TY - JOUR
T1 - Myeloablative Conditioning for Allogeneic Transplantation Results in Superior Disease-Free Survival for Acute Myelogenous Leukemia and Myelodysplastic Syndromes with Low/Intermediate but not High Disease Risk Index: A Center for International Blood and Marrow Transplant Research Study
AU - Bejanyan, N.
AU - Zhang, M.J.
AU - Bo-Subait, K.
AU - Brunstein, C.
AU - Wang, H.L.
AU - Warlick, E.D.
AU - Giralt, S.
AU - Nishihori, T.
AU - Martino, R.
AU - Passweg, J.
AU - Dias, A.
AU - Copelan, E.
AU - Hale, G.
AU - Gale, R.P.
AU - Solh, M.
AU - Kharfan-Dabaja, M.A.
AU - Diaz, M.A.
AU - Ganguly, S.
AU - Gore, S.
AU - Verdonck, L.F.
AU - Hossain, N.M.
AU - Kekre, N.
AU - Savani, B.
AU - Byrne, M.
AU - Kanakry, C.
AU - Cairo, M.S.
AU - Ciurea, S.
AU - Schouten, H.C.
AU - Bredeson, C.
AU - Munker, R.
AU - Lazarus, H.
AU - Cahn, J.Y.
AU - van der Poel, M.
AU - Rizzieri, D.
AU - Yared, J.A.
AU - Freytes, C.
AU - Cerny, J.
AU - Aljurf, M.
AU - Palmisiano, N.D.
AU - Pawarode, A.
AU - Bacher, V.U.
AU - Grunwald, M.R.
AU - Nathan, S.
AU - Wirk, B.
AU - Hildebrandt, G.C.
AU - Seo, S.
AU - Olsson, R.F.
AU - George, B.
AU - de Lima, M.
AU - Hourigan, C.S.
PY - 2021/1/1
Y1 - 2021/1/1
N2 - Compared with reduced-intensity conditioning (RIC), myeloablative conditioning (MAC) is generally associated with lower relapse risk after allogeneic hematopoietic cell transplantation (HCT) for acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). However, disease-specific risk factors in AML/MDS can further inform when MAC and RIC may yield differential outcomes. We analyzed HCT outcomes stratified by the Disease Risk Index (DRI) in 4387 adults (age 40 to 65 years) to identify the impact of conditioning intensity. In the low/ intermediate-risk DRI cohort, RIC was associated with lower nonrelapse mortality (NRM) (hazard ratio [HR],.74; 95% confidence interval [CI],.62 to.88; P <.001) but significantly greater relapse risk (HR, 1.54; 95% CI, 1.35 to 1.76; P <.001) and thus inferior disease-free survival (DFS) (HR, 1.19; 95% CI, 1.07 to 1.33; P =.001). In the high/ very high-risk DRI cohort, RIC was associated with marginally lower NRM (HR,.83; 95% CI,.68 to 1.00; P =.051) and significantly higher relapse risk (HR, 1.23; 95% CI, 1.08 to 1.41; P =.002), leading to similar DFS using either RIC or MAC. These data support MAC over RIC as the preferred conditioning intensity for patients with AML/MDS with low/intermediate-risk DRI, but with a similar benefit as RIC in high/very high-risk DRI. Novel MAC regimens with less toxicity could benefit all patients, but more potent antineoplastic approaches are needed for the high/ very-high risk DRI group. (C) 2020 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.
AB - Compared with reduced-intensity conditioning (RIC), myeloablative conditioning (MAC) is generally associated with lower relapse risk after allogeneic hematopoietic cell transplantation (HCT) for acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). However, disease-specific risk factors in AML/MDS can further inform when MAC and RIC may yield differential outcomes. We analyzed HCT outcomes stratified by the Disease Risk Index (DRI) in 4387 adults (age 40 to 65 years) to identify the impact of conditioning intensity. In the low/ intermediate-risk DRI cohort, RIC was associated with lower nonrelapse mortality (NRM) (hazard ratio [HR],.74; 95% confidence interval [CI],.62 to.88; P <.001) but significantly greater relapse risk (HR, 1.54; 95% CI, 1.35 to 1.76; P <.001) and thus inferior disease-free survival (DFS) (HR, 1.19; 95% CI, 1.07 to 1.33; P =.001). In the high/ very high-risk DRI cohort, RIC was associated with marginally lower NRM (HR,.83; 95% CI,.68 to 1.00; P =.051) and significantly higher relapse risk (HR, 1.23; 95% CI, 1.08 to 1.41; P =.002), leading to similar DFS using either RIC or MAC. These data support MAC over RIC as the preferred conditioning intensity for patients with AML/MDS with low/intermediate-risk DRI, but with a similar benefit as RIC in high/very high-risk DRI. Novel MAC regimens with less toxicity could benefit all patients, but more potent antineoplastic approaches are needed for the high/ very-high risk DRI group. (C) 2020 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.
KW - AML
KW - MDS
KW - DRI
KW - Myeloablative
KW - RIC
KW - ACUTE MYELOID-LEUKEMIA
KW - STEM-CELL TRANSPLANTATION
KW - UNRELATED DONOR TRANSPLANTATION
KW - TERM-FOLLOW-UP
KW - REDUCED-INTENSITY
KW - WORKING PARTY
KW - REGIMENS
KW - IMPACT
KW - MUTATIONS
U2 - 10.1016/j.bbmt.2020.09.026
DO - 10.1016/j.bbmt.2020.09.026
M3 - Article
C2 - 33010430
SN - 2666-6375
VL - 27
JO - Transplantation and Cellular Therapy
JF - Transplantation and Cellular Therapy
IS - 1
ER -