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 complications[1,2]. 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.

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2025
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