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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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

Keywords

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

ASJC Scopus subject areas

  • Hematology
  • Transplantation
  • Immunology and Allergy
  • Cell Biology
  • Molecular Medicine
  • Medicine(all)

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