Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in 86 Pediatric Patients with Aplastic Anemia: A Single-Center Experience

Identifying the ideal donor for allogeneic hematopoietic stem cell transplantation (allo-HSCT) poses a significant challenge in the treatment of pediatric patients with aplastic anemia (AA). We analyzed the outcomes of pediatric patients with AA undergoing unrelated umbilical cord blood transplantation (UCBT) (n=10), haploidentical transplantation (haplo-HSCT) (n=53) and matched sibling donor HSCT (MSD-HSCT) (n=23), registered at the Institute of Hematology and Blood Diseases Hospital in Tianjin, China (2017-2023). Three children with salvage transplantation unfortunately died before achieving hematopoietic reconstruction. In the haplo-HSCT group, two children experienced primary graft failure, while three others had secondary graft failure. They completed hematopoietic reconstruction successfully after undergoing a second transplantation with alternative donors. There was no statistically significant difference in overall survival (OS) (90.0%±9.5%: 92.2%±3.7%: 91.3%±5.9%) and failure free survival (FFS)(90.0%±9.5%：77.3%±5.8%：87.0%±7.0%) among the three groups of UCBT, Haplo-HSCT and MSD-HSCT (P=0.978, P=0.432). Further analysis revealed that transplantation-associated thrombotic microangiopathy (TA-TMA) was an independent risk factor for OS (HR=16.87, 95% CI= 1.51-188.13, P=0.022). Additionally, secondary failure of platelet recovery (SFPR) emerged as an independent risk factor for FFS (HR=15.95. 95%CI= 1.48-171.52, P=0.022). SFPR occurred in nine children between 1 to 5 months post-transplantation. The 3-year OS in the SFPR group was significantly lower compared to the non-SFPR group (74.1%±16.1% : 96.7%±2.3%, P=0.004). Binary logistic regression analysis identified age (OR=1.289, 95% CI=1.019-1.631, P=0.034) and the presence of grade III-IV acute graft-versus-host disease (aGVHD) (OR = 6.132, 95% CI = 1.140-32.968, P=0.035) as significant risk factors for the occurrence of SFPR. Besides, the cumulative incidence of acute graft-versus-host disease (GVHD) and chronic GVHD was significantly different among the groups, with rates of 70.0%, 63.0%, and 31.8% (P=0.036), and 40.0%, 31.1%, and 4.5% (P=0.017), respectively. However, the cumulative incidence of cytomegalovirus viremia (70.0%: 37.7%: 30.4%)、Epstein-Barr virus viremia (0.0%: 17.0%: 8.7%)、TA-TMA(10.0%: 15.1%: 4.3% )、post-transplant lymphoproliferative disorder (0.0%: 7.5%: 8.7%) did not show statistically significant differences (P=0.093, P=0.400, P=0.424, P=1.000). It's worth noting that the cumulative incidence of hemorrhagic cystitis in Haplo-HSCT group (47.2%) was obviously higher than UCBT (30.0%) and MSD-HSCT groups(8.7%)( P=0.003). We conculded that HSCT demonstrates good overall efficacy in treating AA in children, and there is no statistically significant difference in the efficacy of HSCT among UCBT, Haplo-HSCT and MSD-HSCT. MSD-HSCT remains the first-line treatment for severe AA due to its relatively low incidence of GVHD and other complications. Besides, in cases where a matched sibling donor is unavailable, Haplo-HSCT or UCBT is a suitable alternative. Furthermore, TA-TMA and SFPR are identified as independent risk factors for OS and FFS, respectively. Age and grade III-IV acute aGVHD are risk factors for the development of SFPR. Additionally, post-transplant thrombocytopenia is recognized as a serious complication that can significantly impact the therapeutic efficacy of AA following transplantation.