Sequence matters: Total body irradiation (TBI)‐based myeloablative conditioning with post‐transplant cyclophosphamide may reduce the early nonrelapse mortality compared with pretransplant cyclophosphamide plus TBI

Abstract

Objectives High‐dose total body irradiation (TBI) is considered a cornerstone of myeloablative conditioning for allogeneic stem cell transplantation (allo‐SCT). We retrospectively compared the main outcomes of an HLA matched or 1‐allele mismatched related or unrelated allo‐SCT in adult patients affected by acute leukemia (AL) or myelodysplastic syndromes (MDS). Methods Fifty‐nine patients received cyclophosphamide (Cy)‐TBI (13.5 Gy) and graft‐versus‐host disease (GVHD) prophylaxis with a calcineurin‐inhibitor plus methrotrexate (CyTBI group) and 28 patients received fludarabine‐TBI (8.8–13.5 Gy) and GVHD prophylaxis with PTCy and tacrolimus (FluTBI‐PTCy group). Results Median follow‐up for survivors was 82 and 22 months. The 12‐month probability of overall survival and progression‐free survival were similar (p = .18, p = .7). The incidence of Grades 2–4 and 3–4 acute GVHD, and the incidence of moderate‐to‐severe chronic GVHD were higher in the CyTBI group (p = .02, p < .01and p = .03). Nonrelapse mortality (NRM) at 12 months posttransplant was higher in the CyTBI group (p = 0.05), while the incidence of relapse was similar in both groups (p = 0.7). The number of GVHD‐free and relapse‐free patients without systemic immunosuppression (GRFS) at 1‐year posttransplant was higher in the FluTBI‐PTCy group (p = 0.01). Conclusions The study confirms the safety and efficacy of a novel FluTBI‐PTCy platform with reduced incidence of severe acute and chronic GVHD, and early improvement of NRM.