Here we report a boy with disseminated choroid plexus carcinoma diagnosed at an age of 2 years 9 months on the background of de novo germline mutation in ТР53. The patient received 3 cycles of high-dose methotrexate-based chemotherapy and 4 cycles of alternating carboplatin/cyclophosphamide chemotherapy, followed by craniospinal proton beam irradiation. To date, the patient lives with neither progression of the disease nor other extracranial neoplasms for 6 years from the diagnosis. This is the first successful experience of proton irradiation therapy affording long-term survival in a child with Li-Fraumeni syndrome-associated choroid plexus carcinoma.

Background. Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor of infancy commonly associated with Kasabach-Merritt phenomenon (KMP) that includes thrombocytopenia and coagulation dysfunction. Platelet receptor CLEC-2 -tumor cell podoplanin interaction is considered the key mechanism of thrombocytopenia in KMP, however, the effect of long-term exposure to podoplanin on platelet function is unknown. Procedure. Here we examined blood samples from 7 patients with KHE/KMP. Platelet calcium signaling and functional responses to conventional activation and CLEC-2 stimulation were analyzed by continuous and endpoint live cell flow cytometry. Platelet aggregation in response to ADP or rhodocytin was analyzed by low-angle light scattering approach (LaSca). Additionally, ex vivo thrombus formation on collagen was observed in parallel-plate flow chambers. Results. We demonstrate that in KHE/KMP platelet functional responses to strong stimulation were on the lower boundary of age-matched normal ranges, while calcium mobilization and fibrinogen binding upon stimulation with ADP alone were significantly lower than control values. Platelet di-aggregate formation in response to ADP was also diminished in most of the patients. Formation of platelet aggregates in collagen-coated parallel plate flow chambers was also noticeably lower than in the age-matched control group. Calcium mobilization in response to CLEC-2 stimulation was unaltered in the patients and could be blocked by low-molecular-weight inhibitors, 2CP and HB125. Conclusions. While platelet responsiveness in KHE/KMP is moderately altered, platelet CLEC-2 receptors remain functional and respond to inhibition. Therefore, our findings suggest that CLEC-2-targeting molecules are new potential agents in therapeutic management of this life-threatening condition.

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.

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.