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 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.
Carnevale-Schianca
F
F
Clinical Research Division, Fred Hutchinson Cancer Research Center, University of Washington Schools of -Medicine, Seattle, 98109-1024, USA.
Martin
P
P
Sullivan
K
K
Flowers
M
M
Gooley
T
T
Anasetti
C
C
Deeg
J
J
Furlong
T
T
McSweeney
P
P
Storb
R
R
Nash
R A
RA
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D016572:Cyclosporine / Q000008:administration & dosage*; D005260:Female; D006086:Graft vs Host Disease / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D016879:Salvage Therapy; D016559:Tacrolimus / Q000008:administration & dosage*; D014184:Transplantation, Homologous / Q000009:adverse effects; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus