Changing from Cyclosporine to Tacrolimus as Salvage Therapy for Chronic Graft-Versus-Host Disease

Fabrizio Carnevale-Schianca, Paul Martin, Keith Sullivan, Mary Flowers, Ted Gooley, Claudio Anasetti, Joachim Deeg, Terry Furlong, Peter McSweeney, Rainer Storb, Richard A. Nash

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)613-620
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume6
Issue number6
Publication statusPublished - 2000

Keywords

  • Allogeneic bone marrow transplantation
  • Chronic graft-versus-host disease
  • Corticosteroids
  • Refractory chronic graft-versus-host disease
  • Salvage therapy
  • Tacrolimus

ASJC Scopus subject areas

  • Transplantation

Fingerprint Dive into the research topics of 'Changing from Cyclosporine to Tacrolimus as Salvage Therapy for Chronic Graft-Versus-Host Disease'. Together they form a unique fingerprint.

  • Cite this

    Carnevale-Schianca, F., Martin, P., Sullivan, K., Flowers, M., Gooley, T., Anasetti, C., Deeg, J., Furlong, T., McSweeney, P., Storb, R., & Nash, R. A. (2000). Changing from Cyclosporine to Tacrolimus as Salvage Therapy for Chronic Graft-Versus-Host Disease. Biology of Blood and Marrow Transplantation, 6(6), 613-620.