title: Tacrolimus/sirolimus vs tacrolimus/methotrexate as GVHD prophylaxis after matched, related donor allogeneic HCT.
abstract: 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.
authors: Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA;
authors: Corey
authors: C
authors: Cutler
authors: Medical College of Wisconsin, Milwaukee, WI;
authors: Brent
authors: B
authors: Logan
authors: City of Hope Medical Center, Duarte, CA;
authors: Ryotaro
authors: R
authors: Nakamura
authors: Stanford University, Stanford, CA;
authors: Laura
authors: L
authors: Johnston
authors: University of Michigan, Ann Arbor, MI;
authors: Sung
authors: S
authors: Choi
authors: University of Pennsylvania, Philadelphia, PA;
authors: David
authors: D
authors: Porter
authors: Mayo Clinic, Rochester, MN;
authors: William J
authors: WJ
authors: Hogan
authors: Medical College of Wisconsin, Milwaukee, WI;
authors: Marcelo
authors: M
authors: Pasquini
authors: University of Minnesota Medical School, Minneapolis, MN;
authors: Margaret L
authors: ML
authors: MacMillan
authors: University of Florida, Gainesville, FL;
authors: Jack W
authors: JW
authors: Hsu
authors: Winship Cancer Institute, Emory University, Atlanta, GA;
authors: Edmund K
authors: EK
authors: Waller
authors: The Children's Hospital of Philadelphia, Philadelphia, PA;
authors: Stephan
authors: S
authors: Grupp
authors: Roswell Park Cancer Institute, Buffalo, NY; and.
authors: Philip
authors: P
authors: McCarthy
authors: The EMMES Corporation, Rockville, MD.
authors: Juan
authors: J
authors: Wu
authors: Medical College of Wisconsin, Milwaukee, WI;
authors: Zhen-Huan
authors: ZH
authors: Hu
authors: The EMMES Corporation, Rockville, MD.
authors: Shelly L
authors: SL
authors: Carter
authors: Medical College of Wisconsin, Milwaukee, WI;
authors: Mary M
authors: MM
authors: Horowitz
authors: Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA;
authors: Joseph H
authors: JH
authors: Antin
mesh_terms: D000293:Adolescent; D000328:Adult; D064591:Allografts; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000401:mortality / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D020123:Sirolimus / Q000008:administration & dosage*; D013280:Stomatitis / Q000401:mortality / Q000517:prevention & control; D015996:Survival Rate; D016559:Tacrolimus / Q000008:administration & dosage*; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus; D016559:Tacrolimus; D008727:Methotrexate