Survival, disease-free survival and adverse effects of conditioning for allogeneic bone marrow transplantation with busulfan/cyclophosphamide vs total body irradiation: a meta-analysis

Abstract

Randomized, prospective studies comparing BUCY to TBI conditioning regimens for allogeneic bone marrow transplantation have yielded conflicting results. We investigated the overall survival, the disease-free survival and the toxicities of BUCY vs TBI-based regimens by conducting a meta-analysis of all published, randomized, prospective trials comparing these regimens. Five studies were analyzed. We evaluated six endpoints: survival, disease-free survival, veno-occlusive disease (VOD) of the liver, acute GVHD, chronic GVHD, and interstitial pneumonitis. We combined individual study results using a random effects model. Survival and disease-free survival were better with TBI-based regimens than with BUCY, but these differences were not statistically significant (survival odds ratio 1.4, 95% confidence interval 0.9-2.2, P = 0.09; disease-free survival odds ratio 1.2, 95% confidence interval 0.7-2.1, P = 0.44). A power analysis indicated that BUCY was unlikely to have a clinically relevant survival or disease-free survival advantage. The power analysis could not exclude the possibility of such an advantage for TBI-based regimens. A significantly greater incidence of VOD occurred with BUCY (odds ratio 2.5, 95% confidence interval 1.2-5.2, P = 0.02). For the other side-effects, there were no significant differences. We concluded that TBI-based regimens cause less VOD than BUCY and are at least as good for survival and disease-free survival.