Comparison of Tacrolimus and Cyclosporine Combined With Methotrexate for Graft Versus Host Disease Prophylaxis After Allogeneic Hematopoietic Cell Transplantation

BACKGROUND: After patients receive hematopoietic stem cell transplantation (HSCT), both cyclosporine (CsA) and tacrolimus (TAC) in combination with methotrexate (MTX) are recommended as the standard prophylaxis strategy for graft versus host disease (GVHD) by the European Group of Blood and Marrow Transplantation. However, the advantage of TAC combined with MTX lacks conclusive evidence.

METHODS: We searched online databases for studies comparing CsA + MTX and TAC + MTX in patients who received HSCT. The odds ratio (OR) and 95% confidence interval (CI) were applied to compare the pooled data.

RESULTS: We found a significant reduction in the grade II to IV acute GVHD (aGVHD) rate (OR, 0.42; CI, 0.28-0.61; P < 0.00001), grade III to IV aGVHD rate (OR, 0.59; CI, 0.38-0.92; P = 0.02), chronic GVHD rate (OR, 0.79; CI, 0.62-1.00; P = 0.05), and nonrelapse mortality rate (OR, 0.62; CI, 0.40-0.95; P = 0.03) and an increase in the overall survival (OS) rate (only in those received from unrelated donor) (OR, 1.30; CI, 1.15-1.48; P < 0.0001) in the TAC + MTX group. Similar outcomes occurred for the relapse rate and disease-free survival rate in both groups.

CONCLUSIONS: TAC + MTX has a superior effect in the prevention of aGVHD in patients who received HSCT and further prolongs the OS in patients who received from unrelated donor transplants. CsA + MTX prolongs the OS in patients who received HSCT from HLA-identical sibling donors. The leukemic relapse and disease-free survival rate were not different between the 2 regimens. Thus, we conclude that TAC + MTX was superior to CsA + MTX, especially for HSCT patients with nonmalignant disorders. Further studies are still required to evaluate the effect of TAC or CsA combined with other suppressors in the treatment regimen following HSCT.