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.

Background Langerhans cell histiocytosis (LCH) involves abnormal proliferation of Langerhans cells (LC), which is typically driven by the BRAF V600E mutation. High-risk LCH has a poor prognosis. Procedure Fifteen children (5 girls, 10 boys) with BRAF V600E+ LCH received vemurafenib (initial dose median 40 mg/kg/day, range: 11–51.6 mg/kg/day) between March 2016 and February 2020. All patients had previous received LCH-directed chemotherapy. The median age at LCH onset was 2 months (range: 1–28 months) and the median age at the start of vemurafenib treatment was 22 months (range: 13–62 months). The median disease activity score (DAS) at the start of vemurafenib treatment was 12 points (range: 2–22 points). Results The median duration of vemurafenib therapy was 29 months (range: 2.4–45 months). All patients responded to treatment, with median DAS values of 4 points (range: 0–14 points) at week 4 and 1 point (range: 0–3 points) at week 26. Toxicities included skin/hair changes (93%) and non-significant QT prolongation (73%). Two patients died, including 1 patient who experienced hepatic failure after NSAID overdose and 1 patient who developed neutropenic sepsis. Electively stopping vemurafenib treatment resulted in relapse in 5 patients, and complete cessation was only possible for 1 patient. Digital droplet PCR for BRAF V600E using cell-free circulating DNA revealed that 7 patients had mutation statuses that fluctuated over time. Conclusion Our study confirms that vemurafenib treatment is safe and effective for young children with BRAF V600E+ multisystem LCH. However, treatment using vemurafenib does not completely eliminate the disease.

Acquired thrombotic thrombocytopenic purpura (TTP) in children is a rare but severe disease, which is caused by Immunoglobulin G antibodies, which inactivate a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13). Daily high-volume plasma exchange (PEX) and immunosuppression with glucocorticoids and rituximab is the current standard of treatment for TTP. We report two females aged 5 and 12 years, with TTP, induced by anti-ADAMTS13 inhibitory antibodies who relapsed very shortly after PEX, rituximab and glucocorticoids, in whom long-term remission with disappearance of ADAMTS13 inhibitors was achieved after one course of bortezomib.