Effect of Haplo-Allogeneic Hematopoietic Stem Cell Transplantation Timing on Patients with Severe Aplastic Anemia Without Histocompatible Matched Sibling Donor.

Abstract

Background: Comparative studies on frontline haploidentical HSCT (haplo-HSCT) versus salvage haplo-HSCT after immunosuppressive therapy (IST) failure in severe aplastic anemia (SAA) are limited. To evaluate the effects of different transplantation timing on patient survival, the incidence of graft-versus-host disease (GVHD), and the risk of infection on the outcomes of patients with SAA.

Methods: This retrospective study included 82 SAA patients who underwent haplo-HSCT using the "Beijing protocol". Patients who underwent allogeneic HSCT within 3 months after diagnosis were in the first-line HSCT group, and patients who were treated with initial IST and followed with allogeneic HSCT after treatment failure or relapse were in the salvage HSCT group. Patients were categorized into the frontline HSCT group (n=40, 48.8%) and the salvage HSCT group (n=42, 51.2%) based on transplantation timing. All 82 patients received grafts from related haploidentical donors. Follow-up was until January 1, 2024, and all patients were followed for more than 12 months with a median follow-up of 49 (12-126) months, except for dead cases.

Results: Multivariate analysis identified salvage HSCT (HR: 5.344, 95% CI: 1.904-14.995), ferritin levels >1000 (HR: 5.588, 95% CI: 1.696-18.414), and CMV infection (HR: 11.909, 95% CI: 2.335-60.725) as independent risk factors for graft failure. The overall survival rate was significantly higher in the front HSCT group (90%, 36/40) compared to the salvage HSCT group (71.4%, 30/42) with mortality rates of 10.0% (4/40) and 28.6% (12/42), respectively (p=0.029). The expected 5-year OS was significantly higher in the frontline HSCT group compared to the salvage group. Salvage HSCT, ECOG score ≥1, and ferritin levels >1000 were identified as independent risk factors for prognosis.

Conclusion: Frontline haplo-HSCT demonstrates superior survival and safety compared to salvage haplo-HSCT in young SAA patients without a matched sibling donor, warranting further clinical adoption.