Randomized study of 2 reduced‐intensity conditioning strategies for human leukocyte antigen‐matched, related allogeneic peripheral blood stem cell transplantation

BACKGROUND: The optimal intensity of reduced‐intensity conditioning (RIC) before allogeneic hematopoietic stem cell transplantation (allo‐HSCT) remains uncertain. METHODS: In this centrally randomized phase 2 study, the authors compared 2 different strategies of RIC. In total, 139 patients (median age, 54 years; range, 21‐65 years) with hematologic malignancies underwent allo‐HSCT from a human leukocyte antigen‐identical sibling after conditioning combining fludarabine with either busulfan and rabbit antithymocyte‐globulin (BU‐rATG) (n = 69) or total body irradiation (TBI) (n = 70). Postgraft immunosuppression consisted of cyclosporin A in all patients with the addition of mycophenolate‐mophetil after TBI. RESULTS: The median follow‐up was 54 months (range, 26‐88 months). One‐year overall survival rate was identical in both groups. Four patients experienced graft‐failure after TBI. The incidence of grade 2 through 4 acute graft‐versus‐host‐disease was greater after BU‐rATG than after TBI (47% vs 27%; P = .01), whereas no difference was observed with chronic graft‐versus‐host‐disease. The BU‐rATG group had a higher objective response rate (65% vs 46%; P = .05) and a lower relapse rate (27% vs 54%; P < .01). However, the nonrelapse mortality rate was higher after BU‐rATG than after TBI (38% vs 22%; P = .027). At 5 years, the overall and progression‐free survival rates were 41% and 29%, respectively, and did not differ statistically between groups. A detrimental effect on some parameters of quality of life was more pronounced after BU‐rATG, but recovery was identical in both groups. The mean total cost per patient, including the cost to treat disease progression post‐transplantation, did not differ statistically between groups. CONCLUSIONS: Five years after transplantation, the BU‐rATG regimen was associated with greater disease control. However, because of the higher nonrelapse mortality rate, this did not translate into better overall or progression‐free survival. Cancer 2013. © 2012 American Cancer Society. The authors present the results from a randomized phase 2 study comparing 2 reduced‐intensity conditioning strategies with different intensity levels. The more intensive strategy is associated with better disease control but higher nonrelapse mortality.