Feasibility of a Total Body Irradiation-Augmented Reduced-Toxicity Conditioning Regimen with an Antithymocyte Globulin/Post-Transplantation Cyclophosphamide Combination for Haploidentical Donor Transplantation in Adult Acute Lymphoblastic Leukemia

Haploidentical donor transplantation (HIDT) with post-transplantation cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis is a promising alternative donor option for adults with high-risk acute lymphoblastic leukemia (ALL). The optimal conditioning regimen and GVHD prophylaxis strategy in this patient population remain unclear, however. We evaluated a newly optimized reduced-toxicity conditioning regimen consisting of fludarabine 150 mg/m², melphalan 100 mg/m², and low-dose (400 cGy) total body irradiation (FMTBI) with GVHD prophylaxis using an antithymocyte globulin (ATG)/PTCy combination in 26 adult patients with ALL undergoing HIDT. We compared the recipients of the new regimen to 52 historical controls who received fludarabine 150 mg/m² plus busulfan 9.6 mg/kg (FB group) with ATG. Key endpoints included disease-free survival (DFS), overall survival (OS), GVHD-and relapse-free survival (GRFS), relapse, nonrelapse mortality (NRM), and post-transplantation immune reconstitution. At 1 year post-transplantation, the FMTBI group had higher DFS (80.4% versus 51.9%; P = .024) and a trend toward improved GRFS (61.0% versus 34.6%; P = .073). Relapse incidence was slightly lower (11.9% versus 32.7%; P = .059) in the FMTBI group, particularly in the central nervous system. The cumulative incidence of moderate to severe chronic GVHD was lower (0.0% versus 11.5%; P = .074) in the FMTBI group. The rates of OS (82.9% versus 78.8%; P = .465) and NRM (7.7% versus 15.4%; P = .342) were similar in the 2 groups. Natural killer/natural killer T cell recovery was transiently delayed at 3 months after the FMTBI regimen but normalized by 6 months. Compared to the historical FB with ATG alone group, our newly optimized FMTBI and ATG/PTCy combination showed improved DFS and relapse control while reducing chronic GVHD in HIDT for adult ALL.