Comparison of Hematopoietic Stem Cell Transplantation and Repeated Immunosuppressive Therapy As Second-Line Treatment for Relapsed/Refractory Severe Aplastic Anemia

The optimal treatment for patients with severe aplastic anemia (SAA) who fail or have relapse after an initial course of immunosuppressive therapy (IST) has not been established. We conducted a retrospective study to compare the effectiveness of allogeneic hematopoietic stem cell transplantation (allo-HSCT) (n = 36) with repeated IST (n = 33) as salvage therapy for relapsed/refractory SAA between 2007 and 2022. In the repeated IST group, patients were treated with antithymocyte globulin (ATG) (n = 16) or high-dose cyclophosphamide (HD-CTX) (n = 17). The overall response rate was 42.4% at 6 months, and 60.6% at 12 months. In the HSCT group, 6 were matched sibling donor (MSD), 7 were matched unrelated donor (MUD), and 23 were haploidentical donor (HID). All patients achieved neutrophil engraftment and no primary graft failure was observed. The rate of platelet engraftment was 88.9%, with a median time of 16 days. The cumulative incidences of grade II-IV, III-IV acute GVHD was 36.1% ± 0.7%, 13.9% ± 0.3% at day +100, and chronic GVHD was 36.2% ± 0.7% at 5 years. Compared with IST, HSCT recipients showed much higher hematologic recovery rate at 3-, 6- and 12-months post treatment (63.9%, 83.3% and 86.1%, respectively, P < 0.001). The estimated 5-year overall survival (OS) (79.8% ± 6.8% vs. 80.0% ± 7.3%, p = 0.957) were similar; however, the estimated 5-year failure-free survival (FFS) was significantly better in the HSCT group (79.8% ± 6.8% vs. 55.2% ± 9.2%, p = 0.049). In multivariate analysis, age ≤ 35 years at salvage HSCT was the only favorable factor for OS and FFS ( p = 0.019, 95% CI 0.019-0.706). These results suggest that HSCT and repeated IST are both effective for refractory/relapsed SAA in the salvage setting. Considering the superior FFS in the HSCT cohort, especially in younger patients (age ≤ 35 years), we recommend HSCT instead of a second IST for these patients.