Chronic Graft-versus-Host Disease, Nonrelapse Mortality, and Disease Relapse in Older versus Younger Adults Undergoing Matched Allogeneic Peripheral Blood Hematopoietic Cell Transplantation: A Center for International Blood and Marrow Transplant Research Analysis

Vijaya Raj Bhatt, Tao Wang, Karen Chen, Carrie L. Kitko, Margaret L. MacMillan, Joseph A. Pidala, Monzr M. Al Malki, Sherif M. Badawy, Amer Beitinjaneh, Siddhartha Ganguly, Betty Hamilton, Gerhard C. Hildebrandt, Lazaros J. Lekakis, Hongtao Liu, Richard T. Maziarz, Dipenkumar Modi, Hemant S. Murthy, Jaime M. Preussler, Akshay Sharma, Stephen R. SpellmanMukta Arora, Stephanie J. Lee

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

The effect of chronic graft-versus-host disease (cGVHD) on the risk of nonrelapse mortality (NRM) and relapse has not been specifically studied in older adults, who are increasingly undergoing allogeneic hematopoietic cell transplantation (alloHCT) and surviving long-term to develop cGVHD. In this Center for International Blood and Marrow Transplant Research (CIBMTR) analysis, we tested our hypothesis that the risk of NRM was higher with the development of cGVHD, particularly among older adults (age ≥60 years). We included 4429 adults age ≥40 years who underwent a first HLA-matched peripheral blood stem cell alloHCT for acute myelogenous leukemia or myelodysplastic syndrome between 2008 and 2017. We compared outcomes of 4 groups—older adults (≥60 years) and younger adults (40 to 59 years) with cGVHD and older and younger adults without cGVHD—to determine the effect of older age and cGVHD on various outcomes. We used Cox proportional hazard models to determine the risk of NRM, relapse, and overall survival (OS). We treated cGVHD as a time-dependent covariate. The severity of cGVHD was based on the CIBMTR clinical definitions. cGVHD was significantly associated with a higher risk of NRM and lower risk of relapse regardless of age. The risk of NRM was higher for older adults versus younger adults. Adults who developed cGVHD as a group had longer OS compared with age-matched cohorts without cGVHD. Older adults had worse OS regardless of cGVHD. Among adults with cGVHD, clinically moderate or severe cGVHD was associated with a significantly higher risk of NRM and lower risk of relapse; severe cGVHD was associated with shorter OS, whereas mild to moderate cGVHD was associated with longer OS. Among both younger and older adults, the development of cGVHD was associated with a higher risk of NRM, lower risk of relapse, and longer OS. Older adults had a higher risk of NRM, but the increased risk of NRM associated with cGVHD did not differ based on age. The development of mild to moderate cGVHD offered the most favorable balance between minimizing NRM and decreasing the risk of relapse. The relapse risk was lowest for adults with severe cGVHD, but high NRM resulted in shorter OS. Developing strategies to avoid clinically severe cGVHD is critically important.

Original languageEnglish
Pages (from-to)34-42
Number of pages9
JournalTransplantation and Cellular Therapy
Volume28
Issue number1
DOIs
StatePublished - Jan 2022

Bibliographical note

Funding Information:
Data use statement: The CIBMTR supports accessibility of research in accordance with the NIH Data Sharing Policy and the National Cancer Institute (NCI) Cancer Moonshot Public Access and Data Sharing Policy. The CIBMTR only releases deidentified datasets that comply with all relevant global regulations regarding privacy and confidentiality. Financial disclosure: The CIBMTR is supported primarily by Public Health Service Grant U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases (NIAID); Grant HHSH250201700006C from the Health Resources and Services Administration (HRSA); and Awards 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, Adaptive Biotechnologies, Adienne SA, AlloVir, Amgen, Astellas Pharma US, bluebird bio, Bristol Myers Squibb, CareDx, CSL Behring, CytoSen Therapeutics, Daiichi Sankyo, Eurofins Viracor, ExcellThera, Fate Therapeutics, Gamida-Cell, Genentech, Gilead, GlaxoSmithKline, Incyte, Janssen/Johnson & Johnson, Jasper Therapeutics, Jazz Pharmaceuticals, Karyopharm Therapeutics, Kiadis Pharma, Kite Pharma, Kyowa Kirin, Magenta Therapeutics, Medac, Merck & Co, Millennium, Miltenyi Biotec, MorphoSys, Novartis Pharmaceuticals, Omeros, Oncopeptides, Orca Biosystems, Pfizer, Pharmacyclics, Sanofi Genzyme, Seagen, Stemcyte, Takeda Pharmaceuticals, Tscan, Vertex Pharmaceuticals, Vor Biopharma, and Xenikos BV. Conflict of interest statement: V.R.B. reports consulting fees from Agios, Servier, Takeda, Rigel, Partner Therapeutics, Omeros, Genentech, Partnership for Health Analytic Research, and CSL Behring; grants and consulting fees from AbbVie and Incyte; grants from Jazz Pharmaceuticals, Pfizer, the National Marrow Donor Program, and Tolero Pharmaceuticals; and drug support for a clinical trial from Oncoceutics outside the submitted work. R.T.M. reports participation with Novartis as a member of the Data Monitoring and Safety Board for the REACH2 and REACH3 phase IIII studies assessing ruxolitinib for management of advanced aGVHD and cGVHD, and serving on an advisory board for Incyte. H.L. reports receiving research support from BMS and Karyopharm, serving on an advisory board for Agios, and receiving presentation preparation from SITC. H.G. reports receiving consulting fees from Kadmon, Astellas, Sanofi, and Bristol Meyers Squibb and payments from Seattle Genetics, Daiichi Sankyo, and Kite Pharma and serving on advisory boards for Kadmon, BMS, and Sanofi. H.S.M. reports serving on an advisory board for CRISPR Therapeutics. S.J.L. reports receiving research funding from Amgen, AstraZeneca, Incyte, Kadmon, Novartis, Pfizer, Syndax, and Takeda and serving on a clinical trial steering committee for Novartis. D.M. reports serving on advisory boards for MorphoSys and Seagen. Dr. Hildebrandt reports receiving research funding from Takeda, Jazz Pharmaceuticals, Parmacyclics, Incyte, and AstraZeneca; receiving consulting fees from Incyte, Jazz Pharmaceutical, MorphoSys, Alexion Pharmaceuticals, and Kyropharm Therapeutics; receiving support for attending meetings and/or travel from Jazz Pharmaceuticals, Astellas Pharma, Incyte, Falk Foundation, Incyte, and Takeda; having stock and other ownership interests with bluebird bio, Crispr Therapeutics, Scotts Miracle-Gro, CareTrust Reit, Sangamo Bioscience, Charlotte's Web, Medical Properties Trust, Aetna, Angi, Axim Biotechnologies, Juno Therapeutics, Bristol-Myers Squibb/Medarex, Johnson & Johnson, Aimmune, Insys Therapeutics, Cardinal Health, Clovis Oncology, CVS Health, Pfizer, Vertex, Immunomedics, Cellectis, Celgene, Novartis, GW Pharmaceuticals, Endocyte, Kite Pharma, AbbVie, IDEXX Laboratories, Procter & Gamble, and Bayer; serving in a consultant or advisory role with Incyte, Jazz Pharmaceuticals, Pfizer, MorphoSys, Alexion Pharmaceuticals, Seattle Genetics, and Karyopharm Therapeutics; and receiving travel and accommodation expenses from the Falk Foundation, Takeda, Astellas Pharma, Incyte, Jazz Pharmaceuticals, Kite Pharma, and Pfizer. B.H. reports receiving consulting fees from and serving on a data safety monitoring board or advisory board for Syndax and Equilium. Financial disclosure: See Acknowledgments on page 41.

Funding Information:
Conflict of interest statement: V.R.B. reports consulting fees from Agios, Servier, Takeda, Rigel, Partner Therapeutics, Omeros, Genentech, Partnership for Health Analytic Research, and CSL Behring; grants and consulting fees from AbbVie and Incyte; grants from Jazz Pharmaceuticals, Pfizer, the National Marrow Donor Program, and Tolero Pharmaceuticals; and drug support for a clinical trial from Oncoceutics outside the submitted work. R.T.M. reports participation with Novartis as a member of the Data Monitoring and Safety Board for the REACH2 and REACH3 phase IIII studies assessing ruxolitinib for management of advanced aGVHD and cGVHD, and serving on an advisory board for Incyte. H.L. reports receiving research support from BMS and Karyopharm, serving on an advisory board for Agios, and receiving presentation preparation from SITC. H.G. reports receiving consulting fees from Kadmon, Astellas, Sanofi, and Bristol Meyers Squibb and payments from Seattle Genetics, Daiichi Sankyo, and Kite Pharma and serving on advisory boards for Kadmon, BMS, and Sanofi.

Publisher Copyright:
© 2021 The American Society for Transplantation and Cellular Therapy

Keywords

  • Allogeneic Hematopoietic Cell Transplantation
  • Chronic Graft-Versus-Host Disease
  • Non-Relapse Mortality
  • Older Adults
  • Relapse

ASJC Scopus subject areas

  • Transplantation
  • Molecular Medicine
  • Hematology
  • Immunology and Allergy
  • Cell Biology

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