Journal
LANCET HAEMATOLOGY
Volume 6, Issue 11, Pages E573-E584Publisher
ELSEVIER SCI LTD
DOI: 10.1016/S2352-3026(19)30158-9
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Funding
- Varda and Boaz Dotan Research Center in Haemato-Oncology
- Cancer Biology Research Center of Tel Aviv University
- Shalvi Foundation for the Support of Medical Research
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Background The introduction of donors other than HLA-matched siblings has been a pivotal change in stern cell transplantation. We aimed to assess the evolution of outcomes within donor groups over time and explore whether donor-recipient HLA disparity might be advantageous in patients with aggressive disease. Methods In this retrospective, multicentre study, we assessed the outcomes for adult patients (>= 18 years) with haematological malignancies who underwent their first allogeneic hematopoietic stem cell transplantation (HSCT) between Jan 3,2001, and Dec 31,2015, and were reported to the European Society for Blood and Marrow Transplantation. The donor types studied were matched sibling, matched unrelated, mismatched unrelated, haploidentical, and cord blood donors. Unrelated non-cord-blood donors and recipients were typed at the allelic level for HLA-A, HLA-B, HLA-C, and HLA-DRBL We evaluated trends in overall survival, non-relapse mortality, relapse incidence, progression-free survival, acute and chronic graft-versus-host disease (GVHD), and GVHD-free and relapse-free survival following transplantation from various donor types (matched sibling, matched unrelated, mismatched unrelated, haploidentical, and umbilical cord blood), and compared transplantation outcomes across three epochs (epoch 1: 2001-05; epoch 2: 2006-10; and epoch 3: 2011-15). We used Kaplan-Meier estimators for survival probabilities and cumulative incidence functions accounting for competing risks for probabilities of GHVD, relapse, and non-relapse mortality, using multiple imputations by chained equations to deal with missing data. In epoch 3, we directly compared outcomes by donor group, stratified by a novel three-level disease-risk scheme. Findings We induded 106188 patients in our analysis. The median follow-up was 4.1 years (IQR 1.7-7.7). Overall survival at 3 years increased with all donor groups between epochs 2 and 3 (matched sibling: 54.0% [95% CI 53-1-54.8] to 54.6% [53-6-55.6]; matched unrelated: 49.1% [48.0-50.2] to 51.6% [50.7-52.6]; mismatched unrelated: 37.4% [35.7-39.2] to 41.3% [39.5-43.1]; haploidentical: 34.5% [31.4-37.9] to 44.2% [42.1-46.3]; and cord blood 36.3% [33.9-39] to 43.7%140.8-46.8D. Improvement in overall survival seems to be driven by a reduction in non-relapse mortality, except in cord blood HSCT recipients, who had a lower relapse incidence. Comparing donor groups across disease-risk strata using the novel disease-risk scheme, overall survival among recipients of matched sibling transplantations remained better than other donor groups except in high-risk disease, where overall survival with matched unrelated transplantations was not different. Interpretation Overall survival following allogeneic stem cell transplantation is improving with substantial progress among recipients of haploidentical and cord blood HSCT. Nonetheless, the traditional donor hierarchy of matched sibling donors followed by matched unrelated donors and then other donors holds. Our findings warrant further investigation and could inform decision making and the development of donor-selection algorithms. Copyright (C) 2019 Elsevier Ltd. All rights reserved.
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