Abstract Background Aplastic anemia (AA) is a disease characterized by bone marrow failure. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for AA. However, some patients experience transplantation failure or inefficacy result from complications such as graft failure, immune rejection, or infection. In recent years, third-party cell infusion has been considered as an adjunctive therapeutic approach that may improve allo-HSCT efficacy and reduce the risk of complications1,2. However, there are few related studies on AA.This study aims to evaluate the efficacy and safety of haploidentical allogeneic hematopoietic stem cell transplantation combined with third-party cell infusion in AA, and to investigate its impact on transplant success rates, complication incidence, and long-term survival. Aims This study assessed UCB co-infusion in Aplastic anemia (AA) patients receiving haplo allo-HSCT . Methods A total of 251 AA patients undergoing a ATG/G-CSF–based haplo allo-HSCT between 2012 and 2024 were retrospectively analyzed. Patients were stratified into two groups based on the use of third-party UCB: haplo-cord cohort (n=171) and haplo cohort (n=80). All patients received standard BU/CY/FLU/ATG with a single dose of BU，GVHD prophylaxis (CSA/FK506+MMF+sMTX) and were followed longitudinally through 2025-6-30. Results The study included 251 AA patients (136 males, 115 females) with a median age of 23 years (range, 1–63). Median disease duration was 4 months(range, 1–264); and the median interval between transplants was 7.2 months(range, 1–139). Conditioning regimens were all BU/CY/FLU/ATG with a single dose of BU of 0.8 mg/kg, among them 207patients(82.5%) ≤8 doses and 44 patients（17.5%） 8 doses. The median infused cell doses were 13.6 × 10⁸ (range, 2.81–31.93) mononuclear cells/kg and 5.97 × 10⁶ (range, 1.14–24.08) CD34⁺ cells/kg. Patients baseline characteristics and conditioning regimens were respectively well balanced（p＞0.05,respectively） in haplo cohort and haplo-cord cohort，。 By June 2025，there was without Primary graft failure and the media follow-up time was 46.4 months（rang 1.2-141.4）.Median time to neutrophil and platelet engraftment in haplo cohort and haplo-cord cohort were consistent（p＞0.05）,with 9 days and 10 days , respectively. There was no statistically significant difference between two groups in the risk of GVHD, in haplo cohort and haplo-cord cohort patients with DAY100-III-IV grade of aGVHD and the cumulative incidence of moderate-to-severe cGVHD were 24.7%（95% CI 16.9-36.2）vs.21.8%（95% CI 16.4-28.9），p=0.57; 7.6%（95% CI 3.5-16.4）vs.7.1%（95% CI 4.1-12.9），p=0.63。While there was no statistically significant difference between two groups,the virus reaction in haplo cohort was lower.Patiengs with CMV and EBV in DAY 180 were 44.6%（95% CI 35-56.9）vs.56.5%（95% CI 49.5-64.4），p=0.09 and 19.4%（95% CI 12.9-30.9）vs.21.2%（95% CI 15.9-28.3），p=0.73.Besides,there were 33 patients with mixed chimerism in haplo cohort，60 patients in haplo-cord cohort (include UCB mixed chimerism and donor-recipient mixed chimerism)，the incidience rate of mixed chimerism in haplo cohort was approximated to haplo-cord cohort（41.3% vs.35.1%，p=0.35）。Furthermore,there was no statistically significant difference between the two groups in 5-year OS,it respectively was 80%（95% CI 71.2-88.8）vs.76.8%（95% CI 70.4-83.2）, p=0.71。 Multivariable Cox regression and Fine–Gray competing risk models identified no independent predictors for grade III–IV aGVHD, moderate-to-severe cGVHD, or CMV reactivation. ATG formulation (Fresenius vs. Genzyme) was independently associated with increased risk of EBV reactivation (HR = 2.26; 95% CI, 1.12–4.58; p = 0.02). UCB co-infusion, HLA mismatch, age, BU dose, and cell doses (MNC, CD34⁺, CD3⁺) were no significant association with GVHD, viral reactivation, or OS. A trend toward improved OS was observed with reduced BU dose (HR = 0.74; p = 0.07) and higher MNC dose (HR = 1.30; p = 0.09), though not statistically significant. Conclusion In patients with aplastic anemia undergoing haploidentical hematopoietic stem cell transplantation, the combination of third-party cell infusion did not improve the incidence of graft-versus-host disease (GVHD) as expected, but it also did not increase the risk of graft failure or mixed chimerism.
Zhao et al. (Mon,) studied this question.