietic cells in aggressive non-Hodgkin lymphoma patients who underwent a four-course high-dose chemotherapy protocol combined with triple autologous stem cell transplantation. We observed sustained telomere shortening in hematopoietic cells after triple stem cell transplantation with prolonged stem cell replication during the first year after stem cell transplantation.

  2. Autologous hematopoietic stem cell transplantation in classical Hodgkin's lymphoma

    PubMed Central

    Cortez, Afonso José Pereira; Dulley, Frederico Luiz; Saboya, Rosaura; Mendrone Júnior, Alfredo; Amigo Filho, Ulisses; Coracin, Fabio Luiz; Buccheri, Valéria; Linardi, Camila da Cruz Gouveia; Ruiz, Milton Artur; Chamone, Dalton de Alencar Fischer

    2011-01-01

    Background Hodgkin's lymphoma has high rates of cure, but in 15% to 20% of general patients and between 35% and 40% of those in advanced stages, the disease will progress or will relapse after initial treatment. For this group, hematopoietic stem cell transplantation is considered one option of salvage therapy. Objectives To evaluate a group of 106 patients with Hodgkin's lymphoma, who suffered relapse or who were refractory to treatment, submitted to autologous hematopoietic stem cell transplantation in a single transplant center. Methods A retrospective study was performed with data collected from patient charts. The analysis involved 106 classical Hodgkin's lymphoma patients who were consecutively submitted to high-dose chemotherapy followed by autologous transplants in a single institution from April 1993 to December 2006. Results The overall survival rates of this population at five and ten years were 86% and 70%, respectively. The disease-free survival was approximately 60% at five years. Four patients died of procedure-related causes but relapse of classical Hodgkin's lymphoma after transplant was the most frequent cause of death. Univariate analysis shows that sensitivity to pre-transplant treatment and hemoglobin < 10 g/dL at diagnosis had an impact on patient survival. Unlike other studies, B-type symptoms did not seem to affect overall survival. Lactic dehydrogenase and serum albumin concentrations analyzed at diagnosis did not influence patient survival either. Conclusion Autologous hematopoietic stem cell transplantation is an effective treatment strategy for early and late relapse in classical Hodgkin's lymphoma for cases that were responsive to pre-transplant chemotherapy. Refractory to treatment is a sign of worse prognosis. Additionally, a hemoglobin concentration below 10 g/dL at diagnosis of Hodgkin's lymphoma has a negative impact on the survival of patients after transplant. As far as we know this relationship has not been previously reported

  3. Plerixafor and granulocyte colony-stimulating factor for first-line steady-state autologous peripheral blood stem cell mobilization in lymphoma and multiple myeloma: results of the prospective PREDICT trial

    PubMed Central

    Russell, Nigel; Douglas, Kenny; Ho, Anthony D.; Mohty, Mohamad; Carlson, Kristina; Ossenkoppele, G.J.; Milone, Giuseppe; Pareja, Macarena Ortiz; Shaheen, Daniel; Willemsen, Arnold; Whitaker, Nicky; Chabannon, Christian

    2013-01-01

    In Europe, the combination of plerixafor + granulocyte colony-stimulating factor is approved for the mobilization of hematopoietic stem cells for autologous transplantation in patients with lymphoma and myeloma whose cells mobilize poorly. The purpose of this study was to further assess the safety and efficacy of plerixafor + granulocyte colony-stimulating factor for front-line mobilization in European patients with lymphoma or myeloma. In this multicenter, open label, single-arm study, patients received granulocyte colony-stimulating factor (10 μg/kg/day) subcutaneously for 4 days; on the evening of day 4 they were given plerixafor (0.24 mg/kg) subcutaneously. Patients underwent apheresis on day 5 after a morning dose of granulocyte colony-stimulating factor. The primary study objective was to confirm the safety of mobilization with plerixafor. Secondary objectives included assessment of efficacy (apheresis yield, time to engraftment). The combination of plerixafor + granulocyte colony-stimulating factor was used to mobilize hematopoietic stem cells in 118 patients (90 with myeloma, 25 with non-Hodgkin's lymphoma, 3 with Hodgkin's disease). Treatment-emergent plerixafor-related adverse events were reported in 24 patients. Most adverse events occurred within 1 hour after injection, were grade 1 or 2 in severity and included gastrointestinal disorders or injection-site reactions. The minimum cell yield (≥2×106 CD34+ cells/kg) was harvested in 98% of patients with myeloma and in 80% of those with non-Hodgkin's lymphoma in a median of one apheresis. The optimum cell dose (≥5×106 CD34+ cells/kg for non-Hodgkin's lymphoma or ≥6×106 CD34+ cells/kg for myeloma) was harvested in 89% of myeloma patients and 48% of non-Hodgkin's lymphoma patients. In this prospective, multicenter European study, mobilization with plerixafor + granulocyte colony-stimulating factor allowed the majority of patients with myeloma or non-Hodgkin's lymphoma to undergo transplantation with

  4. Effectiveness of autologous serum as an alternative to fetal bovine serum in adipose-derived stem cell engineering.

    PubMed

    Choi, Jaehoon; Chung, Jee-Hyeok; Kwon, Geun-Yong; Kim, Ki-Wan; Kim, Sukwha; Chang, Hak

    2013-09-01

    In cell culture, medium supplemented with fetal bovine serum is commonly used, and it is widely known that fetal bovine serum supplies an adequate environment for culture and differentiation of stem cells. Nevertheless, the use of xenogeneic serum can cause several problems. We compared the effects of four different concentrations of autologous serum (1, 2, 5, and 10%) on expansion and adipogenic differentiation of adipose-derived stem cells using 10% fetal bovine serum as a control. The stem cells were grafted on nude mice and the in vivo differentiation capacity was evaluated. The isolation of adipose-derived stem cells was successful irrespective of the culture medium. The proliferation potential was statistically significant at passage 2, as follows: 10% autologous serum > 10% fetal bovine serum = 5% autologous serum > 2% autologous serum = 1% autologous serum. The differentiation capacity appeared statistically significant at passage 4, as follows: 10% fetal bovine serum > 10% autologous serum = 5% autologous serum > 2% autologous serum = 1% autologous serum. Ten percent autologous serum and 10% fetal bovine serum had greater differentiation capacity than 1 and 2% autologous serum in vivo, and no significant difference was observed between the groups at ≥ 5% concentration at 14 weeks. In conclusion, 10% autologous serum was at least as effective as 10% fetal bovine serum with respect to the number of adipose-derived stem cells at the end of both isolation and expansion, whereas 1 and 2% autologous serum was inferior.

  5. High-dose ifosfamide/carboplatin/etoposide: maximum tolerable doses, toxicities, and hematopoietic recovery after autologous stem cell reinfusion.

    PubMed

    Fields, K K; Elfenbein, G J; Perkins, J B; Janssen, W E; Ballester, O F; Hiemenz, J W; Zorsky, P E; Kronish, L E; Foody, M C

    1994-10-01

    We treated 115 patients in a phase I/II dose-escalation study of ifosfamide/carboplatin/etoposide (ICE) followed by autologous stem cell rescue. Patients treated had a variety of diagnoses, including breast cancer (high-risk stage II disease with eight or more positive nodes, stage III disease, and responsive metastatic disease), non-Hodgkin's lymphoma, Hodgkin's disease, acute leukemia in first remission, and various solid tumors that were responsive to induction therapy. Patients received autologous bone marrow stem cells or peripheral blood stem cells primed by one of several methods. The maximum tolerated dose of ICE was determined to be ifosfamide 20,100 mg/m2, carboplatin 1,800 mg/m2, and etoposide 3,000 mg/m2 when administered as a 6-day regimen. The dose-limiting toxicities included acute renal failure, severe central nervous system toxicity, and "leaky capillary syndrome" with hypoalbuminemia, profound fluid overload, and pulmonary insufficiency. Analysis of hematologic recovery based on stem cell source and influence of hematopoietic growth factor administration was undertaken. Hematopoietic growth factor use significantly reduced neutrophil engraftment time for patients receiving bone marrow stem cells, with evidence of earlier recovery times for patients receiving granulocyte colony-stimulating factor compared with granulocyte-macrophage colony-stimulating factor. Neutrophil recovery times varied based on the source of stem cells used, with the earliest engraftment times seen for patients receiving peripheral blood stem cells primed with cyclophosphamide and granulocyte colony-stimulating factor. Platelet recovery times were not statistically different for any of the subsets. In conclusion, the maximum tolerated dose of ICE has been defined, and the source of stem cells and the use of hematopoietic growth factors influence hematopoietic recovery.

  6. Endocrinopathies after Allogeneic and Autologous Transplantation of Hematopoietic Stem Cells

    PubMed Central

    Muscogiuri, Giovanna; Palomba, Stefano; Serio, Bianca; Sessa, Mariarosaria; Giudice, Valentina; Ferrara, Idalucia; Tauchmanovà, Libuse; Colao, Annamaria; Selleri, Carmine

    2014-01-01

    Early and late endocrine disorders are among the most common complications in survivors after hematopoietic allogeneic- (allo-) and autologous- (auto-) stem cell transplant (HSCT). This review summarizes main endocrine disorders reported in literature and observed in our center as consequence of auto- and allo-HSCT and outlines current options for their management. Gonadal impairment has been found early in approximately two-thirds of auto- and allo-HSCT patients: 90–99% of women and 60–90% of men. Dysfunctions of the hypothalamus-pituitary-growth hormone/insulin growth factor-I axis, hypothalamus-pituitary-thyroid axis, and hypothalamus-pituitary-adrenal axis were documented as later complicances, occurring in about 10, 30, and 40–50% of transplanted patients, respectively. Moreover, overt or subclinical thyroid complications (including persistent low-T3 syndrome, chronic thyroiditis, subclinical hypo- or hyperthyroidism, and thyroid carcinoma), gonadal failure, and adrenal insufficiency may persist many years after HSCT. Our analysis further provides evidence that main recognized risk factors for endocrine complications after HSCT are the underlying disease, previous pretransplant therapies, the age at HSCT, gender, total body irradiation, posttransplant derangement of immune system, and in the allogeneic setting, the presence of graft-versus-host disease requiring prolonged steroid treatment. Early identification of endocrine complications can greatly improve the quality of life of long-term survivors after HSCT. PMID:24883377

  7. Cyclophosphamide-based hematopoietic stem cell mobilization before autologous stem cell transplantation in newly diagnosed multiple myeloma.

    PubMed

    Tuchman, Sascha A; Bacon, Wendi A; Huang, Li-Wen; Long, Gwynn; Rizzieri, David; Horwitz, Mitchell; Chute, John P; Sullivan, Keith; Morris Engemann, Ashley; Yopp, Amanda; Li, Zhiguo; Corbet, Kelly; Chao, Nelson; Gasparetto, Cristina

    2015-06-01

    High-dose cyclophosphamide (Cy) is frequently employed for peripheral blood mobilization of hematopoietic stem cells before high-dose chemotherapy with autologous stem cell transplantation (ASCT) in multiple myeloma (MM). The benefit of mobilization with Cy over filgrastim (granulocyte colony-stimulating factor; G-CSF) alone is unclear. Between 2000 and 2008, 167 patients with newly diagnosed MM underwent single ASCT after melphalan conditioning at our institution. Seventy-three patients were mobilized with G-CSF alone, and 94 patients with Cy plus G-CSF (Cy+G-CSF). We retrospectively analyzed Cy's impact on both toxicity and efficacy. Mobilization efficiency was augmented by Cy; a mean total of 12 versus 5.8 × 10(6) CD34+ cells/kg were collected from patients mobilized with Cy+G-CSF versus G-CSF, respectively, (P < 0.01), over a mean of 1.6 versus 2.2 days of peripheral blood apheresis (p = 0.001). Mobilization-related toxicity was also, however, augmented by Cy; 14% of Cy+G-CSF patients were hospitalized because of complications versus none receiving G-CSF (P < 0.0001). Toxicity, including death, related to ASCT was similar between cohorts. Regarding long-term outcomes, multivariate analysis revealed no difference for Cy+G-CSF versus G-CSF (hazard ratio 0.8 for event-free survival [95% confidence interval {CI} 0.57-1.25] and 0.96 for overall survival [95% CI 0.61-1.54]). In summary, we show that mobilization with Cy increases toxicity without positively impacting long-term outcomes in MM. Our findings place into question Cy's benefit as a routine component of stem cell mobilization regimens in MM. Randomized trials are needed to elucidate the risks and benefits of Cy more definitively.

  8. The potential role of autologous stem cell transplantation in patients with systemic lupus erythematosus.

    PubMed

    Hahn, B H

    1997-05-01

    Transfer of disease by bone marrow cells has been described in experimental models of systemic lupus erythematosus (SLE). In one experiment, marrow ablation followed by transfer of T depleted allogeneic marrow resulted in prolonged survival of animals with SLE. Some experimental studies suggest a rationale for autologous stem cell transplantation indicating this intervention might "reset the thermostat" so that normal immunoregulation can control disease, while others indicate it might not be beneficial. The pros and cons of offering patients with SLE autologous hematopoietic stem cell transplantation are considered. A profile of the patient with SLE who might be considered as a candidate for autologous stem cell transplantation can be constructed by evaluating causes of death and factors that increase mortality. This profile includes life threatening disease, inadequate response to aggressive immunosuppressive therapy, and adequate function of all major organs so that risks associated with stem cell transplantation can be minimized.

  9. Total Marrow Irradiation as Part of Autologous Stem Cell Transplantation for Asian Patients with Multiple Myeloma

    PubMed Central

    Lin, Shih-Chiang; Hsieh, Pei-Ying; Shueng, Pei-Wei; Tien, Hui-Ju; Wang, Li-Ying

    2013-01-01

    To compare the outcomes of melphalan 200 mg/m2 (HDM200) and 8 Gy total marrow irradiation (TMI) delivered by helical tomotherapy plus melphalan 140 mg/m2 (HDM140 + TMI 8 Gy) in newly diagnosed symptomatic multiple myeloma (MM) Asian patients. Between 2007 and 2010, nine consecutive myeloma patients who were scheduled to undergo autologous stem cell transplantation (ASCT) were studied. The patients received three cycles of vincristine-adriamycin-dexamethasone (VAD) regimen as induction chemotherapy, and if they had a partial response, peripheral blood stem cells were collected by dexamethasone-etoposide-cyclophosphamide-cisplatin (DECP). In arm A, six patients received the HDM200. In arm B, three patients received HDM140 + TMI 8 Gy. In arm B, the neutropenic duration was slightly longer than in arm A (P = 0.048). However, hematologic recovery (except for neutrophils), transfusion requirement, median duration of hospitalization, and the dose of G-CSF were similar in both arms. The median duration of overall survival and event-free survival was similar in the two arms (P = 0.387). As a conditioning regiment, HDM140 + TMI 8 Gy provide another chance for MM Asian patients who were not feasible for HDM200. PMID:24089671

  10. Peripheral Nerve Injury: Stem Cell Therapy and Peripheral Nerve Transfer

    PubMed Central

    Sullivan, Robert; Dailey, Travis; Duncan, Kelsey; Abel, Naomi; Borlongan, Cesario V.

    2016-01-01

    Peripheral nerve injury can lead to great morbidity in those afflicted, ranging from sensory loss, motor loss, chronic pain, or a combination of deficits. Over time, research has investigated neuronal molecular mechanisms implicated in nerve damage, classified nerve injury, and developed surgical techniques for treatment. Despite these advancements, full functional recovery remains less than ideal. In this review, we discuss historical aspects of peripheral nerve injury and introduce nerve transfer as a therapeutic option, as well as an adjunct therapy to transplantation of Schwann cells and their stem cell derivatives for repair of the damaged nerve. This review furthermore, will provide an elaborated discussion on the sources of Schwann cells, including sites to harvest their progenitor and stem cell lines. This reflects the accessibility to an additional, concurrent treatment approach with nerve transfers that, predicated on related research, may increase the efficacy of the current approach. We then discuss the experimental and clinical investigations of both Schwann cells and nerve transfer that are underway. Lastly, we provide the necessary consideration that these two lines of therapeutic approaches should not be exclusive, but conversely, should be pursued as a combined modality given their mutual role in peripheral nerve regeneration. PMID:27983642

  11. Management strategies for poor peripheral blood stem cell mobilization.

    PubMed

    Moog, Rainer

    2008-06-01

    Peripheral blood stem cells (PBSC) have nearly replaced bone marrow (BM) as the preferred source of hematopoietic rescue for patients undergoing high-dose chemotherapy. However, some patients fail to mobilize sufficient numbers of PBSC into the peripheral blood thereby putting high-dose chemotherapy at risk. The present article reviews mobilization of PBSC with a special focus on poor mobilizers. Under steady-state conditions less than 0.05% of the white blood cells (WBC) are CD34+ cells. Chemotherapy results in a 5-15-fold increase of PBSC. Combining chemotherapy and growth factors increases CD34+ cells up to 6% of WBC. Several factors affect the mobilization of PBSC: age, gender, type of growth factor, dose of the growth factor and in the autologous setting patient's diagnosis, chemotherapy regimen and number of previous chemotherapy cycles or radiation. Poor mobilizers are defined as patients with less than 10 CD34+ cells/mul in the peripheral blood during mobilization. Promising approaches for those patients rely on remobilization, use of high doses of granulocyte-colony stimulating factor (G-CSF), or the combination of G-CSF and granulocyte macrophage (GM)-CSF, which successfully mobilized the majority of poor mobilizing patients. New agents such as long lasting variants of G-CSF and CXCR4 antagonists are at the horizon and studied in clinical trials as mobilizing agents. Muscle and bone pain are frequent adverse events in stem cell mobilization but are usually tolerated under the use of analgesics. Large volume apheresis (LVL) with a processed volume of more than 4-fold patient's blood volume is an approach to increase the CD34+ yield in patients with low CD34+ pre-counts resulting in higher yields of CD34+ cells for transplantation. Processing of more blood in LVL is achieved by an increase of the blood flow rate and an altered anticoagulation regimen with the occurrence of more citrate reactions.

  12. An autologous endothelial cell:peripheral blood mononuclear cell assay that detects cytokine storm responses to biologics.

    PubMed

    Reed, Daniel M; Paschalaki, Koralia E; Starke, Richard D; Mohamed, Nura A; Sharp, Giles; Fox, Bernard; Eastwood, David; Bristow, Adrian; Ball, Christina; Vessillier, Sandrine; Hansel, Trevor T; Thorpe, Susan J; Randi, Anna M; Stebbings, Richard; Mitchell, Jane A

    2015-06-01

    There is an urgent unmet need for human tissue bioassays to predict cytokine storm responses to biologics. Current bioassays that detect cytokine storm responses in vitro rely on endothelial cells, usually from umbilical veins or cell lines, cocultured with freshly isolated peripheral blood mononuclear cells (PBMCs) from healthy adult volunteers. These assays therefore comprise cells from 2 separate donors and carry the disadvantage of mismatched tissues and lack the advantage of personalized medicine. Current assays also do not fully delineate mild (such as Campath) and severe (such as TGN1412) cytokine storm-inducing drugs. Here, we report a novel bioassay where endothelial cells grown from stem cells in the peripheral blood (blood outgrowth endothelial cells) and PBMCs from the same donor can be used to create an autologous coculture bioassay that responds by releasing a plethora of cytokines to authentic TGN1412 but only modestly to Campath and not to control antibodies such as Herceptin, Avastin, and Arzerra. This assay performed better than the traditional mixed donor assay in terms of cytokine release to TGN1412 and, thus, we suggest provides significant advancement and a definitive system by which biologics can be tested and paves the way for personalized medicine.

  13. Regeneration of Cartilage in Human Knee Osteoarthritis with Autologous Adipose Tissue-Derived Stem Cells and Autologous Extracellular Matrix

    PubMed Central

    Pak, Jaewoo; Lee, Jung Hun; Park, Kwang Seung; Jeong, Byeong Chul; Lee, Sang Hee

    2016-01-01

    Abstract This clinical case series demonstrates that percutaneous injections of autologous adipose tissue-derived stem cells (ADSCs) and homogenized extracellular matrix (ECM) in the form of adipose stromal vascular fraction (SVF), along with hyaluronic acid (HA) and platelet-rich plasma (PRP) activated by calcium chloride, could regenerate cartilage-like tissue in human knee osteoarthritis (OA) patients. Autologous lipoaspirates were obtained from adipose tissue of the abdominal origin. Afterward, the lipoaspirates were minced to homogenize the ECM. These homogenized lipoaspirates were then mixed with collagenase and incubated. The resulting mixture of ADSCs and ECM in the form of SVF was injected, along with HA and PRP activated by calcium chloride, into knees of three Korean patients with OA. The same affected knees were reinjected weekly with additional PRP activated by calcium chloride for 3 weeks. Pretreatment and post-treatment magnetic resonance imaging (MRI) data, functional rating index, range of motion (ROM), and pain score data were then analyzed. All patients' MRI data showed cartilage-like tissue regeneration. Along with MRI evidence, the measured physical therapy outcomes in terms of ROM, subjective pain, and functional status were all improved. This study demonstrates that percutaneous injection of ADSCs with ECM contained in autologous adipose SVF, in conjunction with HA and PRP activated by calcium chloride, is a safe and potentially effective minimally invasive therapy for OA of human knees. PMID:27588219

  14. Autologous stem cell transplantation as first line treatment after incomplete excision of pancreatoblastoma.

    PubMed

    Meneses, Clarice Franco; Osório, Carolina Dame; de Castro Junior, Claudio Galvão; Brunetto, Algemir Lunardi

    2013-01-01

    Pancreatoblastoma is a rare tumor and surgery with complete resection is the main treatment approach. Prognosis for patients with residual disease after surgery is usually dismal. A 14-year-old girl with pancreatoblastoma in the pancreatic body and tail was submitted to preoperative chemotherapy. She underwent surgery and the tumor was resected with microscopic margins. Postoperative chemotherapy was followed by high dose chemotherapy and autologous hematopoietic stem cell transplantation. After four years she remains very well with no evidence of disease. This is the first case reported of pancreatoblastoma that was treated with autologous hematopoietic stem cell transplantation as first line treatment without radiotherapy at the site of the microscopic disease.

  15. Defining "poor mobilizer" in pediatric patients who need an autologous peripheral blood progenitor cell transplantation.

    PubMed

    Sevilla, Julián; Guillén, María; Castillo, Ana; Prudencio, Marta; González-Vicent, Marta; Lassaletta, Álvaro; Cormenzana, María; Ramírez, Manuel; Pérez-Martínez, Antonio; Madero, Luis; Díaz-Pérez, Miguel Ángel

    2013-01-01

    The definition of poor mobilizers is not clear in pediatric patients undergoing autologous peripheral blood hematopoietic progenitor cell (HPC) mobilization. Most studies conducted in children define those variables related to the collection of HPC after leukapheresis, but the information regarding exclusively the mobilization process is scarce. In our experience, most children (92.2%) reach the target CD34(+) cell dose for autologous peripheral blood progenitor cell transplantation if CD34(+) cell count was higher than 10/μL. No differences were observed between those with >20 CD34(+) cells/μL and 11-20 CD34(+) cells/μL. In this study, we analyzed the variables that influence CD34(+) cell count; we found that prior use of radiotherapy was the main variable related to poor mobilization. Patients diagnosed with Ewing sarcoma, treated with radiotherapy and mobilized with standard doses of granulocyte colony-stimulating factor (G-CSF) were also at a high risk of mobilization failure. In these patients, we should consider mobilization with high dose G-CSF and be prepared with new mobilization agents to avoid delay on their course of chemotherapy.

  16. Allogeneic and autologous mode of stem cell transplantation in regenerative medicine: which way to go?

    PubMed

    Mamidi, Murali Krishna; Dutta, Susmita; Bhonde, Ramesh; Das, Anjan Kumar; Pal, Rajarshi

    2014-12-01

    Stem cell transplantation is a generic term covering different techniques. However there is argument over the pros and cons of autologous and allogeneic transplants of mesenchymal stem cells (MSCs) for regenerative therapy. Given that the MSCs have already been proven to be safe in patients, we hypothesize that allogeneic transplantation could be more effective and cost-effective as compared to autologous transplantation specifically in older subjects who are the likely victims of degenerative diseases. This analysis is based on the scientific logic that allogeneic stem cells extracted in large numbers from young and healthy donors could be physiologically, metabolically and genetically more stable. Therefore stem cells from young donors may be expected to exhibit higher vigor in secreting trophic factors leading to activation of host tissue-specific stem cells and also be more efficient in remodeling the micro-environmental niche of damaged tissue.

  17. Untested, unproven, and unethical: the promotion and provision of autologous stem cell therapies in Australia.

    PubMed

    McLean, Alison K; Stewart, Cameron; Kerridge, Ian

    2015-02-09

    An increasing number of private clinics in Australia are marketing and providing autologous stem cell therapies to patients. Although advocates point to the importance of medical innovation and the primacy of patient choice, these arguments are unconvincing. First, it is a stark truth that these clinics are flourishing while the efficacy and safety of autologous stem cell therapies, outside of established indications for hematopioetic stem cell transplantation, are yet to be shown. Second, few of these therapies are offered within clinical trials. Third, patients with chronic and debilitating illnesses, who are often the ones who take up these therapies, incur significant financial burdens in the expectation of benefiting from these treatments. Finally, the provision of these stem cell therapies does not follow the established pathways for legitimate medical advancement. We argue that greater regulatory oversight and professional action are necessary to protect vulnerable patients and that at this time the provision of unproven stem cell therapies outside of clinical trials is unethical.

  18. C3 glomerulopathy associated to multiple myeloma successfully treated by autologous stem cell transplant

    PubMed Central

    Hamzi, M. A.; Zniber, A.; Badaoui, G. E.; Mahtat, E.; Alhamany, Z.; Bayahia, R.; Ouzeddoun, N.

    2017-01-01

    A 32-year-old male presented with advanced renal failure and nephrotic proteinuria due to lambda light chain multiple myeloma. Renal biopsy showed a proliferative glomerulonephritis with isolated C3 deposits. Renal recovery was obtained after chemotherapy and autologous stem cell transplant. We review previously described cases of C3 glomerulopathy associated with monoclonal gammopathy. PMID:28356669

  19. Persistence of Virus Reservoirs in ART-Treated SHIV-Infected Rhesus Macaques after Autologous Hematopoietic Stem Cell Transplant

    PubMed Central

    Lawson, Benton; Lee, S. Thera; Chahroudi, Ann; Kean, Leslie; Silvestri, Guido

    2014-01-01

    Despite many advances in AIDS research, a cure for HIV infection remains elusive. Here, we performed autologous hematopoietic stem cell transplantation (HSCT) in three Simian/Human Immunodeficiency Virus (SHIV)-infected, antiretroviral therapy (ART)-treated rhesus macaques (RMs) using HSCs collected prior to infection and compared them to three SHIV-infected, ART-treated, untransplanted control animals to assess the effect of conditioning and autologous HSCT on viral persistence. As expected, ART drastically reduced virus replication, below 100 SHIV-RNA copies per ml of plasma in all animals. After several weeks on ART, experimental RMs received myeloablative total body irradiation (1080 cGy), which resulted in the depletion of 94–99% of circulating CD4+ T-cells, and low to undetectable SHIV-DNA levels in peripheral blood mononuclear cells. Following HSC infusion and successful engraftment, ART was interrupted (40–75 days post-transplant). Despite the observed dramatic reduction of the peripheral blood viral reservoir, rapid rebound of plasma viremia was observed in two out of three transplanted RMs. In the third transplanted animal, plasma SHIV-RNA and SHIV DNA in bulk PBMCs remained undetectable at week two post-ART interruption. No further time-points could be assessed as this animal was euthanized for clinical reasons; however, SHIV-DNA could be detected in this animal at necropsy in sorted circulating CD4+ T-cells, spleen and lymph nodes but not in the gastro-intestinal tract or tonsils. Furthermore, SIV DNA levels post-ART interruption were equivalent in several tissues in transplanted and control animals. While persistence of virus reservoir was observed despite myeloablation and HSCT in the setting of short term ART, this experiment demonstrates that autologous HSCT can be successfully performed in SIV-infected ART-treated RMs offering a new experimental in vivo platform to test innovative interventions aimed at curing HIV infection in humans. PMID

  20. Mobilization and harvesting of peripheral blood stem cells.

    PubMed

    Moog, Rainer

    2006-05-01

    The use of peripheral blood stem cells (PBSC) as a source of hematopoietic stem cells is steadily increasing and has nearly supplanted bone marrow. The present article reviews mobilization and collection of PBSC as well as its side effects. Specialized harvesting strategies such as large volume leukapheresis (LVL) and pediatric PBSC collection are included in this overview. Under steady state conditions, less than 0.05% of the white blood cells (WBC) are CD34+ cells. Chemotherapy results in a 5-15-fold increase of PBSC. Combining chemotherapy and growth factors increases CD34+ cells up to 6% of WBC. In the allogeneic setting, granulocyte-colony stimulating factor is used alone for PBSC mobilization. Several factors affect the mobilization of PBSC: age, gender, type of growth factor, dose of the growth factor and in the autologous setting, patient's diagnosis, chemotherapy regimen and number of previous chemotherapy cycles or radiation. Harvesting of PBSC can be performed with various blood cell separators using continuous or discontinuous flow technique. Continuous flow separators allow the processing of more blood compared with intermittent flow devices resulting in higher yields of CD34+ cells for transplantation. LVL can be used to increase the CD34+ yield in patients with low CD34+ pre-counts. Processing of more blood in LVL is achieved by an increase of the blood flow rate and an altered anticoagulation regimen. Specialized strategies were developed for pediatric PBSC collection considering the main limiting factors, extracorporeal volume and vascular access. Adverse events in PBSC collection can be subdivided in apheresis associated and mobilization associated side effects. Citrate reactions due to hypocalcemia are frequent during apheresis, especially in pediatric PBSC collection and LVL. Thrombocytopenia is often observed in patients after termination of apheresis due to platelet loss during PBSC harvesting. Muscle and bone pain are frequent adverse events

  1. Transcatheter Arterial Infusion of Autologous CD133+ Cells for Diabetic Peripheral Artery Disease

    PubMed Central

    Zhang, Xiaoping; Lian, Weishuai; Lou, Wensheng; Han, Shilong; Lu, Chenhui; Zuo, Keqiang; Su, Haobo; Xu, Jichong; Cao, Chuanwu; Tang, Tao; Jia, Zhongzhi; Jin, Tao; Uzan, Georges; Gu, Jianping; Li, Maoquan

    2016-01-01

    Microvascular lesion in diabetic peripheral arterial disease (PAD) still cannot be resolved by current surgical and interventional technique. Endothelial cells have the therapeutic potential to cure microvascular lesion. To evaluate the efficacy and immune-regulatory impact of intra-arterial infusion of autologous CD133+ cells, we recruited 53 patients with diabetic PAD (27 of CD133+ group and 26 of control group). CD133+ cells enriched from patients' PB-MNCs were reinfused intra-arterially. The ulcer healing followed up till 18 months was 100% (3/3) in CD133+ group and 60% (3/5) in control group. The amputation rate was 0 (0/27) in CD133+ group and 11.54% (3/26) in control group. Compared with the control group, TcPO2 and ABI showed obvious improvement at 18 months and significant increasing VEGF and decreasing IL-6 level in the CD133+ group within 4 weeks. A reducing trend of proangiogenesis and anti-inflammatory regulation function at 4 weeks after the cells infusion was also found. These results indicated that autologous CD133+ cell treatment can effectively improve the perfusion of morbid limb and exert proangiogenesis and anti-inflammatory immune-regulatory impacts by paracrine on tissue microenvironment. The CD133+ progenitor cell therapy may be repeated at a fixed interval according to cell life span and immune-regulatory function. PMID:26981134

  2. Modulation of Mitogen-Induced Proliferation of Autologous Peripheral Blood Lymphocytes by Human Alveolar Macrophages

    PubMed Central

    Yeager, Henry; Sweeney, Jan A.; Herscowitz, Herbert B.; Barsoum, Ibrahim S.; Kagan, Elliott

    1982-01-01

    Experiments were carried out to determine the effect of cocultivation of T-cell-enriched human peripheral blood lymphocytes with autologous alveolar macrophages on mitogen-induced proliferation as determined by [3H]thymidine uptake. Cells obtained by fiberoptic bronchoscopy and saline bronchial lavage from 14 normal volunteers were enriched for macrophages by adherence in plastic dishes for 1 h in RPMI 1640 medium supplemented with 10% fetal calf serum. Nonadherent mononuclear cells were prepared from heparinized venous blood after Ficoll-Hypaque sedimentation by passage over nylon wool columns. T-cell-enriched populations were incubated with and without alveolar macrophages, either in the presence or absence of phytohemagglutinin. In these experiments, the number of lymphocytes was held constant (105 per well), while the number of alveolar macrophages was varied (0.1 × 105 to 4.0 × 105 per well). Alveolar macrophages generally tended to stimulate phytohemagglutinin-induced lymphoproliferation at lymphocyte/macrophage ratios of 10:1 but consistently and significantly suppressed proliferation at ratios which approach those usually observed in recovered human bronchial lavage fluid, namely, 1:4. The suppressive effect of alveolar macrophages was observed as early as 48 h after culture initiation, while the magnitude of suppression increased with time. Suppression did not appear to be due to alteration in lymphocyte viability, nor was it sensitive to indomethacin. These results indicate that human alveolar macrophages can modulate the in vitro proliferative response of autologous peripheral blood lymphocytes. This observation may have relevance to interactions between alveolar macrophages and bronchial lymphocytes in the human lung in vivo. PMID:6982862

  3. Controversies in autologous and allogeneic hematopoietic cell transplantation in peripheral T/NK-cell lymphomas.

    PubMed

    Shustov, Andrei

    2013-03-01

    Peripheral T-cell and NK-cell lymphomas (PT/NKCL) are a heterogeneous group of lymphoid neoplasms with poor outcomes. There is no consensus on the best front line therapy or management of relapsed/refractory disease. The use of autologous and allogeneic hematopoietic cell transplantation (HCT) has been studied in both settings to improve outcomes. Multiple retrospective and several prospective trials were reported. While at first sight the outcomes in the relapsed/refractory setting appear similar in B-cell and T-cell lymphomas when treated with high dose therapy (HDT) and autologous HCT, it is becoming obvious that only specific subtypes of PTCL benefit from this approach (i.e. anaplastic large cell lymphoma [ALCL] and angioimmunoblastic lymphoma [AITL] in second CR). In less favorable histologies, HDT seems to provide limited benefit, with the majority of patients experiencing post-transplant relapse. The use of autologous HCT to consolidate first remission has been evaluated in several prospective trials. Again, the best results were observed in ALCL, but the superiority of this approach over chemotherapy alone needs confirmation in randomized trials. In less favorable histologies, high-dose consolidation resulted in low survival rates comparable to those obtained with chemotherapy alone, and without randomized trials it is hard to recommend this strategy to all patients with newly diagnosed PT/NKCL. Allogeneic HCT might provide potent and potentially curative graft-vs-lymphoma effect and overcome chemotherapy resistance. Only a few studies have been reported to date on allogeneic HCT in PT/NKCL. Based on available data, eligible patients benefit significantly from this approach, with 50% or more patients achieving long-term disease control or cure, although at the expense of significant treatment related mortality (TRM). Reduced-intensity conditioning regimens appear to have lower TRM and might extend this approach to older patients. With the recent approval of

  4. [Collection and transfusion of peripheral blood stem cells].

    PubMed

    Höcker, P; Wagner, A

    1991-01-01

    Harvesting of peripheral blood stem cells (PBSC) by cytapheresis was performed in 57 patients, who underwent chemotherapy. The best yields were obtained when the leukocyte count was above 1 x 10(9)/l and the platelet count was raised above 80 x 10(9)/l. Using a Haemonetics V-50 or a Baxter CS-3000, 374 PBSC-aphereses were performed with a median of six aphereses per patient. The median number of PBSC (CFU-GM) retransfused in 22 patients who received PBSC for hematological reconstitution only was 3.26 x 10(4)/kg. For 22 patients who received autologous bone marrow plus BPSC, the median number of retransfused PBSC was 2.14 x 10(4)/kg. Myeloid engraftment was achieved in all patients, but megakaryopoiesis was delayed when the number of PBSC was less than 5.0 x 10(4)/kg. The results demonstrate that harvesting of a sufficient number of PBSC after chemotherapy is feasible but further measures like the use of rh GM-CSF will be necessary to reduce apheresis procedures and to obtain high yields to ensure rapid and complete engraftment.

  5. Tbo-Filgrastim versus Filgrastim during Mobilization and Neutrophil Engraftment for Autologous Stem Cell Transplantation.

    PubMed

    Elayan, Mohammed M; Horowitz, Justin G; Magraner, Jose M; Shaughnessy, Paul J; Bachier, Carlos

    2015-11-01

    There are limited data available supporting the use of the recombinant granulocyte colony-stimulating factor (G-CSF), tbo-filgrastim, rather than traditionally used filgrastim to mobilize peripheral blood stem cells (PBSC) or to accelerate engraftment after autologous stem cell transplantation (ASCT). We sought to compare the efficacy and cost of tbo-filgrastim to filgrastim in these settings. Patients diagnosed with lymphoma or plasma cell disorders undergoing G-CSF mobilization, with or without plerixafor, were included in this retrospective analysis. The primary outcome was total collected CD34(+) cells/kg. Secondary mobilization endpoints included peripheral CD34(+) cells/μL on days 4 and 5 of mobilization, adjunctive use of plerixafor, CD34(+) cells/kg collected on day 5, number of collection days and volumes processed, number of collections reaching 5 million CD34(+) cells/kg, and percent reaching target collection goal in 1 day. Secondary engraftment endpoints included time to neutrophil and platelet engraftment, number of blood product transfusions required before engraftment, events of febrile neutropenia, and length of stay. A total of 185 patients were included in the final analysis. Patients receiving filgrastim (n = 86) collected a median of 5.56 × 10(6) CD34(+) cells/kg, compared with a median of 5.85 × 10(6) CD34(+) cells/kg in the tbo-filgrastim group (n = 99; P = .58). There were no statistically significant differences in all secondary endpoints with the exception of apheresis volumes processed (tbo-filgrastim, 17.0 liters versus filgrastim, 19.7 liters; P < .01) and mean platelet transfusions (tbo-filgrastim, 1.7 units versus filgrastim, 1.4 units; P = .04). In conclusion, tbo-filgrastim demonstrated similar CD34(+) yield compared with filgrastim in mobilization and post-transplantation settings, with no clinically meaningful differences in secondary efficacy and safety endpoints. Furthermore, tbo-filgrastim utilization was associated

  6. Autologous blood stem-cell transplantation in patients with advanced Hodgkin's disease and prior radiation to the pelvic site

    SciTech Connect

    Koerbling, M.H.; Holle, R.; Haas, R.; Knauf, W.; Doerken, B.H.; Ho, A.D.; Kuse, R.; Pralle, H.; Fliedner, T.M.; Hunstein, W. )

    1990-06-01

    Patients with relapsed Hodgkin's disease who respond to salvage therapy are successfully treated with cyclophosphamide, carmustine (BCNU), and etoposide (VP-16) (CBV) followed by autologus bone marrow transplantation (ABMT). Because of heavy pretreatment including radiation to the pelvic site, marrow harvest was not feasible in those patients. We therefore used blood-derived hemopoietic precursor cells as an alternative stem-cell source to rescue them after superdose chemotherapy. Hemopoietic precursor cells were mobilized into the peripheral blood either by chemotherapeutic induction of transient myelosuppression followed by an overshooting of blood stem-cell concentration, or by continuous intravenous (IV) granulocyte-macrophage colony-stimulating factor (GM-CSF) administration. The median time to reach 1,000 WBC per microliter, 500 polymorphonuclear cells (PMN) per microliter, or 20,000 platelets per microliter was 10, 20.5, and 38 days, respectively, for 50% of all patients. The platelet counts of two patients never dropped below 20,000/microL following autologous blood stem-cell transplantation (ABSCT), whereas two other patients had to be supported with platelets for 75 and 86 days posttransplant until a stable peripheral platelet count of 20,000/microL was attained. Among the 11 assessable patients, seven are in unmaintained complete remission (CR) at a median follow-up of 318 days. This is a first report on a series of ABSCTs in patients with advanced Hodgkin's disease proving that, despite prior damage to the marrow site, the circulating stem-cell pool is still a sufficient source of hemopoietic precursor cells for stem-cell rescue.

  7. Autologous Hematopoietic Stem Cell Transplantation-10 Years of Data From a Developing Country.

    PubMed

    Ali, Natasha; Adil, Salman Naseem; Shaikh, Mohammad Usman

    2015-08-01

    Intensive chemotherapy followed by autologous stem cell transplantation is the treatment of choice for patients with hematological malignancies. The objective of the present study was to evaluate the outcomes of patients with mainly lymphoma and multiple myeloma after autologous stem cell transplant. The pretransplant workup consisted of the complete blood count, an evaluation of the liver, kidney, lung, and infectious profile, chest radiographs, and a dental review. For lymphoma, all patients who achieved at least a 25% reduction in the disease after salvage therapy were included in the study. Mobilization was done with cyclophosphamide, followed by granulocyte colony-stimulating factor, 300 µg twice daily. The conditioning regimens included BEAM (carmustine, etoposide, cytarabine, melphalan) and high-dose melphalan. A total of 206 transplants were performed from April 2004 to December 2014. Of these, 137 were allogeneic transplants and 69 were autologous. Of the patients receiving an autologous transplant, 49 were male and 20 were female. Of the 69 patients, 26 underwent transplantation for Hodgkin's lymphoma, 23 for non-Hodgkin's lymphoma, and 15 for multiple myeloma and 4 and 1 for Ewing's sarcoma and neuroblastoma, respectively. The median age ± SD was 34 ± 13.1 years (range, 4-64). A mean of 4.7 × 10⁸ ± 1.7 mononuclear cells per kilogram were infused. The median time to white blood cell recovery was 18.2 ± 5.34 days. Transplant-related mortality occurred in 10 patients. After a median follow-up period of 104 months, the overall survival rate was 86%. High-dose chemotherapy, followed by autologous stem cell transplant, is an effective treatment option for patients with hematological malignancies, allowing further consolidation of response.

  8. The Use of Autologous Mesenchymal Stem Cells for Cell Therapy of Patients with Amyotrophic Lateral Sclerosis in Belarus.

    PubMed

    Rushkevich, Yu N; Kosmacheva, S M; Zabrodets, G V; Ignatenko, S I; Goncharova, N V; Severin, I N; Likhachev, S A; Potapnev, M P

    2015-08-01

    We studied a new method of treatment of amyotrophic lateral sclerosis with autologous mesenchymal stem cells. Autologous mesenchymal stem cells were injected intravenously (intact cells) or via lumbar puncture (cells committed to neuronal differentiation). Evaluation of the results of cell therapy after 12-month follow-up revealed slowing down of the disease progression in 10 patients in comparison with the control group consisting of 15 patients. The cell therapy was safe for the patients.

  9. [Peripheral blood hematopoietic stem cell collection].

    PubMed

    Bojanić, Ines; Mazić, Sanja; Cepulić, Branka Golubić

    2009-01-01

    Summary. Peripheral blood hematopoietic stem cells (PBSC) have numerous advatages in comparison with traditionally used bone marrow. PBSC collection by leukapheresis procedure is simpler and better tolerated than bone marrow harvest. PBCS are mobilized by myelosupressive chemotherapy or/and hematopoietic growth factors. Leukapheresis product contains PBSC along with lineage commited progenitors and precursors which contribute to faster hematopoietic recovery. In "poor mobilizers" options are large-volume leukapheresis (LVL) procedure or second generation of mobilising agents (pegfilgrastim, CXCR4 receptor antagonists). Total blood volume is processed 2-3 times in standard procedure compared to more than 3 times in LVL. LVL yields significantly higher numbers of CD34+ cells. Adverse effects of leukapheresis are electrolyte disbalance (hypocalcemia) caused by citrat administration and risk of bleeding due to trobocytopenia and heparin administration. PBSC collection and product quality control are regulated by national and international standards and recommendations.

  10. Autologous Bone Marrow Derived Stem Cells for the Treatment of Multiple Sclerosis

    PubMed Central

    Chahine, Nassim Abi; Wehbe, Tarek; Rashed, Johny; Hilal, Ramzi; Elias, Nada

    2016-01-01

    Stem cell therapy, an evolving, progressive field of therapeutics has shown several successes in areas where classic treatments failed to prevent or stop disability. Starting in 2009, twenty two sequential patients with progressive Multiple Sclerosis (MS) courses were treated with Autologous Bone Marrow Mononuclear stem cells (BM-MNSCs). The cells were given both intravenously and intrathecally. Using the Expanded Disability Status Scale (EDSS) score for evaluation, our data indicates that the majority of the patients benefited on the average one point on the scale. This paper adds to the body of evidence suggesting the safety and efficacy of autologous BM-MNSCs in the treatment of MS and awaits validation through larger, randomized studies. PMID:27788571

  11. Multiple Myeloma Relapse Following Autologous Stem Cell Transplant Presenting With Diffuse Pulmonary Nodules

    PubMed Central

    Sumrall, Bradley; Diethelm, Lisa; Brown, Archie

    2013-01-01

    Background Multiple myeloma is a common disease, accounting for about 10% of hematologic malignancies in the United States. For eligible patients, the treatment of choice includes induction therapy (usually involving newer biologic agents) followed by autologous stem cell transplant; however, this treatment is generally not considered curative, and relapses usually occur. However, extramedullary relapse is an uncommon presentation, and relapses that involve the lungs have only rarely been described. Case Report We report the case of a patient who underwent an autologous stem cell transplant for multiple myeloma and subsequently relapsed with diffuse pulmonary nodules. She then had a rapid clinical and serologic response following initiation of salvage therapy. Conclusion This case is remarkable for both the radiographic appearance of the pulmonary involvement, as well as the rapid resolution of these findings after 2 cycles of treatment with bortezomib, dexamethasone, and lenalidomide. PMID:24358007

  12. [Autologous stem cell transplantation for autoimmune diseases: recommendations from the SFGM-TC].

    PubMed

    Farge, D; Terriou, L; Badoglio, M; Cras, A; Desreumaux, P; Hadj-Khelifa, S; Marjanovic, Z; Moisan, A; Dulery, R; Faucher, C; Hij, A; Martin, T; Vermersch, P; Yakoub-Agha, I

    2014-08-01

    Autologous hematopoietic stem cell transplantation is a valid alternative to immunosuppressive treatment in patients with auto-immune disease; however, the role of this approach remains subject to debate. In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) set up its fourth annual series of workshops which brought together practitioners from all of its member centers. These workshops took place in September 2013 in Lille. In this article we give an overview regarding the indications of autologous stem cell transplantation in auto-immune diseases as well as recommendations regarding post-transplant follow-up of patients.

  13. Autologous transplantation of amniotic fluid-derived mesenchymal stem cells into sheep fetuses.

    PubMed

    Shaw, S W Steven; Bollini, Sveva; Nader, Khalil Abi; Gastaldello, Annalisa; Gastadello, Annalisa; Mehta, Vedanta; Filppi, Elisa; Cananzi, Mara; Gaspar, H Bobby; Qasim, Waseem; De Coppi, Paolo; David, Anna L

    2011-01-01

    Long-term engraftment and phenotype correction has been difficult to achieve in humans after in utero stem cell transplantation mainly because of allogeneic rejection. Autologous cells could be obtained during gestation from the amniotic fluid with minimal risk for the fetus and the mother. Using a sheep model, we explored the possibility of using amniotic fluid mesenchymal stem cells (AFMSCs) for autologous in utero stem cell/gene therapy. We collected amniotic fluid (AF) under ultrasound-guided amniocentesis in early gestation pregnant sheep (n = 9, 58 days of gestation, term = 145 days). AFMSCs were isolated and expanded in all sampled fetal sheep. Those cells were transduced using an HIV vector encoding enhanced green fluorescent protein (GFP) with 63.2% (range 38.3-96.2%) transduction efficiency rate. After expansion, transduced AFMSCs were injected into the peritoneal cavity of each donor fetal sheep at 76 days under ultrasound guidance. One ewe miscarried twin fetuses after amniocentesis. Intraperitoneal injection was successful in the remaining 7 fetal sheep giving a 78% survival for the full procedure. Tissues were sampled at postmortem examination 2 weeks later. PCR analysis detected GFP-positive cells in fetal tissues including liver, heart, placenta, membrane, umbilical cord, adrenal gland, and muscle. GFP protein was detected in these tissues by Western blotting and further confirmed by cytofluorimetric and immunofluorescence analyses. This is the first demonstration of autologous stem cell transplantation in the fetus using AFMSCs. Autologous cells derived from AF showed widespread organ migration and could offer an alternative way to ameliorate prenatal congenital disease.

  14. Transplantation of Reprogrammed Autologous Stem Cells for Chronic Pain and Drug Abuse

    DTIC Science & Technology

    2013-10-01

    Intrathecal xenogeneic chromaffin cell grafts reduce nociceptive behavior in a rodent tonic pain model. Exp Neurol. 2004, 186(2):198-211. 16. Collas, P... nociceptive behavior in a rodent tonic pain model. Exp. Neurol. 186(2):198–211; 2004. Sugaya, I.; Qu, T.; Sugaya, K.; Pappas, G. D. Genetically 41...Autologous Stem Cells for Chronic Pain and Drug Abuse PRINCIPAL INVESTIGATOR: Tingyu Qu

  15. Transplantation of Reprogrammed Autologous Stem Cells for Chronic Pain and Drug Abuse

    DTIC Science & Technology

    2015-10-01

    Tolerance, Drug abuse, Cell cultures, Spinal transplantation of autologous stem cells, Animal behavioral tests 16. SECURITY CLASSIFICATION OF: 17...abuse, Cell cultures, Spinal transplantation, Animal behavioral tests 3. Overall Project Summary This project is a Partnering PI option with Dr...nociceptive behavior in a rodent tonic pain model. Exp Neurol. 2004, 186(2):198-211. 16. Collas, P., and Hakelien, A. M. Teaching cells new tricks. Trends

  16. Differentiation within autologous fibrin scaffolds of porcine dermal cells with the mesenchymal stem cell phenotype

    SciTech Connect

    Puente, Pilar de la

    2013-02-01

    Porcine mesenchymal stem cells (pMSCs) are an attractive source of cells for tissue engineering because their properties are similar to those of human stem cells. pMSCs can be found in different tissues but their dermal origin has not been studied in depth. Additionally, MSCs differentiation in monolayer cultures requires subcultured cells, and these cells are at risk of dedifferentiation when implanting them into living tissue. Following this, we attempted to characterize the MSCs phenotype of porcine dermal cells and to evaluate their cellular proliferation and differentiation in autologous fibrin scaffolds (AFSs). Dermal biopsies and blood samples were obtained from 12 pigs. Dermal cells were characterized by flow cytometry. Frozen autologous plasma was used to prepare AFSs. pMSC differentiation was studied in standard structures (monolayers and pellets) and in AFSs. The pMSCs expressed the CD90 and CD29 markers of the mesenchymal lineage. AFSs afforded adipogenic, osteogenic and chondrogenic differentiation. The porcine dermis can be proposed to be a good source of MSCs with adequate proliferative capacity and a suitable expression of markers. The pMSCs also showed optimal proliferation and differentiation in AFSs, such that these might serve as a promising autologous and implantable material for use in tissue engineering. -- Highlights: ► Low fibrinogen concentration provides a suitable matrix for cell migration and differentiation. ► Autologous fibrin scaffolds is a promising technique in tissue engineering. ► Dermal cells are an easily accessible mesenchymal stem cell source. ► Fibrin scaffolds afforded adipogenic, osteogenic and chondrogenic differentiation.

  17. Differentiation within autologous fibrin scaffolds of porcine dermal cells with the mesenchymal stem cell phenotype.

    PubMed

    de la Puente, Pilar; Ludeña, Dolores; López, Marta; Ramos, Jennifer; Iglesias, Javier

    2013-02-01

    Porcine mesenchymal stem cells (pMSCs) are an attractive source of cells for tissue engineering because their properties are similar to those of human stem cells. pMSCs can be found in different tissues but their dermal origin has not been studied in depth. Additionally, MSCs differentiation in monolayer cultures requires subcultured cells, and these cells are at risk of dedifferentiation when implanting them into living tissue. Following this, we attempted to characterize the MSCs phenotype of porcine dermal cells and to evaluate their cellular proliferation and differentiation in autologous fibrin scaffolds (AFSs). Dermal biopsies and blood samples were obtained from 12 pigs. Dermal cells were characterized by flow cytometry. Frozen autologous plasma was used to prepare AFSs. pMSC differentiation was studied in standard structures (monolayers and pellets) and in AFSs. The pMSCs expressed the CD90 and CD29 markers of the mesenchymal lineage. AFSs afforded adipogenic, osteogenic and chondrogenic differentiation. The porcine dermis can be proposed to be a good source of MSCs with adequate proliferative capacity and a suitable expression of markers. The pMSCs also showed optimal proliferation and differentiation in AFSs, such that these might serve as a promising autologous and implantable material for use in tissue engineering.

  18. Autologous hematopoietic stem cell transplantation for autoimmune disease--is it now ready for prime time?

    PubMed

    Atkins, Harold L; Muraro, Paolo A; van Laar, Jacob M; Pavletic, Steven Z

    2012-01-01

    Current systemic therapies are rarely curative for patients with severe life-threatening forms of autoimmune disease (AID). During the past 15 years, autologous hematopoietic stem cell transplantation (HCT) has been demonstrated to cure some patients with severe AID refractory to all other available therapies, and thus AID has become an emerging indication for cell therapy. The sustained clinical effects after autologous HCT are better explained by qualitative change in the reconstituted immune repertoire rather than transient depletion of immune cells. Since 1996, more than 1300 AID patients have been registered by the European Group for Blood and Marrow Transplantation (EBMT) and almost 500 patients by the Center for International Blood and Marrow Transplant Research (CIBMTR). Autologous HCT is most commonly performed for patients with multiple sclerosis (MS) or systemic sclerosis (SSc). Systemic lupus, Crohn's disease, type I diabetes, and juvenile idiopathic arthritis are other common indications. Allogeneic transplants are still considered too toxic for use in AID, except for cases of immune cytopenia. Although biologic therapies have been effective at controlling the manifestations of the disease, they require continuous administration, thus raising questions about their increasing costs, morbidity, and mortality related to prolonged therapy. Perhaps it is a reasonable time to ask, "Is autologous HCT for severe AID now ready for prime time?" Yet, the paucity of controlled studies, the short-term toxicities, and the upcoming availability of second-generation biologic and targeted immunotherapies argues that perhaps HCT for AID should be still limited to clinical trials. In this article, we focus on the results of autologous HCT for MS and SSc because these are the two most commonly transplanted diseases. The promising data that is emerging may establish these diseases as standard indications for HCT.

  19. Safety Concern between Autologous Fat Graft, Mesenchymal Stem Cell and Osteosarcoma Recurrence

    PubMed Central

    Perrot, Pierre; Rousseau, Julie; Bouffaut, Anne-Laure; Rédini, Françoise; Cassagnau, Elisabeth; Deschaseaux, Frédéric; Heymann, Marie-Françoise; Heymann, Dominique; Duteille, Franck; Trichet, Valérie; Gouin, François

    2010-01-01

    Background Osteosarcoma is the most common malignant primary bone tumour in young adult treated by neo adjuvant chemotherapy, surgical tumor removal and adjuvant multidrug chemotherapy. For correction of soft tissue defect consecutive to surgery and/or tumor treatment, autologous fat graft has been proposed in plastic and reconstructive surgery. Principal Findings We report here a case of a late local recurrence of osteosarcoma which occurred 13 years after the initial pathology and 18 months after a lipofilling procedure. Because such recurrence was highly unexpected, we investigated the possible relationship of tumor growth with fat injections and with mesenchymal stem/stromal cell like cells which are largely found in fatty tissue. Results obtained in osteosarcoma pre-clinical models show that fat grafts or progenitor cells promoted tumor growth. Significance These observations and results raise the question of whether autologous fat grafting is a safe reconstructive procedure in a known post neoplasic context. PMID:20544017

  20. Targeted Drugs as Maintenance Therapy after Autologous Stem Cell Transplantation in Patients with Mantle Cell Lymphoma

    PubMed Central

    Yan, Fengting; Gopal, Ajay K.; Graf, Solomon A.

    2017-01-01

    The treatment landscape for mantle cell lymphoma (MCL) is rapidly evolving toward the incorporation of novel and biologically targeted pharmaceuticals with improved disease activity and gentler toxicity profiles compared with conventional chemotherapeutics. Upfront intensive treatment of MCL includes autologous stem cell transplantation (SCT) consolidation aimed at deepening and lengthening disease remission, but subsequent relapse occurs. Maintenance therapy after autologous SCT in patients with MCL in remission features lower-intensity treatments given over extended periods to improve disease outcomes. Targeted drugs are a natural fit for this space, and are the focus of considerable clinical investigation. This review summarizes recent advances in the field and their potential impact on treatment practices for MCL. PMID:28287430

  1. Early Prognostic Value of Monitoring Serum Free Light Chain in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation.

    PubMed

    Özkurt, Zübeyde Nur; Sucak, Gülsan Türköz; Akı, Şahika Zeynep; Yağcı, Münci; Haznedar, Rauf

    2017-03-16

    We hypothesized the levels of free light chains obtained before and after autologous stem cell transplantation can be useful in predicting transplantation outcome. We analyzed 70 multiple myeloma patients. Abnormal free light chain ratios before stem cell transplantation were found to be associated early progression, although without any impact on overall survival. At day +30, the normalization of levels of involved free light chain related with early progression. According to these results almost one-third reduction of free light chain levels can predict favorable prognosis after autologous stem cell transplantation.

  2. Outcomes of Maintenance Therapy with Bortezomib after Autologous Stem Cell Transplantation for Patients with Multiple Myeloma.

    PubMed

    Sivaraj, Dharshan; Green, Michael M; Li, Zhiguo; Sung, Anthony D; Sarantopoulos, Stefanie; Kang, Yubin; Long, Gwynn D; Horwitz, Mitchell E; Lopez, Richard D; Sullivan, Keith M; Rizzieri, David A; Chao, Nelson J; Gasparetto, Cristina

    2017-02-01

    Comprehensive recommendations for maintenance therapy after autologous stem cell transplantation (ASCT) for patients with multiple myeloma (MM) have yet to be defined. Bortezomib has been utilized as maintenance therapy after ASCT, but data attesting to the safety and efficacy of this agent compared with lenalidomide in the post-ASCT setting are limited. Therefore, we retrospectively analyzed the outcomes of 102 patients with MM who received maintenance therapy with bortezomib after ASCT at Duke University's adult bone marrow transplant clinic between 2005 and 2015. Maintenance with bortezomib was initiated between 60 and 90 days after ASCT as a single agent 1.3 mg/m(2) once every 2 weeks (n = 92) or in combination with lenalidomide (10 mg/day) (n = 10). The median age at ASCT was 64 (range, 31 to 78). Of the 99 patients with molecular data available, 42% had high-risk cytogenetics (including d17p, t(4;14), +1q, and t(14;16) by fluorescein in situ hybridization). Overall, 46% of patients experienced side effects from maintenance therapy, with 31% of all patients experiencing peripheral neuropathy. In total, 2% of patients required discontinuation of bortezomib maintenance because of adverse events. No secondary malignancies were reported from the therapy. The median progression-free survival (PFS) for patients receiving maintenance therapy with bortezomib after ASCT was 36.5 months (95% confidence interval [CI], 21.3 to not available) and median overall survival was 72.7 months (95% CI, 63.9 to not available). The PFS of patients with high-risk cytogenetics was not statistically significantly different from those with standard-risk cytogenetics, suggesting that maintenance with bortezomib may help overcome the impact of high-risk cytogenetics on early progression. These results indicate that maintenance therapy with bortezomib represents a safe, well-tolerated, and efficacious option for patients with high-risk cytogenetics, renal insufficiency, an

  3. Allogeneic cellular and autologous stem cell therapy for sickle cell disease: 'whom, when and how'.

    PubMed

    Freed, J; Talano, J; Small, T; Ricci, A; Cairo, M S

    2012-12-01

    Sickle cell disease (SCD) is an autosomal recessive inherited hematological disorder characterized by chronic hemolysis and vaso-occlusion, resulting in multiorgan dysfunction and premature death. The only known curative therapy for patients with severe SCD is myeloablative conditioning and allo-SCT from HLA-matched sibling donors. In this state of the art review, we discuss current and future considerations including patient selection/eligibility, intensity of conditioning regimens, allogeneic graft sources, graft manipulation, mixed donor chimerism, organ function and stability and autologous gene correction stem cell strategies. Recent novel approaches to promote mixed donor chimerism have included the use of matched unrelated adult donors, umbilical cord blood donors, haploidentical familial donors and the utilization of nonmyeloablative, such as reduced intensity and reduced toxicity conditioning regimens. Future strategies will include gene therapy and autologous gene correction stem cell designs. Prospects are bright for novel stem and cellular approaches for patients with severe SCD, and we are currently at the end of the beginning for utilizing cellular therapeutics for the curative treatment of this chronic and debilitating condition.

  4. Nephrotoxicity of high-dose ifosfamide/carboplatin/etoposide in adults undergoing autologous stem cell transplantation.

    PubMed

    Agaliotis, D P; Ballester, O F; Mattox, T; Hiemenz, J W; Fields, K K; Zorsky, P E; Goldstein, S C; Perkins, J B; Rosen, R M; Elfenbein, G J

    1997-11-01

    The objective of this study was to evaluate nephrotoxicity in adult patients treated with high-dose ifosfamide, carboplatin, and etoposide followed by autologous stem cell transplantation. We conducted a retrospective analysis of clinical and laboratory data from 131 patients with various malignancies who received treatment with escalating doses of ifosfamide, carboplatin, and etoposide followed by autologous stem cell transplantation as part of a phase I/II therapeutic trial. Abnormalities in glomerular filtration were evaluated by measuring peak creatinine levels and tubular dysfunction by the lowest recorded serum levels of potassium, magnesium, and bicarbonate, at different time periods after administration of ifosfamide, carboplatin, and etoposide, and after autologous stem cell transplantation. For the entire group of 131 patients, peak creatinine levels were > 1.5 mg/dL but < 3.0 mg/dL in 37% and levels were > 3.0 mg/dL in 11% at some time during their hospital stay. At the time of discharge, creatinine levels were 1.6 mg/dL to 3.0 mg/dL in 25% of patients and were > 3 mg/dL in 5%. Immediately after high-dose therapy, peak creatinine levels were significantly higher in patients receiving higher doses of ifosfamide compared to those receiving lower doses (P < 0.00001) and those receiving intermediate doses (P < 0.005). There was a dramatic decrease in serum bicarbonate, potassium, and magnesium levels immediately after chemotherapy, and they remained significantly decreased throughout the patient's hospital stay, despite massive replacement efforts (P ranging between < 0.008 and < 0.001). This is the largest adult population study documenting the incidence and severity of ifosfamide/carboplatin/etoposide-associated acute nephrotoxicity. Renal dysfunction was dose related and reversible in the majority of patients.

  5. Neck Rhabdoid Tumors: Clinical Features and Consideration of Autologous Stem Cell Transplant.

    PubMed

    Wolfe, Adam D; Capitini, Christian M; Salamat, Shahriar M; DeSantes, Kenneth; Bradley, Kristin A; Kennedy, Tabassum; Dehner, Louis P; Patel, Neha J

    2017-04-03

    Extrarenal malignant rhabdoid tumors (MRT) have a poor prognosis despite aggressive therapy. Adding high-dose chemotherapy with autologous stem cell rescue (HDC-ASCR) as consolidative therapy for MRT is controversial. We describe 2 patients, age 13 years and 19 months, with unresectable neck MRT. After chemotherapy and radiotherapy, both underwent HDC-ASCR and remain in remission over 4 years later. We reviewed all published cases of neck MRT, and found poorer outcomes and more variable age of presentation and time to progression than MRT at other sites. Neck MRT may represent a higher-risk subset of MRT, and addition of HDC-ASCR merits consideration.

  6. High-dose treatment with autologous stem cell transplantation versus sequential chemotherapy: the GELA experience.

    PubMed

    Bosly, A; Haioun, C; Gisselbrecht, C; Reyes, F; Coiffier, B

    2001-07-01

    Autologous stem-cell transplantation (ASCT) has permitted to deliver high-dose therapy (HDT). In aggressive lymphomas, the GELA group conducted prospective and retrospective studies comparing HDT + ASCT to conventional sequential chemotherapy. In relapsing patients and in partial remission, retrospective studies showed a survival advantage for HDT + ASCT over sequential chemotherapy. In complete response, advantage for HDT + ASCT was demonstrated in a prospective trial only for patients with high intermediate or high risk in the IPI score. The attainment of a maximal reduction of the tumoral mass before going HDT is very important either in first line or in relapsing patients.

  7. Engraftment Syndrome after Autologous Stem Cell Transplantation: An Update Unifying the Definition and Management Approach.

    PubMed

    Cornell, Robert Frank; Hari, Parameswaran; Drobyski, William R

    2015-12-01

    Engraftment syndrome (ES) encompasses a continuum of periengraftment complications after autologous hematopoietic stem cell transplantation. ES may include noninfectious fever, skin rash, diarrhea, hepatic dysfunction, renal dysfunction, transient encephalopathy, and capillary leak features, such as noncardiogenic pulmonary infiltrates, hypoxia, and weight gain with no alternative etiologic basis other than engraftment. Given its pleiotropic clinical presentation, the transplant field has struggled to clearly define ES and related syndromes. Here, we present a comprehensive review of ES in all documented disease settings. Furthermore, we discuss the proposed risk factors, etiology, and clinical relevance of ES. Finally, our current approach to ES is included along with a proposed treatment algorithm for the management of this complication.

  8. Pharmacoeconomic analysis of palifermin to prevent mucositis among patients undergoing autologous hematopoietic stem cell transplantation.

    PubMed

    Nooka, Ajay K; Johnson, Heather R; Kaufman, Jonathan L; Flowers, Christopher R; Langston, Amelia; Steuer, Conor; Graiser, Michael; Ali, Zahir; Shah, Nishi N; Rangaraju, Sravanti; Nickleach, Dana; Gao, Jingjing; Lonial, Sagar; Waller, Edmund K

    2014-06-01

    Trials have shown benefits of palifermin in reducing the incidence and severity of oral mucositis in patients with hematological malignancies undergoing autologous hematopoietic stem cell transplantation (HSCT) with total body irradiation (TBI)-based conditioning regimens. Similar outcome data are lacking for patients receiving non-TBI-based regimens. We performed a retrospective evaluation on the pharmacoeconomic benefit of palifermin in the setting of non-TBI-based conditioning and autologous HSCT. Between January 2002 and December 2010, 524 patients undergoing autologous HSCT for myeloma (melphalan 200 mg/m²) and lymphoma (high-dose busulfan, cyclophosphamide, and etoposide) as preparative regimen were analyzed. Use of patient-controlled analgesia (PCA) was significantly lower in the palifermin-treated groups (myeloma: 13% versus 53%, P < .001; lymphoma: 46% versus 68%, P < .001). Median total transplant charges were significantly higher in the palifermin-treated group, after controlling for inflation (myeloma: $167,820 versus $143,200, P < .001; lymphoma: $168,570 versus $148,590, P < .001). Palifermin treatment was not associated with a difference in days to neutrophil engraftment, length of stay, and overall survival and was associated with an additional cost of $5.5K (myeloma) and $14K (lymphoma) per day of PCA avoided. Future studies are suggested to evaluate the cost-effectiveness of palifermin compared with other symptomatic treatments to reduce transplant toxicity using validated measures for pain and quality of life.

  9. Evaluation of autologous bone marrow in wound healing in animal model: a possible application of autologous stem cells.

    PubMed

    Akela, Ashok; Nandi, Samit Kumar; Banerjee, Dibyajyoti; Das, Partha; Roy, Subhasis; Joardar, Siddhartha Narayan; Mandal, Mohan; Das, Pradip Kumar; Pradhan, Nisith Ranjan

    2012-10-01

    A study was conducted to evaluate the potential of autologous bone marrow-derived cells in comparison with buffy coat of autologous blood for rapid cutaneous wound healing in rabbit model. Three square full-thickness skin excisional wounds were created in 15 selected experimental animals (rabbit) divided randomly into three groups. The wound was treated with autologous bone marrow cells in plasma (group 1), buffy coat of blood in plasma (group 2) and autologous plasma as control (group 3). Wounds were observed for 30 days for granulation tissue formation, biochemical, histomorphological and histochemical evaluation. In this study, granulation tissue appeared significantly lesser in wounds of group 3 animals followed by group 2 and 1 animals. Neovascularisation, granulation tissue formation, denser, thicker and better arranged collagen fibres, reticulin fibres and elastin fibres formation was more in group 1 as compared with other groups. It was concluded that the application of bone marrow-derived nucleated cells into the wound margins resulted in early and significantly faster rate of complete healing as compared with buffy coat of autologous blood and autologous plasma (control). This approach may be beneficial in various surface wounds that heal at a slower rate and recommended for healing of various complicated wound in future.

  10. Clonal Hematopoiesis Associated With Adverse Outcomes After Autologous Stem-Cell Transplantation for Lymphoma.

    PubMed

    Gibson, Christopher J; Lindsley, R Coleman; Tchekmedyian, Vatche; Mar, Brenton G; Shi, Jiantao; Jaiswal, Siddhartha; Bosworth, Alysia; Francisco, Liton; He, Jianbo; Bansal, Anita; Morgan, Elizabeth A; Lacasce, Ann S; Freedman, Arnold S; Fisher, David C; Jacobsen, Eric; Armand, Philippe; Alyea, Edwin P; Koreth, John; Ho, Vincent; Soiffer, Robert J; Antin, Joseph H; Ritz, Jerome; Nikiforow, Sarah; Forman, Stephen J; Michor, Franziska; Neuberg, Donna; Bhatia, Ravi; Bhatia, Smita; Ebert, Benjamin L

    2017-01-09

    Purpose Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition characterized by somatic mutations in the blood of otherwise healthy adults. We hypothesized that in patients undergoing autologous stem-cell transplantation (ASCT) for lymphoma, CHIP at the time of ASCT would be associated with an increased risk of myelodysplastic syndrome and acute myeloid leukemia, collectively termed therapy-related myeloid neoplasm (TMN), and other adverse outcomes. Methods We performed whole-exome sequencing on pre- and post-ASCT samples from 12 patients who developed TMN after autologous transplantation for Hodgkin lymphoma or non-Hodgkin lymphoma and targeted sequencing on cryopreserved aliquots of autologous stem-cell products from 401 patients who underwent ASCT for non-Hodgkin lymphoma between 2003 and 2010. We assessed the effect of CHIP at the time of ASCT on subsequent outcomes, including TMN, cause-specific mortality, and overall survival. Results For six of 12 patients in the exome sequencing cohort, mutations found in the TMN specimen were also detectable in the pre-ASCT specimen. In the targeted sequencing cohort, 120 patients (29.9%) had CHIP at the time of ASCT, which was associated with an increased rate of TMN (10-year cumulative incidence, 14.1% v 4.3% for those with and without CHIP, respectively; P = .002). Patients with CHIP had significantly inferior overall survival compared with those without CHIP (10-year overall survival, 30.4% v 60.9%, respectively; P < .001), including increased risk of death from TMN and cardiovascular disease. Conclusion In patients undergoing ASCT for lymphoma, CHIP at the time of transplantation is associated with inferior survival and increased risk of TMN.

  11. Fast Cars and No Brakes: Autologous Stem Cell Transplantation as a Platform for Novel Immunotherapies.

    PubMed

    Perales, Miguel-Angel; Sauter, Craig S; Armand, Philippe

    2016-01-01

    Autologous stem cell transplantation (ASCT) is indicated in a number of hematologic malignancies, including multiple myeloma, non-Hodgkin lymphoma, and Hodgkin lymphoma. Relapse, however, remains 1 of the main causes of post-ASCT failure, and several strategies are being investigated to decrease the risk of relapse of progression. Recent advances in the treatment of hematological malignancies have included adoptive transfer of genetically modified T cells that express chimeric antigen receptors or T cell receptors, as well the use of checkpoint inhibitors. Early clinical results in nontransplantation patients have been very promising. This review will focus on the use of gene-modified T cells and checkpoint inhibitors in stem cell transplantation.

  12. Fast Cars and No Brakes: Autologous Stem Cell Transplantation as a Platform for Novel Immunotherapies

    PubMed Central

    Perales, Miguel-Angel; Sauter, Craig S.; Armand, Philippe

    2015-01-01

    Autologous stem cell transplantation (ASCT) is indicated in a number of hematologic malignancies, including multiple myeloma, non-Hodgkin lymphoma and Hodgkin lymphoma. Relapse however remains one of the main causes of post-ASCT failures, and several strategies are being investigated to decrease the risk of relapse of progression. Recent advances in the treatment of hematological malignancies have included adoptive transfer of genetically modified T cells that express chimeric antigen receptors or T cell receptors, as well the use of checkpoint inhibitors. Early clinical results in non-transplant patients have been very promising. This review will focus on the use of gene-modified T cells and checkpoint inhibitors in stem cell transplantation. PMID:26485445

  13. Human autologous mesenchymal stem cells with extracorporeal shock wave therapy for nonunion of long bones

    PubMed Central

    Zhai, Lei; Ma, Xin-Long; Jiang, Chuan; Zhang, Bo; Liu, Shui-Tao; Xing, Geng-Yan

    2016-01-01

    Background: Currently, the available treatments for long bone nonunion (LBN) are removing of focus of infection, bone marrow transplantation as well as Ilizarov methods etc. Due to a high percentage of failures, the treatments are complex and debated. To develop an effective method for the treatment of LBN, we explored the use of human autologous bone mesenchymal stems cells (hBMSCs) along with extracorporeal shock wave therapy (ESWT). Materials and Methods: Sixty three patients of LBN were subjected to ESWT treatment and were divided into hBMSCs transplantation group (Group A, 32 cases) and simple ESWT treatment group (Group B, 31 cases). Results: The patients were evaluated for 12 months after treatment. In Group A, 14 patients were healed and 13 showed an improvement, with fracture healing rate 84.4%. In Group B, eight patients were healed and 13 showed an improvement, with fracture healing rate 67.7%. The healing rates of the two groups exhibited a significant difference (P < 0.05). There was no significant difference for the callus formation after 3 months treatment (P > 0.05). However, the callus formation in Group A was significantly higher than that in the Group B after treatment for 6, 9, and 12 months (P < 0.05). Conclusion: Autologous bone mesenchymal stems cell transplantation with ESWT can effectively promote the healing of long bone nonunions. PMID:27746499

  14. How we manage autologous stem cell transplantation for patients with multiple myeloma

    PubMed Central

    Dingli, David

    2014-01-01

    An estimated 22 350 patients had multiple myeloma diagnosed in 2013, representing 1.3% of all new cancers; 10 710 deaths are projected, representing 1.8% of cancer deaths. Approximately 0.7% of US men and women will have a myeloma diagnosis in their lifetime, and with advances in therapy, 77 600 US patients are living with myeloma. The 5-year survival rate was 25.6% in 1989 and was 44.9% in 2005. The median age at diagnosis is 69 years, with 62.4% of patients aged 65 or older at diagnosis. Median age at death is 75 years. The rate of new myeloma cases has been rising 0.7% per year during the past decade. The most common indication for autologous stem cell transplantation in the United States is multiple myeloma, and this article is designed to provide the specifics of organizing a transplant program for multiple myeloma. We review the data justifying use of stem cell transplantation as initial management in myeloma patients. We provide selection criteria that minimize the risks of transplantation. Specific guidelines on mobilization and supportive care through the transplant course, as done at Mayo Clinic, are given. A review of the data on tandem vs sequential autologous transplants is provided. PMID:24973360

  15. Autologous Transplantation of Bone Marrow Adult Stem Cells for the Treatment of Idiopathic Dilated Cardiomyopathy

    PubMed Central

    Westphal, Ricardo João; Bueno, Ronaldo Rocha Loures; Galvão, Paulo Bezerra de Araújo; Zanis Neto, José; Souza, Juliano Mendes; Guérios, Ênio Eduardo; Senegaglia, Alexandra Cristina; Brofman, Paulo Roberto; Pasquini, Ricardo; da Cunha, Claudio Leinig Pereira

    2014-01-01

    Background Morbimortality in patients with dilated idiopathic cardiomyopathy is high, even under optimal medical treatment. Autologous infusion of bone marrow adult stem cells has shown promising preliminary results in these patients. Objective Determine the effectiveness of autologous transplantation of bone marrow adult stem cells on systolic and diastolic left ventricular function, and on the degree of mitral regurgitation in patients with dilated idiopathic cardiomyopathy in functional classes NYHA II and III. Methods We administered 4,54 x 108 ± 0,89 x 108 bone marrow adult stem cells into the coronary arteries of 24 patients with dilated idiopathic cardiomyopathy in functional classes NYHA II and III. Changes in functional class, systolic and diastolic left ventricular function and degree of mitral regurgitation were assessed after 3 months, 6 months and 1 year. Results During follow-up, six patients (25%) improved functional class and eight (33.3%) kept stable. Left ventricular ejection fraction improved 8.9%, 9.7% e 13.6%, after 3, 6 and 12 months (p = 0.024; 0.017 and 0.018), respectively. There were no significant changes neither in diastolic left ventricular function nor in mitral regurgitation degree. A combined cardiac resynchronization and implantable cardioversion defibrillation was implanted in two patients (8.3%). Four patients (16.6%) had sudden death and four patients died due to terminal cardiac failure. Average survival of these eight patients was 2.6 years. Conclusion Intracoronary infusion of bone marrow adult stem cells was associated with an improvement or stabilization of functional class and an improvement in left ventricular ejection fraction, suggesting the efficacy of this intervention. There were no significant changes neither in left ventricular diastolic function nor in the degree of mitral regurgitation. PMID:25590932

  16. Addition of Autologous Mesenchymal Stem Cells to Whole Blood for Bio-Enhanced ACL Repair has No Benefit in the Porcine Model

    PubMed Central

    Proffen, Benedikt L.; Vavken, Patrick; Haslauer, Carla M.; Fleming, Braden C.; Harris, Chad E.; Machan, Jason T.; Murray, Martha M.

    2015-01-01

    Background Co-culture of mesenchymal stem cells (MSCs) from the retropatellar fat pad and peripheral blood has been shown to stimulate anterior cruciate ligament (ACL) fibroblast proliferation and collagen production in vitro. Current techniques of bio-enhanced ACL repair in animal studies involve adding a biologic scaffold, in this case an extracellular matrix based scaffold saturated with autologous whole blood, to a simple suture repair of the ligament. Whether the enrichment of whole blood with MSCs would further improve the in vivo results of bio-enhanced ACL repair was investigated. Hypothesis/Purpose The hypothesis was that the addition of MSCs derived from adipose tissue or peripheral blood to the blood-extracellular matrix composite, which is used in bio-enhanced ACL repair to stimulate healing, would improve the biomechanical properties of a bio-enhanced ACL repair after 15 weeks of healing. Study Design Controlled laboratory study. Methods Twenty-four adolescent Yucatan mini-pigs underwent ACL transection followed by: 1) bio-enhanced ACL repair, 2) bio-enhanced ACL repair with the addition of autologous adipose-derived MSCs and 3) bio-enhanced ACL repair with the addition of autologous peripheral blood derived MSCs. After fifteen weeks of healing, structural properties of the ACL (yield & failure load, linear stiffness) were measured. Cell and vascular density were measured in the repaired ACL via histology, and its tissue structure was qualitatively evaluated using the Advanced Ligament Maturity Index. Results After fifteen weeks of healing, there were no significant improvements in the biomechanical or histological properties with the addition of adipose-derived MSCs. The only significant change with the addition of peripheral blood MSCs was an increase in knee anteroposterior (AP) laxity when measured at 30 degrees of flexion. Conclusions These findings suggest that the addition of adipose or peripheral blood MSCs to whole blood prior to saturation of

  17. Thalidomide in newly diagnosed multiple myeloma: influence of thalidomide treatment on peripheral blood stem cell collection yield.

    PubMed

    Breitkreutz, I; Lokhorst, H M; Raab, M S; Holt, B van der; Cremer, F W; Herrmann, D; Glasmacher, A; Schmidt-Wolf, I G H; Blau, I W; Martin, H; Salwender, H; Haenel, A; Sonneveld, P; Goldschmidt, H

    2007-06-01

    In a phase III randomized, multicenter study, the German-speaking Myeloma-Multicenter Group (GMMG) and the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON) group investigated the influence of thalidomide (Thal) on the outcome of peripheral blood stem cell (PBSC) collection in multiple myeloma (MM) before peripheral autologous blood stem cell transplantation (ABSCT). We analyzed the data of 398 myeloma patients after induction with Thal, doxorubicin and dexamethasone (TAD) in comparison with vincristine, doxorubicin and dexamethasone (VAD) followed by mobilization with cyclophosphamide, doxorubicin, dexamethasone (CAD) and PBSC collection. Within both the study groups, patients treated with TAD showed to collect significantly fewer CD34(+) cells compared with VAD (GMMG, TAD: median 9.8 x 10(6)/kg; range 2.0-33.6; VAD: median 10.9 x 10(6)/kg range 3.0-36.0; P=0.02) (HOVON, TAD: median 7.4 x 10(6)/kg; range 2.0-33.0; VAD: median 9.4 x 10(6)/kg; range 0.0-48.7; P=0.009). However, engraftment after peripheral autologous stem cell transplantation showed no difference between Thal and VAD groups. We conclude that Thal as a part of induction regimen is associated with better response rates (GMMG-HD3: CR/PR 79%, VAD: CR/PR 58%; HOVON-50: TAD: CR/PR 81%, VAD: CR/PR 61%), but significantly affects the yield of PBSC collection. Nevertheless, the number of total CD34(+) cells collected was sufficient for double autologous transplantation in 82% of the Thal patients, with at least 2.5 x 10(6)/kg CD34(+) cells.

  18. Patients with mantle-cell lymphoma relapsing after autologous stem cell transplantation may be rescued by allogeneic transplantation.

    PubMed

    Martínez, C; Carreras, E; Rovira, M; Urbano-Ispizua, A; Esteve, J; Perales, M; Fernández, F; Montserrat, E

    2000-09-01

    Two patients with disseminated mantle-cell lymphoma relapsed 24 and 13 months, respectively, after high-dose chemotherapy and autologous stem cell transplantation (autoSCT). Both patients had an HLA-identical sibling and received an allogeneic stem cell transplant (alloSCT) 32 and 18 months after autologous transplant, after conditioning with fractionated 12 Gy total body irradiation plus cyclophosphamide 120 mg/kg. They are both alive and in complete remission 24 months after transplant. Both patients have developed chronic graft-versus-host disease and their Karnofsky performance status is 90%. AlloSCT may offer a useful approach in a subgroup of patients with mantle-cell lymphoma who have relapsed after autologous transplantation.

  19. Acute graft-versus-host disease and bronchiolitis obliterans after autologous stem cell transplantation in a patient with multiple myeloma

    PubMed Central

    Alonso, Sara; Cabrero, Mónica; Caballero, Juan C; Dávila, Julio; de la Calle, Veronica Gonzalez; López-Godino, Oriana; López-Corral, Lucia; Pérez, Estefanía; Vázquez, Lourdes; Corral, Rocío; Caballero, Dolores; del Cañizo, Consuelo; Mateos, María Victoria

    2015-01-01

    Key Clinical Message Sixty-seven-year-old patient, diagnosed with multiple myeloma who had received autologous stem cell transplantation, following bortezomib, dexamethasone and thalidomide conventional regimen, achieving complete response, developed rash, diarrhea, and severe respiratory failure, 80 days after the transplantation procedure. He was diagnosed with graft-versus-host disease and bronchiolitis obliterans syndrome. PMID:26185631

  20. Generating Peripheral Blood Derived Lymphocytes Reacting Against Autologous Primary AML Blasts.

    PubMed

    Mehta, Rohtesh S; Chen, Xiaohua; Antony, Jeyaraj; Boyiadzis, Michael; Szabolcs, Paul

    2016-01-01

    Expanding on our prior studies with cord blood T cells, we hypothesized that primary acute myeloid leukemia (AML)-reactive autologous T cells could be generated ex vivo under immunomodulatory conditions. We purified AML and T cells from 8 newly diagnosed high-risk patients. After 2 weeks expansion, T cells were stimulated with interferon-γ-treated autologous AML weekly × 3, interleukin-15, and agonistic anti-CD28 antibody. Cytotoxic T cells and ELISpot assays tested functionality; reverse transcriptase quantitative polymerase chain reaction tested AML and T-cell gene expression profiles. On the basis of combined positive ELIspot and cytotoxic T cells assays, T cells reactive against AML were generated in 5 of 8 patients. Treg proportion declined after cocultures in reactive T-cell samples. AML-reactive T cells displayed an activated gene expression profile. "Resistant" AML blasts displayed genes associated with immunosuppressive myeloid-derived suppressor cells. We discuss our approach to creating primary AML-reactive autologous T cell and limitations that require further work. Our study provides a platform for future research targeting on generating autologous leukemia-reactive T cells.

  1. Generating Peripheral Blood Derived Lymphocytes Reacting Against Autologous Primary AML Blasts

    PubMed Central

    Mehta, Rohtesh S.; Chen, Xiaohua; Antony, Jeyaraj; Boyiadzis, Michael; Szabolcs, Paul

    2015-01-01

    Expanding on our prior studies with cord blood T-cells, we hypothesized that primary AML-reactive autologous T-cells could be generated ex vivo under immunomodulatory conditions. We purified AML and T-cells from 8 newly diagnosed high-risk patients. After 2 weeks expansion, T-cells were stimulated with IFN-γ treated autologous AML weekly X 3, IL-15 and agonistic anti-CD28 antibody. CTL and ELISpot assays tested functionality; RT-qPCR tested AML and T-cell gene expression profiles. Based on combined positive ELIspot and CTL assays, T-cells reactive against AML were generated in 5/8 patients. Treg proportion declined post-co-cultures in reactive T-cell samples. AML-reactive T-cells displayed an activated gene expression profile. “Resistant” AML blasts displayed genes associated with immunosuppressive MDSC. We discuss our approach to creating primary AML-reactive autologous T-cell and limitations that require further work. Our study provides a platform for future research targeting on generating autologous leukemia reactive T-cells. PMID:26849076

  2. Autologous hematopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: comparison with secondary progressive multiple sclerosis.

    PubMed

    Casanova, Bonaventura; Jarque, Isidro; Gascón, Francisco; Hernández-Boluda, Juan Carlos; Pérez-Miralles, Francisco; de la Rubia, Javier; Alcalá, Carmen; Sanz, Jaime; Mallada, Javier; Cervelló, Angeles; Navarré, Arantxa; Carcelén-Gadea, María; Boscá, Isabel; Gil-Perotin, Sara; Solano, Carlos; Sanz, Miguel Angel; Coret, Francisco

    2017-04-10

    The main objective of our work is to describe the long-term results of myeloablative autologous hematopoietic stem cell transplant (AHSCT) in multiple sclerosis patients. Patients that failed to conventional therapies for multiple sclerosis (MS) underwent an approved protocol for AHSCT, which consisted of peripheral blood stem cell mobilization with cyclophosphamide and granulocyte colony-stimulating factor (G-CSF), followed by a conditioning regimen of BCNU, Etoposide, Ara-C, Melphalan IV, plus Rabbit Thymoglobulin. Thirty-eight MS patients have been transplanted since 1999. Thirty-one patients have been followed for more than 2 years (mean 8.4 years). There were 22 relapsing-remitting multiple sclerosis (RRMS) patients and 9 secondary progressive multiple sclerosis (SPMS) patients. No death related to AHSCT. A total of 10 patients (32.3%) had at least one relapse during post-AHSCT evolution, 6 patients in the RRMS group (27.2%) and 4 in the SPMS group (44.4%). After AHSCT, 7 patients (22.6%) experienced progression of disability, all within SP form. By contrast, no patients with RRMS experienced worsening of disability after a median follow-up of 5.4 years, 60% of them showed a sustained reduction in disability (SRD), defined as the improvement of 1.0 point in the expanded disability status scale (EDSS) sustains for 6 months (0.5 in cases of EDSS ≥ 5.5). The only clinical variable that predicted a poor response to AHSCT was a high EDSS in the year before transplant. AHSCT using the BEAM-ATG scheme is safe and efficacious to control the aggressive forms of RRMS.

  3. The effect of erythropoietin on autologous stem cell-mediated bone regeneration.

    PubMed

    Nair, Ashwin M; Tsai, Yi-Ting; Shah, Krishna M; Shen, Jinhui; Weng, Hong; Zhou, Jun; Sun, Xiankai; Saxena, Ramesh; Borrelli, Joseph; Tang, Liping

    2013-10-01

    Mesenchymal stem cells (MSCs) although used for bone tissue engineering are limited by the requirement of isolation and culture prior to transplantation. Our recent studies have shown that biomaterial implants can be engineered to facilitate the recruitment of MSCs. In this study, we explore the ability of these implants to direct the recruitment and the differentiation of MSCs in the setting of a bone defect. We initially determined that both stromal derived factor-1alpha (SDF-1α) and erythropoietin (Epo) prompted different degrees of MSC recruitment. Additionally, we found that Epo and bone morphogenetic protein-2 (BMP-2), but not SDF-1α, triggered the osteogenic differentiation of MSCs in vitro. We then investigated the possibility of directing autologous MSC-mediated bone regeneration using a murine calvaria model. Consistent with our in vitro observations, Epo-releasing scaffolds were found to be more potent in bridging the defect than BMP-2 loaded scaffolds, as determined by computed tomography (CT) scanning, fluorescent imaging and histological analyses. These results demonstrate the tremendous potential, directing the recruitment and differentiation of autologous MSCs has in the field of tissue regeneration.

  4. T-cell-replete haploidentical transplantation versus autologous stem cell transplantation in adult acute leukemia: a matched pair analysis.

    PubMed

    Gorin, Norbert-Claude; Labopin, Myriam; Piemontese, Simona; Arcese, William; Santarone, Stella; Huang, He; Meloni, Giovanna; Ferrara, Felicetto; Beelen, Dietrich; Sanz, Miguel; Bacigalupo, Andrea; Ciceri, Fabio; Mailhol, Audrey; Nagler, Arnon; Mohty, Mohamad

    2015-04-01

    Adult patients with acute leukemia in need of a transplant but without a genoidentical donor are usually considered upfront for transplantation with stem cells from any other allogeneic source, rather than autologous stem cell transplantation. We used data from the European Society for Blood and Marrow Transplantation and performed a matched pair analysis on 188 T-cell-replete haploidentical and 356 autologous transplants done from January 2007 to December 2012, using age, diagnosis, disease status, cytogenetics, and interval from diagnosis to transplant as matching factors. "Haploidentical expert" centers were defined as having reported more than five haploidentical transplants for acute leukemia (median value for the study period). The median follow-up was 28 months. Multivariate analyses, including type of transplant categorized into three classes ("haploidentical regular", "haploidentical expert" and autologous), conditioning intensity (reduced intensity versus myeloablative conditioning) and the random effect taking into account associations related to matching, showed that non-relapse mortality was higher following haploidentical transplants in expert (HR: 4.7; P=0.00004) and regular (HR: 8.98; P<10(-5)) centers. Relapse incidence for haploidentical transplants was lower in expert centers (HR:0.39; P=0.0003) but in regular centers was similar to that for autologous transplants. Leukemia-free survival and overall survival rates were higher following autologous transplantation than haploidentical transplants in regular centers (HR: 1.63; P=0.008 and HR: 2.31; P=0.0002 respectively) but similar to those following haploidentical transplants in expert centers. We conclude that autologous stem cell transplantation should presently be considered as a possible alternative to haploidentical transplantation in regular centers that have not developed a specific expert program.

  5. Update on the Role of Autologous Hematopoietic Stem Cell Transplantation in Follicular Lymphoma

    PubMed Central

    Cabrero, Mónica; Redondo, Alba; Martin, Alejandro; Caballero, Dolores

    2012-01-01

    Follicular lymphoma (FL) remains incurable despite advances in new strategies of treatment, including monoclonal antibodies (MoAb). Except for early stages, FL is characterized by responses to treatments and systematic relapses. The main objective in this disease is to achieve a better progression free survival (PFS) and to increase overall survival (OS), mainly in young patients. In order to improve the results of conventional chemotherapy, autologous stem cell transplant (ASCT) is a feasible treatment in these patients. In this moment, ASCT is not recommended as first line treatment, except for transformed FL, but is a good strategy as salvage therapy with an improved PFS and OS. New drugs have been introduced to enhance responses of ASCT, but nowadays they are not part of conventional conditioning regimen. PMID:23205262

  6. Update on the role of autologous hematopoietic stem cell transplantation in follicular lymphoma.

    PubMed

    Cabrero, Mónica; Redondo, Alba; Martin, Alejandro; Caballero, Dolores

    2012-01-01

    Follicular lymphoma (FL) remains incurable despite advances in new strategies of treatment, including monoclonal antibodies (MoAb). Except for early stages, FL is characterized by responses to treatments and systematic relapses. The main objective in this disease is to achieve a better progression free survival (PFS) and to increase overall survival (OS), mainly in young patients. In order to improve the results of conventional chemotherapy, autologous stem cell transplant (ASCT) is a feasible treatment in these patients. In this moment, ASCT is not recommended as first line treatment, except for transformed FL, but is a good strategy as salvage therapy with an improved PFS and OS. New drugs have been introduced to enhance responses of ASCT, but nowadays they are not part of conventional conditioning regimen.

  7. Autologous Induced Stem-Cell-Derived Retinal Cells for Macular Degeneration.

    PubMed

    Mandai, Michiko; Watanabe, Akira; Kurimoto, Yasuo; Hirami, Yasuhiko; Morinaga, Chikako; Daimon, Takashi; Fujihara, Masashi; Akimaru, Hiroshi; Sakai, Noriko; Shibata, Yumiko; Terada, Motoki; Nomiya, Yui; Tanishima, Shigeki; Nakamura, Masahiro; Kamao, Hiroyuki; Sugita, Sunao; Onishi, Akishi; Ito, Tomoko; Fujita, Kanako; Kawamata, Shin; Go, Masahiro J; Shinohara, Chikara; Hata, Ken-Ichiro; Sawada, Masanori; Yamamoto, Midori; Ohta, Sachiko; Ohara, Yasuo; Yoshida, Kenichi; Kuwahara, Junko; Kitano, Yuko; Amano, Naoki; Umekage, Masafumi; Kitaoka, Fumiyo; Tanaka, Azusa; Okada, Chihiro; Takasu, Naoko; Ogawa, Seishi; Yamanaka, Shinya; Takahashi, Masayo

    2017-03-16

    We assessed the feasibility of transplanting a sheet of retinal pigment epithelial (RPE) cells differentiated from induced pluripotent stem cells (iPSCs) in a patient with neovascular age-related macular degeneration. The iPSCs were generated from skin fibroblasts obtained from two patients with advanced neovascular age-related macular degeneration and were differentiated into RPE cells. The RPE cells and the iPSCs from which they were derived were subject to extensive testing. A surgery that included the removal of the neovascular membrane and transplantation of the autologous iPSC-derived RPE cell sheet under the retina was performed in one of the patients. At 1 year after surgery, the transplanted sheet remained intact, best corrected visual acuity had not improved or worsened, and cystoid macular edema was present. (Funded by Highway Program for Realization of Regenerative Medicine and others; University Hospital Medical Information Network Clinical Trials Registry [UMIN-CTR] number, UMIN000011929 .).

  8. Oral Ciprofloxacin Prophylaxis in Patients Undergoing High DoseTherapy and Autologous Hematopoietic Stem Cell Transplantation

    PubMed Central

    Tabarraee, Mahdi; Tavakoli-Ardakani, Maria; Mehdizadeh, Mahshid; Ghadiani, Mojtaba; Rezvani, Hamid; Hajifathali, Abbas; khamsi, Samiyeh

    2016-01-01

    Antibiotic prophylaxis is usually used in allogeneic stem cell transplantation, but its use in Autologous Stem Cell Transplantation (ASCT) is controversial. We evaluated the efficacy of ciprofloxacin prophylaxis in ASCT. To identify the efficacy of ciprofloxacin on the incidence of neutropenic fever and its complications, 72 patients that had been admitted to Taleghani Hospital for ASCT between 2010 and 2012 were evaluated in our study. Oral ciprofloxacin 500 mg every 12 h was administered to 30 patients on the same day of high dose chemotherapy until the first febrile episode or until the recovery of neutropenia and the results were analyzed and compared with the historical control group 42 other transplanted patients who had not previously received ciprofloxacin. The incidence of neutropenic fever was 80% with no difference between the two groups. But in ciprofloxacin group, duration of fever (1.7 days VS 3.5 days P=0.017), hospitalization due to stem cell transfusion (18.2 days VS 12.2 days p=0.03), incidence of bacteremia 3.3 % VS 33.3%, p=0.002) and platelet recovery (13.9 VS 17.7 days= 0.035) and platelet transfusions (P=0.04) were significantly lower than the control group no side effects and no delay in. Based on this study oral ciprofloxacin prophylaxis is rational, efficacious and economic in ASCT. PMID:28228813

  9. Beneficial Effects of Autologous Bone Marrow-Derived Mesenchymal Stem Cells in Naturally Occurring Tendinopathy

    PubMed Central

    Smith, Roger Kenneth Whealands; Werling, Natalie Jayne; Dakin, Stephanie Georgina; Alam, Rafiqul; Goodship, Allen E.; Dudhia, Jayesh

    2013-01-01

    Tendon injuries are a common age-related degenerative condition where current treatment strategies fail to restore functionality and normal quality of life. This disease also occurs naturally in horses, with many similarities to human tendinopathy making it an ideal large animal model for human disease. Regenerative approaches are increasingly used to improve outcome involving mesenchymal stem cells (MSCs), supported by clinical data where injection of autologous bone marrow derived MSCs (BM-MSCs) suspended in marrow supernatant into injured tendons has halved the re-injury rate in racehorses. We hypothesized that stem cell therapy induces a matrix more closely resembling normal tendon than the fibrous scar tissue formed by natural repair. Twelve horses with career-ending naturally-occurring superficial digital flexor tendon injury were allocated randomly to treatment and control groups. 1X107 autologous BM-MSCs suspended in 2 ml of marrow supernatant were implanted into the damaged tendon of the treated group. The control group received the same volume of saline. Following a 6 month exercise programme horses were euthanized and tendons assessed for structural stiffness by non-destructive mechanical testing and for morphological and molecular composition. BM-MSC treated tendons exhibited statistically significant improvements in key parameters compared to saline-injected control tendons towards that of normal tendons and those in the contralateral limbs. Specifically, treated tendons had lower structural stiffness (p<0.05) although no significant difference in calculated modulus of elasticity, lower (improved) histological scoring of organisation (p<0.003) and crimp pattern (p<0.05), lower cellularity (p<0.007), DNA content (p<0.05), vascularity (p<0.03), water content (p<0.05), GAG content (p<0.05), and MMP-13 activity (p<0.02). Treatment with autologous MSCs in marrow supernatant therefore provides significant benefits compared to untreated tendon repair in

  10. Therapeutic Efficacy of Fresh, Autologous Mesenchymal Stem Cells for Severe Refractory Gingivostomatitis in Cats

    PubMed Central

    Mills-Ko, Emily; Verstraete, Frank J.M.; Kol, Amir; Walker, Naomi J.; Badgley, Megan R.; Fazel, Nasim; Murphy, William J.; Vapniarsky, Natalia; Borjesson, Dori L.

    2016-01-01

    Mesenchymal stem cells (MSCs) are a promising therapy for immune-mediated and inflammatory disorders, because of their potent immunomodulatory properties. In this study, we investigated the use of fresh, autologous, adipose-derived MSCs (ASCs) for feline chronic gingivostomatitis (FCGS), a chronic, debilitating, idiopathic, oral mucosal inflammatory disease. Nine cats with refractory FCGS were enrolled in this pilot study. Each cat received 2 intravenous injections of 20 million autologous ASCs, 1 month apart. Oral biopsies were taken before and at 6 months after the first ASC injection. Blood immune cell subsets, serum protein, and cytokine levels were measured at 0, 1, 3, and 6 months after treatment to assess immunomodulatory effects. Seven of the 9 cats completed the study. Five cats responded to treatment by either complete clinical remission (n = 3) or substantial clinical improvement (n = 2). Two cats were nonresponders. Cats that responded to treatment also exhibited systemic immunomodulation demonstrated by decreased numbers of circulating CD8+ T cells, a normalization of the CD4/CD8 ratio, decreased neutrophil counts, and interferon-γ and interleukin (IL)-1β concentration, and a temporary increase in serum IL-6 and tumor necrosis factor-α concentration. No clinical recurrence has occurred following complete clinical remission (follow-up of 6–24 months). In this study, cats with <15% cytotoxic CD8 T cells with low expression of CD8 (CD8lo) cells were 100% responsive to ASC therapy, whereas cats with >15% CD8lo cells were nonresponders. The relative absence of CD8lo cells may be a biomarker to predict response to ASC therapy, and may shed light on pathogenesis of FCGS and mechanisms by which ASCs decrease oral inflammation and affect T-cell phenotype. Significance This study is the first to demonstrate the safety and efficacy of fresh, autologous, adipose-derived stem cell systemic therapy for a naturally occurring, chronic inflammatory disease in cats

  11. Autologous stem cell transplantation for a monoclonal gammopathy of undetermined significance mimicking amyotrophic lateral sclerosis: A case report

    PubMed Central

    XIE, LINNA; ZHOU, FANG

    2014-01-01

    It is rare for patients with monoclonal gammopathy of undetermined significance (MGUS) to present with clinical features of fatal motor neuron disease, for example amyotrophic lateral sclerosis (ALS). There is no standard and effective therapy for either MGUS or ALS. In addition, stem cell transplantation appears to be ineffective for the treatment of this disease. In the present study, a 47-year old female with MGUS that mimicked ALS is presented. The M-protein levels of the patient were normalized following two cycles of chemotherapy and autologous stem cell transplantation treatment. MGUS was found to be alleviated and the symptoms of ALS did not deteriorate. The results showed a positive therapeutic effect of autologous stem cell transplantation for MGUS. PMID:25120635

  12. International Myeloma Working Group Consensus Statement for the Management, Treatment, and Supportive Care of Patients With Myeloma Not Eligible for Standard Autologous Stem-Cell Transplantation

    PubMed Central

    Palumbo, Antonio; Rajkumar, S. Vincent; San Miguel, Jesus F.; Larocca, Alessandra; Niesvizky, Ruben; Morgan, Gareth; Landgren, Ola; Hajek, Roman; Einsele, Hermann; Anderson, Kenneth C.; Dimopoulos, Meletios A.; Richardson, Paul G.; Cavo, Michele; Spencer, Andrew; Stewart, A. Keith; Shimizu, Kazuyuki; Lonial, Sagar; Sonneveld, Pieter; Durie, Brian G.M.; Moreau, Philippe; Orlowski, Robert Z.

    2014-01-01

    Purpose To provide an update on recent advances in the management of patients with multiple myeloma who are not eligible for autologous stem-cell transplantation. Methods A comprehensive review of the literature on diagnostic criteria is provided, and treatment options and management of adverse events are summarized. Results Patients with symptomatic disease and organ damage (ie, hypercalcemia, renal failure, anemia, or bone lesions) require immediate treatment. The International Staging System and chromosomal abnormalities identify high- and standard-risk patients. Proteasome inhibitors, immunomodulatory drugs, corticosteroids, and alkylating agents are the most active agents. The presence of concomitant diseases, frailty, or disability should be assessed and, if present, treated with reduced-dose approaches. Bone disease, renal damage, hematologic toxicities, infections, thromboembolism, and peripheral neuropathy are the most frequent disabling events requiring prompt and active supportive care. Conclusion These recommendations will help clinicians ensure the most appropriate care for patients with myeloma in everyday clinical practice. PMID:24419113

  13. Outcome of intensive immunosuppression and autologous stem cell transplantation in patients with severe rheumatoid arthritis is associated with the composition of synovial T cell infiltration

    PubMed Central

    Verburg, R; Flierman, R; Sont, J; Ponchel, F; van Dreunen, L; Levarht, E; Welling, M; Toes, R; Isaacs, J; van Laar, J M

    2005-01-01

    Objective: To determine clinical and immunological correlates of high dose chemotherapy (HDC) + autologous stem cell transplantation (ASCT) in patients with severe rheumatoid arthritis (RA), refractory to conventional treatment. Methods: Serial samples of peripheral blood and synovial tissue were obtained from seven patients with RA treated with HDC and autologous peripheral blood grafts enriched for CD34+ cells. Disease activity was assessed with the Disease Activity Score (DAS), serum concentrations of C reactive protein (CRP), and human immunoglobulin (HIg) scans, and the extent of immunoablation was determined by immunophenotyping of peripheral blood mononuclear cells, and immunohistochemistry and double immunofluorescence of synovium. Results: Clinical responders (n = 5) had a larger number of cells at baseline expressing CD3, CD4, CD27, CD45RA, CD45RB, and CD45RO in synovium (p<0.05), higher activity on HIg scans (p = 0.08), and a trend towards higher concentrations of CRP in serum than non-responders (n = 2). Subsequent remissions and relapses in responders paralleled reduction and re-expression, respectively, of T cell markers. A relatively increased expression of CD45RB and CD45RO on synovial CD3+ T cells was seen after HDC + ASCT. No correlations were found between DAS and changes in B cells or macrophage infiltration or synoviocytes. Conclusions: HDC + ASCT results in profound but incomplete immunoablation of both the memory and naïve T cell compartment, which is associated with longlasting clinical responses in most patients. The findings provide strong circumstantial evidence for a role of T cells in established RA, and demonstrate a role for the synovium in post-transplantation T cell reconstitution. PMID:15829573

  14. Allogenic stem cell transplantation as salvage therapy for patients relapsing after autologous transplantation: experience from a single institution.

    PubMed

    Martínez, C; Carreras, E; Rovira, M; Urbano-Ispizua, A; Esteve, J; Fernández-Avilés, F; Perales, M; Rives, S; Gómez, M; Montserrat, E

    2001-05-01

    The prognosis of patients relapsing after an autologous transplant (autoSCT) is very poor. Allogenic stem cell transplantation (alloSCT) offers the possibility of curing some of these patients, at the cost, however, of a high transplant related mortality (TRM). The aim of this study was to analyze the outcome of 14 consecutive patients with hematologic malignancies, from a single institution, who underwent alloSCT for progressive disease after autoSCT. Patients had relapsed at a median of 11.5 months (range 2-72) after autoSCT and they underwent alloSCT at a median of 25.5 months (range 7-73) from the first transplant. Ten patients received HLA-identical related peripheral blood progenitor cells, three patients underwent matched-unrelated donor marrow transplants, and one patient received a mismatched related transplant. Conditioning regimens consisted of total body irradiation plus cyclophosphamide (n=5) or melphalan (n=1), or high-dose combination chemotherapy (n=8). Cyclosporin A and methotrexate were administered as graft-versus-host disease (GVHD) prophylaxis. Eight patients (57%) developed grade II-IV acute GVHD. All evaluable patients (n=6) presented extensive chronic GVHD. Overall survival at 1 year was 16% (median 3.5 months, 95% CI 0.7-10.3). Ten patients (71%) died from transplant related complications at a median of 3.5 months (range 0.7-11). Only one patient died of recurrent disease. Three patients remain alive and in complete remission at the time of this report (4, 20 and 20 months, respectively). In conclusion, alloSCT offers the possibility of a sustained control of the disease in some patients who relapse after an autoSCT. However, the procedure is associated with a high transplant-related mortality. Better results might be obtained by carefully selecting patients and by reducing the intensity of the preparative regimen.

  15. Successful mobilization of peripheral blood stem cells in children with cancer using plerixafor (Mozobil) and granulocyte-colony stimulating factor.

    PubMed

    Avramova, Boryana E; Yordanova, Maya N; Konstantinov, Dobrin N; Bobev, Dragan G

    2011-01-01

    This paper describes the successful mobilization of peripheral blood stem cells for autologous transplantation in three children with malignant diseases by using plerixafor (Mozobil; Genzyme Corporation, Cambridge, MA) and granulocyte-colony stimulating factor (G-CSF) after failed previous mobilizations. A median sixfold increase in the number of circulating CD34+ cells after plerixafor treatment as compared with the baseline level was observed. An optimal CD34+ cell count for transplantation with one or two leukapheresis sessions was achieved. Mobilization using plerixafor was found to be safe with no adverse events. Therefore, the combination of G-CSF and plerixafor in children results in effective increases in peripheral CD34+ cell counts and reduces the risk of mobilization failure.

  16. Successful mobilization of peripheral blood stem cells in children with cancer using plerixafor (Mozobil™) and granulocyte-colony stimulating factor

    PubMed Central

    Avramova, Boryana E; Yordanova, Maya N; Konstantinov, Dobrin N; Bobev, Dragan G

    2011-01-01

    This paper describes the successful mobilization of peripheral blood stem cells for autologous transplantation in three children with malignant diseases by using plerixafor (Mozobil™; Genzyme Corporation, Cambridge, MA) and granulocyte-colony stimulating factor (G-CSF) after failed previous mobilizations. A median sixfold increase in the number of circulating CD34+ cells after plerixafor treatment as compared with the baseline level was observed. An optimal CD34+ cell count for transplantation with one or two leukapheresis sessions was achieved. Mobilization using plerixafor was found to be safe with no adverse events. Therefore, the combination of G-CSF and plerixafor in children results in effective increases in peripheral CD34+ cell counts and reduces the risk of mobilization failure. PMID:21966213

  17. Plerixafor as preemptive strategy results in high success rates in autologous stem cell mobilization failure.

    PubMed

    Worel, Nina; Fritsch, Gerhard; Agis, Hermine; Böhm, Alexandra; Engelich, Georg; Leitner, Gerda C; Geissler, Klaus; Gleixner, Karoline; Kalhs, Peter; Buxhofer-Ausch, Veronika; Keil, Felix; Kopetzky, Gerhard; Mayr, Viktor; Rabitsch, Werner; Reisner, Regina; Rosskopf, Konrad; Ruckser, Reinhard; Zoghlami, Claudia; Zojer, Niklas; Greinix, Hildegard T

    2016-08-31

    Plerixafor in combination with granulocyte-colony stimulating factor (G-CSF) is approved for autologous stem cell mobilization in poor mobilizing patients with multiple myeloma or malignant lymphoma. The purpose of this study was to evaluate efficacy and safety of plerixafor in an immediate rescue approach, administrated subsequently to G-CSF alone or chemotherapy and G-CSF in patients at risk for mobilization failure. Eighty-five patients mobilized with G-CSF alone or chemotherapy were included. Primary endpoint was the efficacy of the immediate rescue approach of plerixafor to achieve ≥2.0 × 10(6) CD34(+) cells/kg for a single or ≥5 × 10(6) CD34(+) cells/kg for a double transplantation and potential differences between G-CSF and chemotherapy-based mobilization. Secondary objectives included comparison of stem cell graft composition including CD34(+) cell and lymphocyte subsets with regard to the mobilization regimen applied. No significant adverse events were recorded. A median 3.9-fold increase in CD34(+) cells following plerixafor was observed, resulting in 97% patients achieving at least ≥2 × 10(6) CD34+ cells/kg. Significantly more differentiated granulocyte and monocyte forming myeloid progenitors were collected after chemomobilization whereas more CD19(+) and natural killer cells were collected after G-CSF. Fifty-two patients underwent transplantation showing rapid and durable engraftment, irrespectively of the stem cell mobilization regimen used. The addition of plerixafor in an immediate rescue model is efficient and safe after both, G-CSF and chemomobilization and results in extremely high success rates. Whether the differences in graft composition have a clinical impact on engraftment kinetics, immunologic recovery, and graft durability have to be analysed in larger prospective studies.

  18. Icing oral mucositis: Oral cryotherapy in multiple myeloma patients undergoing autologous hematopoietic stem cell transplant.

    PubMed

    Chen, Joey; Seabrook, Jamie; Fulford, Adrienne; Rajakumar, Irina

    2017-03-01

    Background Up to 70% of patients receiving hematopoietic stem cell transplant develop oral mucositis as a side effect of high-dose melphalan conditioning chemotherapy. Oral cryotherapy has been documented to be potentially effective in reducing oral mucositis. The aim of this study was to examine the effectiveness of the cryotherapy protocol implemented within the hematopoietic stem cell transplant program. Methods A retrospective chart review was conducted of adult multiple myeloma patients who received high-dose melphalan conditioning therapy for autologous hematopoietic stem cell transplant. Primary endpoints were incidence and severity of oral mucositis. Secondary endpoints included duration of oral mucositis, duration of hospital stay, parenteral narcotics use and total parenteral nutrition use. Results One hundred and forty patients were included in the study, 70 patients in both no cryotherapy and cryotherapy groups. Both oral mucositis incidence and severity were found to be significantly lower in the cryotherapy group. Fifty (71.4%) experienced mucositis post cryotherapy compared to 67 (95.7%) in the no cryotherapy group (p < 0.001). The median oral mucositis severity, assessed using the WHO oral toxicity scale from grade 0-4, experienced in the no group was 2.5 vs. 2 in the cryotherapy group (p = 0.03). Oral mucositis duration and use of parenteral narcotics were also significantly reduced. Duration of hospital stay and use of parenteral nutrition were similar between the two groups. Conclusion The cryotherapy protocol resulted in a significantly lower incidence and severity of oral mucositis. These results provide evidence for the continued use of oral cryotherapy, an inexpensive and generally well-tolerated practice.

  19. Autologous Transplantation of Adult Mice Spermatogonial Stem Cells into Gamma Irradiated Testes

    PubMed Central

    Koruji, Morteza; Movahedin, Mansoureh; Mowla, Seyed Javad; Gourabi, Hamid; Pour-Beiranvand, Shahram; Jabbari Arfaee, Ali

    2012-01-01

    Objective: We evaluated structural and functional changes of fresh and frozen-thawed adult mouse spermatogonial stem cells following auto-transplantation into gamma-irradiated testes. Materials and Methods: In this experimental research, the right testes from adult mice (n=25) were collected, then Sertoli and spermatogonial cells were isolated using two-step enzymatic digestion, lectin immobilization and differential plating. Three weeks after cultivation, the Bromodeoxyuridine (BrdU)-labeled spermatogonial cells were transplanted, via rete testis, into the other testis of the same mouse, which had been irradiated with 14Gy. The mice were transplanted with: fresh cells (control 1), fresh cells co-cultured with Sertoli cells (control 2), the frozen-thawed cells (experimental 1) and frozen-thawed cells co-cultured with Sertoli cells (experimental 2). The morphological changes between different transplanted testes groups were compared in 8 weeks after transplantation. The statistical significance between mean values was determined by Kruskal Wallis and one-way analysis of variance in efficiency of transplantation. Results: The statistical analysis revealed significant increases in the mean percentage of testis weight and normal seminiferous tubules following spermatogonial stem cells transplantation in the recipient'fs testes. The normal seminiferous tubules percentage in the co-culture system with fresh cells and frozen-thawed groups were more than those in non-transplanted and fresh cell transplanted groups (p≤0.001). Conclusion: Our results demonstrated that spermatogonial stem cells in the colonies could result sperm production in the recipient’s testes after autologous transplantation. PMID:23507977

  20. Peripheral blood stem cell transplant for POEMS syndrome is associated with high rates of engraftment syndrome

    PubMed Central

    Dispenzieri, Angela; Lacy, Martha Q; Hayman, Suzanne R; Kumar, Shaji K; Buadi, Francis; Dingli, David; Litzow, Mark R; Gastineau, Dennis A; Inwards, David J; Elliott, Michelle A; Micallef, Ivana N; Ansell, Stephen M; Hogan, William J; Porrata, Luis F; Johnston, Patrick A; Afessa, Bekele; Bryce, Alan; Kyle, Robert A; Gertz, Morie A

    2008-01-01

    Polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes (POEMS) syndrome is a devastating syndrome, characterized by peripheral neuropathy, organomegaly, endocrinopathy, monoclonal plasma cells, skin changes, papilledema, volume overload, sclerotic bone lesions, thrombocytosis and high vascular endothelial growth factor (VEGF). High-dose chemotherapy with autologous peripheral blood stem cell transplantation (ASCT) ultimately yields excellent clinical responses, but there can be considerable peritransplant morbidity. We have treated 30 POEMS patients with ASCT at Mayo Clinic, Rochester. During transplant period, patients had high rates of fever, diarrhea, weight gain and rash (93%, 77%, 53% and 43%, respectively). Only 13% remained outpatient, and median time to discharge from hospital was transplant day 17 (range 0–175). Splenomegaly was the baseline factor that best predicted for a complicated peritransplant course. Depending on the definition used, ∼50% of patients satisfied criteria for engraftment syndrome. Earlier and more aggressive use of corticosteroids may be associated with less complicated post-transplant courses. Median overall survival has not been reached; the treatment-related mortality was 3%. In addition, important clinical improvements and reductions in plasma VEGF levels can occur in the absence of significant decrease in the monoclonal protein. Unraveling the mechanisms of the syndrome both in the context of ASCT and in general are challenges for the future. PMID:18221391

  1. Consolidation treatment for high risk solid tumors in children with myeloablative chemotherapy and autologous hematopoietic progenitor stem cell transplantation

    PubMed Central

    Vargas, Alberto Olaya; Luna, Roberto Rivera; Garcia, Martin Perez; Cardos, Rocio Cárdenas; Hidalgo, Liliana Velasco; Jácome, Doris LordMéndez; Gutiérrez, Mariana Campos

    2013-01-01

    Background In childhood cancer, consolidation treatment with chemotherapy followed by autologous hematopoietic progenitor stem cell transplantation is currently an accepted treatment modality in patients with high-risk solid tumors or in patients who have relapsed after conventional treatment. Objectives The objective of this study was to describe the results of transplantation of a group of children who had high-risk solid tumors or relapsed after conventional chemotherapy regimens. Methods A retrospective analysis was conducted from January 1998 to October 2004 of all children with pathologic diagnoses of high-risk solid tumors or children that had previously relapsed after conventional chemotherapy and that were subsequently submitted to autologous hematopoietic progenitor stem cell transplantation. The analysis included overall survival rates, event-free survival rates, mortality rates and chemotherapy complications. Results Nineteen patients were submitted to this approach. The age range was from 27 to 196 months with a median age of 52 months. The overall survival rate at 100 days was observed in 79%, the three-year event-free survival rate was 63%. The mortality rate secondary to the myeloablative chemotherapy regimen was 21% (n = 4). Only three patients (15.8%) relapsed with tumor progression after transplant. Conclusion Autologous hematopoietic progenitor stem cell transplantation is still a successful procedure in patients with solid tumors refractory to conventional chemotherapy. PMID:24255618

  2. Peripheral blood stem cell transplants do not result in endometrial stromal engraftment

    PubMed Central

    Wolff, Erin F.; Uchida, Naoya; Donahue, Robert E.; Metzger, Mark E.; Hsieh, Matthew M.; Libfraind, Lauren L.; Hill, Micah J.; Tisdale, John F.

    2012-01-01

    Objective To determine whether peripheral blood stem cell transplant (PBSCT) result in engraftment of donor stem cells in the recipient uterus. Design Prospective clinical and laboratory research. Setting Translational medicine research hospital. Patient(s)/Animal(s) Macaque and human bone marrow transplant recipients. Intervention(s) Rhesus macaques received autologous transduced immunoselected cytokine-mobilized CD34+ cells after total body irradiation. Vector constructs expressed green fluorescent protein. In the human subjects, prior PBSCT subjects underwent endometrial biopsy and bone marrow aspiration. Macaque and human endometrial and bone marrow cells were isolated and cultured. Fluorescent microscopy, flow cytometry, and polymerase chain reaction (PCR) were used to evaluate for the presence of donor-derived cells. Main Outcome Measure(s) Presence of donor cells in recipient endometrium and bone marrow stroma. Result(s) The macaque endometrial cells did not exhibit evidence of green fluorescent protein labeling. Human endometrial cells were cultured and the absence of donor blood contamination was verified. The PCR evaluation of the human endometrial cells did not demonstrate evidence of donor short tandem repeats. Conclusion(s) The PBSCT did not result in engraftment of donor-derived cells in the endometrium. PMID:23103021

  3. Autologous Adipose Stem Cell Therapy for Autonomic Nervous System Dysfunction in Two Young Patients

    PubMed Central

    Kamdar, Ankur; Young, Jane; Butler, Ian. J.

    2017-01-01

    Postural orthostatic tachycardia syndrome and neurocardiogenic syncope are clinical manifestations of autonomic nervous system dysfunction (dysautonomia) that can lead to impaired daily functions. We report two young patients presenting with dysautonomia and autoimmune disease who both received autologous adipose stem cells (ASCs) infusions. This report is the first description of ASCs therapy for patients with combined dysautonomia and autoimmune disease. Case 1: A 21-year-old female presented at 12 years of age with escalating severe dysautonomia with weight loss and gastrointestinal symptoms. She had elevated autoantibodies and cytokines and received multiple immune modulation therapies. Her dysautonomia was treated by volume expanders, vasoconstrictors, and beta blockers with mild improvement. She received ASCs about 2 years before this report with dramatic improvement in her dysautonomia and autoimmune symptoms with a 10 kg weight gain. Case 2: A 7-year-old boy presented at 2 years of age with polyarthritis. At 5 years of age, he manifested orthostatic intolerance. He received immune modulatory therapies with mild improvement. He received ASCs and showed marked improvement of his dysautonomia and immune symptoms. Dysautonomia symptoms of these two patients improved significantly after modulation of autoimmune components by ASC therapy. Favorable clinical responses of these two cases warrant further case–control studies. PMID:27959743

  4. Bortezomib followed by autologous stem cell transplantation in a patient with rheumatoid arthritis

    PubMed Central

    Liu, Junru; Li, Juan; Chen, Meilan; Kuang, Lifen

    2016-01-01

    Abstract Rationale and Patients concerns: Despite the introduction of varied disease-modifying antirheumatic drugs and biological agents, a substantial proportion of patients remain untreatable. We report a 56-year-old Chinese female patient with a case of refractory rheumatoid arthritis (RA) complicated with multiple myeloma (MM) who was treated successfully with Bortezomib followed by autologous stem cell transplantation (ASCT). Diagnosis and Interventions: We report a 56-year-old Chinese female patient who was diagnosed as RA complicating with MM. She received 4 cycles of Bortezomib-based chemotherapy followed by ASCT. The response of her RA and MM were evaluated after every cycle of Bortezomib-based chemotherapy. Interventions and Outcomes: After the first Bortezomib-based chemotherapy cycle, this patient's symptoms were significantly alleviated and thereafter the RA activity continued to improve. After the 4 courses of Bortezomib-based chemotherapy, the C-reactive protein was <0.5 mg/dL and the disease activity score 28-erythrocyte sedimentation rate was 2.0. No hematological or nonhematological side effects were observed during the treatment of Bortezomib. Lessons: Bortezomib might be a new safe and promising drug for refractory RA patients. PMID:28033292

  5. Absence of spontaneous response improvement beyond day +100 after autologous stem cell transplantation in multiple myeloma.

    PubMed

    Fernández de Larrea, C; Dávila, J; Isola, I; Ocio, E M; Rosiñol, L; García-Sanz, R; Cibeira, M T; Tovar, N; Rovira, M; Mateos, M V; Miguel, J S; Bladé, J

    2017-04-01

    The response evaluation after autologous stem-cell transplantation (ASCT) is usually performed at day +100 in patients with multiple myeloma (MM). A recent report suggests that improvement in the response can be observed beyond day +100. The aim of the present study has been to evaluate the rate of improved response and outcome beyond day +100 after ASCT, with and without maintenance therapy. One hundred and forty-four patients who underwent single ASCT with chemosensitive disease and achieved less than CR at day 100 post ASCT were evaluated. Seventy-four patients (51.4%) did not receive any maintenance with only one of them showing an upgrade in the response. The remaining 70 patients (48.6%) received maintenance therapy; eleven of them (15.7%) improved their response beyond day +100. The outcome of these patients was better than those who did not upgrade their response in both progression-free survival and overall survival (P=0.019 and P=0.031, respectively). In conclusion, the improvement in response beyond day +100 after ASCT in patients not receiving any therapy is exceedingly rare. A minority of patients receiving maintenance therapy after ASCT upgrades their response and this finding is associated with better outcome.

  6. Fractionated stem cell infusions for patients with plasma cell myeloma undergoing autologous hematopoietic cell transplantation.

    PubMed

    Landau, Heather; Wood, Kevin; Chung, David J; Koehne, Guenther; Lendvai, Nikoletta; Hassoun, Hani; Lesokhin, Alexander; Hoover, Elizabeth; Zheng, Junting; Devlin, Sean M; Giralt, Sergio

    2016-08-01

    We conducted a phase II trial investigating the impact of fractionated hematopoietic cell infusions on engraftment kinetics and symptom burden in patients with plasma cell myeloma (PCM) undergoing autologous hematopoietic cell transplant (AHCT). We hypothesized that multiple hematopoietic cell infusions would reduce duration of neutropenia and enhance immune recovery resulting in a better tolerated procedure. Twenty-six patients received high-dose melphalan followed by multiple cell infusions (Days 0, +2, +4, +6) and were compared to PCM patients (N = 77) who received high-dose melphalan and a single infusion (Day 0) (concurrent control group). The primary endpoint was number of days with ANC <500K/mcL. Symptom burden was assessed using the MSK-modified MD Anderson Symptom Inventory. Median duration of neutropenia was similar in study (4 days, range 3-5) and control patients (4 days, range 3-9) (p = 0.654). There was no significant difference in the number of red cell or platelet transfusions, days of fever, diarrhea, antibiotics, number of documented infections, or length of admission. Symptom burden surveys showed that AHCT was well-tolerated in both study and control patients. We conclude that fractionated stem cell infusions following high-dose melphalan do not enhance engraftment kinetics or significantly alter patients' clinical course following AHCT in PCM.

  7. NK Cell Subgroups, Phenotype, and Functions After Autologous Stem Cell Transplantation.

    PubMed

    Jacobs, Benedikt; Tognarelli, Sara; Poller, Kerstin; Bader, Peter; Mackensen, Andreas; Ullrich, Evelyn

    2015-01-01

    High-dose chemotherapy with consecutive autologous stem cell transplantation (autoSCT) is a well-established treatment option for patients suffering from malignant lymphoma or multiple myeloma. Natural killer (NK) cells are an important part of the immune surveillance, and their cell number after autoSCT is predictive for progression-free and overall survival. To improve knowledge about the role of NK cells after autoSCT, we investigated different NK cell subgroups, their phenotype, and their functions in patients treated with autoSCT. Directly after leukocyte regeneration (>1000 leukocytes/μl) following autoSCT, CD56(++) NK cells were the major NK cell subset. Surprisingly, these cells showed unusually high surface expression levels of CD57 and killer Ig-like receptors (KIRs) compared to expression levels before or at later time points after autoSCT. Moreover, these NK cells strongly upregulated KIR2DL2/3/S2 and KIR3DL1, whereas KIR2DL1/S1 remained constant, indicating that this cell population arose from more immature NK cells instead of from activated mature ones. Remarkably, NK cells were already able to degranulate and produce IFN-γ and MIP-1β upon tumor interaction early after leukocyte regeneration. In conclusion, we describe an unusual upregulation of CD57 and KIRs on CD56(++) NK cells shortly after autoSCT. Importantly, these NK cells were functionally competent upon tumor interaction at this early time point.

  8. Phase 1 Trial of Autologous Bone Marrow Stem Cell Transplantation in Patients with Spinal Cord Injury.

    PubMed

    Kakabadze, Zurab; Kipshidze, Nickolas; Mardaleishvili, Konstantine; Chutkerashvili, Gocha; Chelishvili, Irakli; Harders, Albrecht; Loladze, George; Shatirishvili, Gocha; Kipshidze, Nodar; Chakhunashvili, David; Chutkerashvili, Konstantine

    2016-01-01

    Introduction. A total of 18 patients, with complete motor deficits and paraplegia caused by thoracic and lumbar spine trauma without muscle atrophy or psychiatric problems, were included into this study. Materials and Methods. The bone marrow was aspirated from the anterior iliac crest under local anesthesia and the mononuclear fraction was isolated by density gradient method. At least 750 million mononuclear-enriched cells, suspended in 2 mL of saline, were infused intrathecally. Results and Discussion. The study reports demonstrated improvement of motor and sensory functions of various degrees observed in 9 of the 18 (50%) cases after bone marrow stem cell transplantation. Measured by the American Spinal Injury Association (ASIA) scale, 7 (78%) out of the 9 patients observed an improvement by one grade, while two cases (22%) saw an improvement by two grades. However, there were no cases in which the condition was improved by three grades. Conclusions. Analysis of subsequent treatment results indicated that the transplantation of mononuclear-enriched autologous BMSCs is a feasible and safe technique. However, successful application of the BMSCs in the clinical practice is associated with the necessity of executing more detailed examinations to evaluate the effect of BMSCs on the patients with spinal cord injury.

  9. Autologous adipose stem cells and polylactide discs in the replacement of the rabbit temporomandibular joint disc

    PubMed Central

    Ahtiainen, Katja; Mauno, Jari; Ellä, Ville; Hagström, Jaana; Lindqvist, Christian; Miettinen, Susanna; Ylikomi, Timo; Kellomäki, Minna; Seppänen, Riitta

    2013-01-01

    The temporomandibular joint (TMJ) disc lacks functional replacement after discectomy. We investigated tissue-engineered bilayer polylactide (PLA) discs and autologous adipose stem cells (ASCs) as a potential replacement for the TMJ disc. These ASC discs were pre-cultured either in control or in differentiation medium, including transforming growth factor (TGF)-β1 for one week. Prior to implantation, expression of fibrocartilaginous genes was measured by qRT-PCR. The control and differentiated ASC discs were implanted, respectively, in the right and left TMJs of rabbits for six (n = 5) and 12 months (n = 5). Thereafter, the excised TMJ areas were examined with cone beam computed tomography (CBCT) and histology. No signs of infection, inflammation or foreign body reactions were detected at histology, whereas chronic arthrosis and considerable condylar hypertrophy were observed in all operated joints at CBCT. The left condyle treated with the differentiated ASC discs appeared consistently smoother and more sclerotic than the right condyle. The ASC disc replacement resulted in dislocation and morphological changes in the rabbit TMJ. The ASC discs pre-treated with TGF-β1 enhanced the condylar integrity. While adverse tissue reactions were not shown, the authors suggest that with improved attachment and design, the PLA disc and biomaterial itself would hold potential for TMJ disc replacement. PMID:23720535

  10. Juvenile Swine Surgical Alveolar Cleft Model to Test Novel Autologous Stem Cell Therapies.

    PubMed

    Caballero, Montserrat; Morse, Justin C; Halevi, Alexandra E; Emodi, Omri; Pharaon, Michael R; Wood, Jeyhan S; van Aalst, John A

    2015-09-01

    Reconstruction of craniofacial congenital bone defects has historically relied on autologous bone grafts. Engineered bone using mesenchymal stem cells from the umbilical cord on electrospun nanomicrofiber scaffolds offers an alternative to current treatments. This preclinical study presents the development of a juvenile swine model with a surgically created maxillary cleft defect for future testing of tissue-engineered implants for bone generation. Five-week-old pigs (n=6) underwent surgically created maxillary (alveolar) defects to determine critical-sized defect and the quality of treatment outcomes with rib, iliac crest cancellous bone, and tissue-engineered scaffolds. Pigs were sacrificed at 1 month. Computed tomography scans were obtained at days 0 and 30, at the time of euthanasia. Histological evaluation was performed on newly formed bone within the surgical defect. A 1 cm surgically created defect healed with no treatment, the 2 cm defect did not heal. A subsequently created 1.7 cm defect, physiologically similar to a congenitally occurring alveolar cleft in humans, from the central incisor to the canine, similarly did not heal. Rib graft treatment did not incorporate into adjacent normal bone; cancellous bone and the tissue-engineered graft healed the critical-sized defect. This work establishes a juvenile swine alveolar cleft model with critical-sized defect approaching 1.7 cm. Both cancellous bone and tissue engineered graft generated bridging bone formation in the surgically created alveolar cleft defect.

  11. Multiple myeloma treatment at relapse after autologous stem cell transplantation: A practical analysis.

    PubMed

    Malard, F; Harousseau, J L; Mohty, M

    2017-01-01

    Over the past decade, significant advances have been made in the field of multiple myeloma. Introduction of the so-called novel agents, proteasome inhibitors (PI) and immunomodulatory drugs (IMiD), and improved supportive care have resulted in significantly better outcome. Standard first line treatment in fit patients include PI and IMiD based induction, high dose melphalan with autologous hematopoietic stem cell transplantation (ASCT) and consolidation/maintenance. However, despite these progresses MM remains incurable for the majority of patients and most patients will relapse. Next generation PI (carfilzomib, ixazomib) and IMiD (pomalidomide) and new therapeutic classes: monoclonal antibody (elotuzumab, daratumumab) and pan-deacetylase inhibitors (panobinostat) have been successfully evaluated in relapse multiple myeloma. Some of these new agents are now approved for multiple myeloma treatment at relapse. However choosing the most appropriate treatment at relapse may be difficult. This review sum up the most important studies and provide evidence to choose the most relevant therapeutic strategy for relapse after ASCT, based on disease, patient and previous treatment related parameters.

  12. The Mutual Interactions between Mesenchymal Stem Cells and Myoblasts in an Autologous Co-Culture Model

    PubMed Central

    Szczepanska, Izabela; Zarychta-Wisniewska, Weronika; Pajak, Beata; Bojarczuk, Kamil; Dybowski, Bartosz; Paczek, Leszek

    2016-01-01

    Both myoblasts and mesenchymal stem cells (MSC) take part in the muscle tissue regeneration and have been used as experimental cellular therapy in muscular disorders treatment. It is possible that co-transplantation approach could improve the efficacy of this treatment. However, the relations between those two cell types are not clearly defined. The aim of this study was to determine the reciprocal interactions between myoblasts and MSC in vitro in terms of the features important for the muscle regeneration process. Primary caprine muscle-derived cells (MDC) and bone marrow-derived MSC were analysed in autologous settings. We found that MSC contribute to myotubes formation by fusion with MDC when co-cultured directly, but do not acquire myogenic phenotype if exposed to MDC-derived soluble factors only. Experiments with exposure to hydrogen peroxide showed that MSC are significantly more resistant to oxidative stress than MDC, but a direct co-culture with MSC does not diminish the cytotoxic effect of H2O2 on MDC. Cell migration assay demonstrated that MSC possess significantly greater migration ability than MDC which is further enhanced by MDC-derived soluble factors, whereas the opposite effect was not found. MSC-derived soluble factors significantly enhanced the proliferation of MDC, whereas MDC inhibited the division rate of MSC. To conclude, presented results suggest that myogenic precursors and MSC support each other during muscle regeneration and therefore myoblasts-MSC co-transplantation could be an attractive approach in the treatment of muscular disorders. PMID:27551730

  13. Stomatitis-related pain in women with breast cancer undergoing autologous hematopoietic stem cell transplant.

    PubMed

    Fall-Dickson, Jane M; Mock, Victoria; Berk, Ronald A; Grimm, Patricia M; Davidson, Nancy; Gaston-Johansson, Fannie

    2008-01-01

    The purpose of this cross-sectional, correlational study was to describe stomatitis-related pain in women with breast cancer undergoing autologous hematopoietic stem cell transplant. The hypotheses that significant, positive relationships would exist between oral pain and stomatitis, state anxiety, depression, and alteration in swallowing were tested. Stomatitis, sensory dimension of oral pain, and state anxiety were hypothesized to most accurately predict oral pain overall intensity. Thirty-two women were recruited at 2 East Coast comprehensive cancer centers. Data were collected on bone marrow transplantation day +7 +/- 24 hours using Painometer, Oral Mucositis Index-20, Oral Assessment Guide, State-Trait Anxiety Inventory, and Beck Depression Inventory. Data analysis included descriptive statistics, correlations, and stepwise multiple regression. All participants had stomatitis; 47% had oral pain, with a subset reporting continuous moderate to severe oral pain despite pain management algorithms. Significant, positive associations were seen between oral pain, stomatitis, and alteration in swallowing and between oral pain with swallowing and alteration in swallowing. Oral pain was not significantly correlated with state anxiety and depression. Oral sensory and affective pain intensity most accurately predicted oral pain overall intensity. Future research needs to explore factors that affect perception and response to stomatitis-related oropharyngeal pain and individual patient response to opioid treatment.

  14. Ethical and Regulatory Challenges with Autologous Adult Stem Cells: A Comparative Review of International Regulations.

    PubMed

    Lysaght, Tamra; Kerridge, Ian H; Sipp, Douglas; Porter, Gerard; Capps, Benjamin J

    2017-02-28

    Cell and tissue-based products, such as autologous adult stem cells, are being prescribed by physicians across the world for diseases and illnesses that they have neither been approved for or been demonstrated as safe and effective in formal clinical trials. These doctors often form part of informal transnational networks that exploit differences and similarities in the regulatory systems across geographical contexts. In this paper, we examine the regulatory infrastructure of five geographically diverse but socio-economically comparable countries with the aim of identifying similarities and differences in how these products are regulated and governed within clinical contexts. We find that while there are many subtle technical differences in how these regulations are implemented, they are sufficiently similar that it is difficult to explain why these practices appear more prevalent in some countries and not in others. We conclude with suggestions for how international governance frameworks might be improved to discourage the exploitation of vulnerable patient populations while enabling innovation in the clinical application of cellular therapies.

  15. Steroids prevent engraftment syndrome after autologous hematopoietic stem cell transplantation without increasing the risk of infection.

    PubMed

    Mossad, S; Kalaycio, M; Sobecks, R; Pohlman, B; Andresen, S; Avery, R; Rybicki, L; Jarvis, J; Bolwell, B

    2005-02-01

    Engraftment syndrome (ES) following autologous hematopoietic stem cell transplantation (AHSCT) is characterized by fever and rash. In January 2002, we instituted steroid prophylaxis for ES from day +4 to +14. This study was conducted to assess whether this practice increased the risk of infection. In total, 194 consecutive patients were reviewed, 111 did not receive steroid prophylaxis (group A), and 83 did (group B). Initial antimicrobial prophylaxis was the same in both groups. There were no significant differences between groups in age, gender, race, prior radiation therapy, number of prior chemotherapy regimens, disease status at transplant, mobilization regimen, days of leukopheresis, CD34(+) cell dose, and days to platelet and neutrophil engraftment. Group B had significantly fewer patients with non-Hodgkin's lymphoma and multiple myeloma, shorter median duration from diagnosis to transplant, lower risk of ES, and shorter mean length of hospital stay. The incidence of early and late microbiologically confirmed infections was not significantly different between groups. Types of infections and types of organisms identified were similar in both groups. Hospital readmission rates were similar in both groups. Steroid prophylaxis significantly decreases the risk of ES following AHSCT, and is associated with shortened hospitalization, without increasing risk of infection.

  16. Treatment of Recurrent Posttransplant Lymphoproliferative Disorder with Autologous Blood Stem Cell Transplant

    PubMed Central

    Malhotra, Bharat; Rahal, Ahmad K.; Farhoud, Hussam; Moore, Dennis F.; Kallail, K. James

    2015-01-01

    Background. Posttransplant lymphoproliferative disorders (PTLDs) occur after solid organ transplantation. Treatment guidelines include reduction in immunosuppression (RIS), radiation, rituximab, chemotherapy, and immunological agents. We present a rare case of recurrent diffuse large B-cell lymphoma presenting as a PTLD in a heart transplant patient treated with autologous blood stem cell transplant (ASCT) after failure of conventional therapy. Case Presentation. A 66-year-old male presented with a neck mass. He has a history of Hodgkin's disease status after staging laparotomy with splenectomy and heart transplantation due to dilated nonischemic cardiomyopathy 8 years prior to the development of PTLD. His examination was remarkable for right submandibular swelling. An excisional biopsy confirmed the diagnosis of diffuse large B-cell NHL. Patient received RIS, rituximab, chemotherapy, and radiation therapy with a complete remission. His lymphoma relapsed and he subsequently was treated with RICE salvage chemotherapy and consolidative high-dose chemotherapy with BEAC regimen followed by ASCT resulting in a complete remission. Conclusion. Patients with PTLD present a difficult therapeutic challenge. In this case, the patient's prior history of Hodgkin's disease, splenectomy, and a heart transplant appear to be unique features, the significance of which is unclear. ASCT might be a promising therapy for patients with relapsed or refractory PTLD. PMID:26688773

  17. High-dose BCNU followed by autologous hematopoietic stem cell transplantation in supratentorial high-grade malignant gliomas: a retrospective analysis of 114 patients.

    PubMed

    Durando, X; Lemaire, J-J; Tortochaux, J; Van-Praagh, I; Kwiatkowski, F; Vincent, C; Bailly, C; Verrelle, P; Irthum, B; Chazal, J; Bay, J-O

    2003-04-01

    Conventional treatment of high-grade glioma includes maximal surgical resection followed by external radiation therapy. Despite this treatment, the prognosis for patients is poor. High doses of chemotherapy might be another way to increase the response rate and median survival. Increasing doses of BCNU might be more effective, but also provokes unacceptable myelotoxicity. This dose-limiting toxicity can be circumvented by using autologous blood stem cell rescue. We report our experience of high-dose BCNU followed by transplantation of autologous hematopoietic stem cells in 114 patients with high-grade gliomas. Of the 114 gliomas, 78 were glioblastoma multiforme (GM) (68%), 24 anaplastic astrocytomas (AA) (21%), and 12 anaplastic oligodendrogliomas (OD) (11%). Complete surgical resection was performed for 22 patients (18 GM and 4 AA). The median age was 44 years (range 17-65). A total of 84 patients received autologous hematopoietic stem cells from bone marrow harvest, while 30 patients received granulocyte colony-stimulating factor followed by apheresis and received peripheral blood progenitor cells (PBPC). High dose of BCNU (800 mg/m(2)) was given at least 1 month after neurosurgery. Bone marrow or PBPC was transplanted 48-72 h after chemotherapy. Radiotherapy was started approximately 40 days after transplantation to a total of 60 Gy. Median follow-up was 89 months (19-163). The overall survival (OS) was, respectively, 12 months for GM, 37 months for OD and 81 months for AA. Histological type appeared to be the main discriminating factor, with a worse prognosis for GM. Within the GM population, age, completeness of surgery, and response appeared to be one important prognostic factors. The AA and OD populations were small to reliably assess prognostic factors. On multivariate analysis, the main prognostic factors were histologic type, quality of surgery, and age (P<0.005). Five of 114 patients had lethal complications from the procedure. Four of these patients had

  18. Salvage autologous stem cell transplantation for multiple myeloma relapsing or progressing after up-front autologous transplantation.

    PubMed

    Auner, Holger W; Szydlo, Richard; Rone, Alero; Chaidos, Aristeidis; Giles, Chrissy; Kanfer, Ed; Macdonald, Donald H; Marin, David; Milojkovic, Dragana; Pavlu, Jiri; Apperley, Jane F; Rahemtulla, Amin

    2013-10-01

    Progression or relapse occurs in the vast majority of patients with multiple myeloma (MM) who undergo up-front autologous hematopoietic cell transplantation (AHCT1), which remains a cornerstone of treatment in the era of novel agents. Limited data are available regarding the value of salvage therapy with a second AHCT (AHCT2) in patients who relapse/progress after AHCT1. We analyzed the outcome of 83 patients who underwent salvage AHCT2 between 1994 and 2011. Most patients (77%) had received treatment with novel agents between AHCT1 and AHCT2, and 28% of patients were from ethnic minority groups. Median overall survival (OS) from AHCT2 was 31.5 months (95% confidence interval [CI]: 22-41), and median progression-free survival (PFS) was 15.5 months (95% CI: 11-20). In multivariate analysis, only disease status (≥ PR) at AHCT2 was associated with better OS. The 3-year OS rates for patients receiving AHCT2 in > PR and PR were 85.9% (95% CI: 61-96) and 51.3% (95% CI: 34-68), respectively. Disease status at AHCT2 and time to progression/relapse after AHCT1 were associated with PFS in multivariate analysis. In summary, salvage AHCT2 is an effective treatment option in patients with chemosensitive relapse/progression and prolonged remission after a prior autograft.

  19. Post-5-fluorouracil human marrow: stem cell characteristics and renewal properties after autologous marrow transplantation.

    PubMed

    Stewart, F M; Temeles, D; Lowry, P; Thraves, T; Grosh, W W; Quesenberry, P J

    1993-05-01

    The effect of 5-fluorouracil (5-FU) pretreatment on human bone marrow (BM) progenitor/stem cells and recovery of hematopoiesis after autologous marrow transplant was studied. Twenty-one patients were treated with 5-FU (15 mg/kg to 45 mg/kg) intravenously (IV) for 1 to 3 days administered 6 to 22 days before BM harvest. Post-FU marrow was infused into 15 patients after high-dose cyclophosphamide, carmustine (BCNU), and VP-16 (CBV). Seventeen patients (historical controls) were treated with CBV and autologous BM transplantation but did not receive 5-FU before marrow harvest. The groups were comparable for diagnosis and prior therapy. In the 5-FU-treated group and control group, median recovery times for platelet count to 50,000/mm3 were 20 and 30 days, respectively (P = .007), and for platelet count to 100,000/mm3, 23 and 38 days, respectively (P = .007), while neutrophil recovery was not significantly altered. In vitro cultures with 1 to 7 growth factors (interleukin-1 [IL-1], IL-3, IL-4, IL-6, colony-stimulating factor-1 [CSF-1], granulocyte-macrophage colony-stimulating factor [GM-CSF], and G-CSF) were performed. In 8 of 10 patients whose marrow was studied before and after 5-FU treatment, the numbers of CFU-C responsive to the combination of GM-CSF and IL-3 was increased 6.15-fold by 5-FU pretreatment. In 4 of these patients, thymidine suicide of GM-CSF- and IL-3-stimulated CFU-C ranged from 17% to 42%. High proliferative potential colony-forming cell (HPP-CFC) was observed in low frequency in normal marrow and patient's marrow before 5-FU treatment. In 11 of 16 patients pretreated with 5-FU, increased numbers of HPP-CFC were noted. GM-CSF and IL-3 interacted synergistically to stimulate HPP-CFC. Multifactor combinations, especially GM-CSF + G-CSF + IL-3 + IL-6 + IL-1 + CSF-1 did not increase total colony count or classic HPP-CFC but did result in altered morphology, producing huge, loose colonies. The marrow from patients pretreated with 5-FU is enriched with

  20. Acupoint Injection of Autologous Stromal Vascular Fraction and Allogeneic Adipose-Derived Stem Cells to Treat Hip Dysplasia in Dogs

    PubMed Central

    Marx, Camila; Silveira, Maiele Dornelles; Selbach, Isabel; da Silva, Ariel Silveira; Braga, Luisa Maria Gomes de Macedo; Camassola, Melissa; Nardi, Nance Beyer

    2014-01-01

    Stem cells isolated from adipose tissue show great therapeutic potential in veterinary medicine, but some points such as the use of fresh or cultured cells and route of administration need better knowledge. This study aimed to evaluate the effect of autologous stromal vascular fraction (SVF, n = 4) or allogeneic cultured adipose-derived stem cells (ASCs, n = 5) injected into acupuncture points in dogs with hip dysplasia and weak response to drug therapy. Canine ASCs have proliferation and differentiation potential similar to ASCs from other species. After the first week of treatment, clinical evaluation showed marked improvement compared with baseline results in all patients treated with autologous SVF and three of the dogs treated with allogeneic ASCs. On days 15 and 30, all dogs showed improvement in range of motion, lameness at trot, and pain on manipulation of the joints, except for one ASC-treated patient. Positive results were more clearly seen in the SVF-treated group. These results show that autologous SVF or allogeneic ASCs can be safely used in acupoint injection for treating hip dysplasia in dogs and represent an important therapeutic alternative for this type of pathology. Further studies are necessary to assess a possible advantage of SVF cells in treating joint diseases. PMID:25180040

  1. Autologous tissue patch rich in stem cells created in the subcutaneous tissue

    PubMed Central

    Garcia-Gomez, Ignacio; Gudehithlu, Krishnamurthy P; Arruda, Jose A L; Singh, Ashok K

    2015-01-01

    AIM: To investigate whether we could create natural autologous tissue patches in the subcutaneous space for organ repair. METHODS: We implanted the following three types of inert foreign bodies in the subcutaneous tissue of rats to produce autologous tissue patches of different geometries: (1) a large-sized polyvinyl tube (L = 25 mm, internal diameter = 7 mm) sealed at both ends by heat application for obtaining a large flat piece of tissue patch for organ repair; (2) a fine polyvinyl tubing (L = 25 mm, internal diameter = 3 mm) for creating cylindrically shaped grafts for vascular or nerve repair; and (3) a slurry of polydextran particle gel for inducing a bladder-like tissue. Implantation of inert materials was carried out by making a small incision on one or either side of the thoracic-lumbar region of rats. Subcutaneous pockets were created by blunt dissection around the incision into which the inert bodies were inserted (1 or 2 per rat). The incisions were closed with silk sutures, and the animals were allowed to recover. In case of the polydextran gel slurry 5 mL of the slurry was injected in the subcutaneous space using an 18 gauge needle. After implanting the foreign bodies a newly regenerated encapsulating tissue developed around the foreign bodies. The tissues were harvested after 4-42 d of implantation and studied by gross examination, histology, and histochemistry for organization, vascularity, and presence of mesenchymal stem cells (MSCs) (CD271+CD34+ cells). RESULTS: Implanting a large cylindrically shaped polyvinyl tube resulted in a large flat sheet of tissue that could be tailored to a specific size and shape for use as a tissue patch for repairing large organs. Implanting a smaller sized polyvinyl tube yielded a cylindrical tissue that could be useful for repairing nerves and blood vessels. This type of patch could be obtained in different lengths by varying the length of the implanted tube. Implanting a suspension of inert polydextran suspension

  2. Epstein-Barr virus-associated posttransplantation lymphoproliferative disorder after high-dose immunosuppressive therapy and autologous CD34-selected hematopoietic stem cell transplantation for severe autoimmune diseases.

    PubMed

    Nash, Richard A; Dansey, Roger; Storek, Jan; Georges, George E; Bowen, James D; Holmberg, Leona A; Kraft, George H; Mayes, Maureen D; McDonagh, Kevin T; Chen, Chien-Shing; Dipersio, John; Lemaistre, C Fred; Pavletic, Steven; Sullivan, Keith M; Sunderhaus, Julie; Furst, Daniel E; McSweeney, Peter A

    2003-09-01

    High-dose immunosuppressive therapy followed by autologous hematopoietic stem cell transplantation (HSCT) is currently being evaluated for the control of severe autoimmune diseases. The addition of antithymocyte globulin (ATG) to high-dose chemoradiotherapy in the high-dose immunosuppressive therapy regimen and CD34 selection of the autologous graft may induce a higher degree of immunosuppression compared with conventional autologous HSCT for malignant diseases. Patients may be at higher risk of transplant-related complications secondary to the immunosuppressed state, including Epstein-Barr virus (EBV)-associated posttransplantation lymphoproliferative disorder (PTLD), but this is an unusual complication after autologous HSCT. Fifty-six patients (median age, 42 years; range, 23-61 years) with either multiple sclerosis (n = 26) or systemic sclerosis (n = 30) have been treated. The median follow-up has been 24 months (range, 2-60 months). Two patients (multiple sclerosis, n = 1; systemic sclerosis, n = 1) had significant reactivations of herpesvirus infections early after HSCT and then developed aggressive EBV-PTLD and died on days +53 and +64. Multiorgan clonal B-cell infiltrates that were EBV positive by molecular studies or immunohistology were identified at both autopsies. Both patients had positive screening skin tests for equine ATG (Atgam) and had been converted to rabbit ATG (Thymoglobulin) from the first dose. Of the other 54 patients, 2 of whom had partial courses of rabbit ATG because of a reaction to the intravenous infusion of equine ATG, only 1 patient had a significant clinical reactivation of a herpesvirus infection (herpes simplex virus 2) early after HSCT, and none developed EBV-PTLD. The T-cell count in the peripheral blood on day 28 was 0/microL in all 4 patients who received rabbit ATG; this was significantly less than in patients who received equine ATG (median, 174/microL; P =.001; Mann-Whitney ranked sum test). Although the numbers are limited

  3. Development of model for analysing respective collections of intended hematopoietic stem cells and harvests of unintended mature cells in apheresis for autologous hematopoietic stem cell collection.

    PubMed

    Hequet, O; Le, Q H; Rodriguez, J; Dubost, P; Revesz, D; Clerc, A; Rigal, D; Salles, G; Coiffier, B

    2014-04-01

    Hematopoietic stem cells (HSCs) required to perform peripheral hematopoietic autologous stem cell transplantation (APBSCT) can be collected by processing several blood volumes (BVs) in leukapheresis sessions. However, this may cause granulocyte harvest in graft and decrease in patient's platelet blood level. Both consequences may induce disturbances in patient. One apheresis team's current purpose is to improve HSC collection by increasing HSC collection and prevent increase in granulocyte and platelet harvests. Before improving HSC collection it seemed important to know more about the way to harvest these types of cells. The purpose of our study was to develop a simple model for analysing respective collections of intended CD34+ cells among HSC (designated here as HSC) and harvests of unintended platelets or granulocytes among mature cells (designated here as mature cells) considering the number of BVs processed and factors likely to influence cell collection or harvest. For this, we processed 1, 2 and 3 BVs in 59 leukapheresis sessions and analysed corresponding collections and harvests with a referent device (COBE Spectra). First we analysed the amounts of HSC collected and mature cells harvested and second the evolution of the respective shares of HSC and mature cells collected or harvested throughout the BV processes. HSC collections and mature cell harvests increased globally (p<0.0001) and their respective shares remained stable throughout the BV processes (p non-significant). We analysed the role of intrinsic (patient's features) and extrinsic (features before starting leukapheresis sessions) factors in collections and harvests, which showed that only pre-leukapheresis blood levels (CD34+cells and platelets) influenced both cell collections and harvests (CD34+cells and platelets) (p<0.001) and shares of HSC collections and mature unintended cells harvests (p<0.001) throughout the BV processes. Altogether, our results suggested that the main factors likely

  4. Addition of Mesenchymal Stem Cells to Autologous Platelet-Enhanced Fibrin Scaffolds in Chondral Defects

    PubMed Central

    Goodrich, Laurie R.; Chen, Albert C.; Werpy, Natasha M.; Williams, Ashley A.; Kisiday, John D.; Su, Alvin W.; Cory, Esther; Morley, Paul S.; McIlwraith, C. Wayne; Sah, Robert L.; Chu, Constance R.

    2016-01-01

    Background: The chondrogenic potential of culture-expanded bone-marrow-derived mesenchymal stem cells (BMDMSCs) is well described. Numerous studies have also shown enhanced repair when BMDMSCs, scaffolds, and growth factors are placed into chondral defects. Platelets provide a rich milieu of growth factors and, along with fibrin, are readily available for clinical use. The objective of this study was to determine if the addition of BMDMSCs to an autologous platelet-enriched fibrin (APEF) scaffold enhances chondral repair compared with APEF alone. Methods: A 15-mm-diameter full-thickness chondral defect was created on the lateral trochlear ridge of both stifle joints of twelve adult horses. In each animal, one defect was randomly assigned to receive APEF+BMDMSCs and the contralateral defect received APEF alone. Repair tissues were evaluated one year later with arthroscopy, histological examination, magnetic resonance imaging (MRI), micro-computed tomography (micro-CT), and biomechanical testing. Results: The arthroscopic findings, MRI T2 map, histological scores, structural stiffness, and material stiffness were similar (p > 0.05) between the APEF and APEF+BMDMSC-treated repairs at one year. Ectopic bone was observed within the repair tissue in four of twelve APEF+BMDMSC-treated defects. Defects repaired with APEF alone had less trabecular bone edema (as seen on MRI) compared with defects repaired with APEF+BMDMSCs. Micro-CT analysis showed thinner repair tissue in defects repaired with APEF+BMDMSCs than in those treated with APEF alone (p < 0.05). Conclusions: APEF alone resulted in thicker repair tissue than was seen with APEF+BMDMSCs. The addition of BMDMSCs to APEF did not enhance cartilage repair and stimulated bone formation in some cartilage defects. Clinical Relevance: APEF supported repair of critical-size full-thickness chondral defects in horses, which was not improved by the addition of BMDMSCs. This work supports further investigation to determine

  5. Autologous stem cell transplantation: an effective salvage therapy in multiple myeloma.

    PubMed

    Lemieux, Emilie; Hulin, Cyrille; Caillot, Denis; Tardy, Stéphanie; Dorvaux, Véronique; Michel, Jessica; Gastinne, Thomas; Rossi, Cédric; Legouge, Caroline; Touzeau, Cyrille; Planche, Lucie; Loirat, Marion; Lafon, Ingrid; Moreau, Philippe

    2013-03-01

    Eighty-one patients treated with high-dose therapy and autologous stem cell transplantation (ASCT) as part of salvage therapy after a frontline ASCT were included in a retrospective analysis. The median time between the first and the salvage ASCT was 47 months. After salvage ASCT, 75 patients (93%) achieved at least a partial response, including 67% very good partial responses, and no toxic death was reported. Sixteen patients (20%) underwent consolidation therapy, whereas 30 patients (37%) underwent some form of maintenance therapy after salvage ASCT. For all patients, the median overall survival (OS) was 10 years from diagnosis and 4 years from salvage ASCT. The median progression-free survival (PFS) from the date of the first ASCT to the date of the first relapse was 40 months, and the median PFS from the date of salvage ASCT to the date of subsequent progression was 18 months. In the multivariate analysis of prognostic factors, three independent factors unfavorably affected PFS: a short duration of response to the first ASCT (cut-off value of 24 months), a response less than a very good partial response after salvage therapy, and no maintenance treatment after salvage ASCT. Age over 60 years and a short duration of response after the first ASCT were the two factors adversely affecting OS from the time of diagnosis and OS from the time of salvage ASCT. Our data show that salvage ASCT is a feasible option that should be routinely considered at the time of relapse for patients with a response duration of more than 2 years to frontline high-dose therapy.

  6. Importance of Achieving Stringent Complete Response After Autologous Stem-Cell Transplantation in Multiple Myeloma

    PubMed Central

    Kapoor, Prashant; Kumar, Shaji K.; Dispenzieri, Angela; Lacy, Martha Q.; Buadi, Francis; Dingli, David; Russell, Stephen J.; Hayman, Suzanne R.; Witzig, Thomas E.; Lust, John A.; Leung, Nelson; Lin, Yi; Zeldenrust, Steven R.; McCurdy, Arleigh; Greipp, Philip R.; Kyle, Robert A.; Rajkumar, S. Vincent; Gertz, Morie A.

    2013-01-01

    Purpose To study the impact of achieving stringent complete response (sCR), an increasingly attainable goal, after autologous stem-cell transplantation (ASCT) in patients with multiple myeloma (MM). Patients and Methods Maximal response rates were determined in 445 consecutive patients who underwent ASCT within 12 months of diagnosis of MM. The patients achieving varying degrees of complete response (CR) are the focus of our study. Results One hundred and nine patients (25%) achieved sCR after ASCT. The median overall survival (OS) rate from the time of transplantation for patients attaining sCR was not reached (NR), in contrast to those patients achieving conventional complete response (CR; n = 37; OS, 81 months) or near CR (nCR; n = 91; OS, 60 months; P < .001). Five-year OS rates were 80%, 53%, and 47% for sCR, CR, and nCR, respectively. The median time to progression (TTP) from ASCT of patients achieving sCR was significantly longer (50 months) than TTP of patients achieving CR or nCR (20 months and 19 months, respectively). On multivariable analysis, post-ASCT response of sCR was an independent prognostic factor for survival (hazard ratio, 0.44; 95% CI, 0.25 to 0.80; versus CR; P = .008), in addition to proliferation rate, pre-ASCT cytogenetics, and performance status. OS rates of patients attaining sCR continued to remain superior at 2-year landmark (median, NR v 70 months for conventional CR group; P = .007). Conclusion Improved long-term outcome is seen after ASCT with achievement of sCR when compared with lesser degrees of responses. Myeloma trials reporting the response rates should identify patients achieving sCR and CR separately, owing to markedly disparate outcomes of the two categories. PMID:24248686

  7. Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Atypical Teratoid/Rhabdoid Tumor

    PubMed Central

    Sung, Ki Woong; Lim, Do Hoon; Yi, Eun Sang; Choi, Young Bae; Lee, Ji Won; Yoo, Keon Hee; Koo, Hong Hoe; Kim, Ji Hye; Suh, Yeon-Lim; Joung, Yoo Sook; Shin, Hyung Jin

    2016-01-01

    Purpose We prospectively evaluated the effectiveness of tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) in improving the survival of patients with atypical teratoid/rhabdoid tumors while reducing the risks of late adverse effects from radiotherapy (RT). Materials and Methods For young children (< 3 years old), tandem HDCT/auto-SCT was administered after six cycles of induction chemotherapy. RT was deferred until after 3 years of age unless the tumor showed relapse or progression. For older patients (> 3 years old), RT including reduced-dose craniospinal RT (23.4 or 30.6 Gy) was administered either after two cycles of induction chemotherapy or after surgery, and tandem HDCT/auto-SCT was administered after six cycles of induction chemotherapy. Results A total of 13 patients (five young and eight older) were enrolled from November 2004 to June 2012. Eight patients, including all five young patients, had metastatic disease at diagnosis. Six patients (four young and two older) experienced progression before initiation of RT, and seven were able to proceed to HDCT/auto-SCT without progression during induction treatment. Three of six patients who experienced progression during induction treatment underwent HDCT/auto-SCT as salvage treatment. All five young patients died from disease progression. However, four of the eight older patients remain progression-freewith a median follow-up period of 64 months (range, 39 to 108 months). Treatment-related late toxicities were acceptable. Conclusion The required dose of craniospinal RT might be reduced in older patients if the intensity of chemotherapy is increased. However, early administration of RT should be considered to prevent early progression in young patients. PMID:27034140

  8. Bone Marrow Very Small Embryonic-Like Stem Cells: New Generation of Autologous Cell Therapy Soon Ready for Prime Time?

    PubMed

    Smadja, David M

    2017-01-18

    Very small embryonic-like stem cells (VSELs) are major pluripotent stem cells described in human and mouse. In this issue of Stem Cell Reviews and Reports, Shaikh and colleagues show in a valuable work that mouse bone marrow collected after 5FU treatment contains VSELs able to undergo in vitro multi-lineage differentiation into cells from all three germ layers and also in germ and hematopoietic cells. These findings are robust since no confounding factor such as feeder cell fusion with VSELs can occur here. This paper allows one to better appreciate bone marrow-VSELs differentiation potential and opens new perspectives for autologous cell therapy. Furthermore, it might help explaining lots of contradictive data from the past 20 years, in particular related to ability of bone marrow cells to differentiate into cardiomyocytes.

  9. Concise Review: Human Dermis as an Autologous Source of Stem Cells for Tissue Engineering and Regenerative Medicine

    PubMed Central

    Vapniarsky, Natalia; Arzi, Boaz; Hu, Jerry C.; Nolta, Jan A.

    2015-01-01

    The exciting potential for regenerating organs from autologous stem cells is on the near horizon, and adult dermis stem cells (DSCs) are particularly appealing because of the ease and relative minimal invasiveness of skin collection. A substantial number of reports have described DSCs and their potential for regenerating tissues from mesenchymal, ectodermal, and endodermal lineages; however, the exact niches of these stem cells in various skin types and their antigenic surface makeup are not yet clearly defined. The multilineage potential of DSCs appears to be similar, despite great variability in isolation and in vitro propagation methods. Despite this great potential, only limited amounts of tissues and clinical applications for organ regeneration have been developed from DSCs. This review summarizes the literature on DSCs regarding their niches and the specific markers they express. The concept of the niches and the differentiation capacity of cells residing in them along particular lineages is discussed. Furthermore, the advantages and disadvantages of widely used methods to demonstrate lineage differentiation are considered. In addition, safety considerations and the most recent advancements in the field of tissue engineering and regeneration using DSCs are discussed. This review concludes with thoughts on how to prospectively approach engineering of tissues and organ regeneration using DSCs. Our expectation is that implementation of the major points highlighted in this review will lead to major advancements in the fields of regenerative medicine and tissue engineering. Significance Autologous dermis-derived stem cells are generating great excitement and efforts in the field of regenerative medicine and tissue engineering. The substantial impact of this review lies in its critical coverage of the available literature and in providing insight regarding niches, characteristics, and isolation methods of stem cells derived from the human dermis. Furthermore, it

  10. Scaffold-Based Delivery of Autologous Mesenchymal Stem Cells for Mandibular Distraction Osteogenesis: Preliminary Studies in a Porcine Model

    PubMed Central

    Sun, Zongyang; Tee, Boon Ching; Kennedy, Kelly S.; Kennedy, Patrick M.; Kim, Do-Gyoon; Mallery, Susan R.; Fields, Henry W.

    2013-01-01

    Purpose Bone regeneration through distraction osteogenesis (DO) is promising but remarkably slow. To accelerate it, autologous mesenchymal stem cells have been directly injected to the distraction site in a few recent studies. Compared to direct injection, a scaffold-based method can provide earlier cell delivery with potentially better controlled cell distribution and retention. This pilot project investigated a scaffold-based cell-delivery approach in a porcine mandibular DO model. Materials and Methods Eleven adolescent domestic pigs were used for two major sets of studies. The in-vitro set established methodologies to: aspirate bone marrow from the tibia; isolate, characterize and expand bone marrow-derived mesenchymal stem cells (BM-MSCs); enhance BM-MSC osteogenic differentiation using FGF-2; and confirm cell integration with a gelatin-based Gelfoam scaffold. The in-vivo set transplanted autologous stem cells into the mandibular distraction sites using Gelfoam scaffolds; completed a standard DO-course and assessed bone regeneration by macroscopic, radiographic and histological methods. Repeated-measure ANOVAs and t-tests were used for statistical analyses. Results From aspirated bone marrow, multi-potent, heterogeneous BM-MSCs purified from hematopoietic stem cell contamination were obtained. FGF-2 significantly enhanced pig BM-MSC osteogenic differentiation and proliferation, with 5 ng/ml determined as the optimal dosage. Pig BM-MSCs integrated readily with Gelfoam and maintained viability and proliferative ability. After integration with Gelfoam scaffolds, 2.4–5.8×107 autologous BM-MSCs (undifferentiated or differentiated) were transplanted to each experimental DO site. Among 8 evaluable DO sites included in the final analyses, the experimental DO sites demonstrated less interfragmentary mobility, more advanced gap obliteration, higher mineral content and faster mineral apposition than the control sites, and all transplanted scaffolds were completely

  11. Autologous preconditioned mesenchymal stem cell sheets improve left ventricular function in a rabbit old myocardial infarction model

    PubMed Central

    Tanaka, Yuya; Shirasawa, Bungo; Takeuchi, Yuriko; Kawamura, Daichi; Nakamura, Tamami; Samura, Makoto; Nishimoto, Arata; Ueno, Koji; Morikage, Noriyasu; Hosoyama, Tohru; Hamano, Kimikazu

    2016-01-01

    Mesenchymal stem cells (MSCs) constitute one of the most powerful tools for therapeutic angiogenesis in infarcted hearts. However, conventional MSC transplantation approaches result in insufficient therapeutic effects due to poor retention of graft cells in severe ischemic diseases. Cell sheet technology has been developed as a new method to prolong graft cell retention even in ischemic tissue. Recently, we demonstrated that hypoxic pretreatment enhances the therapeutic efficacy of cell sheet implantation in infarcted mouse hearts. In this study, we investigated whether hypoxic pretreatment activates the therapeutic functions of bone marrow-derived MSC (BM-MSC) sheets and improves cardiac function in rabbit infarcted hearts following autologous transplantation. Production of vascular endothelial growth factor (VEGF) was increased in BM-MSC monolayer sheets and it peaked at 48 h under hypoxic culture conditions (2% O2). To examine in vivo effects, preconditioned autologous BM-MSC sheets were implanted into a rabbit old myocardial infarction model. Implantation of preconditioned BM-MSC sheets accelerated angiogenesis in the peri-infarcted area and decreased the infarcted area, leading to improvement of the left ventricular function of the infarcted heart. Importantly, the therapeutic efficacy of the preconditioned BM-MSC sheets was higher than that of standardly cultured sheets. Thus, implantation of autologous preconditioned BM-MSC sheets is a feasible approach for enhancing therapeutic angiogenesis in chronically infarcted hearts. PMID:27347329

  12. Application of Autologous Bone Marrow Derived Mesenchymal Stem Cells to an Ovine Model of Growth Plate Cartilage Injury

    PubMed Central

    McCarty, Rosa C; Xian, Cory J; Gronthos, Stan; Zannettino, Andrew C.W; Foster, Bruce K

    2010-01-01

    Injury to growth plate cartilage in children can lead to bone bridge formation and result in bone growth deformities, a significant clinical problem currently lacking biological treatment. Mesenchymal stem/stromal cells (MSC) offer a promising therapeutic option for regeneration of damaged cartilage, due to their self renewing and multi-lineage differentiation attributes. Although some small animal model studies highlight the therapeutic potential of MSC for growth plate repair, translational research in large animal models, which more closely resemble the human condition, are lacking. Our laboratory has recently characterised MSCs derived from ovine bone marrow, and demonstrated these cells form cartilage-like tissue when transplanted within the gelatin sponge, Gelfoam, in vivo. In the current study, autologous bone marrow MSC were seeded into Gelfoam scaffold containing TGF-β1, and transplanted into a surgically created defect of the proximal ovine tibial growth plate. Examination of implants at 5 week post-operatively revealed transplanted autologous MSC failed to form new cartilage structure at the defect site, but contributed to an increase in formation of a dense fibrous tissue. Importantly, the extent of osteogenesis was diminished, and bone bridge formation was not accelerated due to transplantation of MSCs or the gelatin scaffold. The current study represents the first work that has utilised this ovine large animal model to investigate whether autologous bone marrow derived MSC can be used to initiate regeneration at the injured growth plate. PMID:20721323

  13. Scaffold-free Three-dimensional Graft From Autologous Adipose-derived Stem Cells for Large Bone Defect Reconstruction

    PubMed Central

    Dufrane, Denis; Docquier, Pierre-Louis; Delloye, Christian; Poirel, Hélène A.; André, Wivine; Aouassar, Najima

    2015-01-01

    Abstract Long bone nonunion in the context of congenital pseudarthrosis or carcinologic resection (with intercalary bone allograft implantation) is one of the most challenging pathologies in pediatric orthopedics. Autologous cancellous bone remains the gold standard in this context of long bone nonunion reconstruction, but with several clinical limitations. We then assessed the feasibility and safety of human autologous scaffold-free osteogenic 3-dimensional (3D) graft (derived from autologous adipose-derived stem cells [ASCs]) to cure a bone nonunion in extreme clinical and pathophysiological conditions. Human ASCs (obtained from subcutaneous adipose tissue of 6 patients and expanded up to passage 4) were incubated in osteogenic media and supplemented with demineralized bone matrix to obtain the scaffold-free 3D osteogenic structure as confirmed in vitro by histomorphometry for osteogenesis and mineralization. The 3D “bone-like” structure was finally transplanted for 3 patients with bone tumor and 3 patients with bone pseudarthrosis (2 congenital, 1 acquired) to assess the clinical feasibility, safety, and efficacy. Although minor clones with structural aberrations (aneuploidies, such as tri or tetraploidies or clonal trisomy 7 in 6%–20% of cells) were detected in the undifferentiated ASCs at passage 4, the osteogenic differentiation significantly reduced these clonal anomalies. The final osteogenic product was stable, did not rupture with forceps manipulation, did not induce donor site morbidity, and was easily implanted directly into the bone defect. No acute (<3 mo) side effects, such as impaired wound healing, pain, inflammatory reaction, and infection, or long-term side effects, such as tumor development, were associated with the graft up to 4 years after transplantation. We report for the first time that autologous ASC can be fully differentiated into a 3D osteogenic-like implant without any scaffold. We demonstrated that this engineered tissue can

  14. Long-term results of autologous stem cell transplantation for primary refractory or relapsed Hodgkin's lymphoma.

    PubMed

    Majhail, Navneet S; Weisdorf, Daniel J; Defor, Todd E; Miller, Jeffrey S; McGlave, Philip B; Slungaard, Arne; Arora, Mukta; Ramsay, Norma K C; Orchard, Paul J; MacMillan, Margaret L; Burns, Linda J

    2006-10-01

    Autologous hematopoietic stem cell transplantation (ASCT) has become standard therapy for primary refractory (PR REF) or relapsed (REL) Hodgkin's lymphoma (HL); however, more than half of these patients eventually relapse and die of their disease. We studied long-term outcomes and evaluated factors influencing progression-free survival (PFS) in 141 patients with PR REF or REL HL who underwent ASCT between 1985 and 2003. Median age at ASCT was 30 years (range, 7-60 years); 21 patients had PR REF, and 120 had REL HL. With a median follow-up of 6.3 years (range, 1-20 years), the probability of PFS at 5 and 10 years was 48% (95% confidence interval [CI], 39%-57%) and 45% (95% CI, 36%-54%) and that of overall survival (OS) was 53% (95% CI, 44%-62%) and 47% (95% CI, 37%-57%), respectively. Transplant-related mortality at 100 days was 1.4%. Among 45 5- to 20-year survivors, no late relapses of HL were observed. In multivariate analysis, 3 factors were independently predictive of poor PFS: chemoresistant disease (relative risk [RR], 2.9; 95% CI, 1.7-5.0), B-symptoms at pretransplantation relapse (RR, 2.1; 95% CI, 1.3-3.4), and presence of residual disease at the time of transplantation (RR, 2.3; 95% CI, 1.1-4.8). Patients with 0 or 1 of these 3 adverse factors (low-risk disease) had a 5-year PFS of 67% (95% CI, 55%-79%) compared with 37% (95% CI, 22%-52%) in those with 2 factors (intermediate-risk group) and 9% (95% CI, 0-20%) in those with all 3 factors (high-risk group) (P < .001). The rates of OS at 5 years were 71% (95% CI, 60%-82%), 49% (95% CI, 33%-65%) and 13% (95% CI, 0-27%) in the 3 groups, respectively (P < .001). ASCT is associated with durable PFS in appropriately selected patients with PR REF or REL HL. Using a simple prognostic model, we can identify patients with high-risk disease who have predictably unfavorable outcome after ASCT and require novel therapeutic approaches. A risk-adapted approach should be followed in determining treatment options for

  15. Outcomes in patients with multiple myeloma with TP53 deletion after autologous hematopoietic stem cell transplant.

    PubMed

    Gaballa, Sameh; Saliba, Rima M; Srour, Samer; Lu, Gary; Brammer, Jonathan E; Shah, Nina; Bashir, Qaiser; Patel, Krina; Bock, Fabian; Parmar, Simrit; Hosing, Chitra; Popat, Uday; Delgado, Ruby; Rondon, Gabriela; Shah, Jatin J; Manasanch, Elisabet E; Orlowski, Robert Z; Champlin, Richard; Qazilbash, Muzaffar H

    2016-10-01

    TP53 gene deletion is associated with poor outcomes in multiple myeloma (MM). We report the outcomes of patients with MM with and without TP53 deletion who underwent immunomodulatory drug (IMiD) and/or proteasome inhibitor (PI) induction followed by autologous hematopoietic stem cell transplant (auto-HCT). We identified 34 patients with MM and TP53 deletion who underwent IMiD and/or PI induction followed by auto-HCT at our institution during 2008-2014. We compared their outcomes with those of control patients (n = 111) with MM without TP53 deletion. Median age at auto-HCT was 59 years in the TP53-deletion group and 58 years in the control group (P = 0.4). Twenty-one patients (62%) with TP53 deletion and 69 controls (62%) achieved at least partial remission before auto-HCT (P = 0.97). Twenty-three patients (68%) with TP53 deletion and 47 controls (42%) had relapsed disease at auto-HCT (P = 0.01). Median progression-free survival was 8 months for patients with TP53 deletion and 28 months for controls (P < 0.001). Median overall survival was 21 months for patients with TP53 deletion and 56 months for controls (P < 0.001). On multivariate analysis of both groups, TP53 deletion (hazard ratio 3.4, 95% confidence interval 1.9-5.8, P < 0.001) and relapsed disease at auto-HCT (hazard ratio 2.0, 95% confidence interval 1.2-3.4, P = 0.008) were associated with a higher risk of earlier progression. In MM patients treated with PI and/or IMiD drugs, and auto-HCT, TP53 deletion and relapsed disease at the time of auto-HCT are independent predictors of progression. Novel approaches should be evaluated in this high-risk population. Am. J. Hematol. 91:E442-E447, 2016. © 2016 Wiley Periodicals, Inc.

  16. Autologous adipose tissue-derived mesenchymal stem cells are involved in rat liver regeneration following repeat partial hepatectomy

    PubMed Central

    LIU, TAO; MU, HONG; SHEN, ZHONGYANG; SONG, ZHUOLUN; CHEN, XIAOBO; WANG, YULIANG

    2016-01-01

    Adipose tissue-derived mesenchymal stem cells (ADSCs) have been considered to be attractive and readily available adult mesenchymal stem cells, and they are becoming increasingly popular for use in regenerative cell therapy, as they are readily accessible through minimally invasive techniques. The present study investigated whether autologous ADSC transplantation promoted liver regeneration following a repeat partial hepatectomy in rats. The rats were divided into three groups as follows: 70% partial hepatectomy (PH) group; repeat PH (R-PH) group and R-PH/ADSC group, subjected to R-PH and treated with autologous ADSCs via portal vein injection. In each group, the rats were sacrificed at different time points postoperatively in order to evaluate the changes in liver function and to estimate the liver regenerative response. The expression of proliferating cell nuclear antigen (PCNA) labeling index in the liver was measured using immunohistochemistry. The expression levels of hepatocyte growth factor (HGF) mRNA were measured using reverse transcription polymerase chain reaction. The results showed that regeneration of the remaining liver following R-PH was significantly promoted by ADSC transplantation, as shown by a significant increase in liver to body weight ratio and the PCNA labeling index at 24 h post-hepatectomy. Additionally, ADSC transplantation markedly inhibited the elevation of serum levels of alanine aminotransferase, aspartate aminotransferase and total bilirubin, increased HGF content and also attenuated hepatic vacuolar degeneration 24 h postoperatively. Furthermore, the liver was found to almost fully recover from hepatocellular damage due to hepatectomy among the three groups at 168 h postoperatively. These results indicated that autologous ADSC transplantation enhanced the regenerative capacity of the remnant liver tissues in the early phase following R-PH. PMID:26783183

  17. Transplantation of Autologous Bone Marrow Mesenchymal Stem Cells into the Testes of Infertile Male Rats and New Germ Cell Formation

    PubMed Central

    Ghasemzadeh-Hasankolaei, Mohammad; Batavani, Roozali; Eslaminejad, Mohamadreza Baghaban; Sayahpour, Foroughazam

    2016-01-01

    Background Mesenchymal stem cells (MSCs), have been suggested as a potential choice for treatment of male infertility. Yet, the effects of MSCs on regeneration of germinal epithelium of seminiferous tubules and recovery of spermatogenesis have remained controversial. In this research, we have evaluated and compared the fate of autologous bone marrow (BM)-MSCs during three different periods of time- 4, 6 and 8 weeks after transplantation into the testes of busulfan-induced infertile male rats. Methods Rats BM samples were collected from tibia bone under anesthesia. The samples were directly cultured in culture medium. Isolated, characterized and purified BM-MSCs were labeled with PKH26, and transplanted into the testes of infertile rats. After 4, 6 and 8 weeks, the testes were removed and underwent histological evaluations. Results Immunohistochemical analysis showed that transplanted BM-MSCs survived in all three groups. Some of the cells homed at the germinal epithelium and expressed spermatogonia markers (Dazl and Stella). The number of homed spermatogonia-like cells in 4-week testes, was more than the 6-week testes. The 8-week testes had the least numbers of homed cells (p<0.05). Immunostaining for vimentin showed that BM-MSCs did not differentiate into the sertoli cells in the testes. Conclusions From our results, it could be concluded that, autologous BM-MSCs could survive in the testis, migrate onto the seminiferous tubules basement membrane and differentiate into spermatogonia. Although, no more differentiation was observed in the produced spermatogonia, generation of such endogenous GCs would be a really promising achievement for treatment of male infertility using autologous stem cells. PMID:27430978

  18. Selective purging of human multiple myeloma cells from autologous stem cell transplant grafts using oncolytic myxoma virus

    PubMed Central

    Bartee, Eric; Chan, Winnie S.; Moreb, Jan S.; Cogle, Christopher R.; McFadden, Grant

    2012-01-01

    Autologous stem cell transplantation (ASCT) and novel therapies have improved overall survival of patients with multiple myeloma; however, most patients relapse and eventually succumb to their disease. Evidence indicates that residual cancer cells contaminate autologous grafts and may contribute to early relapses after ASCT. Here, we demonstrate that ex vivo treatment with an oncolytic poxvirus called myxoma virus results in specific elimination of human myeloma cells by inducing rapid cellular apoptosis while fully sparing normal hematopoietic stem and progenitor cells (HSPCs). The specificity of this elimination is based on strong binding of the virus to myeloma cells coupled with an inability of the virus to bind or infect CD34+ HSPCs. These two features allow myxoma to readily identify and distinguish even low levels of myeloma cells in complex mixtures. This ex vivo MYXV treatment also effectively inhibits systemic in vivo engraftment of human myeloma cells into immunodeficient mice and results in efficient elimination of primary CD138+ myeloma cells contaminating patient hematopoietic cell products. We conclude that ex vivo myxoma treatment represents a safe and effective method to selectively eliminate myeloma cells from hematopoietic autografts prior to reinfusion. PMID:22516053

  19. Technologies enabling autologous neural stem cell-based therapies for neurodegenerative disease and injury

    NASA Astrophysics Data System (ADS)

    Bakhru, Sasha H.

    The intrinsic abilities of mammalian neural stem cells (NSCs) to self-renew, migrate over large distances, and give rise to all primary neural cell types of the brain offer unprecedented opportunity for cell-based treatment of neurodegenerative diseases and injuries. This thesis discusses development of technologies in support of autologous NSC-based therapies, encompassing harvest of brain tissue biopsies from living human patients; isolation of NSCs from harvested tissue; efficient culture and expansion of NSCs in 3D polymeric microcapsule culture systems; optimization of microcapsules as carriers for efficient in vivo delivery of NSCs; genetic engineering of NSCs for drug-induced, enzymatic release of transplanted NSCs from microcapsules; genetic engineering for drug-induced differentiation of NSCs into specific therapeutic cell types; and synthesis of chitosan/iron-oxide nanoparticles for labeling of NSCs and in vivo tracking by cellular MRI. Sub-millimeter scale tissue samples were harvested endoscopically from subventricular zone regions of living patient brains, secondary to neurosurgical procedures including endoscopic third ventriculostomy and ventriculoperitoneal shunt placement. On average, 12,000 +/- 3,000 NSCs were isolated per mm 3 of subventricular zone tissue, successfully demonstrated in 26 of 28 patients, ranging in age from one month to 68 years. In order to achieve efficient expansion of isolated NSCs to clinically relevant numbers (e.g. hundreds of thousands of cells in Parkinson's disease and tens of millions of cells in multiple sclerosis), an extracellular matrix-inspired, microcapsule-based culture platform was developed. Initial culture experiments with murine NSCs yielded unprecedented expansion folds of 30x in 5 days, from initially minute NSC populations (154 +/- 15 NSCs per 450 mum diameter capsule). Within 7 days, NSCs expanded as almost perfectly homogenous populations, with 94.9% +/- 4.1% of cultured cells staining positive for

  20. Extracellular matrix from human umbilical cord-derived mesenchymal stem cells as a scaffold for peripheral nerve regeneration

    PubMed Central

    Xiao, Bo; Rao, Feng; Guo, Zhi-yuan; Sun, Xun; Wang, Yi-guo; Liu, Shu-yun; Wang, Ai-yuan; Guo, Quan-yi; Meng, Hao-ye; Zhao, Qing; Peng, Jiang; Wang, Yu; Lu, Shi-bi

    2016-01-01

    The extracellular matrix, which includes collagens, laminin, or fibronectin, plays an important role in peripheral nerve regeneration. Recently, a Schwann cell-derived extracellular matrix with classical biomaterial was used to mimic the neural niche. However, extensive clinical use of Schwann cells remains limited because of the limited origin, loss of an autologous nerve, and extended in vitro culture times. In the present study, human umbilical cord-derived mesenchymal stem cells (hUCMSCs), which are easily accessible and more proliferative than Schwann cells, were used to prepare an extracellular matrix. We identified the morphology and function of hUCMSCs and investigated their effect on peripheral nerve regeneration. Compared with a non-coated dish tissue culture, the hUCMSC-derived extracellular matrix enhanced Schwann cell proliferation, upregulated gene and protein expression levels of brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, and vascular endothelial growth factor in Schwann cells, and enhanced neurite outgrowth from dorsal root ganglion neurons. These findings suggest that the hUCMSC-derived extracellular matrix promotes peripheral nerve repair and can be used as a basis for the rational design of engineered neural niches. PMID:27630705

  1. Lenalidomide consolidation and maintenance therapy after autologous stem cell transplant for multiple myeloma induces persistent changes in T-cell homeostasis.

    PubMed

    Clave, Emmanuel; Douay, Corinne; Coman, Tereza; Busson, Marc; Bompoint, Caroline; Moins-Teisserenc, Helene; Glauzy, Salomé; Carmagnat, Maryvonnick; Gorin, Norbert Claude; Toubert, Antoine; Garderet, Laurent

    2014-08-01

    Whether the efficacy of lenalidomide in the treatment of multiple myeloma (MM) is due to direct tumor toxicity only or to additional immunomodulatory effects is unclear. We studied the effect of lenalidomide treatment on T-cell immune reconstitution in patients with MM who had undergone autologous peripheral blood stem cell transplant (ASCT). Twenty-nine newly diagnosed patients with MM received induction therapy followed by high-dose melphalan and ASCT. After ASCT, 11 patients received lenalidomide consolidation therapy for 2 months followed by maintenance therapy until disease progression. The remaining 18 patients received no treatment. Serial analysis of thymic output, as given by numbers of T-cell receptor excision circles (sjTRECs), and T-cell phenotyping was performed until 18 months post-ASCT. Lenalidomide impaired long-term thymic T-cell reconstitution, decreased CD4 + and CD8 + CD45RA + CCR7 - effector-terminal T-cell absolute counts and increased CD4 + CD25 + CD127 - /low regulatory T-cells. Lenalidomide consolidation and long-term maintenance therapy, administered post-ASCT, may have a potentially negative impact on immune surveillance.

  2. Potential new strategies for the treatment of ovarian infertility and degenerative diseases with autologous ovarian stem cells.

    PubMed

    Bukovsky, Antonin; Copas, Pleas; Virant-Klun, Irma

    2006-04-01

    The 50-year-old and currently prevailing view that all oocytes in adult human ovaries persist from the fetal period of life is controversial as it clashes with Darwinian evolutionary theory. Studies of oogenesis and follicular renewal in adult human ovaries, and of the role of hormonal signals and third-party cells (tissue macrophages and T cells), could all be helpful in providing better understanding of the causes of ovarian infertility, its prevention and potential therapy. In addition, the authors recently reported differentiation of distinct cell types and the production of new eggs in cultures derived from premenopausal and postmenopausal human ovaries. It is possible that fertilisation of such eggs will open up new opportunities for providing genetically related children to infertile women for whom conventional in vitro fertilisation has failed. As ovarian stem cells appear to represent a new type of totipotent adult stem cell, they could also be utilised for autologous stem cell therapy of degenerative diseases, without any involvement of allogeneic embryonic stem cells and somatic cell nuclear transfer.

  3. POEMS Syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Gammopathy and Skin Changes) Treated with Autologous Hematopoietic Stem Cell Transplantation: A Case Report and Literature Review

    PubMed Central

    Arana, Carlos; Pérez de León, José Antonio; Gómez-Moreno, Gerardo; Pérez-Cano, Ramón; Hernández, Tomás Martín

    2015-01-01

    Patient: Male, 62 Final Diagnosis: POEMS syndrome Symptoms: General malaise • pretibial edemas • weight loss Medication: — Clinical Procedure: Autologous hematopoietic stem cell transplantation Specialty: Hematology Objective: Rare disease Background: POEMS syndrome is a rare systemic pathology of paraneoplastic origin that is associated with plasma cell dyscrasia. It is characterized by the presence of sensorimotor polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes, and other systemic manifestations. The pathogenesis of the syndrome is unknown but over-production of vascular endothelial growth factor is probably responsible for most of the more characteristic symptoms. There is no standard treatment for POEMS syndrome and no randomized controlled clinical trials of treatment exist in the available literature. High-dose melphalan with autologous hematopoietic stem cell transplantation should be considered for younger patients with widespread osteosclerotic lesions, and for patients with rapidly progressive neuropathy. Case Report: This is the case of a 62-year-old Caucasian man who was admitted to our center presenting pretibial edema accompanied by significant weight loss and difficulty walking. POEMS criteria were present and an immunofixation test confirmed the presence of a monoclonal plasmaproliferative disorder. After autologous hematopoietic stem cell transplantation, the monoclonal component disappeared and the patient’s clinical status improved markedly. Conclusions: Autologous hematopoietic stem cell transplantation following high-dose melphalan is an effective therapy for younger patients with widespread osteosclerotic lesions in POEMS syndrome. PMID:25726020

  4. Autologous mesenchymal stem cell (MSCs) transplantation for critical-sized bone defect following a wide excision of osteofibrous dysplasia

    PubMed Central

    Dilogo, Ismail Hadisoebroto; Kamal, Achmad Fauzi; Gunawan, Bambang; Rawung, Rangga Valentino

    2015-01-01

    Introduction Osteofibrous dysplasia is a rare non-neoplastic disease that is almost exclusive to pediatric tibial diaphysis. Wide excision of the lesion is recommended to avoid recurrence. However, such radical surgery will results in large segmental bone defects that will require further extensive reconstructive surgery. We report a novel approach of treating bone defect by implementing the diamond concept of bone healing using autologous bone marrow derived mesenchymal stem cells (BM-MSCs). Presentation of case An eight-year-old Indonesian male presented with severe bowing deformity of the left lower leg. Radiographic and histological analysis confirmed the diagnosis of osteofibrous dysplasia. A wide excision of the defect was made leaving a critical-sized bone defect. A combination of autologous transplantation of 50 million BM-MSCs, hydroxyapatite (HA) granules, bone morphogenic protein 2 (BMP-2) and Djoko-Zarov hybrid circular external fixator was used to treat the defect. The outcomes measured were subjective complaints, functionality based on LEFS and radiological assessments. Discussion Radiographic assessments showed successful new bone tissue formation and integration of implanted HA granules. The external fixator was removed at 42 weeks after adequate callus formation and clinical stability was achieved. The patient underwent progressive functional improvements and reached a near normal functionality of 90% LEFS at 84 week. No therapy side effect or complication was reported. Conclusion Osteofibrous dysplasia was successfully excised without signs of recurrence after 84-week follow-up. Autologous transplantation of augmented BM-MSCs has successfully created new normal bone tissue without causing any side effect and had significantly improved the patient’s quality of life. PMID:26599503

  5. Phase I study of cord blood-derived natural killer cells combined with autologous stem cell transplantation in multiple myeloma.

    PubMed

    Shah, Nina; Li, Li; McCarty, Jessica; Kaur, Indreshpal; Yvon, Eric; Shaim, Hila; Muftuoglu, Muharrem; Liu, Enli; Orlowski, Robert Z; Cooper, Laurence; Lee, Dean; Parmar, Simrit; Cao, Kai; Sobieiski, Catherine; Saliba, Rima; Hosing, Chitra; Ahmed, Sairah; Nieto, Yago; Bashir, Qaiser; Patel, Krina; Bollard, Catherine; Qazilbash, Muzaffar; Champlin, Richard; Rezvani, Katy; Shpall, Elizabeth J

    2017-03-14

    Multiple myeloma (MM) is a disease with known immune dysregulation. Natural killer (NK) cells have shown preclinical activity in MM. We conducted a first-in-human study of umbilical cord blood-derived (CB) NK cells for MM patients undergoing high dose chemotherapy and autologous haematopoietic stem cell transplantation (auto-HCT). Patients received lenalidomide (10 mg) on days -8 to -2, melphalan 200 mg/m(2) on day -7, CB-NK cells on day -5 and auto-HCT on day 0. Twelve patients were enrolled, three on each of four CB-NK cell dose levels: 5 × 10(6) , 1 × 10(7) , 5 × 10(7) and 1 × 10(8) CB-NK cells/kg. Ten patients had either high-risk chromosomal changes or a history of relapsed/progressed disease. There were no infusional toxicities and no graft-versus-host disease. One patient failed to engraft due to poor autologous graft quality and was rescued with a back-up autologous graft. Overall, 10 patients achieved at least a very good partial response as their best response, including eight with near complete response or better. With a median follow-up of 21 months, four patients have progressed or relapsed, two of whom have died. CB-NK cells were detected in vivo in six patients, with an activated phenotype (NKG2D(+) /NKp30(+) ). These data warrant further development of this novel cellular therapy.

  6. Determining Toxoplasma high-risk autologous and allogeneic hematopoietic stem cell transplantation patients by systematic pre-transplant PCR screening of stem cell originated buffy coat.

    PubMed

    Caner, Ayşe; Dönmez, Ayhan; Döşkaya, Mert; Değirmenci, Aysu; Tombuloğlu, Murat; Cağirgan, Seçkin; Guy, Edward; Francis, Janet; Soyer, Nur Akad; Gürüz, Yüksel

    2012-12-01

    The diagnosis of Toxoplasma infection or disease in hematopoietic stem cell transplantation (HSCT) patients is achieved mainly by PCR screening; however screening did not find wide field of use in practice due to costly expenditures of PCR. This study aimed to determine patients at high risk of Toxoplasma infection or disease before transplantation by stem cell originated buffy coat PCR and subsequently to screen them. Buffy coats collected from 12 autologous and 18 allogeneic HSCT patients' donors were investigated by PCR before transplantation. After transplantation, blood and sera collected at fixed time intervals were screened by two PCR methods and serological assays. Screening results first time assessed a toxoplasmosis incidence level as 25% in autologous HSCT patients and increased incidence level in allogeneic HSCT patients to 22%. Importantly, buffy coat PCR was first time performed before transplantation, to determine the risk of toxoplasmosis. Buffy coat PCR results showed that four patients were at high risk of toxoplasmosis before transplantation. After transplantation, these patients experienced toxoplasmosis. In conclusion, for the determination of patients at risk of toxoplasmosis, clinicians should consider buffy coat PCR in combination with serology before transplantation. After transplantation, PCR screening can be initiated in high risk patients upon clinical suspicion.

  7. Long-term outcomes of high dose treatment and autologous stem cell transplantation in follicular and mantle cell lymphomas – a single centre experience

    PubMed Central

    Boltezar, Lucka; Pintaric, Karlo; Pretnar, Jože; Pohar Perme, Maja

    2017-01-01

    Abstract Background Advanced follicular lymphoma (FL) and mantle cell lymphoma (MCL) are incurable diseases with conventional treatment. The high dose treatment (HDT) with autologous stem cell transplantation (ASCT), however, offers a certain proportion of these patients the prospect of a prolonged disease-free and overall survival. The aim of this study was to investigate the event free survival (EFS) and overall survival (OS) in patients with FL and MCL treated with ASCT. Patients and methods Seventeen patients with FL and 29 patients with MCL were included, 15 of them were transplanted to consolidate the response to second line treatment and 24 to consolidate their first remission, respectively. All were conditioned with total body irradiation (TBI) and high dose cyclophosphamide between 2006 and 2014 and all were transplanted with peripheral blood stem cells. Results The estimated 5-year OS for FL was 87.8% (95% confidence interval [CI] 59.5%–96.8%) and for MCL 79.3% (95% CI 56.1%–91.1%), respectively. The estimated 5-year EFS for FL was 76.0% (95% CI 48.0%–90.3%) and for MCL 69.8% (95% CI 45.5%–84.8%), respectively. There were no secondary hematological malignancies observed in either group. Conclusions Based on above results, the ASCT with TBI is a good treatment option in terms of long-term survival for patients with follicular and mantle cell lymphoma demonstrating a relatively low rate of late toxicities and secondary malignancies.

  8. Stem cell treatment for patients with autoimmune disease by systemic infusion of culture-expanded autologous adipose tissue derived mesenchymal stem cells

    PubMed Central

    2011-01-01

    Prolonged life expectancy, life style and environmental changes have caused a changing disease pattern in developed countries towards an increase of degenerative and autoimmune diseases. Stem cells have become a promising tool for their treatment by promoting tissue repair and protection from immune-attack associated damage. Patient-derived autologous stem cells present a safe option for this treatment since these will not induce immune rejection and thus multiple treatments are possible without any risk for allogenic sensitization, which may arise from allogenic stem cell transplantations. Here we report the outcome of treatments with culture expanded human adipose-derived mesenchymal stem cells (hAdMSCs) of 10 patients with autoimmune associated tissue damage and exhausted therapeutic options, including autoimmune hearing loss, multiple sclerosis, polymyotitis, atopic dermatitis and rheumatoid arthritis. For treatment, we developed a standardized culture-expansion protocol for hAdMSCs from minimal amounts of fat tissue, providing sufficient number of cells for repetitive injections. High expansion efficiencies were routinely achieved from autoimmune patients and from elderly donors without measurable loss in safety profile, genetic stability, vitality and differentiation potency, migration and homing characteristics. Although the conclusions that can be drawn from the compassionate use treatments in terms of therapeutic efficacy are only preliminary, the data provide convincing evidence for safety and therapeutic properties of systemically administered AdMSC in human patients with no other treatment options. The authors believe that ex-vivo-expanded autologous AdMSCs provide a promising alternative for treating autoimmune diseases. Further clinical studies are needed that take into account the results obtained from case studies as those presented here. PMID:22017805

  9. Comparison of characteristics of bacterial bloodstream infection between adult patients with allogeneic and autologous hematopoietic stem cell transplantation.

    PubMed

    Hong, Junshik; Moon, Song Mi; Ahn, Hee Kyung; Sym, Sun Jin; Park, Yoon Soo; Park, Jinny; Cho, Yong Kyun; Cho, Eun Kyung; Shin, Dong Bok; Lee, Jae Hoon

    2013-06-01

    Although autologous and allogeneic hematopoietic stem cell transplantation (HSCT) are fundamentally different procedures, a tailored approach to bacterial bloodstream infection (BSI) according to the type of HSCT has not yet been suggested. We evaluated the characteristics of BSI after HSCT, with a focus on comparison of BSIs between recipients of autologous HSCT (auto-HSCT) and allogeneic HSCT (allo-HSCT). Among 134 patients (59 received allo-HSCT and 75 received auto-HSCT) who underwent HSCT, BSIs were reported earlier in patients who underwent auto-HSCT, compared with those who underwent allo-HSCT (mean 12.1 ± 3.4 days versus 32.8 ± 27.1 days, P = .006). Among patients receiving allo-HSCT, postneutrophil-engraftment bacterial BSI showed an association with grade ≥ 2 acute graft-versus-host disease (GVHD). In patients who underwent auto-HSCT, results of multivariate analysis showed that not receiving prophylactic antibiotics (P = .004) and having elevated serum C-reactive protein (P = .034) were risk factors of BSI. Elevated CRP (P = .01) and acute GVHD ≥ grade 2 (P = .002) were independent risk factors in patients who underwent allo-HSCT. Those differences originated mainly from the impact of acute GVHD-related postengraftment BSIs of patients who underwent allo-HSCT. To establish the best defense strategy against BSI, the distinctive natures of bacterial BSI after HSCT between auto-HSCT and allo-HSCT should be considered.

  10. Repeated Autologous Bone Marrow-Derived Mesenchymal Stem Cell Injections Improve Radiation-Induced Proctitis in Pigs

    PubMed Central

    Busson, Elodie; Holler, Valerie; Strup-Perrot, Carine; Lacave-Lapalun, Jean-Victor; Lhomme, Bruno; Prat, Marie; Devauchelle, Patrick; Sabourin, Jean-Christophe; Simon, Jean-Marc; Bonneau, Michel; Lataillade, Jean-Jacques; Benderitter, Marc

    2013-01-01

    The management of proctitis in patients who have undergone very-high-dose conformal radiotherapy is extremely challenging. The fibrosis-necrosis, fistulae, and hemorrhage induced by pelvic overirradiation have an impact on morbidity. Augmenting tissue repair by the use of mesenchymal stem cells (MSCs) may be an important advance in treating radiation-induced toxicity. Using a preclinical pig model, we investigated the effect of autologous bone marrow-derived MSCs on high-dose radiation-induced proctitis. Irradiated pigs received repeated intravenous administrations of autologous bone marrow-derived MSCs. Immunostaining and real-time polymerase chain reaction analysis were used to assess the MSCs' effect on inflammation, extracellular matrix remodeling, and angiogenesis, in radiation-induced anorectal and colon damages. In humans, as in pigs, rectal overexposure induces mucosal damage (crypt depletion, macrophage infiltration, and fibrosis). In a pig model, repeated administrations of MSCs controlled systemic inflammation, reduced in situ both expression of inflammatory cytokines and macrophage recruitment, and augmented interleukin-10 expression in rectal mucosa. MSC injections limited radiation-induced fibrosis by reducing collagen deposition and expression of col1a2/col3a1 and transforming growth factor-β/connective tissue growth factor, and by modifying the matrix metalloproteinase/TIMP balance. In a pig model of proctitis, repeated injections of MSCs effectively reduced inflammation and fibrosis. This treatment represents a promising therapy for radiation-induced severe rectal damage. PMID:24068742

  11. The Use Of Laser Irradiation To Stimulate Adipose Derived Stem Cell Proliferation And Differentiation For Use In Autologous Grafts

    NASA Astrophysics Data System (ADS)

    Abrahamse, Heidi

    2009-09-01

    Stem cells are characterized by the qualities of self-renewal, long term viability, and the ability to differentiate into various cell types. Historically, stem cells have been isolated from the inner cell mass of blastocysts and harvesting these cells resulted in the death of the embryo leading to religious, political and ethical issues. The identification and subsequent isolation of adult stem cells from bone marrow stroma have been welcomed as an alternate source for stem cells. The clinical use of Mesenchymal Stem Cells (MSCs) presented problems such as limited cell number, pain and morbidity upon isolation. Adipose tissue is derived from the mesenchyme, is easily isolated, a reliable source of stem cells and able to differentiate into different cell types including smooth muscle. Over the past few years, the identification and characterization of stem cells has led the potential use of these cells as a promising alternative to cell replacement therapy. Smooth muscle is a major component of human tissues and is essential for the normal functioning of many different organs. Low intensity laser irradiation has been shown to increase viability, protein expression and migration of stem cells in vitro, and to stimulate proliferation of various types of stem cells. In addition, the use of laser irradiation to stimulate differentiation in the absence of growth factors has also been demonstrated in normal human neural progenitor cells (NHNPCs) in vitro where NHNPCs are not only capable of being sustained by light in the absence of growth factors, but that they are also able to differentiate normally as assessed by neurite formation. Our work has focused on the ability of laser irradiation to proliferate adipose derived stem cells (ADSCs), maintain ADSC character and increase the rate and maintenance of differentiation of ADSCs into smooth muscle and skin fibroblast cells. Current studies are also investigating the effect of different irradiation wavelengths and

  12. Comparison of SPE, IFE, and FLC in Monitoring Patients with Multiple Myeloma After Autologous Stem Cell Transplantation.

    PubMed

    Li, Wei; Zhou, Jia-Zi; Chang, Hui-Rong; Dai, Li-Jun; Zhu, Zi-Ling; Feng, Yu-Feng; Gong, Fei-Ran; Wu, De-Pei

    2015-12-01

    Conventionally, serum protein electrophoresis (SPE) and serum immunofixation electrophoresis (IFE) are used as primary methods to diagnose and monitor multiple myeloma (MM). Recently, serum-free light chain (FLC) assay has been incorporated into hematological screening programs for myeloma. The purpose of this study is to compare the performance of the three methods in monitoring MM patients after autologous stem cell transplantation (ASCT). SPE, serum IFE and serum FLC assay were performed on 38 MM patients who underwent ASCT. In total, four patients had unexpected protein bands (UPBs) and 13 patients had relapsed after ASCT. Our results indicate that IFE is more sensitive than SPE and FLC assay in detection of UPBs and relapse. The results of IFE may provide useful information in advance of patient relapse.

  13. Successful Treatment of Gastric Relapse in Multiple Myeloma with Bortezomib after Autologous Hematopoietic Stem Cell Transplantation (autoHSCT)

    PubMed Central

    Sivgin, Serdar; Baldane, Suleyman; Kaynar, Leylagul; Kurnaz, Fatih; Baskol, Mevlut; Kula, Mustafa; Eroglu, Celalettin; Deniz, Kemal; Eser, Bulent; Unal, Ali; Cetin, Mustafa

    2013-01-01

    We report a case of 59-year-old Turkish man with history of mitral valve replacement (MVR) and chronic obstructive pulmonary disease (COPD) who was diagnosed with stage IIIA IgG lambda multiple myeloma (MM) in 1997. He underwent autologous hematopoietic stem cell transplantation after a conditioning regimen with melphalan 200mg per body area (m2) in February 2006. On February 2011, he was admitted to the emergency service of university hospital with complaints of hematemesis and melena. Pathological evaluation of gastric biopsy, obtained from a lesion of small gastric curvature, showed the gastric mucosa infiltrated by neoplastic plasma cells, monoclonal lambda light chain positive. The patient was considered as having local gastric relapsed disease and was treated with 2 cycles of bortezomib. He achieved an excellent local response after 2 cycles of bortezomib, cyclophosphamide and prednisone (BEP) regimen, with healing of gastric ulcer and no recurrence of the hematemesis or melena. PMID:23350019

  14. Use of autologous mesenchymal stem cells derived from bone marrow for the treatment of naturally injured spinal cord in dogs.

    PubMed

    Penha, Euler Moraes; Meira, Cássio Santana; Guimarães, Elisalva Teixeira; Mendonça, Marcus Vinícius Pinheiro; Gravely, Faye Alice; Pinheiro, Cláudia Maria Bahia; Pinheiro, Taiana Maria Bahia; Barrouin-Melo, Stella Maria; Ribeiro-Dos-Santos, Ricardo; Soares, Milena Botelho Pereira

    2014-01-01

    The use of stem cells in injury repair has been extensively investigated. Here, we examined the therapeutic effects of autologous bone marrow mesenchymal stem cells (MSC) transplantation in four dogs with natural traumatic spinal cord injuries. MSC were cultured in vitro, and proliferation rate and cell viability were evaluated. Cell suspensions were prepared and surgically administered into the spinal cord. The animals were clinically evaluated and examined by nuclear magnetic resonance. Ten days after the surgical procedure and MSC transplantation, we observed a progressive recovery of the panniculus reflex and diminished superficial and deep pain response, although there were still low proprioceptive reflexes in addition to a hyperreflex in the ataxic hind limb movement responses. Each dog demonstrated an improvement in these gains over time. Conscious reflex recovery occurred simultaneously with moderate improvement in intestine and urinary bladder functions in two of the four dogs. By the 18th month of clinical monitoring, we observed a remarkable clinical amelioration accompanied by improved movement, in three of the four dogs. However, no clinical gain was associated with alterations in magnetic resonance imaging. Our results indicate that MSC are potential candidates for the stem cell therapy following spinal cord injury.

  15. Comparative epigenetic influence of autologous versus fetal bovine serum on mesenchymal stem cells through in vitro osteogenic and adipogenic differentiation.

    PubMed

    Fani, Nesa; Ziadlou, Reihane; Shahhoseini, Maryam; Baghaban Eslaminejad, Mohamadreza

    2016-06-10

    Mesenchymal stem cells (MSCs) derived from bone marrow (BM) represents a useful source of adult stem cells for cell therapy and tissue engineering. MSCs are present at a low frequency in the BM; therefore expansion is necessary before performing clinical studies. Fetal bovine serum (FBS) as a nutritional supplement for in vitro culture of MSCs is a suitable additive for human cell culture, but not regarding subsequent use of these cells for clinical treatment of human patients due to the risk of viral and prion transmission as well as xenogeneic immune responses after transplantation. Recently, autologous serum (AS) has been as a supplement to replace FBS in culture medium. We compared the effect of FBS versus AS on the histone modification pattern of MSCs through in vitro osteogenesis and adipogenesis. Differentiation of stem cells under various serum conditions to a committed state involves global changes in epigenetic patterns that are critically determined by chromatin modifications. Chromatin immunoprecipitation (ChIP) coupled with real-time PCR showed significant changes in the acetylation and methylation patterns in lysine 9 (Lys9) of histone H3 on the regulatory regions of stemness (Nanog, Sox2, Rex1), osteogenic (Runx2, Oc, Sp7) and adipogenic (Ppar-γ, Lpl, adiponectin) marker genes in undifferentiated MSCs, FBS and AS. All epigenetic changes occurred in a serum dependent manner which resulted in higher expression level of stemness genes in undifferentiated MSCs compared to differentiated MSCs and increased expression levels of osteogenic genes in AS compared to FBS. Adipogenic genes showed greater expression in FBS compared to AS. These findings have demonstrated the epigenetic influence of serum culture conditions on differentiation potential of MSCs, which suggest that AS is possibly more efficient serum for osteogenic differentiation of MSCs in cell therapy purposes.

  16. Neural stem cell-like cells derived from autologous bone mesenchymal stem cells for the treatment of patients with cerebral palsy

    PubMed Central

    2013-01-01

    Background Stem cell therapy is a promising treatment for cerebral palsy, which refers to a category of brain diseases that are associated with chronic motor disability in children. Autologous MSCs may be a better cell source and have been studied for the treatment of cerebral palsy because of their functions in tissue repair and the regulation of immunological processes. Methods To assess neural stem cell–like (NSC-like) cells derived from autologous marrow mesenchymal stem cells as a novel treatment for patients with moderate-to-severe cerebral palsy, a total of 60 cerebral palsy patients were enrolled in this open-label, non-randomised, observer-blinded controlled clinical study with a 6-months follow-up. For the transplantation group, a total of 30 cerebral palsy patients received an autologous NSC-like cells transplantation (1-2 × 107 cells into the subarachnoid cavity) and rehabilitation treatments whereas 30 patients in the control group only received rehabilitation treatment. Results We recorded the gross motor function measurement scores, language quotients, and adverse events up to 6 months post-treatment. The gross motor function measurement scores in the transplantation group were significantly higher at month 3 (the score increase was 42.6, 95% CI: 9.8–75.3, P=.011) and month 6 (the score increase was 58.6, 95% CI: 25.8–91.4, P=.001) post-treatment compared with the baseline scores. The increase in the Gross Motor Function Measurement scores in the control group was not significant. The increases in the language quotients at months 1, 3, and 6 post-treatment were not statistically significant when compared with the baseline quotients in both groups. All the 60 patients survived, and none of the patients experienced serious adverse events or complications. Conclusion Our results indicated that NSC-like cells are safe and effective for the treatment of motor deficits related to cerebral palsy. Further randomised clinical trials are necessary to

  17. Autograft HIV-DNA load predicts HIV-1 peripheral reservoir after stem cell transplantation for AIDS-related lymphoma patients.

    PubMed

    Zanussi, Stefania; Bortolin, Maria Teresa; Pratesi, Chiara; Tedeschi, Rosamaria; Basaglia, Giancarlo; Abbruzzese, Luciano; Mazzucato, Mario; Spina, Michele; Vaccher, Emanuela; Tirelli, Umberto; Rupolo, Maurizio; Michieli, Mariagrazia; Di Mascio, Michele; De Paoli, Paolo

    2015-01-01

    Autologous stem cell transplantation (ASCT) is a widely used procedure for AIDS-related lymphomas, and it represents an opportunity to evaluate strategies curing HIV-1 infection. The association of autograft HIV-DNA load with peripheral blood HIV-1 reservoir before ASCT and its contribution in predicting HIV-1 reservoir size and stability during combination antiretroviral therapy (cART) after transplantation are unknown. Aiming to obtain information suggesting new functional cure strategies by ASCT, we retrospectively evaluated HIV-DNA load in autograft and in peripheral blood before and after transplantation in 13 cART-treated HIV-1 relapse/refractoring lymphoma patients. Among them seven discontinued cART after autograft infusion. HIV-DNA was evaluated by a sensitive quantitative real-time polymerase chain reaction (PCR). After debulking chemotherapy/mobilization, the autograft HIV-1 reservoir was higher than and not associated with the peripheral HIV-1 reservoir at baseline [median 215 HIV-DNA copies/10(6) autograft mononuclear cells, range 13-706 vs. 82 HIV-DNA copies/10(6) peripheral blood mononuclear cells (PBMCs), range 13-479, p = 0.03]. After high dose chemotherapy and autograft infusion, HIV-DNA levels reached a plateau between month 6 and 12 of follow-up. No association was found between peripheral HIV-DNA levels at baseline and after infusion in both cART interrupting and not interrupting patients. Only in the last subgroup, a stable significant linear association between autograft and peripheral blood HIV-1 reservoir emerged from month 1 (R(2) = 0.84, p = 0.01) to month 12 follow-up (R(2) = 0.99, p = 0.0005). In summary, autograft HIV-1 reservoir size could be influenced by the mobilization phase and predicts posttransplant peripheral HIV-1 reservoir size in patients on continuous cART. These findings could promote new research on strategies reducing the HIV-1 reservoir by using the ASCT procedure.

  18. Autologous Peripheral Blood Stem Cell Transplantation in Patients With Life Threatening Autoimmune Diseases

    ClinicalTrials.gov

    2005-06-23

    Purpura, Schoenlein-Henoch; Graft Versus Host Disease; Anemia, Hemolytic, Autoimmune; Rheumatoid Arthritis; Churg-Strauss Syndrome; Hypersensitivity Vasculitis; Wegener's Granulomatosis; Systemic Lupus Erythematosus; Giant Cell Arteritis; Pure Red Cell Aplasia; Juvenile Rheumatoid Arthritis; Polyarteritis Nodosa; Autoimmune Thrombocytopenic Purpura; Takayasu Arteritis

  19. Tantalum coating of porous carbon scaffold supplemented with autologous bone marrow stromal stem cells for bone regeneration in vitro and in vivo.

    PubMed

    Wei, Xiaowei; Zhao, Dewei; Wang, Benjie; Wang, Wei; Kang, Kai; Xie, Hui; Liu, Baoyi; Zhang, Xiuzhi; Zhang, Jinsong; Yang, Zhenming

    2016-03-01

    Porous tantalum metal with low elastic modulus is similar to cancellous bone. Reticulated vitreous carbon (RVC) can provide three-dimensional pore structure and serves as the ideal scaffold of tantalum coating. In this study, the biocompatibility of domestic porous tantalum was first successfully tested with bone marrow stromal stem cells (BMSCs) in vitro and for bone tissue repair in vivo. We evaluated cytotoxicity of RVC scaffold and tantalum coating using BMSCs. The morphology, adhesion, and proliferation of BMSCs were observed via laser scanning confocal microscope and scanning electron microscopy. In addition, porous tantalum rods with or without autologous BMSCs were implanted on hind legs in dogs, respectively. The osteogenic potential was observed by hard tissue slice examination. At three weeks and six weeks following implantation, new osteoblasts and new bone were observed at the tantalum-host bone interface and pores. At 12 weeks postporous tantalum with autologous BMSCs implantation, regenerated trabecular equivalent to mature bone was found in the pore of tantalum rods. Our results suggested that domestic porous tantalum had excellent biocompatibility and could promote new bone formation in vivo. Meanwhile, the osteogenesis of porous tantalum associated with autologous BMSCs was more excellent than only tantalum implantation. Future clinical studies are warranted to verify the clinical efficacy of combined implantation of this domestic porous tantalum associated with autologous BMSCs implantation and compare their efficacy with conventional autologous bone grafting carrying blood vessel in patients needing bone repairing.

  20. Tantalum coating of porous carbon scaffold supplemented with autologous bone marrow stromal stem cells for bone regeneration in vitro and in vivo

    PubMed Central

    Wei, Xiaowei; Wang, Benjie; Wang, Wei; Kang, Kai; Xie, Hui; Liu, Baoyi; Zhang, Xiuzhi; Zhang, Jinsong; Yang, Zhenming

    2016-01-01

    Porous tantalum metal with low elastic modulus is similar to cancellous bone. Reticulated vitreous carbon (RVC) can provide three-dimensional pore structure and serves as the ideal scaffold of tantalum coating. In this study, the biocompatibility of domestic porous tantalum was first successfully tested with bone marrow stromal stem cells (BMSCs) in vitro and for bone tissue repair in vivo. We evaluated cytotoxicity of RVC scaffold and tantalum coating using BMSCs. The morphology, adhesion, and proliferation of BMSCs were observed via laser scanning confocal microscope and scanning electron microscopy. In addition, porous tantalum rods with or without autologous BMSCs were implanted on hind legs in dogs, respectively. The osteogenic potential was observed by hard tissue slice examination. At three weeks and six weeks following implantation, new osteoblasts and new bone were observed at the tantalum–host bone interface and pores. At 12 weeks postporous tantalum with autologous BMSCs implantation, regenerated trabecular equivalent to mature bone was found in the pore of tantalum rods. Our results suggested that domestic porous tantalum had excellent biocompatibility and could promote new bone formation in vivo. Meanwhile, the osteogenesis of porous tantalum associated with autologous BMSCs was more excellent than only tantalum implantation. Future clinical studies are warranted to verify the clinical efficacy of combined implantation of this domestic porous tantalum associated with autologous BMSCs implantation and compare their efficacy with conventional autologous bone grafting carrying blood vessel in patients needing bone repairing. PMID:26843518

  1. Transplantation of autologous bone marrow mesenchymal stem cells in the treatment of complete and chronic cervical spinal cord injury.

    PubMed

    Dai, Guanghui; Liu, Xuebin; Zhang, Zan; Yang, Zhijun; Dai, Yiwu; Xu, Ruxiang

    2013-10-02

    Neuronal injuries have been a challenging problem for treatment, especially in the case of complete and chronic cervical spinal cord injury (SCI). Recently, particular attention is paid to the potential of stem cell in treating SCI, but there are only few clinical studies and insufficient data. This study explored the efficacy of autologous bone marrow mesenchymal stem cells (BMMSCs) transplantation in the treatment of SCI. Forty patients with complete and chronic cervical SCI were selected and randomly assigned to one of the two experimental groups, treatment group and control group. The treatment group received BMMSCs transplantation to the area surrounding injury, while the control group was not treated with any cell transplantation. Both the transplant recipients and the control group were followed up to 6 months, postoperatively. Preoperative and postoperative neurological functions were evaluated with AIS grading, ASIA score, residual urine volume and neurophysiological examination. Results showed that in the treatment group 10 patients had a significant clinical improvement in terms of motor, light touch, pin prick sensory and residual urine volume, while nine patients showed changes in AIS grade. Neurophysiological examination was consistent with clinical observations. No sign of tumor was evident until 6 months postoperatively. In the control group, no improvement was observed in any of the neurological functions specified above. BMMSCs transplantation improves neurological function in patients with complete and chronic cervical SCI, providing valuable information on applications of BMMSCs for the treatment of SCI.

  2. High-Dose Chemotherapy With Autologous Hematopoietic Stem-Cell Transplantation in Metastatic Breast Cancer: Overview of Six Randomized Trials

    PubMed Central

    Berry, Donald A.; Ueno, Naoto T.; Johnson, Marcella M.; Lei, Xiudong; Caputo, Jean; Smith, Dori A.; Yancey, Linda J.; Crump, Michael; Stadtmauer, Edward A.; Biron, Pierre; Crown, John P.; Schmid, Peter; Lotz, Jean-Pierre; Rosti, Giovanni; Bregni, Marco; Demirer, Taner

    2011-01-01

    Purpose High doses of effective chemotherapy are compelling if they can be delivered safely. Substantial interest in supporting high-dose chemotherapy with bone marrow or autologous hematopoietic stem-cell transplantation in the 1980s and 1990s led to the initiation of randomized trials to evaluate its effect in the treatment of metastatic breast cancer. Methods We identified six randomized trials in metastatic breast cancer that evaluated high doses of chemotherapy with transplant support versus a control regimen without stem-cell support. We assembled a single database containing individual patient information from these trials. The primary analysis of overall survival was a log-rank test comparing high dose versus control. We also used Cox proportional hazards regression, adjusting for known covariates. We addressed potential treatment differences within subsets of patients. Results The effect of high-dose chemotherapy on overall survival was not statistically different (median, 2.16 v 2.02 years; P = .08). A statistically significant advantage in progression-free survival (median, 0.91 v 0.69 years) did not translate into survival benefit. Subset analyses found little evidence that there are groups of patients who might benefit from high-dose chemotherapy with hematopoietic support. Conclusion Overall survival of patients with metastatic breast cancer in the six randomized trials was not significantly improved by high-dose chemotherapy; any benefit from high doses was small. No identifiable subset of patients seems to benefit from high-dose chemotherapy. PMID:21768454

  3. The Role of Autologous and Allogeneic Stem Cell Transplantation in Follicular Lymphoma in The New Drugs Era

    PubMed Central

    Maura, Francesco; Farina, Lucia; Corradini, Paolo

    2016-01-01

    Follicular lymphoma (FL) is the second most common histotype of non-Hodgkin’s lymphoma, and it is generally characterized by a heterogeneous clinical course. Despite recent therapeutic and diagnostic improvements, a significant fraction of FL patients still relapsed. In younger and/or fit FL relapsed patients bone marrow transplant (BMT) has represented the main salvage therapy for many years. Thanks to the ability of high-dose chemotherapy to overcome the lymphoma resistance and refractoriness, autologous stem cell transplantation (ASCT) can achieve a high complete remission rate (CR) and favorable outcome regarding progression-free survival (PFS) and overall survival (OS). Allogeneic stem cell transplantation (alloSCT) combines the high dose chemotherapy effect together with the immune reaction of the donor immune system against lymphoma, the so-called ‘graft versus lymphoma’ (GVL) effect. Considering the generally higher transplant-related mortality (TRM), alloSCT is mostly indicated for FL relapsed after ASCT. During the last years, there have been a great spread of novel effective and feasible drugs Although these and future novel drugs will probably change our current approach to FL, the OS post-BMT (ASCT and alloSCT) has never been reproduced by any novel combination. In this scenario, it is important to correctly evaluate the disease status, the relapse risk and the comorbidity profile of the relapsed FL patients in order to provide the best salvage therapy and eventually transplant consolidation. PMID:27648208

  4. Tweaking the immune system: gene therapy-assisted autologous haematopoietic stem cell transplantation as a treatment for autoimmune disease.

    PubMed

    Alderuccio, Frank; Chan, James; Toh, Ban-Hock

    2008-12-01

    Autoimmune diseases represent a major challenge for medical research. The aberrant self-recognition by the immune system leads to a range of pathologies for which cures have not been forthcoming. Treatments are commonly non-specific and often lead to unwanted side-effects. A number of strategies are currently being explored to tackle autoimmunity; aimed at eliminating existing pathogenic clones and the induction of immune tolerance through resetting or regulating the immune system. Autologous haematopoietic stem cell transplantation (HSCT) is one such strategy and is being trailed in a number of autoimmune diseases. However, a common feature of this strategy is disease relapse and may indicate incomplete tolerance mechanisms. It is well known that bone marrow derived cells have a major influence on immune tolerance. It is also well documented that ectopic expression of antigens within the immune system can promote robust tolerance. This review considers these observations in the context of promoting a strategy involving genetic manipulation of haematopoietic stem cells together with HSCT to induce immune tolerance and tackle autoimmunity.

  5. Adoptive immunotherapy with donor lymphocyte infusions and interleukin-2 after high-dose therapy and autologous stem cell rescue for multiple myeloma.

    PubMed

    Ballester, O F; Fang, T; Raptis, A; Ballester, G; Wilcox, P; Hiemenz, J; Tan, B

    2004-09-01

    In an attempt to induce a graft-versus-myeloma effect, we administered donor lymphocyte infusions (DLI) after high-dose therapy with autologous stem cell transplant rescue to seven patients with refractory or relapsed multiple myeloma. High-dose therapy consisted of melphalan, idarubicin and etoposide (days -9 to -6) followed by autologous stem cell infusion on day 0. DLI (five of seven donors with two or three HLA antigens mismatched) were administered on days +1, +5 and +10 along with IL-2 (from day +1 through +12). Six of the seven patients developed acute graft-versus-host disease (GVHD), which resolved spontaneously, coincidentally with autologous hematopoietic reconstitution. One patient failed to engraft and received a second autologous graft. One patient died from complications of a pulmonary hemorrhage after experiencing GVHD. With a minimum follow-up of 38 months, five patients remain without disease progression in complete remission or with minimal residual disease. In this setting, DLI/IL-2 is biologically active resulting in GVHD. A graft-versus-myeloma effect is suggested by the improved outcome of our small cohort of high-risk patients. The use of partially mismatched related donors makes this approach potentially available to nearly all patients.

  6. Prospective evaluation of pulmonary function in cancer patients treated with total body irradiation, high-dose melphalan, and autologous hematopoietic stem cell transplantation

    SciTech Connect

    Gandola, L.; Siena, S.; Bregni, M.; Sverzellati, E.; Piotti, P.; Stucchi, C.; Gianni, A.M.; Lombardi, F. )

    1990-09-01

    Pulmonary function tests (standard vital capacity, SVC; total lung capacity, TLC; forced expiratory volume in 1 second-forced vital capacity ratio, FEV1/FVC; carbon monoxide transfer factor, DLCO) were prospectively evaluated in patients (median age 25 years, 13-52 years; median follow-up 20 months, 6-51 months) with Hodgkin's disease (15 patients), non-Hodgkin's lymphoma (9 patients), and inflammatory breast cancer (3 patients) treated with sequential high-dose therapy comprising the following phases over approximately 2 months: (a) cyclophosphamide (7 g/m2); (b) vincristine (1.4 mg/m2), methotrexate (8 g/m2), and cisplatinum (120 mg/m2) or etoposide (2 g/m2); (c) total body irradiation (TBI; 12.5 gy, 5 fractions over 48 hours), intravenous melphalan (120-180 mg/m2), and transplantation of autologous peripheral blood and/or bone marrow hematopoietic stem cells. Within 2 months after transplantation, 12 patients also received 25 Gy radiotherapy boost to mediastinum and clavicular regions. In vivo dosimetry evaluations of fractionated TBI treatments showed that mean radiation dose absorbed by lungs was 12.18 Gy (97.4% of TBI dose). Despite such a high radiation dose, we observed only transient and subclinical decrease of SVC, TLC, and DLCO. The decrease of SVC, TLC, and DLCO was more evident and prolonged in patients receiving radiotherapy boost. All parameters progressively recovered to normal values within 2 years after transplantation. In contrast, FEV1/FVC remained within normal limits in all patients, thus demonstrating the absence of obstructive ventilatory changes. In addition, no interstitial pneumonia was observed.

  7. Debrided Skin as a Source of Autologous Stem Cells for Wound Repair

    DTIC Science & Technology

    2011-08-01

    mean fold change (6 SD). The serrated line in (A), (B), and (C) shows genes with higher than equal to twofold change. Photomicrographs of adipogenic ...viability of skin, dsASCs displayed adipogenesis through the classical pathway of transcription activation of adipogenic -specific genes involved in early...designated as debrided skin adipose-derived stem cells (dsASCs). Gene expression analysis of stem cell specific transcripts showed that the dsASCs maintained

  8. The Impact of the German Tissue Act on the Manufacturing of Autologous and Allogeneic Stem Cell Preparations.

    PubMed

    Schlenke, Peter; Tapernon, Karin; Ahlke, Christoph; Mertens, Alexandra; Sibrowski, Walter

    2008-01-01

    SUMMARY: Cellular therapeutic agents considerably contribute to the optimal treatment of patients with hematological malignancies such as leukemia or nonhematological disorders. Over the last 50 years especially the transplantation of autologous and allogeneic stem cells from different sources after high-dose or myeloablative chemotherapy became a well-established standard therapy that cures or alleviates the symptoms in more than 50,000 patients/year worldwide. In the near future, the current progress in fundamental research on stem cells and immunobiology will allow for the clinical implementation of novel advanced cellular therapies, including gene therapeutic options. The European and German legislation have realized the need of international regulations for improved standardization and harmonization of stem cell transplants, associated cell-therapeutic agents as well as various tissue-engineered preparations in the emerging field of regenerative medicine. The Tissue Directive 2004/23/EC, issued and ratified by the European Parliament in March 2004, and its national transition into the German Tissue Act which came into force in July 2007 define the quality and safety standards for the donation, procurement, testing, processing, preservation, storage, and distribution of human tissues and cells. These standards are of high relevance to ensure the efficient prevention of the transmission of viral and nonviral infectious pathogens and to achieve the same safeguards as in the population's blood supply. This review discusses the pros and cons of the new legislation and argues for keeping the administrative and regulative demands in reasonable limits and for offering innovative approaches of cellular therapies to the European citizens.

  9. Whole blood tissue factor procoagulant activity remains detectable during severe aplasia following bone marrow and peripheral blood stem cell transplantation.

    PubMed

    Ozcan, M; Morton, C T; Solovey, A; Dandelet, L; Bach, R R; Hebbel, R P; Slungaard, A; Key, N S

    2001-02-01

    Using a novel whole blood assay, we recently demonstrated that tissue factor procoagulant activity (TF PCA) is present in normal individuals. Preliminary experiments suggested that this activity is localized in the mononuclear cell fraction. Postulating that whole blood TF PCA would therefore be undetectable when monocytes and neutrophils are absent from peripheral blood, we assayed TF PCA during the peri-transplant period in 15 consecutive patients undergoing allogeneic (n = 12) or autologous (n = 3) bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT). Baseline (pre-transplant) mean TF PCA was higher in patients compared to normal controls (P <0.005). Unexpectedly, although TF PCA during the period of profound aplasia was significantly reduced compared to baseline (p <0.05), fully 55% of the initial activity remained detectable. During the engraftment phase, TF PCA returned to pre-transplant levels, with a linear correlation between monocyte counts and TF PCA (r = 0.63). In contrast to normal whole blood, incubation of aplastic samples with E. Coli lipopolysaccharide ex vivo failed to induce TF PCA. Throughout the period of study--but especially during the aplastic phase--the absolute number of circulating endothelial cells (CECs) that were TF antigen-positive was increased compared to normals (P <0.001). However, removal of these cells from whole blood samples failed to significantly diminish total TF PCA indicating that CECs alone could not account for the detectable TF PCA during aplasia. We conclude that neither circulating mature myelo-monocytic cells nor endothelial cells can account for all the functionally intact TF in peripheral blood. Further studies are needed to identify the other source(s) of TF PCA.

  10. Hepatic veno-occlusive disease (VOD) with complete occlusion of liver venules after tandem autologous stem cell transplantation-- successful treatment with high-dose methylprednisolone and defibrotide.

    PubMed

    Sayer, H G; Will, U; Schilling, K; Vogt, T; Wollina, K; Höffken, K

    2002-03-01

    Veno-occlusive disease (VOD) is a life-threatening complication following allogeneic or autologous stem cell transplantation. We report on a patient with a high grade B-cell lymphoma who presented 28 days after the second autologous stem cell transplantation with weight gain, ascites, hyperbilirubinemia, and liver venules occlusion as demonstrated by sonography. Starting with high-dose methylprednisolone treatment followed by defibrotide maintenance therapy the patient showed dramatic complete response of VOD, resulting in a normal sonography of the liver and normalization of laboratory values. The response of the occlusion of nearly all liver venules underlines the value of anti-inflammatory treatment combined with new thrombolytic medication such as defibrotide for the treatment of severe VOD.

  11. [The BCTRIMS Expanded Consensus on treatment of multiple sclerosis: I. The evidences for the use of immunosuppressive agents, plasma exchange and autologous hematopoietic stem cell transplantation].

    PubMed

    Callegaro, Dagoberto; Lana-Peixoto, Marco Aurélio; Moreira, Marcos Aurélio; Marchiori, Paulo Eurípedes; Bacheschi, Luiz Alberto; Arruda, Walter Oleschko; Campos, Gilberto Belisário; Lino, Angelina Maria Martins; Melo, Aílton Souza; Rocha, Fernando Coronetti Gomes; Ferreira, Maria Lúcia Brito; Ataide, Luiz; Maciel, Damacio Ramón Kaimen

    2002-09-01

    Since the sixties immunosuppressive agents have been used in the treatment of multiple sclerosis as there was cumulating evidence of the inflammatory nature of the disease. Cyclophosphamide, azathioprine and methotrexate have been the most frequently employed drugs whereas other agents such as cyclosporine and cladribine have been recently tested for RRMS. Mithoxantrone, on the other hand, was approved by the FDA for treatment of aggressive forms of the disease. Other immunointerventions such as plasma exchange and autologous hematopoietic stem cell transplantation have recently been employed in some special circumstances. This paper analyses the most important published data on the use of the immunosuppressive agents, plasma exchange and autologous hematopoietic stem cell transplantation according to the classes of evidences and types of recommendations of these drugs and immunointerventions. It provides sufficient information to support the guidelines expressed in the BCTRIMS Expanded Consensus on Treatment of MS.

  12. An animal model of peripheral nerve regeneration after the application of a collagen-polyvinyl alcohol scaffold and mesenchymal stem cells.

    PubMed

    Marinescu, Silviu Adrian; Zărnescu, Otilia; Mihai, Ioana Ruxandra; Giuglea, Carmen; Sinescu, Ruxandra Diana

    2014-01-01

    Extensive nerve injuries often leading to nerve gaps can benefit, besides the gold standard represented by autologous nerve grafts, by the inciting field of tissue engineering. To enhance the role of biomaterials in nerve regeneration, the nerve conduits are associated with Schwann or Schwann-like cells. In this study, we evaluated rat sciatic nerve regeneration, by using a biodegradable nerve guide composed of Collagen (COL) and Polyvinyl Alcohol (PVA), associated with mesenchymal stem cells (MSC). After the exposure of the rat sciatic nerve, a nerve gap was created by excising 1 cm of the nerve. Three experimental groups were used for nerve gap bridging: autografts, nerve conduits filled with medium culture and nerve conduits filled with MSC. The methods of sensory and motor assessment consisted of the functional evaluation of sciatic nerve recovery - toe-spread, pinprick tests and gastrocnemius muscle index (GMI). The histological and immunocytochemical analysis of the probes that were harvested from the repair site was performed at 12 weeks. Successful nerve regeneration was noted in all three groups at the end of the 12th week. The functional and immunocytochemical results suggested that COL-PVA tubes supported with mesenchymal stem cells could be considered similar to autologous nerve grafts in peripheral nerve regeneration, without the drawbacks of the last ones. The functional results were better for the autografts and the ultrastructural data were better for the nerve conduits, but there were not noticed any statistical differences.

  13. Mobilization of hematopoietic stem cells into the peripheral blood.

    PubMed

    Damon, Lloyd E; Damon, Lauren E

    2009-12-01

    Hematopoietic stem cells can be mobilized out of the bone marrow into the blood for the reconstitution of hematopoiesis following high-dose therapy. Methods to improve mobilization efficiency and yields are rapidly emerging. Traditional methods include chemotherapy with or without myeloid growth factors. Plerixafor, a novel agent that disrupts the CXCR4-CXCL12 bond, the primary hematopoietic stem cell anchor in the bone marrow, has recently been US FDA-approved for mobilizing hematopoietic stem cells in patients with non-Hodgkin lymphoma and multiple myeloma. Plerixafor and myeloid growth factors as single agents appear safe to use in family or volunteer hematopoietic stem cells donors. Plerixafor mobilizes leukemic stem cells and is not approved for use in patients with acute leukemia. Patients failing to mobilize adequate hematopoietic stem cells with myeloid growth factors can often be successfully mobilized with chemotherapy plus myeloid growth factors or with plerixafor and granulocyte colony-stimulating factor.

  14. Myeloablative allogeneic hematopoietic stem cell transplantation in patients who experience relapse after autologous stem cell transplantation for lymphoma: a report of the International Bone Marrow Transplant Registry.

    PubMed

    Freytes, César O; Loberiza, Fausto R; Rizzo, J Douglas; Bashey, Asad; Bredeson, Christopher N; Cairo, Mitchell S; Gale, Robert Peter; Horowitz, Mary M; Klumpp, Thomas R; Martino, Rodrigo; McCarthy, Philip L; Molina, Arturo; Pavlovsky, Santiago; Pecora, Andrew L; Serna, Derek S; Tsai, Tsuong; Zhang, Mei-Jie; Vose, Julie M; Lazarus, Hillard M; van Besien, Koen

    2004-12-01

    Myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) is increasingly used in patients with lymphoma who experience disease relapse after autologous hematopoietic stem cell transplantation (auto-HSCT) because the allograft is tumor free and may induce a graft-versus-tumor effect. We analyzed 114 patients treated with this approach from 1990 to 1999 to assess disease progression, progression-free survival (PFS), and overall survival (OS). Cumulative incidence of disease progression at 3 years was 52%, whereas treatment-related mortality was 22%, lower than previously reported. Three-year probabilities of OS and PFS were 33% and 25%, respectively. With prolonged follow-up, however, nearly all patients experienced disease progression, and 5-year probabilities were 24% and 5%, respectively. Complete remission at the time of allo-HSCT and use of total body irradiation (TBI) in patients with non-Hodgkin lymphoma (NHL) were associated with lower rates of disease progression and higher rates of OS. In summary, allo-HSCT is feasible for patients with lymphoma who have relapses after auto-HSCT and can result in prolonged survival for some, but it is usually not curative. Most likely to benefit are patients who have HLA-matched sibling donors, are in remission, and have good performance status.

  15. Bilayer hydrogel with autologous stem cells derived from debrided human burn skin for improved skin regeneration.

    PubMed

    Natesan, Shanmugasundaram; Zamora, David O; Wrice, Nicole L; Baer, David G; Christy, Robert J

    2013-01-01

    The objective of this study was to demonstrate that stem cells isolated from discarded skin obtained after debridement can be used with collagen and fibrin-based scaffolds to develop a tissue-engineered vascularized dermal equivalent. Discarded tissue samples were collected from severely burned patients undergoing wound debridement. Stem cells were isolated from the adipose tissue layer and their growth and immunophenotype characterized. To develop a skin equivalent, debrided skin adipose stem cells (dsASCs) were added to a collagen-polyethylene glycol (PEG) fibrin-based bilayer hydrogel and analyzed in vitro. The effect of the bilayered hydrogels on wound healing was demonstrated using an excision wound model in athymic rats. The dsASCs isolated from all samples were CD90, CD105, and stromal cell surface protein-1 positive, similar to adipose stem cells isolated from normal human lipoaspirates. Within the bilayer hydrogels, dsASCs proliferated and differentiated, maintained a spindle-shaped morphology in collagen, and developed a tubular microvascular network in the PEGylated fibrin. Rat excision wounds treated with bilayer hydrogels showed less wound contraction and exhibited better dermal matrix deposition and epithelial margin progression than controls. Stem cells can be isolated from the adipose layer of burned skin obtained during debridement. When dsASCs are incorporated within collagen-PEGylated fibrin bilayer hydrogels, they develop stromal and vascular phenotypes through matrix-directed differentiation without use of growth factors. Preliminary in vivo studies indicate that dsASC-bilayer hydrogels contribute significantly to wound healing and provide support for their use as a vascularized dermal substitute for skin regeneration to treat large surface area burns.

  16. Tolerability of piperacillin/tazobactam in children and adolescents after high dose radio-/chemotherapy and autologous stem cell transplantation.

    PubMed

    Nürnberger, W; Bönig, H; Burdach, S; Göbel, U

    1998-01-01

    The combination of piperacillin with tazobactam (PIP/TAZ) extends the activity of piperacillin against gram-positive, gram-negative, and anaerobic bacteria. The broad-spectrum of this formulation, together with its low degree of organ toxicity observed in adults, makes PIP/TAZ a tempting choice for children with radio-/chemotherapy-induced neutropenia. However, the use of PIP/TAZ is not yet approved for children under 12 years of age. The tolerability of PIP/TAZ was assessed in 19 children and adolescents between 2 and 18 years of age who developed a fever during aplasia after high dose radio-/chemotherapy and autologous stem cell transplantation (HD-SCT) for primary multifocal or relapsed solid tumours. Treatment with PIP/TAZ was initiated on average 3 days after HD-SCT, and the treatment was continued for approximately 10 days. Both clinical observation and laboratory studies showed no relevant alterations that would have been attributable to PIP/TAZ treatment. These results indicate that PIP/TAZ appears to be well tolerated in children during the acute phase of HD-SCT.

  17. Transplantation of Autologous Bone Marrow Mesenchymal Stem Cells with Platelet-Rich Plasma Accelerate Distraction Osteogenesis in A Canine Model

    PubMed Central

    Dehghan, Mohammad Mehdi; Baghaban Eslaminejad, Mohamadreza; Motallebizadeh, Nader; Ashrafi Halan, Javad; Tagiyar, Leila; Soroori, Sarang; Nikmahzar, Agbibi; Pedram, Mirsepehr; Shahverdi, Abdolhossein; Kazemi Mehrjerdi, Hossein; Izadi, Sadra

    2015-01-01

    Objective Distraction osteogenesis (DO) is a surgical procedure used to generate large volumes of new bone for limb lengthening. Materials and Methods In this animal experimental study, a 30% lengthening of the left tibia (mean distraction distance: 60.8 mm) was performed in ten adult male dogs by callus distraction after osteotomy and application of an Ilizarov fixator. Distraction was started on postoperative day seven with a distraction rate of 0.5 mm twice per day and carried out at a rate of 1.5 mm per day until the end of the study. Autologous bone marrow mesenchymal stem cells (BM-MSCs) and platelet-rich plasma (PRP) as the treatment group (n=5) or PRP alone (control group, n=5) were injected into the distracted callus at the middle and end of the distraction period. At the end of the consolidation period, the dogs were sacrificed after which computerized tomography (CT) and histomorphometric evaluations were performed. Results Radiographic evaluationsrevealed that the amount and quality of callus formations were significantly higher in the treatment group (P<0.05). As measured by CT scan, the healing parametersin dogs of the treatment group were significantly greater (P<0.05). New bone formation in the treatment group was significantly higher (P<0.05). Conclusion The present study showed that the transplantation of BM-MSCs positively affects early bony consolidation in DO. The use of MSCs might allow a shortened period of consolidation and therefore permit earlier device removal. PMID:26199903

  18. Detection of Minimal Residual Disease by Flow Cytometry for Patients with Multiple Myeloma Submitted to Autologous Hematopoietic Stem Cell Transplantation

    PubMed Central

    Dal Bó, Suzane; Pezzi, Annelise; Amorin, Bruna; Valim, Vanessa; Isabel Bittencourt, Rosane; Silla, Lucia

    2013-01-01

    The treatment strategy in multiple myeloma (MM) is to get complete remission followed by high-dose chemotherapy and autologous Hematopoietic Stem Cell Transplantation (HSCT). Neoplastic Plasma Cells (NPCs) are CD45−/dim, CD38+high, CD138+, CD19−, and  CD56+high in most cases. The description of this immunophenotype is of major importance as it leads to the correct identification of minimal residual disease (MRD). Samples from 44 Patients were analyzed prospectively in this study. We analyzed if the presence of MRD at three months after HSCT was predictive of relapse or death. There were 40 evaluable patients of whom 16/40 patients had MRD at three moths after HSCT and there were none in cytological relapse. The mean overall survival (OS) was 34 months and disease-free survival (RFS) was 28 months after HSCT. There was no significant difference in the log rank analysis comparing OS and the presence of MRD (P = 0,611) and RFS (P = 0,3106). Here, we demonstrate that three color flow cytometry (FCM) is more sensitive for MDR evaluation than cytological analyzes. However, based in our data we can not affirm that MRD is a good predictor of MM relapse or death. In conclusion, our results could be attributed to a short followup, small sample size, and over most to the inability of a three-color FCM to detect the NPC population. PMID:23864957

  19. Absolute lymphocyte count as predictor of overall survival for patients with multiple myeloma treated with single autologous stem cell transplant.

    PubMed

    Jimenez-Zepeda, Victor H; Reece, Donna E; Trudel, Suzanne; Chen, Christine; Franke, Norman; Winter, Andrew; Tiedemann, Rodger; Kukreti, Vishal

    2015-01-01

    Post-autologous stem cell transplant (ASCT) studies have demonstrated that absolute lymphocyte count (ALC) recovery is associated with prolonged survival in some hematological malignancies. To assess whether ALC recovery has prognostic significance in patients with multiple myeloma (MM) undergoing single ASCT, we conducted a retrospective analysis of ALC at different time-points in patients with MM. In total 769 consecutive patients who underwent single ASCT from January 2000 to December 2007 were evaluated. An ALC of ≥ 1400 cells/μL at day 0, day 15 and day 90 significantly correlated with a better overall survival (OS) (median OS of 111, 90.7 and 84 months vs. 74, 70.5 and 65 months, respectively, p < 0.001 for all time-points). Multivariate analysis showed that ALC is an independent prognostic factor for OS after ASCT. In conclusion, ALC is a surrogate marker of the host immune system that correlates with better survival in patients with MM undergoing single ASCT. Immunomodulatory drugs, vaccination strategies and cellular therapies in MM should be investigated.

  20. Miconazole mucoadhesive buccal tablet in high-dose therapy with autologous stem cell transplantation (HDT/ASCT)-induced mucositis.

    PubMed

    Orvain, C; Moles-Moreau, M P; François, S; Mercier, M; Moal, F; Hamel, J F; Parot-Schinkel, E; Ifrah, N; Hunault-Berger, M; Tanguy-Schmidt, A

    2015-02-01

    Oral mucositis is a major cause of morbidity in high-dose therapy/autologous stem cell transplantation (HDT/ASCT), where microbial colonization has an important pathological implication. In this study, we evaluated the impact of miconazole mucoadhesive buccal tablet (MBT) on mucositis-related complications. During two consecutive 34-month periods, patients treated with HDT/ASCT in our hematology department received either miconazole MBT (60 patients) or conventional oral amphotericin B suspensions three times a day (44 patients) in order to prevent or decrease chemotherapy-induced mucositis. The use of miconazole MBT is associated with less infectious complications as indicated by shorter antibiotic use (7.8 vs. 12.3 days; p < 0.0001), shorter intravenous antifungal use (1.4 vs. 3.6 days; p = 0.02), and a trend towards less yeast contamination in stool samples. Less patients required any analgesic drugs during hospitalization in the miconazole MBT group (18 vs. 7 %; p = 0.09). Indirect indicators of chemotherapy-induced mucositis (duration of hospitalization, morphine use) were in favor of miconazole MBT in patients with multiple myeloma (MM) but not for those with lymphoma. This study suggests that miconazole MBT provides a valid alternative to oral amphotericin B suspensions in regards to mucositis-related complications. A prospective and randomized study is warranted to establish the definite role of miconazole MBT.

  1. Multiparameter flow cytometric remission is the most relevant prognostic factor for multiple myeloma patients who undergo autologous stem cell transplantation

    PubMed Central

    Paiva, Bruno; Vidriales, Maria-Belén; Cerveró, Jorge; Mateo, Gema; Pérez, Jose J.; Montalbán, Maria A.; Sureda, Anna; Montejano, Laura; Gutiérrez, Norma C.; de Coca, Alfonso García; de las Heras, Natalia; Mateos, Maria V.; López-Berges, Maria C.; García-Boyero, Raimundo; Galende, Josefina; Hernández, Jose; Palomera, Luis; Carrera, Dolores; Martínez, Rafael; de la Rubia, Javier; Martín, Alejandro; Bladé, Joan; Lahuerta, Juan J.; Orfao, Alberto

    2008-01-01

    Minimal residual disease (MRD) assessment is standard in many hematologic malignancies but is considered investigational in multiple myeloma (MM). We report a prospective analysis of the prognostic importance of MRD detection by multiparameter flow cytometry (MFC) in 295 newly diagnosed MM patients uniformly treated in the GEM2000 protocol VBMCP/VBAD induction plus autologous stem cell transplantation [ASCT]). MRD status by MFC was determined at day 100 after ASCT. Progression-free survival (PFS; median 71 vs 37 months, P < .001) and overall survival (OS; median not reached vs 89 months, P = .002) were longer in patients who were MRD negative versus MRD positive at day 100 after ASCT. Similar prognostic differentiation was seen in 147 patients who achieved immunofixation-negative complete response after ASCT. Moreover, MRD− immunofixation-negative (IFx−) patients and MRD− IFx+ patients had significantly longer PFS than MRD+ IFx− patients. Multivariate analysis identified MRD status by MFC at day 100 after ASCT as the most important independent prognostic factor for PFS (HR = 3.64, P = .002) and OS (HR = 2.02, P = .02). Our findings demonstrate the clinical importance of MRD evaluation by MFC, and illustrate the need for further refinement of MM re-sponse criteria. This trial is registered at http://clinicaltrials.gov under identifier NCT00560053. PMID:18669875

  2. Successful management of gastropulmonary fistula due to invasive fungal infection after chemotherapy and autologous stem cell transplantation: a case report

    PubMed Central

    Ričardas, Janilionis; Lina, Lukoševičiūtė; Virgilijus, Beiša; Valdemaras, Jotautas; Roberta, Petrauskaitė; Valdas, Pečeliūnas; Renata, Jucaitienė

    2016-01-01

    Background. Invasive fungal infections (IFI) contribute significantly to mortality and morbidity in patients receiving myelosuppressive chemotherapy for hematologic malignancies. Acquired gastropulmonary fistula is a rare complication of IFI. Material and methods. We present a case history of a patient with malignant myeloma. She was treated with autologous stem cell transplantation and chemotherapy for three years. She had been treated with antifungal agents as well. Following a specific treatment, she developed an invasive fungal infection (IFI) of the left lung which had been complicated with left gastropulmonary fistula. The patient’s general condition was deteriorating, so it was decided to perform a surgical intervention. At the first procedure, open-window thoracostomy was created in order to facilitate treatment by daily packing of the cavity. Four weeks after the thoracostomy, a thoracomyoplasty was performed to repair a gastropleural fistula. During the laparotomy, the gastric fundus was freed from adjacent tissues and repaired. Intrathoracic transposition of the latissimus dorsi and anterior serratus muscle flaps was performed simultaneously to create a new diaphragm. The open-window thoracostomy was left open due to some small bronchial fistulas. The thoracostomy opening healed spontaneously during the following six months. Conclusion. We report what is, to the best of our knowledge, the first case of an invasive fungal infection (Geotrichum capitatum) successfully treated with intravenous amphotericin B, voriconazole, and surgery on infected soft tissues (organs) for a patient with multiple myeloma in prolonged neutropenia. The efficacy and safety of the surgery for infected soft tissues requires further evaluation. PMID:28356805

  3. Preparation of a nano- and micro-fibrous decellularized scaffold seeded with autologous mesenchymal stem cells for inguinal hernia repair

    PubMed Central

    Zhang, Yinlong; Zhou, Yuanyuan; Zhou, Xu; Zhao, Bin; Chai, Jie; Liu, Hongyi; Zheng, Yifei; Wang, Jinling; Wang, Yaozong; Zhao, Yilin

    2017-01-01

    Prosthetic meshes used for hernioplasty are usually complicated with chronic pain due to avascular fibrotic scar or mesh shrinkage. In this study, we developed a tissue-engineered mesh (TEM) by seeding autologous bone marrow-derived mesenchymal stem cells onto nanosized fibers decellularized aorta (DA). DA was achieved by decellularizing the aorta sample sequentially with physical, mechanical, biological enzymatic digestion, and chemical detergent processes. The tertiary structure of DA was constituted with micro-, submicro-, and nanosized fibers, and the original strength of fresh aorta was retained. Inguinal hernia rabbit models were treated with TEMs or acellular meshes (AMs). After implantation, TEM-treated rabbit models showed no hernia recurrence, whereas AM-treated animals displayed bulges in inguinal area. At harvest, TEMs were thicker, have less adhesion, and have stronger mechanical strength compared to AMs (P<0.05). Moreover, TEM showed better cell infiltration, tissue regeneration, and neovascularization (P<0.05). Therefore, these cell-seeded DAs with nanosized fibers have potential for use in inguinal hernioplasty. PMID:28260890

  4. Cost-Effectiveness of Autologous Stem Cell Treatment as Compared to Conventional Chemotherapy for Treatment of Multiple Myeloma in India.

    PubMed

    Prinja, Shankar; Kaur, Gunjeet; Malhotra, Pankaj; Jyani, Gaurav; Ramachandran, Raja; Bahuguna, Pankaj; Varma, Subhash

    2017-03-01

    Recent innovations in treatment of multiple myeloma include autologous stem cell transplantation (ASCT) along with high dose chemotherapy (HDC). We undertook this study to estimate incremental cost per quality adjusted life year gained (QALY) with use of ASCT along with HDC as compared to conventional chemotherapy (CC) alone in treatment of multiple myeloma. A combination of decision tree and markov model was used to undertake the analysis. Incremental costs and effects of ASCT were compared against the baseline scenario of CC (based on Melphalan and Prednisolone regimen) in the patients of multiple myeloma. A lifetime study horizon was used and future costs and consequences were discounted at 5%. Consequences were valued in terms of QALYs. Incremental cost per QALY gained using ASCT as against CC for treatment of multiple myeloma was estimated using both a health system and societal perspective. The cost of providing ASCT (with HDC) for multiple myeloma patients was INR 500,631, while the cost of CC alone was INR 159,775. In the long run, cost per patient per year for ASCT and CC arms was estimated to be INR 119,740 and INR 111,565 respectively. The number of QALYs lived per patient in case of ASCT and HDC alone were found to be 4.1 and 3.5 years respectively. From a societal perspective, ASCT was found to incur an incremental cost of INR 334,433 per QALY gained. If the ASCT is initiated early to patients, the incremental cost for ASCT was found to be INR 180,434 per QALY gained. With current mix of patients, stem cell treatment for multiple myeloma is not cost effective at a threshold of GDP per capita. It becomes marginally cost-effective at 3-times the GDP per capita threshold. However, accounting for the model uncertainties, the probability of ASCT to be cost effective is 59%. Cost effectiveness of ASCT can be improved with early detection and initiation of treatment.

  5. Tonsil-Derived Mesenchymal Stem Cells Differentiate into a Schwann Cell Phenotype and Promote Peripheral Nerve Regeneration

    PubMed Central

    Jung, Namhee; Park, Saeyoung; Choi, Yoonyoung; Park, Joo-Won; Hong, Young Bin; Park, Hyun Ho Choi; Yu, Yeonsil; Kwak, Geon; Kim, Han Su; Ryu, Kyung-Ha; Kim, Jae Kwang; Jo, Inho; Choi, Byung-Ok; Jung, Sung-Chul

    2016-01-01

    Schwann cells (SCs), which produce neurotropic factors and adhesive molecules, have been reported previously to contribute to structural support and guidance during axonal regeneration; therefore, they are potentially a crucial target in the restoration of injured nervous tissues. Autologous SC transplantation has been performed and has shown promising clinical results for treating nerve injuries and donor site morbidity, and insufficient production of the cells have been considered as a major issue. Here, we performed differentiation of tonsil-derived mesenchymal stem cells (T-MSCs) into SC-like cells (T-MSC-SCs), to evaluate T-MSC-SCs as an alternative to SCs. Using SC markers such as CAD19, GFAP, MBP, NGFR, S100B, and KROX20 during quantitative real-time PCR we detected the upregulation of NGFR, S100B, and KROX20 and the downregulation of CAD19 and MBP at the fully differentiated stage. Furthermore, we found myelination of axons when differentiated SCs were cocultured with mouse dorsal root ganglion neurons. The application of T-MSC-SCs to a mouse model of sciatic nerve injury produced marked improvements in gait and promoted regeneration of damaged nerves. Thus, the transplantation of human T-MSCs might be suitable for assisting in peripheral nerve regeneration. PMID:27834852

  6. Tonsil-Derived Mesenchymal Stem Cells Differentiate into a Schwann Cell Phenotype and Promote Peripheral Nerve Regeneration.

    PubMed

    Jung, Namhee; Park, Saeyoung; Choi, Yoonyoung; Park, Joo-Won; Hong, Young Bin; Park, Hyun Ho Choi; Yu, Yeonsil; Kwak, Geon; Kim, Han Su; Ryu, Kyung-Ha; Kim, Jae Kwang; Jo, Inho; Choi, Byung-Ok; Jung, Sung-Chul

    2016-11-09

    Schwann cells (SCs), which produce neurotropic factors and adhesive molecules, have been reported previously to contribute to structural support and guidance during axonal regeneration; therefore, they are potentially a crucial target in the restoration of injured nervous tissues. Autologous SC transplantation has been performed and has shown promising clinical results for treating nerve injuries and donor site morbidity, and insufficient production of the cells have been considered as a major issue. Here, we performed differentiation of tonsil-derived mesenchymal stem cells (T-MSCs) into SC-like cells (T-MSC-SCs), to evaluate T-MSC-SCs as an alternative to SCs. Using SC markers such as CAD19, GFAP, MBP, NGFR, S100B, and KROX20 during quantitative real-time PCR we detected the upregulation of NGFR, S100B, and KROX20 and the downregulation of CAD19 and MBP at the fully differentiated stage. Furthermore, we found myelination of axons when differentiated SCs were cocultured with mouse dorsal root ganglion neurons. The application of T-MSC-SCs to a mouse model of sciatic nerve injury produced marked improvements in gait and promoted regeneration of damaged nerves. Thus, the transplantation of human T-MSCs might be suitable for assisting in peripheral nerve regeneration.

  7. Osteogenesis of peripheral blood mesenchymal stem cells in self assembling peptide nanofiber for healing critical size calvarial bony defect

    PubMed Central

    Wu, Guofeng; Pan, Mengjie; Wang, Xianghai; Wen, Jinkun; Cao, Shangtao; Li, Zhenlin; Li, Yuanyuan; Qian, Changhui; Liu, Zhongying; Wu, Wutian; Zhu, Lixin; Guo, Jiasong

    2015-01-01

    Peripheral blood mesenchymal stem cells (PBMSCs) may be easily harvested from patients, permitting autologous grafts for bone tissue engineering in the future. However, the PBMSC’s capabilities of survival, osteogenesis and production of new bone matrix in the defect area are still unclear. Herein, PBMSCs were seeded into a nanofiber scaffold of self-assembling peptide (SAP) and cultured in osteogenic medium. The results indicated SAP can serve as a promising scaffold for PBMSCs survival and osteogenic differentiation in 3D conditions. Furthermore, the SAP seeded with the induced PBMSCs was splinted by two membranes of poly(lactic)-glycolic acid (PLGA) to fabricate a composited scaffold which was then used to repair a critical-size calvarial bone defect model in rat. Twelve weeks later the defect healing and mineralization were assessed by H&E staining and microcomputerized tomography (micro-CT). The osteogenesis and new bone formation of grafted cells in the scaffold were evaluated by immunohistochemistry. To our knowledge this is the first report with solid evidence demonstrating PBMSCs can survive in the bone defect area and directly contribute to new bone formation. Moreover, the present data also indicated the tissue engineering with PBMSCs/SAP/PLGA scaffold can serve as a novel prospective strategy for healing large size cranial defects. PMID:26568114

  8. Autologous stem cell-based therapy for sickle cell leg ulcer: a pilot study.

    PubMed

    Meneses, José Válber L; Fortuna, Vitor; de Souza, Eliane Silva; Daltro, Gildasio Cerqueira; Meyer, Roberto; Minniti, Caterina P; Borojevic, Radovan

    2016-12-01

    Recurrent chronic leg ulcers are among the most severe vasculopathic complications of sickle cell disease (SCD). Their treatment remains a challenge. Stem cell therapy with bone marrow mononuclear cells (BMMC) is a promising new therapeutic option for other forms of chronic ulcers. This prospective pilot study was performed to evaluate safety and feasibility of BMMC implantation in patients with SCD and chronic leg ulcers (SCLU). Ulcer closure, recurrence and local pain were evaluated. BMMC were successfully administered to 23 SCLU patients and no serious adverse events occurred. During the 6-month follow-up period, 91·3% of patients had improved ulcer pain compared with baseline and 29·2% of the treated ulcers achieved total healing. The frequency of progenitor stem cells (CD34CD45(low) and fibroblast colony-forming units) in BMMC was found to be significantly reduced in SCLU patients and compared to SCD patients without ulcers (P < 0·004 and P < 0·01, respectively). No relationship was observed between treatment outcome and the number of implanted BM progenitor stem cells. In conclusion, BMMC implantation is a feasible and safe procedure, showing favourable outcomes for the treatment of SCLU, and encouraging further controlled clinical trials.

  9. Using Stem Cells to Grow Artificial Tissue for Peripheral Nerve Repair

    PubMed Central

    Bhangra, Kulraj Singh; Busuttil, Francesca

    2016-01-01

    Peripheral nerve injury continues to pose a clinical hurdle despite its frequency and advances in treatment. Unlike the central nervous system, neurons of the peripheral nervous system have a greater ability to regenerate. However, due to a number of confounding factors, this is often both incomplete and inadequate. The lack of supportive Schwann cells or their inability to maintain a regenerative phenotype is a major factor. Advances in nervous system tissue engineering technology have led to efforts to build Schwann cell scaffolds to overcome this and enhance the regenerative capacity of neurons following injury. Stem cells that can differentiate along a neural lineage represent an essential resource and starting material for this process. In this review, we discuss the different stem cell types that are showing promise for nervous system tissue engineering in the context of peripheral nerve injury. We also discuss some of the biological, practical, ethical, and commercial considerations in using these different stem cells for future clinical application. PMID:27212954

  10. Amniotic mesenchymal stem cells display neurovascular tropism and aid in the recovery of injured peripheral nerves.

    PubMed

    Li, YongNan; Guo, Longzhe; Ahn, Hyun Sook; Kim, Moo Hyun; Kim, Sung-Whan

    2014-06-01

    Recently, we reported that human amniotic membrane-derived mesenchymal stem cells (AMMs) possess great angiogenic potential. In this study, we determined whether local injection of AMMs ameliorates peripheral neuropathy. AMMs were transplanted into injured sciatic nerves. AMM injection promoted significant recovery of motor nerve conduction velocity and voltage amplitude compared to human adipose-derived mesenchymal stem cells. AMM implantation also augmented blood perfusion and increased intraneural vascularity. Whole-mount fluorescent imaging analysis demonstrated that AMMs exhibited higher engraftment and endothelial incorporation abilities in the sciatic nerve. In addition, the higher expression of pro-angiogenic factors was detected in AMMs injected into the peripheral nerve. Therefore, these data provide novel therapeutic and mechanistic insights into stem cell biology, and AMM transplantation may represent an alternative therapeutic option for treating peripheral neuropathy.

  11. Autologous Bone Marrow-Derived Mesenchymal Stem Cells Modulate Molecular Markers of Inflammation in Dogs with Cruciate Ligament Rupture

    PubMed Central

    Muir, Peter; Hans, Eric C.; Racette, Molly; Volstad, Nicola; Sample, Susannah J.; Heaton, Caitlin; Holzman, Gerianne; Schaefer, Susan L.; Bloom, Debra D.; Bleedorn, Jason A.; Hao, Zhengling; Amene, Ermias; Suresh, M.; Hematti, Peiman

    2016-01-01

    Mid-substance rupture of the canine cranial cruciate ligament rupture (CR) and associated stifle osteoarthritis (OA) is an important veterinary health problem. CR causes stifle joint instability and contralateral CR often develops. The dog is an important model for human anterior cruciate ligament (ACL) rupture, where rupture of graft repair or the contralateral ACL is also common. This suggests that both genetic and environmental factors may increase ligament rupture risk. We investigated use of bone marrow-derived mesenchymal stem cells (BM-MSCs) to reduce systemic and stifle joint inflammatory responses in dogs with CR. Twelve dogs with unilateral CR and contralateral stable partial CR were enrolled prospectively. BM-MSCs were collected during surgical treatment of the unstable CR stifle and culture-expanded. BM-MSCs were subsequently injected at a dose of 2x106 BM-MSCs/kg intravenously and 5x106 BM-MSCs by intra-articular injection of the partial CR stifle. Blood (entry, 4 and 8 weeks) and stifle synovial fluid (entry and 8 weeks) were obtained after BM-MSC injection. No adverse events after BM-MSC treatment were detected. Circulating CD8+ T lymphocytes were lower after BM-MSC injection. Serum C-reactive protein (CRP) was decreased at 4 weeks and serum CXCL8 was increased at 8 weeks. Synovial CRP in the complete CR stifle was decreased at 8 weeks. Synovial IFNγ was also lower in both stifles after BM-MSC injection. Synovial/serum CRP ratio at diagnosis in the partial CR stifle was significantly correlated with development of a second CR. Systemic and intra-articular injection of autologous BM-MSCs in dogs with partial CR suppresses systemic and stifle joint inflammation, including CRP concentrations. Intra-articular injection of autologous BM-MSCs had profound effects on the correlation and conditional dependencies of cytokines using causal networks. Such treatment effects could ameliorate risk of a second CR by modifying the stifle joint inflammatory response

  12. Hematopoietic stem and progenitor cells: their mobilization and homing to bone marrow and peripheral tissue.

    PubMed

    Schulz, Christian; von Andrian, Ulrich H; Massberg, Steffen

    2009-01-01

    Hematopoietic stem and progenitor cells (HSPCs) are a rare population of precursor cells that possess the capacity for self-renewal and multilineage differentiation. In the bone marrow (BM), HSPCs warrant blood cell homeostasis. In addition, they may also replenish tissue-resident myeloid cells and directly participate in innate immune responses once they home to peripheral tissues. In this review, we summarize recent data on the signaling molecules that modulate the mobilization of HSPCs from BM and their migration to peripheral tissues.

  13. Single or tandem autologous stem-cell transplantation for first-relapsed or refractory Hodgkin lymphoma: 10-year follow-up of the prospective H96 trial by the LYSA/SFGM-TC study group

    PubMed Central

    Sibon, David; Morschhauser, Franck; Resche-Rigon, Matthieu; Ghez, David; Dupuis, Jehan; Marçais, Ambroise; Deau-Fischer, Bénédicte; Bouabdallah, Reda; Sebban, Catherine; Salles, Gilles; Brice, Pauline

    2016-01-01

    We assessed the long-term results of autologous stem-cell transplantation for patients with first-relapsed or refractory Hodgkin lymphoma included in the prospective Lymphoma Study Association/Société Française de Greffe de Moelle H96 trial. This large multicenter phase II trial evaluated a risk-adapted strategy with single or tandem autologous stem-cell transplantation for 245 Hodgkin lymphoma patients. Poor-risk patients (n=150) had primary refractory Hodgkin lymphoma (n=77) or ≥2 risk factors at first relapse (n=73) and were eligible for tandem autologous stem-cell transplantation. Intermediate-risk patients (n=95) had one risk factor at first relapse and were eligible for single autologous stem-cell transplantation. With a median follow-up of 10.3 years, 10-year freedom from second failure and overall survival rates were, respectively: 64% (95% CI, 54% to 74%) and 70% (95% CI, 61% to 80%) for the intermediate-risk group, and 41% (95% CI, 33% to 49%) and 47% (95% CI, 39% to 55%) for the poor-risk group. Considering only patients who did not relapse after completing autologous stem-cell transplantation, the 15-year cumulative incidences of second primary malignancies were 24% for the 70 intermediate-risk patients and 2% for the 75 poor-risk ones. With long-term follow-up, the risk-adapted strategy remains appropriate. Tandem autologous stem-cell transplantation can still be considered an option for poor-risk patients, but integration of positron-emission tomography findings and new drugs may help to refine the need for a second autologous stem-cell transplant and possibly improve outcomes of patients with first-relapsed or refractory Hodgkin lymphoma. PMID:26721893

  14. High-dose therapy and autologous stem cell transplantation in patients with POEMS syndrome: a retrospective study of the Plasma Cell Disorder sub-committee of the Chronic Malignancy Working Party of the European Society for Blood & Marrow Transplantation.

    PubMed

    Cook, Gordon; Iacobelli, Simona; van Biezen, Anja; Ziagkos, Dimitris; LeBlond, Veronique; Abraham, Julie; McQuaker, Grant; Schoenland, Stefan; Rambaldi, Alessandro; Halaburda, Kazimierz; Rovira, Maria; Sica, Simona; Byrne, Jenny; Sanz, Ramon Garcia; Nagler, Arnon; van de Donk, Niels W C J; Sinisalo, Marjatta; Cook, Mark; Kröger, Nicolaus; De Witte, Theo; Morris, Curly; Garderet, Laurant

    2017-01-01

    POEMS syndrome is a rare para-neoplastic syndrome secondary to a plasma cell dyscrasia. Effective treatment can control the disease-related symptom complex. We describe the clinical outcome of autologous stem cell transplantation for patients with POEMS syndrome, determining the impact of patient- and disease-specific factors on prognosis. One hundred and twenty-seven patients underwent an autologous stem cell transplantation between 1997-2010 with a median age of 50 years (range 26-69 years). Median time from diagnosis to autologous stem cell transplantation was 7.5 months with 32% of patients receiving an autologous stem cell transplantation more than 12 months from diagnosis. Engraftment was seen in 97% patients and engraftment syndrome was documented in 23% of autologous stem cell transplantation recipients. Hematologic response was characterized as complete response in 48.5%, partial response in 20.8%, less than partial repsonse in 30.7%. With a median follow up of 48 months (95%CI: 38.3, 58.6), 90% of patients are alive and 16.5% of patients have progressed. The 1-year non-relapse mortality was 3.3%. The 3-year probabilities of progression-free survival and overall survival are 84% and 94%, respectively, with 5-year probabilities of progression-free survival and overall survival of 74% and 89%. In a cohort of graft recipients, detailed organ-specific symptom response demonstrated clear symptom benefit after autologous stem cell transplantation especially in relation to neurological symptom control. The data analyzed in this study demonstrate the clinical utility of autologous stem cell transplantation for patients with POEMS syndrome.

  15. High-dose therapy and autologous stem cell transplantation in patients with POEMS syndrome: a retrospective study of the Plasma Cell Disorder sub-committee of the Chronic Malignancy Working Party of the European Society for Blood & Marrow Transplantation

    PubMed Central

    Cook, Gordon; Iacobelli, Simona; van Biezen, Anja; Ziagkos, Dimitris; LeBlond, Veronique; Abraham, Julie; McQuaker, Grant; Schoenland, Stefan; Rambaldi, Alessandro; Halaburda, Kazimierz; Rovira, Maria; Sica, Simona; Byrne, Jenny; Sanz, Ramon Garcia; Nagler, Arnon; van de Donk, Niels W.C.J.; Sinisalo, Marjatta; Cook, Mark; Kröger, Nicolaus; De Witte, Theo; Morris, Curly; Garderet, Laurant

    2017-01-01

    POEMS syndrome is a rare para-neoplastic syndrome secondary to a plasma cell dyscrasia. Effective treatment can control the disease-related symptom complex. We describe the clinical outcome of autologous stem cell transplantation for patients with POEMS syndrome, determining the impact of patient- and disease-specific factors on prognosis. One hundred and twenty-seven patients underwent an autologous stem cell transplantation between 1997–2010 with a median age of 50 years (range 26–69 years). Median time from diagnosis to autologous stem cell transplantation was 7.5 months with 32% of patients receiving an autologous stem cell transplantation more than 12 months from diagnosis. Engraftment was seen in 97% patients and engraftment syndrome was documented in 23% of autologous stem cell transplantation recipients. Hematologic response was characterized as complete response in 48.5%, partial response in 20.8%, less than partial repsonse in 30.7%. With a median follow up of 48 months (95%CI: 38.3, 58.6), 90% of patients are alive and 16.5% of patients have progressed. The 1-year non-relapse mortality was 3.3%. The 3-year probabilities of progression-free survival and overall survival are 84% and 94%, respectively, with 5-year probabilities of progression-free survival and overall survival of 74% and 89%. In a cohort of graft recipients, detailed organ-specific symptom response demonstrated clear symptom benefit after autologous stem cell transplantation especially in relation to neurological symptom control. The data analyzed in this study demonstrate the clinical utility of autologous stem cell transplantation for patients with POEMS syndrome. PMID:27634201

  16. Single or tandem autologous stem-cell transplantation for first-relapsed or refractory Hodgkin lymphoma: 10-year follow-up of the prospective H96 trial by the LYSA/SFGM-TC study group.

    PubMed

    Sibon, David; Morschhauser, Franck; Resche-Rigon, Matthieu; Ghez, David; Dupuis, Jehan; Marçais, Ambroise; Deau-Fischer, Bénédicte; Bouabdallah, Reda; Sebban, Catherine; Salles, Gilles; Brice, Pauline

    2016-04-01

    We assessed the long-term results of autologous stem-cell transplantation for patients with first-relapsed or refractory Hodgkin lymphoma included in the prospective Lymphoma Study Association/Société Française de Greffe de Moelle H96 trial. This large multicenter phase II trial evaluated a risk-adapted strategy with single or tandem autologous stem-cell transplantation for 245 Hodgkin lymphoma patients. Poor-risk patients (n=150) had primary refractory Hodgkin lymphoma (n=77) or ≥2 risk factors at first relapse (n=73) and were eligible for tandem autologous stem-cell transplantation. Intermediate-risk patients (n=95) had one risk factor at first relapse and were eligible for single autologous stem-cell transplantation. With a median follow-up of 10.3 years, 10-year freedom from second failure and overall survival rates were, respectively: 64% (95% CI, 54% to 74%) and 70% (95% CI, 61% to 80%) for the intermediate-risk group, and 41% (95% CI, 33% to 49%) and 47% (95% CI, 39% to 55%) for the poor-risk group. Considering only patients who did not relapse after completing autologous stem-cell transplantation, the 15-year cumulative incidences of second primary malignancies were 24% for the 70 intermediate-risk patients and 2% for the 75 poor-risk ones. With long-term follow-up, the risk-adapted strategy remains appropriate. Tandem autologous stem-cell transplantation can still be considered an option for poor-risk patients, but integration of positron-emission tomography findings and new drugs may help to refine the need for a second autologous stem-cell transplant and possibly improve outcomes of patients with first-relapsed or refractory Hodgkin lymphoma.

  17. Stem Cell Ophthalmology Treatment Study (SCOTS): improvement in serpiginous choroidopathy following autologous bone marrow derived stem cell treatment

    PubMed Central

    Weiss, Jeffrey N.; Benes, Susan C.; Levy, Steven

    2016-01-01

    We report results in a 77-year-old male patient with visual loss from long-standing serpiginous choroidopathy treated with bone marrow derived stem cells (BMSC) within the Stem Cell Ophthalmology Treatment Study (SCOTS). SCOTS is an Institutional Review Board approved clinical trial and the largest ophthalmology stem cell study registered at the National Institutes of Health to date (ClinicalTrials.gov Identifier: NCT01920867). Eight months after treatment by a combination of retrobulbar, subtenon, intravitreal and intravenous injection of BMSC, the patient's best corrected Snellen acuity improved from 20/80– to 20/60+1 in the right eye and from 20/50– to 20/20–3 in the left eye. The Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity continued to improve over the succeeding 8 months and the optical coherence tomography macular volume increased. The increases in visual acuity and macular volume are encouraging and suggest that the use of BMSC as provided in SCOTS may be a viable approach to treating serpiginous choroidopathy. PMID:27857759

  18. Current progress in use of adipose derived stem cells in peripheral nerve regeneration

    PubMed Central

    Zack-Williams, Shomari DL; Butler, Peter E; Kalaskar, Deepak M

    2015-01-01

    Unlike central nervous system neurons; those in the peripheral nervous system have the potential for full regeneration after injury. Following injury, recovery is controlled by schwann cells which replicate and modulate the subsequent immune response. The level of nerve recovery is strongly linked to the severity of the initial injury despite the significant advancements in imaging and surgical techniques. Multiple experimental models have been used with varying successes to augment the natural regenerative processes which occur following nerve injury. Stem cell therapy in peripheral nerve injury may be an important future intervention to improve the best attainable clinical results. In particular adipose derived stem cells (ADSCs) are multipotent mesenchymal stem cells similar to bone marrow derived stem cells, which are thought to have neurotrophic properties and the ability to differentiate into multiple lineages. They are ubiquitous within adipose tissue; they can form many structures resembling the mature adult peripheral nervous system. Following early in vitro work; multiple small and large animal in vivo models have been used in conjunction with conduits, autografts and allografts to successfully bridge the peripheral nerve gap. Some of the ADSC related neuroprotective and regenerative properties have been elucidated however much work remains before a model can be used successfully in human peripheral nerve injury (PNI). This review aims to provide a detailed overview of progress made in the use of ADSC in PNI, with discussion on the role of a tissue engineered approach for PNI repair. PMID:25621105

  19. Evaluation of a biosimilar granulocyte colony-stimulating factor (filgrastim XM02) for peripheral blood stem cell mobilization and transplantation: a single center experience in Japan

    PubMed Central

    Yoshimura, Hideaki; Hotta, Masaaki; Nakanishi, Takahisa; Fujita, Shinya; Nakaya, Aya; Satake, Atsushi; Ito, Tomoki; Ishii, Kazuyoshi; Nomura, Shosaku

    2017-01-01

    Background Biosimilar granulocyte colony-stimulating factor (G-CSF) has recently been introduced into clinical practice. G-CSFs are used to mobilize CD34+ cells and accelerate engraftment after transplantation. However, in Asia, particularly in Japan, data for peripheral blood stem cell (PBSC) mobilization by this biosimilar G-CSF are currently lacking. Therefore, the clinical efficacy and safety of biosimilar G-CSF for hematopoietic stem cell transplantation needs to be evaluated in a Japanese context. Materials and methods The subjects included two groups of patients with malignant lymphoma and multiple myeloma. All patients received chemotherapy priming for the mobilization of PBSCs. All patients were treated with chemotherapy followed by the administration of either the biosimilar G-CSF, filgrastim XM02 (FBNK), or the originators, filgrastim, or lenograstim. Results There were no significant differences among FBNK, filgrastim, and lenograstim treatments in the numbers of CD34+ cells in harvested PBSCs, the scores for granulocyte/macrophage colony forming units, or for malignant lymphoma and multiple myeloma patients evaluated as separate or combined cohorts. In addition, there were no significant differences in safety, side effects, complications, or the time to engraftment after autologous hematopoietic stem cell transplantation. Conclusion Biosimilar FBNK shows the same efficacy and safety as originator G-CSFs for facilitating bone marrow recovery in Japanese malignant lymphoma and multiple myeloma patients undergoing stem cell transplantation. In addition, it is less expensive than the originators, reducing hospitalization costs. PMID:28182150

  20. Melphalan Culprit or Confounder in Acute Encephalopathy during Autologous Hematopoietic Stem Cell Transplantation?

    PubMed Central

    Alayón-Laguer, Diógenes; Alsina, Melissa; Ochoa-Bayona, Jose L.; Ayala, Ernesto

    2012-01-01

    We report a case of a female patient with Durie-Salmon stage 3A/ISS stage I IgG kappa multiple myeloma (MM) who developed encephalopathy after high-dose melphalan and hematopoietic stem cell transplant (HSCT). The most common etiologies for encephalopathy such as infection, narcotic medications, metabolic-electrolyte disturbance, stroke, and central nervous system (CNS) hemorrhages were ruled out. The patient recovered from the altered mental status spontaneously. The possibilities of melphalan-induced encephalopathy versus critical-state delirium versus hypercytokinemia induce encephalopathy were contemplated. PMID:23259145

  1. Stem Cell Transplantation for Peripheral Nerve Regeneration: Current Options and Opportunities

    PubMed Central

    Jiang, Liangfu; Jones, Salazar; Jia, Xiaofeng

    2017-01-01

    Peripheral nerve regeneration is a complicated process highlighted by Wallerian degeneration, axonal sprouting, and remyelination. Schwann cells play an integral role in multiple facets of nerve regeneration but obtaining Schwann cells for cell-based therapy is limited by the invasive nature of harvesting and donor site morbidity. Stem cell transplantation for peripheral nerve regeneration offers an alternative cell-based therapy with several regenerative benefits. Stem cells have the potential to differentiate into Schwann-like cells that recruit macrophages for removal of cellular debris. They also can secrete neurotrophic factors to promote axonal growth, and remyelination. Currently, various types of stem cell sources are being investigated for their application to peripheral nerve regeneration. This review highlights studies involving the stem cell types, the mechanisms of their action, methods of delivery to the injury site, and relevant pre-clinical or clinical data. The purpose of this article is to review the current point of view on the application of stem cell based strategy for peripheral nerve regeneration. PMID:28067783

  2. Impact of Prophylactic Levofloxacin on Rates of Bloodstream Infection and Fever in Neutropenic Patients with Multiple Myeloma Undergoing Autologous Hematopoietic Stem Cell Transplantation.

    PubMed

    Satlin, Michael J; Vardhana, Santosh; Soave, Rosemary; Shore, Tsiporah B; Mark, Tomer M; Jacobs, Samantha E; Walsh, Thomas J; Gergis, Usama

    2015-10-01

    Few studies have evaluated the role of antibacterial prophylaxis during neutropenia in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation (HSCT). At our center, levofloxacin prophylaxis was initiated in June 2006 in patients with myeloma who were undergoing autologous HSCT. We compared the incidence of bloodstream infection (BSI) and fever and neutropenia (FN) within 30 days of transplantation before (January 2003 to May 2006) and after (June 2006 to April 2010) the initiation of levofloxacin prophylaxis in patients undergoing autologous HSCT for myeloma. We also compared rates of BSI and FN during the same time periods in autologous HSCT recipients with lymphoma who did not receive antibacterial prophylaxis during either time period. After the initiation of levofloxacin prophylaxis, the BSI rate decreased from 41.2% (49 of 119) to 14.7% (23 of 156) and the rate of FN decreased from 91.6% to 60.9% in patients with myeloma (P < .001, for each). In contrast, rates of BSI (43.1% versus 47.3%; P = .50) and FN (98.8% versus 97.1%; P = .63) did not change in patients with lymphoma. Levofloxacin prophylaxis was independently associated with decreased odds of BSI (odds ratio, .27; 95% confidence interval, .14 to .51; P < .001) and FN (odds ratio, .18; 95% confidence interval, .09 to .36; P < .001) in multivariate analysis. Patients with myeloma had a nonsignificant increase in the risk of BSI due to levofloxacin-resistant Enterobacteriaceae (5% versus 1%, P = .08) and Clostridium difficile infection (7% versus 3%, P = .12) after the initiation of levofloxacin prophylaxis but did not have higher rates of BSI due to other resistant bacteria. Levofloxacin prophylaxis is associated with decreased risk of BSI and FN in patients with myeloma undergoing autologous HSCT.

  3. Granulomatosis after autologous stem cell transplantation in nonHodgkin lymphoma – experience of single institution and a review of literature

    PubMed Central

    Boltezar, Lucka; Zagar, Ivana

    2016-01-01

    Abstract Background Sarcoidosis before and after treatment of malignancy is an important differential diagnosis that has to be distinguished from lymphoma. Patients and methods Hodgkin lymphoma, diffuse large B-cell lymphoma and aggressive follicular lymphoma are being staged and treatment effect is evaluated with PET-CT. We report three cases of aggressive lymphoma after high dose therapy and autologous stem cell transplantation with positive lymph nodes on PET-CT, which were histologically diagnosed as sarcoidosis/granulomatosis. In the literature, we found that false positive lymph nodes were more common after allogeneic than after autologous transplantation. Conclusions Post-treatment PET-CT positive lymph nodes should always be examined histologically prior to any further treatment decision to avoid unnecessary toxic procedures. PMID:27904442

  4. Autologous adipose tissue-derived stem cells treatment demonstrated favorable and sustainable therapeutic effect for Crohn's fistula.

    PubMed

    Lee, Woo Yong; Park, Kyu Joo; Cho, Yong Beom; Yoon, Sang Nam; Song, Kee Ho; Kim, Do Sun; Jung, Sang Hun; Kim, Mihyung; Yoo, Hee-Won; Kim, Inok; Ha, Hunjoo; Yu, Chang Sik

    2013-11-01

    Fistula is a representative devastating complication in Crohn's patients due to refractory to conventional therapy and high recurrence. In our phase I clinical trial, adipose tissue-derived stem cells (ASCs) demonstrated their safety and therapeutic potential for healing fistulae associated with Crohn's disease. This study was carried out to evaluate the efficacy and safety of ASCs in patients with Crohn's fistulae. In this phase II study, forty-three patients were treated with ASCs. The amount of ASCs was proportioned to fistula size and fistula tract was filled with ASCs in combination with fibrin glue after intralesional injection of ASCs. Patients without complete closure of fistula at 8 weeks received a second injection of ASCs containing 1.5 times more cells than the first injection. Fistula healing at week 8 after final dose injection and its sustainability for 1-year were evaluated. Healing was defined as a complete closure of external opening without any sign of drainage and inflammation. A modified per-protocol analysis showed that complete fistula healing was observed in 27/33 patients (82%) by 8 weeks after ASC injection. Of 27 patients with fistula healing, 26 patients completed additional observation study for 1-year and 23 patients (88%) sustained complete closure. There were no adverse events related to ASC administration. ASC treatment for patients with Crohn's fistulae was well tolerated, with a favorable therapeutic outcome. Furthermore, complete closure was well sustained. These results strongly suggest that autologous ASC could be a novel treatment option for the Crohn's fistula with high-risk of recurrence.

  5. High-dose chemotherapy followed by autologous stem cell transplantation changes prognosis of IgD multiple myeloma.

    PubMed

    Maisnar, V; Hájek, R; Scudla, V; Gregora, E; Büchler, T; Tichý, M; Kotoucek, P; Kafková, A; Forraiová, L; Minarík, J; Radocha, J; Bláha, V; Malý, J

    2008-01-01

    Immunoglobulin D (IgD) multiple myeloma (MM) is a rare plasma cell disorder constituting less than 2% of all MM cases. Survival of patients with IgD MM is generally shorter than that of patients with other types of monoclonal (M-) protein. We have retrospectively analyzed patients with IgD MM participating in clinical trials of the Czech Myeloma Group. Twenty-six IgD MM patients treated between 1996 and 2006 were identified, 14 (54%) men and 12 (46%) women. The median age was 61 years (range: 37-79 years). Ten of 26 patients (39%) were treated with first-line high-dose chemotherapy (HDCT) using melphalan 200 mg/m(2) followed by autologous stem cell transplantation (ASCT). Thirteen of 26 patients (50%) received conventional chemotherapy (CHT), mostly melphalan and prednisone or a vincristine/doxorubicin/dexamethasone (VAD) regimen. Treatment responses were evaluable for 23 of 26 (89%) patients. All HDCT patients had treatment responses, including seven patients (70%) with complete responses and three patients (30%) with partial responses. The median progression-free survival was 18 months for HDCT patients and 20 months for CHT patients. The median overall survival (OS) for all patients was 34 months. The median OS for the HDCT group has not yet been reached (70% of the patients are still alive). In contrast, the median OS for CHT patients was only 16 months. The difference in OS between the two groups was statistically significant (P=0.005). In conclusion, the overall response rate for patients with IgD MM aged 65 years or less treated with HDCT and ASCT is similar to that seen in other MM types.

  6. Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for High-Grade Gliomas in Children and Adolescents

    PubMed Central

    2017-01-01

    With the aim to investigate the outcome of tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) for high-grade gliomas (HGGs), we retrospectively reviewed the medical records of 30 patients with HGGs (16 glioblastomas, 7 anaplastic astrocytomas, and 7 other HGGs) between 2006 and 2015. Gross or near total resection was possible in 11 patients. Front-line treatment after surgery was radiotherapy (RT) in 14 patients and chemotherapy in the remaining 16 patients including 3 patients less than 3 years of age. Eight of 12 patients who remained progression free and 5 of the remaining 18 patients who experienced progression during induction treatment underwent the first HDCT/auto-SCT with carboplatin + thiotepa + etoposide (CTE) regimen and 11 of them proceeded to the second HDCT/auto-SCT with cyclophosphamide + melphalan (CyM) regimen. One patient died from hepatic veno-occlusive disease (VOD) during the second HDCT/auto-SCT; otherwise, toxicities were manageable. Four patients in complete response (CR) and 3 of 7 patients in partial response (PR) or second PR at the first HDCT/auto-SCT remained event free: however, 2 patients with progressive tumor experienced progression again. The probabilities of 3-year overall survival (OS) after the first HDCT/auto-SCT in 11 patients in CR, PR, or second PR was 58.2% ± 16.9%. Tumor status at the first HDCT/auto-SCT was the only significant factor for outcome after HDCT/auto-SCT. There was no difference in survival between glioblastoma and other HGGs. This study suggests that the outcome of HGGs in children and adolescents after HDCT/auto-SCT is encouraging if the patient could achieve CR or PR before HDCT/auto-SCT. PMID:28049229

  7. Defective expression of apoptosis-related molecules in multiple sclerosis patients is normalized early after autologous haematopoietic stem cell transplantation.

    PubMed

    de Oliveira, G L V; Ferreira, A F; Gasparotto, E P L; Kashima, S; Covas, D T; Guerreiro, C T; Brum, D G; Barreira, A A; Voltarelli, J C; Simões, B P; Oliveira, M C; de Castro, F A; Malmegrim, K C R

    2017-03-01

    Defective apoptosis might be involved in the pathogenesis of multiple sclerosis (MS). We evaluated apoptosis-related molecules in MS patients before and after autologous haematopoietic stem cell transplantation (AHSCT) using BCNU, Etoposide, AraC and Melphalan (BEAM) or cyclophosphamide (CY)-based conditioning regimens. Patients were followed for clinical and immunological parameters for 2 years after AHSCT. At baseline, MS patients had decreased proapoptotic BAD, BAX and FASL and increased A1 gene expression when compared with healthy counterparts. In the BEAM group, BAK, BIK, BIMEL , FAS, FASL, A1, BCL2, BCLXL , CFLIPL and CIAP2 genes were up-regulated after AHSCT. With the exception of BIK, BIMEL and A1, all genes reached levels similar to controls at day + 720 post-transplantation. Furthermore, in these patients, we observed increased CD8(+) Fas(+) T cell frequencies after AHSCT when compared to baseline. In the CY group, we observed increased BAX, BCLW, CFLIPL and CIAP1 and decreased BIK and BID gene expressions after transplantation. At day + 720 post-AHSCT, the expression of BAX, FAS, FASL, BCL2, BCLXL and CIAP1 was similar to that of controls. Protein analyses showed increased Bcl-2 expression before transplantation. At 1 year post-AHSCT, expression of Bak, Bim, Bcl-2, Bcl-xL and cFlip-L was decreased when compared to baseline values. In summary, our findings suggest that normalization of apoptosis-related molecules is associated with the early therapeutic effects of AHSCT in MS patients. These mechanisms may be involved in the re-establishment of immune tolerance during the first 2 years post-transplantation.

  8. [Successful autologous haematopoietic stem cell transplantation in severe, therapy-resistant childhood Crohn's disease. Report on the first case in Hungary].

    PubMed

    Kriván, Gergely; Szabó, Dolóresz; Kállay, Krisztián; Benyó, Gábor; Kassa, Csaba; Sinkó, János; Goda, Vera; Arató, András; Veres, Gábor

    2014-05-18

    The biological therapy of Crohn's disease, such as infliximab is a powerful approach in the therapy of inflammatory bowel diseases. However, in some patients with aggressive disease course, even a combined immunosuppressive therapy will not result in permanent remission. Hematopoietic stem cell transplantation has emerged as a new potential therapeutic tool for inflammatory bowel diseases. The authors report the case of a 15-year-old boy with severe Crohn's disease resistant to combined immunosuppressive therapy. After a 3-years course of unsuccessful conventional therapy including infliximab, autologous hematopoietic stem cell transplantation was performed which resulted in a complete remission. One year after transplantation the patient has relapsed, but he could be treated effectively with conventional therapy regiments. To the best of knowledge of the authors, this is the first report in Hungary presenting hematopoietic stem cell therapy in patient with severe Crohn's disease.

  9. Randomized Comparison of Allogeneic Vs. Autologous Mesenchymal Stem Cells for Non-lschemic Dilated Cardiomyopathy: POSEIDON-DCM Trial

    PubMed Central

    Hare, Joshua M.; DiFede, Darcy L; Castellanos, Angela M; Florea, Victoria; Landin, Ana M; El-Khorazaty, Jill; Khan, Aisha; Mushtaq, Muzammil; Lowery, Maureen H; Byrnes, John J; Hendel, Robert C; Cohen, Mauricio G; Alfonso, Carlos E; Valasaki, Krystalenia; Pujol, Marietsy V; Golpanian, Samuel; Ghersin, Eduard; Fishman, Joel E; Pattany, Pradip; Gomes, Samirah A; Delgado, Cindy; Miki, Roberto; Abuzeid, Fouad; Vidro-Casiano, Mayra; Premer, Courtney; Medina, Audrey; Porras, Valeria; Hatzistergos, Konstantinos E.; Anderson, Erica; Mendizabal, Adam; Mitrani, Raul; Heldman, Alan W.

    2016-01-01

    Background While human mesenchymal stem cells (hMSCs) have been tested in ischemic cardiomyopathy, few studies exist in chronic non-ischemic dilated cardiomyopathy (NIDCM). Objectives The POSEIDON-DCM trial is a randomized comparison of safety and efficacy of autologous (auto) vs. allogeneic (allo) bone marrow-derived hMSCs in NIDCM. Methods Thirty-seven patients were randomized to either allo- or auto-hMSCs in a 1:1 ratio. Patients were recruited between December 2011 and July 2015 at the University of Miami Hospital. Patients (age: 55.8 ± 11.2; 32% female) received hMSCs (100 million) by transendocardial stem cell injection (TESI) in ten left ventricular sites by NOGA Catheter. Treated patients were evaluated at baseline, 30 days, 3-, 6-, and 12-months for safety: serious adverse events (SAE), and efficacy endpoints: Ejection Fraction (EF), Minnesota Living with Heart Failure Questionnaire (MLHFQ), Six Minute Walk Test (6MWT), MACE, and immune-biomarkers. This trial is registered with ClinicalTrials.gov, #NCT01392625. Results There were no 30-day treatment-emergent (TE)-SAEs. 12-month SAE incidence was 28.2% (95% CI: 12.8, 55.1) in allo, and 63.5% (95% CI: 40.8, 85.7; p=0.1004) in auto. One allo-group patient developed an elevated donor specific cPRA. EF increased in allo by 8.0 units (95% Cl: 2.8, 13.2; p=0.004), and in auto: 5.4 units (95% Cl: −1.4, 12.1; p=0.116, allo vs. auto p=0.4887). 6MWT increased for allo: 37.0 meters (95% Cl: 2.0 to 72.0; p=0.04), but not auto: 7.3 meters (95% Cl: −47.8, 33.3; p=0.71, auto vs. allo p=0.0168). MLHFQ score decreased in allo (p=0.0022), and auto (p=0.463; p=0.172). The MACE rate was lower in allo vs. auto (p=0.0186). Tumor necrosis factor alpha (TNF-α) decreased (p=0.0001 for each), to a greater extent in allo vs. auto at six-months (p=0.05). Conclusion These findings demonstrate safety and support greater, clinically meaningful efficacy of allo-hMSC vs. auto-hMSC in NIDCM patients. Pivotal trials of allo-hMSCs are

  10. Autologous Stem-Cell Transplantation Without Hematopoietic Support for the Treatment of Hematologic Malignancies in Jehovah's Witnesses

    PubMed Central

    Ford, Patricia A.; Grant, Shakira J.; Mick, Rosemarie; Keck, Gina

    2015-01-01

    Purpose Autologous stem-cell transplantation (ASCT) has shown to provide curative benefit in patients with relapsed lymphoma and multiple myeloma (MM), often requiring hematopoietic support until marrow engraftment. Because of Jehovah's Witnesses' (JW) refusal of blood products, treatment challenges arise. This study represents 125 JWs with lymphoma (n = 55), MM (n = 68), or amyloidosis (n = 2), treated with high-dose chemotherapy (HDC) and ASCT without transfusions. Patients and Methods Priming with intravenous iron and erythropoietin occurred to increase hemoglobin (Hb) pretransplantation. Cytokine mobilization of stem-cells was used. Delay to HDC was done to allow Hb and platelets to approach 11 g/dL and 100 × 103/μL, respectively. Patients with MM received a standard dose of melphalan 200 mg/m2, with dose reduction for severe kidney dysfunction. Patients with lymphoma received carmustine 300 mg/m2, cyclophosphamide 1,500 mg/m2 on days 2 through 5 (total 6 g/m2), and etoposide 700 mg/m2 per day on days 2 through 4 (total 2,100 mg/m2). Post-transplantation, a combination of granulocyte colony-stimulating factor, erythropoietin, aminocaproic acid, and phytonadione was administered. Results There were two major and 15 minor bleeding complications, none occurring at platelets less than 5.0 × 103/μL, with six (4.8%) treatment-related mortalities. The median decrease in Hb was 5.0 g/dL, with median Hb nadir of 7.0 g/dL. The median number of days with platelet count less than 10 × 103/μL was 3, with median platelet nadir of 5.0 × 103/μL. Cardiac complications occurred in 40 patients (32%). Conclusion ASCT can safely be performed without transfusion support. A platelet transfusion trigger of ≤ 5 × 103/μL may be appropriate in select patients. Pharmacotherapy and cardiac monitoring are effective in the management of cardiac complications. PMID:25870085

  11. An improved technique for peripheral blood stem cell collection in small patients.

    PubMed

    Landolfo, A; Angioni, A; Deb, G; Jenkner, A; Orlando, P; Donfrancesco, A; Balloni, P

    1991-03-01

    Peripheral Blood Stem Cell collection in adults is a consolidated method for autografting. The same procedure is less easily performed in pediatric patients due to low weight, vascular access problems and anticoagulant side effects. Great efforts have been made to overcome technical difficulties and make apheresis in children a reliable and safe procedure.

  12. Treatment of aggressive multiple myeloma by high-dose chemotherapy and total body irradiation followed by blood stem cells autologous graft

    SciTech Connect

    Fermand, J.P.; Levy, Y.; Gerota, J.; Benbunan, M.; Cosset, J.M.; Castaigne, S.; Seligmann, M.; Brouet, J.C.

    1989-01-01

    Eight patients with stage III aggressive multiple myeloma, refractory to current chemotherapy in six cases, were treated by high-dose chemotherapy (nitrosourea, etoposide, and melphalan) (HDC) and total body irradiation (TBI), followed by autografting with blood stem cells. These cells were previously collected by leukapheresis performed during hematologic recovery following cytotoxic drug-induced bone marrow aplasia. Seven patients were alive 9 to 17 months after HDC-TBI and graft. One died at day 40 from cerebral bleeding. All living patients achieved a 90% or greater reduction in tumor mass. In two cases, a complete remission (CR) has persisted at a follow-up of 15 and 16 months. Three patients have been well and off therapy with stable minimal residual disease (RD) since 10, 11, and 17 months, respectively. A patient in apparent CR and another with RD have relapsed 9 to 12 months posttreatment. Autologous blood-derived hematopoietic stem cells induced successful and sustained engraftment in all living patients. These results, although still preliminary, indicate that HDC and TBI, followed by blood stem cells autograft, which has both practical and theoretical interest over allogeneic or autologous bone marrow transplantation, deserve consideration in selected patients with multiple myeloma.

  13. Clinical outcomes of osteonecrosis of the femoral head after autologous bone marrow stem cell implantation: a meta-analysis of seven case-control studies.

    PubMed

    Yuan, Heng-Feng; Zhang, Jing; Guo, Chang-An; Yan, Zuo-Qin

    2016-02-01

    The purpose of this study was to evaluate the clinical outcomes of osteonecrosis of the femoral head after autologous bone marrow stem cell implantation. We searched the PubMed, Embase and Web of Science databases and included all case-control trials that reported on the clinical outcomes of osteonecrosis progression, incidence of total hip arthroplasty and improvement in Harris hip scores. Overall, seven case-control trials were included. Compared with the controls, patients treated with the bone marrow stem cells implantation treatment showed improved clinical outcomes with delayed osteonecrosis progression (odds ratio = 0.17, 95% CI: 0.09 - 0.32; p <0.001), a lower total hip arthroplasty incidence (odds ratio = 0.30, 95% CI: 0.12 - 0.72; p <0.01) and increased Harris hip scores (mean difference = 4.76, 95% CI: 1.24 - 8.28; p<0.01). The heterogeneity, publication bias, and sensitivity analyses showed no statistical difference significant differences between studies. Thus, our study suggests that autologous bone marrow stem cells implantation has a good therapeutic effect on osteonecrosis of the femoral, resulting in beneficial clinical outcomes. However, trials with larger sample sizes are needed to confirm these findings.

  14. Phase I/II Trial of Autologous Bone Marrow Stem Cell Transplantation with a Three-Dimensional Woven-Fabric Scaffold for Periodontitis

    PubMed Central

    Baba, Shunsuke; Komuro, Akira; Yotsui, Yoritaka; Umeda, Makoto; Shimuzutani, Kimishige; Nakamura, Sayaka

    2016-01-01

    Regenerative medicine is emerging as a promising option, but the potential of autologous stem cells has not been investigated well in clinical settings of periodontal treatment. In this clinical study, we evaluated the safety and efficacy of a new regenerative therapy based on the surgical implantation of autologous mesenchymal stem cells (MSCs) with a biodegradable three-dimensional (3D) woven-fabric composite scaffold and platelet-rich plasma (PRP). Ten patients with periodontitis, who required a surgical procedure for intrabony defects, were enrolled in phase I/II trial. Once MSCs were implanted in each periodontal intrabony defect, the patients were monitored during 36 months for a medical exam including laboratory tests of blood and urine samples, changes in clinical attachment level, pocket depth, and linear bone growth (LBG). All three parameters improved significantly during the entire follow-up period (p < 0.0001), leading to an average LBG of 4.7 mm after 36 months. Clinical mobility measured by Periotest showed a decreasing trend after the surgery. No clinical safety problems attributable to the investigational MSCs were identified. This clinical trial suggests that the stem cell therapy using MSCs-PRP/3D woven-fabric composite scaffold may constitute a novel safe and effective regenerative treatment option for periodontitis. PMID:27990164

  15. Follow-up of relapsed B-cell lymphoma patients treated with iodine-131-labeled anti-CD20 antibody and autologous stem-cell rescue

    SciTech Connect

    Liu, S Y.; Eary, Janet F.; Petersdorf, S H.; Martin, P J.; Maloney, D G.; Applebaum, F. R.; Matthews, D. C.; Bush, S A.; Durack, L. D.; Fisher, Darrell R. ); Gooley, T A.; Bernstein, I. D.; Press, O. W.

    1997-11-01

    Radioimmunotherapy (RIT) is a promising treatment approach for B-cell lymphomas. This is our first opportunity to report long-term follow-up data and late toxicities in 29 patients treated with myeloablative doses of iodine-131-anti-CD20 antibody (anti-B1) and autologous stem-cell rescue. PATIENTS AND METHODS: Trace-labeled biodistribution studies first determined the ability to deliver higher absorbed radiation doses to tumor sites than to lung, liver, or kidney at varying amounts of anti-B1 protein (0.35, 1.7, or 7 mg/kg). Twenty- nine patients received therapeutic infusions of single-agent (131)I- anti-B1, given at the protein dose found optimal in the biodistribution study, labeled with amounts of (131)I (280 to 785 mCi[10.4 to 29.0 GBq]) calculated to deliver specific absorbed radiation doses to the normal organs, followed by autologous stem-cell support. RESULTS: Major responses occurred in 25 patients (86%), with 23 complete responses (CRs; 79%). The nonhematopoietic do se-limiting toxicity was reversible cardiopulmonary insufficiency, which occurred in two patients at RIT doses that delivered > or = 27 Gy to the lungs. With a median follow-up time of 42 months, the estimated overall and progression-free survival rates are 68% and 42%, respectively. Currently, 14 of 29 patients remain in unmaintained remissions that range from 27+ to 87+ months after RIT. Late toxicities have been uncommon except for elevated thyroid-stimulating hormone (TSH) levels found in approximately 60% of the subjects. Two patients developed second malignancies, but none have developed myelodysplasia (MDS). CONCLUSION: Myeloablative (131)I-anti- B1 RIT is relatively well tolerated when given with autologous stem- cell support and often results in prolonged remission durations with few late toxicities.

  16. Fungal Colonization of the Respiratory Tract in Allogeneic and Autologous Hematopoietic Stem Cell Transplant Recipients: A Study of 573 Transplanted Patients

    PubMed Central

    Markowski, Jarosław; Helbig, Grzegorz; Widziszowska, Agnieszka; Likus, Wirginia; Kyrcz-Krzemień, Sławomira; Jarosz, Urszula; Dziubdziela, Włodzimierz; Markiewicz, Mirosław

    2015-01-01

    Background Fungal colonization and infections remain a major cause of infection morbidity and mortality following hematopoietic stem cell transplantation (HSCT) in patients with hematological malignancies. The aim of this study was to analyze the spectrum of fungal microflora of the respiratory tract (oral cavity, pharynx, epiglottis, and sputum) in patients undergoing HSCT and to evaluate the relationship between HSCT type and incidence of mycotic colonization and infections. Material/Methods Retrospective analysis of fungal isolates collected from the respiratory tract (oral cavity, pharynx, epiglottis, and sputum) of 573 patients undergoing HSCT was performed. Results The overall rate of fungal colonization in patients undergoing HSCT was 8.7%. Patients undergoing allogeneic HSCT were statistically significantly more often colonized (12.95%) compared to autologous HSCT recipients (4.7%). Colonizing cultures were mainly C. albicans and C. krusei, and sporadically C. glabrata, C. famata, Aspergillus spp. and Saccharomyces cerevisiae. C. albicans was the most frequent species found in isolates from the pharynx, sputum, and oral cavity collected from patients undergoing HSCT. Aspergillosis was more common after allogeneic than after autologous HSCT. The pharynx was the most frequently colonized site. Conclusions Allogeneic HSCT recipients are more susceptible to fungal infections compared to the autologous group. Selection of species during prophylaxis and antifungal therapy requires developing more effective prevention and treatment strategies based on new antifungal drugs and microbe-specific diagnoses. PMID:25907308

  17. Dermal Mesenchymal Stem Cells (DMSCs) Inhibit Skin-Homing CD8+ T Cell Activity, a Determining Factor of Vitiligo Patients’ Autologous Melanocytes Transplantation Efficiency

    PubMed Central

    Wu, Ji-long; Lin, Fu-quan; Fu, Li-fang; Wang, Sui-quan; Guan, Cui-ping; Wang, Hong-lin; Xu, Aie

    2013-01-01

    We here investigated the efficiency of autologous melanocyte transplantation of 23 vitiligo patients by focusing on perilesional skin homing CD8+ T lymphocytes, and studied the potential effect of dermal mesenchymal stem cells (DMSCs) on CD8+ T cell activities in vitro. Out of 23 patients with the autologous melanocyte transplantation, 12 patients (52.17%) had an excellent re-pigmentation, 6 patients (26.09%) had a good re-pigmentation, 5 patients (21.74%) had a fair or poor re-pigmentation. CD8+ T cells infiltrating was observed in the perilesional vitiligo area of all patients. Importantly, the efficiency of the transplantation was closely associated with skin-homing CD8+ T cell activities. The patients with high number of perilesional CD8+ T cells or high level of cytokines/chemokines were associated with poor re-pigmentation efficiency. For in-vitro experiments, we successfully isolated and characterized human DMSCs and skin-homing CD8+ T cells. We established DMSCs and CD8+ T cell co-culture system, where DMSCs possessed significant inhibitory effects against skin homing CD8+ T lymphocytes. DMSCs inhibited CD8+ T cells proliferation, induced them apoptosis and regulated their cytokines/chemokines production. Our results suggest that vitiligo patients’ autologous melanocytes transplantation efficiency might be predicted by perilesional skin-homing CD8+ T cell activities, and DMSCs might be used as auxiliary agent to improve transplantation efficacy. PMID:23577097

  18. Randomized Placebo-Controlled Phase II Trial of Autologous Mesenchymal Stem Cells in Multiple Sclerosis

    PubMed Central

    Blanco, Yolanda; Marín, Pedro; Moreno, Beatriz; Berenguer, Joan; Gabilondo, Iñigo; Martínez-Heras, Eloy; Sola-Valls, Nuria; Arnaiz, Joan-Albert; Andreu, Enrique J.; Fernández, Begoña; Bullich, Santi; Sánchez-Dalmau, Bernardo; Graus, Francesc; Villoslada, Pablo; Saiz, Albert

    2014-01-01

    Objective Uncontrolled studies of mesenchymal stem cells (MSCs) in multiple sclerosis suggested some beneficial effect. In this randomized, double-blind, placebo-controlled, crossover phase II study we investigated their safety and efficacy in relapsing-remitting multiple sclerosis patients. Efficacy was evaluated in terms of cumulative number of gadolinium-enhancing lesions (GEL) on magnetic resonance imaging (MRI) at 6 months and at the end of the study. Methods Patients unresponsive to conventional therapy, defined by at least 1 relapse and/or GEL on MRI scan in past 12 months, disease duration 2 to 10 years and Expanded Disability Status Scale (EDSS) 3.0–6.5 were randomized to receive IV 1–2×106 bone-marrow-derived-MSCs/Kg or placebo. After 6 months, the treatment was reversed and patients were followed-up for another 6 months. Secondary endpoints were clinical outcomes (relapses and disability by EDSS and MS Functional Composite), and several brain MRI and optical coherence tomography measures. Immunological tests were explored to assess the immunomodulatory effects. Results At baseline 9 patients were randomized to receive MSCs (n = 5) or placebo (n = 4). One patient on placebo withdrew after having 3 relapses in the first 5 months. We did not identify any serious adverse events. At 6 months, patients treated with MSCs had a trend to lower mean cumulative number of GEL (3.1, 95% CI = 1.1–8.8 vs 12.3, 95% CI = 4.4–34.5, p = 0.064), and at the end of study to reduced mean GEL (−2.8±5.9 vs 3±5.4, p = 0.075). No significant treatment differences were detected in the secondary endpoints. We observed a non-significant decrease of the frequency of Th1 (CD4+ IFN-γ+) cells in blood of MSCs treated patients. Conclusion Bone-marrow-MSCs are safe and may reduce inflammatory MRI parameters supporting their immunomodulatory properties. ClinicalTrials.gov NCT01228266 PMID:25436769

  19. Approaches to Peripheral Nerve Repair: Generations of Biomaterial Conduits Yielding to Replacing Autologous Nerve Grafts in Craniomaxillofacial Surgery

    PubMed Central

    Knipfer, Christian; Hadlock, Tessa

    2016-01-01

    Peripheral nerve injury is a common clinical entity, which may arise due to traumatic, tumorous, or even iatrogenic injury in craniomaxillofacial surgery. Despite advances in biomaterials and techniques over the past several decades, reconstruction of nerve gaps remains a challenge. Autografts are the gold standard for nerve reconstruction. Using autografts, there is donor site morbidity, subsequent sensory deficit, and potential for neuroma development and infection. Moreover, the need for a second surgical site and limited availability of donor nerves remain a challenge. Thus, increasing efforts have been directed to develop artificial nerve guidance conduits (ANCs) as new methods to replace autografts in the future. Various synthetic conduit materials have been tested in vitro and in vivo, and several first- and second-generation conduits are FDA approved and available for purchase, while third-generation conduits still remain in experimental stages. This paper reviews the current treatment options, summarizes the published literature, and assesses future prospects for the repair of peripheral nerve injury in craniomaxillofacial surgery with a particular focus on facial nerve regeneration. PMID:27556032

  20. Stem Cell-Derived Immature Human Dorsal Root Ganglia Neurons to Identify Peripheral Neurotoxicants

    PubMed Central

    Klima, Stefanie; Karreman, Christiaan; Grinberg, Marianna; Meisig, Johannes; Henry, Margit; Rotshteyn, Tamara; Rahnenführer, Jörg; Blüthgen, Nils; Sachinidis, Agapios; Waldmann, Tanja; Leist, Marcel

    2016-01-01

    Safety sciences and the identification of chemical hazards have been seen as one of the most immediate practical applications of human pluripotent stem cell technology. Protocols for the generation of many desirable human cell types have been developed, but optimization of neuronal models for toxicological use has been astonishingly slow, and the wide, clinically important field of peripheral neurotoxicity is still largely unexplored. A two-step protocol to generate large lots of identical peripheral human neuronal precursors was characterized and adapted to the measurement of peripheral neurotoxicity. High content imaging allowed an unbiased assessment of cell morphology and viability. The computational quantification of neurite growth as a functional parameter highly sensitive to disturbances by toxicants was used as an endpoint reflecting specific neurotoxicity. The differentiation of cells toward dorsal root ganglia neurons was tracked in relation to a large background data set based on gene expression microarrays. On this basis, a peripheral neurotoxicity (PeriTox) test was developed as a first toxicological assay that harnesses the potential of human pluripotent stem cells to generate cell types/tissues that are not otherwise available for the prediction of human systemic organ toxicity. Testing of more than 30 chemicals showed that human neurotoxicants and neurite growth enhancers were correctly identified. Various classes of chemotherapeutic agents causing human peripheral neuropathies were identified, and they were missed when tested on human central neurons. The PeriTox test we established shows the potential of human stem cells for clinically relevant safety testing of drugs in use and of new emerging candidates. Significance The generation of human cells from pluripotent stem cells has aroused great hopes in biomedical research and safety sciences. Neurotoxicity testing is a particularly important application for stem cell-derived somatic cells, as

  1. Autologous Stem Cell Application in Periodontal Regeneration Technique (SAI-PRT) Using PDLSCs Directly From an Extracted Tooth···An Insight

    PubMed Central

    Vandana, KL; Desai, Rajendra; Dalvi, Priyanka Jairaj

    2015-01-01

    Periodontal regeneration represents the ultimate goal of periodontal therapy. The current regenerative techniques have limited success rates especially in advanced periodontal defects. Currently the research is focused on novel cell-based approaches for periodontal regeneration to overcome the limitations of existing treatment. The human clinical trial on stem cells based periodontal regeneration is promising. The plethora of animal studies provide sound evidence to support the belief that periodontal ligament stem cells (PDLSCs) can be used for periodontal regeneration. The direct application of autologous periodontal stem cells in treatment of intrabony defects is attempted for the first time in periodontal literature. Stem cell Application in Periodontal Regeneration Technique (SAI-PRT) using direct PDLSCs has overcome the limitations and concerns of ex- vivo stem cell culture methods like high cost, technique sensitivity, loss of stemness during cell passage, genetic manipulation and tumorigenic potential. Clinical feasibility, success and cost effectiveness over currently available techniques are encouraging. The clinical utility of this novel idea is recommended. PMID:26634072

  2. KIR and HLA Genotypes are Associated with Disease Progression and Survival following Autologous Hematopoietic Stem Cell Transplantation for High-Risk Neuroblastoma

    PubMed Central

    Venstrom, Jeffrey M.; Zheng, Junting; Noor, Nabila; Danis, Karen E.; Yeh, Alice W.; Cheung, Irene Y.; Dupont, Bo; O’Reilly, Richard J.; Cheung, Nai-Kong V.; Hsu, Katharine C.

    2009-01-01

    Purpose Natural killer (NK) cells exhibit cytotoxicity against neuroblastoma. Gene polymorphisms governing NK cell function, therefore, may influence prognosis. Two highly polymorphic genetic loci instrumental in determining NK cell responses encode the NK cell killer immunoglobulin-like receptors (KIR) and their class I human leukocyte antigen (HLA) ligands. We hypothesized that patients with a “missing ligand” KIR-HLA compound genotype may uniquely benefit from autologous hematopoietic stem cell transplantation (HSCT). Experimental Design 169 patients treated with autologous HSCT for stage 4 neuroblastoma underwent KIR and HLA genotyping. Patients were segregated according to presence or absence of HLA ligands for autologous inhibitory KIR. Univariate and multivariate analyses were performed for overall and progression-free survival. Results 64% of patients lacked one or more HLA ligands for inhibitory KIR. Patients lacking an HLA ligand had a 46% lower risk of death (HR 0.54; 95% CI, 0.35–0.85, P=.007) and a 34% lower risk of progression (HR 0.66; 95% CI, 0.44–1.0; P=.047) at 3 years compared with patients who possessed all ligands for his/her inhibitory KIR. Among all KIR-HLA combinations, 16 patients lacking the HLA-C1 ligand for KIR2DL2/2DL3 experienced the highest 3-year survival rate of 81% (95% CI: 64–100). Survival was more strongly associated with “missing ligand” than with tumor MYCN gene amplification. Conclusion KIR-HLA immunogenetics represents a novel prognostic marker for patients undergoing autologous HSCT for high-risk neuroblastoma. PMID:19934297

  3. Scaffold-free Three-dimensional Graft From Autologous Adipose-derived Stem Cells for Large Bone Defect Reconstruction: Clinical Proof of Concept.

    PubMed

    Dufrane, Denis; Docquier, Pierre-Louis; Delloye, Christian; Poirel, Hélène A; André, Wivine; Aouassar, Najima

    2015-12-01

    Long bone nonunion in the context of congenital pseudarthrosis or carcinologic resection (with intercalary bone allograft implantation) is one of the most challenging pathologies in pediatric orthopedics. Autologous cancellous bone remains the gold standard in this context of long bone nonunion reconstruction, but with several clinical limitations. We then assessed the feasibility and safety of human autologous scaffold-free osteogenic 3-dimensional (3D) graft (derived from autologous adipose-derived stem cells [ASCs]) to cure a bone nonunion in extreme clinical and pathophysiological conditions. Human ASCs (obtained from subcutaneous adipose tissue of 6 patients and expanded up to passage 4) were incubated in osteogenic media and supplemented with demineralized bone matrix to obtain the scaffold-free 3D osteogenic structure as confirmed in vitro by histomorphometry for osteogenesis and mineralization. The 3D "bone-like" structure was finally transplanted for 3 patients with bone tumor and 3 patients with bone pseudarthrosis (2 congenital, 1 acquired) to assess the clinical feasibility, safety, and efficacy. Although minor clones with structural aberrations (aneuploidies, such as tri or tetraploidies or clonal trisomy 7 in 6%-20% of cells) were detected in the undifferentiated ASCs at passage 4, the osteogenic differentiation significantly reduced these clonal anomalies. The final osteogenic product was stable, did not rupture with forceps manipulation, did not induce donor site morbidity, and was easily implanted directly into the bone defect. No acute (<3 mo) side effects, such as impaired wound healing, pain, inflammatory reaction, and infection, or long-term side effects, such as tumor development, were associated with the graft up to 4 years after transplantation. We report for the first time that autologous ASC can be fully differentiated into a 3D osteogenic-like implant without any scaffold. We demonstrated that this engineered tissue can safely promote

  4. Prognostic value of pretransplant FDG-PET in refractory/relapsed Hodgkin lymphoma treated with autologous stem cell transplantation: systematic review and meta-analysis.

    PubMed

    Adams, Hugo J A; Kwee, Thomas C

    2016-04-01

    This study aimed to systematically review the prognostic value of pretransplant (18)F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in refractory/relapsed Hodgkin lymphoma treated with autologous stem cell transplantation (SCT). MEDLINE was systematically searched for appropriate studies. Included studies were methodologically appraised. Results of individual studies were meta-analyzed, if possible. Eleven studies, comprising a total of 745 refractory/relapsed Hodgkin lymphoma patients who underwent FDG-PET before autologous SCT, were included. The overall methodological quality of these studies was moderate. The proportion of pretransplant FDG-PET positive patients ranged between 25 and 65.2 %. Progression-free survival ranged between 0 and 52 % in pretransplant FDG-PET positive patients, and between 55 and 85 % in pretransplant FDG-PET negative patients. Overall survival ranged between 17 and 77 % in pretransplant FDG-PET positive patients, and between 78 and 100 % in FDG-PET negative patients. Based on five studies that provided sufficient data for meta-analysis, pooled sensitivity and specificity of pretransplant FDG-PET in predicting treatment failure (i.e., either progressive, residual, or relapsed disease) were 67.2 % (95 % confidence interval [CI] 58.2-75.3 %) and 70.7 % (95 % CI 64.2-76.5 %), respectively. Based on two studies that provided sufficient data for meta-analysis, pooled sensitivity and specificity of pretransplant FDG-PET in predicting death during follow-up were 74.4 % (95 % CI 58.8-86.5 %) and 58.0 % (95 % CI 49.3-66.3 %), respectively. In conclusion, the moderate quality evidence suggests pretransplant FDG-PET to have value in predicting outcome in refractory/relapsed Hodgkin lymphoma patients treated with autologous SCT. Nevertheless, a considerable proportion of pretransplant FDG-PET positive patients remains disease free and a considerable proportion of pretransplant FDG-PET negative patients develops disease relapse

  5. Novel Peripherally Derived Neural-Like Stem Cells as Therapeutic Carriers for Treating Glioblastomas.

    PubMed

    Birbrair, Alexander; Sattiraju, Anirudh; Zhu, Dongqin; Zulato, Gilberto; Batista, Izadora; Nguyen, Van T; Messi, Maria Laura; Solingapuram Sai, Kiran Kumar; Marini, Frank C; Delbono, Osvaldo; Mintz, Akiva

    2017-02-01

    Glioblastoma (GBM), an aggressive grade IV astrocytoma, is the most common primary malignant adult brain tumor characterized by extensive invasiveness, heterogeneity, and angiogenesis. Standard treatment options such as radiation and chemotherapy have proven to be only marginally effective in treating GBM because of its invasive nature. Therefore, extensive efforts have been put forth to develop tumor-tropic stem cells as viable therapeutic vehicles with potential to treat even the most invasive tumor cells that are harbored within areas of normal brain. To this end, we discovered a newly described NG2-expressing cell that we isolated from a distinct pericyte subtype found abundantly in cultures derived from peripheral muscle. In this work, we show the translational significance of these peripherally derived neural-like stem cells (NLSC) and their potential to migrate toward tumors and act as therapeutic carriers. We demonstrate that these NLSCs exhibit in vitro and in vivo GBM tropism. Furthermore, NLSCs did not promote angiogenesis or transform into tumor-associated stromal cells, which are concerns raised when using other common stem cells, such as mesenchymal stem cells and induced neural stem cells, as therapeutic carriers. We also demonstrate the potential of NLSCs to express a prototype therapeutic, tumor necrosis factor α-related apoptosis-inducing ligand and kill GBM cells in vitro. These data demonstrate the therapeutic potential of our newly characterized NLSC against GBM. Stem Cells Translational Medicine 2017;6:471-481.

  6. Novel Adult Stem Cells for Peripheral Nerve Regeneration

    DTIC Science & Technology

    2012-09-01

    Circulation 103, 882–888 (2001). 52. Biernaskie, J. et al. SKPs derive from hair follicle precursors and exhibit properties of adult dermal stem cells...3). * indicates significant difference between indicated groups using Holm’s t- test . (P < 0.01). (l–s) Immunostaining of isolated sm-mHC − cells...and the tissue from which the cells were derived using student’s t- test (P < 0.05). † indicates significant difference between inferior vena cava and

  7. Mobilization and collection of CD34+ cells for autologous transplantation of peripheral blood hematopoietic progenitor cells in children: analysis of two different granulocyte-colony stimulating factor doses

    PubMed Central

    Eid, Kátia Aparecida de Brito; Miranda, Eliana Cristina Martins; Aguiar, Simone dos Santos

    2015-01-01

    Introduction The use of peripheral hematopoietic progenitor cells (HPCs) is the cell choice in autologous transplantation. The classic dose of granulocyte-colony stimulating factor (G-CSF) for mobilization is a single daily dose of 10 μg/kg of patient body weight. There is a theory that higher doses of granulocyte-colony stimulating factor applied twice daily could increase the number of CD34+ cells collected in fewer leukapheresis procedures. Objective The aim of this study was to compare a fractionated dose of 15 μg G-CSF/kg of body weight and the conventional dose of granulocyte-colony stimulating factor in respect to the number of leukapheresis procedures required to achieve a minimum collection of 3 × 106 CD34+ cells/kg body weight. Methods Patients were divided into two groups: Group 10 – patients who received a single daily dose of 10 μg G-CSF/kg body weight and Group 15 – patients who received a fractioned dose of 15 μg G-CSF/kg body weight daily. The leukapheresis procedure was carried out in an automated cell separator. The autologous transplantation was carried out when a minimum number of 3 × 106 CD34+ cells/kg body weight was achieved. Results Group 10 comprised 39 patients and Group 15 comprised 26 patients. A total of 146 apheresis procedures were performed: 110 (75.3%) for Group 10 and 36 (24.7%) for Group 15. For Group 10, a median of three (range: 1–7) leukapheresis procedures and a mean of 8.89 × 106 CD34+ cells/kg body weight (±9.59) were collected whereas for Group 15 the corresponding values were one (range: 1–3) and 5.29 × 106 cells/kg body weight (±4.95). A statistically significant difference was found in relation to the number of apheresis procedures (p-value <0.0001). Conclusions To collect a minimum target of 3 × 106 CD34+ cells/kg body weight, the administration of a fractionated dose of 15 μg G-CSF/kg body weight significantly decreased the number of leukapheresis procedures performed. PMID:26041417

  8. Infusion of autologous adipose tissue derived neuronal differentiated mesenchymal stem cells and hematopoietic stem cells in post-traumatic paraplegia offers a viable therapeutic approach

    PubMed Central

    Thakkar, Umang G.; Vanikar, Aruna V.; Trivedi, Hargovind L.; Shah, Veena R.; Dave, Shruti D.; Dixit, Satyajit B.; Tiwari, Bharat B.; Shah, Harda H.

    2016-01-01

    Background: Spinal cord injury (SCI) is not likely to recover by current therapeutic modalities. Stem cell (SC) therapy (SCT) has promising results in regenerative medicine. We present our experience of co-infusion of autologous adipose tissue derived mesenchymal SC differentiated neuronal cells (N-Ad-MSC) and hematopoietic SCs (HSCs) in a set of patients with posttraumatic paraplegia. Materials and Methods: Ten patients with posttraumatic paraplegia of mean age 3.42 years were volunteered for SCT. Their mean age was 28 years, and they had variable associated complications. They were subjected to adipose tissue resection for in vitro generation of N-Ad-MSC and bone marrow aspiration for generation of HSC. Generated SCs were infused into the cerebrospinal fluid (CSF) below injury site in all patients. Results: Total mean quantum of SC infused was 4.04 ml with a mean nucleated cell count of 4.5 × 104/μL and mean CD34+ of 0.35%, CD45−/90+ and CD45−/73+ of 41.4%, and 10.04%, respectively. All of them expressed transcription factors beta-3 tubulin and glial fibrillary acid protein. No untoward effect of SCT was noted. Variable and sustained improvement in Hauser's index and American Spinal Injury Association score was noted in all patients over a mean follow-up of 2.95 years. Mean injury duration was 3.42 years against the period of approximately 1-year required for natural recovery, suggesting a positive role of SCs. Conclusion: Co-infusion of N-Ad-MSC and HSC in CSF is safe and viable therapeutic approach for SCIs. PMID:27110548

  9. Involved Field Radiation After Autologous Stem Cell Transplant for Diffuse Large B-Cell Lymphoma in the Rituximab Era

    SciTech Connect

    Biswas, Tithi; Dhakal, Sughosh; Chen Rui; Hyrien, Ollivier; Bernstein, Steven; Friedberg, Jonathan W.; Fisher, Richard I.; Liesveld, Jane; Phillips, Gordon; Constine, Louis S.

    2010-05-01

    Purpose: For patients with recurrent or refractory large B-cell non-Hodgkin's lymphoma, high-dose chemotherapy and autologous stem cell transplant (ASCT) is the treatment of choice. We evaluated the role of involved field radiation therapy (IFRT) post-ASCT for patients initially induced with cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) or, more recently, rituximab-CHOP (R-CHOP). Materials and Methods: Between May 1992 and April 2005, 176 patients underwent ASCT for recurrent or refractory large B-cell non-Hodgkin's lymphoma; 164 patients were evaluable for endpoint analysis. Fifty percent of the CHOP group (n = 131), and 39% of the R-CHOP group (n = 33), received IFRT. Follow-up from the time of transplant was a median/mean of 1.7/3 years (range, 0.03-13 years). Results: The 5-year overall survival (OS) and disease-specific survival (DSS) improved with IFRT in both the R-CHOP (p = 0.006 and 0.02, respectively) and CHOP (p = 0.02 and p = 0.04, respectively) groups. IFRT was associated with a 10% (p = 0.17) reduction in local failure, alone or with a distant site. On univariate analysis, IFRT was associated with superior OS (hazard ratio [HR] = 0.50 [95% CI 0.32, 0.78]; p = 0.002) and DSS (HR = 0.53 [95% CI 0.33, 0.86]; p = 0.009). Presence of B symptoms was adverse (p = 0.03). On multivariate analysis, only IFRT was associated with significant improvement in OS (HR = 0.35 [0.18, 0.68]; p = 0.002) and DSS (HR = 0.39 [95% CI 0.18, 0.84]; p = 0.01). Conclusions: Recognizing that positive and negative patient selection bias exists for the use of IFRT post-ASCT, patients initially treated with CHOP or R-CHOP and who undergo ASCT for recurrent or refractory disease may benefit from subsequent IFRT presumably due to enhanced local control that can translate into a survival advantage.

  10. Immunological Balance Is Associated with Clinical Outcome after Autologous Hematopoietic Stem Cell Transplantation in Type 1 Diabetes

    PubMed Central

    Malmegrim, Kelen C. R.; de Azevedo, Júlia T. C.; Arruda, Lucas C. M.; Abreu, Joana R. F.; Couri, Carlos E. B.; de Oliveira, Gislane L. V.; Palma, Patricia V. B.; Scortegagna, Gabriela T.; Stracieri, Ana B. P. L.; Moraes, Daniela A.; Dias, Juliana B. E.; Pieroni, Fabiano; Cunha, Renato; Guilherme, Luiza; Santos, Nathália M.; Foss, Milton C.; Covas, Dimas T.; Burt, Richard K.; Simões, Belinda P.; Voltarelli, Júlio C.; Roep, Bart O.; Oliveira, Maria C.

    2017-01-01

    Autologous hematopoietic stem cell transplantation (AHSCT) increases C-peptide levels and induces insulin independence in patients with type 1 diabetes. This study aimed to investigate how clinical outcomes may associate with the immunological status, especially concerning the balance between immunoregulation and autoreactivity. Twenty-one type 1 diabetes patients were monitored after AHSCT and assessed every 6 months for duration of insulin independence, C-peptide levels, frequencies of islet-specific autoreactive CD8+ T cells (CTL), regulatory lymphocyte subsets, thymic function, and T-cell repertoire diversity. In median follow-up of 78 (range 15–106) months, all patients became insulin-independent, resuming insulin after median of 43 (range 6–100) months. Patients were retrospectively divided into short- or prolonged-remission groups, according to duration of insulin independence. For the entire follow-up, CD3+CD4+ T-cell numbers remained lower than baseline in both groups, whereas CD3+CD8+ T-cell levels did not change, resulting in a CD4/CD8 ratio inversion. Memory CTL comprehended most of T cells detected on long-term follow-up of patients after AHSCT. B cells reconstituted to baseline levels at 2–3 months post-AHSCT in both patient groups. In the prolonged-remission-group, baseline islet-specific T-cell autoreactivity persisted after transplantation, but regulatory T cell counts increased. Patients with lower frequencies of autoreactive islet-specific T cells remained insulin-free longer and presented greater C-peptide levels than those with lower frequencies of these cells. Therefore, immune monitoring identified a subgroup of patients with superior clinical outcome of AHSCT. Our study shows that improved immunoregulation may balance autoreactivity endorsing better metabolic outcomes in patients with lower frequencies of islet-specific T cells. Development of new strategies of AHSCT is necessary to increase frequency and function of T and B

  11. Role of Salvage Radiation Therapy for Patients With Relapsed or Refractory Hodgkin Lymphoma Who Failed Autologous Stem Cell Transplant

    SciTech Connect

    Goda, Jayant S.; Massey, Christine; Kuruvilla, John; Gospodarowicz, Mary K.; Wells, Woodrow; Hodgson, David C.; Sun, Alexander; Keating, Armand; Crump, Michael; Tsang, Richard W.

    2012-11-01

    Purpose: To analyze, through chart review, the efficacy of salvage radiation therapy (sRT) for relapsed or progressive Hodgkin lymphoma (HL) patients who failed autologous stem cell transplant (ASCT). Patients and Methods: Among 347 patients with recurrent/refractory HL who received ASCT from 1986-2006, 163 had post-ASCT progression or relapse. Of these, 56 received sRT and form the basis of this report. Median age at sRT was 30 years (range, 17-59 years). Disease was confined to lymph nodes in 27 patients, whereas 24 had both nodal and extranodal disease. Salvage radiation therapy alone was given in 34 patients (61%), and sRT plus chemotherapy was given in 22 (39%). Median interval from ASCT to sRT was 0.8 years (range, 0.1-5.6 years). The median dose was 35 Gy (range, 8-40.3 Gy). The sRT technique was extended-field in 14 patients (25%) and involved-field in 42 (75%). Results: The median follow-up from sRT was 31.3 months (range, 0.2-205.5 months). Overall response rate was 84% (complete response: 36%; partial response: 48%). The median overall survival was 40.8 months (95% confidence interval, 34.2-56.3 months). The 5-year overall survival was 29% (95% confidence interval, 14%-44%). The 2-year progression-free survival (PFS) was 16%; the 2-year local PFS was 65%, whereas the 2-year systemic PFS was 17%. The 1-year PFS was higher in patients in whom all diseased sites were irradiated (49%) compared with those in whom only the symptomatic site was treated (22%, P=.07). Among 20 alive patients, 5 were disease free (at 6.4, 6.8, 7.4, 7.9, and 17.1 years). Conclusion: For patients with HL who fail ASCT, a selective use of RT provides a durable local control rate of 65% at 2 years and should be considered as part of the standard management plan for the palliation of incurable HL. Occasionally irradiation of truly localized disease can lead to long-term survival.

  12. Transfusion of ABO non-identical platelets does not influence the clinical outcome of patients undergoing autologous haematopoietic stem cell transplantation

    PubMed Central

    Solves, Pilar; Carpio, Nelly; Balaguer, Aitana; Romero, Samuel; Iacoboni, Gloria; Gómez, Inés; Lorenzo, Ignacio; Moscardó, Federico; Sanz, Jaime; Lopez, Francisca; Martin, Guillermo; Jarque, Isidro; Montesinos, Pau; de la Rubia, Javier; Sanz, Guillermo; Sanz, Miguel A.

    2015-01-01

    Background There are ABO antigens on the surface of platelets, but whether ABO compatible platelets are necessary for transfusions is a matter of ongoing debate. We retrospectively reviewed the ABO matching of platelet transfusions in a subset of patients undergoing autologous haematopoietic progenitor cell transplantation during a 14-year period. Our aim was to analyse the characteristics and outcomes of patients who received platelet transfusions that were or were not ABO identical. Material and methods We analysed 529 consecutive patients with various haematological and non-haematological diseases who underwent 553 autologous progenitor stem cell transplants at the University Hospital la Fe between January 2000 and December 2013. We retrospectively analysed and compared transfusion and clinical outcomes of patients according to the ABO match of the platelet transfusions received. The period analysed was the time from transplantation until discharge. Results The patients received a total of 2,772 platelet concentrates, of which 2,053 (74.0%) were ABO identical and 719 (26.0%) ABO non-identical; of these latter 309 were compatible and 410 incompatible with the patients’ plasma. Considering all transplants, 36 (6.5%) did not require any platelet transfusions, while in 246 (44.5%) cases, the patients were exclusively transfused with ABO identical platelets and in 47 (8.5%) cases they received only ABO non-identical platelet transfusions. The group of patients who received both ABO identical and ABO non-identical platelet transfusions had higher transfusion needs and worse clinical outcomes compared to patients who received only ABO identical or ABO non-identical platelets. Discussion In our hospital, patients undergoing autologous haematopoietic stem cell transplantation who received ABO identical or ABO non-identical platelet transfusions had similar transfusion and clinical outcomes. The isolated fact of receiving ABO non-identical platelets did not influence

  13. Phase I/II study of bortezomib-BEAM and autologous hematopoietic stem cell transplantation for relapsed indolent non-Hodgkin lymphoma, transformed, or mantle cell lymphoma.

    PubMed

    William, Basem M; Allen, Mary S; Loberiza, Fausto R; Bociek, Robert Gregory; Bierman, Philip J; Armitage, James O; Vose, Julie M

    2014-04-01

    A phase I/II trial was designed to evaluate the safety and efficacy of adding bortezomib to standard BEAM (BCNU, etoposide, cytarabine, melphalan) and autologous hematopoietic stem cell transplantation (ASCT). Eligible patients had relapsed/refractory indolent or transformed non-Hodgkin lymphoma or mantle cell lymphoma (MCL) that was relapsed/refractory or in first partial (PR) or complete remission (CR). Patients received bortezomib on days -11, -8, -5, and -2 before ASCT. Phase I had 4 dose cohorts (.8, 1, 1.3, and 1.5 mg/m(2)) and 3 patients were accrued to each. Any nonhematological ASCT-related toxicity >2 on the Bearman scale occurring between day -11 and engraftment defined the maximum tolerated dose (MTD). After the MTD has been reached, another 20 patients were enrolled at this dose to determine a preliminary overall response rate (ORR). Patients who were in CR or PR at day +100 were considered responders. The study enrolled 42 patients through August 14, 2009. The median age was 58 (range, 34 to 73) years, with 33 males and 9 females. The most common diagnoses were MCL (23 patients) and follicular lymphoma (7 patients). The median number of prior therapies was 1 (range, 0 to 6). The median follow-up was 4.88 (range, 1.07 to 6.98) years. Thirteen patients were treated in phase I and 29 patients were treated in phase II. The MTD was initially determined to be 1.5 mg/m(2) but it was later decreased to 1 mg/m(2) because of excessive gastrointestinal toxicity and peripheral neuropathy. The ORR was 95% at 100 days and 87% at 1 year. For all 38 evaluable patients at 1 year, responses were CR 84%, PR 1%, and progressive disease 13%. Progression-free survival (PFS) was 83% (95% CI, 68% to 92%) at 1 year, and 32% (15% to 51%) at 5 years. Overall survival (OS) was 91% (95% CI, 79% to 96%) at 1 year and 67% (50% to 79%) at 5 years. The most common National Cancer Institute grade 3 toxicities were neutropenic fever (59%), anorexia (21%), peripheral neuropathy (19

  14. Autologous mesenchymal stem cells applied on the pressure ulcers had produced a surprising outcome in a severe case of neuromyelitis optica

    PubMed Central

    Dulamea, Adriana Octaviana; Sirbu-Boeti, Mirela-Patricia; Bleotu, Coralia; Dragu, Denisa; Moldovan, Lucia; Lupescu, Ioana; Comi, Giancarlo

    2015-01-01

    Recent studies provided evidence that mesenchymal stem cells (MSCs) have regenerative potential in cutaneous repair and profound immunomodulatory properties making them a candidate for therapy of neuroimmunologic diseases. Neuromyelitis optica (NMO) is an autoimmune, demyelinating central nervous system disorder characterized by a longitudinally extensive spinal cord lesion. A 46-year-old male diagnosed with NMO had relapses with paraplegia despite treatment and developed two stage IV pressure ulcers (PUs) on his legs. The patient consented for local application of autologous MSCs on PUs. MSCs isolated from the patient's bone marrow aspirate were multiplied in vitro during three passages and embedded in a tridimensional collagen-rich matrix which was applied on the PUs. Eight days after MSCs application the patient showed a progressive healing of PUs and improvement of disability. Two months later the patient was able to walk 20 m with bilateral assistance and one year later he started to walk without assistance. For 76 months the patient had no relapse and no adverse event was reported. The original method of local application of autologous BM-MSCs contributed to healing of PUs. For 6 years the patient was free of relapses and showed an improvement of disability. The association of cutaneous repair, sustained remission of NMO and improvement of disability might be explained by a promotion/optimization of recovery mechanisms in the central nervous system even if alternative hypothesis should be considered. Further studies are needed to assess the safety and efficacy of mesenchymal stem cells in NMO treatment. PMID:26807122

  15. [Altered gut bacterial flora and organic acids in feces of patients undergoing autologous stem cell transplantation with quinolone-based antibacterial prophylaxis].

    PubMed

    Hagiwara, Shotaro; Hagiwara, Shotaro; Asahara, Takashi; Nomoto, Koji; Morotomi, Masami; Ishizuka, Naoki; Miwa, Akiyoshi; O Yoshida, Takato

    2010-06-01

    Gastrointestinal toxicity and various infections are serious problems associated with high-dose chemotherapy. Antibacterial chemoprophylaxis reduces the incidence of gram-negative bacterial infection; however, it may affect the normal intestinal flora and induce drug resistance in organisms. We evaluated the chronological changes in fecal bacteria and organic acids in 6 patients undergoing autologous stem cell transplantation with quinolone-based chemoprophylaxis. All patients developed grade 2-3 diarrhea. Four patients developed grade 3 febrile neutropenia. The total count of obligatory anaerobic bacteria was significantly decreased on Day 7, but total facultative anaerobic bacterial count did not change throughout transplantation. However, Enterobacteriaceae and Lactobacillus were decreased on Day 7 and Staphylococcus was increased after transplantation. Total organic acid concentration and short-chain fatty acids were decreased on Day 7. The bacterial flora and organic acids in the gut were significantly altered in patients who underwent autologous stem cell transplantation with quinolonebased chemoprophylaxis. These changes may contribute to gastrointestinal toxicity and infections.

  16. High-dose Chemotherapy With Autologous Stem Cell Rescue in Saudi Children Less Than 3 Years of Age With Embryonal Brain Tumors.

    PubMed

    Alsultan, Abdulrahman; Alharbi, Musa; Al-Dandan, Sadeq; Bayoumi, Yasser; Alharbi, Talal; Alsudairy, Reem; Alomari, Ali; Aljamaan, Khalid; Musleh, Othman; Alharbi, Qasim; Jarrar, Mohammed

    2015-04-01

    High-dose chemotherapy with autologous stem cell rescue (HDC/ASCR) has been used in children under the age of 3 years with embryonal brain tumors to avoid or delay the use of radiation. We reviewed the medical records of 10 Saudi children less than 3 years of age with embryonal brain tumors who underwent HDC/ASCR. All 10 patients underwent surgical resection followed by 3 to 5 cycles of induction chemotherapy and 1 to 3 cycles of HDC/ASCR using carboplatin and thiotepa. Isotretinoin was used as a maintenance therapy in 4 patients. Five patients had medulloblastoma, 3 had atypical teratoid/rhabdoid tumors, 1 had an embryonal tumor with abundant neuropil and true rosettes, and 1 had pineoblastoma. The median age of the patients was 1.9 years. A total of 19 HDC/ASCR procedures were performed. Radiotherapy (RT) was administered to 5 patients after HDC/ASCR and as a salvage therapy in 1 patient. The progression-free survival rate was 50% at 1 year and at 2 years, with a median follow-up of 24 months. All 5 patients with medulloblastoma are still alive without evidence of disease, but the other patients died secondary to tumor progression. This experience suggests that strategies combining myeloablative chemotherapy and autologous stem cell rescue appear to be feasible for children with embryonal brain tumors in the Middle East.

  17. Rituximab maintenance after autologous stem cell transplantation prolongs response duration in non-naive rituximab follicular lymphoma patients: a single institution experience.

    PubMed

    Bourcier, J; Gastinne, T; Leux, C; Moreau, A; Bossard, C; Mahé, B; Blin, N; Dubruille, V; Touzeau, C; Voldoire, M; Guillaume, T; Peterlin, P; Gallas, P; Garnier, A; Maisonneuve, H; Moreau, P; Juge-Morineau, N; Jardel, H; Chevallier, P; Moreau, P; Le Gouill, S

    2016-08-01

    We retrospectively evaluated the role of rituximab (R) in maintenance treatment after autologous stem cell transplantation performed in patients with relapsed follicular lymphoma. We compared the outcome of 67 follicular lymphoma (FL) patients according to the use of rituximab maintenance (RM) or not. All patients received rituximab plus chemotherapy before autologous stem-cell transplantation (ASCT). Patients received median of two lines of prior therapy. The RM schedule was one injection of rituximab every 3 months for 2 years. Median follow-up is 4.6 years. The 3-year progression-free survival (PFS) after ASCT was 86 % with RM vs. 46 % without (p = 0.0045). Median is not reached in the RM arm vs. 31 months in non-RM arm. The 3-year OS was 96 % with RM vs. 78 % without (p = 0.059). The present monocentric study shows that 2 years of RM after ASCT significantly increases response duration for non-naive rituximab relapsed FL patients compared with observation.

  18. Novel Peripherally Derived Neural-Like Stem Cells as Therapeutic Carriers for Treating Glioblastomas.

    PubMed

    Birbrair, Alexander; Sattiraju, Anirudh; Zhu, Dongqin; Zulato, Gilberto; Batista, Izadora; Nguyen, Van T; Messi, Maria Laura; Solingapuram Sai, Kiran Kumar; Marini, Frank C; Delbono, Osvaldo; Mintz, Akiva

    2016-09-14

    : Glioblastoma (GBM), an aggressive grade IV astrocytoma, is the most common primary malignant adult brain tumor characterized by extensive invasiveness, heterogeneity, and angiogenesis. Standard treatment options such as radiation and chemotherapy have proven to be only marginally effective in treating GBM because of its invasive nature. Therefore, extensive efforts have been put forth to develop tumor-tropic stem cells as viable therapeutic vehicles with potential to treat even the most invasive tumor cells that are harbored within areas of normal brain. To this end, we discovered a newly described NG2-expressing cell that we isolated from a distinct pericyte subtype found abundantly in cultures derived from peripheral muscle. In this work, we show the translational significance of these peripherally derived neural-like stem cells (NLSC) and their potential to migrate toward tumors and act as therapeutic carriers. We demonstrate that these NLSCs exhibit in vitro and in vivo GBM tropism. Furthermore, NLSCs did not promote angiogenesis or transform into tumor-associated stromal cells, which are concerns raised when using other common stem cells, such as mesenchymal stem cells and induced neural stem cells, as therapeutic carriers. We also demonstrate the potential of NLSCs to express a prototype therapeutic, tumor necrosis factor α-related apoptosis-inducing ligand and kill GBM cells in vitro. These data demonstrate the therapeutic potential of our newly characterized NLSC against GBM.

  19. Cytomegalovirus reactivation after autologous stem cell transplantation in myeloma and lymphoma patients: A single-center study

    PubMed Central

    Marchesi, Francesco; Pimpinelli, Fulvia; Gumenyuk, Svitlana; Renzi, Daniela; Palombi, Francesca; Pisani, Francesco; Romano, Atelda; Spadea, Antonio; Papa, Elena; Canfora, Marco; Ensoli, Fabrizio; Mengarelli, Andrea

    2015-01-01

    AIM: To determine the incidence of and the risk factors for cytomegalovirus (CMV) symptomatic infection and end-organ disease after autologous stem cell transplantation (ASCT). METHODS: A total of 327 consecutive non CD34+ selected autografts performed from the Hematology and Stem Cell Transplantation Unit of Regina Elena National Cancer Institute of Rome (Italy) in the period comprised between January 2003 to January 2015, were reviewed. Over the 327 autografts, 201 were performed in patients with multiple myeloma, whereas the remaining 126 in patients affected by non-Hodgkin’s lymphoma and Hodgkin’s lymphoma. The patients who underwent an ASCT for an acute leukemia (n = 20) in the same period were excluded from this analysis. CMV DNA load in the blood has been determined by polymerase-chain reaction in the case of a clinical suspicion of reactivation, therefore, no routine monitoring strategy was adopted. In the presence of signs and symptoms of CMV reactivation an antiviral treatment was performed. RESULTS: Overall, 36 patients (11%) required a specific antiviral treatment for a symptomatic CMV reactivation (n = 32) or an end-organ disease (n = 4). We observed 20 and 16 cases of CMV reactivation among lymphoma (16%) and myeloma patients (8%), respectively. Among cases of end-organ disease, 3 were diagnosed as interstitial pneumonia and one remaining case as hemorrhagic enteritis. All cases of CMV reactivation were observed in IgG seropositive patients, with no documented cases of primary CMV infection. All patients were treated with a specific antiviral therapy, with a global rate of hospitalization of 55%; four patients received intravenous immunoglobulins. Transplant-related mortality was significantly higher in patients who experienced a CMV reactivation (8.4% ± 4.7% vs 1.7% ± 0.8%; P = 0.047). In univariate analysis, a pre-transplant HBcIgG seropositivity, a diagnosis of T-cell non-Hodgkin’s lymphoma and higher median age at transplant were

  20. Autologous serum improves bone formation in a primary stable silica-embedded nanohydroxyapatite bone substitute in combination with mesenchymal stem cells and rhBMP-2 in the sheep model

    PubMed Central

    Boos, Anja M; Weigand, Annika; Deschler, Gloria; Gerber, Thomas; Arkudas, Andreas; Kneser, Ulrich; Horch, Raymund E; Beier, Justus P

    2014-01-01

    New therapeutic strategies are required for critical size bone defects, because the gold standard of transplanting autologous bone from an unharmed area of the body often leads to several severe side effects and disadvantages for the patient. For years, tissue engineering approaches have been seeking a stable, axially vascularized transplantable bone replacement suitable for transplantation into the recipient bed with pre-existing insufficient conditions. For this reason, the arteriovenous loop model was developed and various bone substitutes have been vascularized. However, it has not been possible thus far to engineer a primary stable and axially vascularized transplantable bone substitute. For that purpose, a primary stable silica-embedded nanohydroxyapatite (HA) bone substitute in combination with blood, bone marrow, expanded, or directly retransplanted mesenchymal stem cells, recombinant human bone morphogenetic protein 2 (rhBMP-2), and different carrier materials (fibrin, cell culture medium, autologous serum) was tested subcutaneously for 4 or 12 weeks in the sheep model. Autologous serum lead to an early matrix change during degradation of the bone substitute and formation of new bone tissue. The best results were achieved in the group combining mesenchymal stem cells expanded with 60 μg/mL rhBMP-2 in autologous serum. Better ingrowth of fibrovascular tissue could be detected in the autologous serum group compared with the control (fibrin). Osteoclastic activity indicating an active bone remodeling process was observed after 4 weeks, particularly in the group with autologous serum and after 12 weeks in every experimental group. This study clearly demonstrates the positive effects of autologous serum in combination with mesenchymal stem cells and rhBMP-2 on bone formation in a primary stable silica-embedded nano-HA bone grafting material in the sheep model. In further experiments, the results will be transferred to the sheep arteriovenous loop model in

  1. Engineered neural tissue with aligned, differentiated adipose-derived stem cells promotes peripheral nerve regeneration across a critical sized defect in rat sciatic nerve.

    PubMed

    Georgiou, Melanie; Golding, Jon P; Loughlin, Alison J; Kingham, Paul J; Phillips, James B

    2015-01-01

    Adipose-derived stem cells were isolated from rats and differentiated to a Schwann cell-like phenotype in vitro. The differentiated cells (dADSCs) underwent self-alignment in a tethered type-1 collagen gel, followed by stabilisation to generate engineered neural tissue (EngNT-dADSC). The pro-regenerative phenotype of dADSCs was enhanced by this process, and the columns of aligned dADSCs in the aligned collagen matrix supported and guided neurite extension in vitro. EngNT-dADSC sheets were rolled to form peripheral nerve repair constructs that were implanted within NeuraWrap conduits to bridge a 15 mm gap in rat sciatic nerve. After 8 weeks regeneration was assessed using immunofluorescence imaging and transmission electron microscopy and compared to empty conduit and nerve graft controls. The proportion of axons detected in the distal stump was 3.5 fold greater in constructs containing EngNT-dADSC than empty tube controls. Our novel combination of technologies that can organise autologous therapeutic cells within an artificial tissue construct provides a promising new cellular biomaterial for peripheral nerve repair.

  2. Mobilization and collection of peripheral blood stem cells: guidelines for blood volume to process, based on CD34-positive blood cell count in adults and children.

    PubMed

    Anguita-Compagnon, A T; Dibarrart, M T; Palma, J; Paredes, L; Mosso, C; Montalva, R; Salas, L; Araos, D; Delgado, I; Majlis, A

    2010-01-01

    We report 189 mobilizations and 489 collections of peripheral blood stem cells (PBSC) performed in 139 autologous transplantation patients and in 28 donors for allogeneic transplantations whose ages ranged from 2-68 years. We observed a correlation (P < .001; Pearson's coefficient 0.64) between CD34-positive cells and granulocyte-macrophage colony-forming units examined to estimate PBSC. In a subset of 287 collections (97 adults and 49 children) we obtained peripheral blood (PB) CD34-positive cell counts at 2 to 4 hours before leukapheresis. We noted a correlation between PB CD34-positive cell counts before leukapheresis and the number of CD34-positive cells per kilogram of body weight collected in the whole apheresis of the day (P < .001; Pearson's coefficient 0.82). An even better correlation was obtained between PB CD34-positive cells preapheresis and the yield of each individual blood volume (BV) processed (P < .001; Pearson's coefficient 0.87). Healthy donors and patients in each age group behaved similarly. In addition, the collection yield was greater among children than adults. These findings allowed us to develop a simple predictive model to estimate the BV to process for a target dose of CD34-positive cells per kilogram, based on the level of PBSC before apheresis in children and adults.

  3. Depletion of autoreactive immunologic memory followed by autologous hematopoietic stem cell transplantation in patients with refractory SLE induces long-term remission through de novo generation of a juvenile and tolerant immune system.

    PubMed

    Alexander, Tobias; Thiel, Andreas; Rosen, Oliver; Massenkeil, Gero; Sattler, Arne; Kohler, Siegfried; Mei, Henrik; Radtke, Hartmut; Gromnica-Ihle, Erika; Burmester, Gerd-Rüdiger; Arnold, Renate; Radbruch, Andreas; Hiepe, Falk

    2009-01-01

    Clinical trials have indicated that immunoablation followed by autologous hematopoietic stem cell transplantation (ASCT) has the potential to induce clinical remission in patients with refractory systemic lupus erythematosus (SLE), but the mechanisms have remained unclear. We now report the results of a single-center prospective study of long-term immune reconstitution after ASCT in 7 patients with SLE. The clinical remissions observed in these patients are accompanied by the depletion of autoreactive immunologic memory, reflected by the disappearance of pathogenic anti-double-stranded DNA (dsDNA) antibodies and protective antibodies in serum and a fundamental resetting of the adaptive immune system. The latter comprises recurrence of CD31(+)CD45RA(+)CD4(+) T cells (recent thymic emigrants) with a doubling in absolute numbers compared with age-matched healthy controls at the 3-year follow-up (P = .016), the regeneration of thymic-derived FoxP3(+) regulatory T cells, and normalization of peripheral T-cell receptor (TCR) repertoire usage. Likewise, responders exhibited normalization of the previously disturbed B-cell homeostasis with numeric recovery of the naive B-cell compartment within 1 year after ASCT. These data are the first to demonstrate that both depletion of the autoreactive immunologic memory and a profound resetting of the adaptive immune system are required to reestablish self-tolerance in SLE.

  4. [Successful long-term control of recurrent primary central nervous system anaplastic large cell lymphoma after autologous hematopoietic stem cell transplantation with concurrent whole brain and spinal cord radiotherapy].

    PubMed

    Hiroshima, Yuki; Kaiume, Hiroko; Kirihara, Takehiko; Takeda, Wataru; Kurihara, Taro; Sato, Keijiro; Shimizu, Ikuo; Ueki, Toshimitsu; Sumi, Masahiko; Ueno, Mayumi; Ichikawa, Naoaki; Asano, Naoko; Watanabe, Masahide; Kobayashi, Hikaru

    2015-12-01

    A 24-year-old woman was hospitalized with seizures in 2002. Magnetic resonance imaging demonstrated an intraspinal mass and inhomogeneous gadolinium enhancement along the cerebrospinal meninges. Cerebrospinal fluid (CSF) cytology showed large atypical cells expressing CD2, cytoplasmic CD3, CD7, CD13 and CD30. The patient was finally diagnosed with primary central nervous system anaplastic large cell lymphoma (ALCL). She completed 5 courses of methotrexate (MTX)/ procarbazine (PCZ)/ vincristine (VCR) (MPV) chemotherapy, followed by 2 courses of high dose cytarabine (AraC) and achieved a complete remission. In 2003, she suffered from headache. CSF analysis showed atypical lymphoid cells expressing CD 30. First CNS relapse was diagnosed. She then underwent autologous peripheral blood stem cell transplantation (auto-PBSCT) after administration of thiotepa, buslfan, and cyclophosphamide. However, second CNS relapse occurred in 2004. She received 5 courses of MPV chemotherapy followed by 36 Gy of craniospinal irradiation. Although there was no recurrence of the CNS disease, a third relapse was detected in the right breast in 2009. Pathological and immunohistochemistry analysis revealed ALK-1 positive ALCL. She was treated with 6 courses of cyclophosphamide/adriamycin/vincristine/predonine (CHOP) chemotherapy and 30.6 Gy of local radiation therapy. She has remained in remission for 6 years, to date, since the last therapy and has an excellent quality of life.

  5. Long-term follow-up of tandem high-dose therapy with autologous stem cell support for adults with high-risk age-adjusted international prognostic index aggressive non-Hodgkin Lymphomas: a GOELAMS pilot study.

    PubMed

    Monjanel, Hélène; Deconinck, Eric; Perrodeau, Elodie; Gastinne, Thomas; Delwail, Vincent; Moreau, Anne; François, Sylvie; Berthou, Christian; Gyan, Emmanuel; Milpied, Noël

    2011-06-01

    Single high-dose therapy (HDT) followed by autologous peripheral blood stem cell (PBSC) support improves complete response and overall survival (OS) in untreated aggressive non-Hodgkin's lymphoma (NHL). However, patients with a high age-adjusted international prognostic index (aa-IPI equal to 3) still have poor clinical outcome despite high dose intensity regimen. To improve complete response in this subgroup, the French Groupe Ouest-Est des Leucémies et Autres Maladies du Sang (GOELAMS) conducted a pilot phase II trial (073) evaluating tandem HDT with PBSC support in a series of 45 patients with aa-IPI equal to 3 untreated aggressive non-Hodgkin's lymphoma. After induction with an anthracyclin-containing regimen, responders underwent tandem HDT conditioned by high-dose mitoxantrone plus cytarabine for the first HDT and total-body irradiation (TBI), carmustine, etoposide, and cyclophosphamide for the second HDT. Thirty-one patients out of 41 evaluable patients completed the program. There were 4 toxic deaths. The complete response rate was 49%. With a median follow-up of 114 months for surviving patients, the OS was 51%, and 19 out of the 22 patients (86%) who reached a complete response are alive and relapse-free. Recent prospective evaluation of quality of life and comorbidities of surviving patients does not reveal long-term toxicities of the procedure. In the era of monoclonal antibodies and response-adapted therapy, the role of tandem HDT still need to be determined.

  6. Safety reporting on implantation of autologous adipose tissue-derived stem cells with platelet-rich plasma into human articular joints

    PubMed Central

    2013-01-01

    Background Adipose tissue-derived stem cells (ADSCs), a type of mesenchymal stem cells (MSCs), have great potential as therapeutic agents in regenerative medicine. Numerous animal studies have documented the multipotency of ADSCs, showing their capabilities to differentiate into tissues such as muscle, bone, cartilage, and tendon. However, the safety of autologous ADSC injections into human joints is only beginning to be understood and the data are lacking. Methods Between 2009 and 2010, 91 patients were treated with autologous ADSCs with platelet-rich plasma (PRP) for various orthopedic conditions. Stem cells in the form of stromal vascular fraction (SVF) were injected with PRP into various joints (n = 100). All patients were followed for symptom improvement with visual analog score (VAS) at one month and three months. Approximately one third of the patients were followed up with third month magnetic resonance imaging (MRI) of the injected sites. All patients were followed up by telephone questionnaires every six months for up to 30 months. Results The mean follow-up time for all patients was 26.62 ± 0.32 months. The follow-up time for patients who were treated in 2009 and early 2010 was close to three years. The relative mean VAS of patients at the end of one month follow-up was 6.55 ± 0.32, and at the end of three months follow-up was 4.43 ± 0.41. Post-procedure MRIs performed on one third of the patients at three months failed to demonstrate any tumor formation at the implant sites. Further, no tumor formation was reported in telephone long-term follow-ups. However, swelling of injected joints was common and was thought to be associated with death of stem cells. Also, tenosinovitis and tendonitis in elderly patients, all of which were either self-limited or were remedied with simple therapeutic measures, were common as well. Conclusions Using both MRI tracking and telephone follow ups in 100 joints in 91 patients treated, no neoplastic complications were

  7. Episomal Induced Pluripotent Stem Cells Promote Functional Recovery of Transected Murine Peripheral Nerve

    PubMed Central

    Kao, Huang-Kai; Cardona, Esteban; Chuang, Sheng-Hao

    2016-01-01

    Traumatic peripheral nerve neurotmesis occurs frequently and functional recovery is often slow and impaired. Induced pluripotent stem cells (iPSCs) have shown much promise in recent years due to its regenerative properties similar to that of embryonic stem cells. However, the potential of iPSCs in promoting the functional recovery of a transected peripheral nerve is largely unknown. This study is the first to investigate in vivo effects of episomal iPSCs (EiPSCs) on peripheral nerve regeneration in a murine sciatic nerve transection model. Episomal iPSCs refer to iPSCs that are generated via Oct3/4-Klf4-Sox2 plasmid reprogramming instead of the conventional viral insertion techniques. It represents a relatively safer form of iPSC production without permanent transgene integration which may raise questions regarding risks of genomic mutation. A minimal number of EiPSCs were added directly to the transected nerve. Functional recovery of the EiPSC group was significantly improved compared to the negative control group when assessed via serial five-toe spread measurement and gait analysis of ankle angles. EiPSC promotion of nerve regeneration was also evident on stereographic analysis of axon density, myelin thickness, and axonal cross-sectional surface area. Most importantly, the results observed in EiPSCs are similar to that of the embryonic stem cell group. A roughly ten-fold increase in neurotrophin-3 levels was seen in EiPSCs which could have contributed to peripheral nerve regeneration and recovery. No abnormal masses or adverse effects were noted with EiPSC administration after one year of follow-up. We have hence shown that functional recovery of the transected peripheral nerve can be improved with the use of EiPSC therapy, which holds promise for the future of nerve regeneration. PMID:27736950

  8. Tissue engineering with peripheral blood-derived mesenchymal stem cells promotes the regeneration of injured peripheral nerves.

    PubMed

    Pan, Mengjie; Wang, Xianghai; Chen, Yijing; Cao, Shangtao; Wen, Jinkun; Wu, Guofeng; Li, Yuanyuan; Li, Lixia; Qian, Changhui; Qin, Zhenqi; Li, Zhenlin; Tan, Dandan; Fan, Zhihao; Wu, Wutian; Guo, Jiasong

    2017-03-07

    Peripheral nerve injury repair can be enhanced by Schwann cell (SC) transplantation, but clinical applications are limited by the lack of a cell source. Thus, alternative systems for generating SCs are desired. Herein, we found the peripheral blood-derived mesenchymal stem cells (PBMSCs) could be induced into SC like cells with expressing SC-specific markers (S100, P75NTR and CNPase) and functional factors (NGF, NT-3, c-Fos, and Krox20). When the induced PBMSCs (iPBMSCs) were transplanted into crushed rat sciatic nerves, they functioned as SCs by wrapping the injured axons and expressing myelin specific marker of MBP. Furthermore, iPBMSCs seeded in an artificial nerve conduit to bridge a 10-mm defect in a sciatic nerve achieved significant nerve regeneration outcomes, including axonal regeneration and remyelination, nerve conduction recovery, and restoration of motor function, and attenuated myoatrophy and neuromuscular junction degeneration in the target muscle. Overall, the data from this study indicated that PBMSCs can transdifferentiate towards SC-like cells and have potential as grafting cells for nerve tissue engineering.

  9. Microcircuit formation following transplantation of mouse embryonic stem cell-derived neurons in peripheral nerve.

    PubMed

    Magown, Philippe; Rafuse, Victor F; Brownstone, Robert M

    2017-04-01

    Motoneurons derived from embryonic stem cells can be transplanted in the tibial nerve, where they extend axons to functionally innervate target muscle. Here, we studied spontaneous muscle contractions in these grafts 3 mo following transplantation. One-half of the transplanted grafts generated rhythmic muscle contractions of variable patterns, either spontaneously or in response to brief electrical stimulation. Activity generated by transplanted embryonic stem cell-derived neurons was driven by glutamate and was modulated by muscarinic and GABAergic/glycinergic transmission. Furthermore, rhythmicity was promoted by the same transmitter combination that evokes rhythmic locomotor activity in spinal cord circuits. These results demonstrate that there is a degree of self-assembly of microcircuits in these peripheral grafts involving embryonic stem cell-derived motoneurons and interneurons. Such spontaneous activity is reminiscent of embryonic circuit development in which spontaneous activity is essential for proper connectivity and function and may be necessary for the grafts to form functional connections with muscle.NEW & NOTEWORTHY This manuscript demonstrates that, following peripheral transplantation of neurons derived from embryonic stem cells, the grafts are spontaneously active. The activity is produced and modulated by a number of transmitter systems, indicating that there is a degree of self-assembly of circuits in the grafts.

  10. The Role of ABO Incompatibility in Allogeneic Peripheral Blood Stem Cell Transplant.

    PubMed

    Arslan, Önder; Coşkun, Hasan Şanol; Arat, Mutlu; Soydan, Ender; Özcan, Muhit; Gürman, Günhan; Çelebi, Harika; Demirer, Taner; Akan, Hamdi; İlhan, Osnman; Konuk, Nahide; Uysal, Akın; Berksaç, Meral; Koç, Haluk

    2002-09-05

    ABO incompatibility is not a contraindication for allogeneic bone marrow transplantation, but this procedure requires an extra effort for erythrocyte or plasma depletion in certain well established conditions. Some acute or delayed immunohematological complications such as acute or chronic hemolysis and pure red cell aplasia may be encountered. In this study the outcome and transplant related complications of ABO incompatible and identical cases, who have received allogeneic peripheral blood stem cells from their HLA identical siblings were compared with each other. Ninety-one patients (CML 36, AML 37, other 18) were analyzed retrospectively including 51 (60.4%) ABO identical patients and 36 (39.6%) ABO mismatched (MM) patients, who have a bi-directional MM (n= 5), major MM (n= 16), minor MM (n= 9) and Rh MM (n= 6). Median follow up was 13 (0.5-43.0) months. We did not observed any significant differences between two groups (identical vs non-identical) in terms of acute hemolysis preceding stem cell infusion, peritransplant transfusion demand, acute- and chronic graft versus host disease. There was no change in estimated disease free survival and overall survival durations. We did not observed any influence of ABO/Rh incompatibility on short term outcome in allogeneic peripheral blood stem cell transplantation in our series and did not recommend further manipulation of the infused stem cells.

  11. Recovery of polyclonal immunoglobulins one year after autologous stem cell transplantation as a long-term predictor marker of progression and survival in multiple myeloma.

    PubMed

    González-Calle, Verónica; Cerdá, Seila; Labrador, Jorge; Sobejano, Eduardo; González-Mena, Beatriz; Aguilera, Carmen; Ocio, Enrique María; Vidriales, María Belén; Puig, Noemí; Gutiérrez, Norma Carmen; Garcĺa-Sanz, Ramón; Alonso, Jose' Marĺa; López, Rosa; Aguilar, Carlos; Garcĺa de Coca, Alfonso; Hernández, Roberto; Hernández, José Mariano; Escalante, Fernando; Mateos, María-Victoria

    2017-01-25

    Immunoparesis or suppression of polyclonal immunoglobulins is a very common condition in newly diagnosed myeloma patients. However, the recovery of polyclonal immunoglobulins in the setting of immune reconstitution after autologous stem cell transplantation and its effect on outcome has not been explored to date. We conducted this study in a cohort of 295 patients who had undergone autologous transplantation. In order to explore the potential role of immunoglubulin recovery as a dynamic predictor of progression or survival after transplantation, conditional probabilities of progression-free survival and overall survival were estimated, according to immunoglobulin recovery, at different time points using a landmark approach. One year after transplant, when B-cell reconstitution is expected to be completed, among 169 patients alive and progression-free, 88 patients (52%) had recovered immunoglobulins and 81 (48%) had not. Interestingly, the group with immunoglobulin recovery had a significantly longer median progression-free survival than the group with persistent immunoparesis (median 60.4 vs. 27.9 months, respectively; hazard ratio=0.45, 95% CI: 0.31-0.66; P<0.001), and improved overall survival (11.3 vs.7.3 years; hazard ratio=0.45, 95% CI=0.27-0.74, P=0.002). Furthermore, the percentage of normal plasma cells detected by flow cytometry in the bone marrow assessed at day 100 after transplantation was associated with the immunoglobulin recovery at that time and may predict immunoglobulin recovery in the subsequent months: 9 months and 1 year. In conclusion, the recovery of polyclonal immunoglobulins 1 year after autologous transplantation in myeloma patients is an independent long-term predictor marker for progression and survival.

  12. The use of autologous neurogenically-induced bone marrow-derived mesenchymal stem cells for the treatment of paraplegic dogs without nociception due to spinal trauma

    PubMed Central

    BESALTI, Omer; AKTAS, Zeynep; CAN, Pinar; AKPINAR, Eylul; ELCIN, Ayse Eser; ELCIN, Yasar Murat

    2016-01-01

    The aim of this study was to investigate the effects of percutaneous transplanted autologous neurogenically-induced bone marrow-derived mesenchymal stem cells (NIBM-MSCs) in paraplegic dogs without deep pain perception (DPP) secondary to external spinal trauma. Thirteen client owned dogs that had failed in improvement neurologically at least 42 days after conservative management, decompression and decompression-stabilization were included in the study. Each dog received two doses of autologous 5.0 × 106 NIBM-MSCs suspension, which were positive to 2′,3′-Cyclic-nucleotide-3′-phosphodiesterase (CNPase) and Microtubule-associated protein 2 (MAP-2), as well as to Glial fibrillary acidic protein (GFAP) and beta III tubulin. The cells were injected into the spinal cord through the hemilaminectomy or laminectomy defects percutaneously with 21 days interval for 2 times. The results were evaluated using Texas Spinal Cord Injury Scale (TSCIS), somatosensory evoked potentials (SEP) and motor evoked potentials (MEP) at the admission time, cell transplantation procedures and during 2, 5, 7 and 12th months after the second cell transplantation. Improvement after cell transplantation in gait, nociception, proprioception, SEP and MEP results was observed in just 2 cases, and only gait score improvement was seen in 6 cases, and no improvement was recorded in 5 cases. All progresses were observed until 2nd month after the second cell transplantation, however, there was no improvement after this period. In conclusion, percutaneous transplantation of autologous NIBM-MSCs is a promising candidate modality for cases with spinal cord injury after spinal trauma and poor prognosis. PMID:27301583

  13. Alternative generation of CNS neural stem cells and PNS derivatives from neural crest-derived peripheral stem cells.

    PubMed

    Weber, Marlen; Apostolova, Galina; Widera, Darius; Mittelbronn, Michel; Dechant, Georg; Kaltschmidt, Barbara; Rohrer, Hermann

    2015-02-01

    Neural crest-derived stem cells (NCSCs) from the embryonic peripheral nervous system (PNS) can be reprogrammed in neurosphere (NS) culture to rNCSCs that produce central nervous system (CNS) progeny, including myelinating oligodendrocytes. Using global gene expression analysis we now demonstrate that rNCSCs completely lose their previous PNS characteristics and acquire the identity of neural stem cells derived from embryonic spinal cord. Reprogramming proceeds rapidly and results in a homogenous population of Olig2-, Sox3-, and Lex-positive CNS stem cells. Low-level expression of pluripotency inducing genes Oct4, Nanog, and Klf4 argues against a transient pluripotent state during reprogramming. The acquisition of CNS properties is prevented in the presence of BMP4 (BMP NCSCs) as shown by marker gene expression and the potential to produce PNS neurons and glia. In addition, genes characteristic for mesenchymal and perivascular progenitors are expressed, which suggests that BMP NCSCs are directed toward a pericyte progenitor/mesenchymal stem cell (MSC) fate. Adult NCSCs from mouse palate, an easily accessible source of adult NCSCs, display strikingly similar properties. They do not generate cells with CNS characteristics but lose the neural crest markers Sox10 and p75 and produce MSC-like cells. These findings show that embryonic NCSCs acquire a full CNS identity in NS culture. In contrast, MSC-like cells are generated from BMP NCSCs and pNCSCs, which reveals that postmigratory NCSCs are a source for MSC-like cells up to the adult stage.

  14. Clinical-scale laser-based scanning and processing of live cells: selective photothermal killing of fluorescent tumor targets for autologous stem cell transplantation

    NASA Astrophysics Data System (ADS)

    Koller, Manfred R.; Hanania, Elie G.; Eisfeld, Timothy; O'Neal, Robert A.; Khovananth, Kevin M.; Palsson, Bernhard O.

    2001-04-01

    High-dose chemotherapy, followed by autologous hematopoietic stem cell (HSC) transplantation, is widely used for the treatment of cancer. However, contaminating tumor cells within HSC harvests continue to be of major concern since re-infused tumor cells have proven to contribute to disease relapse. Many tumor purging methods have been evaluated, but all leave detectable tumor cells in the transplant and result in significant loss of HSCs. These shortcomings cause engraftment delays and compromise the therapeutic value of purging. A novel approach integrating automated scanning cytometry, image analysis, and selective laser-induced killing of labeled cells within a cell mixture is described here. Non-Hodgkin's lymphoma (NHL) cells were spiked into cell mixtures, and fluorochrome-conjugated antibodies were used to label tumor cells within the mixture. Cells were then allowed to settle on a surface, and as the surface was scanned with a fluorescence excitation source, a laser pulse was fired at every detected tumor cell using high-speed beam steering mirrors. Tumor cells were selectively killed with little effect on adjacent non-target cells, demonstrating the feasibility of this automated cell processing approach. This technology has many potential research and clinical applications, one example of which is tumor cell purging for autologous HSC transplantation.

  15. A Long-Gap Peripheral Nerve Injury Therapy Using Human Skeletal Muscle-Derived Stem Cells (Sk-SCs): An Achievement of Significant Morphological, Numerical and Functional Recovery

    PubMed Central

    Hirata, Maki; Nakajima, Nobuyuki; Saito, Kosuke; Hashimoto, Hiroyuki; Soeda, Shuichi; Uchiyama, Yoshiyasu; Watanabe, Masahiko

    2016-01-01

    Losses in vital functions of the somatic motor and sensory nervous system are induced by severe long-gap peripheral nerve transection injury. In such cases, autologous nerve grafts are the gold standard treatment, despite the unavoidable sacrifice of other healthy functions, whereas the prognosis is not always favorable. Here, we use human skeletal muscle-derived stem cells (Sk-SCs) to reconstitute the function after long nerve-gap injury. Muscles samples were obtained from the amputated legs from 9 patients following unforeseen accidents. The Sk-SCs were isolated using conditioned collagenase solution, and sorted as CD34+/45- (Sk-34) and CD34-/45-/29+ (Sk-DN/29+) cells. Cells were separately cultured/expanded under optimal conditions for 2 weeks, then injected into the athymic nude mice sciatic nerve long-gap model (7-mm) bridging an acellular conduit. After 8–12 weeks, active cell engraftment was observed only in the Sk-34 cell transplanted group, showing preferential differentiation into Schwann cells and perineurial/endoneurial cells, as well as formation of the myelin sheath and perineurium/endoneurium surrounding regenerated axons, resulted in 87% of numerical recovery. Differentiation into vascular cell lineage (pericyte and endothelial cells) were also observed. A significant tetanic tension recovery (over 90%) of downstream muscles following electrical stimulation of the sciatic nerve (at upper portion of the gap) was also achieved. In contrast, Sk-DN/29+ cells were completely eliminated during the first 4 weeks, but relatively higher numerical (83% vs. 41% in axon) and functional (80% vs. 60% in tetanus) recovery than control were observed. Noteworthy, significant increase in the formation of vascular networks in the conduit during the early stage (first 2 weeks) of recovery was observed in both groups with the expression of key factors (mRNA and protein levels), suggesting the paracrine effects to angiogenesis. These results suggested that the human Sk

  16. Autologous bone marrow-derived cultured mesenchymal stem cells delivered in a fibrin spray accelerate healing in murine and human cutaneous wounds.

    PubMed

    Falanga, Vincent; Iwamoto, Satori; Chartier, Molly; Yufit, Tatyana; Butmarc, Janet; Kouttab, Nicholas; Shrayer, David; Carson, Polly

    2007-06-01

    The nonhematopoietic component of bone marrow includes multipotent mesenchymal stem cells (MSC) capable of differentiating into fat, bone, muscle, cartilage, and endothelium. In this report, we describe the cell culture and characterization, delivery system, and successful use of topically applied autologous MSC to accelerate the healing of human and experimental murine wounds. A single bone marrow aspirate of 35-50 mL was obtained from patients with acute wounds (n = 5) from skin cancer surgery and from patients with chronic, long-standing, nonhealing lower extremity wounds (n = 8). Cells were grown in vitro under conditions favoring the propagation of MSC, and flow cytometry and immunostaining showed a profile (CD29+, CD44+, CD105+, CD166+, CD34-, CD45-) highly consistent with published reports of human MSC. Functional induction studies confirmed that the MSC could differentiate into bone, cartilage, and adipose tissue. The cultured autologous MSC were applied up to four times to the wounds using a fibrin polymer spray system with a double-barreled syringe. Both fibrinogen (containing the MSC) and thrombin were diluted to optimally deliver a polymerized gel that immediately adhered to the wound, without run-off, and yet allowing the MSC to remain viable and migrate from the gel. Sequential adjacent sections from biopsy specimens of the wound bed after MSC application showed elongated spindle cells, similar to their in vitro counterparts, which immunostained for MSC markers. Generation of new elastic fibers was evident by both special stains and antibodies to human elastin. The application of cultured cells was safe, without treatment-related adverse events. A strong direct correlation was found between the number of cells applied (greater than 1 x 10(6) cells per cm2 of wound area) and the subsequent decrease in chronic wound size (p = 0.0058). Topical application of autologous MSC also stimulated closure of full-thickness wounds in diabetic mice (db

  17. Human Herpesvirus-6 cytopathic inclusions: an exceptional and recognizable finding on skin biopsy during HHV6 reactivation after autologous stem-cell transplantation.

    PubMed

    Roux, Jennifer; Battistella, Maxime; Fornecker, Luc; Legoff, Jérôme; Deau, Bénédicte; Houhou, Nadira; Bouaziz, Jean-David; Thieblemont, Catherine; Janin, Anne

    2012-08-01

    Skin rash are common in immunocompromised patients, particularly after bone marrow transplantation. Human herpes virus 6 (HHV6) reactivation is often suspected, but its clinical presentation and the routine laboratory tests may be unspecific, thus leading to late diagnosis. In this case, we report specific intralymphocytic cytopathic inclusions on skin biopsy as a sign of systemic HHV6 reactivation. A 56-year-old patient presented progressive erythroderma and fever occurring after autologous hematopoietic stem-cell transplantation for mantle cell lymphoma. The skin biopsy showed a perivascular infiltrate of medium-to-large lymphocytes with irregular nuclei containing a large central basophilic inclusion surrounded by a clear halo. High levels of HHV-6 genomic in skin biopsy confirm HHV-6-induced cytopathic effect. The clinical course improved with intravenous foscavir. The specific histopathological findings encountered in this case are exceptional but recognizable, and along with HHV-6 DNA detection allow a prompt recognition of HHV6 skin rash.

  18. Outcomes of MYC-associated lymphomas after R-CHOP with and without consolidative autologous stem cell transplant: Subset analysis of randomized trial intergroup SWOG S9704

    PubMed Central

    Puvvada, Soham D.; Stiff, Patrick J.; Leblanc, Michael; Cook, James R.; Couban, Stephen; Leonard, John P.; Kahl, Brad; Marcellus, Deborah; Shea, Thomas C.; Winter, Jane N.; Li, Hongli; Rimsza, Lisa M.; Friedberg, Jonathan W.; Smith, Sonali M.

    2016-01-01

    Summary Double hit lymphoma (DHL) and double protein-expressing (MYC and BCL2) lymphomas (DPL) fare poorly with R-CHOP; consolidative autologous stem cell transplant (ASCT) may improve outcomes. S9704, a phase III randomized study of CHOP +/−R with or without ASCT allows evaluation of intensive consolidation. Immunohistochemical analysis identified 27 of 198 patients (13.6%) with MYC IHC overexpression and 20 (74%) harboring concurrent BCL2 overexpression. Four had DHL and 16 had DPL only. With median follow-up 127 months, there is a trend favoring outcomes after consolidative ASCT in DPL and MYC protein overexpressing patients, whereas all DHL patients have died irrespective of ASCT. PMID:27072903

  19. AL amyloidosis with IgD-lambda monoclonal gammopathy and lambda-type Bence-Jones protein: successful treatment by autologous stem cell transplantation.

    PubMed

    Sakurai-Chin, Chanhyok; Ubara, Yoshifumi; Suwabe, Tatsuya; Hoshino, Junichi; Yonaha, Tomoki; Hasegawa, Eiko; Sumida, Keiichi; Hiramatsu, Rikako; Yamanouchi, Masayuki; Hayami, Noriko; Yamauchi, Junji; Tominaga, Naoyuki; Sawa, Naoki; Takemoto, Fumi; Masuoka, Kazuhiro; Takaichi, Kenmei; Oohashi, Kenichi

    2010-10-01

    A 45-year-old Japanese woman had been diagnosed with monoclonal gammopathy of undetermined significance (MGUS) featuring urinary Bence-Jones protein of the lambda type (BJP-lambda) for 11 years. She then developed eyelid purpura, dyspnea, and flank pain. Abdominal CT scans revealed renal infarction. Biopsy of the kidney, heart, jejunum, and skin demonstrated amyloid deposits in the vessel walls, but not in the glomeruli. She was diagnosed as having AL amyloidosis with IgD-lambda monoclonal gammopathy and BJP-lambda. Autologous stem cell transplantation (SCT) was done after chemotherapy with vincristine, daunorubicin, dexamethasone (VAD), and high-dose melphalan (HDM). This reduced the IgD level from 156 to 0.1 mg/dL, along with the disappearance of BJP, despite cerebral infarction during chemotherapy. We recommend SCT for patients with IgD-associated AL amyloidosis.

  20. Nitric Oxide Signaling and Neural Stem Cell Differentiation in Peripheral Nerve Regeneration

    PubMed Central

    Tao Li, Jessica; Somasundaram, Chandra; Bian, Ka; Xiong, Weijun; Mahmooduddin, Faiz; Nath, Rahul K.; Murad, Ferid

    2010-01-01

    Objective: The objective was to examine whether nitric oxide signaling plays a role in human embryonic stem cell differentiation into neural cells. This article reviews current literature on nitric oxide signaling and neural stem cell differentiation for potential therapeutic application to peripheral nerve regeneration. Methods: Human embryonic H9-stem cells were grown, maintained on mitomycin C–treated mouse embryonic fibroblast feeder layer, cultured on Matrigel to be feeder-free, and used for all the experiments. Fluorescent dual-immunolabeling and confocal image analysis were used to detect the presence of the neural precursor cell markers nestin and nitric oxide synthase-1. Fluorescence-activated cell sorting analysis was used to determine the percentage of expression. Results: We have shown the confocal image of stage 1 human embryonic stem cells coexpressing nestin and nitric oxide synthase-1. Fluorescence-activated cell sorting analysis indicated 24.3% positive labeling of nitric oxide synthase-1. Adding retinoic acid (10−6 M) to the culture medium increased the percent of nitric oxide synthase-1 positive cells to 33.9%. Combining retinoic acid (10−6 M) with 8-brom cyclic guanosine monophosphate (10−5 M), the fluorescence-activated cell sorting analysis demonstrated a further increase of nitric oxide synthase-1 positive cells to 45.4%. Our current results demonstrate a prodifferentiation potency of nitric oxide synthase-1, stimulated by retinoic acid with and without cyclic guanosine monophosphate. Conclusion: We demonstrated for the first time how nitric oxide/cyclic guanosine monophosphate signaling contributes to the development of neural precursors derived from human embryonic stem cells and enhances the differentiation of precursors toward functional neurons for peripheral nerve regeneration. PMID:20563304

  1. Comparison of osteogenic potentials of BMP4 transduced stem cells from autologous bone marrow and fat tissue in a rabbit model of calvarial defects.

    PubMed

    Lin, Lin; Shen, Qi; Wei, Xuelei; Hou, Yu; Xue, Tao; Fu, Xin; Duan, Xiaoning; Yu, Changlong

    2009-07-01

    We compared bone marrow stem cells (BMSCs) and adipose-derived stem cells (ADSCs) of adult rabbits under identical conditions in terms of their culture characteristics, proliferation capacity, osteogenic differentiation potentials induced by adenovirus-containing bone morphogenetic protein 4 (Ad-BMP4) in vitro, and capacity to repair calvarial defects in the rabbit model by autologous transplantation ex vivo. According to the results of growth curve, cell cycle, and telomerase activity analysis, ADSCs possess a higher proliferation potential. Both of the Ad-BMP4 transduced MSCs expressed BMP4 mRNA and protein and underwent osteogenic differentiation. Up-regulated mRNA expression of all osteogenic genes was observed in differentiated BMSCs and ADSCs, but with different patterns confirmed by real-time RT-PCR. Deposition of calcified extracellular matrix was significantly greater in differentiated ADSCs compared with differentiated BMSCs. X-ray and histological examination indicated significant bone regeneration in the calvarial defects transplanted with Ad-BMP4 transduced autologous MSCs compared to the control groups. There was no significant difference in new bone formation in Ad-BMP4 transduced MSCs based on quantitative digital analysis of histological sections. The use of ADSCs often resulted in the growth of fat tissue structures in the control groups, and the fat tissue structures were not seen with BMSC cells. Our data demonstrate that BMP4 can be potently osteoinductive in vivo, resulting in bone repair. ADSCs may be an attractive alternative to BMSCs for bone tissue engineering under appropriate stimuli. But the easy adipogenic differentiation needs to be considered when choosing adipose tissue for specific clinical application.

  2. Guided bone regeneration in pig calvarial bone defects using autologous mesenchymal stem/progenitor cells - a comparison of different tissue sources.

    PubMed

    Stockmann, Philipp; Park, Jung; von Wilmowsky, Cornelius; Nkenke, Emeka; Felszeghy, Endre; Dehner, Jan-Friedrich; Schmitt, Christian; Tudor, Christian; Schlegel, Karl Andreas

    2012-06-01

    Due to donor side morbidity and the absence of osteogenic properties in bone substitutes, there is a growing need for an alternative to traditional bone grafting within the scope of tissue engineering. This animal study was conducted to compare the in vivo osteogenic potential of adipose-derived (AD), periosteum-derived (PD) and bone marrow-derived (BM) mesenchymal stem/progenitor cells (MSC). Autologous mesenchymal stem/progenitor cells of named tissue origin were induced into osteogenic differentiation following in vitro cell expansion. Ex vivo cultivated cells were seeded on a collagen scaffold and subsequently added to freshly created monocortical calvarial bone defects in 21 domestic pigs. Pure collagen scaffold served as a control defect. The animals were sacrificed at specific time points and de novo bone formation was quantitatively analyzed by histomorphometry. Bone volume/total defect volume (BV/TV) and the mineralization rate of newly formed bone were compared among the groups. In the early stages of wound healing, up to 30 days, the test defects did not show better bone regeneration than those in the control defect, but the bone healing process in the test defects was accelerated in the later stage compared to those in the control defect. All the test defects showed complete osseous healing after 90 days compared to those in the control defect. During the observation period, no significant differences in BV/TV and mineralization of newly formed bone among the test defects were observed. Irrespective of the tissue sources of MSC, the speed and pattern of osseous healing after cell transplantations into monocortical bone defects were comparable. Our results indicate that the efficiency of autologous AD-MSC, PD-MSC and BM-MSC transplantation following ex vivo cell expansion is not significantly different for the guided regeneration of bone defects.

  3. Human breast adipose‑derived stem cells: characterization and differentiation into mammary gland‑like epithelial cells promoted by autologous activated platelet‑rich plasma.

    PubMed

    Cui, Shi-En; Li, Hong-Mian; Liu, Da-Lie; Nan, Hua; Xu, Kun-Ming; Zhao, Pei-Ran; Liang, Shuang-Wu

    2014-08-01

    Human adipose‑derived stem cells (ASCs) isolated from various body sites have been widely investigated in basic and clinical studies. However, ASCs derived from human breast tissue (hbASCs) have not been extensively investigated. In order to expand our understanding of hbASCs and examine their potential applications in stem cell research and cell‑based therapy, hbASCs were isolated from discarded surgical fat tissue following reduction mammoplasty and a comprehensive characterization of these hbASCs was performed, including analysis of their cellular morphology, growth features, cell surface protein markers and multilineage differentiation capacity. These hbASCs expressed cluster of differentiation (CD)44, CD49d, CD90 and CD105, but did not express CD31 and CD34. Subsequently, the hbASCs were differentiated into adipocytes, osteocytes and chondrocytes in vitro. In order to examine the potential applications of hbASCs in breast reconstruction, an approach to promote in vitro differentiation of hbASCs into mammary gland‑like epithelial cells (MGECs) was developed using activated autologous platelet‑rich plasma (PRP). A proliferation phase and a subsequent morphological conversion phase were observed during this differentiation process. PRP significantly promoted the growth of hbASCs in the proliferation phase and increased the eventual conversion rate of hbASCs into MGECs. Thus, to the best of our knowledge, the present study provided the first comprehensive characterization of hbASCs and validated their multipotency. Furthermore, it was revealed that activated autologous PRP was able to enhance the differentiation efficiency of hbASCs into MGECs. The present study and other studies of hbASCs may aid the development of improved breast reconstruction strategies.

  4. The effect of leukocyte-reduced platelet-rich plasma on the proliferation of autologous adipose-tissue derived mesenchymal stem cells.

    PubMed

    Loibl, Markus; Lang, Siegmund; Brockhoff, Gero; Gueorguiev, Boyko; Hilber, Franz; Worlicek, Michael; Baumann, Florian; Grechenig, Stephan; Zellner, Johannes; Huber, Michaela; Valderrabano, Victor; Angele, Peter; Nerlich, Michael; Prantl, Lukas; Gehmert, Sebastian

    2016-01-01

    Clinical application of platelet-rich plasma (PRP) and stem cells has become more and more important in regenerative medicine during the last decade. However, differences in PRP preparations may contribute to variable PRP compositions with unpredictable effects on a cellular level. In the present study, we modified the centrifugation settings in order to provide a leukocyte-reduced PRP and evaluated the interactions between PRP and adipose-tissue derived mesenchymal stem cells (ASCs).PRP was obtained after modification of three different centrifugation settings and investigated by hemogram analysis, quantification of protein content and growth factor concentration. ASCs were cultured in serum-free α-MEM supplemented with autologous 10% or 20% leukocyte-reduced PRP. Cell cycle kinetics of ASCs were analyzed using flow cytometric analyses after 48 hours.Thrombocytes in PRP were concentrated, whereas erythrocytes, and white blood cells (WBC) were reduced, independent of centrifugation settings. Disabling the brake further reduced the number of WBCs. A higher percentage of cells in the S-phase in the presence of 20% PRP in comparison to 10% PRP and 20% fetal calf serum (FCS) advocates the proliferation stimulation of ASCs.These findings clearly demonstrate considerable differences between three PRP separation settings and assist in safeguarding the combination of leukocyte-reduced PRP and stem cells for regenerative therapies.

  5. Allogeneic peripheral stem cell transplantation in a case of hereditary sideroblastic anaemia.

    PubMed

    González, M I; Caballero, D; Vázquez, L; Cañizo, C; Hernández, R; López, C; Izarra, A; Arroyo, J L; González, M; García, R; San Miguel, J F

    2000-06-01

    We report on a case of pyridoxine refractory hereditary sideroblastic anaemia (HSA) in a 19-year-old man who underwent peripheral blood stem cell transplantation (PBSCT) from his HLA-identical brother. By using short tandem repeat polymorphism, 100% donor cells were observed in peripheral blood on day +21; bone marrow showed mixed chimaerism from day +21 to day +221, when 100% cells of donor origin were observed. The patient developed extensive chronic graft-versus-host disease with favourable response to treatment. When the haemoglobin range was normal, a programme of phlebotomies reduced serum ferritin levels. Three years after transplantation, the patient has an ECOG rating of 0, with completely normal haemoglobin values (15 g/dl). To our knowledge, this is the first PBSCT reported in a case of hereditary sideroblastic anaemia.

  6. Consolidation with autologous stem cell transplantation in first remission is safe and effective in AML patients above 65 years.

    PubMed

    Heini, Alexander D; Berger, Martin D; Seipel, Katja; Taleghani, Behrouz Mansouri; Baerlocher, Gabriela M; Leibundgut, Kurt; Banz, Yara; Novak, Urban; Pabst, Thomas

    2017-02-01

    The outcome of AML patients ≥65 years remains disappointing. Current post-induction strategies for elderly AML patients fit for intensive treatment involve additional cycles of chemotherapy or allogeneic transplantation. Consolidation with autologous transplantation (ASCT) is poorly studied in these patients. In this single-center retrospective analysis, we determined survival rates of AML patients ≥65 years undergoing busulfan/cyclophosphamide conditioning before ASCT in first remission between 2007 and 2015. We found elderly AML patients with ASCT to have longer progression-free survival (PFS; 16.3 vs. 5.1 months, P=0.0166) and overall survival (OS; n.r. vs. 8.2 months; P=0.0255) than elderly AML patients without ASCT consolidation. In addition, elderly AML patients undergoing ASCT had comparable PFS (P=0.9462) and OS (P=0.7867) as AML patients below 65 years receiving ASCT consolidation in CR1. Our data suggest that ASCT is an option in elderly fit AML patients who appear to benefit from autologous consolidation similarly to younger AML patients.

  7. Darbepoetin-alfa and intravenous iron administration after autologous hematopoietic stem cell transplantation: a prospective multicenter randomized trial.

    PubMed

    Beguin, Yves; Maertens, Johan; De Prijck, Bernard; Schots, Rik; Seidel, Laurence; Bonnet, Christophe; Hafraoui, Kaoutar; Willems, Evelyne; Vanstraelen, Gaetan; Servais, Sophie; Jaspers, Aurélie; Fillet, Georges; Baron, Frederic

    2013-12-01

    We conducted a randomized study analyzing the impact of darbepoetin alfa (DA) administration with or without intravenous (i.v.) iron on erythroid recovery after autologous hematopoietic cell transplantation (HCT). Patients were randomized between no DA (Arm 1), DA 300 μg every 2 weeks starting on Day 28 after HCT (Arm 2), or DA plus i.v. iron 200 mg on Days 28, 42, and 56 (Arm 3). The proportion achieving complete hemoglobin (Hb) response within 18 weeks (primary end point) was 21% in Arm 1 (n = 24), 79% in Arm 2 (n = 25), and 100% in Arm 3 (n = 23; P < 0.0001). Erythropoietic response was shown to be significantly higher in Arm 3 (n = 46) than in Arm 2 (n = 50; P = 0.008), resulting in lower DA use, reduced drug costs, and improved quality of life scores, but the effect on transfusions was not significant. In multivariate analysis, DA administration (P < 0.0001), i.v. iron administration (P = 0.0010), high baseline Hb (P < 0.0001), and low baseline creatinine (P = 0.0458) were independently associated with faster achievement of complete Hb response. In conclusion, DA is highly effective to ensure full erythroid reconstitution after autologous HCT when started on Day 28 post-transplant. I.v. iron sucrose further improves erythroid recovery.

  8. Does the FDA have regulatory authority over adult autologous stem cell therapies? 21 CFR 1271 and the emperor's new clothes

    PubMed Central

    2012-01-01

    FDA has recently asserted that many autologous cell therapies once considered the practice of medicine are in fact drugs. These changes began with the creation of new sections of 21 CFR 1271 and a subsequent one word change where the FDA, without public commentary, altered a single word in its regulatory language regarding cell and tissue based therapies that asserted the authority to classify autologous tissue as drugs. The bright line between medical care and drug production can be delineated in many ways, but a simple metric that defines the dichotomy is the consent status of the patient. In healthcare, a patient can either be consented individually for a medical procedure or exposed to an unconsented risk where regulatory assurances are already in place. These new FDA policies apply rules meant to keep drugs safe in a drug factory (unconsented mass production risks) to individually consented surgical procedures. We argue that there is little societal benefit to these changes and that they are already stifling medical innovation. PMID:22448812

  9. Prospective noninterventional study on peripheral blood stem cell mobilization in patients with relapsed lymphomas.

    PubMed

    van Gorkom, Gwendolyn; Finel, Herve; Giebel, Sebastian; Pohlreich, David; Shimoni, Avichai; Ringhoffer, Mark; Sucak, Gülsan; Schaap, Nicolaas; Dreger, Peter; Sureda, Anna; Schouten, Harry C

    2016-09-10

    High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) to rescue hematopoiesis is considered standard care for patients with a relapsed chemosensitive lymphoma, but diagnosis of lymphoma has been a risk factor for poor mobilization in several studies. The aim of this prospective noninterventional clinical audit was to review the mobilization strategies used by EBMT centers in relapsed lymphoma and to evaluate their efficacy. Between 2010 and 2014, 275 patients with relapsed lymphoma from 30 EBMT centers were prospectively registered. Almost all patients were mobilized with chemotherapy plus G-CSF (96%), but there was a large variation in chemotherapy schedules. Thirty (11%) of them were poor mobilizers (<2 × 10(6) CD 34+ cells/kg body weight) at the first mobilization. Poor mobilization was not associated with gender, age, bone marrow involvement at diagnosis, primary diagnosis, number of previous chemotherapy lines, previous radiotherapy or mobilization with G-CSF alone. The use of high dose cyclophosphamide alone was associated with mobilization failure (P = 0.0006), whereas the use of a platinum-containing regimen was associated with a good mobilization outcome (P = 0.013). Because failure rate is low, we can conclude from this study that PBSC mobilization failure in relapsed lymphomas is not an important problem in the EBMT centers.

  10. A case report and literature review of primary resistant Hodgkin lymphoma: a response to anti-PD-1 after failure of autologous stem cell transplantation and brentuximab vedotin

    PubMed Central

    Xu, Peipei; Wang, Fan; Guan, Chaoyang; Ouyang, Jian; Shao, Xiaoyan; Chen, Bing

    2016-01-01

    Hodgkin lymphoma (HL) is a highly curable hematologic malignancy, and ~70% of cases can be cured with combination chemotherapy with or without radiation. However, patients with primary resistant disease have a cure rate of <30%. For such patients, high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is considered to be the standard treatment. If patients fail to respond to ASCT or relapse soon thereafter, they usually receive another ASCT, allogeneic stem cell transplantation or treatment with novel agents. This case report presents the case of a 54-year-old patient with primary resistant HL who received single-agent treatment, brentuximab vedotin, after ASCT relapse. Despite treatment with brentuximab vedotin, the disease continued to progress. In patients with such highly resistant disease, the treatment options are limited. Depending on the physical condition and the willingness of the patient, pembrolizumab, a programmed cell death protein-1 inhibitor, can be given as salvage therapy. But, out of our expectation, the patient achieved a very good partial response after four cycles of pembrolizumab. No serious adverse events were observed with pembrolizumab treatment. This case provides support for a new and effective strategy for treating primary resistant Hodgkin lymphoma. PMID:27703376

  11. Intraventricular Transplantation of Autologous Bone Marrow Mesenchymal Stem Cells via Ommaya Reservoir in Persistent Vegetative State Patients after Haemorrhagic Stroke: Report of Two Cases & Review of the Literature

    PubMed Central

    Fauzi, Asra Al; Suroto, Nur Setiawan; Bajamal, Abdul Hafid; Machfoed, Moh. Hasan

    2016-01-01

    Background: One of the most devastating diseases, stroke, is a leading cause of death and disability worldwide with severe emotional and economic consequences. The purpose of this article is mainly to report the effect of intraventricular transplantation via an Ommaya reservoir using autologous bone marrow mesenchymal stem cells (BM-MSCs) in haemorrhagic stroke patients. Case Presentations: Two patients, aged 51 and 52, bearing sequels of haemorrhagic stroke were managed by intraventricular transplantation of BM-MSCs obtained from their own bone marrow. Before the procedure, both patients were bedridden, tracheostomised, on nasogastric (NG) tube feeding and in hemiparesis. The cells were transplanted intraventricularly (20 x 106 cells/2.5 ml) using an Ommaya reservoir, and then repeated transplantations were done after 1 and 2 months consecutively. The safety and efficacy of the procedures were evaluated 3, 6 and 12 months after treatment. The National Institute of Health Stroke Scale (NIHSS) was used to evaluate the patients’ neurological status before and after treatment. No adverse events derived from the procedures or transplants were observed in the one-year follow-up period, and the neurological status of both patients improved after treatment. Conclusions: Our report demonstrates that the intraventricular transplantation of BM-MSCs via an Ommaya reservoir is safe and it improves the neurological status of post-haemorrhagic stroke patients. The repeated transplantation procedure is easier and safer to perform via a subcutaneously implanted Ommaya reservoir. Key Words: Haemorrhagic stroke, bone marrow mesenchymal stem cells (BM-MSCs), intraventricular transplantation PMID:28096634

  12. Putative Epimutagens in Maternal Peripheral and Cord Blood Samples Identified Using Human Induced Pluripotent Stem Cells

    PubMed Central

    Arai, Yoshikazu; Hayakawa, Koji; Arai, Daisuke; Ito, Rie; Iwasaki, Yusuke; Saito, Koichi; Akutsu, Kazuhiko; Takatori, Satoshi; Ishii, Rie; Hayashi, Rumiko; Izumi, Shun-Ichiro; Sugino, Norihiro; Kondo, Fumio; Horie, Masakazu; Nakazawa, Hiroyuki; Makino, Tsunehisa; Hirosawa, Mitsuko; Shiota, Kunio; Ohgane, Jun

    2015-01-01

    The regulation of transcription and genome stability by epigenetic systems are crucial for the proper development of mammalian embryos. Chemicals that disturb epigenetic systems are termed epimutagens. We previously performed chemical screening that focused on heterochromatin formation and DNA methylation status in mouse embryonic stem cells and identified five epimutagens: diethyl phosphate (DEP), mercury (Hg), cotinine, selenium (Se), and octachlorodipropyl ether (S-421). Here, we used human induced pluripotent stem cells (hiPSCs) to confirm the effects of 20 chemicals, including the five epimutagens, detected at low concentrations in maternal peripheral and cord blood samples. Of note, these individual chemicals did not exhibit epimutagenic activity in hiPSCs. However, because the fetal environment contains various chemicals, we evaluated the effects of combined exposure to chemicals (DEP, Hg, cotinine, Se, and S-421) on hiPSCs. The combined exposure caused a decrease in the number of heterochromatin signals and aberrant DNA methylation status at multiple gene loci in hiPSCs. The combined exposure also affected embryoid body formation and neural differentiation from hiPSCs. Therefore, DEP, Hg, cotinine, Se, and S-421 were defined as an “epimutagen combination” that is effective at low concentrations as detected in maternal peripheral and cord blood. PMID:26339649

  13. Granulocyte colony-stimulating factor increases the platelet volume in peripheral stem cell apheresis donors.

    PubMed

    Ihara, Akihiro; Matsui, Keiko; Minami, Ryouta; Uchida, Shuzou; Ueda, Shuji; Nishiura, Tetsuo

    2008-01-01

    We investigated the short-term influence of granulocyte colony-stimulating factor (G-CSF) administration on platelet counts and platelet indices in 12 donors (8 males and 4 females; median age 34 years, range 16-49) for peripheral stem cell transplantation using an automated blood cell analyzer. On day 3 (D3) compared with D0, 11 donors with normal laboratory and physical findings showed increases in platelet indices (chi(2) = 12.0, p = 0.0025). Furthermore, mean platelet volume (MPV) was significantly increased (p = 0.04). Also, platelet count decreased, and platelet distribution width and platelet-large cell ratio were increased, but these were not significant. On the contrary, 1 donor with abnormal laboratory findings who had large platelets (MPV 11.4 fl) before G-CSF administration showed decreases in platelet indices (MPV 10.3 fl) on D3, although platelet count (18.2 x 10(4)/microl) decreased after G-CSF administration. G-CSF administration induces an inflammatory process with endothelial cell activation. This is probably the reason why platelet volume increases after G-CSF use. This is the first report showing that G-CSF administration immediately induces increases in large platelets in peripheral stem cell transplant donors before harvest.

  14. Determination of hematopoietic stem cells in peripheral blood by an automated hematology analyzer (SE-9000).

    PubMed

    Takekawa, K; Yamane, T; Hino, M; Tatsumi, N

    1998-12-01

    We evaluated the usefulness of an automated hematology analyzer (SE-9000) for the identification and counting of peripheral blood stem cells (PBSCs). The samples tested were from 14 patients with hematological malignancies. Peripheral blood samples were collected from the subjects before and after a course of chemotherapy. From the leukapheresis sample, CD34+ cells, assumed to be hematopoietic stem cells, were obtained with an immunomagnetic cell separator. The CD34+ cells obtained accumulated in the gate corresponding to low recurrent frequencies of the automated hematology analyzer. This gate shows results of the 'immature information' (IMI) channel. Software for detection of only the cells that accumulated in this gate was therefore developed. With this trial program, the regression coefficient between the percentage of leukocytes from the blood samples that were CD34+ and the percentage of such leukocytes that appeared on the IMI channel was 0.79. With this analyzer, the number of PBSC could be counted in about 80 s. The identification and counting of cells picked up by the IMI channel should be clinically useful for the monitoring of changes in PBSC after chemotherapy for mobilization.

  15. Proceedings from the National Cancer Institute's Second International Workshop on the Biology, Prevention, and Treatment of Relapse after Hematopoietic Stem Cell Transplantation: part II. Autologous Transplantation-novel agents and immunomodulatory strategies.

    PubMed

    Avigan, David; Hari, Parameswaran; Battiwalla, Minoo; Bishop, Michael R; Giralt, Sergio A; Hardy, Nancy M; Kröger, Nicolaus; Wayne, Alan S; Hsu, Katharine C

    2013-12-01

    In the National Cancer Institute's Second International Workshop on the Biology, Prevention, and Treatment of Relapse after Hematopoietic Stem Cell Transplantation, the Scientific/Educational Session on Autologous Transplantation addressed the role of novel agents and immunomodulatory strategies in management of relapse after autologous hematopoietic stem cell transplantation (AHSCT). Concepts were illustrated through in-depth discussion of multiple myeloma, with broader discussion of areas relevant for relapse of other malignancies as well as in the setting of allogeneic transplantation. Dr. Hari provided an overview of the epidemiology of relapse after AHSCT in multiple myeloma, addressing clinical patterns, management implications, and treatment options at relapse, highlighting the implications of novel therapeutic agents in initial, maintenance, and relapse treatment. Dr. Avigan discussed current concepts in tumor vaccine design, including whole cell and antigen-specific strategies, use of an AHSCT platform to reverse tumor-associated immunosuppression and tolerance, and combining vaccines with immunomodulatory agents to promote establishment of durable antitumor immunity. Dr. Hsu reviewed the immunogenetics of natural killer (NK) cells and general NK biology, the clinical importance of autologous NK activity (eg, lymphoma and neuroblastoma), the impact of existing therapies on promotion of NK cell activity (eg, immunomodulatory drugs, monoclonal antibodies), and strategies for enhancing autologous and allogeneic NK cell effects through NK cell gene profiling.

  16. Veno-occlusive disease of the liver after high-dose cytoreductive therapy with busulfan and melphalan for autologous blood stem cell transplantation in multiple myeloma patients.

    PubMed

    Carreras, Enric; Rosiñol, Laura; Terol, Maria José; Alegre, Adrián; de Arriba, Felipe; García-Laraña, José; Bello, José Luis; García, Raimundo; León, Angel; Martínez, Rafael; Peñarrubia, M Jesús; Poderós, Concha; Ribas, Paz; Ribera, Josep Maria; San Miguel, Jesús; Bladé, Joan; Lahuerta, Juan José

    2007-12-01

    Veno-occlusive disease of the liver (VOD) is a potentially severe complication of high-dose cytoreductive therapy (HDT) used for stem cell transplantation (SCT). This complication is uncommon after HDT for autologous SCT (ASCT) in patients with multiple myeloma (MM). The Spanish Myeloma Group/PETHEMA conducted a study (MM2000) for patients with newly diagnosed MM consisting of induction with alternating VBMCP/VBAD chemotherapy followed by intensification with busulfan/melphalan (Bu/MEL) with a second high-dose therapy procedure in patients not achieving at least near-complete remission with the first procedure. After 2 years of the trial, a number of episodes resembling classical VOD but with a late onset were recognized. Consequently, the protocol was modified, and Bu/MEL was replaced by melphalan 200 mg/m(2) (MEL-200). Three years later, after a total of 734 patients had undergone first autologous SCT, the incidence and characteristics of VOD episodes were analyzed in the whole series. Nineteen cases of VOD (8%) were observed among the first 240 patients receiving Bu/MEL, whereas only 2 (0.4%) were observed among the 494 patients treated with MEL-200 (P < .0001). VOD manifestations in the Bu/MEL group appeared at a median of 29 days (range, 3-57 days) after ASCT. Mortality directly attributable to VOD was 2% in the Bu/MEL group and 0.2% in the MEL-200 group (P = .026). This high incidence of severe VOD probably had a multifactorial origin (busulfan followed by melphalan and previous use of BCNU). This observation should be kept in mind when designing future trials for the treatment of MM.

  17. Autologous Hematopoietic Stem Cells transplantation and genetic modification of CCR5 m303/m303 mutant patient for HIV/AIDS.

    PubMed

    Esmaeilzadeh, Abdolreza; Farshbaf, Alieh; Erfanmanesh, Maryam

    2015-03-01

    HIV and AIDS is one of the biggest challenges all over the world. There are an approximately 34 million people living with the virus, and a large number of them become infected each year. Although there are some antiviral drugs for HIV viral load reduction, they are not sufficient. There is no cure for AIDS. Nowadays natural resistance or immunity has absorbed attentions. Because in some HIV positive patients progression trend is slow or even they indicate resistance to AIDS. One of the most interesting approaches in this category is CCR5 gene. CCR5 is a main cc-chemokine co-receptor that facilitates HIV-1 entry to macrophage and CD4(+) T cells. To now, many polymorphisms have been known by CCR5 gene that produces a truncated protein with no function. So, HIV-1 could not entry to immune-cells and the body resistant to HIV/AIDS. Δ32/Δ32 and m303/m303 homozygotes are example of mutations that could create this resistance mechanism. There is a new treatment, such as Hematopoietic Stem Cell transplantation (HSCT) in Berlin and Boston patients for Δ32/Δ32 mutation. It could eliminate co-receptor antagonist and highly-active-anti retroviral therapy (HAART) drugs problems such as toxicity, low safety and side-effects. Now there, the aim of this hypothesis will be evaluation of a new mutation CCR5 m303/m303 as autologous HSCT. This novel hypothesis indicates that autologous HSCT for m303/m303 could be effective treatment for anyone HIV/AIDS affected patient worldwide.

  18. Clinical significance of peripheral blood erythroblastosis after hematopoietic stem cell transplantation.

    PubMed

    Goyama, Susumu; Kanda, Yoshinobu; Nannya, Yasuhito; Ogawa, Seishi; Asano-Moki, Yuki; Ogawa, Natsu; Nakagawa, Masahiro; Sakata-Yanagimoto, Mamiko; Kawazu, Masahito; Komeno, Yukiko; Imai, Yoichi; Hangaishi, Akira; Kurokawa, Mineo; Tsujino, Shiho; Aoki, Katsunori; Chiba, Shigeru; Motokura, Toru; Hirai, Hisamaru

    2004-12-01

    Erythroblasts (EBL) are normally not observed in peripheral blood, but may be found in patients suffering from a variety of severe diseases. The detection of EBL in peripheral blood has been shown to be associated with a poor prognosis. However, the clinical significance of peripheral erythroblastosis after hematopoietic stem cell transplantation (HSCT) has not been evaluated. We retrospectively analyzed the records of 161 patients who underwent HSCT at our hospital from June 1995 to October 2001. EBL at any level were detected in 94% of the patients. Forty-four and 11 patients experienced erythroblastosis exceeding 200 and 1,000/ul, respectively. The erythroblast count was higher in patients who died than in the survivors (geometric mean value 184 vs. 100/ul, P=0.01). High-level erythroblastosis ( >1,000/ul) within 180 days after HSCT was associated with an extremely poor prognosis (median survival 22.5 days). Among the possible confounding factors, the use of total body irradiation (RR 2.35, 95% CI 1.22 - 4.54, P=0.011) and the disease status before transplantation (RR 2.51, 95% CI 1.15 - 5.49, P=0.021) were independent significant factors for erythroblastosis after HSCT. As for post-transplant events, a high EBL concentration was frequently preceded by graft-vs.-host disease, thrombotic microangiopathy, hypoxia, and hematological relapse.

  19. Stage-related results in treatment of hip osteonecrosis with core-decompression and autologous mesenchymal stem cells.

    PubMed

    Persiani, Pietro; De Cristo, Claudia; Graci, Jole; Noia, Giovanni; Gurzì, Michele; Villani, Ciro

    2015-09-01

    Our aim is to analyse the clinical outcome of a series of patients affected by avascular necrosis of the femoral head and treated with core-decompression technique and autologous stromal cells of the bone marrow.We enrolled in our study 29 patients with 31 hips in total affected by avascular necrosis of the femoral head. The clinical and radiological outcome has been assessed through self-administered questionnaires (HHS, VAS and SF12) X-ray and Magnetic Resonance.Of all the examined hips, 25 showed a relief of the symptoms and a resolution of the osteonecrosis, 11 of these were at Stage I and 14 at Stage II. The progression of the disease occurred in 6 hips (2 Stage II, 2 Stage III and 2 Stage IV). Our results show a significant decrease in joint pain level and a success in avoiding or delaying the need of hip replacement in early stages of osteonecrosis.

  20. Derivation of autism spectrum disorder-specific induced pluripotent stem cells from peripheral blood mononuclear cells.

    PubMed

    DeRosa, Brooke A; Van Baaren, Jessica M; Dubey, Gaurav K; Lee, Joycelyn M; Cuccaro, Michael L; Vance, Jeffery M; Pericak-Vance, Margaret A; Dykxhoorn, Derek M

    2012-05-10

    Induced pluripotent stem cells (iPSCs) hold tremendous potential both as a biological tool to uncover the pathophysiology of disease by creating relevant cell models and as a source of stem cells for cell-based therapeutic applications. Typically, iPSCs have been derived by the transgenic overexpression of transcription factors associated with progenitor cell or stem cell function in fibroblasts derived from skin biopsies. However, the need for skin punch biopsies to derive fibroblasts for reprogramming can present a barrier to study participation among certain populations of individuals, including children with autism spectrum disorders (ASDs). In addition, the acquisition of skin punch biopsies in non-clinic settings presents a challenge. One potential mechanism to avoid these limitations would be the use of peripheral blood mononuclear cells (PBMCs) as the source of the cells for reprogramming. In this article we describe, for the first time, the derivation of iPSC lines from PBMCs isolated from the whole blood of autistic children, and their subsequent differentiation in GABAergic neurons.

  1. Clinical efficacy and safety of autologous stem cell transplantation for patients with ST-segment elevation myocardial infarction

    PubMed Central

    Li, Rong; Li, Xiao-Ming; Chen, Jun-Rong

    2016-01-01

    Purpose The purpose of this study is to evaluate the therapeutic efficacy and safety of stem cells for the treatment of patients with ST-segment elevation myocardial infarction (STEMI). Materials and methods We performed a systematic review and meta-analysis of relevant published clinical studies. A computerized search was conducted for randomized controlled trials of stem cell therapy for STEMI. Results Twenty-eight randomized controlled trials with a total of 1,938 STEMI patients were included in the present meta-analysis. Stem cell therapy resulted in an improvement in long-term (12 months) left ventricular ejection fraction of 3.15% (95% confidence interval 1.01–5.29, P<0.01). The 3-month to 4-month, 6-month, and 12-month left ventricular end-systolic volume showed favorable results in the stem cell therapy group compared with the control group (P≤0.05). Significant decrease was also observed in left ventricular end-diastolic volume after 3-month to 4-month and 12-month follow-up compared with controls (P<0.05). Wall mean score index was reduced significantly in stem cell therapy group when compared with the control group at 6-month and 12-month follow-up (P=0.01). Moreover, our analysis showed a significant change of 12-month infarct size decrease in STEMI patients treated with stem cells compared with controls (P<0.01). In addition, no significant difference was found between treatment group and control in adverse reactions (P>0.05). Conclusion Overall, stem cell therapy is efficacious in the treatment of patients with STEMI, with low rates of adverse events compared with control group patients. PMID:27536122

  2. The role of exosomes in peripheral nerve regeneration

    PubMed Central

    Ching, Rosanna C.; Kingham, Paul J.

    2015-01-01

    Peripheral nerve injuries remain problematic to treat, with poor functional recovery commonly observed. Injuries resulting in a nerve gap create specific difficulties for axonal regeneration. Approaches to address these difficulties include autologous nerve grafts (which are currently the gold standard treatment) and synthetic conduits, with the latter option being able to be impregnated with Schwann cells or stem cells which provide an appropriate micro-environment for neuronal regeneration to occur. Transplanting stem cells, however, infers additional risk of malignant transformation as well as manufacturing difficulties and ethical concerns, and the use of autologous nerve grafts and Schwann cells requires the sacrifice of a functioning nerve. A new approach utilizing exosomes, secreted extracellular vesicles, could avoid these complications. In this review, we summarize the current literature on exosomes, and suggest how they could help to improve axonal regeneration following peripheral nerve injury. PMID:26109947

  3. Tailored strategy for AML patients receiving allogeneic peripheral blood stem cell transplantation.

    PubMed

    Sohn, Sang Kyun; Kim, Jong Gwang; Kim, Dong Hwan

    2006-10-01

    Considering the heterogeneity of acute myelogenous leukemia (AML), along with the pros and cons of allogeneic peripheral blood stem cell transplantation (PBSCT), a tailored strategy is needed to minimize the transplant-related mortality and maximize the transplant outcomes in AML patients exhibiting certain factors that have an impact on the post-transplant quality of life and outcomes. The factors that need to be considered when tailoring a strategy in an allogeneic PBSCT setting include the recipient's performance status and co-morbid disease include AML risk stratification, disease status, expected severity of graft-versus-host disease, and the necessity of a graft-versus-leukemia effect. Accordingly, this review article describes a possible tailoring strategy for AML patients receiving allogeneic PBSCT based on certain factors influencing the transplant outcome.

  4. Successful treatment of acquired pure red cell aplasia (PRCA) by allogeneic peripheral blood stem cell transplantation.

    PubMed

    Tseng, Shih-Bin; Lin, Sheng-Fung; Chang, Chao-Sung; Liu, Ta-Chih; Hsiao, Hui-Hua; Liu, Yi-Chang; Tsai, Hui-Jen; Chen, Tyen-Po

    2003-12-01

    A 37-year-old male was treated successfully by peripheral blood stem cell transplantation (PBSCT) from his HLA-identical sister for refractory acquired pure red cell aplasia (PRCA). The conditioning regimen was cyclophosphamide 50 mg/kg/day for 4 days plus TBI 300 cGy in a single fraction. Absolute neutrophil count (ANC) >500/microl and platelet counts >20,000/microl were achieved 8 days after PBSCT without transfusion. Chimerism study on day 218 revealed full donor chimerism. The hemoglobin level was stable around 12-13 g/dl with normal leukocyte and platelet counts after PBSCT during a long follow-up period. From this case, PBSCT should be considered for patients with refractory acquired PRCA with an HLA-identical donor.

  5. Autologous adipose-derived stem cells: Basic science, technique, and rationale for application in ulcer and wound healing.

    PubMed

    Zollino, Ilaria; Zuolo, Michele; Gianesini, Sergio; Pedriali, Massimo; Sibilla, Maria Grazia; Tessari, Mirko; Carinci, Francesco; Occhionorelli, Savino; Zamboni, Paolo

    2017-04-01

    Objectives The present review represents a translational boundary between basic research and surgery, particularly focusing on the promising application of adipose-derived stem cells harvested intra-operatively during debridement of venous leg ulcers. Methods We reviewed 830 out of 5578 articles on MEDLINE starting from 1997 and sorted by the relevance option. Results The technique currently used for adipose-derived stem cells intra-operative harvesting is presented, including a safety evaluation on a cohort of 5089 revised patients who underwent plastic surgery and maxillo-facial surgical procedures. Complications were reported in 169 cases (3.3%). One hundred and forty-one (2.77%) patients were classified as having minor complications, specifically: nodularity/induration 93 (1.83%), dysesthesia 14 (0.26%), hematoma 12 (0.23%), superficial infection 11 (0.21%), pain 7 (0.13%), poor cosmesis 3 (0.06%), and abnormal breast secretion 1 (0.02%), while 28 patients (0.55%) were classified as having major complications, specifically: deep infection 22 (0.43%), sepsis 3 (0.06%), abdominal hematoma 2 (0.04%), and pneumothorax 1 (0.02%). Application of cell therapy in venous leg ulcer is currently used only for patients not responding to the standard treatment. The review shows the lack of randomized clinical trials for application of adipose-derived stem cells among treatments for venous leg ulcer. Finally, adipose-derived stem cells implantation at the wound site promotes a new tissue formation rich in vascular structures and remodeling collagen. Conclusion Adipose-derived stem cells strategy represents a great opportunity for the treatment of chronic wounds, due to the simplicity of the technique and the application of cell treatment in the operating room immediately following debridement. However, clinical studies and data from randomized trials are currently lacking.

  6. Highly favorable outcome in BRCA-mutated metastatic breast cancer patients receiving high-dose chemotherapy and autologous hematopoietic stem cell transplantation.

    PubMed

    Boudin, L; Gonçalves, A; Sabatier, R; Moretta, J; Sfumato, P; Asseeva, P; Livon, D; Bertucci, F; Extra, J-M; Tarpin, C; Houvenaegel, G; Lambaudie, E; Tallet, A; Resbeut, M; Sobol, H; Charafe-Jauffret, E; Calmels, B; Lemarie, C; Boher, J-M; Viens, P; Eisinger, F; Chabannon, C

    2016-08-01

    Breast cancer carrying BRCA mutation may be highly sensitive to DNA-damaging agents. We hypothesized a better outcome for BRCA-mutated (BRCA(mut)) metastatic breast cancer (MBC) patients receiving high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HDC AHSCT) versus unaffected BRCA (BRCA wild type; (BRCA(wt))) or patients without documented BRCA mutation (BRCA untested (BRCA(ut))). All female patients treated for MBC with AHSCT at Institut Paoli-Calmettes between 2003 and 2012 were included. BRCA(mut) and BRCA(wt) patients were identified from our institutional genetic database. Overall survival (OS) was the primary end point. A total of 235 patients were included. In all, 15 patients were BRCA(mut), 62 BRCA(wt) and 149 BRCA(ut). In multivariate analyses, the BRCA(mut) status was an independent prognostic factor for OS (hazard ratio (HR): 3.08, 95% confidence interval (CI): 1.10-8.64, P=0.0326) and PFS (HR: 2.52, 95% CI :1.29-4.91, P=0.0069). In this large series of MBC receiving HDC AHSCT, we report a highly favorable survival outcome in the subset of patients with documented germline BRCA mutations.

  7. Longitudinal effects of high-dose chemotherapy and autologous stem cell transplantation on quality of life in the treatment of metastatic breast cancer.

    PubMed

    Carlson, L E; Koski, T; Glück, S

    2001-05-01

    This study determined the effects of high-dose chemotherapy (HDCT) with autologous blood stem cell transplantation (ASCT) on quality of life (QL) in women with metastatic breast cancer prior to, and during treatment, and up to 1-year post-ASCT. Thirty-three women diagnosed with metastatic breast cancer participated in a phase 1 clinical trial of a new combination of cyclophosphamide (CTX) and mitoxantrone (MXT), with dose escalation of paclitaxel. Longitudinal QL data were collected using the functional living index-cancer (FLIC) and symptom scales at seven time periods: pre-induction chemotherapy (CT), post-induction CT, post-high dose CT (HDCT), and at 3, 6, 9 and 12 months post-ASCT. FLIC scores indicated that the worst problems for patients were feelings of hardship on themselves and their families, followed by psychological functioning and physical functioning problems. The time around diagnosis of the metastatic disease and following HDCT were the worst times for all levels of quality of life, but anxiety and depression symptoms continued to increase in severity across the entire follow-up period. The symptoms that were most problematic were worry about the future, loss of sexual interest, anxiety about the treatment, general worrying, and joint pain. These data highlight the problems that women with metastatic breast cancer encounter at different stages of the disease and treatment process, and can be used to tailor psychosocial interventions appropriate for treating the relevant issues at different points in time.

  8. Immunoablation and autologous hematopoietic stem cell transplantation in the treatment of new-onset type 1 diabetes mellitus: long-term observations.

    PubMed

    Snarski, E; Milczarczyk, A; Hałaburda, K; Torosian, T; Paluszewska, M; Urbanowska, E; Król, M; Boguradzki, P; Jedynasty, K; Franek, E; Wiktor-Jedrzejczak, W

    2016-03-01

    The activity of the autoimmune mechanism underlying type 1 diabetes mellitus (T1DM) can be suppressed when immunoablation and autologous hematopoietic stem cell transplantation (AHSCT) are applied early in the course of the disease. We report here a single centre experience with this treatment modality. Twenty-four patients underwent a AHSCT preceded by immunoablative conditioning with high-dose cyclophosphamide and anti-thymocyte globulin. During the 52-month median time of follow-up 20 out of 23 patients (87%) remained for at least 9.5 months without the use of exogenous insulin. The median time of T1DM remission for these patients was 31 months (range of 9.5-80 months). Among the patients available for follow-up (n=20), four remain insulin free (for 80, 61, 42 and 34 months). The average glycated hemoglobin (HbA1c) concentrations were 10.9% at diagnosis, 5.9% at 1 year, 6.4% at 2 years, 6.8% at 3 years and 7.1% at 4 years after AHSCT. No severe complications of diabetes were seen, however one of the patients died of pseudomonas sepsis in the course of neutropenia after AHSCT. AHSCT leads to a remission of T1DM with good glycemic control in the vast majority of patients, with the period of remission lasting over 5 years in some patients.

  9. Zevalin and BEAM (Z-BEAM) versus rituximab and BEAM (R-BEAM) conditioning chemotherapy prior to autologous stem cell transplantation in patients with mantle cell lymphoma.

    PubMed

    Berger, Martin D; Branger, Giacomo; Klaeser, Bernd; Taleghani, Behrouz Mansouri; Novak, Urban; Banz, Yara; Mueller, Beatrice U; Pabst, Thomas

    2016-09-01

    Early relapse is common in patients with mantle cell lymphoma (MCL) highlighting the unmet need for further improvement of therapeutic options for these patients. CD20 inhibition combined with induction chemotherapy as well as consolidation with high-dose chemotherapy (HDCT) is increasingly considered cornerstones within current therapy algorithms of MCL whereas the role of radioimmunotherapy is unclear. This retrospective single center study compared 46 consecutive MCL patients receiving HDCT in first or second remission. Thirty-five patients had rituximab and BEAM (R-BEAM), and 11 patients received ibritumomab tiuxetan (Zevalin®), an Yttrium-90 labeled CD20 targeting antibody, prior to BEAM (Z-BEAM) followed by autologous stem cell transplantation (ASCT). We observed that the 5-year overall survival (OS) in the R-BEAM and Z-BEAM groups was 55% and 71% (p = 0.288), and the 4-year progression free survival (PFS) was 32% and 41%, respectively (p = 0.300). There were no treatment related deaths in both groups, and we observed no differences in toxicities, infection rates or engraftment. Our data suggest that the Z-BEAM conditioning regimen followed by ASCT is well tolerated, but was not associated with significantly improved survival compared to R-BEAM. Copyright © 2015 John Wiley & Sons, Ltd.

  10. High-risk cytogenetics and persistent minimal residual disease by multiparameter flow cytometry predict unsustained complete response after autologous stem cell transplantation in multiple myeloma.

    PubMed

    Paiva, Bruno; Gutiérrez, Norma C; Rosiñol, Laura; Vídriales, María-Belén; Montalbán, María-Ángeles; Martínez-López, Joaquín; Mateos, María-Victoria; Cibeira, María-Teresa; Cordón, Lourdes; Oriol, Albert; Terol, María-José; Echeveste, María-Asunción; de Paz, Raquel; de Arriba, Felipe; Palomera, Luis; de la Rubia, Javier; Díaz-Mediavilla, Joaquín; Sureda, Anna; Gorosquieta, Ana; Alegre, Adrian; Martin, Alejandro; Hernández, Miguel T; Lahuerta, Juan-José; Bladé, Joan; San Miguel, Jesús F

    2012-01-19

    The achievement of complete response (CR) after high-dose therapy/autologous stem cell transplantation (HDT/ASCT) is a surrogate for prolonged survival in multiple myeloma; however, patients who lose their CR status within 1 year of HDT/ASCT (unsustained CR) have poor prognosis. Thus, the identification of these patients is highly relevant. Here, we investigate which prognostic markers can predict unsustained CR in a series of 241 patients in CR at day +100 after HDT/ASCT who were enrolled in the Spanish GEM2000 (n = 140) and GEM2005 < 65y (n = 101) trials. Twenty-nine (12%) of the 241 patients showed unsustained CR and a dismal outcome (median overall survival 39 months). The presence of baseline high-risk cytogenetics by FISH (hazard ratio 17.3; P = .002) and persistent minimal residual disease by multiparameter flow cytometry at day +100 after HDT/ASCT (hazard ratio 8.0; P = .005) were the only independent factors that predicted unsustained CR. Thus, these 2 parameters may help to identify patients in CR at risk of early progression after HDT/ASCT in whom novel treatments should be investigated.

  11. A Comprehensive Assessment of Toxicities in Patients with Central Nervous System Lymphoma Undergoing Autologous Stem Cell Transplantation Using Thiotepa, Busulfan, and Cyclophosphamide Conditioning.

    PubMed

    Scordo, Michael; Bhatt, Valkal; Hsu, Meier; Omuro, Antonio M; Matasar, Matthew J; DeAngelis, Lisa M; Dahi, Parastoo B; Moskowitz, Craig H; Giralt, Sergio A; Sauter, Craig S

    2017-01-01

    High-dose therapy and autologous stem cell transplantation (ASCT) with thiotepa, busulfan, and cyclophosphamide (TBC) conditioning has emerged as an effective postinduction treatment strategy for patients with primary central nervous system lymphoma (PCNSL) or secondary central nervous system lymphoma (SCNSL), but it is associated with considerable toxicity and transplantation-related mortality (TRM) in the modern era. Forty-three adult patients with chemosensitive PCNSL or SCNSL underwent TBC-conditioned ASCT between 2006 and 2015. Twenty-eight of these patients received pharmacokinetically (PK)-targeted busulfan dosing. The median number of clinically relevant individual grade ≥3 nonhematologic toxicities per patient was 5. We found no association between pretransplantation patient characteristics and the presence of more than 5 grade ≥3 nonhematologic toxicities. Patients with elevated first-dose busulfan area under the curve values did not experience more toxicity. Paradoxically, patients treated with more than 2 regimens before undergoing ASCT had lower first-dose busulfan AUC values. With a median follow-up among survivors of 20 months, 1-year progression-free survival (PFS) and overall survival (OS) from the time of ASCT were 83% and 87%, respectively. Although this study reaffirms the favorable PFS and OS associated with TBC-conditioned ASCT for PCNSL or SCNSL, this treatment strategy carries a large toxicity burden.

  12. Combination of cytogenetic classification and MRD status correlates with outcome of autologous versus allogeneic stem cell transplantation in adults with primary acute myeloid leukemia in first remission.

    PubMed

    Yao, Jianfeng; Zhang, Guixin; Liang, Chen; Li, Gang; Chen, Xin; Ma, Qiaoling; Zhai, Weihua; Yang, Donglin; He, Yi; Jiang, Erlie; Feng, Sizhou; Han, Mingzhe

    2017-04-01

    Both autologous and allogeneic stem cell transplantation (auto- and allo-SCT) are treatment choice for adults with acute myeloid leukemia (AML) after complete remission (CR). However, the decision-making remains controversial in some situations. To figure out the treatment choice, we retrospectively investigated 172 consecutive patients with primary AML who received auto- (n=46) or allo-SCT (n=126) from a single transplant center. Auto- and allo-SCT group demonstrated comparable overall survival (OS) and disease-free survival (DFS) (P=0.616, P=0.559, respectively). Cytogenetic classification and minimal residual disease (MRD) after one course of consolidation were identified as independent risk factors for DFS (hazard ratio (HR), 1.800; 95% CI, 1.172-2.763; P=0.007; HR, 2.042; 95%CI, 1.003-4.154; P=0.049; respectively). We subsequently found that auto- and allo-SCT offered comparable DFS to patients with favorable or intermediate risk and were tested MRD(neg) after one course of consolidation (P=0.270) otherwise auto-SCT were inferior due to increased risk of leukemia relapse. Our study indicated that the combination of cytogenetic classification and MRD monitoring correlated with outcome of auto- versus allo-SCT and might help the choice between the two types of SCT for adults with primary AML, which is of significance for patients with expected intermediate prognosis in the current scenario.

  13. Autologous stem cell transplantation as a first-line treatment strategy for chronic lymphocytic leukemia: a multicenter, randomized, controlled trial from the SFGM-TC and GFLLC.

    PubMed

    Sutton, Laurent; Chevret, Sylvie; Tournilhac, Olivier; Diviné, Marine; Leblond, Véronique; Corront, Bernadette; Leprêtre, Stéphane; Eghbali, Houchingue; Van Den Neste, Eric; Michallet, Mauricette; Maloisel, Frédéric; Bouabdallah, Krimo; Decaudin, Didier; Berthou, Christian; Brice, Pauline; Gonzalez, Hugo; Chapiro, Elise; Radford-Weiss, Isabelle; Leporrier, Nathalie; Maloum, Karim; Nguyen-Khac, Florence; Davi, Frédéric; Lejeune, Julie; Merle-Béral, Hélène; Leporrier, Michel

    2011-06-09

    Long-term responses have been reported after autologous stem cell transplantation (ASCT) for chronic lymphocytic leukemia (CLL). We conducted a prospective, randomized trial of ASCT in previously untreated CLL patients. We enrolled 241 patients < 66 years of age with Binet stage B or C CLL. They received 3 courses of mini-CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone/prednisolone) and then 3 courses of fludarabine. Patients in complete response (CR) were then randomized to ASCT or observation, whereas the other patients were randomized to dexamethasone, high-dose aracytin, cisplatin (DHAP) salvage followed by either ASCT or 3 courses of fludarabine plus cyclophosphamide (FC). The primary end point was event-free survival (EFS). After up-front treatment, 105 patients entered CR and were randomized between ASCT (n = 52) and observation (n = 53); their respective 3-year EFS rates were 79.8% and 35.5%; the adjusted hazard ratio was 0.3 (95% CI: 0.1-0.7; P = .003). Ninety-four patients who did not enter CR were randomized between ASCT (n = 46) and FC (n = 48); their respective 3-year EFS rates were 48.9% and 44.4%, respectively; the adjusted hazard ratio was 1.7 (95% CI: 0.9-3.2; P = .13). No difference in overall survival was found between the 2 response subgroups. In young CLL patients in CR, ASCT consolidation markedly delayed disease progression. No difference was observed between ASCT and FC in patients requiring DHAP salvage.

  14. The role of children's bone marrow mesenchymal stromal cells in the ex vivo expansion of autologous and allogeneic hematopoietic stem cells.

    PubMed

    Pelagiadis, Iordanis; Stiakaki, Eftichia; Choulaki, Christianna; Kalmanti, Maria; Dimitriou, Helen

    2015-10-01

    The recognition of the role of Mesenchymal Stromal Cells (MSC) in hematopoiesis, as part of the bone marrow microenvironment, renewed the interest for cord blood (CB) ex vivo expansion as a source of HSC for transplantation. MSC from children are recognized to have different biological properties compared to the ones from adults. The current study focuses on the evaluation of the effects of children's bone marrow MSC on the ex vivo expansion capacity of both allogeneic cord blood and autologous bone marrow (BM) CD34(+) hematopoietic stem cells (HSCs) when used as a cell feeder layer with or without recombinant cytokines. Our results showed that children's bone marrow-derived MSC expand more primitive populations in co culture with CD34 and that the expansion is further enhanced when the culture is supplemented with growth factors. No additive effect was seen either with the early- or late-acting growth factors' cocktails used. Biological features of CB hematopoietic progenitors seem to make them more suitable than their BM counterparts for ex vivo expansion. Clinical implementation will be facilitated by methodological standardization and guidelines' establishment.

  15. Technological progress and challenges towards cGMP manufacturing of human pluripotent stem cells based therapeutic products for allogeneic and autologous cell therapies.

    PubMed

    Abbasalizadeh, Saeed; Baharvand, Hossein

    2013-12-01

    Recent technological advances in the generation, characterization, and bioprocessing of human pluripotent stem cells (hPSCs) have created new hope for their use as a source for production of cell-based therapeutic products. To date, a few clinical trials that have used therapeutic cells derived from hESCs have been approved by the Food and Drug Administration (FDA), but numerous new hPSC-based cell therapy products are under various stages of development in cell therapy-specialized companies and their future market is estimated to be very promising. However, the multitude of critical challenges regarding different aspects of hPSC-based therapeutic product manufacturing and their therapies have made progress for the introduction of new products and clinical applications very slow. These challenges include scientific, technological, clinical, policy, and financial aspects. The technological aspects of manufacturing hPSC-based therapeutic products for allogeneic and autologous cell therapies according to good manufacturing practice (cGMP) quality requirements is one of the most important challenging and emerging topics in the development of new hPSCs for clinical use. In this review, we describe main critical challenges and highlight a series of technological advances in all aspects of hPSC-based therapeutic product manufacturing including clinical grade cell line development, large-scale banking, upstream processing, downstream processing, and quality assessment of final cell therapeutic products that have brought hPSCs closer to clinical application and commercial cGMP manufacturing.

  16. Post-autologous stem cell transplantation administration of rituximab improves the outcome of patients with aggressive B cell non-Hodgkin's lymphoma.

    PubMed

    Tsirigotis, Panagiotis; Dray, Liliane; Resnick, Igor B; Ackerstein, Aliza; Gesundheit, Benjamin; Elad, Sharon; Or, Reuven; Shapira, Michael-Yechiel

    2010-03-01

    The major cause of treatment failure following high-dose therapy with autologous stem cell transplantation (ASCT) for aggressive B cell non-Hodgkin's lymphoma (NHL) is persistent disease or recurrence. We describe our experience with the administration of rituximab post-ASCT, either as maintenance therapy or for the treatment of relapsed disease in patients with aggressive B cell NHL. Fifty-six patients achieved complete remission post-transplant, and 19 of them received maintenance with rituximab. Maintenance with rituximab resulted in statistically significant superior outcome in terms of progression free (PFS; p = 0.002) and overall survival (OS; p = 0.011). The median PFS and OS of patients in the maintenance arm has not been reached yet, while the median PFS and OS of patients in the control arm were 29 and 42 months, respectively. Fifty-four patients had disease progression or relapsed post-ASCT, and 15 of them received rituximab in combination with chemo- and/or radiotherapy in order to achieve disease remission. Therapeutic administration of rituximab resulted in statistically significant prolongation of OS (p = 0.021). The median OS of patients treated with rituximab was 17 months, while median OS of patients in the control group was 10 months. We consider that the results of our study are promising but need to be verified within large randomized trials.

  17. Low-dose acyclovir prophylaxis for the prevention of herpes simplex virus and varicella zoster virus diseases after autologous hematopoietic stem cell transplantation.

    PubMed

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

    2015-08-01

    Limited data are available on prophylaxis for herpes simplex virus (HSV) and varicella zoster virus (VZV) disease following autologous hematopoietic stem cell transplantation (auto-HCT). We retrospectively reviewed the clinical charts of 105 consecutive patients who underwent their first auto-HCT at our institution between September 2007 and June 2014. Before August 2009, 30 patients received oral acyclovir at 1000 mg/day until engraftment, whereas after September 2009, 69 patients received oral acyclovir at 200 mg/day. After engraftment, acyclovir was continued at 200 mg/day at the discretion of the attending physicians in both groups. The cumulative incidence of HSV disease at 1 year after auto-HCT was 7.7 and 4.5 % in patients who received oral acyclovir at 1000 and 200 mg/day, respectively (P = 0.75). Patients were next divided into three groups according to the timing at which acyclovir prophylaxis was stopped after auto-HCT; at engraftment, between engraftment and 1 year after auto-HCT, and later than 1 year. The cumulative incidence of VZV disease was 25.8, 7.7, and 0.0 % at 1 year, respectively. This study suggests that low-dose acyclovir prophylaxis may be effective for preventing HSV and VZV disease after auto-HCT. Our findings support the recommendation of acyclovir prophylaxis within the first year after auto-HCT.

  18. Intensive dose ifosfamide, carboplatin, and etoposide followed by autologous stem cell rescue: results of a phase I/II study in breast cancer patients.

    PubMed

    Fields, K K; Perkins, J P; Hiemenz, J W; Zorsky, P E; Janssen, W E; Kronish, L E; Machak, M C; Elfenbein, G J

    1993-01-01

    We have recently treated 66 women with breast cancer with escalating doses of ifosfamide, carboplatin, and etoposide (ICE) followed by autologous stem cell rescue (ASCR). Patients received ifosfamide (6000-24,000 mg m-2), carboplatin (1200-2100 mg m-2), and etoposide (1800-3000 mg m-2) divided over 6 days with ASCR 48 h after completion of chemotherapy. Our patient population consisted of seven patients with stage II disease with eight or more positive nodes being treated in the adjuvant setting, 16 patients with a history of stage III or inflammatory breast cancer, and 43 patients with stage IV disease. Six patients were not evaluable for response due to early death from infection (three patients) and incomplete restaging (three patients). The overall response rate in patients with measurable metastatic disease was 50%. Of those patients with stage II disease, 85% remain alive and progression-free with a median follow-up of greater than one year. The two most frequent toxicities encountered were reversible elevations of liver function tests and mucositis/enteritis. The dose-limiting toxicities were central nervous system toxicity and nephrotoxicity.

  19. Infectious Complications during Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Children with High-Risk or Recurrent Solid Tumors

    PubMed Central

    Kang, Ji-Man; Lee, Ji Won; Yoo, Keon Hee; Kim, Yae-Jean; Sung, Ki Woong; Koo, Hong Hoe

    2016-01-01

    We retrospectively analyzed infectious complications during tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) in children and adolescents with high-risk or recurrent solid tumors. A total of 324 patients underwent their first HDCT/auto-SCT between October 2004 and September 2014, and 283 of them proceeded to their second HDCT/auto-SCT (a total of 607 HDCT/auto-SCTs). During the early transplant period of 607 HDCT/auto-SCTs (from the beginning of HDCT to day 30 post-transplant), bacteremia, urinary tract infection (UTI), respiratory virus infection, and varicella zoster virus (VZV) reactivation occurred in 7.1%, 2.3%, 13.0%, and 2.5% of HDCT/auto-SCTs, respectively. The early transplant period of the second HDCT/auto-SCT had infectious complications similar to the first HDCT/auto-SCT. During the late transplant period of HDCT/auto-SCT (from day 31 to 1 year post-transplant), bacteremia, UTI, and VZV reactivation occurred in 7.5%, 2.5%, and 3.9% of patients, respectively. Most infectious complications in the late transplant period occurred during the first 6 months post-transplant. There were no invasive fungal infections during the study period. Six patients died from infectious complications (4 from bacterial sepsis and 2 from respiratory virus infection). Our study suggests that infectious complications are similar following second and first HDCT/auto-SCT in children. PMID:27627440

  20. Thalidomide-prednisone maintenance following autologous stem cell transplant for multiple myeloma: effect on thrombin generation and procoagulant markers in NCIC CTG MY.10.

    PubMed

    Kovacs, Michael J; Davies, Gwynivere A; Chapman, Judy-Anne W; Bahlis, Nizar; Voralia, Michael; Roy, Jean; Kouroukis, C Tom; Chen, Christine; Belch, Andrew; Reece, Donna; Zhu, Liting; Meyer, Ralph M; Shepherd, Lois; Stewart, Keith A

    2015-02-01

    Venous thromboembolism (VTE) has an increased incidence in patients with multiple myeloma (MM), especially during chemotherapy. Mechanisms including upregulation of procoagulant factors, such as factor VIII, have been postulated. The National Cancer Institute of Canada Clinical Trials Group MY.10 phase III clinical trial compared thalidomide-prednisone to observation for 332 patients with MM post-autologous stem cell transplantation (ASCT), with a primary endpoint of overall survival and various secondary endpoints including the incidence of VTE. One hundred and fifty-three patients had biomarker data, including D-dimer, factor VIII and thrombin anti-thrombin (TAT) levels collected post-ASCT at baseline and 2 months after intervention investigating in-vivo thrombin generation. Differences between the time-points included a significant reduction over time in D-dimer, factor VIII and TAT levels in the observation group and sustained elevation of D-dimer, significant increase in factor VIII and reduction in TAT levels in the thalidomide-prednisone group. Eight VTE events were reported in this subset of study patients, all in the thalidomide-prednisone arm, with a trend to increase in D-dimer levels over time in those patients with VTE. This study provides physiological and clinical evidence for an increased risk of VTE associated with thalidomide-prednisone maintenance therapy post-ASCT for MM.

  1. Treatment of patients with secondary central nervous system lymphoma with high-dose busulfan/thiotepa-based conditioning and autologous stem cell transplant.

    PubMed

    Oh, Danielle H; Chua, Neil; Street, Lesley; Stewart, Douglas A

    2016-01-01

    Although the survival rates are extremely low for patients with secondary central nervous system lymphoma (SCNSL) treated with conventional chemotherapy and radiotherapy, more encouraging outcomes have recently been reported in small series with high-dose (HD) therapy and autologous stem cell transplant (ASCT). The optimal HD regimen for SCNSL is unknown. Despite reports of thiotepa/busulfan-based conditioning for primary CNS lymphoma, very little data exist regarding the use of this regimen for SCNSL. We analyzed 23 patients with SCNSL (median age 62 years) who underwent ASCT at two Alberta centers using thiotepa, busulfan, cyclophosphamide (TBC) in six patients prior to 2011 and rituximab-busulfan, melphalan, thiotepa (R-BuMelTt) in 17 patients after 2011. At a median follow-up of 27.8 months (4.2-113.6), the 2-year actuarial rate of progression-free survival was 76.1%. In conclusion, our results demonstrate encouraging survival outcomes for patients with SCNSL treated with R-BuMelTt and ASCT.

  2. Outcomes of diffuse large B-cell lymphoma patients relapsing after autologous stem cell transplantation: an analysis of patients included in the CORAL study.

    PubMed

    Van Den Neste, E; Schmitz, N; Mounier, N; Gill, D; Linch, D; Trneny, M; Bouadballah, R; Radford, J; Bargetzi, M; Ribrag, V; Dührsen, U; Ma, D; Briere, J; Thieblemont, C; Bachy, E; Moskowitz, C H; Glass, B; Gisselbrecht, C

    2017-02-01

    In the CORAL study, 255 chemosensitive relapses with diffuse large B-cell lymphoma (DLBCL) were consolidated with autologous stem cell transplantation (ASCT), and 75 of them relapsed thereafter. The median time between ASCT and progression was 7.1 months. The median age was 56.1 years; tertiary International Prognosis Index (tIPI) observed at relapse was 0-2 in 71.6% of the patients and >2 in 28.4%. The overall response rate to third-line chemotherapy was 44%. The median overall survival (OS) was 10.0 months (median follow-up: 32.8 months). Thirteen patients received an allogeneic SCT, and three a second ASCT. The median OS was shorter among patients who relapsed <6 months (5.7 months) compared with those relapsing ⩾12 months after ASCT (12.6 months, P=0.0221). The median OS in patients achieving CR, PR or no response after the third-line regimen was 37.7 (P<0.0001), 10.0 (P=0.03) and 6.3 months, respectively. The median OS varied according to tIPI: 0-2: 12.6 months and >2: 5.3 months (P=0.0007). In multivariate analysis, tIPI >2, achievement of response and remission lasting <6 months predicted the OS. This report identifies the prognostic factors for DLBCL relapsing after ASCT and thus helps to select patients for experimental therapy.

  3. Autologous hematopoietic stem cell transplantation for autoimmune diseases: an observational study on 12 years’ experience from the European Group for Blood and Marrow Transplantation Working Party on Autoimmune Diseases

    PubMed Central

    Farge, Dominique; Labopin, Myriam; Tyndall, Alan; Fassas, Athanasios; Mancardi, Gian Luigi; Van Laar, Jaap; Ouyang, Jian; Kozak, Tomas; Moore, John; Kötter, Ina; Chesnel, Virginie; Marmont, Alberto; Gratwohl, Alois; Saccardi, Riccardo

    2010-01-01

    Background Autologous hematopoietic stem cell transplantation has been used since 1996 for the treatment of severe autoimmune diseases refractory to approved therapies. We evaluated the long-term outcomes of these transplants and aimed to identify potential prognostic factors. Design and Methods In this observational study we analyzed all first autologous hematopoietic stem cell transplants for autoimmune diseases reported to the European Group for Blood and Marrow Transplantation (EBMT) registry between 1996–2007. The primary end-points for analysis were overall survival, progression-free survival and transplant-related mortality at 100 days. Results Nine hundred patients with autoimmune diseases (64% female; median age, 35 years) who underwent a first autologous hematopoietic stem cell transplant were included. The main diseases were multiple sclerosis (n=345), systemic sclerosis (n=175), systemic lupus erythematosus (n=85), rheumatoid arthritis (n=89), juvenile arthritis (n=65), and hematologic immune cytopenia (n=37). Among all patients, the 5-year survival was 85% and the progression-free survival 43%, although the rates varied widely according to the type of autoimmune disease. By multivariate analysis, the 100-day transplant-related mortality was associated with the transplant centers’ experience (P=0.003) and type of autoimmune disease (P=0.03). No significant influence of transplant technique was identified. Age less than 35 years (P=0.004), transplantation after 2000 (P=0.0015) and diagnosis (P=0.0007) were associated with progression-free survival. Conclusions This largest cohort studied worldwide shows that autologous hematopoietic stem cell transplantation can induce sustained remissions for more than 5 years in patients with severe autoimmune diseases refractory to conventional therapy. The type of autoimmune disease, rather than transplant technique, was the most relevant determinant of outcome. Results improved with time and were associated with

  4. Therapeutic potential of Mesenchymal Stem Cells for the treatment of diabetic peripheral neuropathy.

    PubMed

    Monfrini, Marianna; Donzelli, Elisabetta; Rodriguez-Menendez, Virginia; Ballarini, Elisa; Carozzi, Valentina Alda; Chiorazzi, Alessia; Meregalli, Cristina; Canta, Annalisa; Oggioni, Norberto; Crippa, Luca; Avezza, Federica; Silvani, Sara; Bonandrini, Barbara; Figliuzzi, Marina; Remuzzi, Andrea; Porretta-Serapiglia, Carla; Bianchi, Roberto; Lauria, Giuseppe; Tredici, Giovanni; Cavaletti, Guido; Scuteri, Arianna

    2017-02-01

    Type-1 Diabetes is generally treated with exogenous insulin administration. Despite treatment, a very common long term consequence of diabetes is the development of a disabling and painful peripheral neuropathy. The transplantation of pancreatic islets is an advanced alternative therapeutic approach, but its clinical application is still very limited, mainly because of the great number of islets required to complete the procedure and of their short-term survival. An intriguing method to improve the performance of pancreatic islets transplantation is the co-transplantation of Mesenchymal Stem Cells (MSCs), adult stem cells already known to support the survival of different cellular populations. In this proof-of-concept study, we demonstrated using an in vivo model of diabetes, the ability of allogenic MSCs to reduce the number of pancreatic islets necessary to achieve glycemic control in diabetic rats, and overall their positive effect on diabetic neuropathy, with the reduction of all the neuropathic signs showed after disease induction. The cutback of the pancreatic islet number required to control glycemia and the regression of the painful neuropathy make MSC co-transplantation a very promising tool to improve the clinical feasibility of pancreatic islet transplantation for diabetes treatment.

  5. Alignment of the Fibrin Network Within an Autologous Plasma Clot.

    PubMed

    Gessmann, Jan; Seybold, Dominik; Peter, Elvira; Schildhauer, Thomas Armin; Köller, Manfred

    2016-01-01

    Autologous plasma clots with longitudinally aligned fibrin fibers could serve as a scaffold for longitudinal axonal regrowth in cases of traumatic peripheral nerve injuries. Three different techniques for assembling longitudinally oriented fibrin fibers during the fibrin polymerization process were investigated as follows: fiber alignment was induced by the application of either a magnetic field or-as a novel approach-electric field or by the induction of orientated flow. Fiber alignment was characterized by scanning electron microscopy analysis followed by image processing using fast Fourier transformation (FFT). Besides FFT output images, area xmin to xmax, as well as full width at half maximum (FWHM) of the FFT graph plot peaks, was calculated to determine the relative degree of fiber alignment. In addition, fluorescently labeled human fibrinogen and mesenchymal stem cells (MSCs) were used to visualize fibrin and cell orientation in aligned and nonaligned plasma clots. Varying degrees of fiber alignment were achieved by the three different methods, with the electric field application producing the highest degree of fiber alignment. The embedded MSCs showed a longitudinal orientation in the electric field-aligned plasma clots. The key feature of this study is the ability to produce autologous plasma clots with aligned fibrin fibers using physical techniques. This orientated internal structure of an autologous biomaterial is promising for distinct therapeutic applications, such as a guiding structure for cell migration and growth dynamics.

  6. Donor cell-derived acute myeloblastic leukemia after allogeneic peripheral blood hematopoietic stem cell transplantation for juvenile myelomonocytic leukemia.

    PubMed

    Cetin, Zafer; Tezcan, Gulsun; Karauzum, Sibel Berker; Kupesiz, Alphan; Manguoglu, Ayse Esra; Yesilipek, Akif; Luleci, Guven; Hazar, Volkan

    2006-11-01

    Despite its rarity, donor cell leukemia (DCL) is a most intriguing entity. We report here the case of a 5 year-old girl with juvenile myelomonocytic leukemia and normal female karyotype who developed acute myeloblastic leukemia with a karyotype of 46, X, t(X; 7) (p21; p11.2), der(7) t(3; 7) (q13.3; q22) 5 months after peripheral blood hematopoietic stem cell transplantation from her HLA-matched sister. We performed the analysis of short tandem repeat sequence markers to DNA obtained from donor peripheral blood, patient's peripheral blood including leukemic blasts and patient's hair root. This analysis showed that the leukemic blood DNA matched the donor blood DNA and not the patient's DNA, thus confirming DCL. To our knowledge, this is the first case of DCL after peripheral blood SCT for juvenile myelomonocytic leukemia.

  7. Sowing the Seeds of a Fruitful Harvest: Hematopoietic Stem Cell Mobilization

    PubMed Central

    Hoggatt, Jonathan; Speth, Jennifer M.; Pelus, Louis M.

    2014-01-01

    Hematopoietic stem cell transplantation is the only curative option for a number of malignant and non-malignant diseases. As the use of hematopoietic transplant has expanded, so too has the source of stem and progenitor cells. The predominate source of stem and progenitors today, particularly in settings of autologous transplantation, is mobilized peripheral blood. This review will highlight the historical advances which lead to the widespread use of peripheral blood stem cells for transplantation, with a look towards future enhancements to mobilization strategies. PMID:24123398

  8. High-dose Chemotherapy and the Treatment of Metastatic Breast Cancer: Selecting the Regimen and the Source of Stem Cells.

    PubMed

    Fields; Agaliotis; Janssen; Perkins; Ballester; Hiemenz; Zorsky; Elfenbein

    1994-05-01

    High-dose chemotherapy followed by autologous stem cell rescue has been associated with an increased overall response rate and improved progression-free survival for patients with metastatic breast cancer when compared retrospectively to standard therapy. The optimal source of stem cells - peripheral blood or autologous bone marrow - has not been determined. We present results from two high-dose regimens - ifosfamide, carboplatin, and etoposide (ICE) or mitoxantrone and thiotepa (MITT) followed by autologous stem cell rescue - and analyze the outcomes for patients based on the regimen used and the source of stem cells. Disease responsiveness at the time of high-dose therapy is the most important factor for determining outcome. The source of stem cells did not affect progression-free survival for either group.

  9. Combining Autologous Peripheral Blood Mononuclear Cells with Fibroblast Growth Factor Therapy Along with Stringent Infection Control Leading to Successful Limb Salvage in Diabetic Patient with Chronic Renal Failure and Severe Toe Gangrene

    PubMed Central

    Osawa, Hiroshi; Orii, Kouan; Terunuma, Hiroshi; Abraham, Samuel JK

    2014-01-01

    Peripheral arterial disease (PAD) is a common complication of Diabetes Mellitus (DM) and often culminates in amputation of the affected foot. Pseudomonas aeruginosa infections associated with PAD are difficult to treat due to their multi-drug resistance. Herein we report a 38 year old male who reported with DM, chronic kidney disease (CKD) and rest pain of the right second toe in October 2011. He underwent percutaneous transluminal angioplasty (PTA) which was unsuccessful. The gangrene of the toes worsened and amputation of the right second toe was done. Bacteriological examination showed presence of P. aeruginosa which during the course of antibiotic therapy became multi-drug resistant. Gangrene and abscess of the foot worsened and amputation of the right third toe was performed. Then autologous peripheral blood mononuclear cell (PBMNC) therapy was performed but as infection control could not still be achieved, the fourth toe was amputated. A protocol of foot bath using carbonic water, local usage of antibiotics (Polymyxin-B), and basic fibroblast growth factor (b-FGF) spray was then employed after which the infection could be controlled and improvement in vascularity of the right foot could be observed in angiography. This combined approach after proper validation could be considered for similar cases. PMID:25473454

  10. A randomized trial of amifostine in patients with high-dose VIC chemotherapy plus autologous blood stem cell transplanation

    PubMed Central

    Hartmann, J T; Vangerow, A von; Fels, L M; Knop, S; Stolte, H; Kanz, L; Bokemeyer, C

    2001-01-01

    This pilot study evaluates the degree of side effects during high-dose chemotherapy (HD-VIC) plus autologous bone marrow transplant (HDCT) and its possible prevention by the cytoprotective thiol-derivate amifostine. Additionally, the in-patient medical costs of both treatment arms were compared. 40 patients with solid tumours were randomized to receive HD-VIC chemotherapy with or without amifostine (910 mg/m2 at day 1–3) given as a short infusion prior to carboplatin and ifosfamide. Patients were stratified according to pretreatment. HDCT consisted of an 18 h infusion of carboplatin (500 mg/m2/d over 18 h), ifosfamide (4 g/m2/d over 4 h) and etoposide (500 mg/m2/d) all given for 3 consecutive days. All patients received prophylactic application of G-CSF (5 μg kg−1 subcutaneously) to ameliorate neutropenia after treatment. Patients were monitored for nephrotoxicity, gastrointestinal side effects, haematopoietic recovery, as well as frequency of fever and infections. The median fall of the glomerular filtration rate (GFR) was 10% from baseline in the amifostine group (105 to 95 ml min−1) and 37% in the control patient group (107 to 67 ml min−1) (P< 0.01). Amifostine-treated patients revealed a less pronounced increase in albumine and low molecular weight protein urinary excretion. Stomatitis grade III/IV occurred in 25% without versus 0% of patients with amifostine (P = 0.01). Acute nausea/vomiting was frequently observed immediately during or after the application of amifostine despite intensive antiemetic prophylaxis consisting of 5-HT3-receptor antagonists/dexamethasone/trifluorpromazine. However, delayed emesis occurred more often in the control patients. Engraftment of neutrophil (> 500 μl−1) and thrombocytes (> 25 000 μl−1)were observed at days 9 versus 10 and 10 versus 12, respectively, both slightly in favour of the amifostine arm. In addition, a lower number of days with fever and a shortened duration of hospital stay were observed in the

  11. Steady State Peripheral Blood Provides Cells with Functional and Metabolic Characteristics of Real Hematopoietic Stem Cells.

    PubMed

    Bourdieu, A; Avalon, M; Lapostolle, V; Ismail, S; Mombled, M; Debeissat, C; Guérinet, M; Duchez, P; Chevaleyre, J; Vlaski-Lafarge, M; Villacreces, A; Praloran, V; Ivanovic, Z; Brunet de la Grange, P

    2017-03-01

    Hematopoietic stem cells (HSCs), which are located in the bone marrow, also circulate in cord and peripheral blood. Despite high availability, HSCs from steady state peripheral blood (SSPB) are little known and not used for research or cell therapy. We thus aimed to characterize and select HSCs from SSPB by a direct approach with a view to delineating their main functional and metabolic properties and the mechanisms responsible for their maintenance. We chose to work on Side Population (SP) cells which are highly enriched in HSCs in mouse, human bone marrow, and cord blood. However, no SP cells from SSBP have as yet been characterized. Here we showed that SP cells from SSPB exhibited a higher proliferative capacity and generated more clonogenic progenitors than non-SP cells in vitro. Furthermore, xenotransplantation studies on immunodeficient mice demonstrated that SP cells are up to 45 times more enriched in cells with engraftment capacity than non-SP cells. From a cell regulation point of view, we showed that SP activity depended on O2 concentrations close to those found in HSC niches, an effect which is dependent on both hypoxia-induced factors HIF-1α and HIF-2α. Moreover SP cells displayed a reduced mitochondrial mass and, in particular, a lower mitochondrial activity compared to non-SP cells, while they exhibited a similar level of glucose incorporation. These results provided evidence that SP cells from SSPB displayed properties of very primitive cells and HSC, thus rendering them an interesting model for research and cell therapy. This article is protected by copyright. All rights reserved.

  12. Infections following Transplantation of Bone Marrow or Peripheral-Blood Stem Cells from Unrelated Donors

    PubMed Central

    Young, Jo-Anne H.; Logan, Brent R.; Wu, Juan; Wingard, John R.; Weisdorf, Daniel J.; Mudrick, Cathryn; Knust, Kristin; Horowitz, Mary M.; Confer, Dennis L.; Dubberke, Erik R.; Pergam, Steven A.; Marty, Francisco M.; Strasfeld, Lynne M.; Brown, Janice (Wes) M.; Langston, Amelia A.; Schuster, Mindy G.; Kaul, Daniel R.; Martin, Stanley I.; Anasetti, Claudio

    2015-01-01

    Infection is a major complication of hematopoietic cell transplantation. Prolonged neutropenia and graft versus host disease are the two major complications with an associated risk for infection, and these complications differ according to the graft source. A phase 3, multicenter, randomized trial (BMT CTN 0201) of transplantation of bone marrow (BM) versus peripheral-blood stem cells (PBSC) from unrelated donors (URD) showed no significant differences in two-year survival between these graft sources. In an effort to provide data regarding whether bone marrow or peripheral-blood stem cells could be used as a preferential graft source for transplantation, we report a detailed analysis of the infectious complications for 2 years following transplantation from the BMT CTN 0201 trial. A total of 499 patients in this study had full audits of infection data. A total of 1347 infection episodes of moderate or greater severity were documented in 384 (77%) patients; 201/249 (81%) of the evaluable patients had received a BM graft and 183/250 (73%) had received a PBSC graft. Of 1347 infection episodes, 373 were severe and 123 were life-threatening and/or fatal; 710 (53%) of these episodes occurred on the BM arm and 637 (47%) on the PBSC arm, resulting in a two-year cumulative incidence 84.7% (95% confidence interval [CI]: 79.6–89.8) for BM vs. 79.7% (95%CI, 73.9–85.5) for PBSC, P = .013. The majority of these episodes, 810 (60%), were due to bacteria, with a two-year cumulative incidence of 72.1% and 62.9% in BM versus PBSC recipients, respectively (P = .003). The cumulative incidence of bloodstream bacterial infections during the first 100 days was 44.8% (95%CI, 38.5–51.1) for BM vs. 35.0% (95%CI, 28.9–41.1) for PBSC (P = .027). The total infection density (# infection events / 100 patient days at risk) was .67 for BM and .60 for PBSC. The overall infection density for bacterial infections was .4 in both arms; for viral infections was .2 in both arms; and for fungal

  13. Isolation and characterization of ovine mesenchymal stem cells derived from peripheral blood

    PubMed Central

    2012-01-01

    Background Mesenchymal stem cells (MSCs) are multipotent stem cells with capacity to differentiate into several mesenchymal lineages. This quality makes MSCs good candidates for use in cell therapy. MSCs can be isolated from a variety of tissues including bone marrow and adipose tissue, which are the most common sources of these cells. However, MSCs can also be isolated from peripheral blood. Sheep has been proposed as an ideal model for biomedical studies including those of orthopaedics and transmissible spongiform encephalopathies (TSEs). The aim of this work was to advance these studies by investigating the possibility of MSC isolation from ovine peripheral blood (oPB-MSCs) and by subsequently characterizing there in vitro properties. Results Plastic-adherent fibroblast-like cells were obtained from the mononuclear fraction of blood samples. These cells were analysed for their proliferative and differentiation potential into adipocytes, osteoblasts and chondrocytes, as well as for the gene expression of cell surface markers. The isolated cells expressed transcripts for markers CD29, CD73 and CD90, but failed to express the haematopoietic marker CD45 and expressed only low levels of CD105. The expression of CD34 was variable. The differentiation potential of this cell population was evaluated using specific differentiation media. Although the ability of the cultures derived from different animals to differentiate into adipocytes, osteoblasts and chondrocytes was heterogeneous, we confirmed this feature using specific staining and analysing the gene expression of differentiation markers. Finally, we tested the ability of oPB-MSCs to transdifferentiate into neuronal-like cells. Morphological changes were observed after 24-hour culture in neurogenic media, and the transcript levels of the neurogenic markers increased during the prolonged induction period. Moreover, oPB-MSCs expressed the cellular prion protein gene (PRNP), which was up-regulated during neurogenesis

  14. The Effects of Oral Cryotherapy on Chemotherapy-Induced Oral Mucositis in Patients Undergoing Autologous Transplantation of Blood Stem Cells: A Clinical Trial

    PubMed Central

    Askarifar, Marzieh; Lakdizaji, Sima; Ramzi, Mani; Rahmani, Azad; Jabbarzadeh, Faranak

    2016-01-01

    Background Oral mucositis is one of the irritating side effects of chemotherapy in patients undergoing bone marrow transplantation. However, up until now, the common methods of oral mucositis therapy have failed to show significant effects. Objectives The aim of this study was to investigate the effects of local cryotherapy on the intensity of chemotherapy-induced oral mucositis in autologous bone marrow transplantation patients. Patients and Methods In this single, blinded, randomized clinical trial, 29 patients undergoing stem cell transplantation in Iran were selected by convenience sampling, and randomly allocated to control (n = 13) and intervention groups (n = 16). In the intervention group, cryotherapy was applied, while the control group received a normal saline mouthwash. The severity of the mucositis and neutrophil rate were investigated in five periods, based on the world health organization (WHO) scales. The data were analyzed using descriptive statistics, the Mann-Whitney test, repeated measures analysis of variance (ANOVA), and linear regression. Results In both groups, the mucositis reached its peak intensity on the 7th day, and the least intensity was obtained on the 21st day. The neutrophil rate reached the minimum value on the 7th day, then increased up to the 21st day. The two groups showed no significant differences between the mucositis severity on the 14th and 21st days (P = 0.164), while the severity of the mucositis in the cryotherapy group was significantly less than that in the saline mouthwash group (1.81 < 2.54 and 0.13 < 0.92, respectively) on the 7th and 14th days (P < 0.05). There was no significant difference in the neutrophil rate between the groups. Conclusions The results showed that cryotherapy is more effective than the saline mouthwash in reducing the severity of mucositis. This method is recommended for the prevention of mucositis in bone marrow transplantation. PMID:27257512

  15. Promising treatment results with blood brain barrier disruption (BBBD) based immunochemotherapy combined with autologous stem cell transplantation (ASCT) in patients with primary central nervous system lymphoma (PCNSL).

    PubMed

    Kuitunen, Hanne; Tokola, Susanna; Siniluoto, Topi; Isokangas, Matti; Sonkajärvi, Eila; Alahuhta, Seppo; Turpeenniemi-Hujanen, Taina; Jantunen, Esa; Nousiainen, Tapio; Vasala, Kaija; Kuittinen, Outi

    2017-01-01

    Primary central nervous system lymphoma (PCNSL) is a rare brain tumour with a dismal prognosis. Several phase II studies with high-dose methotrexate-based regimens have shown promising early results, but in all hospital-based data published so far, the disease outcome has been poor. Patients with relapsed or refractory disease have a dismal prognosis. We performed retrospective analysis to evaluate results and tolerabilities of BBBD therapy in combination with high-dose therapy supported by autologous stem cell transplantation. We analysed 25 patients (age range: 40-71 years) who were treated in first or second line with BBBD therapy. When we started BBBD treatment, patients had relapsed or refractory PCNSL or they did not tolerate Bonn-like therapy. In recent years, some of the patients were treated in first line. We found promising response rates. Altogether 19 (76 %) of the patients achieved a complete response (CR). Two-year progression-free survival (PFS) and overall survival (OS) rates were 61 and 57 % respectively and the five-year OS was 47 %. Patients who were treated with a five-drug therapy had a very promising prognosis. The CR rate was 100 % in first-line therapy and 60 % in relapsed cases. These findings suggest that BBBD is a promising therapy for PCNSL, especially for patients in first line, but also for patients with relapsed or refractory disease after conventional chemotherapy, who commonly have a very poor prognosis. Treatment-related toxicity was generally manageable. Thus, BBBD followed by ASCT could be a treatment of choice in transplant-eligible patients with PCNSL.

  16. Risk stratification in myeloma by detection of circulating plasma cells prior to autologous stem cell transplantation in the novel agent era

    PubMed Central

    Chakraborty, R; Muchtar, E; Kumar, S K; Jevremovic, D; Buadi, F K; Dingli, D; Dispenzieri, A; Hayman, S R; Hogan, W J; Kapoor, P; Lacy, M Q; Leung, N; Gertz, M A

    2016-01-01

    The impact of circulating plasma cells (CPCs) prior to autologous stem cell transplantation (ASCT) for multiple myeloma has not been defined in the novel agent era. We evaluated the impact of pre-transplant CPCs, detected by six-color flow cytometry in patients undergoing early ASCT on post-transplant response, progression-free survival (PFS) and overall survival (OS). CPCs were detected in 162 out of 840 (19.3%) patients, with the median number of CPCs being 58 per 150 000 events. Ninety-nine percent of patients had received proteasome inhibitor and/or immunomodulator-based induction. The incidence of post-transplant stringent complete response (sCR) in the subgroups with and without CPCs was 15% and 38%, respectively, (P<0.001). The median PFS in the subgroups with and without CPCs was 15.1 (95% confidence interval (CI), 12.5–17.8) and 29.6 months (95% CI, 26.2–32.8), respectively, and the median OS was 41.0 months (95% CI, 32.6–58.2) and not reached (NR) (95% CI, 99.1-NR), respectively, (P<0.001 for both). On multivariate analysis for OS, factors independently predictive of mortality were the presence of CPCs (hazard ratio (HR) 2.5; 95% CI, 1.8–3.6; P<0.001) and sCR post transplant (HR 0.4; 95% CI, 0.2–0.6; P<0.001). Presence of CPCs prior to transplant has a high prognostic impact and should be prospectively validated in clinical trials. PMID:27983726

  17. Conditioning regimens in autologous stem cell transplantation for multiple myeloma: a comparative study of efficacy and toxicity from the Spanish Registry for Transplantation in Multiple Myeloma.

    PubMed

    Lahuerta, J J; Martinez-Lopez, J; Grande, C; Bladé, J; de la Serna, J; Alegre, A; García-Laraña, J; Caballero, D; Sureda, A; de la Rubia, J; Alvarez, A M; Marín, J; Escudero, A; Conde, E; Perez-Equiza, K; García Ruiz, J C; Moraleda, J M; León, A; Bargay, J; Cabrera, R; Hernandez-García, M T; Diaz-Mediavilla, J; Miguel, J S

    2000-04-01

    High-dose chemoradiotherapy conditioning regimens for autologous stem cell transplantation (ASCT) are generally held to give similar results in multiple myeloma (MM), but no specific comparative study has been published. We addressed this issue by comparing the main high-dose chemoradiotherapy regimens used in the Spanish Registry. Patient cohorts included 315 cases treated with 200 mg/m2 melphalan (MEL200), 127 patients with 140 mg/m2 melphalan plus total body irradiation (MEL140 + TBI) and 121 cases with 12 mg/kg busulphan plus 140 mg/m2 melphalan (BUMEL). After ASCT, granulocyte and platelet recovery time was similar in all conditioning groups. There were no differences in transplant-related mortality. All regimens yielded a similar response in reference to pre-ASCT MM status, although BUMEL produced a slightly better overall response when compared with the other regimens (97% vs. 89% and 92%, P = 0.003). The 5-year overall survival (OS) with BUMEL was 47% [95% confidence interval (CI) 26-68] compared with 43% (CI 31-54) for MEL140 + TBI and 37% (CI: 18-56) for MEL200. The median survival for the BUMEL group was 64 months compared with 45 and 37 months for the MEL200 and MEL140 + TBI groups respectively. These differences were non-significant (P = 0.2). The median event-free survival (EFS) was better for BUMEL (32 months) than for MEL200 (22 months) or for MEL140 + TBI (20 months). The differences in EFS between BUMEL and the other conditioning regimens reached statistical significance (P = 0.01). Nevertheless, the adjusted multivariate analysis for OS and EFS revealed that the conditioning regimens had no independent prognostic value. We concluded that three different conditioning regimens, commonly used for ASCT in MM, have a similar antimyeloma effect. However, the trend for better results observed in our series with BUMEL requires a prospective trial.

  18. CD4(+) memory T cells retain surface expression of CD31 independently of thymic function in patients with lymphoproliferative disorders following autologous hematopoietic stem-cell transplantation.

    PubMed

    Batorov, Egor V; Tikhonova, Marina A; Kryuchkova, Irina V; Sergeevicheva, Vera V; Sizikova, Svetlana A; Ushakova, Galina Y; Batorova, Dariya S; Gilevich, Andrey V; Ostanin, Alexander A; Shevela, Ekaterina Y; Chernykh, Elena R

    2017-03-14

    High-dose chemotherapy with autologous hematopoietic stem-cell transplantation (AHSCT) causes severe and long-lasting immunodeficiency in patients with lymphoproliferative disorders. The thymus begins to restore the T-cell repertoire approximately from the sixth month post-transplant. We assessed the dynamics of post-transplant recovery of CD4(+)CD45RA(+)CD31(+) T cells, "recent thymic emigrants" (RTEs), and a poorly described subtype of CD4(+)CD45RA(-)CD31(+) T cells in 90 patients with lymphoproliferative disorders following high-dose chemotherapy with AHSCT. Relative and absolute counts of CD4(+)CD31(+) naïve and memory T cells were evaluated before AHSCT, at the day of engraftment, and 6- and 12-month post-transplant. The pre-transplant count of CD4(+)CD45RA(+)CD31(+) T cells was lower than in healthy controls, and did not reach donors' values during the 12-month period. The pre-transplant number of CD4(+)CD45RA(-)CD31(+) T cells was higher than in healthy controls and was restored rapidly following AHSCT. Post-transplant mediastinal radiotherapy reduced counts of RTEs and elongated recovery period. Non-thymic tissue irradiation did not reduce this subset. The obtained data indicate that homeostatic proliferation may decrease the significance of CD31 expression on CD4(+)CD45RA(+) T cells as a marker of RTEs, and suggest that evaluation of RTEs recovery by flow cytometry requires an accurate gating strategy to exclude CD31(+) memory T cells.

  19. Relapsed or Refractory Double-Expressor and Double-Hit Lymphomas Have Inferior Progression-Free Survival After Autologous Stem-Cell Transplantation.

    PubMed

    Herrera, Alex F; Mei, Matthew; Low, Lawrence; Kim, Haesook T; Griffin, Gabriel K; Song, Joo Y; Merryman, Reid W; Bedell, Victoria; Pak, Christine; Sun, Heather; Paris, Tanya; Stiller, Tracey; Brown, Jennifer R; Budde, Lihua E; Chan, Wing C; Chen, Robert; Davids, Matthew S; Freedman, Arnold S; Fisher, David C; Jacobsen, Eric D; Jacobson, Caron A; LaCasce, Ann S; Murata-Collins, Joyce; Nademanee, Auayporn P; Palmer, Joycelynne M; Pihan, German A; Pillai, Raju; Popplewell, Leslie; Siddiqi, Tanya; Sohani, Aliyah R; Zain, Jasmine; Rosen, Steven T; Kwak, Larry W; Weinstock, David M; Forman, Stephen J; Weisenburger, Dennis D; Kim, Young; Rodig, Scott J; Krishnan, Amrita; Armand, Philippe

    2017-01-01

    Purpose Double-hit lymphomas (DHLs) and double-expressor lymphomas (DELs) are subtypes of diffuse large B-cell lymphoma (DLBCL) associated with poor outcomes after standard chemoimmunotherapy. Data are limited regarding outcomes of patients with relapsed or refractory (rel/ref) DEL or DHL who undergo autologous stem-cell transplantation (ASCT). We retrospectively studied the prognostic impact of DEL and DHL status on ASCT outcomes in patients with rel/ref DLBCL. Methods Patients with chemotherapy-sensitive rel/ref DLBCL who underwent ASCT at two institutions and in whom archival tumor material was available were enrolled. Immunohistochemistry for MYC, BCL2, and BCL6 and fluorescence in situ hybridization (FISH) for MYC were performed. In cases with MYC rearrangement or copy gain, FISH for BCL2 and BCL6 was also performed. Results A total of 117 patients were included; 44% had DEL and 10% had DHL. DEL and DHL were associated with inferior progression-free survival (PFS), and DHL was associated with poorer overall survival (OS). The 4-year PFS in patients with DEL compared with those with non-DEL was 48% versus 59% ( P = .049), and the 4-year OS was 56% versus 67% ( P = .10); 4-year PFS in patients with DHL compared with those with non-DHL was 28% versus 57% ( P = .013), and 4-year OS was 25% versus 61% ( P = .002). The few patients with concurrent DEL and DHL had a poor outcome (4-year PFS, 0%). In multivariable models, DEL and DHL were independently associated with inferior PFS, whereas DHL and partial response ( v complete response) at transplant were associated with inferior OS. Conclusion DEL and DHL are both associated with inferior outcomes after ASCT in patients with rel/ref DLBCL. Although ASCT remains a potentially curative approach, these patients, particularly those with DHL, are a high-risk subset who should be targeted for investigational strategies other than standard ASCT.

  20. Poor outcomes for IgD multiple myeloma patients following high-dose melphalan and autologous stem cell transplantation: a single center experience.

    PubMed

    Chong, Yong Pil; Kim, Shin; Ko, Ok Bae; Koo, Ja Eun; Lee, Danbi; Park, Sang Hyoung; Park, Soo Jung; Lee, Daeho; Kim, Sang We; Suh, Cheolwon

    2008-10-01

    Immunoglobulin (Ig) D multiple myeloma (MM) accounts for 2% of all MM cases and has been reported to be associated with poor prognosis compared with other MM subtypes. The aim of the present study was to compare the effects of high-dose melphalan treatment and autologous stem cell transplantation (ASCT) on the survival of patients with IgD MM and patients with other MM subtypes. Between November 1998 and January 2005, a total of 77 patients with MM who underwent ASCT at the Asan Medical Center were enrolled in this study. High-dose melphalan (total 200 mg/m2) was used as high-dose chemotherapy. The study population was divided into two groups based on MM subtype: those with IgD MM; and those with other MM subtypes. A total of 8 patients with IgD MM were identified, accounting for about 10% of the study population. Thirty-six patients (47%) had IgG MM, 17 patients (22%) had IgA MM, and 16 patients (20%) had free light-chain MM. The two groups were similar in baseline characteristics. The median follow-up was 17 months and the median overall survival (OS) was 39 months. In the IgD MM group, median eventfree survival (EFS) and OS were 6.9 and 12 months, respectively. In the patients with other MM subtypes, median EFS and OS were 11.5 and 55.5 months (p=0.01, p<0.01), respectively. Multivariate analysis of all patients identified IgD subtype (p=0.002) and Southwest Oncology Group (SWOG) stage 2 or greater at the time of ASCT (p=0.01) as adverse prognostic factors for survival. In this small study at a single center in Korea, patients with IgD MM had poorer outcomes after ASCT than did patients with other MM subtypes.

  1. The different roles of molecular classification according to upfront autologous stem cell transplantation in advanced-stage diffuse large B cell lymphoma patients with elevated serum lactate dehydrogenase.

    PubMed

    Kim, Yu Ri; Kim, Soo-Jeong; Cheong, June-Won; Yang, Deok-Hwan; Lee, Hyewon; Eom, Hyeon-Seok; Sung, Yong Oh; Kim, Hyo Jung; Kang, Hye Jin; Lee, Won-Sik; Park, Yong; Yang, Woo-Ick; Min, Yoo Hong; Kim, Jin Seok

    2016-09-01

    The non-germinal center B cell (non-GCB) subtype of diffuse large B cell lymphoma (DLBCL) is more related to poor prognosis than the GCB subtype. To investigate the role of molecular classification according to upfront autologous hematopoietic stem cell transplantation (ASCT), we retrospectively evaluated 219 newly diagnosed high-risk DLBCL patients. Eighty-one patients were in the ASCT group, and 138 patients were in the non-ASCT group. The ASCT group yielded significantly better overall survival (OS) and progression-free survival (PFS) than the non-ASCT group (p = 0.038 and p = 0.007), and patients with the non-GCB subtype were more related to inferior PFS than those with the GCB subtype (p = 0.020). After performing age-matching by using propensity scores, upfront ASCT continued to show better OS and PFS than non-ASCT (p = 0.046 and p = 0.026). In the non-ASCT group, the non-GCB subtype showed worse OS and PFS than the GCB subtype (p = 0.039 and p = 0.007). Patients who achieved complete response showed differences in OS and PFS according to molecular subtype (p = 0.007 and p = 0.002). In the ASCT group, there were no significant differences in OS and PFS according to molecular classification (p = 0.277 and p = 0.892). In conclusion, non-GCB subtype DLBCL patients showed poor OS and PFS in the non-ASCT group while they did not show clinical significance in the ASCT group. This suggests the possibility that upfront ASCT may improve the poor prognosis of non-GCB subtype in high-risk DLBCL.

  2. High-dose radioimmunotherapy versus conventional high-dose therapy and autologous hematopoietic stem cell transplantation for relapsed follicular non-Hodgkin lymphoma: a multivariable cohort analysis.

    PubMed

    Gopal, Ajay K; Gooley, Theodore A; Maloney, David G; Petersdorf, Stephen H; Eary, Janet F; Rajendran, Joseph G; Bush, Sharon A; Durack, Lawrence D; Golden, Jane; Martin, Paul J; Matthews, Dana C; Appelbaum, Frederick R; Bernstein, Irwin D; Press, Oliver W

    2003-10-01

    We performed a multivariable comparison of 125 consecutive patients with follicular lymphoma (FL) treated at our centers with either high-dose radioimmunotherapy (HD-RIT) using 131I-anti-CD20 (n = 27) or conventional high-dose therapy (C-HDT) (n = 98) and autologous hematopoietic stem cell transplantation. The groups were similar, although more patients treated with HD-RIT had an elevated pretransplantation level of lactate dehydrogenase (41% versus 20%, P =.03) and elevated international prognostic score (41% versus 19%, P =.02). Patients treated with HD-RIT received individualized therapeutic doses of 131I-tositumomab (median, 19.7 GBq [531 mCi]) to deliver 17 to 31 Gy (median, 27 Gy) to critical organs. Patients treated with C-HDT received total body irradiation plus chemotherapy (70%) or chemotherapy alone (30%). Patients treated with HD-RIT experienced improved overall survival (OS) (unadjusted hazard ratio [HR] for death = 0.4 [95% confidence interval (95% CI), 0.2-0.9], P =.02; adjusted HR, 0.3, P =.004) and progression-free survival (PFS) (unadjusted HR =.6 [95% C.I., 0.3-1.0], P =.06; adjusted HR, 0.5, P =.03) versus patients treated with C-HDT. The estimated 5-year OS and PFS were 67% and 48%, respectively, for HD-RIT and 53% and 29%, respectively, for C-HDT. One hundred-day treatment-related mortality was 3.7% in the HD-RIT group and 11% in the C-HDT group. The probability of secondary myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) was estimated to be.076 at 8 years in the HD-RIT group and.086 at 7 years in the C-HDT group. HD-RIT may improve outcomes versus C-HDT in patients with relapsed FL.

  3. High-Dose Chemotherapy and Autologous Stem Cell Transplantation in Children with High-Risk or Recurrent Bone and Soft Tissue Sarcomas

    PubMed Central

    2016-01-01

    Despite increasing evidence that high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) might improve the survival of patients with high-risk or recurrent solid tumors, therapy effectiveness for bone and soft tissue sarcoma treatment remains unclear. This study retrospectively investigated the feasibility and effectiveness of HDCT/auto-SCT for high-risk or recurrent bone and soft tissue sarcoma. A total of 28 patients (18 high-risk and 10 recurrent) underwent single or tandem HDCT/auto-SCT between October 2004 and September 2014. During follow-up of a median 15.3 months, 18 patients exhibited disease progression and 2 died of treatment-related toxicities (1 veno-occlusive disease and 1 sepsis). Overall, 8 patients remained alive and progression-free. The 3-year overall survival (OS) and event-free survival (EFS) rates for all 28 patients were 28.7% and 26.3%, respectively. In the subgroup analysis, OS and EFS rates were higher in patients with complete or partial remission prior to HDCT/auto-SCT than in those with worse responses (OS, 39.1% vs. 0.0%, P = 0.002; EFS, 36.8% vs. 0.0%, P < 0.001). Therefore, careful selection of patients who can benefit from HDCT/auto-SCT and maximal effort to reduce tumor burden prior to treatment will be important to achieve favorable outcomes in patients with high-risk or recurrent bone and soft tissue sarcomas. PMID:27366002

  4. Cryopreservation in Closed Bag Systems as an Alternative to Clean Rooms for Preparations of Peripheral Blood Stem Cells.

    PubMed

    Spoerl, Silvia; Peter, Robert; Krackhardt, Angela M

    2016-01-01

    Autologous and allogeneic stem cell transplantation (SCT) represents a therapeutic option widely used for hematopoietic malignancies. One important milestone in the development of this treatment strategy was the development of effective cryopreservation technologies resulting in a high quality with respect to cell viability as well as lack of contamination of the graft.Stem cell preparations have been initially performed within standard laboratories as it is routinely still the case in many countries. With the emergence of cleanrooms, manufacturing of stem cell preparations within these facilities has become a new standard mandatory in Europe. However, due to high costs and laborious procedures, novel developments recently emerged using closed bag systems as reliable alternatives to conventional cleanrooms. Several hurdles needed to be overcome including the addition of the cryoprotectant dimethylsulfoxide (DMSO) as a relevant manipulation. As a result of the development, closed bag systems proved to be comparable in terms of product quality and patient outcome to cleanroom products. They also comply with the strict regulations of good manufacturing practice.With closed systems being available, costs and efforts of a cleanroom facility may be substantially reduced in the future. The process can be easily extended for other cell preparations requiring minor modifications as donor lymphocyte preparations. Moreover, novel developments may provide solutions for the production of advanced-therapy medicinal products in closed systems.

  5. Separation of hematopoietic stem cells from human peripheral blood through modified polyurethane foaming membranes.

    PubMed

    Higuchi, Akon; Sekiya, Mayu; Gomei, Yumiko; Sakurai, Masaru; Chen, Wen-Yih; Egashira, Satsuki; Matsuoka, Yuki

    2008-06-15

    Cell separation from peripheral blood was investigated using polyurethane (PU) foam membranes having 5.2 mum pore size and coated with Pluronic F127 or hyaluronic acid. The permeation ratio of hematopoietic stem cells (CD34(+) cells) and lymphocytes through the membranes was lower than for red blood cells and platelets. Adhered cells were detached from membrane surfaces using human serum albumin (HSA) solution after permeation of blood through the membranes, allowing isolation of CD34(+) cells in the permeate (recovery) solution. High-yield isolation of CD34(+) cells was achieved using Pluronic-coated membranes. This was because the Pluronic coating dissolved into the recovery solution at 4 degrees C, releasing adhered cells from the surfaces of the membranes during permeation of HSA solution through these membranes. Dextran and/or bovine serum albumin solutions were also evaluated for use as recovery solutions after blood permeation. A high recovery ratio of CD34(+) cells was achieved at 4 degrees C in a process using 20% dextran solution through PU membranes having carboxylic acid groups.

  6. Chondrogenic Potential of Peripheral Blood Derived Mesenchymal Stem Cells Seeded on Demineralized Cancellous Bone Scaffolds

    PubMed Central

    Wang, Shao-Jie; Jiang, Dong; Zhang, Zheng-Zheng; Huang, Ai-Bing; Qi, Yan-Song; Wang, Hai-Jun; Zhang, Ji-Ying; Yu, Jia-Kuo

    2016-01-01

    As a cell source with large quantity and easy access, peripheral blood mesenchymal stem cells (PBMSCs) were isolated and seeded in porcine demineralized cancellous bone (DCB) scaffolds, cultured in chondrogenic medium and evaluated for in vitro chondrogenesis. Bone marrow MSCs (BMMSCs) and articular cartilage chondrocytes (ACCs) underwent the same process as controls. The morphology, viability and proliferation of PBMSCs in DCB scaffolds were similar to those of BMMSCs and ACCs. PBMSCs and BMMSCs showed similar chondrogenesis potential with consistent production of COL 2 and SOX 9 protein and increased COL 2 and AGC mRNA expressions at week 3 but the COL 2 protein production was still less than that of ACCs. Minimal increase of hypertrophic markers was found in all groups. Relatively higher ALP and lower COL 10 mRNA expressions were found in both MSCs groups at week 3 than that in ACCs, whereas no significant difference of COL 1 and SOX 9 mRNA and MMP 13 protein was found among all groups. To conclude, PBMSCs shared similar proliferation and chondrogenic potential with BMMSCs in DCB scaffolds and could be an alternative to BMMSCs for cartilage tissue engineering. Further optimization of chondrogenesis system is needed regardless of the promising results. PMID:27821864

  7. Very Small Embryonic-like Stem Cells Are Mobilized in Human Peripheral Blood during Hypoxemic COPD Exacerbations and Pulmonary Hypertension.

    PubMed

    Guerin, Coralie L; Blandinières, Adeline; Planquette, Benjamin; Silvestre, Jean-Sébastien; Israel-Biet, Dominique; Sanchez, Olivier; Smadja, David M

    2017-03-11

    Very small embryonic-like stem cells (VSELs) are major pluripotent stem cells involved in vascular and tissue regeneration and constitute a recruitable pool of stem/progenitor cells with putative instrumental role in organ repair. Here, we hypothesized that VSELs might be mobilized from the bone marrow (BM) to peripheral blood (PB) in patients with hypoxic lung disease or pulmonary hypertension (PH). The objective of the present study was then to investigate the changes in VSELs number in peripheral blood of patients with hypoxic lung disease and PH. We enrolled 26 patients with Chronic Obstructive Pulmonary Disease (COPD) with or without hypoxemia, 13 patients with PH and 20 controls without any respiratory or cardiovascular diseases. In PH patients, VSELs levels have been determined during right heart catheterization in pulmonary blood and PB. For this purpose, mononuclear cells were separated by density gradient and VSELs have been quantified by using a multiparametric flow cytometry approach. The number of PB-VSELs in hypoxic COPD patients was significantly increased compared with non-hypoxic COPD patients or controls (p = 0.0055). In patients with PH, we did not find any difference in VSELs numbers between arterial pulmonary blood and venous PB (p = 0.93). However, we found an increase in VSELs in the peripheral blood of patients with PH (p = 0.03). In conclusion, we unraveled that circulating VSELs were increased in peripheral blood of patients with hypoxic COPD or with PH. Thus, VSELs may serve as a reservoir of pluripotent stem cells that can be recruited into PB and may play an important role in promoting lung repair.

  8. Autologous stem cell transplantation in the treatment of systemic sclerosis: report from the EBMT/EULAR Registry

    PubMed Central

    Farge, D; Passweg, J; van Laar, J M; Marjanovic, Z; Besenthal, C; Finke, J; Peter, H; Breedveld, F; Fibbe, W; Black, C; Denton, C; Koetter, I; Locatelli, F; Martini, A; Schattenberg, A; van den Hoogen, F; van de Putte, L; Lanza, F; Arnold, R; Bacon, P; Bingham, S; Ciceri, F; Didier, B; Diez-Martin, J; Emery, P; Feremans, W; Hertenstein, B; Hiepe, F; Luosujarvi, R; Leon, L; Marmont, A; Martinez, A; Pascual, C; Bocelli-Tyndall, C; Gluckman, E; Gratwohl, A; Tyndall, A

    2004-01-01

    Objective: To analyse the durability of the responses after haematopoietic stem cell transplantation (HSCT) for severe systemic sclerosis (SSc) and determine whether the high transplant related mortality (TRM) improved with experience. This EBMT/EULAR report describes the longer outcome of patients originally described in addition to newly recruited cases. Methods: Only patients with SSc, treated by HSCT in European phase I–II studies from 1996 up to 2002, with more than 6 months of follow up were included. Transplant regimens were according to the international consensus statements. Repeated evaluations analysed complete, partial, or non-response and the probability of disease progression and survival after HSCT (Kaplan-Meier). Results: Given as median (range). Among 57 patients aged 40 (9.1–68.7) years the skin scores improved at 6 (n = 37 patients), 12 (n = 30), 24 (n = 19), and 36 (n = 10) months after HSCT (p<0.005). After 22.9 (4.5–81.1) months, partial (n = 32) or complete response (n = 14) was seen in 92% and non-response in 8% (n = 4) of 50 observed cases. 35% of the patients with initial partial (n = 13/32) or complete response (n = 3/14) relapsed within 10 (2.2–48.7) months after HSCT. The TRM was 8.7% (n = 5/57). Deaths related to progression accounted for 14% (n = 8/57) of the 23% (n = 13/57) total mortality rate. At 5 years, progression probability was 48% (95% CI 28 to 68) and the projected survival was 72% (95% CI 59 to 75). Conclusion: This EBMT/EULAR report showed that response in two thirds of the patients after HSCT was durable with an acceptable TRM. Based on these results prospective, randomised trials are proceeding. PMID:15249325

  9. Effects of Intracoronary Administration of Autologous Adipose Tissue-Derived Stem Cells on Acute Myocardial Infarction in a Porcine Model

    PubMed Central

    Lee, Hye Won; Park, Jong Ha; Kim, Bo Won; Ahn, Jinhee; Kim, Jin Hee; Park, Jin Sup; Oh, Jun-Hyok; Choi, Jung Hyun; Cha, Kwang Soo; Hong, Taek Jong; Park, Tae Sik; Kim, Sang-Pil; Song, Seunghwan; Kim, Ji Yeon; Park, Mi Hwa; Jung, Jin Sup

    2015-01-01

    Purpose Adipose-derived stem cells (ADSCs) are known to be potentially effective in regeneration of damaged tissue. We aimed to assess the effectiveness of intracoronary administration of ADSCs in reducing the infarction area and improving function after acute transmural myocardial infarction (MI) in a porcine model. Materials and Methods ADSCs were obtained from each pig's abdominal subcutaneous fat tissue by simple liposuction. After 3 passages of 14-days culture, 2 million ADSCs were injected into the coronary artery 30 min after acute transmural MI. At baseline and 4 weeks after the ADSC injection, 99mTc methoxyisobutylisonitrile-single photon emission computed tomography (MIBI-SPECT) was performed to evaluate the left ventricular volume, left ventricular ejection fraction (LVEF; %), and perfusion defects as well as the myocardial salvage (%) and salvage index. At 4 weeks, each pig was sacrificed, and the heart was extracted and dissected. Gross and microscopic analyses with specific immunohistochemistry staining were then performed. Results Analysis showed improvement in the perfusion defect, but not in the LVEF in the ADSC group (n=14), compared with the control group (n=14) (perfusion defect, -13.0±10.0 vs. -2.6±12.0, p=0.019; LVEF, -8.0±15.4 vs. -15.9±14.8, p=0.181). There was a tendency of reducing left ventricular volume in ADSC group. The ADSCs identified by stromal cell-derived factor-1 (SDF-1) staining were well co-localized by von Willebrand factor and Troponin T staining. Conclusion Intracoronary injection of cultured ADSCs improved myocardial perfusion in this porcine acute transmural MI model. PMID:26446632

  10. Human peripheral blood granulocytes and myeloid leukemic cell lines express both transcripts encoding for stem cell factor.

    PubMed

    Ramenghi, U; Ruggieri, L; Dianzani, I; Rosso, C; Brizzi, M F; Camaschella, C; Pietsch, T; Saglio, G

    1994-09-01

    Stem cell factor (SCF), the ligand for the c-kit proto-oncogene, has been shown to play a critical role in the migration of melanocytes and germ cells during embryogenesis as well as in the proliferative control of the hematopoietic compartment. In this study we investigated the expression of both the soluble and transmembrane SCF forms in purified peripheral blood populations and in several hematopoietic cell lines. Expression of both transcripts, though in different ratios, was identified in whole bone marrow, in bone marrow stromal cells and in human peripheral blood. In peripheral blood, SCF expression could be ascribable to polymorphonuclear leukocytes (PMN), whereas no SCF expression was detected in isolated lymphocytes, monocytes and in some T lymphoid cell lines. Conversely, some hematopoietic myeloid cell lines, such as HL-60, KG1 and K562, express SCF with similar patterns.

  11. Concomitant systemic and central nervous system non-Hodgkin lymphoma: the role of consolidation in terms of high dose therapy and autologous stem cell transplantation. A 60-case retrospective study from LYSA and the LOC network.

    PubMed

    Damaj, Gandhi; Ivanoff, Sarah; Coso, Diane; Ysaebert, Loïc; Choquet, Sylvain; Houillier, Caroline; Parcelier, Anne; Abarah, Wajed; Marjanovic, Zora; Gressin, Rémy; Garidi, Reda; Diouf, Momar; Gac, Anne-Claire; Dupuis, Jehan; Troussard, Xavier; Morschhauseur, Franck; Ghesquières, Hervé; Soussain, Carole

    2015-09-01

    The purpose of our study is to determine the outcome of patients with systemic non-Hodgkin lymphoma presenting with neurologic localization at diagnosis, as well as the impact of consolidation in terms of high-dose therapy followed by autologous stem cell transplantation. Newly diagnosed non-Hodgkin lymphoma patients with concomitant systemic and neurological involvement at diagnosis were included in this study. Sixty patients (37 males; 25 females) were included. Median age was 61 years (23-85 years). Histological subtype was mainly diffuse large B-cell lymphoma (n = 54; 90%). The International prognostic index was over 2 in 41 (72%) patients. Median number of extranodal sites was 2 (range: 1-5). Central nervous system involvement alone was documented in 48 patients. Paravertebral involvement with epidural mass and cord compression and positive cerebrospinal fluid were present in 7 patients. Five patients had both central nervous system and epidural involvement. First-line chemotherapy was mainly anthracycline-based (88%) plus high-dose methotrexate (74%) with or without cytarabine. Consolidation with high-dose therapy followed by autologous stem cell transplantation was performed in 19 patients. For the whole population, overall response rate after induction chemotherapy was 76%. Three-year progression-free survival and overall survival were 42 ± 7% and 44 ± 7%, respectively. For patients under 66 years of age, consolidation strategy using high-dose therapy followed by autologous stem cell transplantation positively impacted 3-year overall survival and progression free survival (P = 0.008) and (P = 0.003), respectively. In multivariate analysis, high-dose therapy had a positive impact on 3-year overall survival and progression-free survival for the whole population as well as for patients under 66 years old in CR after induction therapy (OS [HR=0.22 (0.07-0.67)] and progression-free survival [HR = 0.17 (0.05-0.54)]). In conclusion, non-Hodgkin lymphoma

  12. Circulating tumor cells with a putative stem cell phenotype in peripheral blood of patients with breast cancer.

    PubMed

    Theodoropoulos, Panayiotis A; Polioudaki, Hara; Agelaki, Sofia; Kallergi, Galatea; Saridaki, Zacharenia; Mavroudis, Dimitris; Georgoulias, Vassilis

    2010-02-01

    The CD44(+)/CD24(-/low) and ALDH1(+) cell phenotypes are associated with stemness and enhanced tumorigenic potential in breast cancer. We assessed the expression of CD44, CD24 and ALDH1 on tumor cells circulating in the peripheral blood (CTCs) of patients with metastatic breast cancer using triple-marker immunofluorescence microscopy. Among a total of 1439 CTCs identified in 20 (66.7%) out of 30 patients, 35.2% had the stem-like/tumorigenic phenotype CD44(+)/CD24(-/low), whereas 17.7% of the CTCs analyzed in seven patients, were ALDH1(high)/CD24(-/low). In conclusion, we report the existence of a subpopulation of CTCs with putative stem cell progenitor phenotypes in patients with metastatic breast cancer.

  13. Dose-Modified Ifosfamide, Epirubicin, and Etoposide is a Safe and Effective Salvage Therapy with High Peripheral Blood Stem Cell Mobilization Capacity for Poorly Mobilized Hodgkin's Lymphoma and Non-Hodgkin's Lymphoma Patients.

    PubMed

    Fukunaga, Akiko; Hyuga, Mizuki; Iwasaki, Makoto; Nakae, Yoshiki; Kishimoto, Wataru; Maesako, Yoshitomo; Arima, Nobuyoshi

    2016-01-01

    A dose modified ifosfamide, epirubicin, and etoposide (IVE) regimen was prospectively assessed for its efficacy in mobilizing peripheral blood stem cells for autologous transplantation. Two patients with Hodgkin's lymphoma and two with non-Hodgkin's lymphoma who were undergoing stem cell therapy were studied. All patients had a history of multiple treatments with insufficient stem cell mobilization. The dose modified IVE regimen consisted of ifosfamide 3 g/m(2) intravenously (IV) administered on days 1-2 in combination with epirubicin 50 mg/m(2) IV on day 1 and etoposide 200 mg/m(2) (100 mg/m(2) in two patients with complete remission) IV on days 1-3. The ifosfamide dosage was reduced to two-thirds of the original protocol. A substantial high yield of CD34(+) cells was achieved when patients were treated with a dose-modified IVE regimen, compared with that during the previous regimen (two with the ifosfamide, carboplatin, and etoposide [ICE] regimen, one with high-dose cyclophosphamide and one with the original IVE regimen). Two patients who had refractory and residual disease received a 200 mg/m(2) dose of etoposide, which resulted in tumor reduction (one patient with complete remission and one with further reduction in tumor size). After the IVE regimen, all four patients had a sufficient yield of CD34(+) cells in total, which was available for stem cell transplantation. Hematological and non-hematological toxicities were comparable in all regimens. This single-center prospective study demonstrated that the dose-modified IVE regimen can be used as a safe treatment with high mobilizing efficacy in heavily pretreated lymphoma patients.

  14. Large-volume leukapheresis for peripheral blood stem cell collection in patients with hematologic malignancies.

    PubMed

    Malachowski, M E; Comenzo, R L; Hillyer, C D; Tiegerman, K O; Berkman, E M

    1992-10-01

    Large-volume leukapheresis (LVL, 15-35 L) was performed in two groups of patients (n = 10) with hematologic malignancies to obtain peripheral blood stem cells for bone marrow rescue following high-dose chemotherapy. The target cell count was 7 x 10(8) mononuclear cells (MNCs = lymphocytes and monocytes) per kg of body weight. Group A patients (n = 4) were studied on Day 1 of LVL, and components were collected from them as four sequential samples. Total MNCs collected averaged 1.29 x 10(10), total colony-forming-units granulocyte-macrophage (CFU-GM) averaged 12.1 x 10(6), and a 1.8-fold mobilization of CFU-GM was observed (p < 0.05, Sample 1 vs. Sample 4). Group B patients (n = 6) were studied throughout the three consecutive planned days of 5-hour LVL. An average of three LVL procedures per patient was performed (range, 1.25-4), and an average of 27 L (range, 24-33) of blood per LVL was processed. The blood:ACD-A ratio was 24:1 with 3000 units of heparin per 500 mL of ACD-A; heparin was also added to the collection bags. The component had an average hematocrit (Hct) of 0.02 and MNC content of 93 percent. The patients' pre-LVL and post-LVL average Hct varied significantly (before Day 1, 0.36 +/- 0.08; after Day 3, 0.28 +/- 0.06; p < 0.05). Platelet counts also decreased, with post-Day 3 counts averaging 19 percent of the average pre-Day 1 counts (p < 0.05). A decrease in the average MNC count after LVL was significant on Day 1 only (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Ex Vivo Expansion of Human Mobilized Peripheral Blood Stem Cells Using Epigenetic Modifiers

    PubMed Central

    Saraf, Santosh; Araki, Hiroto; Petro, Benjamin; Park, Youngmin; Taioli, Simona; Yoshinaga, Kazumi G; Koca, Emre; Rondelli, Damiano; Mahmud, Nadim

    2014-01-01

    Background Epigenetic modifications likely control fate of hematopoietic stem cells (HSC). The chromatin modifying agents (CMA), 5-aza-2’-deoxyctidine (5azaD) and trichostatin A (TSA) have previously been shown to expand HSC from cord blood and bone marrow. Here we assessed whether CMA can also expand HSCs present in growth factor mobilized human peripheral blood (MPB). Study Design & Methods 5azaD and TSA were sequentially added to CD34+ MPB cells in the presence of cytokines and the cells were cultured for nine days. Results Following culture, a 3.6 ± 0.5 fold expansion of CD34+CD90+ cells, a 10.1 ± 0.5 fold expansion of primitive colony forming unit (CFU)-mix, and a 2.2 ± 0.5 fold expansion of long-term cobble stone-area forming cells (CAFC) was observed in 5azaD/TSA expanded cells. By contrast, cells cultured in cytokines without 5azaD/TSA displayed no expansion; rather a reduction in CD34+CD90+ cells (0.7 ± 0.1 fold) and CAFCs (0.3 ± 0.1) from their initial numbers was observed. Global hypomethylation corresponding with increased transcript levels of several genes implicated in HSC self-renewal, including HOXB4, GATA2, and EZH2, was observed in 5azaD/TSA expanded MPB cells in contrast to controls. 5azaD/TSA expanded MPB cells retained in vivo hematopoietic engraftment capacity. Conclusion MPB CD34+ cells from donors can be expanded using 5azaD/TSA and these expanded cells retain in vivo hematopoietic reconstitution capacity. This strategy may prove to be potentially useful to augment HSCs numbers for patients who fail to mobilize. PMID:25363624

  16. Disseminated aspergillosis caused by Aspergillus ustus in a patient following allogeneic peripheral stem cell transplantation.

    PubMed

    Iwen, P C; Rupp, M E; Bishop, M R; Rinaldi, M G; Sutton, D A; Tarantolo, S; Hinrichs, S H

    1998-12-01

    The first case of disseminated aspergillosis caused by Aspergillus ustus in an allogeneic peripheral stem cell transplant patient is described. The patient, a 46-year-old female with a history of myelodysplastic syndrome, underwent high-dose chemotherapy and total body irradiation prior to transplantation. She was released from the hospital 49 days posttransplant (p.t.) in a stable condition with an absolute neutrophil count (ANC) of 2,700 cells per microl. Multiple antimicrobial agents, including itraconazole (ITR), were prescribed during hospitalization and at the time of discharge. Three days after discharge, the patient was readmitted with hemorrhagic cystitis, persistent thrombocytopenia, and bilateral pulmonary consolidation, although no fever was present. The ANC at the time of readmission was 3,500. Upon detection of a pulmonary nodule (day 67 p.t.), a bronchoalveolar lavage was performed; the lavage fluid was positive for both cytomegalovirus and parainfluenza virus and negative for fungus. The patient was placed on ganciclovir. A biopsy specimen from a leg lesion also noted on day 67 p.t. revealed septate hyphae consistent with Aspergillus species, and a culture subsequently yielded Aspergillus ustus. Confirmation detection of A. ustus was made by demonstration of characteristic reproductive structures with the presence of Hülle cells. On day 67 p.t., ITR was discontinued and liposomal amphotericin B (AMB) was initiated. The patient's condition worsened, and she died 79 days p.t. At the time of autopsy, septate hyphae were present in heart, thyroid, and lung tissues, with lung tissue culture positive for A. ustus. In vitro susceptibility testing indicated probable resistance to AMB but not to ITR. This case supports the need for the development of rapid methods to determine antifungal susceptibility.

  17. Enhanced genetic modification of adult growth factor mobilized peripheral blood hematopoietic stem and progenitor cells with rapamycin.

    PubMed

    Li, Lijing; Torres-Coronado, Mónica; Gu, Angel; Rao, Anitha; Gardner, Agnes M; Epps, Elizabeth W; Gonzalez, Nancy; Tran, Chy-Anh; Wu, Xiwei; Wang, Jin-Hui; DiGiusto, David L

    2014-10-01

    Genetic modification of adult human hematopoietic stem and progenitor cells (HSPCs) with lentiviral vectors leads to long-term gene expression in the progeny of the HSPCs and has been used to successfully treat several monogenic diseases. In some cases, the gene-modified cells have a selective growth advantage over nonmodified cells and eventually are the dominant engrafted population. However, in disease indications for which the gene-modified cells do not have a selective advantage, optimizing transduction of HSPC is paramount to successful stem cell-based gene therapy. We demonstrate here that transduction of adult CD34+ HSPCs with lentiviral vectors in the presence of rapamycin, a widely used mTORC1 inhibitor, results in an approximately threefold increase in stable gene marking with minimal effects on HSPC growth and differentiation. Using this approach, we have demonstrated that we can enhance the frequency of gene-modified HSPCs that give rise to clonogenic progeny in vitro without excessive increases in the number of vector copies per cell or changes in integration pattern. The genetic marking of HSPCs and expression of transgenes is durable, and transplantation of gene-modified HSPCs into immunodeficient mice results in high levels of gene marking of the lymphoid and myeloid progeny in vivo. The prior safe clinical history of rapamycin in other applications supports the use of this compound to generate gene-modified autologous HSPCs for our HIV gene therapy clinical trials.

  18. In-Hospital Mortality and Post-Transplant Complications in Elderly Multiple Myeloma Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation: a Population-Based Study.

    PubMed

    Sanchez, Larysa; Sylvester, Michael; Parrondo, Ricardo; Mariotti, Veronica; Eloy, Jean Anderson; Chang, Victor T

    2017-03-09

    Autologous hematopoietic stem cell transplantation (auto-HSCT) has improved survival in patients with multiple myeloma (MM) and is increasingly used in elderly patients. The aim of this study was to characterize and compare in-hospital complications and mortality after auto-HSCT in younger (< age 65) vs. elderly (≥ age 65) MM patients utilizing the Nationwide Inpatient Sample (NIS). Over a three-year period (2008-2010), 2209 patients with MM were admitted to U.S. Hospitals for auto-HSCT. The median age was 59 years, with 1650 patients (74.7%) younger than age 65 and 559 patients (25.3%) age 65 or older. Overall, in-hospital mortality in MM patients following auto-HSCT was rare (1.5%) and there was no significant difference in mortality between elderly and younger patients. Elderly patients did have a significantly increased mean length of stay (18.6 days + 10.8 days (standard deviation) vs. 16.8 days + 7.2 days, p<0.001) and mean total hospital charges ($161,117 + $105,008 vs. $151,192 + $78,342, p=0.018) compared to younger pts. Elderly patients were significantly more likely than younger patients to develop major in-hospital post-transplant complications such as severe sepsis (OR 2.70, 95% CI: 1.40-5.21, p=0.003), septic shock, (OR 3.10, 95% CI: 1.43-6.71, p=0.004), pneumonia (OR 1.62, 95% CI: 1.06-2.46, p=0.024), acute respiratory failure (OR 3.44, 95% CI: 1.70-6.96, p=0.001), endotracheal intubation requiring prolonged mechanical ventilation (OR 2.19, 95% CI: 1.06-4.55, p=0.035), acute renal failure (OR 2.14, 95% CI: 1.38-3.33, p=0.001), and cardiac arrhythmias (OR 2.06, 95% CI: 1.52-2.79, <0.001). This data may help guide informed consent discussions and provide a focus for future studies to reduce treatment-related morbidity in elderly MM patients undergoing auto-HSCT.

  19. Efficacy of Autologous Bone Marrow-Derived Mesenchymal Stem Cell and Mononuclear Cell Transplantation in Type 2 Diabetes Mellitus: A Randomized, Placebo-Controlled Comparative Study.

    PubMed

    Bhansali, Shobhit; Dutta, Pinaki; Kumar, Vinod; Yadav, Mukesh Kumar; Jain, Ashish; Mudaliar, Sunder; Bhansali, Shipra; Sharma, Ratti Ram; Jha, Vivekanand; Marwaha, Neelam; Khandelwal, Niranjan; Srinivasan, Anand; Sachdeva, Naresh; Hawkins, Meredith; Bhansali, Anil

    2017-04-01

    Drugs targeting β-cells have provided new options in the management of T2DM; however, their role in β-cell regeneration remains elusive. The recent emergence of cell-based therapies such as autologous bone marrow-derived mesenchymal stem cells (ABM-MSCs) and mononuclear cells (ABM-MNCs) seems to offer a pragmatic approach to augment β-cell function/mass. This study aims to examine the efficacy and safety of ABM-MSC and ABM-MNC transplantation in T2DM and explores alterations in glucose-insulin homeostasis by metabolic studies. Thirty patients of T2DM with duration of disease ≥5 years, receiving triple oral antidiabetic drugs along with insulin (≥0.4 IU/Kg/day) with HbA1c ≤7.5%(≤58.0 mmol/mol), were randomized to receive ABM-MSCs or ABM-MNCs through targeted approach and a sham procedure (n = 10 each). The primary endpoint was a reduction in insulin requirement by ≥50% from baseline, while maintaining HbA1c <7.0% (<53.0 mmol/mol) during 1-year follow-up. Six of 10 (60%) patients in both the ABM-MSC and ABM-MNC groups, but none in the control group, achieved the primary endpoint. At 12 months, there was a significant reduction in insulin requirement in ABM-MSC (P < 0.05) and ABM-MNC groups (P < 0.05), but not in controls (P = 0.447). There was a significant increase in second-phase C-peptide response during hyperglycemic clamp in the ABM-MNC (P < 0.05) group, whereas a significant improvement in insulin sensitivity index (P < 0.05) accompanied with an increase in insulin receptor substrate-1 gene expression was observed in the ABM-MSC group. In conclusion, both ABM-MSCs and ABM-MNCs result in sustained reduction in insulin doses in T2DM. Improvement in insulin sensitivity with MSCs and increase in C-peptide response with MNCs provide newer insights in cell-based therapies.

  20. Outcome analysis of high-dose chemotherapy and autologous stem cell transplantation in adolescent and young adults with relapsed or refractory Hodgkin lymphoma.

    PubMed

    Akhtar, Saad; Rauf, Shahzad M; Elhassan, Tusneem A M; Maghfoor, Irfan

    2016-09-01

    High-dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT) can salvage many patients with relapsed or refractory Hodgkin's lymphoma (HL). We are reporting the outcome of HDC auto-SCT and the impact of 21 prognostic factors in relapsed and refractory adolescent (14-21 years) and young adult (>21-30 years) (AYA) HL patients. We used Fine and Gray's competing risk analysis method and regression model for outcome analysis. From 1996 to 2013, 290 consecutive patients with biopsy-proven HL underwent HDC auto-SCT for relapsed/refractory HL; 216 patients (74.5 %) were AYA at the time of auto-SCT. Male/female were equal, median age at auto-SCT was 22.4 years, and there were 94 adolescent (43.5 %) and 122 young adults (56.5 %). There was refractory disease in 121 (56 %) patients, relapsed in 95 (44 %). Median follow-up was 72.6 months. The Kaplan-Meier method estimated that 5-year overall survival is 62.7 % (adolescents (63.5 %), young adults (62 %)) and event-free survival was 51.3 %. Five-year cumulative incidence of disease-specific death (DS-death) is 33 % and that of DS-event is 45 %. For DS-death, the multivariate analysis identified complete remission (CR) duration of <12 months (hazard ratio (HR) 3.61, P = 0.0009), no CR after salvage (HR: 3.93, P = 0.0002), and nodular sclerosis pathology (HR 3.3, P = 0.016) and positive B symptoms (HR 2, P = 0.028) as negative factors. For DS-event, CR duration of <12 months (HR 1.88, P = 0.02), no CR after salvage (HR 3.47, P = 0.000005) and nodular sclerosis pathology (HR 1.88, P = 0.02) were found significant. The Kaplan-Meier method estimated overall survival (OS) at 36 months with 0-2:3:4 factors being 93.6:54:21 %, respectively (P value <0.001). Kaplan-Meier estimated event-free survival (EFS) at 36 months with 0-1:2:3 factors being 84.6:65:31 %, respectively (P value <0.001). Clinically, adolescents have similar outcomes as young adults.

  1. [Effects of local transplantation of autologous adipose-derived mesenchymal stem cells on the formation of hyperplastic scar on rabbit ears].

    PubMed

    Chen, L; Wang, D L; Wei, Z R; Wang, B; Qi, J P; Sun, G F

    2016-10-20

    Objective: To investigate the effects of local transplantation of autologous adipose-derived mesenchymal stem cells (ADSCs) on the formation of hyperplastic scar on rabbit ears. Methods: ADSCs were isolated from inguinal fat of six New Zealand rabbits and then sub-cultured. ADSCs of the third passage of each rabbit were used in the following experiments. Six full-thickness skin defect wounds with diameter of 6 mm on the ventral surface of every rabbit ear were made. Wound healing and local-tissue proliferation were observed, and complete epithelization time of wounds and formation time of hyperplastic scar were recorded. The wounds on left ears were selected as group ADSCs, and the wounds on right ears were selected as control group, with 36 wounds in each group. After the complete epithelization of wounds (post injury day 25), 0.2 mL bromodeoxyuridine (BrdU) labeled autologous ADSCs with the concentration of 5×10(6) per milliliter were injected into each wound of the rabbit of group ADSCs, while the same amount of phosphate buffer solution was injected into each wound of the rabbit of control group. The frequency of injection was once every 5 days, totally for 3 times, and the latter 2 times were injected into scars generated from healed wound. Hyperplastic scars of rabbits of two groups were harvested on the fifth day after the third injection, then the morphology was observed by HE staining, and the arrangement of collagen in hyperplastic scar was observed by VG staining. The distribution of BrdU-labeled ADSCs in the hyperplastic scar was observed with fluorescence microscope. The protein content of type Ⅰ collagen, type Ⅲ collagen, transforming growth factor β1 (TGF-β1), and decorin in hyperplastic scar were detected by enzyme-linked immunosorbent assay, and the mRNA expression of decorin and TGF-β1 in hyperplastic scar were tested by real-time fluorescent quantitative reverse transcription-polymerase chain reaction. Data were processed with paired t

  2. Acceleration of Regeneration of Large-Gap Peripheral Nerve Injuries Using Accellular Nerve Allografts Plus Amniotic Fluid Derived Stem Cells (AFS)

    DTIC Science & Technology

    2015-09-01

    Nerve Allografts plus amniotic Fluid Derived Stem Cells (AFS). PRINCIPAL INVESTIGATOR: Li, Zhongyu CONTRACTING ORGANIZATION: Wake Forest...Gap Peripheral Nerve Injuries Using 5a. CONTRACT NUMBER Acellular Nerve Allografts plus amniotic Fluid Derived Stem Cells (AFS). 5b. GRANT NUMBER...Major accomplishments this year include successful seeding of AFS into ANA. This accomplishment also documented that these cells remained viable up

  3. A cautionary tale for autologous vascular tissue engineering: impact of human demographics on the ability of adipose-derived mesenchymal stem cells to recruit and differentiate into smooth muscle cells.

    PubMed

    Krawiec, Jeffrey T; Weinbaum, Justin S; St Croix, Claudette M; Phillippi, Julie A; Watkins, Simon C; Rubin, J Peter; Vorp, David A

    2015-02-01

    Autologous tissue-engineered blood vessels (TEBVs) generated using adult stem cells have shown promising results, but many preclinical evaluations do not test the efficacy of stem cells from patient populations likely to need therapy (i.e., elderly and diabetic humans). Two critical functions of these cells will be (i) secreting factors that induce the migration of host cells into the graft and (ii) differentiating into functional vascular cells themselves. The purpose of this study was to analyze whether adipose-derived mesenchymal stem cells (AD-MSCs) sourced from diabetic and elderly patients have a reduced ability to promote human smooth muscle cell (SMC) migration and differentiation potential toward SMCs, two important processes in stem cell-based tissue engineering of vascular grafts. SMC monolayers were disrupted in vitro by a scratch wound and were induced to close the wound by exposure to media conditioned by AD-MSCs from healthy, elderly, and diabetic patients. Media conditioned by AD-MSCs from healthy patients promoted the migration of SMCs and did so in a dose-dependent manner; heating the media to 56°C eliminated the media's potency. AD-MSCs from diabetic and elderly patients had a decreased ability to differentiate into SMCs under angiotensin II stimulation; however, only AD-MSCs from elderly donors were unable to promote SMC migration. Gender and body-mass index of the patients showed no effect on either critical function of AD-MSCs. In conclusion, AD-MSCs from elderly patients may not be suitable for autologous TEBVs due to inadequate promotion of SMC migration and differentiation.

  4. Enhancing nerve regeneration in the peripheral nervous system using polymeric scaffolds, stem cell engineering and nanoparticle delivery system

    NASA Astrophysics Data System (ADS)

    Sharma, Anup Dutt

    Peripheral nerve regeneration is a complex biological process responsible for regrowth of neural tissue following a nerve injury. The main objective of this project was to enhance peripheral nerve regeneration using interdisciplinary approaches involving polymeric scaffolds, stem cell therapy, drug delivery and high content screening. Biocompatible and biodegradable polymeric materials such as poly (lactic acid) were used for engineering conduits with micropatterns capable of providing mechanical support and orientation to the regenerating axons and polyanhydrides for fabricating nano/microparticles for localized delivery of neurotrophic growth factors and cytokines at the site of injury. Transdifferentiated bone marrow stromal cells or mesenchymal stem cells (MSCs) were used as cellular replacements for lost native Schwann cells (SCs) at the injured nerve tissue. MSCs that have been transdifferentiated into an SC-like phenotype were tested as a substitute for the myelinating SCs. Also, genetically modified MSCs were engineered to hypersecrete brain- derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) to secrete therapeutic factors which Schwann cell secrete. To further enhance the regeneration, nerve growth factor (NGF) and interleukin-4 (IL4) releasing polyanhydrides nano/microparticles were fabricated and characterized in vitro for their efficacy. Synergistic use of these proposed techniques was used for fabricating a multifunctional nerve regeneration conduit which can be used as an efficient tool for enhancing peripheral nerve regeneration.

  5. Safety and Efficacy of Pentostatin and Low Dose TBI With Allogenic Peripheral Blood Stem Cell Transplant

    ClinicalTrials.gov

    2010-12-02

    Acute Myelogenous Leukemia; Acute Lymphocytic Leukemia; Chronic Myelogenous Leukemia; Chronic Lymphocytic Leukemia; Myelodysplastic Syndromes; Multiple Myeloma; Non-Hodgkins Lymphoma; Hodgkins Disease; Peripheral T-Cell Lymphoma

  6. Infections after Transplantation of Bone Marrow or Peripheral Blood Stem Cells from Unrelated Donors.

    PubMed

    Young, Jo-Anne H; Logan, Brent R; Wu, Juan; Wingard, John R; Weisdorf, Daniel J; Mudrick, Cathryn; Knust, Kristin; Horowitz, Mary M; Confer, Dennis L; Dubberke, Erik R; Pergam, Steven A; Marty, Francisco M; Strasfeld, Lynne M; Brown, Janice Wes M; Langston, Amelia A; Schuster, Mindy G; Kaul, Daniel R; Martin, Stanley I; Anasetti, Claudio

    2016-02-01

    Infection is a major complication of hematopoietic cell transplantation. Prolonged neutropenia and graft-versus-host disease are the 2 major complications with an associated risk for infection, and these complications differ according to the graft source. A phase 3, multicenter, randomized trial (Blood and Marrow Transplant Clinical Trials Network [BMT CTN] 0201) of transplantation of bone marrow (BM) versus peripheral blood stem cells (PBSC) from unrelated donors showed no significant differences in 2-year survival between these graft sources. In an effort to provide data regarding whether BM or PBSC could be used as a preferential graft source for transplantation, we report a detailed analysis of the infectious complications for 2 years after transplantation from the BMT CTN 0201 trial. A total of 499 patients in this study had full audits of infection data. A total of 1347 infection episodes of moderate or greater severity were documented in 384 (77%) patients; 201 of 249 (81%) of the evaluable patients had received a BM graft and 183 of 250 (73%) had received a PBSC graft. Of 1347 infection episodes, 373 were severe and 123 were life-threatening and/or fatal; 710 (53%) of these episodes occurred on the BM arm and 637 (47%) on the PBSC arm, resulting in a 2-year cumulative incidence 84.7% (95% confidence interval [CI], 79.6 to 89.8) for BM versus 79.7% (95% CI, 73.9 to 85.5) for PBSC, P = .013. The majority of these episodes, 810 (60%), were due to bacteria, with a 2-year cumulative incidence of 72.1% and 62.9% in BM versus PBSC recipients, respectively (P = .003). The cumulative incidence of bloodstream bacterial infections during the first 100 days was 44.8% (95% CI, 38.5 to 51.1) for BM versus 35.0% (95% CI, 28.9 to 41.1) for PBSC (P = .027). The total infection density (number of infection events/100 patient days at risk) was .67 for BM and .60 for PBSC. The overall infection density for bacterial infections was .4 in both arms; for viral infections

  7. CD14+ cells from peripheral blood positively regulate hematopoietic stem and progenitor cell survival resulting in increased erythroid yield.

    PubMed

    Heideveld, Esther; Masiello, Francesca; Marra, Manuela; Esteghamat, Fatemehsadat; Yağcı, Nurcan; von Lindern, Marieke; Migliaccio, Anna Rita F; van den Akker, Emile

    2015-11-01

    Expansion of erythroblasts from human peripheral blood mononuclear cells is 4- to 15-fold more efficient than that of CD34(+) cells purified from peripheral blood mononuclear cells. In addition, purified CD34(+) and CD34(-) populations from blood do not reconstitute this erythroid yield, suggesting a role for feeder cells present in blood mononuclear cells that increase hematopoietic output. Immunodepleting peripheral blood mononuclear cells for CD14(+) cells reduced hematopoietic stem and progenitor cell expansion. Conversely, the yield was increased upon co-culture of CD34(+) cells with CD14(+) cells (full contact or transwell assays) or CD34(+) cells re-constituted in conditioned medium from CD14(+) cells. In particular, CD14(++)CD16(+) intermediate monocytes/macrophages enhanced erythroblast outgrowth from CD34(+) cells. No effect of CD14(+) cells on erythroblasts themselves was observed. However, 2 days of co-culturing CD34(+) and CD14(+) cells increased CD34(+) cell numbers and colony-forming units 5-fold. Proliferation assays suggested that CD14(+) cells sustain CD34(+) cell survival but not proliferation. These data identify previously unrecognized erythroid and non-erythroid CD34(-) and CD34(+) populations in blood that contribute to the erythroid yield. A flow cytometry panel containing CD34/CD36 can be used to follow specific stages during CD34(+) differentiation to erythroblasts. We have shown modulation of hematopoietic stem and progenitor cell survival by CD14(+) cells present in peripheral blood mononuclear cells which can also be found near specific hematopoietic niches in the bone marrow.

  8. Combining an autologous peripheral nervous system "bridge" and matrix modification by chondroitinase allows robust, functional regeneration beyond a hemisection lesion of the adult rat spinal cord.

    PubMed

    Houle, John D; Tom, Veronica J; Mayes, Debra; Wagoner, Gail; Phillips, Napoleon; Silver, Jerry

    2006-07-12

    Chondroitinase-ABC (ChABC) was applied to a cervical level 5 (C5) dorsal quadrant aspiration cavity of the adult rat spinal cord to degrade the local accumulation of inhibitory chondroitin sulfate proteoglycans. The intent was to enhance the extension of regenerated axons from the distal end of a peripheral nerve (PN) graft back into the C5 spinal cord, having bypassed a hemisection lesion at C3. ChABC-treated rats showed (1) gradual improvement in the range of forelimb swing during locomotion, with some animals progressing to the point of raising their forelimb above the nose, (2) an enhanced ability to use the forelimb in a cylinder test, and (3) improvements in balance and weight bearing on a horizontal rope. Transection of the PN graft, which cuts through regenerated axons, greatly diminished these functional improvements. Axonal regrowth from the PN graft correlated well with the behavioral assessments. Thus, many more axons extended for much longer distances into the cord after ChABC treatment and bridge insertion compared with the control groups, in which axons regenerated into the PN graft but growth back into the spinal cord was extremely limited. These results demonstrate, for the first time, that modulation of extracellular matrix components after spinal cord injury promotes significant axonal regeneration beyond the distal end of a PN bridge back into the spinal cord and that regenerating axons can mediate the return of useful function of the affected limb.

  9. Catheter-related bacteremia due to Kocuria rosea in a patient undergoing peripheral blood stem cell transplantation

    PubMed Central

    Altuntas, Fevzi; Yildiz, Orhan; Eser, Bülent; Gündogan, Kürsat; Sumerkan, Bulent; Çetin, Mustafa

    2004-01-01

    Background Micrococcus species may cause intracranial abscesses, meningitis, pneumonia, and septic arthritis in immunosuppressed or immunocompetent hosts. In addition, strains identified as Micrococcus spp. have been reported recently in infections associated with indwelling intravenous lines, continuous ambulatory peritoneal dialysis fluids, ventricular shunts and prosthetic valves. Case presentation We report on the first case of a catheter-related bacteremia caused by Kocuria rosea, a gram-positive microorganism belonging to the family Micrococcaceae, in a 39-year-old man undergoing peripheral blood stem cell transplantation due to relapsed Hodgkin disease. This uncommon pathogen may cause opportunistic infections in immunocompromised patients. Conclusions This report presents a case of Kocuria rosea catheter related bacteremia after stem cell transplantation successfully treated with vancomycin and by catheter removal. PMID:15615593

  10. Generation of Patient-Specific induced Pluripotent Stem Cell from Peripheral Blood Mononuclear Cells by Sendai Reprogramming Vectors.

    PubMed

    Quintana-Bustamante, Oscar; Segovia, Jose C

    2016-01-01

    Induced pluripotent stem cells (iPSC) technology has changed preclinical research since their generation was described by Shinya Yamanaka in 2006. iPSCs are derived from somatic cells after being reprogrammed back to an embryonic state by specific combination of reprogramming factors. These reprogrammed cells resemble all the characteristic of embryonic stem cells (ESC). The reprogramming technology is even more valuable to research diseases biology and treatment by opening gene and cell therapies in own patient's iPSC. Patient-specific iPSC can be generated from a large variety of patient cells by any of the myriad of reprogramming platforms described. Here, we describe the generation of patient-specific iPSC from patient peripheral blood mononuclear cells by Sendai Reprogramming vectors.

  11. High-speed flow cytometric analysis of nanoparticle targeting to rare leukemic stem cells in peripheral human blood: preliminary in-vitro studies

    NASA Astrophysics Data System (ADS)

    Cooper, Christy L.; Leary, James F.

    2014-03-01

    Leukemic cancer stem cells are both stem-like and leukemic-like. This complicates their detection as rare circulating tumor cells in peripheral blood of leukemia patients. The leukemic stem cells are also highly resistant to standard chemotherapeutic regimens so new therapeutic strategies need to be designed to kill the leukemic stem cells without killing normal stem cells. In these initial studies we have designed an antibody-targeted and fluorescent (Cy5.5) nanoparticle for targeting these leukemic stem cells and then introducing new strategies for killing them. Multicolor flow cytometric analyses were performed on a BD FACS Aria III. Human leukemic stem cell-like cell line RS4;11 (with putative immunophenotype CD123+/CD24+/CD38-/CD10-/Flt-3-) was used as a model human leukemic stem cell systems and were spiked into normal human peripheral blood cells containing normal blood stem-progenitor cells (immunophenotype CD123-/CD34+/CD38-) and Cy5.5-labeled nanoparticles with targeting molecule anti-CD123 antibody. An irrelevant antibody (CD71) which should not bind to any live leukemic stem cell or normal stem cell (binds erythrocytes) was used as a way of distinguishing between true-positive live and false-positive damaged/dead cells, the latter occurring at much higher frequencies than the very rare (e.g. 0.001 to 0.0001 percent frequency true leukemic stem cells). These studies are designed to measure the targeting sensitivity and specificity of the fluorescent nanoparticles to the putative rare leukemic stem cells with the eventual design to use the nanoparticles to direct killing therapeutic doses to the leukemic stem cells but not to the normal stem-progenitor cells.

  12. A pilot study of cytoreductive chemotherapy combined with infusion of additional peripheral blood stem cells reserved at time of harvest for transplantation in case of relapsed hematologic malignancies after allogeneic peripheral blood stem cell transplant.

    PubMed

    Kim, J G; Sohn, S K; Kim, D H; Lee, N Y; Suh, J S; Lee, K S; Lee, K B

    2004-01-01

    Reharvesting leukocytes from donors for a donor leukocyte infusion (DLI) is inconvenient and occasionally impossible in case of unrelated donors. It is well known that the effect of a growth factor-primed DLI is comparable to that of a nonprimed DLI. In total, 42 patients with hematologic malignancies and a high risk of relapse were allocated, on an intent-to-treat basis, a peripheral blood stem cell transplantation (PBSCT) from HLA-matched sibling donors, and then at the time of harvest, additional peripheral blood stem cells (PBSCs) were also reserved for a therapeutic primed DLI in case of relapse. In all, 12 patients who relapsed after allogeneic PBSCT were treated with mainly cytarabine-based chemotherapy followed by a cryopreserved PBSC infusion. The median dose of CD3+ and CD34+ cells for the primed DLIs was 1.43 x 10(8)/kg and 4.75 x 10(6)/kg, respectively. Six of the 12 relapsed patients exhibited a complete response after the primed DLI, plus their 1-year survival rate was 33%. The new development or progression of graft-versus-host disease after a primed DLI was observed in 50% of the patients. Overall, the survival at 1 year was 16.7%. Accordingly, the induction of a graft-versus-leukemia effect through a primed DLI, using additional PBSCs reserved at the original time of harvest, would appear to be feasible for patients with relapsed hematologic malignancies. Furthermore, this approach is also more convenient for donors.

  13. Long-Term Reduction in Peripheral Blood HIV Type 1 Reservoirs Following Reduced-Intensity Conditioning Allogeneic Stem Cell Transplantation

    PubMed Central

    Henrich, Timothy J.; Hu, Zixin; Li, Jonathan Z.; Sciaranghella, Gaia; Busch, Michael P.; Keating, Sheila M.; Gallien, Sebastien; Lin, Nina H.; Giguel, Francoise F.; Lavoie, Laura; Ho, Vincent T.; Armand, Philippe; Soiffer, Robert J.; Sagar, Manish; LaCasce, Ann S.; Kuritzkes, Daniel R.

    2013-01-01

    Background. The long-term impact of allogeneic hematopoietic stem cell transplantation (HSCT) on human immunodeficiency virus type 1 (HIV-1) reservoirs in patients receiving combination antiretroviral therapy (cART) is largely unknown. Methods. We studied the effects of a reduced-intensity conditioning allogeneic HSCT from donors with wild-type–CCR5+ cells on HIV-1 peripheral blood reservoirs in 2 patients heterozygous for the ccr5Δ32 mutation. In-depth analyses of the HIV-1 reservoir size in peripheral blood, coreceptor use, and specific antibody responses were performed on samples obtained before and up to 3.5 years after HSCT receipt. Results. Although HIV-1 DNA was readily detected in peripheral blood mononuclear cells (PBMCs) before and 2–3 months after HSCT receipt, HIV-1 DNA and RNA were undetectable in PBMCs, CD4+ T cells, or plasma up to 21 and 42 months after HSCT. The loss of detectable HIV-1 correlated temporally with full donor chimerism, development of graft-versus-host disease, and decreases in HIV-specific antibody levels. Conclusions. The ability of donor cells to engraft without evidence of ongoing HIV-1 infection suggests that HIV-1 replication may be fully suppressed during cART and does not contribute to maintenance of viral reservoirs in peripheral blood in our patients. HSCTs with wild-type–CCR5+ donor cells can lead to a sustained reduction in the size of the peripheral reservoir of HIV-1. PMID:23460751

  14. Combination of fibrin-agarose hydrogels and adipose-derived mesenchymal stem cells for peripheral nerve regeneration

    NASA Astrophysics Data System (ADS)

    Carriel, Víctor; Garrido-Gómez, Juan; Hernández-Cortés, Pedro; Garzón, Ingrid; García-García, Salomé; Sáez-Moreno, José Antonio; Sánchez-Quevedo, María del Carmen; Campos, Antonio; Alaminos, Miguel

    2013-04-01

    Objective. The objective was to study the effectiveness of a commercially available collagen conduit filled with fibrin-agarose hydrogels alone or with fibrin-agarose hydrogels containing autologous adipose-derived mesenchymal stem cells (ADMSCs) in a rat sciatic nerve injury model. Approach. A 10 mm gap was created in the sciatic nerve of 48 rats and repaired using saline-filled collagen conduits or collagen conduits filled with fibrin-agarose hydrogels alone (acellular conduits) or with hydrogels containing ADMSCs (ADMSC conduits). Nerve regeneration was assessed in clinical, electrophysiological and histological studies. Main results. Clinical and electrophysiological outcomes were more favorable with ADMSC conduits than with the acellular or saline conduits, evidencing a significant recovery of sensory and motor functions. Histological analysis showed that ADMSC conduits produce more effective nerve regeneration by Schwann cells, with higher remyelination and properly oriented axonal growth that reached the distal areas of the grafted conduits, and with intensely positive expressions of S100, neurofilament and laminin. Extracellular matrix was also more abundant and better organized around regenerated nerve tissues with ADMSC conduits than those with acellular or saline conduits. Significance. Clinical, electrophysiological and histological improvements obtained with tissue-engineered ADMSC conduits may contribute to enhancing axonal regeneration by Schwann cells.

  15. Post-transplantation Cyclophosphamide and Sirolimus after Haploidentical Hematopoietic Stem Cell Transplantation Using a Treosulfan-based Myeloablative Conditioning and Peripheral Blood Stem Cells.

    PubMed

    Cieri, Nicoletta; Greco, Raffaella; Crucitti, Lara; Morelli, Mara; Giglio, Fabio; Levati, Giorgia; Assanelli, Andrea; Carrabba, Matteo G; Bellio, Laura; Milani, Raffaella; Lorentino, Francesca; Stanghellini, Maria Teresa Lupo; De Freitas, Tiago; Marktel, Sarah; Bernardi, Massimo; Corti, Consuelo; Vago, Luca; Bonini, Chiara; Ciceri, Fabio; Peccatori, Jacopo

    2015-08-01

    Haploidentical hematopoietic stem cell transplantation (HSCT) performed using bone marrow (BM) grafts and post-transplantation cyclophosphamide (PTCy) has gained much interest for the excellent toxicity profile after both reduced-intensity and myeloablative conditioning. We investigated, in a cohort of 40 high-risk hematological patients, the feasibility of peripheral blood stem cells grafts after a treosulfan-melphalan myeloablative conditioning, followed by a PTCy and sirolimus-based graft-versus-host disease (GVHD) prophylaxis (Sir-PTCy). Donor engraftment occurred in all patients, with full donor chimerism achieved by day 30. Post-HSCT recovery of lymphocyte subsets was broad and fast, with a median time to CD4 > 200/μL of 41 days. Cumulative incidences of grade II to IV and III-IV acute GVHD were 15% and 7.5%, respectively, and were associated with a significant early increase in circulating regulatory T cells at day 15 after HSCT, with values < 5% being predictive of subsequent GVHD occurrence. The 1-year cumulative incidence of chronic GVHD was 20%. Nonrelapse mortality (NRM) at 100 days and 1 year were 12% and 17%, respectively. With a median follow-up for living patients of 15 months, the estimated 1-year overall and disease-free survival (DFS) was 56% and 48%, respectively. Outcomes were more favorable in patients who underwent transplantation in complete remission (1-year DFS 71%) versus patients who underwent transplantation with active disease (DFS, 34%; P = .01). Overall, myeloablative haploidentical HSCT with peripheral blood stem cells (PBSC) and Sir-PTCy is a feasible treatment option: the low rates of GVHD and NRM as well as the favorable immune reconstitution profile pave the way for a prospective comparative trial comparing BM and PBSC in this specific transplantation setting.

  16. Phase I/II trial of autologous stem cell transplantation in systemic sclerosis: procedure related mortality and impact on skin disease

    PubMed Central

    Binks, M; Passweg, J; Furst, D; McSweeney, P; Sullivan, K; Besenthal, C; Finke, J; Peter, H; van Laar, J; Breedveld, F; Fibbe, W; Farge, D; Gluckman, E; Locatelli, F; Martini, A; van den Hoogen, F; van de Putte, L; Schattenberg, A; Arnold, R; Bacon, P; Emery, P; Espigado, I; Hertenstein, B; Hiepe, F; Kashyap, A; Kotter, I; Marmont, A; Martinez, A; Pascual, M; Gratwohl, A; Prentice, H; Black, C; Tyndall, A

    2001-01-01

    BACKGROUND—Systemic sclerosis (SSc, scleroderma) in either its diffuse or limited skin forms has a high mortality when vital organs are affected. No treatment has been shown to influence the outcome or significantly affect the skin score, though many forms of immunosuppression have been tried. Recent developments in haemopoietic stem cell transplantation (HSCT) have allowed the application of profound immunosuppression followed by HSCT, or rescue, to autoimmune diseases such as SSc.
METHODS—Results for 41 patients included in continuing multicentre open phase I/II studies using HSCT in the treatment of poor prognosis SSc are reported. Thirty seven patients had a predominantly diffuse skin form of the disease and four the limited form, with some clinical overlap. Median age was 41 years with a 5:1 female to male ratio. The skin score was >50% of maximum in 20/33 (61%) patients, with some lung disease attributable to SSc in 28/37 (76%), the forced vital capacity being <70% of the predicted value in 18/36 (50%). Pulmonary hypertension was described in 7/37 (19%) patients and renal disease in 5/37 (14%). The Scl-70 antibody was positive in 18/32 (56%) and the anticentromere antibody in 10% of evaluable patients. Peripheral blood stem cell mobilisation was performed with cyclophosphamide or granulocyte colony stimulating factor, alone or in combination. Thirty eight patients had ex vivo CD34 stem cell selection, with additional T cell depletion in seven. Seven conditioning regimens were used, but six of these used haemoimmunoablative doses of cyclophosphamide +/- anti-thymocyte globulin +/- total body irradiation. The median duration of follow up was 12 months (3-55).
RESULTS—An improvement in skin score of >25% after transplantation occurred in 20/29 (69%) evaluable patients, and deterioration in 2/29 (7%). Lung function did not change significantly after transplantation. One of five renal cases deteriorated but with no new occurrences of renal disease

  17. Preclinical Study of Cell Therapy for Osteonecrosis of the Femoral Head with Allogenic Peripheral Blood-Derived Mesenchymal Stem Cells

    PubMed Central

    Fu, Qiang; Tang, Ning-Ning; Zhang, Qian; Liu, Yi; Peng, Jia-Chen; Fang, Ning; Yu, Li-Mei; Liu, Jin-Wei

    2016-01-01

    Purpose To explore the value of transplanting peripheral blood-derived mesenchymal stem cells from allogenic rabbits (rPBMSCs) to treat osteonecrosis of the femoral head (ONFH). Materials and Methods rPBMSCs were separated/cultured from peripheral blood after granulocyte colony-stimulating factor mobilization. Afterwards, mobilized rPBMSCs from a second passage labeled with PKH26 were transplanted into rabbit ONFH models, which were established by liquid nitrogen freezing, to observe the effect of rPBMSCs on ONFH repair. Then, the mRNA expressions of BMP-2 and PPAR-γ in the femoral head were assessed by RT-PCR. Results After mobilization, the cultured rPBMSCs expressed mesenchymal markers of CD90, CD44, CD29, and CD105, but failed to express CD45, CD14, and CD34. The colony forming efficiency of mobilized rPBMSCs ranged from 2.8 to 10.8 per million peripheral mononuclear cells. After local transplantation, survival of the engrafted cells reached at least 8 weeks. Therein, BMP-2 was up-regulated, while PPAR-γ mRNA was down-regulated. Additionally, bone density and bone trabeculae tended to increase gradually. Conclusion We confirmed that local transplantation of rPBMSCs benefits ONFH treatment and that the beneficial effects are related to the up-regulation of BMP-2 expression and the down-regulation of PPAR-γ expression. PMID:27189298

  18. A Mexican way to cope with stem cell grafting.

    PubMed

    Ruiz-Delgado, Guillermo J; Ruiz-Argüelles, Guillermo J

    2012-04-01

    The widespread practice of stem cell grafting faces several problems in the world, derived mainly from the high costs of the procedure when conducted using traditional methods. In order to cope with this problem, we have implemented in México procedures to make stem cell grafting, both autologous and allogeneic, more affordable to patients living in our country and in other developing countries. The simplification of these procedures which have been done in our country are described; they have resulted in and increased number of patients both autografted and allografted in México. In the case of autografts, the changes have relied on the use of non-frozen autologous peripheral blood stem cells and short conditioning schedules delivered as outpatients, whereas in the case of allografts, changes have relied mainly in conducting the allografts fully on an outpatient basis and employing reduced-intensity conditioning preparative schedules.

  19. Immunomodulatory effects of the Agaricus blazei Murrill-based mushroom extract AndoSan in patients with multiple myeloma undergoing high dose chemotherapy and autologous stem cell transplantation: a randomized, double blinded clinical study.

    PubMed

    Tangen, Jon-Magnus; Tierens, Anne; Caers, Jo; Binsfeld, Marilene; Olstad, Ole Kristoffer; Trøseid, Anne-Marie Siebke; Wang, Junbai; Tjønnfjord, Geir Erland; Hetland, Geir

    2015-01-01

    Forty patients with multiple myeloma scheduled to undergo high dose chemotherapy with autologous stem cell support were randomized in a double blinded fashion to receive adjuvant treatment with the mushroom extract AndoSan, containing 82% of Agaricus blazei Murrill (19 patients) or placebo (21 patients). Intake of the study product started on the day of stem cell mobilizing chemotherapy and continued until the end of aplasia after high dose chemotherapy, a period of about seven weeks. Thirty-three patients were evaluable for all study endpoints, while all 40 included patients were evaluable for survival endpoints. In the leukapheresis product harvested after stem cell mobilisation, increased percentages of Treg cells and plasmacytoid dendritic cells were found in patients receiving AndoSan. Also, in this group, a significant increase of serum levels of IL-1ra, IL-5, and IL-7 at the end of treatment was found. Whole genome microarray showed increased expression of immunoglobulin genes, Killer Immunoglobulin Receptor (KIR) genes, and HLA genes in the Agaricus group. Furthermore, AndoSan displayed a concentration dependent antiproliferative effect on mouse myeloma cells in vitro. There were no statistically significant differences in treatment response, overall survival, and time to new treatment. The study was registered with Clinicaltrials.gov NCT00970021.

  20. Immunomodulatory Effects of the Agaricus blazei Murrill-Based Mushroom Extract AndoSan in Patients with Multiple Myeloma Undergoing High Dose Chemotherapy and Autologous Stem Cell Transplantation: A Randomized, Double Blinded Clinical Study

    PubMed Central

    Tierens, Anne; Caers, Jo; Binsfeld, Marilene; Olstad, Ole Kristoffer; Trøseid, Anne-Marie Siebke; Wang, Junbai; Tjønnfjord, Geir Erland; Hetland, Geir

    2015-01-01

    Forty patients with multiple myeloma scheduled to undergo high dose chemotherapy with autologous stem cell support were randomized in a double blinded fashion to receive adjuvant treatment with the mushroom extract AndoSan, containing 82% of Agaricus blazei Murrill (19 patients) or placebo (21 patients). Intake of the study product started on the day of stem cell mobilizing chemotherapy and continued until the end of aplasia after high dose chemotherapy, a period of about seven weeks. Thirty-three patients were evaluable for all study endpoints, while all 40 included patients were evaluable for survival endpoints. In the leukapheresis product harvested after stem cell mobilisation, increased percentages of Treg cells and plasmacytoid dendritic cells were found in patients receiving AndoSan. Also, in this group, a significant increase of serum levels of IL-1ra, IL-5, and IL-7 at the end of treatment was found. Whole genome microarray showed increased expression of immunoglobulin genes, Killer Immunoglobulin Receptor (KIR) genes, and HLA genes in the Agaricus group. Furthermore, AndoSan displayed a concentration dependent antiproliferative effect on mouse myeloma cells in vitro. There were no statistically significant differences in treatment response, overall survival, and time to new treatment. The study was registered with Clinicaltrials.gov NCT00970021. PMID:25664323

  1. Mesenchymal stem cells do not exert direct beneficial effects on CNS remyelination in the absence of the peripheral immune system.

    PubMed

    Salinas Tejedor, Laura; Berner, Gabriel; Jacobsen, Kristin; Gudi, Viktoria; Jungwirth, Nicole; Hansmann, Florian; Gingele, Stefan; Prajeeth, Chittappen K; Baumgärtner, Wolfgang; Hoffmann, Andrea; Skripuletz, Thomas; Stangel, Martin

    2015-11-01

    Remyelination is the natural repair mechanism in demyelinating disorders such as multiple sclerosis (MS) and it was proposed that it might protect from axonal loss. For unknown reasons, remyelination is often incomplete or fails in MS lesions and therapeutic treatments to enhance remyelination are not available. Recently, the transplantation of exogenous mesenchymal stem cells (MSC) has emerged as a promising tool to enhance repair processes. This included the animal model experimental autoimmune encephalomyelitis (EAE), a commonly used model for the autoimmune mechanisms of MS. However, in EAE it is not clear if the beneficial effect of MSC derives from a direct influence on brain resident cells or if this is an indirect phenomenon via modulation of the peripheral immune system. The aim of this study was to determine potential regenerative functions of MSC in the toxic cuprizone model of demyelination that allows studying direct effects on de- and remyelination without the influence of the peripheral immune system. MSC from three different species (human, murine, canine) were transplanted either intraventricularly into the cerebrospinal fluid or directly into the lesion of the corpus callosum at two time points: at the onset of oligodendrocyte progenitor cell (OPC) proliferation or the peak of OPC proliferation during cuprizone induced demyelination. Our results show that MSC did not exert any regenerative effects after cuprizone induced demyelination and oligodendrocyte loss. During remyelination, MSC did not influence the dynamics of OPC proliferation and myelin formation. In conclusion, MSC did not exert direct regenerative functions in a mouse model where peripheral immune cells and especially T lymphocytes do not play a role. We thus suggest that the peripheral immune system is required for MSC to exert their effects and this is independent from a direct influence of the central nervous system.

  2. Cord Blood Banking Standards: Autologous Versus Altruistic.

    PubMed

    Armitage, Sue

    2015-01-01

    Cord blood (CB) is either donated to public CB banks for use by any patient worldwide for whom it is a match or stored in a private bank for potential autologous or family use. It is a unique cell product that has potential for treating life-threatening diseases. The majority of CB products used today are for hematopoietic stem cell transplantation and are accessed from public banks. CB is still evolving as a hematopoietic stem cell source, developing as a source for cellular immunotherapy products, such as natural killer, dendritic, and T-cells, and fast emerging as a non-hematopoietic stem cell source in the field of regenerative medicine. This review explores the regulations, standards, and accreditation schemes that are currently available nationally and internationally for public and private CB banking. Currently, most of private banking is under regulated as compared to public banking. Regulations and standards were initially developed to address the public arena. Early responses from the medical field regarding private CB banking was that at the present time, because of insufficient scientific data to support autologous banking and given the difficulty of making an accurate estimate of the need for autologous transplantation, private storage of CB as "biological insurance" should be discouraged (1, 2, 3). To ensure success and the true realization of the full potential of CB, whether for autologous or allogeneic use, it is essential that each and every product provided for current and future treatments meets high-quality, international standards.

  3. Rationale and design of the Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis in Dilated Cardiomyopathy (the POSEIDON-DCM study): a phase I/II, randomized pilot study of the comparative safety and efficacy of transendocardial injection of autologous mesenchymal stem cell vs. allogeneic mesenchymal stem cells in patients with non-ischemic dilated cardiomyopathy.

    PubMed

    Mushtaq, Muzammil; DiFede, Darcy L; Golpanian, Samuel; Khan, Aisha; Gomes, Samirah A; Mendizabal, Adam; Heldman, Alan W; Hare, Joshua M

    2014-12-01

    While accumulating clinical trials have focused on the impact of cell therapy in patients with acute myocardial infarction (MI) and ischemic cardiomyopathy, there are fewer efforts to examine cell-based therapy in patients with non-ischemic cardiomyopathy (NICM). We hypothesized that cell therapy could have a similar impact in NICM. The POSEIDON-DCM trial is a phase I/II trial designed to address autologous vs. allogeneic bone marrow-derived mesenchymal stem cells (MSCs) in patients with NICM. In this study, cells will be administered transendocardially with the NOGA injection-catheter system to patients (n = 36) randomly allocated to two treatment groups: group 1 (n = 18 auto-human mesenchymal stem cells (hMSC)) and group 2 (n = 18 allo-hMSCs). The primary and secondary objectives are, respectively, to demonstrate the safety and efficacy of allo-hMSCS vs. auto-hMSCs in patients with NICM. This study will establish safety of transendocardial injection of stem cells (TESI), compare phenotypic outcomes, and offer promising advances in the field of cell-based therapy in patients with NICM.

  4. Pure red cell aplasia after ABO major-mismatched allogeneic peripheral blood stem cell transplantation successfully treated with plasma exchange and low-dose steroid: two case reports.

    PubMed

    Tsai, Hui-Jen; Lin, Sheng-Fung; Liu, Ta-Chih; Chang, Chao-Sung; Hsiao, Hui-Hua; Chen, Tyen-Po

    2004-03-01

    Pure red cell aplasia (PRCA) is a complication of ABO-incompatible allogeneic stem cell transplantation. The mechanism is not well known, although the isoagglutinin titer before transplantation or cyclosporine use is considered to be the cause. Patients with this complication require more blood transfusions than those without it. There is no standard treatment. We report two cases of PRCA after allogeneic peripheral blood stem cell transplantation that were successfully treated with plasma exchange and low-dose steroid.

  5. Enhanced activation of B cells in a granulocyte colony-stimulating factor-mobilized peripheral blood stem cell graft.

    PubMed

    Tayebi, H; Lapierre, V; Saas, P; Lienard, A; Sutton, L; Milpied, N; Attal, M; Cahn, J Y; Kuentz, M; Blaise, D; Hervé, P; Tiberghien, P; Robinet, E

    2001-09-01

    In a randomized study that compared human leucocyte antigen-identical allogeneic granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cell (PBSC) versus bone marrow (BM) transplantation, the expression of activation markers, CD23, CD25 and CD45RO by B cells, was compared in blood before and after G-CSF mobilization and in PBSC versus BM grafts. The fractions of CD23+ and CD25+ B cells were higher in PBSC than in BM grafts. Moreover, we observed a G-CSF-induced increase in B-cell fractions in blood as well as in PBSC grafts when compared with BM grafts. Such an enhanced B-cell activation could contribute to the accelerated kinetics of immuno-haematological reconstitution, the occurrence of acute haemolysis in the ABO minor incompatibility setting, as well as the increased incidence of chronic graft-versus-host disease observed after PBSC transplantation.

  6. The role of chemokine activation of Rac GTPases in hematopoietic stem cell marrow homing, retention, and peripheral mobilization.

    PubMed

    Cancelas, Jose A; Jansen, Michael; Williams, David A

    2006-08-01

    Signaling downstream from the chemokine receptor CXCR4, the tyrosine kinase receptor c-kit and beta1-integrins has been shown to be crucial in the regulation of migration, homing, and engraftment of hematopoietic stem cells and progenitors. Each of these receptors signal through Rac-type Rho guanosine triphosphatases (GTPases). Rac GTPases play a major role in the organization of the actin cytoskeleton and also in the control of gene expression and the activation of proliferation and survival pathways. Here we review the specific roles of the members of the Rac subfamily of the Rho GTPase family in regulating the intracellular signaling of hematopoietic cells responsible for regulation of homing, marrow retention, and peripheral mobilization.

  7. Scrub typhus induced by peripheral blood stem cell transplantation in the immunocompromised patient: diagnostic usefulness of nested polymerase chain reaction.

    PubMed

    Kang, Seung-Ji; Park, Kyung-Hwa; Jung, Sook-In; Jang, Hee Chang; Ji, Soo Young; Ahn, Jae Sook; Kim, Hyeoung Joon; Shin, Jong-Hee; Kim, Dong Min

    2010-02-01

    Scrub typhus (Orientia tsutsugamushi) is a Gram-negative rickettsial disease in parts of Asia, transmitted from wild rodents to human by mites. This is a case report of scrub typhus contraction in an acute leukemia patient by transfusion of peripheral blood stem cells collected during the incubation period. Although human-to-human transmission of scrub typhus by needle-stick injury or transplacental transmission has previously been reported, this is the first case confirmed by polymerase chain reaction (PCR) and DNA sequencing. This type of incident shows the need to heighten awareness of the threat of rickettsial agents in transfused blood. Nested PCR is a useful diagnostic method to confirm the diagnosis during incubation period and in the early phase of disease, especially for immunocompromised patients.

  8. Infusion of hemolyzed red blood cells within peripheral blood stem cell grafts in patients with and without sickle cell disease.

    PubMed

    Fitzhugh, Courtney D; Unno, Hayato; Hathaway, Vincent; Coles, Wynona A; Link, Mary E; Weitzel, R Patrick; Zhao, Xiongce; Wright, Elizabeth C; Stroncek, David F; Kato, Gregory J; Hsieh, Matthew M; Tisdale, John F

    2012-06-14

    Peripheral blood stem cell (PBSC) infusions are associated with complications such as elevated blood pressure and decreased creatinine clearance. Patients with sickle cell disease experience similar manifestations, and some have postulated release of plasma-free hemoglobin with subsequent nitric oxide consumption as causative. We sought to evaluate whether the infusion of PBSC grafts containing lysed red blood cells (RBCs) leads to the toxicity observed in transplant subjects. We report a prospective cohort study of 60 subjects divided into 4 groups based on whether their infusions contained dimethyl sulfoxide (DMSO) and lysed RBCs, no DMSO and fresh RBCs, DMSO and no RBCs, or saline. Our primary end point, change in maximum blood pressure compared with baseline, was not significantly different among groups. Tricuspid regurgitant velocity and creatinine levels also did not differ significantly among groups. Our data do not support free hemoglobin as a significant contributor to toxicity associated with PBSC infusions. This study was registered at clinicaltrials.gov (NCT00631787).

  9. Human hair follicle pluripotent stem (hfPS) cells promote regeneration of peripheral-nerve injury: an advantageous alternative to ES and iPS cells.

    PubMed

    Amoh, Yasuyuki; Kanoh, Maho; Niiyama, Shiro; Hamada, Yuko; Kawahara, Katsumasa; Sato, Yuichi; Hoffman, Robert M; Katsuoka, Kensei

    2009-08-01

    The optimal source of stem cells for regenerative medicine is a major question. Embryonic stem (ES) cells have shown promise for pluripotency but have ethical issues and potential to form teratomas. Pluripotent stem cells have been produced from skin cells by either viral-, plasmid- or transposon-mediated gene transfer. These stem cells have been termed induced pluripotent stem cells or iPS cells. iPS cells may also have malignant potential and are inefficiently produced. Embryonic stem cells may not be suited for individualized therapy, since they can undergo immunologic rejection. To address these fundamental problems, our group is developing hair follicle pluripotent stem (hfPS) cells. Our previous studies have shown that mouse hfPS cells can differentiate to neurons, glial cells in vitro, and other cell types, and can promote nerve and spinal cord regeneration in vivo. hfPS cells are located above the hair follicle bulge in what we have termed the hfPS cell area (hfPSA) and are nestin positive and keratin 15 (K-15) negative. Human hfPS cells can also differentiate into neurons, glia, keratinocytes, smooth muscle cells, and melanocytes in vitro. In the present study, human hfPS cells were transplanted in the severed sciatic nerve of the mouse where they differentiated into glial fibrillary-acidic-protein (GFAP)-positive Schwann cells and promoted the recovery of pre-existing axons, leading to nerve generation. The regenerated nerve recovered function and, upon electrical stimulation, contracted the gastrocnemius muscle. The hfPS cells can be readily isolated from the human scalp, thereby providing an accessible, autologous and safe source of stem cells for regenerative medicine that have important advantages over ES or iPS cells.

  10. Allogeneic peripheral blood stem cell rescue of late graft failure after bone marrow transplantation in patients with aplastic anemia.

    PubMed Central

    Chung, Ik-Joo; Lee, Je-Jung; Park, Moo-Rim; Kook, Hoon; Cho, Sang-Hee; Hwang, Tai-Ju; Kim, Hyeoung-Joon

    2002-01-01

    We investigated the effect and outcome of allogeneic peripheral blood stem cell (PBSC) rescue for aplastic anemia (AA) patients with graft failure after allogeneic bone marrow transplantation (BMT). Seven (28%) of 25 AA patients who received BMT from HLA-identical sibling donors developed late graft failure at a median of 7 months (range, 2.0-9.3 months) after transplantation. The patients with graft failure were treated with PBSC collected from the original donor after mobilization with granulocyte-colony stimulating factor (G-CSF). The median boost dose of peripheral blood mononuclear cells was 3.1 x 10(8)/kg (range, 1.4-11.9 x 10(8)/kg). Median times to reach an absolute neutrophil count greater than 0.5 x 10(9)/L and a platelet count greater than 50 x 10(9)/L were 7 days (range, 4-14 days) and 9 days (range, 3-41 days), respectively. There was sustained graft function in 6 of 7 patients, with a median follow-up duration of 3.3 yr (range, 1.0-6.2 yr). Grade-I acute graft-versus-host disease (GVHD) occurred in 2 patients, while extensive chronic GVHD developed in 3 patients. This report shows that G-CSF-mobilized allogeneic PBSC rescue is very effective in achieving complete and sustained engraftment in patients with AA after graft failure. However, more efficacious measures to prevent extensive chronic GVHD remain to be developed. PMID:12172040

  11. Timing of peripheral blood stem cell yield: comparison of alternative methods with the classic method for CD34+ cell determination.

    PubMed

    Fatorova, I; Blaha, M; Lanska, M; Vokurkova, D; Rezacova, V; Zak, P

    2014-01-01

    Hematopoietic stem cells (HSCs), still represent a certain mystery in biology, have a unique property of dividing into equal cells and repopulating the hematopoietic tissue. This potential enables their use in transplantation treatments. The quality of the HSC grafts for transplantation is evaluated by flow cytometric determination of the CD34(+) cells, which enables optimal timing of the first apheresis and the acquisition of maximal yield of the peripheral blood stem cells (PBSCs). To identify a more efficient method for evaluating CD34(+) cells, we compared the following alternative methods with the reference method: hematopoietic progenitor cells (HPC) enumeration (using the Sysmex XE-2100 analyser), detection of CD133(+) cells, and quantification of aldehyde dehydrogenase activity in the PBSCs. 266 aphereses (84 patients) were evaluated. In the preapheretic blood, the new methods produced data that were in agreement with the reference method. The ROC curves have shown that for the first-day apheresis target, the optimal predictive cut-off value was 0.032 cells/mL for the HPC method (sensitivity 73.4%, specificity 69.3%). HPC method exhibited a definite practical superiority as compared to other methods tested. HPC enumeration could serve as a supplementary method for the optimal timing of the first apheresis; it is simple, rapid, and cheap.

  12. Allogeneic CD34+ -selected peripheral stem cell transplantation from parental donors in children with non-malignant diseases.

    PubMed

    Kremens, B; Basu, O; Peceny, R; Grosse-Wilde, H; Schaefer, U W; Havers, W

    2002-01-01

    Allogeneic peripheral stem cell transplantation in six children with non-malignant hematologic or metabolic diseases which are eventually fatal was carried out with parental donors. Given three to five HLA mismatches, all grafts underwent CD34+ cell selection as graft-versus-host prophylaxis. The patients received median doses of 16.7 x 10(6) CD34+ cells/kg and 1.2 x 10(4) CD3+ cells/kg. All transplants engrafted. Neutrophils >0.5/nl were reached on day 11 (9-19) and platelets >50/nl on day 13 (10-25). Acute GVHD responding to steriods occured in three of six patients; it was restricted to the skin and overall did not exceed grade I. Two patients died of viral infections and four are alive with stable blood counts for 13, 15, 25 and 26 months. For children with non-malignant diseases which will eventually be fatal and which can be cured or ameliorated by allogeneic BMT, CD34+-selected stem cell transplants from mismatched or even haploidentical parents can be used if no other suitable donor is available. With high CD34+ cell doses and low CD3+ cell numbers, engraftment and avoidance of acute GVHD can be expected. Infections after transplantation remain the primary threat to survival.

  13. Autologous platelet-labeling in thrombocytopenia

    SciTech Connect

    Sinzinger, H.; Virgolini, I.; Vinazzer, H. )

    1990-11-01

    Field studies performed with peripheral platelets obtained from 6 male volunteers aged 23 to 29 years revealed an extraordinary dependence of labeling efficiency on incubation time and platelet concentration after {sup 111}In-oxine platelet labeling. Since the monitoring of in vivo-platelet function in patients with thrombocytopenia may cause problems due to insufficient labeling results and homologous platelets may show a different in vivo behaviour to autologous ones, we have searched for the minimal amount of platelets necessary to allow appropriate labeling and imaging in patients with thrombocytopenia. In 15 patients with untreated thrombocytopenia aged 14 to 79 years demonstrating a mean peripheral platelet count of 2.509 +/- 1.45 x 10(4) cells/microliters autologous {sup 111}In-oxine platelet labeling was performed. The results indicate that approximately 1 x 10(8) (concentrated) platelets/ml are necessary to obtain an adequate labeling efficiency and recovery. This platelet concentration can be easily achieved by drawing one more Monovette of whole blood per each 5 x 10(4) platelets/microliter peripheral platelet count less than 2 x 10(5)/microliter. It is concluded, that calculation of the required number of platelets in advance, variation of the blood volume drawn and the volume of incubation buffer allow informative, qualitative and quantitative results using autologous platelets. The method presented effectively circumvents the requirement of homologous platelets for radiolabeling in thrombocytopenia.

  14. Management of psychiatric complications in unrelated donor before unrelated peripheral hematopoietic stem cell collections

    PubMed Central

    Hequet, Olivier; Mialou, Valerie; Audat, Francoise; Wattel, Eric; Chapel, Valerie; Revesz, Damiela; Jouet, Jean-Piere; Fisseaux, Brigitte; Saoud, Mohamed; Michallet, Mauricette

    2017-01-01

    Allogeneic hematopoietic stem cell transplantation can efficiently treat patients with severe hematological diseases. A human leukocyte antigen-compatible donor is required for performing transplantation. The occurrence of unexpected acute severe diseases in a donor can compromise the feasibility of allogeneic hematopoietic stem cell transplantation. However, when a severe health problem occurs in a donor while the recipient has already received a conditioning regimen, hematologists have to find the best solutions for the recipient, while the team in charge of the donor has to find the best medical solutions for the donor. We describe here the occurrence of psychiatric acute complications in an unrelated donor while the myeloablative conditioning regimen had already been given to the recipient. We report the successive decisions that were made in an emergency based upon the expertise of physicians specialized in hematology, apheresis, cell therapy, and psychiatry to preserve the donor’s health and recipient’s life. PMID:28115876

  15. Challenges for heart disease stem cell therapy

    PubMed Central

    Hoover-Plow, Jane; Gong, Yanqing

    2012-01-01

    Cardiovascular diseases (CVDs) are the leading cause of death worldwide. The use of stem cells to improve recovery of the injured heart after myocardial infarction (MI) is an important emerging therapeutic strategy. However, recent reviews of clinical trials of stem cell therapy for MI and ischemic heart disease recovery report that less than half of the trials found only small improvements in cardiac function. In clinical trials, bone marrow, peripheral blood, or umbilical cord blood cells were used as the source of stem cells delivered by intracoronary infusion. Some trials administered only a stem cell mobilizing agent that recruits endogenous sources of stem cells. Important challenges to improve the effectiveness of stem cell therapy for CVD include: (1) improved identification, recruitment, and expansion of autologous stem cells; (2) identification of mobilizing and homing agents that increase recruitment; and (3) development of strategies to improve stem cell survival and engraftment of both endogenous and exogenous sources of stem cells. This review is an overview of stem cell therapy for CVD and discusses the challenges these three areas present for maximum optimization of the efficacy of stem cell therapy for heart disease, and new strategies in progress. PMID:22399855

  16. Cryopreservation of hematopoietic stem/progenitor cells for therapeutic use.

    PubMed

    Watt, Suzanne M; Austin, Eric; Armitage, Sue

    2007-01-01

    To date, more than 25,000 hematopoietic transplants have been carried out across Europe for hematological disorders, the majority being for hematological malignancies. At least 70% of these are autologous transplants, the remaining 30% being allogeneic, which are sourced from related (70% of the allogeneic) or unrelated donors. Peripheral blood mobilized with granulocyte colony stimulating factor is the major source of stem cells for transplantation, being used in approx 95% of autologous transplants and in approx 65% of allogeneic transplants. Other cell sources used for transplantation are bone marrow and umbilical cord blood. One crucial advance in the treatment of these disorders has been the development of the ability to cryopreserve hematopoietic stem cells for future transplantation. For bone marrow and mobilized peripheral blood, the majority of cryopreserved harvests come from autologous collections that are stored prior to a planned infusion following further treatment of the patient or at the time of a subsequent relapse. Other autologous harvests are stored as backup or "rainy day" harvests, the former specifically being intended to rescue patients who develop graft failure following an allogeneic transplant or who may require this transplant at a later date. Allogeneic bone marrow and mobilized peripheral blood are less often cryopreserved than autologous harvests. This is in contrast to umbilical cord blood that may be banked for directed or sibling (related) hematopoietic stem cell transplants, for allogeneic unrelated donations, and for autologous donations. Allogeneic unrelated donations are of particular use for providing a source of hematopoietic stem cells for ethnic minorities, patients with rare human leukocyte antigen types, or where the patient urgently requires a transplant and cannot wait for the weeks to months required to prepare a bone marrow donor. There are currently more than 200,000 banked umbilical cord blood units registered with

  17. A randomized double blind control trial comparing filgrastim and pegfilgrastim in cyclophosphamide peripheral blood hematopoietic stem cell mobilization.

    PubMed

    Kuan, Jew-Win; Su, Anselm-Ting; Wong, Shu-Ping; Sim, Xavier Yoon-Han; Toh, See-Guan; Ong, Tee-Chuan; Rajasuriarr, Jay-Suria; Lim, Su-Hong; Guan, Yong-Khee; Liew, Hong-Keng; Liew, Pek-Kuen; Tan, Jerome Tsen-Chuen; Kori, Ahlam-Naila; Cheng, Yuin-Yin; Tan, Sen-Mui; Chang, Kian-Meng

    2015-10-01

    There are few randomized trials comparing filgrastim and pegfilgrastim in peripheral blood stem cell mobilization (PBSCM). None of the trials studied the effects of the timing of pegfilgrastim administration on the outcomes of mobilization. We conducted a randomized triple blind control trial comparing the outcomes of filgrastim 5 µg/kg daily from day 3 onwards, 'early' pegfilgrastim 6 mg on day 3 and 'delayed' pegfilgrastim 6 mg on day 7 in cyclophosphamide PBSCM in patients with no previous history of mobilization. Peripheral blood (PB) CD34+ cell count was checked on day 8 and day 11 onward. Apheresis was started when PB CD34+ ≥ 10/µl from day 11 onward. The primary outcome was the successful mobilization rate, defined as cumulative collection of ≥ 2 × 10(6)/kg CD34+ cells in three or less apheresis. The secondary outcomes were the day of neutrophil and platelet engraftment post transplantation. There were 156 patients randomized and 134 patients' data analyzed. Pegfilgrastim 6 mg day 7 produced highest percentage of successful mobilization, 34 out of 48 (70.8%) analyzed patients, followed by daily filgrastim, 28 out of 44 (63.6%) and day 3 pegfilgrastim, 20 out of 42 (47.6%) (p = 0.075). Pegfilgrastim day 7 and daily filgrastim reported 1.48 (p = 0.014) and 1.49 (p = 0.013) times higher successful mobilization rate respectively as compared to pegfilgrastim day 3 after adjusting for disease, gender and exposure to myelotoxic agent. Multiple myeloma patients were three times more likely to achieve successful mobilization as compared to acute leukemia or lymphoma patients. Pegfilgrastim avoided the overshoot of white cells compared to filgrastim. There was no difference in the duration of both white cells and platelet recovery post transplantation between the three interventional arms.

  18. In vitro incubation of bone marrow and peripheral stem cells with vincristine and methylprednisolone: functional T-cell depletion for haploidentical and autologous transplants.

    PubMed

    Fragonas, E; Perticarari, S; Presani, G; Rabusin, M; Andolina, M; Mangiarotti, M A

    2000-11-01

    A mismatched bone marrow transplantation is feasible only if the donor's marrow lymphocytes are eliminated from the graft. This can be achieved by several methods, but all have the disadvantage of inducing a long-lasting immune deficiency while the risk of graft rejection and leukemic relapse increase. We use a sort of functional T-cell depletion by treating the cells with vincristine and methylprednisolone. This method is surely the cheapest and has allowed us to perform 60 transplants with a tolerable risk of GVHD. The treatment of the donor's lymphocytes has already been demonstrated to be able to block the mixed lymphocyte culture reaction in vitro. In this experiment Th1 and Th2 activities were almost completely blocked without reduction of lymphocyte viability and apoptosis induction.

  19. Anti-thymocyte globulin as graft-versus-host disease prevention in the setting of allogeneic peripheral blood stem cell transplantation: a review from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

    PubMed Central

    Baron, Frédéric; Mohty, Mohamad; Blaise, Didier; Socié, Gérard; Labopin, Myriam; Esteve, Jordi; Ciceri, Fabio; Giebel, Sebastian; Gorin, Norbert Claude; Savani, Bipin N; Schmid, Christoph; Nagler, Arnon

    2017-01-01

    Allogeneic hematopoietic stem cell transplantation is increasingly used as treatment for patients with life-threatening blood diseases. Its curative potential is largely based on immune-mediated graft-versus-leukemia effects caused by donor T cells contained in the graft. Unfortunately, donor T cells are also the cause of graft-versus-host disease. The vast majority of human leukocyte antigen-matched allogeneic hematopoietic stem cell transplants are nowadays carried out with peripheral blood stem cells as the stem cell source. In comparison with bone marrows, peripheral blood stem cells contain more hematopoietic stem/progenitor cells but also one log more T cells. Consequently, the use of peripheral blood stem cells instead of bone marrow has been associated with faster hematologic recovery and a lower risk of relapse in patients with advanced disease, but also with a higher incidence of chronic graft-versus-host disease. These observations have been the basis for several studies aimed at assessing the impact of immunoregulation with anti-thymocyte globulin on transplantation outcomes in patients given human leukocyte antigen-matched peripheral blood stem cells from related or unrelated donors. After a brief introduction on anti-thymocyte globulin, this article reviews recent studies assessing the impact of anti-thymocyte globulin on transplantation outcomes in patients given peripheral blood stem cells from human leukocyte antigen-matched related or unrelated donors as well as in recipients of grafts from human leukocyte antigen haploidentical donors. PMID:27927772

  20. The peripheral chimerism of bone marrow-derived stem cells after transplantation: regeneration of gastrointestinal tissues in lethally irradiated mice.

    PubMed

    Filip, Stanislav; Mokrý, Jaroslav; Vávrová, Jiřina; Sinkorová, Zuzana; Mičuda, Stanislav; Sponer, Pavel; Filipová, Alžběta; Hrebíková, Hana; Dayanithi, Govindan

    2014-05-01

    Bone marrow-derived cells represent a heterogeneous cell population containing haematopoietic stem and progenitor cells. These cells have been identified as potential candidates for use in cell therapy for the regeneration of damaged tissues caused by trauma, degenerative diseases, ischaemia and inflammation or cancer treatment. In our study, we examined a model using whole-body irradiation and the transplantation of bone marrow (BM) or haematopoietic stem cells (HSCs) to study the repair of haematopoiesis, extramedullary haematopoiesis and the migration of green fluorescent protein (GFP(+)) transplanted cells into non-haematopoietic tissues. We investigated the repair of damage to the BM, peripheral blood, spleen and thymus and assessed the ability of this treatment to induce the entry of BM cells or GFP(+) lin(-) Sca-1(+) cells into non-haematopoietic tissues. The transplantation of BM cells or GFP(+) lin(-) Sca-1(+) cells from GFP transgenic mice successfully repopulated haematopoiesis and the haematopoietic niche in haematopoietic tissues, specifically the BM, spleen and thymus. The transplanted GFP(+) cells also entered the gastrointestinal tract (GIT) following whole-body irradiation. Our results demonstrate that whole-body irradiation does not significantly alter the integrity of tissues such as those in the small intestine and liver. Whole-body irradiation also induced myeloablation and chimerism in tissues, and induced the entry of transplanted cells into the small intestine and liver. This result demonstrates that grafted BM cells or GFP(+) lin(-) Sca-1(+) cells are not transient in the GIT. Thus, these transplanted cells could be used for the long-term treatment of various pathologies or as a one-time treatment option if myeloablation-induced chimerism alone is not sufficient to induce the entry of transplanted cells into non-haematopoietic tissues.

  1. Hypoxia Pre-Conditioned Embryonic Mesenchymal Stem Cell Secretome Reduces IL-10 Production by Peripheral Blood Mononuclear Cells

    PubMed Central

    Lotfinia, Majid; Lak, Shirin; Ghahhari, Nastaran Mohammadi; Johari, Behrooz; Maghsood, Faezeh; Parsania, Sara; Tabrizi, Bahareh Sadegh; Kadivar, Mehdi

    2017-01-01

    Background: Mesenchymal stem cells (MSCs) are important candidates for MSC-based cellular therapy. Current paradigm states that MSCs support local progenitor cells in damaged tissue through paracrine signaling. Therefore, the study of paracrine effects and secretome of MSCs could lead to the appreciation of mechanisms and molecules associated with the therapeutic effects of these cells. This study analyzed anti-inflammatory and immune-modulatory effects of MSC secretomes derived from embryonic stem cells (ESCs) and bone marrow cells after hypoxia and normoxia preconditioning. Methods: ESCs differentiated into MSCs and characterized by flow cytometry as well as by differentiation into adipocytes and osteoblasts. The experimental groups were consisted of individual groups of ESC-MSCs and BM-MSCs (bone marrow-derived mesenchymal stromal cells), which were preconditioned with either hypoxia or normoxia for 24, 48 and 72 h. After collecting the cell-free medium from each treatment, secretomes were concentrated by centrifugal filters. Using a peripheral blood mononuclear cell (PBMC) assay and ELISA, IL-10 concentration in PBMCs was evaluated after their incubation with different secretomes from preconditioned and non-preconditioned MSCs. Results: A significant difference was observed between ESC-MSC normoxia and ESC-MSC hypoxia in IL-10 concentration, and normoxia secretomes increased IL-10 secretion from PBMCs. Moreover, the strongest IL-10 secretion from PBMCs could be detected after the stimulation by ESC-MSC conditioned secretomes, but not BM-MSC conditioned medium. Conclusions: Human hypoxia preconditioned ESC-MSC secretome indicated stronger immune-modulatory effects compared to BM-MSC conditioned medium. It could be suggested that induced MSCs confer less immune-modulatory effects but produce more inflammatory molecules such as tumor necrosis factor α, which needs further investigation. PMID:27132108

  2. Donor Peripheral Stem Cell Transplant in Treating Patients With Hematolymphoid Malignancies

    ClinicalTrials.gov

    2016-11-17

    Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Relapsing Chronic Myelogenous Leukemia; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

  3. The road to purified hematopoietic stem cell transplants is paved with antibodies

    PubMed Central

    Logan, Aaron C.; Weissman, Irving L.; Shizuru, Judith A.

    2016-01-01

    Hematopoietic progenitor cell replacement therapy remains a surprisingly unrefined process. In general, unmanipulated bone marrow or mobilized peripheral blood grafts which carry potentially harmful passenger cells are administered after treating recipients with high-dose chemo- and/or radiotherapy to eradicate malignant disease, eliminate immunologic barriers to allogeneic cell engraftment, and to “make space” for rare donor stem cells within the stem cell niche. The sequalae of such treatments are substantial, including direct organ toxicity and non-specific inflammation that contributes to the development of graft-versus-host disease and poor immune reconstitution. Passenger tumor cells that contaminate autologous hematopoietic grafts may contribute to relapse post-transplant. Use of antibodies to rid grafts of unwanted cell populations, and to eliminate or minimize the need for non-specifically cytotoxic therapies used to condition transplant recipients, will dramatically improve the safety profile of allogeneic and gene-modified autologous hematopoietic stem cell therapies. PMID:22939368

  4. Blood and Bone Marrow Hematopoietic Stem Cells for Transplantation: A Comparative Review.

    PubMed

    Janssen; Hiemenz; Fields; Zorsky; Ballester; Goldstein; Elfenbein

    1994-05-01

    Classical bone marrow transplantation collects bone marrow from a normal individual. This is infused into a patient rendered aplastic by high-dose chemoradiotherapy. Shortcomings include a limited donor pool and morbidity and mortality from graft-vs-host and graft rejection phenomena. Autologous marrow transplantation, in which the marrow of the patient to be transplanted is harvested, cryopreserved, and stored until needed, is not so constrained. Although marrow cannot be collected from some individuals due to hypocellularity, fibrosis, or infiltration with malignant disease, the presence of peripheral blood stem cells in the circulation allows these individuals to be treated with autologous transplantation therapy. It has been postulated that these hematopoietic progenitors have advantages over bone marrow collected stem cells, including safer and less expensive collections and accelerated rates of hematopoietic recovery following high-dose therapy and stem cell reinfusion.

  5. Nonmyeloablative peripheral blood haploidentical stem cell transplantation for refractory severe aplastic anemia.

    PubMed

    Clay, Jennifer; Kulasekararaj, Austin G; Potter, Victoria; Grimaldi, Francesco; McLornan, Donal; Raj, Kavita; de Lavallade, Hugues; Kenyon, Michelle; Pagliuca, Antonio; Mufti, Ghulam J; Marsh, Judith C W

    2014-11-01

    New transplant approaches are urgently needed for patients with refractory severe aplastic anemia (SAA) who lack a matched sibling or unrelated donor (UD) or who have failed UD or cord blood transplant. Patients with refractory SAA are at risk of later clonal evolution to myelodysplastic syndrome and acute leukemia. We report our pilot findings with haploidentical hematopoietic stem cell transplantation (haploHSCT) using uniform reduced-intensity conditioning with postgraft high-dose cyclophosphamide in 8 patients with refractory SAA or patients who rejected a prior UD or cord blood transplant. Six of 8 patients engrafted. Graft failure was associated with donor-directed HLA antibodies, despite intensive pre-HSCT desensitization with plasma exchange and rituximab. There was only 1 case of grade II skin graft-versus-host disease. We show that haploHSCT can successfully rescue refractory SAA patients who lack donor-directed HLA antibodies but not in the presence of donor-directed HLA antibodies. This novel protocol for haploHSCT for SAA has been adopted by the European Group for Blood and Marrow Transplantation Severe Aplastic Anaemia Working Party for a future noninterventional, observational study to further evaluate its efficacy.

  6. Survival of multiple myeloma patients aged 65-70 years in the era of novel agents and autologous stem cell transplantation. A multicenter retrospective collaborative study of the Japanese Society of Myeloma and the European Myeloma Network.

    PubMed

    Ozaki, Shuji; Harada, Takeshi; Saitoh, Takayuki; Shimazaki, Chihiro; Itagaki, Mitsuhiro; Asaoku, Hideki; Kuroda, Yoshiaki; Chou, Takaaki; Yoshiki, Yumiko; Suzuki, Kenshi; Murakami, Hirokazu; Hayashi, Kunihiko; Mina, Roberto; Palumbo, Antonio; Shimizu, Kazuyuki

    2014-01-01

    Novel agents such as thalidomide, lenalidomide and bortezomib have dramatically changed the treatment paradigm of multiple myeloma (MM). However, it is not clear whether these agents improve the prognosis of elderly patients who have undergone autologous stem cell transplantation (auto-SCT). We retrospectively analyzed the outcome of 318 newly diagnosed patients aged 65–70 years who were treated between January 1, 2004, and December 31, 2009. As initial therapy, 192 patients were treated with conventional chemotherapy,88 with novel agent-containing regimens, 21 with conventional chemotherapy plus auto-SCT and the remaining 17 with novel agents plus auto-SCT. The median progression-free survival was 19.1, 24.5, 26.8 and 35.2 months, respectively, and the 5-year overall survival (OS) was 40, 62, 63 and 87%, respectively. Initial therapy with novel agents (p < 0.001) or auto-SCT (p < 0.02) significantly improved OS compared with the group without these treatment modalities. Salvage therapy with novel agents also significantly improved survival after relapse compared with conventional chemotherapy alone (p < 0.04). In a multivariate analysis, the use of novel agents was an independent prognostic factor significantly associated with extended OS(p < 0.003). These results indicate that novel agents and auto-SCT had a major impact on OS in eligible patients in this subgroup of MM.

  7. The Role of E-Cadherin in Maintaining the Barrier Function of Corneal Epithelium after Treatment with Cultured Autologous Oral Mucosa Epithelial Cell Sheet Grafts for Limbal Stem Deficiency

    PubMed Central

    Hoft, Richard H.; Wood, Andrew; Oliva, Joan; Niihara, Hope; Makalinao, Andrew; Thropay, Jacquelyn; Pan, Derek; Tiger, Kumar; Garcia, Julio; Laporte, Amanda; French, Samuel W.; Niihara, Yutaka

    2016-01-01

    The role of E-cadherin in epithelial barrier function of cultured autologous oral mucosa epithelial cell sheet (CAOMECS) grafts was examined. CAOMECS were cultured on a temperature-responsive surface and grafted onto rabbit corneas with Limbal Stem Cell Deficiency (LSCD). E-cadherin levels were significantly higher in CAOMECS compared to normal and LSCD epithelium. Beta-catenin colocalized with E-cadherin in CAOMECS cell membranes while phosphorylated beta-catenin was significantly increased. ZO-1, occludin, and Cnx43 were also strongly expressed in CAOMECS. E-cadherin and beta-catenin localization at the cell membrane was reduced in LSCD corneas, while CAOMECS-grafted corneas showed a restoration of E-cadherin and beta-catenin expression. LSCD corneas did not show continuous staining for ZO-1 or for Cnx43, while CAOMECS-grafted corneas showed a positive expression of ZO-1 and Cnx43. Cascade Blue® hydrazide did not pass through CAOMECS. Because E-cadherin interactions are calcium-dependent, EGTA was used to chelate calcium and disrupt cell adhesion. EGTA-treated CAOMECS completely detached from cell culture surface, and E-cadherin levels were significantly decreased. In conclusion, E cadherin high expression contributed to CAOMECS tight and gap junction protein recruitment at the cell membrane, thus promoting cellular adhesion and a functional barrier to protect the ocular surface. PMID:27777792

  8. Autologous hematopoietic stem cell transplantation for pediatric multiple sclerosis: a registry-based study of the Autoimmune Diseases Working Party (ADWP) and Pediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT).

    PubMed

    Burman, J; Kirgizov, K; Carlson, K; Badoglio, M; Mancardi, G L; De Luca, G; Casanova, B; Ouyang, J; Bembeeva, R; Haas, J; Bader, P; Snowden, J; Farge, D

    2017-03-20

    Autologous hematopoietic stem cell transplantation (aHSCT) is a promising therapy for multiple sclerosis (MS), which has mainly been used in adults. The purpose of this study was to investigate efficacy and adverse events of aHSCT in the treatment of children with MS using data from the European Society for Blood and Marrow Transplantation registry. Twenty-one patients with a median follow-up time of 2.8 years could be identified. PFS at 3 years was 100%, 16 patients improved in expanded disability status scale score and only 2 patients experienced a clinical relapse. The procedure was generally well tolerated and only two instances of severe transplant-related toxicity were recorded. There was no treatment-related mortality, although one patient needed intensive care. aHSCT may be a therapeutic option for children with disease that does not respond to standard care.Bone Marrow Transplantation advance online publication, 20 March 2017; doi:10.1038/bmt.2017.40.

  9. Effect of melphalan 140 mg/m(2) vs 200 mg/m(2) on toxicities and outcomes in multiple myeloma patients undergoing single autologous stem cell transplantation-a single center experience.

    PubMed

    Katragadda, Lakshmikanth; McCullough, Lindsay M; Dai, Yunfeng; Hsu, Jack; Byrne, Michael; Hiemenz, John; May, Stratford; Cogle, Christopher R; Norkin, Maxim; Brown, Randy A; Wingard, John R; Chang, Myron; Moreb, Jan S

    2016-08-01

    Although melphalan at a dose of 140 mg/m(2) (MEL140) is an acceptable conditioning regimen for autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients, very few studies compared it to the most commonly used dose of 200 mg/m(2) (MEL200). A retrospective review of records of MM patients (2001-2010) identified 33 patients who received MEL140 and 96 patients who received MEL200. As expected, significantly higher percentage of patients in the MEL140 arm were >65 years or had cardiac ejection fraction <50%, had Karnofsky score <80, or had creatinine >2 at the time of ASCT (P≤.01). There were no significant differences in incidence of treatment related mortality and morbidity. At a median follow-up of 74 months from ASCT, there were no significant differences in relapse free survival (RFS) and overall survival (OS) between the two groups. Similar proportion had myeloma status improve to ≥VGPR at 3 months post-ASCT. Usage of post-ASCT maintenance was similar. In multivariate cox proportional hazards model, only disease status of ≥VGPR at the time of ASCT significantly improved RFS (P=.024), but not OS (P=.104). In conclusion, MM patients who received MEL140 had similar long-term outcomes to MEL200 patients despite their older age and co-morbidities.

  10. Sequential myeloablative autologous stem cell transplantation and reduced intensity allogeneic hematopoietic cell transplantation is safe and feasible in children, adolescents and young adults with poor-risk refractory or recurrent Hodgkin and non-Hodgkin lymphoma.

    PubMed

    Satwani, P; Jin, Z; Martin, P L; Bhatia, M; Garvin, J H; George, D; Chaudhury, S; Talano, J; Morris, E; Harrison, L; Sosna, J; Peterson, M; Militano, O; Foley, S; Kurtzberg, J; Cairo, M S

    2015-02-01

    The outcome of children, adolescents and young adults (CAYA) with poor-risk recurrent/refractory lymphoma is dismal (⩽30%). To overcome this poor prognosis, we designed an approach to maximize an allogeneic graft vs lymphoma effect in the setting of low disease burden. We conducted a multi-center prospective study of myeloablative conditioning (MAC) and autologous stem cell transplantation (AutoSCT), followed by a reduced intensity conditioning (RIC) and allogeneic hematopoietic cell transplantation (AlloHCT) in CAYA, with poor-risk refractory or recurrent lymphoma. Conditioning for MAC AutoSCT consisted of carmustine/etoposide/cyclophosphamide, RIC consisted of busulfan/fludarabine. Thirty patients, 16 Hodgkin lymphoma (HL) and 14 non-Hodgkin lymphoma (NHL), with a median age of 16 years and median follow-up of 5years, were enrolled. Twenty-three patients completed both MAC AutoSCT and RIC AlloHCT. Allogeneic donor sources included unrelated cord blood (n=9), unrelated donor (n=8) and matched siblings (n=6). The incidence of transplant-related mortality following RIC AlloHCT was only 12%. In patients with HL and NHL, 10 year EFS was 59.8% and 70% (P=0.613), respectively. In summary, this approach is safe, and long-term EFS with this approach is encouraging considering the poor-risk patient characteristics and the use of unrelated donors for RIC AlloHCT in the majority of cases.

  11. High incidence of post-transplant cytomegalovirus reactivations in myeloma patients undergoing autologous stem cell transplantation after treatment with bortezomib-based regimens: a survey from the Rome transplant network.

    PubMed

    Marchesi, F; Mengarelli, A; Giannotti, F; Tendas, A; Anaclerico, B; Porrini, R; Picardi, A; Cerchiara, E; Dentamaro, T; Chierichini, A; Romeo, A; Cudillo, L; Montefusco, E; Tirindelli, M C; De Fabritiis, P; Annino, L; Petti, M C; Monarca, B; Arcese, W; Avvisati, G

    2014-02-01

    The incidence of cytomegalovirus (CMV) reactivations in patients with multiple myeloma (MM) receiving autologous stem cell transplantation (ASCT) is relatively low. However, the recent increased use of novel agents, such as bortezomib and/or immunomodulators, before transplant, has led to an increasing incidence of Herpesviridae family virus infections. The aim of the study was to establish the incidence of post-engraftment symptomatic CMV reactivations in MM patients receiving ASCT, and to compare this incidence with that of patients treated with novel agents or with conventional chemotherapy before transplant. The study was a survey of 80 consecutive patients who underwent ASCT after treatment with novel agents (Group A). These patients were compared with a cohort of 89 patients treated with VAD regimen (vincristine, doxorubicin, and dexamethasone) before ASCT (Group B). Overall, 7 patients (4.1%) received an antiviral treatment for a symptomatic CMV reactivation and 1 died. The incidence of CMV reactivations was significantly higher in Group A than in Group B (7.5% vs. 1.1%; P = 0.048). When compared with Group B, the CMV reactivations observed in Group A were significantly more frequent in patients who received bortezomib, whether or not associated with immunomodulators (9.4% vs. 1.1%; P = 0.019), but not in those treated with immunomodulators only (3.7% vs. 1.1%; P = 0.396). These results suggest that MM patients treated with bortezomib-based regimens are at higher risk of developing a symptomatic CMV reactivation after ASCT.

  12. Severe regimen-related toxicity occurring in a patient with XYY syndrome receiving allogeneic peripheral blood stem cell transplantation.

    PubMed

    Shibata, S; Kami, M; Kishi, Y; Hamaki, T; Ueyama, J-I; Miyakoshi, S; Morinaga, S-I; Hirabayashi, N; Kanda, Y; Mutou, Y

    2002-07-01

    A 23-year-old man with chronic myelocytic leukemia (CML) in the first chronic phase underwent allogeneic peripheral blood stem cell transplantation (PBSCT) from his HLA-identical sibling. Pretransplant evaluations showed that he had a low risk of transplantation-related mortality and that the interval between the diagnosis of CML and PBSCT was only 6 months. However, he developed a variety of complications, including acute renal failure requiring hemodialysis, severe hepatic damage, hemorrhagic cystitis, and gastrointestinal hemorrhage leading to hypovolemic shock. Pathological examination of the colonic mucosa showed vascular endothelial damage and thrombotic lesions, leading to the diagnosis of thrombotic microangiopathy. Later, we found that he had the constitutional abnormality XYY. XYY syndrome is a frequent congenital abnormality, and mental disorders and congenital abnormalities of kidney and liver are common manifestations. Considering his clinical course, it was interesting that complications were severe in the organs which are frequently involved in cases of XYY syndrome. These organs may have poor function or poor reserves and may be more vulnerable to endothelial damage caused by high-dose cytotoxic chemotherapy. Patients with XYY syndrome might have a high risk of transplantation-related mortality.

  13. Donor demographic and laboratory predictors of allogeneic peripheral blood stem cell mobilization in an ethnically diverse population.

    PubMed

    Vasu, Sumithira; Leitman, Susan F; Tisdale, John F; Hsieh, Matthew M; Childs, Richard W; Barrett, A John; Fowler, Daniel H; Bishop, Michael R; Kang, Elizabeth M; Malech, Harry L; Dunbar, Cynthia E; Khuu, Hanh M; Wesley, Robert; Yau, Yu Y; Bolan, Charles D

    2008-09-01

    A reliable estimate of peripheral blood stem cell (PBSC) mobilization response to granulocyte colony-stimulating factor (G-CSF) may identify donors at risk for poor mobilization and help optimize transplantation approaches. We studied 639 allogeneic PBSC collections performed in 412 white, 75 black, 116 Hispanic, and 36 Asian/Pacific adult donors who were prescribed G-CSF dosed at either 10 or 16 microg/kg per day for 5 days followed by large-volume leukapheresis (LVL). Additional LVL (mean, 11 L) to collect lymphocytes for donor lymphocyte infusion (DLI) and other therapies was performed before G-CSF administration in 299 of these donors. Day 5 preapheresis blood CD34(+) cell counts after mobilization were significantly lower in whites compared with blacks, Hispanics, and Asian/Pacific donors (79 vs 104, 94, and 101 cells/microL, P < .001). In addition, donors who underwent lymphapheresis before mobilization had higher CD34(+) cell counts than donors who did not (94 vs 79 cells/microL, P < .001). In multivariate analysis, higher post-G-CSF CD34(+) cell counts were most strongly associated with the total amount of G-CSF received, followed by the pre-G-CSF platelet count, pre-G-CSF mononuclear count, and performance of prior LVL for DLI collection. Age, white ethnicity, and female gender were associated with significantly lower post-G-CSF CD34(+) cell counts.

  14. Donor demographic and laboratory predictors of allogeneic peripheral blood stem cell mobilization in an ethnically diverse population

    PubMed Central

    Vasu, Sumithira; Leitman, Susan F.; Tisdale, John F.; Hsieh, Matthew M.; Childs, Richard W.; Barrett, A. John; Fowler, Daniel H.; Bishop, Michael R.; Kang, Elizabeth M.; Malech, Harry L.; Dunbar, Cynthia E.; Khuu, Hanh M.; Wesley, Robert; Yau, Yu Y.

    2008-01-01

    A reliable estimate of peripheral blood stem cell (PBSC) mobilization response to granulocyte colony-stimulating factor (G-CSF) may identify donors at risk for poor mobilization and help optimize transplantation approaches. We studied 639 allogeneic PBSC collections performed in 412 white, 75 black, 116 Hispanic, and 36 Asian/Pacific adult donors who were prescribed G-CSF dosed at either 10 or 16 μg/kg per day for 5 days followed by large-volume leukapheresis (LVL). Additional LVL (mean, 11 L) to collect lymphocytes for donor lymphocyte infusion (DLI) and other therapies was performed before G-CSF administration in 299 of these donors. Day 5 preapheresis blood CD34+ cell counts after mobilization were significantly lower in whites compared with blacks, Hispanics, and Asian/Pacific donors (79 vs 104, 94, and 101 cells/μL, P < .001). In addition, donors who underwent lymphapheresis before mobilization had higher CD34+ cell counts than donors who did not (94 vs 79 cells/μL, P < .001). In multivariate analysis, higher post–G-CSF CD34+ cell counts were most strongly associated with the total amount of G-CSF received, followed by the pre–G-CSF platelet count, pre–G-CSF mononuclear count, and performance of prior LVL for DLI collection. Age, white ethnicity, and female gender were associated with significantly lower post–G-CSF CD34+ cell counts. PMID:18523146

  15. Pretransplant pulmonary function tests predict risk of mortality following fractionated total body irradiation and allogeneic peripheral blood stem cell transplant

    SciTech Connect

    Singh, Anurag K. . E-mail: singan@mail.nih.gov; Karimpour, Shervin E.; Savani, Bipin N.; Guion, Peter M.S.; Hope, Andrew J.; Mansueti, John R.; Ning, Holly; Altemus, Rosemary M. Ph.D.; Wu, Colin O.; Barrett, A. John

    2006-10-01

    Purpose: To determine the value of pulmonary function tests (PFTs) done before peripheral blood stem cell transplant (PBSCT) in predicting mortality after total body irradiation (TBI) performed with or without dose reduction to the lung. Methods and Materials: From 1997 to 2004, 146 consecutive patients with hematologic malignancies received fractionated TBI before PBSCT. With regimen A (n = 85), patients were treated without lung dose reduction to 13.6 gray (Gy). In regimen B (n = 35), total body dose was decreased to 12 Gy (1.5 Gy twice per day for 4 days) and lung dose was limited to 9 Gy by use of lung shielding. In regimen C (n = 26), lung dose was reduced to 6 Gy. All patients received PFTs before treatment, 90 days after treatment, and annually. Results: Median follow-up was 44 months (range, 12-90 months). Sixty-one patients had combined ventilation/diffusion capacity deficits defined as both a forced expiratory volume in the first second (FEV{sub 1}) and a diffusion capacity of carbon dioxide (DLCO) <100% predicted. In this group, there was a 20% improvement in one-year overall survival with lung dose reduction (70 vs. 50%, log-rank test p = 0.042). Conclusion: Among those with combined ventilation/diffusion capacity deficits, lung dose reduction during TBI significantly improved survival.

  16. Urokinase type plasminogen activator mediates Interleukin-17-induced peripheral blood mesenchymal stem cell motility and transendothelial migration.

    PubMed

    Krstić, Jelena; Obradović, Hristina; Jauković, Aleksandra; Okić-Đorđević, Ivana; Trivanović, Drenka; Kukolj, Tamara; Mojsilović, Slavko; Ilić, Vesna; Santibañez, Juan F; Bugarski, Diana

    2015-02-01

    Mesenchymal stem cells (MSCs) have the potential to migrate toward damaged tissues increasing tissue regeneration. Interleukin-17 (IL-17) is a proinflammatory cytokine with pleiotropic effects associated with many inflammatory diseases. Although IL-17 can modulate MSC functions, its capacity to regulate MSC migration is not well elucidated so far. Here, we studied the role of IL-17 on peripheral blood (PB) derived MSC migration and transmigration across endothelial cells. IL-17 increased PB-MSC migration in a wound healing assay as well as cell mobilization from collagen gel. Concomitantly IL-17 induced the expression of urokinase type plasminogen activator (uPA) without affecting matrix metalloproteinase expression. The incremented uPA expression mediated the capacity of IL-17 to enhance PB-MSC migration in a ERK1,2 MAPK dependent way. Also, IL-17 induced PB-MSC migration alongside with changes in cell polarization and uPA localization in cell protrusions. Moreover, IL-17 increased PB-MSC adhesion to endothelial cells and transendothelial migration, as well as increased the capacity of PB-MSC adhesion to fibronectin, in an uPA-dependent fashion. Therefore, our data suggested that IL-17 may act as chemotropic factor for PB-MSCs by incrementing cell motility and uPA expression during inflammation development.

  17. Effect of subcutaneous treatment with human umbilical cord blood-derived multipotent stem cells on peripheral neuropathic pain in rats

    PubMed Central

    Lee, Min Ju; Yoon, Tae Gyoon; Kang, Moonkyu

    2017-01-01

    In this study, we aim to determine the in vivo effect of human umbilical cord blood-derived multipotent stem cells (hUCB-MSCs) on neuropathic pain, using three, principal peripheral neuropathic pain models. Four weeks after hUCB-MSC transplantation, we observed significant antinociceptive effect in hUCB-MSC–transplanted rats compared to that in the vehicle-treated control. Spinal cord cells positive for c-fos, CGRP, p-ERK, p-p 38, MMP-9 and MMP 2 were significantly decreased in only CCI model of hUCB-MSCs-grafted rats, while spinal cord cells positive for CGRP, p-ERK and MMP-2 significantly decreased in SNL model of hUCB-MSCs-grafted rats and spinal cord cells positive for CGRP and MMP-2 significantly decreased in SNI model of hUCB-MSCs-grafted rats, compared to the control 4 weeks or 8weeks after transplantation (p<0.05). However, cells positive for TIMP-2, an endogenous tissue inhibitor of MMP-2, were significantly increased in SNL and SNI models of hUCB-MSCs-grafted rats. Taken together, subcutaneous injection of hUCB-MSCs may have an antinociceptive effect via modulation of pain signaling during pain signal processing within the nervous system, especially for CCI model. Thus, subcutaneous administration of hUCB-MSCs might be beneficial for improving those patients suffering from neuropathic pain by decreasing neuropathic pain activation factors, while increasing neuropathic pain inhibition factor. PMID:28280408

  18. Allelic Exclusion and Peripheral Reconstitution by TCR Transgenic T Cells Arising From Transduced Human Hematopoietic Stem/Progenitor Cells

    PubMed Central

    Giannoni, Francesca; Hardee, Cinnamon L; Wherley, Jennifer; Gschweng, Eric; Senadheera, Shantha; Kaufman, Michael L; Chan, Rebecca; Bahner, Ingrid; Gersuk, Vivian; Wang, Xiaoyan; Gjertson, David; Baltimore, David; Witte, Owen N; Economou, James S; Ribas, Antoni; Kohn, Donald B

    2013-01-01

    Transduction and transplantation of human hematopoietic stem/progenitor cells (HSPC) with the genes for a T-cell receptor (TCR) that recognizes a tumor-associated antigen may lead to sustained long-term production of T cells expressing the TCR and confer specific antitumor activity. We evaluated this using a lentiviral vector (CCLc-MND-F5) carrying cDNA for a human TCR specific for an HLA-A*0201-restricted peptide of Melanoma Antigen Recognized by T cells (MART-1). CD34+ HSPC were transduced with the F5 TCR lentiviral vector or mock transduced and transplanted into neonatal NSG mice or NSG mice transgenic for human HLA-A*0201 (NSG-A2). Human CD8+ and CD4+ T cells expressing the human F5 TCR were present in the thymus, spleen, and peripheral blood after 4–5 months. Expression of human HLA-A*0201 in NSG-A2 recipient mice led to significantly increased numbers of human CD8+ and CD4+ T cells expressing the F5 TCR, compared with control NSG recipients. Transduction of the human CD34+ HSPC by the F5 TCR transgene caused a high degree of allelic exclusion, potently suppressing rearrangement of endogenous human TCR-β genes during thymopoiesis. In summary, we demonstrated the feasibility of engineering human HSPC to express a tumor-specific TCR to serve as a long-term source of tumor-targeted mature T cells for immunotherapy of melanoma. PMID:23380815

  19. Advanced flow cytometric analysis of nanoparticle targeting to rare leukemic stem cells in peripheral human blood in a defined model system

    NASA Astrophysics Data System (ADS)

    Cooper, Christy L.; Leary, James F.

    2015-03-01

    Leukemia stem cells are both stem-like and leukemic-like. This complicates their detection as rare circulating tumor cells in the peripheral blood of leukemia patients. Since leukemic stem cells are also resistant to standard chemotherapeutic regimens, new therapeutic strategies need to be designed to kill the leukemic stem cells without killing normal stem cells. In these initial targeting studies we utilized a bioinformatics approach to design an antibodyfluorescent nanoparticle conjugate for targeting to these leukemic stem cells and to minimize targeting to normal stemprogenitor cells. Multicolor flow cytometric analyses were performed on a BD FACS Aria III. Human leukemic stem cell-like cell RS4;11 (with putative immunophenotype CD133+/CD24+/-, CD34+/-, CD38+, CD10-/Flt3+) was spiked into normal hematopoietic stem-progenitor cells obtained from a "buffy coat" prep (with putative immunophenotype CD133- /CD34+/CD38-/CD10-/Flt-3-) to be used as a model human leukemia patient. To analyze the model system, digital data mixtures of the two cell types were first created and assigned classifiers in order to create truth sets. ROC (Receiver Operating Characteristic) and multidimensional cluster analyses were used to evaluate the specificity and sensitivity of the immunophenotyping panel and for automated cell population identification, respectively. Costs of misclassification (false targeting) were also accounted for by this analysis scheme. Ultimately, this analysis scheme will be applied to use of nanoparticle-antibody conjugates at therapeutic doses for targeted killing of leukemia stem cells preferentially to normal stem -progenitor cells.

  20. Acute graft-versus-host disease, invasive aspergillosis and Clostridium difficile colitis after peripheral blood stem cell transplantation: A complex network of causalities and a challenge for prevention.

    PubMed

    Khanafer, Nagham; Neuraz, Antoine; Bénet, Thomas; Cour, Martin; Persat, Florence; Labussière, Hélène; Argaud, Laurent; Michallet, Mauricette; Vanhems, Philippe

    2015-06-01

    Graft-versus-host disease (GVHD) is a known risk factor for invasive aspergillosis (IA), but remains poorly studied in relation to Clostridium difficile infection (CDI). We report a case of a 58-years-old patient who developed an IA within a protected room, CDI and GVHD after allogeneic allogeneic peripheral blood stem cell transplantation (PBSCT). Factors associated with this complex condition in patients receiving allogeneic PBSCT need to be identified.

  1. A Randomized Comparative Study on the Efficacy of Intracoronary Infusion of Autologous Bone Marrow Mononuclear Cells and Mesenchymal Stem Cells in Patients With Dilated Cardiomyopathy.

    PubMed

    Xiao, Wentao; Guo, Suping; Gao, Chuanyu; Dai, Guoyou; Gao, Yongjv; Li, Muwei; Wang, Xianpei; Hu, Dayi

    2017-02-13

    Stem cell therapy has shown therapeutic benefit in dilated cardiomyopathy (DCM), but doubt remains about the most appropriate stem cell subpopulation. The current study compared the efficacy of intracoronary administration of bone marrow mononuclear cells (BMMC) or mesenchymal stem cells (BMSC) in patients with DCM.Fifty-three patients with DCM and reduced (< 40%) left ventricular ejection fraction (LVEF), were randomized to intracoronary infusion of BMMC (BMMC group, n = 16) or BMSC (BMSC group, n = 17) or equal volume normal saline (CTRL group, n = 20). LVEF, New York Heart Association (NYHA) class, left ventricular end-diastolic diameter (LVEDd), and myocardial perfusion were assessed at baseline and at 3-month and 12-month follow-ups. Major adverse cardiovascular events (MACE) were also recorded.At the 3-month follow-up, LVEF, NYHA class, and myocardial perfusion had improved significantly in the BMSC group (P = 0.004, 0.020 and 0.019, respectively) along with significant changes in LVEF and NYHA class in the BMMC group compared with CTRL (P = 0.042 and 0.047, respectively), however, LVEDd remained unchanged. In comparison with CTRL, LVEF, NYHA class, and myocardial perfusion improved significantly in the BMSC group at the 12-month follow-up (P = 0.005, 0.050 and 0.038 respectively), but not in the BMMC group (P > 0.05). There were no significant differences between the transplantation groups during follow-up (P > 0.05). There were no differences in MACE among the 3 groups (P = 0.817).Intracoronary bone marrow stem cell transplantation in DCM is safe and effective, while BMSC and BMMC infusion possess comparable effectiveness.

  2. [Stem cell perspectives in myocardial infarctions].

    PubMed

    Aceves, José Luis; Archundia, Abel; Díaz, Guillermo; Páez, Araceli; Masso, Felipe; Alvarado, Martha; López, Manuel; Aceves, Rocío; Ixcamparij, Carlos; Puente, Adriana; Vilchis, Rafael; Montaño, Luis Felipe

    2005-01-01

    Myocardial infarction is the leading cause of congestive heart failure and death in industrializated countries. The cellular cardiomyoplasty has emerged as an alternative treatment in the regeneration of infarted myocardial tissue. In animals' models, different cellular lines such as cardiomyocites, skeletal myoblasts, embryonic stem cells and adult mesenchymal stem cells have been used, resulting in an improvement in ventricular function and decrease in amount of infarcted tissue. The first three cells lines have disvantages as they are allogenics and are difficult to obtain. The adult mesenchymal stem cells are autologous and can be obtained throught the aspiration of bone marrow or from peripherical circulation, after stimulating with cytokines (G-CSF). The implantation in humans with recent and old myocardial infarction have shown improvements similar to those shown in animal models. These findings encourage the continued investigation in the mechanism of cellular differentiation and implantation methods in infarcted myocardial tissue.

  3. Primary systemic amyloidosis presenting as a colonic stricture: successful treatment with left hemicolectomy followed by autologous hematopoietic stem-cell transplantation: report of a case.

    PubMed

    Rives, S; Pera, M; Rosiñol, L; Vidal, O; Miquel, R; Solé, M; García-Valdecasas, J; Bladé, J

    2002-09-01

    Intestinal tract involvement by primary systemic amyloidosis is frequent but usually asymptomatic. Ischemic colitis caused by amyloid infiltration of wall blood vessels can occasionally be observed. We report a 62-year-old female with primary systemic amyloidosis who presented with intestinal obstruction caused by ischemic stricture of the sigmoid colon, secondary to submucosal amyloid deposition. The patient was successfully treated with surgical resection followed by high-dose chemotherapy and hematopoietic stem-cell transplantation. The clinical manifestations and differential diagnosis of gastrointestinal involvement of primary systemic amyloidosis, as well as its current treatment, are discussed.

  4. High-Dose Chemotherapy With or Without Total-Body Irradiation Followed by Autologous Stem Cell Transplant in Treating Patients With Hematologic Cancer or Solid Tumors

    ClinicalTrials.gov

    2017-03-30

    Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor (PNET); Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Plasma Cell Neoplasm; Primary Systemic Amyloidosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2

  5. Advanced lytic lesion is a poor mobilization factor in peripheral blood stem cell collection in patients with multiple myeloma.

    PubMed

    Jung, Sung-Hoon; Yang, Deok-Hwan; Ahn, Jae-Sook; Kim, Yeo-Kyeoung; Kim, Hyeoung-Joon; Lee, Je-Jung

    2014-12-01

    This study examined the incidence and predictors of peripheral blood stem cell (PBSC) mobilization failure in patients with multiple myeloma (MM). Retrospective data for 104 patients who received granulocyte colony-stimulating factor (G-CSF) alone or with cyclophosphamide as mobilization regimens were analyzed. The rates of mobilization failure using two definitions of failure (< 2 × 10(6) and < 4 × 10(6) CD34(+) cells/kg) following the first collection attempt were 16.3 and 33.7%, respectively. Predictors of mobilization failure were evaluated using logistic regression analysis which included age, advanced osteolytic lesions, bone marrow cellularity before mobilization, platelet count, body mass index before mobilization, and mobilization method. Lytic bone lesions were assessed using a conventional skeletal survey, and advanced osteolytic lesions were defined as lytic lesions in more than three skeletal sites regardless of the number of lytic lesions. On multivariate analysis, advanced osteolytic lesions [hazard ratio (HR) = 10.95, P = 0.001] and age ≥60 years (HR = 5.45, P = 0.016) were associated with a PBSC yield < 2 × 10(6) CD34(+) cells/kg, and advanced osteolytic lesions (HR = 5.08, P = 0.006), white blood cell count ≤4,000/µL before mobilization (HR = 4.72, P = 0.005), and G-CSF only mobilization (HR 10.52, P < 0.001) were associated with PBSC yield < 4 × 10(6) CD34(+) cells/kg. The data suggest that an advanced osteolytic lesion is a significant predictor of mobilization failure in MM patients.

  6. Perspectives of employing mesenchymal stem cells from the Wharton's jelly of the umbilical cord for peripheral nerve repair.

    PubMed

    Ribeiro, Jorge; Gartner, Andrea; Pereira, Tiago; Gomes, Raquel; Lopes, Maria Ascensão; Gonçalves, Carolina; Varejão, Artur; Luís, Ana Lúcia; Maurício, Ana Colette

    2013-01-01

    Mesenchymal stem cells (MSCs) from Wharton's jelly present high plasticity and low immunogenicity, turning them into a desirable form of cell therapy for the injured nervous system. Their isolation, expansion, and characterization have been performed from cryopreserved umbilical cord tissue. Great concern has been dedicated to the collection, preservation, and transport protocols of the umbilical cord after the parturition to the laboratory in order to obtain samples with higher number of viable MSCs without microbiological contamination. Different biomaterials like chitosan-silicate hybrid, collagen, PLGA90:10, poly(DL-lactide-ɛ-caprolactone), and poly(vinyl alcohol) loaded with electrical conductive materials, associated to MSCs have also been tested in the rat sciatic nerve in axonotmesis and neurotmesis lesions. The in vitro studies of the scaffolds included citocompatibility evaluation of the biomaterials used and cell characterization by imunocytochemistry, karyotype analysis, differentiation capacity into neuroglial-like cells, and flow cytometry. The regeneration process follow-up has been performed by functional analysis and the repaired nerves processed for stereological studies permitted the morphologic regeneration evaluation. The MSCs from Wharton's jelly delivered through tested biomaterials should be regarded a potentially valuable tool to improve clinical outcome especially after trauma to sensory nerves. In addition, these cells represent a noncontroversial source of primitive mesenchymal progenitor cells, which can be harvested after birth, cryogenically stored, thawed, and expanded for therapeutic uses. The importance of a longitudinal study concerning tissue engineering of the peripheral nerve, which includes a multidisciplinary team able to develop biomaterials associated to cell therapies, to perform preclinical trials concerning animal welfare and the appropriate animal model is here enhanced.

  7. Long term follow-up of BEAM-autologous and BEAM-alemtuzumab allogeneic stem cell transplantation in relapsed advanced stage follicular lymphoma.

    PubMed

    Noriega, Victor; Kaur, Harpreet; Devereux, Stephen; Byrne, Jennifer; Marcus, Robert; Haynes, Andrew; Yallop, Deborah; McMillan, Andrew; Ingram, Wendy; Khan, Anjum; Kenyon, Michelle; Potter, Victoria; Russell, Nigel; Mufti, Ghulam J; Pagliuca, Antonio

    2014-07-01

    This is an analysis in 171 patients comparing BEAM-Auto and BEAM-Allo (alemtuzumab)-hematopoietic stem cell transplantation in relapsed follicular lymphoma. BEAM-Allo group had a lower 10 years cumulative incidence of relapse(31.4% vs 55.1%, p=0.042), a trend to a plateau in survival but no statistical differences in OS or DFS, and a TRM of 24%. When transplanted in CR BEAM-Allo patients had better OS and DFS. Incidence of acute and chronic GVHD was 16.6% and 22%. 29% of BEAM-Allo patients received DLI (all but two remain in CR and alive). Our data supports Allo-HSCT as a potential curative treatment for selected patients with FL.

  8. Interaction between IL-6 and TNF-α genotypes associated with bacteremia in multiple myeloma patients submitted to autologous stem cell transplantation (ASCT).

    PubMed

    Trigo, Fernanda M B; Luizon, Marcelo R; Dutra, Hélio S; Maiolino, Angelo; Nucci, Márcio; Simões, Belinda P

    2014-01-01

    Stem cell transplantation affects patient׳s vulnerability to infections due to immunological changes related to chemotherapy. Multiple myeloma is characterized by susceptibility to infections, and IL-6 and TNF-α increased levels affect immune response (IR). Polymorphisms in promoter region of cytokine genes may alter expression levels and affect IR. We performed interaction analysis of IL-6 (-174G/C) and TNF-α (-308G/A) polymorphisms with infection susceptibility in 148 patients classified accordingly to infection status and found an interaction when compared groups with and without bacteremia (p=0.0380). The interaction may be more important than single effects for the IR associated with the infection susceptibility in ASCT.

  9. High-Dose [131I]Tositumomab (anti-CD20) Radioimmunotherapy and Autologous Hematopoietic Stem Cell Transplantation for Adults ≥ 60 Years Old with Relapsed or Refractory B-Cell Lymphoma

    SciTech Connect

    Gopal, Ajay K.; Rajendran, Joseph G.; Gooley, Ted; Pagel, John M.; Fisher, Darrell R.; Petersdorf, Stephen; Maloney, David G.; Eary, Janet F.; Appelbaum, Frederick R.; Press, Oliver W.

    2007-04-10

    Purpose: The majority of patients with relapsed or refractory B-cell, non-Hodgkin’s lymphoma (NHL) are over 60 years of age, yet they are often denied potentially curative high-dose therapy and autologous stem cell transplants (ASCT) due to the risk of excessive treatment-related morbidity and mortality. Myeloablative anti-CD20 radioimmunotherapy (RIT) can deliver curative radiation doses to tumor sites while limiting exposure to normal organs and may be particularly suited for older adults requiring high-dose therapy. Methods: Patients over age 60 with relapsed B-NHL received infusions of tositumomab anti-CD20 antibody labeled with 5-10mCi I-131 tracer for dosimetry purposes followed 10 days later by individualized therapeutic infusions of I-131-tositumomab (median 525 mCi, range 328-1154 mCi) to deliver 25-27Gy to the critical normal organ receiving the highest radiation dose. ASCT was performed approximately 2 weeks after therapy. Results: Twenty-four patients with a median age of 64 (range 60-76) who had received a median of four prior regimens (range 2-14) were treated. Thirteen (54%) had chemotherapy-resistant disease. The estimated 3-year overall and progression-free survivals were 59% and 51%, respectively with a median follow-up of 2.9 years (range 1-6 years). All patients experienced expected myeloablation with engraftment of platelets (≥20K/µL) and neutrophils (≥500/µL) occurring a median of 9 and 15 days, respectively following ASCT. There were no treatment-related deaths, and only two patients experienced grade 4 non-hematologic toxicity. Conclusions: Myeloablative RIT and ASCT is a safe and effective therapeutic option for older adults with relapsed B-NHL.

  10. Rituximab Maintenance Therapy After Autologous Stem-Cell Transplantation in Patients With Relapsed CD20+ Diffuse Large B-Cell Lymphoma: Final Analysis of the Collaborative Trial in Relapsed Aggressive Lymphoma

    PubMed Central

    Gisselbrecht, Christian; Schmitz, Norbert; Mounier, Nicolas; Singh Gill, Devinder; Linch, David C.; Trneny, Marek; Bosly, Andre; Milpied, Noel J.; Radford, John; Ketterer, Nicolas; Shpilberg, Ofer; Dührsen, Ulrich; Hagberg, Hans; Ma, David D.; Viardot, Andreas; Lowenthal, Ray; Brière, Josette; Salles, Gilles; Moskowitz, Craig H.; Glass, Bertram

    2012-01-01

    Purpose The standard treatment for relapsed diffuse large B-cell lymphoma (DLBCL) is salvage chemotherapy followed by high-dose therapy and autologous stem-cell transplantation (ASCT). The impact of maintenance rituximab after ASCT is not known. Patients and Methods In total, 477 patients with CD20+ DLBCL who were in their first relapse or refractory to initial therapy were randomly assigned to one of two salvage regimens. After three cycles of salvage chemotherapy, the responding patients received high-dose chemotherapy followed by ASCT. Then, 242 patients were randomly assigned to either rituximab every 2 months for 1 year or observation. Results After ASCT, 122 patients received rituximab, and 120 patients were observed only. The median follow-up time was 44 months. The 4-year event-free survival (EFS) rates after ASCT were 52% and 53% for the rituximab and observation groups, respectively (P = .7). Treatment with rituximab was associated with a 15% attributable risk of serious adverse events after day 100, with more deaths (six deaths v three deaths in the observation arm). Several factors affected EFS after ASCT (P < .05), including relapsed disease within 12 months (EFS: 46% v 56% for relapsed disease after 12 months), secondary age-adjusted International Prognostic Index (saaIPI) more than 1 (EFS: 37% v 61% for saaIPI < 1), and prior treatment with rituximab (EFS: 47% v 59% for no prior rituximab). A significant difference in EFS between women (63%) and men (46%) was also observed in the rituximab group. In the Cox model for maintenance, the saaIPI was a significant prognostic factor (P < .001), as was male sex (P = .01). Conclusion In relapsed DLBCL, we observed no difference between the control group and the rituximab maintenance group and do not recommend rituximab after ASCT. PMID:23091101

  11. A phase II, single-arm, prospective study of bendamustine plus melphalan conditioning for second autologous stem cell transplantation in de novo multiple myeloma patients through a tandem transplant strategy.

    PubMed

    Martino, M; Tripepi, G; Messina, G; Vincelli, I D; Console, G; Recchia, A G; Gentile, M; Molica, S; Morabito, F

    2016-09-01

    This phase II trial evaluates, for the first time, the safety and efficacy of bendamustine plus high-dose melphalan (HDM) as a conditioning regimen before the second autologous stem cell transplantation (ASCT) in previously untreated multiple myeloma (MM) patients. In total, 32 ASCT patients received HDM (200 mg/m(2)) as conditioning for the first ASCT. After 3-6 months from the first ASCT, responding patients underwent a second ASCT following bendamustine (200 mg/m(2)) and HDM (140 mg/m(2)). High-dose chemotherapy and ASCT were performed with complete neutrophil and platelet recovery in all patients. The median number of days to neutrophil and platelet engraftment was 11 (range 9-15) and 12 (range 10-19), respectively. Only one subject experienced grade 3 diarrhea; the rate of mucositis and vomiting was significantly lower with the bendamustine plus HDM regimen compared with the HDM-only regimen (81.2 vs 96.9%, P=0.025 and 78.1 vs 100%, P=0.008). Overall response rate (ORR) was 81.2% after the first transplant, and 90.6% after the second, while complete response rates were 46.8 and 62.5%, respectively (P=0.016). Actuarial 2-year PFS and OS were 79% (95% confidence interval (CI), 60-98) and 97% (95% CI, 91-100), respectively. Bendamustine+HDM is feasible as the conditioning regimen for second ASCT in MM patients. The present study may pave the way for phase III studies specifically aimed at further investigating this combination strategy. The role of this combination in MM for conditioning regimen in a first or single ASCT setting should be also investigated.

  12. Rituximab with dose-adjusted EPOCH as first-line treatment in patients with highly aggressive diffuse large B-cell lymphoma and autologous stem cell transplantation in selected patients

    PubMed Central

    Pejša, Vlatko; Prka, Željko; Lucijanić, Marko; Mitrović, Zdravko; Piršić, Mario; Jakšić, Ozren; Ajduković, Radmila; Kušec, Rajko

    2017-01-01

    Aim To assess the benefit of rituximab with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-DA-EPOCH) regimen as a first-line treatment for patients with diffuse large B-cell lymphoma (DLBCL) presenting with unfavorable or aggressive features, and autologous stem cell transplantation (ASCT) as a part of the first-line treatment for selected DLBCL patients with additional aggressive features. Methods We retrospectively analyzed 75 newly diagnosed DLBCL patients with Ki-67+≥80% or International Prognostic Index ≥2 who were treated with R-DA-EPOCH between 2005 and 2015. Of 24 DLBCL patients with additional aggressive features (Ki-67+≥90% or age-adjusted IPI≥2) who were planned to receive consolidation with ASCT, 17 patients underwent the procedure. We determined the overall response rate (ORR), complete remission (CR), partial remission (PR), 5-year overall survival (OS), and progression free survival (PFS) in all DLBCL patients and specifically those planned to receive ASCT. Results All 75 patients included in the analysis started one or more cycles of therapy. The ORR, CR, and PR rates were 80%, 55%, and 25%, respectively. The response was non-evaluable in 10 of 75 patients due to treatment discontinuation. The OS and PFS rates for all 75 patients were 70% and 61%, respectively, and 80% and 79%, respectively, for 24 planned-to-receive-ASCT patients. Age (≤65 vs >65 years) had no prognostic impact on OS and PFS (P = 0.994 and P = 0.827, respectively). Conclusion Our retrospective analysis of one of the largest DLBCL patient cohorts outside the US National Cancer Institute showed that R-DA-EPOCH is a very effective therapeutic option as a first-line treatment of DLBCL patients with unfavorable prognostic features irrespective of their age. ASCT provided additional benefit for DLBCL patients with additional aggressive features. PMID:28252874

  13. Prognostic Factors and a New Prognostic Index Model for Children and Adolescents with Hodgkin’s Lymphoma Who Underwent Autologous Hematopoietic Stem Cell Transplantation: A Multicenter Study of the Turkish Pediatric Bone Marrow Transplantation Study Group

    PubMed Central

    Kesik, Vural; Ataş, Erman; Karakükcü, Musa; Aksoylar, Serap; Erbey, Fatih; Taçyıldız, Nurdan; Küpesiz, Alphan; Öniz, Haldun; Ünal, Ekrem; Kansoy, Savaş; Öztürk, Gülyüz; Elli, Murat; Kaya, Zühre; Ünal, Emel; Hazar, Volkan; Yılmaz Bengoa, Şebnem; Karasu, Gülsün; Atay, Didem; Dağdemir, Ayhan; Ören, Hale; Koçak, Ülker; Yeşilipek, M. Akif

    2016-01-01

    Objective: The prognostic factors and a new childhood prognostic index after autologous hematopoietic stem cell transplantation (AHSCT) in patients with relapsed/refractory Hodgkin’s lymphoma (HL) were evaluated. Materials and Methods: The prognostic factors of 61 patients who underwent AHSCT between January 1990 and December 2014 were evaluated. In addition, the Age-Adjusted International Prognostic Index and the Childhood International Prognostic Index (CIPI) were evaluated for their impact on prognosis. Results: The median age of the 61 patients was 14.8 years (minimum-maximum: 5-20 years) at the time of AHSCT. There were single relapses in 28 patients, ≥2 relapses in eight patients, and refractory disease in 25 patients. The chemosensitivity/chemorefractory ratio was 36/25. No pretransplant radiotherapy, no remission at the time of transplantation, posttransplant white blood cell count over 10x103/µL, posttransplant positron emission tomography positivity at day 100, and serum albumin of <2.5 g/dL at diagnosis were correlated with progression-free survival. No remission at the time of transplantation, bone marrow positivity at diagnosis, and relapse after AHSCT were significant parameters for overall survival. Conclusion: The major factors affecting the progression-free and overall survival were clearly demonstrated. A CIPI that uses a lactate dehydrogenase level of 500 IU/L worked well for estimating the prognosis. We recommend AHSCT at first complete remission for relapsed cases, and it should also be taken into consideration for patients with high prognostic scores at diagnosis. PMID:27094103

  14. Results of a retrospective single institution analysis of targeted skeletal radiotherapy with (166)Holmium-DOTMP as conditioning regimen for autologous stem cell transplant for patients with multiple myeloma. Impact on transplant outcomes.

    PubMed

    Christoforidou, Anna V; Saliba, Rima M; Williams, Patricia; Qazilbash, Muzaffar; Roden, Linda; Aleman, Ana; Weber, Donna; Mendoza, Floralyn; Podoloff, Donald; Wendt, Richard; Breitz, Hazel; Alexanian, Raymond; Champlin, Richard; Giralt, Sergio

    2007-05-01

    (166)Holmium-DOTMP is a beta-emitting radiophosphonate that localizes specifically to the bone surfaces and can deliver high-dose radiation to the bone marrow. Phase I/II trials showed feasibility and tolerability when combined with high-dose melphalan with or without total-body irradiation (TBI) in patients with multiple myeloma (MM) undergoing autologous stem cell transplantation (ASCT). The purpose of this study was to define the potential impact of (166)Holmium-DOTMP on outcomes in patients with MM undergoing ASCT. Retrospective review of transplant outcomes among patients with MM who received an ASCT between January 1998 to December 2001 with either melphalan 200 mg/m(2) or a (166)Holmium-DOTMP containing regimen as part of their initial therapy. Univariate analysis was performed for response, overall survival (OS), and event free survival (EFS). One hundred four patients were identified, of which 41 received a (166)Holmium-DOTMP containing regimen and 63 received melphalan alone. The (166)Holmium-DOTMP patients were divided into 2 groups according to the dose received (<2400 mCi versus > or = 2400 mCi). The (166)Holmium-DOTMP group had a trend towards a higher complete remission (CR) rate compared to patients receiving melphalan alone (51% versus 32%). The median EFS for the low-dose (166)Holmium-DOTMP, the high-dose (166)Holmium-DOTMP, and melphalan alone was 30, 23, and 19 months, respectively; the OS rate at 5 years for the 3 groups was 61%, 40%, and 43%, respectively. (166)Holmium-DOTMP, in combination with high-dose melphalan, can result in higher CR rates when given in optimal doses (<2400 mCi) when compared to melphalan alone, and should be further tested in phase III trials in patients with MM undergoing ASCT.

  15. High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation as Adjuvant Treatment in High-Risk Breast Cancer: Data from the European Group for Blood and Marrow Transplantation Registry.

    PubMed

    Martino, Massimo; Lanza, Francesco; Pavesi, Lorenzo; Öztürk, Mustafa; Blaise, Didier; Leno Núñez, Rubén; Schouten, Harry C; Bosi, Alberto; De Giorgi, Ugo; Generali, Daniele; Rosti, Giovanni; Necchi, Andrea; Ravelli, Andrea; Bengala, Carmelo; Badoglio, Manuela; Pedrazzoli, Paolo; Bregni, Marco

    2016-03-01

    The aim of this retrospective study was to assess toxicity and efficacy of adjuvant high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation (AHSCT) in 583 high-risk breast cancer (BC) patients (>3 positive nodes) who were transplanted between 1995 and 2005 in Europe. All patients received surgery before transplant, and 55 patients (9.5%) received neoadjuvant treatment before surgery. Median age was 47.1 years, 57.3% of patients were premenopausal at treatment, 56.5% had endocrine-responsive tumors, 19.5% had a human epidermal growth factor receptor 2 (HER2)-negative tumor, and 72.4% had ≥10 positive lymph nodes at surgery. Seventy-nine percent received a single HDC procedure. Overall transplant-related mortality was 1.9%, at .9% between 2001 and 2005, whereas secondary tumor-related mortality was .9%. With a median follow-up of 120 months, overall survival and disease-free survival rates at 5 and 10 years in the whole population were 75% and 64% and 58% and 44%, respectively. Subgroup analysis demonstrated that rates of overall survival were significantly better in patients with endocrine-responsive tumors, <10 positive lymph nodes, and smaller tumor size. HER2 status did not affect survival probability. Adjuvant HDC with AHSCT has a low mortality rate and provides impressive long-term survival rates in patients with high-risk BC. Our results suggest that this treatment modality should be considered in selected high-risk BC patients and further investigated in clinical trials.

  16. Autologous stem cell transplantation for relapsed/refractory diffuse large B-cell lymphoma: efficacy in the rituximab era and comparison to first allogeneic transplants. A report from the EBMT Lymphoma Working Party.

    PubMed

    Robinson, S P; Boumendil, A; Finel, H; Blaise, D; Poiré, X; Nicolas-Virelizier, E; Or, R; Malladi, R; Corby, A; Fornecker, L; Caballero, D; Pohlreich, D; Nagler, A; Thieblemont, C; Finke, J; Bachy, E; Vincent, L; Schroyens, W; Schouten, H; Dreger, P

    2016-03-01

    In the era of chemoimmunotherapy, the optimal treatment paradigm for relapsed and refractory diffuse large B-cell lymphoma has been challenged. We reviewed the outcome of standard salvage therapy with an autologous stem cell transplant (autoSCT) over the last two decades and the outcome of allogeneic SCT (alloSCT) in the most recent decade. AutoSCT recipients diagnosed between 1992 and 2002 (n=2737) were compared with those diagnosed between 2002 and 2010 (n=3980). Patients diagnosed after 2002 had a significantly lower non-relapse mortality (NRM) and relapse incidence (RI) and a superior PFS and overall survival (OS). A total of 4210 patients diagnosed between 2002 and 2010 underwent either an autoSCT or an alloSCT as their first transplant procedure. Two-hundred and thirty patients received an alloSCT (myeloablative (MACalloSCT) n=132, reduced intensity (RICalloSCT) n=98). The 4-year NRM rates were 7%, 20% and 27% for autoSCT, RICalloSCT and MACalloSCT, respectively. The 4-year RI was 45%, 40% and 38% for autoSCT, RICalloSCT and MACalloSCT, respectively (NS). The 4-year PFS were 48%, 52% and 35% for autoSCT, RICalloSCT and MACalloSCT, respectively. The 4-year OS was 60%, 52% and 38% for autoSCT, RIC alloSCT and MACalloSCT, respectively. After adjustment for confounding factors NRM was significantly worse for patients undergoing alloSCT whilst there was no differen