TY - JOUR
T1 - Predictors of overall survival among patients treated with sirolimus/tacrolimus vs methotrexate/tacrolimus for GvHD prevention
AU - Khimani, F.
AU - Kim, J.
AU - Chen, L.
AU - Dean, E.
AU - Rizk, V.
AU - Betts, B.
AU - Nishihori, T.
AU - Locke, F.
AU - Mishra, A.
AU - Perez, L.
AU - Ayala, E.
AU - Kharfan-Dabaja, M.
AU - Nieder, M.
AU - Fernandez, H.
AU - Anasetti, C.
AU - Pidala, J.
N1 - Publisher Copyright:
© 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2017/7/1
Y1 - 2017/7/1
N2 - Sirolimus (SIR)/tacrolimus (TAC) is an alternative to methotrexate (MTX)/TAC. However, rational selection among these GvHD prophylaxis approaches to optimize survival of individual patients is not possible based on current evidence. We compared SIR/TAC (n=293) to MTX/TAC (n=414). The primary objective was to identify unique predictors of overall survival (OS). Secondary objective was to compare acute and chronic GvHD, relapse, non-relapse mortality, thrombotic microangiopathy (TMA), hepatic veno-occlusive disease (VOD/SOS), and acute kidney injury. Day 100 grades II-IV acute GvHD was significantly reduced in SIR/TAC vs MTX/TAC group (63 vs 73%, P=0.02). An interaction between GvHD prophylaxis groups and comorbidity index (hematopoietic cell transplantation (HCT)-CI) significantly impacted OS. Patients with HCT-CI' 3/44 had significantly worse OS with MTX/TAC (HR 1.86, 95% CI 1.14-3.04, P=0.01) while no such effect was seen for SIR/TAC (HR 0.78, 95% CI 0.48-1.26, P=0.31). Other end points did not significantly differ between groups except TMA and VOD/SOS were increased in the SIR/TAC group, but excess death from these complications was not observed. We conclude, GvHD prophylaxis approach of SIR/TAC is associated with reduced grades II-IV acute GvHD, comparable toxicity profile to MTX/TAC, and improved OS among patients with HCT-CI' 3/44.
AB - Sirolimus (SIR)/tacrolimus (TAC) is an alternative to methotrexate (MTX)/TAC. However, rational selection among these GvHD prophylaxis approaches to optimize survival of individual patients is not possible based on current evidence. We compared SIR/TAC (n=293) to MTX/TAC (n=414). The primary objective was to identify unique predictors of overall survival (OS). Secondary objective was to compare acute and chronic GvHD, relapse, non-relapse mortality, thrombotic microangiopathy (TMA), hepatic veno-occlusive disease (VOD/SOS), and acute kidney injury. Day 100 grades II-IV acute GvHD was significantly reduced in SIR/TAC vs MTX/TAC group (63 vs 73%, P=0.02). An interaction between GvHD prophylaxis groups and comorbidity index (hematopoietic cell transplantation (HCT)-CI) significantly impacted OS. Patients with HCT-CI' 3/44 had significantly worse OS with MTX/TAC (HR 1.86, 95% CI 1.14-3.04, P=0.01) while no such effect was seen for SIR/TAC (HR 0.78, 95% CI 0.48-1.26, P=0.31). Other end points did not significantly differ between groups except TMA and VOD/SOS were increased in the SIR/TAC group, but excess death from these complications was not observed. We conclude, GvHD prophylaxis approach of SIR/TAC is associated with reduced grades II-IV acute GvHD, comparable toxicity profile to MTX/TAC, and improved OS among patients with HCT-CI' 3/44.
UR - http://www.scopus.com/inward/record.url?scp=85016952022&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85016952022&partnerID=8YFLogxK
U2 - 10.1038/bmt.2017.63
DO - 10.1038/bmt.2017.63
M3 - Article
C2 - 28368376
AN - SCOPUS:85016952022
VL - 52
SP - 1003
EP - 1009
JO - Bone Marrow Transplantation
JF - Bone Marrow Transplantation
SN - 0268-3369
IS - 7
ER -