Department of Hematology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Department of Pediatric Hematology, Oncology and Bone Marrow Transplantation, Cleveland Clinic, Cleveland, Ohio, USA.
Pediatr Blood Cancer. 2021 Aug;68(8):e29066. doi: 10.1002/pbc.29066. Epub 2021 Apr 15.
Immunosuppressive therapy with horse antithymocyte globulin and cyclosporine currently remains the standard therapy for children with severe aplastic anemia (SAA) who lack human leukocyte antigen (HLA)-identical sibling. The thrombopoietin receptor agonist eltrombopag has been recently approved for SAA patients 2 years and older. However, there are limited data on its safety and efficacy in pediatric cohorts.
We conducted a retrospective study of patients ≤18 years old consecutively diagnosed with SAA between 2000 and 2018. Patients received either standard immunosuppressive therapy (IST-Std) or IST with eltrombopag (IST-Epag). The primary outcome was the objective response (OR), including partial and complete response (CR), at 6 and 12 months after starting therapy.
We identified 16 patients receiving IST-Std and nine IST-Epag treatment (seven of nine as upfront therapy and two of seven after previously failed IST). The OR at 6 and 12 months in IST-Std arm was 71% and 100%, with CR in 29% and 58%, respectively. Seven patients receiving upfront IST-Epag had OR at 6 and 12 months, with two of seven (29%) achieving CR at 6 and 12 months. Two patients who previously failed standard IST did not respond to eltrombopag. No significant differences were observed in both cohorts with regard to infections. One IST-Epag-treated patient developed transient grade 3 transaminitis. Finally, no changes in paroxysmal nocturnal hemoglobinuria (PNH) clone size and cytogenetic abnormalities were seen in either cohort.
The addition of eltrombopag to standard IST was well tolerated and resulted in satisfactory hematological response at 6 and 12 months in this single-institution experience. A larger cohort with longer follow-up is required to assess response durability.
对于缺乏人类白细胞抗原（HLA）匹配同胞供体的重型再生障碍性贫血（SAA）患儿，目前仍采用马抗胸腺细胞球蛋白和环孢素的免疫抑制疗法作为标准治疗。血小板生成素受体激动剂艾曲波帕最近已被批准用于 2 岁及以上的 SAA 患者。然而，关于其在儿科患者中的安全性和疗效的数据有限。
我们对 2000 年至 2018 年间连续诊断为 SAA 的≤18 岁患者进行了回顾性研究。患者接受标准免疫抑制治疗（IST-Std）或 IST 联合艾曲波帕（IST-Epag）治疗。主要结局是治疗开始后 6 个月和 12 个月时的客观缓解（OR），包括部分缓解和完全缓解（CR）。
我们共纳入 16 例接受 IST-Std 治疗的患者和 9 例接受 IST-Epag 治疗的患者（9 例中有 7 例为一线治疗，7 例中有 2 例为二线治疗）。IST-Std 组的 OR 在 6 个月和 12 个月时分别为 71%和 100%，CR 分别为 29%和 58%。7 例接受一线 IST-Epag 治疗的患者 OR 在 6 个月和 12 个月时分别为 71%和 100%，其中 2 例（29%）在 6 个月和 12 个月时达到 CR。2 例先前 IST 治疗失败的患者对艾曲波帕无反应。两组在感染方面无显著差异。1 例接受 IST-Epag 治疗的患者出现短暂的 3 级肝转氨酶升高。最后，在两组患者中均未观察到阵发性睡眠性血红蛋白尿（PNH）克隆大小和细胞遗传学异常的变化。
在本单中心经验中，在标准 IST 基础上添加艾曲波帕治疗耐受性良好，6 个月和 12 个月时的血液学缓解效果令人满意。需要更大的队列和更长的随访时间来评估缓解的持久性。
