Conditioning regimens for second allogeneic hematopoietic stem cell transplantation for patients with primary graft failure.

Background: 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.

Objective: We retrospectively analysed the outcomes of 19 patients with PGF who underwent a second HSCT between 2017 and 2024. Eleven patients (58%) received a novel one-day conditioning regimen comprising fludarabine, cyclophosphamide, alemtuzumab, and low-dose total body irradiation (Group I), while eight received a multi-day reduced intensity conditioning regimen (fludarabine-busulfan-2Gy total body irradiation) (Group II).

Results: 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=0.22). Platelet engraftment by day +28 was observed in 70% of patients in Group I and 54% in Group II (p=0.61). The median follow-up of survivors after second HSCT was 16.5 months (95% CI: 5.9-39). The 12-month overall survival (OS) was 53.3% in Group I and 37.5% in Group II (p=0.29). The day +100 non-relapse mortality (NRM) was 30.3% in Group I and 62.5% in Group II (p=0.12). No patients developed grade III-IV acute graft-versus-host disease (GvHD) or chronic GvHD.

Conclusions: A one-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-2Gy total body irradiation regimen.