Efficacy and safety of ruxolitinib in ineffective erythropoiesis suppression as a pretransplantation treatment for pediatric patients with beta-thalassemia major

Background 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. Procedure 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: 20-30 mg/m(2) total daily dose. HSCT was performed in 8 of 10 patients. Results 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. Conclusion Ruxolitinib is promising as a short-term pre-HSCT treatment for pediatric patients with TDT and pronounced IE.