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Sirolimus demonstrates activity in the primary therapy of acute graft-versus-host disease without systemic glucocorticoids

2011; Ferrata Storti Foundation; Volume: 96; Issue: 9 Linguagem: Inglês

10.3324/haematol.2011.041236

1592-8721

Joseph Pidala, Marcie Tomblyn, T. Nishihori, Teresa Field, Ernesto Ayala, Janelle Perkins, Hugo F. Fernández, Frederick L. Locke, L. Perez, J. L. Ochoa, Melissa Alsina, Claudio Anasetti,

Renal Transplantation Outcomes and Treatments

Advances in acute graft-versus-host disease therapy are needed.We examined the efficacy of sirolimus as primary therapy for acute graft-versus-host disease in 32 patients.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.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.