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

Chronic graft-versus-host disease (GVHD) is the principal cause of transpla ntation-related morbidity and nonrelapse mortality late after allogeneic he matopoietic stem cell transplantation. The safety and potential efficacy of tacrolimus for the salvage treatment of chronic GVHD was evaluated in a si ngle-arm, open-label phase 2 study. A total of 39 evaluable patients with c hronic GVHD who failed previous immunosuppressive therapy with cyclosporine and prednisone were treated with tacrolimus starting at a median of 20 mon ths (range, 3-68 months) after transplantation. At 3 years after the start of treatment, 5 patients (13%) had discontinued tacrolimus and were in comp lete remission, and 3 were considered clinically stable but not able to dis continue tacrolimus. A total of 31 patients (79%) experienced treatment fai lure; 22 (56%) who failed therapy had a change in immunosuppressive regimen because of progression (n = 18) or toxicity (n = 4). Nine patients (23%) d ied during continued treatment with tacrolimus. Two patients were lost to f ollow-up, at 11 and 19 months. The median duration of treatment with tacrol imus 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 deter ioration in renal function. The Kaplan-Meier estimate of survival was 64% ( 95% confidence interval, 49%-79%) at 3 years posttransplantation. Seven pat ients had discontinued all immunosuppression at last contact, leading to an estimated 29% probability of stopping all immunosuppression by 3 years pos ttransplantation. Four patients died after relapse of malignancy. The respo nse rate is consistent with previous reports of salvage treatment for chron ic GVHD, indicating that a small group of patients failing cyclosporine may respond or stabilize with tacrolimus.