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 clearly superior in heavily transfused patients (pts) with TDT accompanied by prominent IE. Therefore, a pre-transplantation treatment bridging to HSCT is often used to reduce allosensibilization and IE. Ruxolitinib (RUX) is a JAK-1/JAK-2-inhibitor and has showed its efficacy to suppress IE and the immune system. A previously published study on RUX in adult pts with TDT has revealed that this treatment significantly reduces spleen size and is well tolerated. Procedure: Ten pts (5-14 y.o.) with TDT and an enlarged spleen were enrolled. The dose of RUX was adjusted for age: for pts younger < 11 years: 40 - 100 mg/m2 and for pts >11 years: 20 - 30 mg/m2. HSCT was performed in 8 out of the 10 pts. Results: After the first 3 months of RUX therapy the spleen volume decreased in 9 out of the 10 cases by 9.1 – 67.5% (M = 35.4%) compared to the initial size (р = 0.003). The adverse events of RUX included infectious complications, moderate thrombocytopenia as well as headache and were successfully managed by reducing the dose. The outcomes of HSCT were favorable in 7 out of the 8 cases. Conclusion: RUX is promising as a short-term pre-HSCT treatment for pediatric pts with TDT and pronounced IE.