Outcomes of Haploidentical Stem Cell Transplantation in Upfront and Salvage Settings for Adult Patients with Severe...

Thanks to advances in controlling graft failure and graft-versus-host disease (GVHD), haploidentical stem cell transplantation from a related mismatched donor (Haplo-SCT) is possible in adult patients with severe aplastic anemia (SAA). However, because of concerns about morbidity and mortality, Haplo-SCT has been used as salvage treatment after the failure of immunosuppressive therapy. In this study, we aimed to evaluate the feasibility of Haplo-SCT for adult patients with SAA in both the upfront and salvage settings. We analyzed 68 consecutive patients who underwent Haplo-SCT between October 2014 and January 2023. Thirty-six (52.9%) patients received salvage Haplo-SCT, and 32 (47.1%) patients underwent upfront Haplo-SCT. All patients received a conditioning regimen of 600 cGy fractionated TBI (200 cGy, 3 times) and fludarabine (30 mg/m²/day) for 5 days. GVHD prophylaxis consisted of antithymocyte globulin (2.5 mg/kg/day for 2 days), tacrolimus, and methotrexate. All patients received peripheral blood as a stem cell source. Outcomes between upfront and salvage Haplo-SCT groups were compared with Log-rank test or Gray's test. Cox proportional hazard model was used to assess factors affecting the GVHD-free failure-free survival (GFFS). The mean age was 37.1 ± 13.0 yr, and 30 (44.1%) patients had very SAA at transplantation. The haploidentical donors were parents (n = 18), siblings (n = 30), offspring (n = 17), and others (n = 3). All patients achieved primary engraftment. The cumulative incidence of acute GVHD (grade ≥II) and chronic GVHD (≥moderate) was 26.5% at 100 days and 9.3% at 4 yr, respectively, and it did not differ between upfront and salvage Haplo-SCT (31.2% versus 22.2%; P = .50, 13.0% versus 5.9%; P = .266). During a median follow-up of 54 mo, the 4-yr overall survival (OS) and failure-free survival were 93.9% and 92.4%, respectively. Four-year OS after upfront and salvage Haplo-SCT was 93.8% and 94.2%, respectively (P = .874). Four-year GFFS was 78.9%, and it did not differ significantly between upfront and salvage Haplo-SCT (71.3% versus 85.8%, P = .143). Furthermore, after adjusting for potential factors affecting GFFS (patient age and comorbidity index), no difference in GFFS was shown between upfront and salvage Haplo-SCT. Our results suggest that Haplo-SCT can be an effective option in both upfront and salvage settings when fully matched donors are not available.