Nonmyeloablative conditioning regimen including low dose total marrow/lymphoid irradiation before haploidentical transplant with post-transplantation cyclophosphamide in patients with advanced lymphoprolipherative diseases

Abstract Background Low dose total-body-irradiation (TBI) has been used in non-myeloablative (NMA) conditioning regimen before allogeneic-stem-cell-transplantation from haploidentical donors (haplo-SCT). More recently, total-marrow lymphoid-irradiation (TMLI) in place of TBI is under investigation. Objective Aim of this study was to evaluate the outcome in a cohort of patients treated with low dose TMLI in terms of engraftment, full donor chimerism status, graft versus host disease (GVHD), and extra-hematological toxicities. These results were compared with a cohort of patients receiving conventional TBI. Study Design This is a retrospective single centre study. One hundred patients with advanced hematological malignancies, received haploidentical transplantation. From 2009 and 2011, NMA conditioning regimen consisted of cyclophosphamide, fludarabine, and low dose TBI (2Gy), and from 2011 TBI was replaced by TMLI (2Gy). Patients received post-transplantation cyclophosphamide, calcineurin inhibitor and mycofenolate mofetil as graft versus host disease prophylaxis. Results For all patients, median time and 30-day incidence of absolute neutrophil recovery was 21 days (range 15-49), and 97% (95%CI 89-99); unsupported platelet count was 26 days (range12-67), and 60-day platelet engraftment was 99% (95%CI 89-100). Full donor chimerism was achieved in 95% of evaluable patients (range 27-109). Grade 2-4 acute GVHD occurred in 35% (95%CI 26-45) of patients at a median time of 40 days (range 23-166). Moderate-severe chronic GVHD was 5% (95%CI 2-10). No differences were recorded between TBI and TMLI cohort in terms of engraftment, full donor chimerism, and GVHD. No organs toxicity was observed in the first months after transplantation. Two-year-OS, and 2-year-PFS rates were 63%, and 54%, respectively, comparable in the two groups (p=0.548). Conclusions The strongest finding was that TBI can be safely replaced by TMLI in terms of engraftment, achievement of full donor chimerism status, GVHD incidence, and extra-hematological toxicities.