National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Institute of Blood and Marrow Transplantation of Soochow University, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Bone Marrow Transplant. 2024 Oct;59(10):1449-1457. doi: 10.1038/s41409-024-02377-1. Epub 2024 Aug 1.
Matched-related donor hematopoietic stem cell transplantation (HSCT) remains the preferred first-line option for severe aplastic anemia (SAA) patients aged <40 years even in the era of eltrombopag (EPAG). However, there has not been any direct comparison between immunosuppressive therapy (IST) plus EPAG (IST + EPAG) and haploidentical HSCT (Haplo-HSCT) as first-line therapy. This study prospectively compared the efficacy, safety and health-related quality of life (HRQoL) of Haplo-HSCT (n = 147) and IST + EPAG (n = 121) as first-line treatment for patients with SAA. The results showed that 86.3% of patients in the Haplo-HSCT group and 24.1% of patients in the IST + EPAG group achieved normal complete blood count (CBC) (P < 0.001) after 6 months of treatment. The time to achieve transfusion independence and absolute neutrophil count ≥ 1.0 × 10/L were shorter in the Haplo-HSCT group than in the IST + EPAG group (P < 0.05). In the IST + EPAG and Haplo-HSCT, 3-year overall survival (OS) was 92.4 ± 2.4% and 82.8 ± 3.1% (P = 0.017), whereas 3-year failure-free survival (FFS) was 69.4 ± 4.2% and 81.6 ± 3.2% (P = 0.002), respectively. Similar results were observed in patients with <40 years of age. Among patients with ≥40 years of age, there was no difference in 3-year OS (88.6 ± 4.8% vs. 82.4 ± 8.1%, P = 0.517) between the IST + EPAG and Haplo-HSCT groups, whereas 3-year FFS was lower in the IST + EPAG (58.7 ± 7.5% vs. 82.4 ± 8.1%, P = 0.043). Subgroup analysis for populations aged <40 years indicated that SAA benefited more from IST + EPAG, and very SAA (vSAA) benefited more from Haplo-HSCT. Patients treated with haplo-HSCT scored significantly better in the HRQoL than treated with IST + EPAG (P < 0.0001). Multivariate analysis showed that first-line Haplo-HSCT was associated with normal CBC at 6 months, better FFS and led to a better HRQoL (P < 0.001). In summary, the IST + EPAG achieved better OS for <40 years SAA patients, while the Haplo-HSCT accelerated hematopoietic recovery and HRQoL, achieved better FFS even for those <40 years vSAA and ≥40 years patients.
对于年龄<40 岁的重型再生障碍性贫血（SAA）患者，即使在血小板生成素受体激动剂（EPAG）时代，匹配相关供体造血干细胞移植（HSCT）仍然是首选的一线治疗方案。然而，EPAG 联合免疫抑制治疗（IST）与单倍体 HSCT（Haplo-HSCT）作为一线治疗方案之间尚未进行直接比较。本研究前瞻性比较了 Haplo-HSCT（n=147）和 IST+EPAG（n=121）作为 SAA 患者一线治疗的疗效、安全性和健康相关生活质量（HRQoL）。结果显示，6 个月后，Haplo-HSCT 组 86.3%的患者和 IST+EPAG 组 24.1%的患者实现了正常的完全血细胞计数（CBC）（P<0.001）。Haplo-HSCT 组达到输血独立和绝对中性粒细胞计数≥1.0×10/L的时间短于 IST+EPAG 组（P<0.05）。在 IST+EPAG 和 Haplo-HSCT 中，3 年总生存率（OS）分别为 92.4±2.4%和 82.8±3.1%（P=0.017），3 年无失败生存率（FFS）分别为 69.4±4.2%和 81.6±3.2%（P=0.002）。在年龄<40 岁的患者中观察到类似的结果。在年龄≥40 岁的患者中，IST+EPAG 和 Haplo-HSCT 组 3 年 OS 无差异（88.6±4.8% vs. 82.4±8.1%，P=0.517），但 IST+EPAG 组 3 年 FFS 较低（58.7±7.5% vs. 82.4±8.1%，P=0.043）。<40 岁人群的亚组分析表明，IST+EPAG 更有益于 SAA 患者，而极重型再生障碍性贫血（vSAA）患者则更受益于 Haplo-HSCT。接受 Haplo-HSCT 治疗的患者在 HRQoL 方面的评分明显优于接受 IST+EPAG 治疗的患者（P<0.0001）。多变量分析显示，一线 Haplo-HSCT 与 6 个月时的正常 CBC、更好的 FFS 相关，并导致更好的 HRQoL（P<0.001）。总之，IST+EPAG 对<40 岁的 SAA 患者获得更好的 OS，而 Haplo-HSCT 加速造血恢复和 HRQoL，甚至对<40 岁的 vSAA 和≥40 岁的患者获得更好的 FFS。
