A Retrospective Comparison of Tacrolimus Vs. Cyclosporine for Immunosuppression After Allogeneic Hematopoietic Cell Transplantation with G-CSF-Mobilized Blood Cells

Graft-versus-host disease (GVHD) is a common immunologic complication after allogeneic hematopoietic cell transplantation (HCT). Cyclosporine or tacrolimus in combination with other agents represent widely accepted standards of care as immunosuppressive regimens after HCT. Results of open-label randomized prospective phase III studies have indicated that the risk of grades II-IV acute GVHD after bone marrow transplantation with related or unrelated donors is lower with the use of tacrolimus as compared to cyclosporine, in combination with methotrexate. The current study was carried out to compare results with tacrolimus versus cyclosporine after HCT with G-CSF-mobilized blood cells.

The study cohort included 510 consecutive patients who received a first G-CSF-mobilized blood cell graft from related or unrelated donors after high-intensity conditioning for treatment of hematological malignancies between 7/1/2003 and 2009 at our center. All patients received ursodeoxycholic acid from 2 weeks before conditioning until 90 days after HCT to prevent hepatic complications, and all patients received immunosuppression with either tacrolimus or cyclosporine in combination with methotrexate after HCT. Endpoints included grades II-IV acute GVHD, grades III-IV acute GVHD, chronic GVHD, end of treatment for chronic GVHD, overall survival, disease-free survival, recurrent malignancy and nonrelapse mortality. Multivariate Cox regression models were used to evaluate hazard ratios for these endpoints with tacrolimus as compared to cyclosporine. The models were adjusted for patient age, donor type, recipient and donor gender combination, disease type, disease risk category, use of total body irradiation in the conditioning regimen, and year of HCT. The analysis was carried out as of July, 2010.

The median age of patients was 47 (range, 1 to 66) years. Diagnosis at HCT was acute myeloid leukemia in 200 (39%) patients, acute lymphoblastic leukemia in 73 (14%), chronic myeloid leukemia in 49 (10%), myelodysplastic syndrome or myeloproliferative disorders in 160 (31%) and other lymphoid malignancies in 28 (5%). Total body irradiation was used for conditioning in 168 (33%) patients. Of the 510 patients, 277 (54%) had HLA-matched related donors, 203 (40%) had HLA-matched unrelated donors, and 30 (6%) had HLA-mismatched related or unrelated donors. Outcomes according to immunosuppression with tacrolimus or cyclosporine are shown in Table 1. Multivariate analysis showed no statistically significant differences between tacrolimus and cyclosporine for any of the endpoints tested (Table 2), although the results showed a trend suggesting that the risk of non-relapse mortality might be lower with tacrolimus as compared to cyclosporine.

In this retrospective analysis, tacrolimus offered no statistically significant advantage over cyclosporine for preventing grades II-IV acute GVHD after HCT with G-CSF-mobilized blood cells, and results for other outcomes also showed no statistically significant differences. Although our data support the hypothesis that either regimen could be an acceptable standard of care for immunosuppression, the number of patients analyzed in this study is not sufficient to completely exclude clinically meaningful differences in outcomes with the two regimens.

Off Label Use: Tacrolimus and cyclosporine for immunosuppression after allogeneic hematopoietic cell transplantation.