Objective: To investigate the safety and efficacy of haplo-identical hematopoietic stem cell transplantation (haplo-HSCT) conditioning with the same dosage form of antithymoglobulin (ATG) in patients with severe aplastic anemia (SAA) failure to ATG. Methods: This was a retrospective cohort study. A total of 65 patients with SAA who failed ATG treatment and received haplo-HSCT conditioning with the same dosage of ATG at the Institute of Hematology, Peking University People's Hospital between July 2008 and October 2020 were included as the ATG treatment failure group. An additional 65 SAA patients who applied ATG for the first time during haplo-HSCT were randomly selected by stratified sampling as the first-line haplo-HSCT group. Baseline clinical data and follow-up data of the two groups were collected. Conditioning-related toxicity within 10 days after ATG application and long-term prognosis were analyzed. The Kaplan-Meier was used to calculate the overall survival rate, and the Log-rank test was applied to compare the rates of the two groups. Results: In the ATG treatment failure group, there were 36 males and 29 females, and the age at the time of transplantation [M (Q1, Q3)] was 16 (8, 25) years. In the first-line haplo-HSCT group, there were 35 males and 30 females, with a median age of 17 (7, 26) years. Within 10 days of ATG application, the incidence of noninfectious fever, noninfectious diarrhea, and liver injury in the ATG treatment failure group was 78% (51 cases), 45% (29 cases), and 28% (18 cases), respectively, and in the first-line haplo-HSCT group was 74% (48 cases), 54% (35 cases), and 25% (16 cases), respectively; the difference between the two groups was not statistically significant for any of these three parameters (all P>0.05). For graft-versus-host disease (GVHD), there was no significant difference between the ATG treatment failure group and the first-line haplo-HSCT group in the development of 100 day Ⅱ to Ⅳ acute GVHD (29.51%±0.35% vs. 25.42%±0.33%), Ⅲ to Ⅳ acute GVHD (6.56%±0.10% vs. 6.78%±0.11%), and 3-year chronic GVHD (26.73%±0.36% vs. 21.15%±0.30%) (all P>0.05). Three-year overall survival (79.6%±5.1% vs. 84.6%±4.5%) and 3-year failure-free survival (79.6%±5.1% vs. 81.5%±4.8%) were also comparable between these two groups (both P>0.05). Conclusions: Compared with no exposure to ATG before HSCT, similar early adverse effects and comparable survival outcomes were achieved in patients with SAA who failed previous ATG treatment and received haplo-HSCT conditioning with the same dosage form of ATG. This might indicate that previous failure of ATG treatment does not significantly impact the efficacy and safety of salvaging haplo-HSCT in patients with SAA.
目的： 探究抗胸腺球蛋白（ATG）治疗失败的重型再生障碍性贫血（SAA）患者接受含相同剂型ATG预处理的单倍体异基因造血干细胞移植（haplo-HSCT）的安全性和疗效。 方法： 回顾性队列研究。纳入2008年7月至2020年10月在北京大学血液病研究所因ATG治疗失败接受含相同剂型ATG预处理haplo-HSCT的SAA患者65例（ATG治疗失败组），以患者年龄和移植时间设置分层，采用分层抽样法随机抽取同期行haplo-HSCT且预处理期间首次应用ATG的65例SAA患者作为对照（一线移植组）。收集两组患者基线临床资料及治疗随访资料，分析患者ATG应用后10 d内的预处理相关毒性发生情况及远期预后。采用Kaplan-Meier法计算总体生存率，率的比较应用Log-rank检验。 结果： ATG治疗失败组中，男36例，女29例，接受移植时年龄［M（Q1，Q3）］为16（8，25）岁；一线移植组中，男35例，女30例，接受移植时年龄为17（7，26）岁。在预处理ATG应用10 d内，ATG治疗失败组与一线移植组的非感染性发热、非感染性腹泻、肝损伤发生率分别为78%（51例）和74%（48例）、45%（29例）和54%（35例）、28%（18例）和25%（16例），差异均无统计学意义（均P>0.05）；两组患者移植后100 d Ⅱ~Ⅳ度急性移植物体抗宿主病（GVHD）的累积发生率（29.51%±0.35%比25.42%±0.33%）、Ⅲ~Ⅳ度急性GVHD累积发生率（6.56%±0.10%比6.78%±0.11%）、移植后3年慢性GVHD累积发生率（26.73%±0.36%比21.15%±0.30%）、移植后3年总体生存率（79.6%±5.1%比84.6%±4.5%）及移植后3年无失败生存率（79.6%±5.1%比81.5%±4.8%）差异均无统计学意义（均P>0.05）。 结论： ATG治疗失败的SAA患者，接受含相同剂型ATG预处理的haplo-HSCT治疗，早期不良反应和远期生存与未经ATG治疗的移植患者相当。说明ATG治疗失败不显著影响挽救haplo-HSCT对SAA患者的疗效和安全性。.