State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
Tianjin Institutes of Health Science, Tianjin, China.
Front Immunol. 2024 Aug 16;15:1425076. doi: 10.3389/fimmu.2024.1425076. eCollection 2024.
The optimal treatment for patients with severe aplastic anemia (SAA) who fail an initial course of antithymocyte globulin (ATG) plus cyclosporine has not yet been established. We compared the effectiveness of allogeneic hematopoietic stem cell transplantation (allo-HSCT) ( = 36) with repeated immunosuppressive therapy (IST) ( = 33) for relapsed/refractory SAA between 2007 and 2022. In the IST group, patients were retreated with ATG ( = 16) or high-dose cyclophosphamide ( = 17). The overall response rate was 57.6% at 6 months and 60.6% at 12 months. In the allo-HSCT group, patients received a transplant from a matched sibling donor ( = 6), matched unrelated donor ( = 7), or haploidentical donor ( = 23). All patients achieved neutrophil engraftment, and there were no cases of primary graft failure. The cumulative incidences (CIs) of grades II-IV and III-IV acute graft-versus-host disease (GVHD) were 36.1% ± 0.7% and 13.9% ± 0.3% at day +100, respectively. The 4-year CI of chronic GVHD (cGVHD) was 36.2% ± 0.7%, with moderate to severe cGVHD at 14.9% ± 0.4%. Compared with IST, HSCT recipients showed much higher hematologic recovery rate at 3, 6, and 12 months (63.9%, 83.3%, and 86.1%, respectively, < 0.001). The estimated 4-year overall survival (OS) (79.8% ± 6.8% vs. 80.0% ± 7.3%, = 0.957) was similar; however, the failure-free survival (FFS) was significantly better in the HSCT group (79.8% ± 6.8% vs. 56.6% ± 8.8%, = 0.049). Of note, children in the HSCT cohort were all alive without treatment failures, exhibiting superior OS (100% vs. 50.0% ± 17.7%, = 0.004) and FFS (100% vs. 50.0% ± 17.7%, = 0.004) than children in the IST cohort. Subgroup analysis revealed that younger patients (age ≤ 35 years), especially children, and those with refractory SAA benefited more from HSCT. Therefore, for these patients, salvage HSCT may be more preferable than a second course of IST.
对于初始接受抗胸腺细胞球蛋白（ATG）+环孢素治疗后复发/难治性重型再生障碍性贫血（SAA）患者，尚未确定最佳治疗方法。我们比较了 2007 年至 2022 年间复发/难治性 SAA 患者接受异体造血干细胞移植（allo-HSCT）（n=36）与重复免疫抑制治疗（IST）（n=33）的疗效。在 IST 组中，患者接受 ATG（n=16）或大剂量环磷酰胺（n=17）治疗。6 个月时总缓解率为 57.6%，12 个月时为 60.6%。在 allo-HSCT 组中，患者接受了匹配同胞供者（n=6）、匹配无关供者（n=7）或单倍体相合供者（n=23）的移植。所有患者均实现了中性粒细胞植入，且无原发性移植物失败。第 100 天时，Ⅱ-Ⅳ级和Ⅲ-Ⅳ级急性移植物抗宿主病（GVHD）的累积发生率（CI）分别为 36.1%±0.7%和 13.9%±0.3%。第 4 年慢性 GVHD（cGVHD）CI 为 36.2%±0.7%，中重度 cGVHD 发生率为 14.9%±0.4%。与 IST 相比，HSCT 组在 3、6 和 12 个月时的血液学恢复率更高（分别为 63.9%、83.3%和 86.1%，均<0.001）。4 年总生存（OS）估计值（79.8%±6.8%比 80.0%±7.3%，=0.957）相似；然而，HSCT 组的无失败生存（FFS）明显更好（79.8%±6.8%比 56.6%±8.8%，=0.049）。值得注意的是，HSCT 组的所有儿童均未发生治疗失败且存活，OS（100%比 50.0%±17.7%，=0.004）和 FFS（100%比 50.0%±17.7%，=0.004）均优于 IST 组。亚组分析显示，年轻患者（≤35 岁），尤其是儿童和难治性 SAA 患者从 HSCT 中获益更多。因此，对于这些患者，挽救性 HSCT 可能比接受第二次 IST 治疗更可取。
