Phase III study comparing tacrolimus (FK506) with cyclosporine for graft-versus-host disease prophylaxis after allogeneic bone marrow transplantation.
We report the results of a phase III trial comparing tacrolimus (FK506) with cyclosporine for GVHD prophylaxis after allogeneic BMT. From February 1995 to July 1996, 136 patients were enrolled and followed up to September 1997. During the first 100 days post-transplant the incidence of grade II-IV acute GVHD (the primary end-point) was lower in the tacrolimus group (17.5%) compared with the cyclosporine group (48.0%, P < 0.0001). A significant difference was observed between the tacrolimus and cyclosporine groups when subset analyses were performed based on recipients from HLA-matched siblings (13.3% vs 41.3%, P = 0.015) or donors other than HLA-matched siblings (21.4% vs 53.8%, P= 0.0029). The incidence of chronic GVHD (47.3% and 47.8%) and Kaplan-Meier estimate of overall survival (62.9% and 65.2%) were similar between the tacrolimus and cyclosporine groups, respectively. The overall leukemia relapse rate was not significantly different between the tacrolimus and cyclosporine groups (19.6% and 11.4%, respectively). However, the relapse rate among recipients from HLA-matched siblings was significantly higher in the tacrolimus group (30.9%) compared with the cyclosporine group (3.6%, P = 0.013). These results suggest the merit of tacrolimus for the prophylaxis of acute GVHD, but a lack of merit for a graft-versus-leukemia effect among recipients from HLA-matched sibling donors.
Hiraoka
A
A
Fifth Department of Internal Medicine, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
Ohashi
Y
Y
Okamoto
S
S
Moriyama
Y
Y
Nagao
T
T
Kodera
Y
Y
Kanamaru
A
A
Dohy
H
H
Masaoka
T
T
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000401:mortality; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000517:prevention & control*; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015994:Incidence; D007938:Leukemia / Q000401:mortality / Q000628:therapy*; D008212:Lymphocyte Depletion; D008297:Male; D009679:Nuclear Family; D012008:Recurrence; D015996:Survival Rate; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus