scholarly journals Experience with Alemtuzumab, Fludarabine, and Melphalan Reduced-Intensity Conditioning Hematopoietic Cell Transplantation in Patients with Nonmalignant Diseases Reveals Good Outcomes and That the Risk of Mixed Chimerism Depends on Underlying Disease, Stem Cell Source, and Alemtuzumab Regimen

2015 ◽  
Vol 21 (8) ◽  
pp. 1460-1470 ◽  
Author(s):  
Rebecca A. Marsh ◽  
Marepalli B. Rao ◽  
Aharon Gefen ◽  
Denise Bellman ◽  
Parinda A. Mehta ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Underlying Disease ◽  
Hematopoietic Cell ◽  
Mixed Chimerism ◽  
Reduced Intensity Conditioning ◽  
Stem Cell Source ◽  
Cell Source ◽  
Reduced Intensity

scholarly journals HLA-C expression levels define permissible mismatches in hematopoietic cell transplantation

Blood ◽  
2014 ◽  
Vol 124 (26) ◽  
pp. 3996-4003 ◽  
Author(s):  
Effie W. Petersdorf ◽  
Theodore A. Gooley ◽  
Mari Malkki ◽  
Andrea P. Bacigalupo ◽  
Anne Cesbron ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Transplant Outcome ◽  
Stem Cell Source ◽  
Key Points ◽  
Cell Source ◽  
Unrelated Donors

Key Points The expression level of patient HLA-C allotypes affects GVHD and mortality after HCT from HLA-C-mismatched unrelated donors. Transplant outcome can be improved by avoiding high-risk HLA-C-mismatched donors when no matched stem cell source is available.

scholarly journals Comparison of Outcomes of Allogeneic Hematopoietic Cell Transplantation for Primary Myelofibrosis Among Stem Cell Source Groups

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3466-3466
Author(s):  
Makoto Murata ◽  
Katsuto Takenaka ◽  
Naoyuki Uchida ◽  
Yukiyasu Ozawa ◽  
Kazuteru Ohashi ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Performance Status ◽  
Univariate Analysis ◽  
High Risk Group ◽  
Hematopoietic Cell ◽  
Stem Cell Source ◽  
Cell Source

Abstract Allogeneic hematopoietic cell transplantation (HCT) is the only treatment modality that can either cure or prolong life of patients with primary myelofibrosis (PMF). However, the issues of the choice of stem cell source, the choice of conditioning regimen, and the timing of HCT are currently under debate. To determine whether a difference in stem cell source affects the outcome of HCT for PMF patients, a retrospective study was conducted using the national registry data on 224 patients who received first allogeneic HCT in Japan with bone marrow (BM), peripheral blood stem cells (PBSC) or umbilical cord blood (UCB). This study was approved by the Data Management Committee of the Japan Society for Hematopoietic Cell Transplantation and by the ethics committee of the Nagoya University School of Medicine. One hundred fifty-two male and 72 female, with a median age of 55 years (range, 21-79 years), were treated with a myeloablative (48%) or non-myeloablative (52%) preconditioning and GVHD prophylaxis such as calcineurin inhibitor with methotrexate (78%) between 1993 and 2016. Stem cell sources were HLA-A, -B and -DR 6/6 matched related BM (Rtd-BM) (n = 22), HLA-A, -B and -DR 6/6 matched related PBSC (Rtd-PBSC) (n = 48), HLA-A, -B, -C and -DRB1 alleles 8/8 or 7/8 matched unrelated BM (UR-BM) (n = 91), unrelated UCB (UR-UCB) (n = 29) and others (n = 34) including HLA 5/6 or 4/6 matched related BM and PBSC, HLA-haploidentical related BM and PBSC, HLA alleles 6/8 or 5/8 matched unrelated BM, and HLA alleles 8/8 or 7/8 matched unrelated PBSC. All UR-UCB transplantation was performed with a single unit. The median follow-up term for living patients was 48 (0.3-202) months. Cumulative incidences of neutrophil recovery (≥0.5 × 109/L) on day 60 were 100% in Rtd-BM (median days to recovery, 21 days), 94% in Rtd-PBSC (16 days), 86% in UR-BM (21 days), 79% in UR-UCB (25 days) and 91% in other transplantation (23 days). Cumulative incidences of grade II-IV and III-IV acute GVHD on day 100 were 23% and 5% in Rtd-BM, 27% and 19% in Rtd-PBSC, 27% and 10% in UR-BM, 31% and 10% in UR-UCB, and 26% and 15% in other transplantation, respectively. Cumulative incidences of chronic GVHD at 2 years after HCT were 35% in Rtd-BM, 41% in Rtd-PBSC, 34% in UR-BM, 19% in UR-UCB and 13% in other transplantation. Non-relapse mortality (NRM) at 2 years after HCT were 22% in Rtd-BM, 41% in Rtd-PBSC, 39% in UR-BM, 47% in UR-UCB and 48% in other transplantation. Multivariate analysis demonstrated that RBC transfusion ≥20 times before HCT (HR, 2.05; 95% CI, 1.06-3.98), PLT transfusion 10-19 times before HCT (3.56, 1.57-8.05), UR-UCB transplantation (4.70, 1.13-19.6) and other transplantation (4.38, 1.05-18.3) were predictive factors for higher NRM. Although performance status ≥2 at HCT was significant for higher NRM in univariate analysis, it was not significant in multivariate analysis. Relapse rates at 2 years after HCT were 14% in Rtd-BM, 17% in Rtd-PBSC, 13% in UR-BM, 24% in UR-UCB and 15% in other transplantation. Multivariate analysis demonstrated that no factor was associated with the incidence of relapse, although high-risk group of chromosome karyotype was significant for higher relapse rate in univariate analysis. Neither stem cell source groups nor DIPSS was not significant in univariate analysis. Overall survival (OS) rates at 2 and 5 years after HCT were 71% and 71% in Rtd-BM, 52% and 52% in Rtd-PBSC, 54% and 46% in UR-BM, 43% and 27% in UR-UCB, and 48% and 33% in other transplantation, respectively. Multivariate analysis demonstrated that age of 46-55 years (HR, 2.14; 95% CI, 1.00-4.56) and ≥56 years (2.69, 1.32-5.48), RBC transfusion ≥20 times before HCT (1.91, 1.13-3.25) and PLT transfusion 10-19 times before HCT (3.51, 1.64-7.52) predicted lower OS rate. Although performance status ≥2 at HCT, DIPSS intermediate-2 or high at HCT, high-risk group of chromosome karyotype, UR-UCB transplantation and other transplantation were significant for lower OS in univariate analysis, they were not significant in multivariate analysis. The present study could not find an advantage of use of JAK1/2 inhibitor before HCT, use of anti-thymoglobulin as a preconditioning, and non-myeloablative preconditioning regimen in terms of decreasing NRM or increasing OS rate. Our results suggest that allogeneic HCT provide a curative treatment for PMF patients, however careful management is required in HCT with other than Rtd-BM, Rtd-PB and UR-BM. Further analysis in a large cohort is required. Disclosures No relevant conflicts of interest to declare.

scholarly journals Poor Outcomes of HLA-Mismatched Allogeneic Hematopoietic Cell Transplantation and High Ferritin Levels after a Reduced-Intensity Conditioning Regimen in Patients with Advanced Myelofibrosis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5742-5742
Author(s):  
Han Bi Lee ◽  
Jae-Ho Yoon ◽  
Gi June Min ◽  
Sung-Soo Park ◽  
Silvia Park ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Cell Transplantation ◽  
Research Funding ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Reduced Intensity Conditioning ◽  
Advisory Committees ◽  
Reduced Intensity

Allogeneic hematopoietic cell transplantation (allo-HCT) preconditioning intensity, donor choice, and graft-versus-host disease (GVHD) prophylaxis for advanced myelofibrosis (MF) have not been fully elucidated. Thirty-five patients with advanced MF were treated with reduced-intensity conditioning (RIC) allo-HCT. We searched for matched sibling (n=16) followed by matched (n=10) or mismatched (n=5) unrelated and familial mismatched donors (n=4). Preconditioning regimen consisted of fludarabine (total 150 mg/m2) and busulfan (total 6.4 mg/kg) with total body irradiation≤ 400cGy. All showed engraftments, but four (11.4%) showed either leukemic relapse (n=3) or delayed graft failure (n=1). Two-year overall survival (OS) and non-relapse mortality (NRM) was 60.0% and 29.9%, respectively. Acute GVHD was observed in 19 patients, and grade III-IV acute GVHD was higher with HLA-mismatch (70% vs. 20%, p=0.008). Significant hepatic GVHD was observed in nine patients (5 acute, 4 chronic), and six of them died. Multivariate analysis revealed inferior OS with HLA-mismatch (HR=6.40, 95%CI 1.6-25.7, p=0.009) and in patients with high ferritin level at post-HCT D+21 (HR=7.22, 95%CI 1.9-27.5, p=0.004), which were related to hepatic GVHD and high NRM. RIC allo-HCT can be a valid choice for advanced MF. However, HLA-mismatch and high post-HCT ferritin levels related to significant hepatic GVHD should be regarded as poor-risk parameters. Disclosures Kim: Handok: Honoraria; Amgen: Honoraria; Celgene: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Hanmi: Consultancy, Honoraria; AGP: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; SL VaxiGen: Consultancy, Honoraria; Novartis: Consultancy; Janssen: Honoraria; Daiichi Sankyo: Honoraria, Membership on an entity's Board of Directors or advisory committees; Otsuka: Honoraria; BL & H: Research Funding; Chugai: Honoraria; Yuhan: Honoraria; Sanofi-Genzyme: Honoraria, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Lee:Alexion: Consultancy, Honoraria, Research Funding; Achillion: Research Funding.

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