Comparative prognostic analysis of allogeneic hematopoietic stem cell transplantation regimens in the treatment of severe aplastic anemia.

BACKGROUND

Severe aplastic anemia (SAA) is a fatal bone marrow failure disorder. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the definitive curative treatment for SAA. This study evaluated the prognosis of patients with severe aplastic anemia (SAA) receiving different allo-HSCT regimens.

METHODS

A retrospective analysis was performed on 62 patients with aplastic anemia who underwent allo-HSCT between January 2015 and August 2024. The cohort comprised 32 males and 30 females, with a median age of 12 years (range, 1.5-44 years) at transplantation; 28 patients were ≥14 years old and 34 were <14 years. Forty-eight patients were diagnosed with severe AA (SAA) and 14 with very severe AA (VSAA). Twenty-two patients underwent HLA-matched sibling donor transplantation(MSD-HSCT), and 40 underwent HLA-haploidentical sibling donor transplantation(Haplo-HSCT).Three conditioning regimens were administered: cyclophosphamide plus anti-thymocyte globulin (CY+ATG, CA, n=11), fludarabine + cyclophosphamide + ATG (Flu+CY+ATG, FCA, n=26), and fludarabine + melphalan + ATG (Flu+Mel+ATG, FMA, n=25).

RESULTS

The median follow-up duration of the 62 patients was 38 months (range: 0-136 months). Twelve deaths occurred during follow-up. Post-transplant complications included post-transplant lymphoproliferative disorder (PTLD) in 3 patients (4.84%), acute graft-versus-host disease (aGVHD) in 7 patients (11.29%), chronic GVHD (cGVHD) in 2 patients (3.23%), Epstein-Barr virus (EBV) viremia in 10 patients (16.13%), and invasive fungal disease in 1 patient (1.62%). The median time to neutrophil engraftment was 13 days (evaluable in 55 patients). Kaplan-Meier survival analysis revealed no statistically significant difference in 5-year overall survival (OS) between MSD-HSCT and Haplo-HSCT groups (P = 0.582). The 5-year OS rate was 76.8% for the MSD-HSCT (n=22) and 80.6% for the Haplo-HSCT group (n=40). No significant intergroup difference in 5-year OS was detected across the three conditioning regimens (P = 0.85); the 5-year OS rates of the CA, FCA, and FMA groups were 81.6%, 76.8%, and 84.0%, respectively.

CONCLUSIONS

(1)MSD-HSCT and Haplo-HSCT yield comparable 5-year OS. Haploidentical related donors serve as a reliable alternative when fully matched donors are unavailable. (2) No statistically significant difference in 5-year overall survival (OS) was observed among the CA, FCA, and FMA conditioning regimens. (3) the FMA regimen may be considered as a favorable alternative to avoid the cyclophosphamide related toxicities.