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