Conditioning Regimens for Second Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Primary Graft Failure

Abstract

Primary graft failure (PGF) is a life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT). The optimal conditioning strategies for salvage HSCT in PGF remain undefined. We retrospectively analyzed the outcomes of 19 patients with PGF who underwent a second HSCT between 2017 and 2024. Eleven patients (58%) received a novel 1-day conditioning regimen comprising fludarabine, cyclophosphamide, alemtuzumab, and low-dose total body irradiation (TBI) (Group I), while eight received a multi-day reduced-intensity conditioning regimen (fludarabine-busulfan-2 Gy TBI) (Group II). All patients in Group I engrafted neutrophils compared to 50% in Group II. The cumulative incidence of neutrophil engraftment at day +28 was 82% in Group I and 50% in Group II (P = .22). Platelet engraftment by day +28 was observed in 70% of patients in Group I and 54% in Group II (P = .61). The median follow-up of survivors after second HSCT was 16.5 months (95% CI: 5.9 to 39). The 12-month overall survival (OS) was 53.3% in Group I and 37.5% in Group II (P = .29). The day +100 non-relapse mortality (NRM) was 30.3% in Group I and 62.5% in Group II (P = .12). No patients developed grade III to IV acute graft-versus-host disease (GvHD) or chronic GvHD. A 1-day alemtuzumab-based conditioning regimen for salvage HSCT appears to be well tolerated and may be associated with improved engraftment, NRM, and OS when compared to the fludarabine-busulfan-2 Gy TBI regimen.

Keywords: Alemtuzumab; Conditioning regimen; Non-relapse mortality; Primary graft failure; Second allogeneic stem cell transplant.