The Effect of the Order of Total Body Irradiation and Chemotherapy on Graft-Versus-Host Disease

BACKGROUND: Graft-versus-host disease (GVHD) is one of the most important complications in allogeneic hematopoietic stem cell transplantation. Intensity of conditioning regimen is one of the risk factors, which is associated with acute GVHD, and some studies have shown that alteration of the administration order from busulfan to cyclophosphamide to cyclophosphamide to busulfan could decrease cytokine levels and organ toxicity. METHODS: To investigate whether the order of total body irradiation (TBI) and chemotherapy is associated with the incidence of GVHD, we reviewed the charts of 124 consecutive hematopoietic stem cell transplantation, which was performed in Saitama Children's Medical Centre and University of Tokyo Hospital between 1995 and 2010. RESULTS: TBI performed before chemotherapy (TBI-CT) showed an increased risk for grades II to IV acute GVHD (61.6±7.8%) compared with the TBI performed after chemotherapy (CT-TBI) (42.8±7.2%) (P=0.048), whereas the incidence of grades III and IV GVHD were similar between TBI-CT and CT-TBI. Multivariate analysis showed that TBI-CT was associated with a higher risk of grades II to IV acute GVHD. However, overall survival probability of TBI-CT cohort was similar to that of CT-TBI cohort. CONCLUSIONS: Our results provided a novel risk factor for acute GVHD, which can be easily controlled by the physician.