title: Predictors of overall survival among patients treated with sirolimus/tacrolimus vs methotrexate/tacrolimus for GvHD prevention.
abstract: 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⩾4 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⩾4.
authors.affiliation: Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: F
authors.initials: F
authors.lastname: Khimani
authors.affiliation: Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Medicine, University of South Florida, Tampa, FL, USA.
authors.forename: E
authors.initials: E
authors.lastname: Dean
authors.affiliation: Division of Hematology and Medical Oncology, University of South Florida, Tampa, FL, USA.
authors.forename: V
authors.initials: V
authors.lastname: Rizk
authors.affiliation: Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: B
authors.identifier: http://orcid.org/0000-0001-7643-2422
authors.initials: B
authors.lastname: Betts
authors.affiliation: Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: T
authors.identifier: http://orcid.org/0000-0002-2621-7924
authors.initials: T
authors.lastname: Nishihori
authors.affiliation: Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: F
authors.initials: F
authors.lastname: Locke
authors.affiliation: Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: A
authors.initials: A
authors.lastname: Mishra
authors.affiliation: Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: L
authors.initials: L
authors.lastname: Perez
authors.affiliation: Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: E
authors.initials: E
authors.lastname: Ayala
authors.affiliation: Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: M
authors.initials: M
authors.lastname: Kharfan-Dabaja
authors.affiliation: Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: M
authors.initials: M
authors.lastname: Nieder
authors.affiliation: Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: H
authors.initials: H
authors.lastname: Fernandez
authors.affiliation: Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: C
authors.initials: C
authors.lastname: Anasetti
authors.affiliation: Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: J
authors.initials: J
authors.lastname: Pidala
mesh_terms: D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000401:mortality* / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D020123:Sirolimus / Q000008:administration & dosage* / Q000009:adverse effects; D015996:Survival Rate; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D020123:Sirolimus; D016559:Tacrolimus; D008727:Methotrexate