Comparison of Haploidentical-Hematopoietic Stem Cell Transplantation Using Modified Post-Transplantation Cyclophosphamide and Eltrombopag Combined With Immunosuppression for the Treatment of Severe Aplastic Anemia.

First-line treatments for severe aplastic anemia (SAA) patients include HLA-matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) for young patients and immunosuppressive therapy (IST) for those without suitable donors or with advanced age. Nevertheless, MSD-HSCT is limited by donor availability, while IST is associated with high relapse and clonal evolution risks. Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is commonly recommended as salvage therapy for SAA patients following primary IST failure. Recently, advancements integrate eltrombopag (EPAG) with IST to enhance hematologic responses, but long-term clonal risks persist. Haplo-HSCT with post-transplant cyclophosphamide protocols (PTCy) expanded donor options and improved survival. However, no studies have directly compared the outcomes of haplo-HSCT using modified PTCy and IST +EPAG in SAA patients. We compared outcomes of haplo-HSCT using modified PTCy and IST plus EPAG in 191 SAA patients from the multicenter registry of the Chinese Eastern Collaboration Group of Anemia (CECGA) between January 2018 and December 2023. At 6 mo post-treatment, 85.85% (91/106) of haplo-HSCT patients and 18.82% (16/85) in the IST+EPAG group, respectively, exhibited normal blood routines (P < .001). While 3-yr OS rates were comparable (haplo-HSCT 84.9% versus IST+EPAG 91.8%, P = .111), haplo-HSCT demonstrated superior 3-yr failure-free survival (81.1% versus 61.2%, P = .016). Multivariate analysis identified age <40 yr as a favorable factor for FFS and OS, and age <40 yr and haplo-HSCT were associated with better normal blood routine at 6 mo. After propensity score matching (PSM), 3-yr OS in the IST+EPAG group was comparable to that of the haplo-HSCT group (95.8% versus 85.4%, P = .078); 3-yr FFS and the normal blood routine rate at 6 mo were significantly lower in the IST+EPAG than in the haplo-HSCT group (62.5% versus 85.4%, P = .032; 22.92% versus 87.50%, P < .001, respectively). Patients in the haplo-HSCT group had higher percentages of hematopoietic overall response rate (ORR) at 3 mo after treatment than those in the IST+EPAG group (P = .005). Multivariate analysis identified age <40 yr and haplo-HSCT as favorable factors for FFS, and haplo-HSCT was associated with better normal blood routine at 6 mo. These findings suggest haplo-HSCT as a viable alternative for young SAA patients lacking matched donors, while IST+EPAG may be preferable for older patients.