Changing from cyclosporine to tacrolimus as salvage therapy for chronic graft-versus-host disease.

Journal Article (Clinical Trial;Journal Article)

Chronic graft-versus-host disease (GVHD) is the principal cause of transplantation-related morbidity and nonrelapse mortality late after allogeneic hematopoietic stem cell transplantation. The safety and potential efficacy of tacrolimus for the salvage treatment of chronic GVHD was evaluated in a single-arm, open-label phase 2 study. A total of 39 evaluable patients with chronic GVHD who failed previous immunosuppressive therapy with cyclosporine and prednisone were treated with tacrolimus starting at a median of 20 months (range, 3-68 months) after transplantation. At 3 years after the start of treatment, 5 patients (13%) had discontinued tacrolimus and were in complete remission, and 3 were considered clinically stable but not able to discontinue tacrolimus. A total of 31 patients (79%) experienced treatment failure; 22 (56%) who failed therapy had a change in immunosuppressive regimen because of progression (n = 18) or toxicity (n = 4). Nine patients (23%) died during continued treatment with tacrolimus. Two patients were lost to follow-up, at 11 and 19 months. The median duration of treatment with tacrolimus was 9 months (range, 1-29 months). Infections (144 episodes) were the most frequent adverse event. Nephrotoxicity occurred in 16 patients (41%); tacrolimus was discontinued in only 2 patients because of progressive deterioration in renal function. The Kaplan-Meier estimate of survival was 64% (95% confidence interval, 49%-79%) at 3 years posttransplantation. Seven patients had discontinued all immunosuppression at last contact, leading to an estimated 29% probability of stopping all immunosuppression by 3 years posttransplantation. Four patients died after relapse of malignancy. The response rate is consistent with previous reports of salvage treatment for chronic GVHD, indicating that a small group of patients failing cyclosporine may respond or stabilize with tacrolimus.

Full Text

Duke Authors

Cited Authors

  • Carnevale-Schianca, F; Martin, P; Sullivan, K; Flowers, M; Gooley, T; Anasetti, C; Deeg, J; Furlong, T; McSweeney, P; Storb, R; Nash, RA

Published Date

  • 2000

Published In

Volume / Issue

  • 6 / 6

Start / End Page

  • 613 - 620

PubMed ID

  • 11128811

International Standard Serial Number (ISSN)

  • 1083-8791

Digital Object Identifier (DOI)

  • 10.1016/s1083-8791(00)70026-7


  • eng

Conference Location

  • United States