66512
document
Tacrolimus/sirolimus vs tacrolimus/methotrexate as GVHD prophylaxis after matched , related donor allogeneic HCT . Grades 2-4 acute graft-versus-host disease ( GVHD ) occurs in approximately 35 % of matched , related donor ( MRD ) allogeneic hematopoietic cell transplantation ( HCT ) recipients . We sought to determine if the combination of tacrolimus and sirolimus ( Tac/Sir ) was more effective than tacrolimus and methotrexate ( Tac/Mtx ) in preventing acute GVHD and early mortality after allogeneic MRD HCT in a phase 3 , multicenter trial . The primary end point of the trial was to compare 114-day grades 2-4 acute GVHD-free survival using an intention-to-treat analysis of 304 randomized subjects . There was no difference in the probability of day 114 grades 2-4 acute GVHD-free survival ( 67 % vs 62 % , P = .38 ) . Grades 2-4 GVHD was similar in the Tac/Sir and Tac/Mtx arms ( 26 % vs 34 % , P = .48 ) . Neutrophil and platelet engraftment were more rapid in the Tac/Sir arm ( 14 vs 16 days , P < .001 ; 16 vs 19 days , P = .03 ) . Oropharyngeal mucositis was less severe in the Tac/Sir arm ( peak Oral Mucositis Assessment Scale score 0.70 vs 0.96 , P < .001 ) , but otherwise toxicity was similar . Chronic GVHD , relapse-free survival , and overall survival at 2 years were no different between study arms ( 53 % vs 45 % , P = .06 ; 53 % vs 54 % , P = .77 ; and 59 % vs 63 % , P = .36 ) . Based on similar long-term outcomes , more rapid engraftment , and less oropharyngeal mucositis , the combination of Tac/Sir is an acceptable alternative to Tac/Mtx after MRD HCT . This study was funded by the National Heart , Lung , and Blood Institute and the National Cancer Institute ; and the trial was registered at www.clinicaltrials.gov as # NCT00406393 .
66513
Intervention_Pharmacological
Tacrolimus/sirolimus vs tacrolimus/methotrexate
66514
Intervention_Pharmacological
tacrolimus and sirolimus ( Tac/Sir )
66515
Intervention_Pharmacological
tacrolimus and methotrexate ( Tac/Mtx )
66516
Outcome_Mortality
114-day grades 2-4 acute GVHD-free survival
66517
Outcome_Mortality
Grades 2-4 GVHD
66518
Outcome_Physical
Neutrophil and platelet engraftment
66519
Outcome_Physical
Oropharyngeal mucositis
66520
Outcome_Physical
Oral Mucositis Assessment Scale score
66521
Outcome_Adverse-effects
toxicity
66522
Outcome_Mortality
Chronic GVHD , relapse-free survival , and overall survival at 2 years
66523
Participant_Condition
donor allogeneic HCT
66524
Participant_Sample-size
304