Bone marrow graft as a source of allogeneic hematopoietic stem cells in patients undergoing a reduced intensity conditioning regimen

Abstract

In an attempt to reduce the incidence of chronic GVHD (cGVHD) after reduced-intensity conditioning (RIC), we used BM instead of PBSC and added melphalan 100 mg/m(2) to the classical association of fludarabine, 30 mg/m(2)/day for 3 days and TBI, 200 cGy (FLUIM regimen). Between 2000 and 2012, 51 patients received BM with the FLUIM regimen (group A), and 124 received BM (n=22) or PBSC (n=102) with another RIC regimen (group B). Donors were siblings (n=123) or HLA-matched 10/10 unrelated (n=52). Full donor-type chimerism at day 100 was more often recorded in group A (86%) than in group B (62%); P<0.001. There was no difference between the two groups in terms of OS and EFS, acute GVHD, relapse and non-relapse mortality incidence. cGVHD occurred more often in group B (41%) than in group A (23%); P=0.021. In multivariate analysis, the two risk factors associated with the development of cGVHD were conditioning in group B (hazard ratio (HR)=2.871, 95% confidence interval (CI) (1.372-6.006); P=0.005) and CD34(+) count (HR=1.009, 95% CI (1.006-1.011); P<0.001). In conclusion, the FLUIM regimen followed by BM leads to more frequent full-donor chimerism and a reduced incidence of cGVHD without compromising relapse and survival.