Relapse and Disease-Free Survival in Patients With Myelodysplastic Syndrome Undergoing Allogeneic Hematopoietic Cell Transplantation Using Older Matched Sibling Donors vs Younger Matched Unrelated Donors

Guru Subramanian Guru Murthy, Soyoung Kim, Zhen Huan Hu, Noel Estrada-Merly, Muhammad Bilal Abid, Mahmoud Aljurf, Ulrike Bacher, Sherif M. Badawy, Amer Beitinjaneh, Chris Bredeson, Jean Yves Cahn, Jan Cerny, Miguel Angel Diaz Perez, Nosha Farhadfar, Robert Peter Gale, Siddhartha Ganguly, Usama Gergis, Gerhard C. Hildebrandt, Michael R. Grunwald, Shahrukh HashmiNasheed M. Hossain, Matt Kalaycio, Rammurti T. Kamble, Mohamed A. Kharfan-Dabaja, Betty Ky Hamilton, Hillard M. Lazarus, Jane Liesveld, Mark Litzow, David I. Marks, Hemant S. Murthy, Sunita Nathan, Aziz Nazha, Taiga Nishihori, Sagar S. Patel, Attaphol Pawarode, David Rizzieri, Bipin Savani, Sachiko Seo, Melhem Solh, Celalettin Ustun, Marjolein van der Poel, Leo F. Verdonck, Ravi Vij, Baldeep Wirk, Betul Oran, Ryotaro Nakamura, Bart Scott, Wael Saber

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

IMPORTANCE Matched sibling donors (MSDs) are preferred for allogeneic hematopoietic cell transplantation (allo-HCT) in myelodysplastic syndrome even if they are older. However, whether older MSDs or younger human leukocyte antigen-matched unrelated donors (MUDs) are associated with better outcomes remains unclear. OBJECTIVE To investigate whether allo-HCT for myelodysplastic syndrome using younger MUDs would be associated with improved disease-free survival and less relapse compared with older MSDs. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study assessed data reported to the Center for International Blood and Marrow Transplant Research database from 1761 adults 50 years or older with myelodysplastic syndrome who underwent allo-HCT using an older MSD or younger MUD between January 1, 2011, and December 31, 2017, with a median follow-up of 48 months. Data analysis was performed from January 8, 2019, to December 30, 2020. INTERVENTIONS/EXPOSURES Allo-HCT from an older MSD (donor age ≥50 years) or a younger MUD (donor age ≤35 years). MAIN OUTCOMES AND MEASURES The primary outcome was disease-free survival. Secondary outcomes were overall survival, relapse, nonrelapse mortality, acute graft-vs-host disease (GVHD), chronic GVHD, and GVHD-free relapse-free survival. RESULTS Of 1761 patients (1162 [66%] male; median [range] age, 64.9 [50.2-77.6] years in the MSD cohort and 66.5 [50.4-80.9] years in MUD cohort), 646 underwent allo-HCT with an older MSD and 1115 with a younger MUD. In multivariable analysis, the rate of disease-free survival was significantly lower in allo-HCTs with older MSDs compared with younger MUDs (hazard ratio [HR], 1.17; 95% CI, 1.02-1.34; P =.02), whereas the difference in overall survival rate of allo-HCT with younger MUDs vs older MSDs was not statistically significant (HR, 1.13; 95% CI, 0.98-1.29; P =.07). Allo-HCT with older MSDs was associated with significantly higher relapse (HR, 1.62; 95% CI, 1.32-1.97; P <.001), lower nonrelapse mortality (HR, 0.76; 95% CI, 0.59-0.96; P =.02), lower acute GVHD (HR, 0.52; 95% CI, 0.42-0.65; P <.001), chronic GVHD (HR, 0.77; 95% CI, 0.64-0.92; P =.005), and a lower rate of GVHD-free relapse-free survival beyond 12 months after allo-HCT (HR, 1.42; 95% CI, 1.02-1.98; P =.04). CONCLUSIONS AND RELEVANCE This cohort study found higher disease-free survival and lower relapse for allo-HCT in myelodysplastic syndrome using younger MUDs compared with older MSDs. The risk of nonrelapse mortality and GVHD was lower with older MSDs. These results suggest that the use of younger MUDs should be considered in the donor selection algorithm for myelodysplastic syndrome, in which it is pivotal to minimize relapse given limited treatment options for managing relapsed disease.

Original languageEnglish
Pages (from-to)404-411
Number of pages8
JournalJAMA Oncology
Volume8
Issue number3
DOIs
StatePublished - 2022

Bibliographical note

Funding Information:
Blood and Marrow Transplant Research is supported primarily by Public Health Service grant U24CA076518 from the National Cancer Institute, the National Heart, Lung and Blood Institute, and the National Institute of Allergy and Infectious Diseases; grant HHSH250201700006C from the Health Resources and Services Administration; and grants N00014-20-1-2705 and N00014-20-1-2832 from the Office of Naval Research. Support is also provided by Be the Match Foundation, the Medical College of Wisconsin, the National Marrow Donor Program, and the following commercial entities: AbbVie; Accenture; Actinium Pharmaceuticals Inc; Adaptive Biotechnologies Corporation; Adienne SA; Allovir Inc; Amgen Inc; Astellas Pharma US; Bluebird Bio Inc; Bristol Myers Squibb Co; CareDx; CSL Behring; CytoSen Therapeutics Inc; Daiichi Sankyo Co Ltd; Eurofins Viracor; ExcellThera; Fate Therapeutics; Gamida-Cell Ltd; Genentech Inc; Gilead; GlaxoSmithKline; Incyte Corporation; Janssen/Johnson & Johnson; Jasper Therapeutics; Jazz Pharmaceuticals Inc; Karyopharm Therapeutics; Kiadis Pharma; Kite, a Gilead Company; Kyowa Kirin; Magenta Therapeutics; Medac GmbH; Merck & Co; Millennium, the Takeda Oncology Co; Miltenyi Biotec Inc; MorphoSys; Novartis Pharmaceuticals Corporation; Omeros Corporation; Oncopeptides Inc; Orca Biosystems Inc; Pfizer Inc; Pharmacyclics LLC; Sanofi Genzyme; Seagen Inc; Stemcyte; Takeda Pharmaceuticals; Tscan; Vertex; Vor Biopharma; and Xenikos. Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Funding Information:
reported receiving honoraria from Cardinal Health, TG Therapeutics, DAVA Oncology, and Curio Science and serving as a consultant for Cancerexpert, Qessential, and Techspert outside the submitted work. Dr Hu reported receiving grants from the National Institutes of Health during the conduct of the study. Dr Cerny reported receiving personal fees from the Allovir Inc Data Safety Monitory Board, the Pfizer Inc Advisory Board, the Amgen Inc Advisory Board, and the Jazz Pharmaceuticals Advisory Board and owning stocks in Actinium Pharmaceuticals, Bluebird Bio Inc, Dynavax Pharma, Atyr Pharma, Gamida Cell, Miragen Therapeutics, Mustang Bio, Novavax, Ovid Therapeutics, Sorrento Therapeutics, TG Therapeutics, Vaxart Inc, and Veru Inc outside the submitted work. Dr Ganguly reported receiving personal fees from Seattle Genetics, Kite Pharma, Sanofi, Janssen, Astra Zeneca, Bristol Myers Squibb, Daiichi Sankyo, and Astellas outside the submitted work. Dr Grunwald reported receiving personal fees from AbbVie, Agios, Amgen, Astellas, Blueprint Medicines, Bristol Myers Squibb, Cardinal Health, Daiichi Sankyo, Gamida Cell, Genentech/Roche, Gilead, Incyte, Invitae, Karius, Ono Pharmaceutical, Pfizer, Premier, Sierra Oncology, Stemline, and Trovagene, nonfinancial support from Amgen, Incyte, and Genentech/Roche, and grants from Janssen and Incyte outside the submitted work. Dr Kharfan-Dabaja reported receiving consultancy fees from Daiichi Sankyo outside the submitted work. Dr Hamilton reported serving on the advisory boards of Syndax and Equilium outside the submitted work. Dr Liesveld reported receiving honoraria from Bristol Myers Squibb and Blueprint sciences and serving on the Onconova Data Safety Monitoring Board outside the submitted work. Dr Murthy reported receiving consultancy fees from CRISPR Therapeutics Research Funding outside the submitted work. Dr Nazha reported owning stock in Amazon Web Services outside the submitted work. Dr Nishihori reported receiving trial support and funding from Novartis and Karyopharm outside the submitted work. Dr Patel reported receiving personal fees from Kite Pharma, GLG Pharma, and Medexus outside the submitted work. Dr Pawarode reported receiving grants from Celgene Cooperation and Angiocrine Bioscience outside the submitted work. Dr Seo reported receiving personal fees from Janssen Pharmaceutical KK outside the submitted work. Dr Ustun reported receiving honoraria from Blueprint and Novartis outside the submitted work. Dr Scott reported receiving grants from Celgene/ Bristol Myers Squibb outside the submitted work. No other disclosures were reported.

Publisher Copyright:
© 2022 American Medical Association

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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