BACKGROUND: Advances in acute graft-versus-host disease therapy are needed. DESIGN AND METHODS: We examined the efficacy of sirolimus as primary therapy for acute graft-versus-host disease in 32 patients. RESULTS: Acute graft-versus-host disease involved the skin in 53% of cases, gastrointestinal tract in 66%, liver in 16%. The syndrome was overall grade 1 in 12% cases, grade 2 in 75%, and grade 3 in 13%. Sirolimus was targeted to achieve serum trough levels of 5-14 ng/mL. Sixteen (50%) patients achieved sustained, complete resolution of acute graft-versus-host disease with sirolimus alone. In contrast, 19 of 32 (59%) matched historical controls treated with standard 1 mg/kg steroids achieved complete response (P=0.47). With median follow-up time for surviving patients of 16 (range 6-26) months, one year overall survival was 56% (95% CI 38-74%). The cumulative incidence of relapse at one year was 37% (95% CI 23-60%), and mortality in remission was 20% (95% CI 10-42%). The cumulative incidence of chronic graft-versus-host disease was 55% (95% CI 39-79%). Thrombotic microangiopathy occurred in 3 cases (grade 1 n=1; grade 2 n=2), and responded to dose reduction of calcineurin inhibitor. CONCLUSIONS: In this retrospective series, sirolimus demonstrates activity comparable to that of high-dose glucocorticoids in the primary therapy of acute graft-versus-host disease. Confirmation of this activity requires prospective clinical trials.
BACKGROUND: Advances in acute graft-versus-host disease therapy are needed. DESIGN AND METHODS: We examined the efficacy of sirolimus as primary therapy for acute graft-versus-host disease in 32 patients. RESULTS: Acute graft-versus-host disease involved the skin in 53% of cases, gastrointestinal tract in 66%, liver in 16%. The syndrome was overall grade 1 in 12% cases, grade 2 in 75%, and grade 3 in 13%. Sirolimus was targeted to achieve serum trough levels of 5-14 ng/mL. Sixteen (50%) patients achieved sustained, complete resolution of acute graft-versus-host disease with sirolimus alone. In contrast, 19 of 32 (59%) matched historical controls treated with standard 1 mg/kg steroids achieved complete response (P=0.47). With median follow-up time for surviving patients of 16 (range 6-26) months, one year overall survival was 56% (95% CI 38-74%). The cumulative incidence of relapse at one year was 37% (95% CI 23-60%), and mortality in remission was 20% (95% CI 10-42%). The cumulative incidence of chronic graft-versus-host disease was 55% (95% CI 39-79%). Thrombotic microangiopathy occurred in 3 cases (grade 1 n=1; grade 2 n=2), and responded to dose reduction of calcineurin inhibitor. CONCLUSIONS: In this retrospective series, sirolimus demonstrates activity comparable to that of high-dose glucocorticoids in the primary therapy of acute graft-versus-host disease. Confirmation of this activity requires prospective clinical trials.
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Authors: P J Martin; G Schoch; L Fisher; V Byers; C Anasetti; F R Appelbaum; P G Beatty; K Doney; G B McDonald; J E Sanders Journal: Blood Date: 1990-10-15 Impact factor: 22.113
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Authors: Joseph Pidala; Mehdi Hamadani; Peter Dawson; Michael Martens; Amin M Alousi; Madan Jagasia; Yvonne A Efebera; Saurabh Chhabra; Iskra Pusic; Shernan G Holtan; James L M Ferrara; John E Levine; Marco Mielcarek; Claudio Anasetti; Joseph H Antin; Javier Bolaños-Meade; Alan Howard; Brent R Logan; Eric S Leifer; Theresa S Pritchard; Mary M Horowitz; Margaret L MacMillan Journal: Blood Date: 2020-01-09 Impact factor: 22.113
Authors: Paul J Martin; Stephanie J Lee; Donna Przepiorka; Mary M Horowitz; John Koreth; Georgia B Vogelsang; Irwin Walker; Paul A Carpenter; Linda M Griffith; Gorgun Akpek; Mohamad Mohty; Daniel Wolff; Steven Z Pavletic; Corey S Cutler Journal: Biol Blood Marrow Transplant Date: 2015-05-15 Impact factor: 5.742