Impact of immune modulation with in vivo T cell depletion and myleoablative total body irradiation conditioning regimen on outcomes after unrelated donor transplantation for acute lymphoblastic leukemia in children.

Keywords:

Abstract:

To determine whether in vivo T cell depletion, which lowers graft-versus-host disease (GVHD), abrogates the anti-leukaemic benefits of myeloablative TBI-based conditioning and unrelated donor transplantation, we analyzed 715 children with acute lymphoblastic leukemia (ALL). Patients were grouped for analysis according to whether conditioning included ATG (n=191) or alemtuzumab (n=132) and no in vivo T-cell depletion (n=392). The median follow-up of patients is 3.5 years for the ATG group and 5-years for alemtuzumab and T-cell replete groups. Using Cox regression analysis we compared transplantation outcomes between groups. Compared to no T-cell depletion, grade 2-4 acute and chronic GVHD rates were significantly lower after in vivo T cell depletion with ATG (RR 0.66, p=0.005; RR 0.55, p<0.0001,) or alemtuzumab (RR 0.09, p<0.003; RR 0.21, p<0.0001). Despite lower GVHD rates after in vivo T-cell depletion non-relapse mortality, relapse, overall and leukemia-free survival (LFS) did not differ significantly among the treatment groups. The 3-year probabilities of LFS after ATG-containing, alemtuzumab-containing and T-cell replete transplantations were 43%, 49% and 46%, respectively. These data suggest that in vivo T cell depletion lowers GVHD without compromising LFS among children with ALL who are undergoing unrelated donor transplantation with myeloablative TBI-based containing regimens.