TY - JOUR
T1 - Chronic Graft-versus-Host Disease, Nonrelapse Mortality, and Disease Relapse in Older versus Younger Adults Undergoing Matched Allogeneic Peripheral Blood Hematopoietic Cell Transplantation
T2 - A Center for International Blood and Marrow Transplant Research Analysis
AU - Bhatt, Vijaya Raj
AU - Wang, Tao
AU - Chen, Karen
AU - Kitko, Carrie L.
AU - MacMillan, Margaret L.
AU - Pidala, Joseph A.
AU - Al Malki, Monzr M.
AU - Badawy, Sherif M.
AU - Beitinjaneh, Amer
AU - Ganguly, Siddhartha
AU - Hamilton, Betty
AU - Hildebrandt, Gerhard C.
AU - Lekakis, Lazaros J.
AU - Liu, Hongtao
AU - Maziarz, Richard T.
AU - Modi, Dipenkumar
AU - Murthy, Hemant S.
AU - Preussler, Jaime M.
AU - Sharma, Akshay
AU - Spellman, Stephen R.
AU - Arora, Mukta
AU - Lee, Stephanie J.
N1 - Publisher Copyright:
© 2021 The American Society for Transplantation and Cellular Therapy
PY - 2022/1
Y1 - 2022/1
N2 - 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.
AB - 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.
KW - Allogeneic Hematopoietic Cell Transplantation
KW - Chronic Graft-Versus-Host Disease
KW - Non-Relapse Mortality
KW - Older Adults
KW - Relapse
UR - http://www.scopus.com/inward/record.url?scp=85119079197&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85119079197&partnerID=8YFLogxK
U2 - 10.1016/j.jtct.2021.10.002
DO - 10.1016/j.jtct.2021.10.002
M3 - Article
C2 - 34637965
AN - SCOPUS:85119079197
SN - 2666-6375
VL - 28
SP - 34
EP - 42
JO - Transplantation and Cellular Therapy
JF - Transplantation and Cellular Therapy
IS - 1
ER -