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HLA Matching in Unrelated Stem Cell Transplantation up to Date.

ABSTRACT: Unrelated hematopoietic stem cell transplantation (HSCT) has evolved from an experimental protocol to a potentially curative first-line treatment in certain disease instances. Factors enabling this transformation were the optimization of treatment protocols and supportive care as well as the availability of a large number of donors worldwide along with the higher quality and reliability of HLA typing. The main criterion for donor selection is HLA compatibility. In this review we discuss the current clinical evidence of HLA matching in unrelated HSCT. In this context, we address methodical aspects of transplantation immunobiology research and discuss the impact of locus and resolution of HLA differences. Furthermore, we address special constellations such as unidirectional mismatches or the presence of nonexpressed alleles as well as HLA alloimmunization and describe the perspective for HLA typing and matching strategies in the future, given the implementation of novel complete or near-complete gene typing approaches using next-generation sequencing short read technology, which are now entering the standard of clinical care.

SUBMITTER: Furst D

PROVIDER: S-EPMC6876603 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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HLA Matching in Unrelated Stem Cell Transplantation up to Date.

Fürst Daniel D Neuchel Christine C Tsamadou Chrysanthi C Schrezenmeier Hubert H Mytilineos Joannis J

Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie 20190903 5

Unrelated hematopoietic stem cell transplantation (HSCT) has evolved from an experimental protocol to a potentially curative first-line treatment in certain disease instances. Factors enabling this transformation were the optimization of treatment protocols and supportive care as well as the availability of a large number of donors worldwide along with the higher quality and reliability of HLA typing. The main criterion for donor selection is HLA compatibility. In this review we discuss the curr ...[more]

PMID: 31832058

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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

HLA Matching in Unrelated Stem Cell Transplantation up to Date.

Publications

HLA Matching in Unrelated Stem Cell Transplantation up to Date.

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