Objective: To evaluated the clinical efficacy of a reduced-intensity preconditioning regimen for single non-blood-related umbilical cord blood transplantation (sUCBT) in the treatment of severe aplastic anemia (SAA) . Methods: The clinical data of 63 patients with SAA who underwent sUCBT from January 2021 to July 2023 at the Department of Hematology of the First Affiliated Hospital of USTC were retrospectively analyzed. Fifty-two patients received total body irradiation/total bone marrow irradiation (TMI) combined with fludarabine or a cyclophosphamide- conditioning regimen (non-rATG group) , while 11 patients received rabbit anti-human thymocyte immunoglobulin (rATG) combined with TMI, fludarabine, or the cyclophosphamide-conditioning regimen (rATG group) . All patients received cyclosporine A and mycophenolate mofetil for graft-versus-host disease (GVHD) prophylaxis. Complications post-transplantation and long-term survival were compared between the two groups. Results: The baseline parameters were balanced between the two groups (P>0.05) . In the rATG group, all patients achieved stem cell engraftment, and in the non-rATG group, five patients had primary graft failure. There was no significant difference in the cumulative incidence of neutrophil engraftment at 42 days after transplantation or platelet engraftment at 60 days between the two groups. The incidence of grade Ⅱ-Ⅳ acute GVHD in the rATG group was significantly lower than in the non-rATG group (10.0% vs. 46.2% , P=0.032) , and the differences in the cumulative incidences of grade Ⅲ/Ⅳ acute GVHD and 1-year chronic GVHD were not statistically significant (P=0.367 and P=0.053, respectively) . There were no significant differences in the incidences of pre-engraftment syndrome, bacterial bloodstream infections, cytomegalovirus viremia, or hemorrhagic cystitis between the two groups (P>0.05 for all) . The median follow-up time for surviving patients was 536 (61-993) days, and the 1-year transplantation related mortality (TRM) of all patients after transplantation was 13.0% (95% CI 6.7% -24.3% ) . Among the patients in the non-rATG and rATG groups, 15.5% (95% CI 8.1% -28.6% ) and 0% (P=0.189) , respectively, had mutations. The 1-year overall survival (OS) rate of all patients after transplantation was 87.0% (95% CI 75.7% -93.3% ) . The 1-year OS rates in the rATG group and non-rATG group after transplantation were 100% and 84.5% , respectively (95% CI 71.4% -91.9% ) (P=0.198) . Conclusion: The preliminary results of sUCBT with a low-dose irradiation-based reduced-intensity conditioning regimen with fludarabine/cyclophosphamide for the treatment of patients with SAA showed good efficacy. Early application of low-dose rATG can reduce the incidence of acute GVHD after transplantation without increasing the risk of implantation failure or infection.
目的： 评价减低强度预处理（RIC）方案单份非血缘脐带血移植（sUCBT）治疗重型再生障碍性贫血（SAA）的临床疗效。 方法： 纳入2021年1月至2023年7月在中国科学技术大学附属第一医院（安徽省立医院）血液科接受sUCBT的63例SAA患者，对其临床资料进行回顾性分析。移植预处理均采用RIC方案：全身放射治疗（TBI）/全骨髓照射（TMI）4 Gy+氟达拉滨（Flu）（总量200 mg/m(2)，分5 d给药）+环磷酰胺（Cy）（总量120 mg/kg，分2 d给药），其中11例患者在上述预处理方案基础上加用兔抗人胸腺细胞免疫球蛋白（rATG）2 mg/kg（rATG组）。以环孢素A（CsA）联合霉酚酸酯（MMF）方案预防移植物抗宿主病（GVHD）。 结果： rATG组与非rATG组患者一般资料及移植物情况差异均无统计学意义（P>0.05）。rATG组所有患者均获得造血重建，非rATG组5例患者发生原发性植入失败。两组移植后42 d中性粒细胞累积植入率及60 d血小板累积植入率差异无统计学意义。rATG组Ⅱ～Ⅳ度急性GVHD发生率低于非rATG组[10.0%（95%CI 0.5%～37.4%）对46.2%（95% CI 32.1%～59.1%），P＝0.032]，两组Ⅲ/Ⅳ度急性GVHD及慢性GVHD发生率差异均无统计学意义（P＝0.428，P＝0.107）。两组植入前综合征（PES）、血流感染、巨细胞病毒（CMV）血症及出血性膀胱炎发生率差异均无统计学意义（P>0.05）。存活患者中位随访时间为536（61～993）d，全部患者移植后1年移植相关死亡率（TRM）为13.0%（95%CI 6.7%～24.3%），非rATG组、rATG组分别为15.5%（95% CI 8.1%～28.6%）、0%（P＝0.189）。全部患者移植后1年总生存（OS）率为87.0%（95%CI 75.7%～93.3%）。rATG组、非rATG组移植后1年OS率分别为100%、84.5%（95%CI 71.4%～91.9%）（P＝0.198）。 结论： 含TBI或TMI联合Flu/Cy的RIC方案sUCBT治疗SAA具有较好的疗效。早期应用小剂量rATG可降低移植后急性GVHD发生率，未增加植入失败及感染风险。.
Keywords: Antithymocyte globulin; Reduced-intensity conditioning, RIC; Severe aplastic anemia; Umbilical cord blood.