Department of Pediatric Hematology and Oncology, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
Department of Hematopoietic Stem Cell Transplantation, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
Pediatr Blood Cancer. 2021 Nov;68(11):e29338. doi: 10.1002/pbc.29338. Epub 2021 Sep 14.
Ineffective erythropoiesis (IE) is the most prominent feature of transfusion-dependent beta-thalassemia (TDT), which leads to extramedullary hemopoiesis. The rejection rate in allogeneic hematopoietic stem cell transplantation (HSCT) is high in heavily transfused patients with TDT accompanied by prominent IE. Therefore, a pretransplantation treatment bridging to HSCT is often used to reduce allosensitization and IE. Ruxolitinib is a JAK-1/JAK-2 inhibitor and has showed its efficacy in suppressing IE and the immune system. A previously published study on RUX in adult patients with TDT has revealed that this treatment significantly reduces spleen size and is well tolerated.
Ten patients (5-14 years old) with TDT and an enlarged spleen were enrolled. The dose of ruxolitinib was adjusted for age: for patients <11 years: 40-100 mg/m total daily dose and for patients >11 years: 20-30 mg/m total daily dose. HSCT was performed in 8 of 10 patients.
After the first 3 months of ruxolitinib therapy, spleen volume decreased in 9 of 10 cases by 9.1%-67.5% (M = 35.4%) compared with the initial size (P = 0.003). The adverse events of ruxolitinib (infectious complications, moderate thrombocytopenia, and headache) were successfully managed by reducing the dose. The outcomes of HSCT were favorable in seven of eight cases.
Ruxolitinib is promising as a short-term pre-HSCT treatment for pediatric patients with TDT and pronounced IE.
无效造血（IE）是依赖输血的β-地中海贫血（TDT）最显著的特征，导致髓外造血。在伴有明显 IE 的重度输血 TDT 患者中，异基因造血干细胞移植（HSCT）的排斥率很高。因此，通常使用移植前桥接治疗来减少同种异体致敏和 IE。芦可替尼是一种 JAK-1/JAK-2 抑制剂，已显示出抑制 IE 和免疫系统的功效。一项关于 RUX 在 TDT 成年患者中的先前发表的研究表明，这种治疗方法显著降低了脾脏大小，并且具有良好的耐受性。
10 名（5-14 岁）伴有脾脏肿大的 TDT 患者入组。芦可替尼的剂量根据年龄进行调整：<11 岁的患者：40-100mg/m2 总日剂量；>11 岁的患者：20-30mg/m2 总日剂量。10 例患者中有 8 例进行了 HSCT。
在接受芦可替尼治疗的前 3 个月后，与初始大小相比，10 例中有 9 例的脾脏体积减少了 9.1%-67.5%（M=35.4%）（P=0.003）。通过减少剂量成功控制了芦可替尼的不良反应（感染性并发症、中度血小板减少和头痛）。8 例 HSCT 中有 7 例结果良好。
芦可替尼有望成为伴有明显 IE 的 TDT 儿科患者的 HSCT 短期预处理药物。
