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Decision analysis for donor selection in stem cell transplantation-HLA-8/8 allele-matched unrelated donor vs HLA-1 AG mismatched related donor.

ABSTRACT: Risk of relapse during the unrelated donor coordination period biases comparisons between allogeneic hematopoietic stem cell transplantation from an HLA 8 of 8 allele-matched unrelated donor (8/8 MUD) and that from a related donor with an HLA-1 antigen mismatch in the graft-versus-host (GVH) direction (RD/1AGMM-GVH). To reduce this bias, we performed a decision analysis focusing on acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) in first complete remission (CR1). The primary outcome measure was 5-year survival probability with or without quality-of-life (QOL) adjustment. A baseline analysis showed that the decision to perform MUD transplantation was superior to that to perform RD/1AGMM-GVH transplantation for patients with AML or ALL. However, in the ALL cohort, the direction of superiority was reversed when the interval between CR1 and 8/8 MUD transplantation was >5.5 months (without QOL adjustment) or >6 months (after QOL adjustment) or when overall survival of RD/1AGMM-GVH transplantation improved by 1.3% without QOL adjustment and 2.1% after QOL adjustment. In conclusion, 8/8 MUD should be prioritized in transplantation for AML and ALL in CR1. However, the MUD coordination period and improvements in RD/1AGMM-GVH transplantation might change the donor selection priority in transplantation for ALL in CR1.

SUBMITTER: Kanda J

PROVIDER: S-EPMC4315891 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Decision analysis for donor selection in stem cell transplantation-HLA-8/8 allele-matched unrelated donor vs HLA-1 AG mismatched related donor.

Kanda J J Fuji S S Kato S S Takami A A Tanaka J J Miyamura K K Ohashi K K Fukuda T T Ozawa Y Y Kanamori H H Eto T T Kobayashi N N Iwato K K Morishima Y Y Sakamaki H H Atsuta Y Y Kanda Y Y

Blood cancer journal 20141205

Risk of relapse during the unrelated donor coordination period biases comparisons between allogeneic hematopoietic stem cell transplantation from an HLA 8 of 8 allele-matched unrelated donor (8/8 MUD) and that from a related donor with an HLA-1 antigen mismatch in the graft-versus-host (GVH) direction (RD/1AGMM-GVH). To reduce this bias, we performed a decision analysis focusing on acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) in first complete remission (CR1). The primary ...[more]

PMID: 25479570

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Project description:PurposeHematopoietic cell transplantation (HCT) is curative for hematologic disorders, but outcomes are historically inferior when using HLA-mismatched donors. Despite unrelated donor registries listing > 38 million volunteers, 25%-80% of US patients lack an HLA-matched unrelated donor, with significant disparity across ethnic groups. We hypothesized that HCT with a mismatched unrelated donor (MMUD) using post-transplant cyclophosphamide (PTCy), a novel strategy successful in overcoming genetic disparity using mismatched related donors, would be feasible and increase access to HCT.Patients and methodsWe performed a prospective phase II study of MMUD bone marrow HCT with PTCy for patients with hematologic malignancies. The primary end point was 1-year overall survival (OS), hypothesized to be 65% or better. 80 patients enrolled at 11 US transplant centers (December 2016-March 2019). Following myeloablative or reduced-intensity conditioning-based HCT, patients received PTCy on days +3, +4, with sirolimus and mycophenolate mofetil starting on day +5. We compared outcomes to Center for International Blood and Marrow Transplant Research contemporary controls receiving PTCy.ResultsNotably, 48% of patients enrolled were ethnic minorities. 39% of pairs were matched for 4-6 out of 8 HLA alleles. The primary end point was met, with 1-year OS of 76% (90% CI, 67.3 to 83.3) in the entire cohort, and 72% and 79% in the myeloablative and reduced-intensity conditioning strata, respectively. Secondary end points related to engraftment and graft-versus-host-disease were reached. Multivariate analysis comparing the study group with other mismatched HCT controls found no significant differences in OS.ConclusionOur prospective study demonstrates the feasibility and effectiveness of HCT with an MMUD in the setting of PTCy. Remarkably, nearly half of the study participants belonged to an ethnic minority population, suggesting this approach may significantly expand access to HCT.

Project description:High-dose post-transplantation cyclophosphamide (PTCy) is an effective platform for prevention of severe graft-versus-host disease (GVHD) after allogeneic bone marrow (BM) transplantation with mismatched unrelated donors (mMUDs). Previous studies evaluating PTCy with mMUDs favored BM allografts over peripheral blood stem cell transplantation (PBSCT) due to concerns that PBSCT may be associated with an increased risk of acute and chronic GVHD. In addition, haploidentical PBSCT is associated with high rates of cytokine release syndrome (CRS), which is another concern with mMUD PBSCT. This study was conducted to determine the feasibility and safety of using mMUD PBSCT with PTCy as GVHD prophylaxis. Patients who received mMUD PBSCT using a PTCy-based GVHD prophylaxis at Johns Hopkins Hospital as part of a prospective clinical trial of mMUD and non-first-degree relative haploidentical transplantation with PTCy (ClinicalTrials.gov identifier NCT01203722) were included. All patients underwent T cell-replete PBSCT between November 2012 and August 2020. Statistical analyses were performed using the Kaplan-Meier method and proportional subdistribution hazard regression model for competing risks. The 29 patients in the study had a median age of 54 years, with 10 patients (34%) age ≥60 years. Nineteen grafts (66%) were matched for 9/10 HLA loci, 6 (21%) were match for 8/10, and 4 (14%) were matched for 7/10. No primary or secondary graft failure occurred. The median time to neutrophil recovery (≥500/µL) was 17 days, and that to platelet recovery (≥20,000/µL) was 28 days. Full donor chimerism was achieved in all patients by day +60. The cumulative incidence (CuI) of grade II-IV acute GVHD at 180 days was 15% (90% confidence interval [CI], 3% to 26%). There were no cases of severe chronic GVHD, 3 cases of mild chronic GVHD, and 1 case of moderate chronic GVHD. The CuI of nonrelapse mortality (NRM) was 7% (90% CI, NA to 18%) at 1 year. Eighteen patients (62%) experienced mild CRS (grade 1-2), and 1 patient (3%) experienced severe CRS (grade 3-5). At 1 year, the CuI of relapse was 29% (90% CI, 8% to 50%), overall survival was 93% (90% CI, 85% to 100%), progression-free survival was 64% (90% CI, 46% to 88%), GVHD-free relapse-free survival was 41% (90% CI, 23% to 73%), and chronic GVHD-free relapse-free survival was 64% (90% CI, 46% to 88%). Our data indicate that mMUD PBSCT using PTCy-based GVHD prophylaxis is safe and feasible. All patients engrafted, and rates of NRM (7%) and acute GVHD (15%) at 1 year were low. There was only 1 case (3%) of severe CRS. Compared with previously published outcomes, mMUD PBSCT using PTCy-based GVHD prophylaxis has a safety and efficacy profile that may not be different from that of PBSCT from matched donors. These results further solidify that all patients who require blood or BM transplantation should be able to find an acceptable donor.

Dataset Information

Decision analysis for donor selection in stem cell transplantation-HLA-8/8 allele-matched unrelated donor vs HLA-1 AG mismatched related donor.

Publications

Decision analysis for donor selection in stem cell transplantation-HLA-8/8 allele-matched unrelated donor vs HLA-1 AG mismatched related donor.

Similar Datasets

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