HLA-haploidentical vs matched unrelated donor transplants with posttransplant cyclophosphamide-based prophylaxis

Mahasweta Gooptu, Rizwan Romee, Andrew St. Martin, Mukta Arora, Monzr Al Malki, Joseph H. Antin, Christopher N. Bredeson, Claudio G. Brunstein, Saurabh Chhabra, Ephraim J. Fuchs, Nilanjan Ghosh, Michael R. Grunwald, Christopher G. Kanakry, Natasha Kekre, Jospeh P. McGuirk, Ian K. McNiece, Rohtesh S. Mehta, Marco Mielcarek, Fillipo Milano, Dipenkumar ModiRan Reshef, Scott R. Solomon, Mark A. Schroeder, Edmund K. Waller, Yoshiro Inamoto, Robert J. Soiffer, Mary Eapen

Research output: Contribution to journalArticlepeer-review

Abstract

Posttransplant cyclophosphamide (PTCy) graft-versus-host disease (GVHD) prophylaxis has enabled haploidentical (Haplo) transplantation to be performed with results similar to those after matched unrelated donor (MUD) transplantation with traditional prophylaxis. The relative value of transplantation with MUD vs Haplo donors when both groups receive PTCy/calcineurin inhibitor/mycophenolate GVHD prophylaxis is not known. We compared outcomes after 2036 Haplo and 284 MUD transplantations with PTCy GVHD prophylaxis for acute leukemia or myelodysplastic syndrome in adults from 2011 through 2018. Cox regression models were built to compare outcomes between donor types. Recipients of myeloablative and reduced-intensity regimens were analyzed separately. Among recipients of reduced-intensity regimens, 2-year graft failure (3% vs 11%), acute grades 2 to 4 GVHD (hazards ratio [HR], 0.70; P = .022), acute grades 3 and 4 GVHD (HR, 0.41; P = .016), and nonrelapse mortality (HR, 0.43; P = .0008) were lower after MUD than with Haplo donor transplantation. Consequently, disease-free (HR, 0.74; P = .008; 55% vs 41%) and overall (HR, 0.65; P = .001; 67% vs 54%) survival were higher with MUD than with Haplo transplants. Among recipients of myeloablative regimens, day-100 platelet recovery (95% vs 88%) was higher and grades 3 and 4 acute (HR, 0.39; P = .07) and chronic GVHD (HR, 0.66; P = .05) were lower after MUD than with Haplo donor transplantation. There were no differences in graft failure, relapse, nonrelapse mortality, and disease-free and overall survival between donor types with myeloablative conditioning regimens. These data extend and confirm the importance of donor-recipient HLA matching for allogeneic transplantation. A MUD is the preferred donor, especially for transplantations with reduced-intensity conditioning regimens.

Original languageEnglish (US)
Pages (from-to)273-282
Number of pages10
JournalBlood
Volume138
Issue number3
DOIs
StatePublished - Jul 22 2021

Bibliographical note

Funding Information:
This work was supported primarily by National Institutes of Health (NIH)/National Cancer Institute (NCI) grant U24-CA076518, the NIH/National Heart, Lung and Blood Institute (NHLBI), the NIH/National Institute of Allergy and Infectious Diseases (NIAID), and contract HHSH250201200016C from the Health Resources and Services Administration/Department of Health and Human Services (HRSA/DHHS). The views expressed in this article do not reflect the official policy or position of the NIH, HRSA, or any other agency of the US Government.

Funding Information:
This work was supported primarily by National Institutes of Health (NIH)/National Cancer Institute (NCI) grant U24-CA076518, the NIH/National Heart, Lung and Blood Institute (NHLBI), the NIH/National Institute of Allergy and Infectious Diseases (NIAID), and contract HHSH250201200016C from the Health Resources and Services Administration/Department of Health and Human Services (HRSA/DHHS). The views expressed in this article do not reflect the official policy or position of the NIH, HRSA, or any other agency of the US Government.

Funding Information:
Conflict-of-interest disclosure: M.R.G. has received consulting fees from AbbVie, Agios, Amgen, Astellas, Cardinal Health, Bristol-Myers Squibb/Celgene, Daiichi Sankyo, Gilead, Incyte, Karius, Merck, Pfizer, Premier, Stemline, and Trovagene and research funding from Forma Therapeutics, Genentech/Roche, Incyte, and Janssen. R.J.S. serves on the Board of Directors for Kiadis and Be The Match/National Marrow Donor Program; has provided consulting for Gilead, Rheos Therapeutics, VOR Biopharma, and Novartis; and has served on the Data Safety Monitoring Board for Juno, Celgene, and BMS. The remaining authors declare no competing financial interests.

Publisher Copyright:
© 2021 American Society of Hematology

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