Thrombocytopenia is one of the significant complications of chemotherapeutic regimens used in treating childhood solid tumors. Most often, the chemotherapeutic regimens used are myelosuppressive and often lead to hematological toxicity, including chemotherapy-induced

thrombocytopenia (CIT). Thrombocytopenia is a decrease of platelet counts in peripheral blood below 100 × 103/uL. The more severe the fall in platelet count, the higher risk of bleeding. Usually, CIT is seen at 7-10 days after chemotherapy with recovery occurring after 2-3 weeks.

Profound thrombocytopenia can lead to delays in administration of chemotherapy, reduced relative dose intensity (RDI), requirement of platelet transfusions, as well as increase the risk of significant bleeding episodes thereby leading to morbidity, hospitalization, an even a higher risk of mortality. RDI of chemotherapy can reduce the effectiveness of chemotherapy administered, thereby affecting the survival chances of children. Platelet transfusions have inherent risks of complications, including platelet refractoriness, allergic and febrile reactions, sepsis, and lung injury.

Prior studies done in adult patients have shown the prevalence of CIT to be 10%-38% in solid tumors. In children with solid tumors, it has been observed that mean platelet transfusion requirement in high-risk neuroblastoma and Ewing sarcoma were 13 and 9, respectively. Also 56% and 65% of high-risk and intermediate-risk patients received RDI modified chemotherapy, mainly due to CIT. The effect of CIT was more observed in the final chemotherapy cycles.

The main strategies used in managing CIT are prophylactic platelet transfusions, anti-fibrinolytics, and thrombopoietin receptor agonists (TPO-RAs). TPO-RAs including eltrombopag and romiplostim increase platelet production through interactions with the thrombopoietin receptor on megakaryocytes. The binding of the drug to the thrombopoietin receptor leads to activation of signal transduction pathways, which induce proliferation and differentiation of megakaryocytes. They are licensed for use in the treatment of aplastic anemia and immune thrombocytopenia in children aged 1 year above. In adults with solid tumors, TPO-Ras have been used more frequently in mitigating CIT, with the aim of preventing treatment delays. Most of the evidence is retrospective or phase 2 trials. In a study of romiplostim in patients with glioblastoma treated with temozolamide, a good response was observed in 60% of patients with addition of romiplostim. A Cochrane review on the effects of TPO-Ras could not yield a definitive conclusion due to the weak available data.

In children, the use of romiplostim to mitigate CIT evidence is scarce and limited to case series. A retrospective report on 5 children who were treated with romiplostim for refractory CIT illustrated that use of romiplostim was tolerated well, as well as effective. There were no adverse effects noted. Currently, an NIH trial (NCT04671901) is exploring the use of romiplostim in children aged 1-21 years with solid tumors, receiving chemotherapy to prevent thrombocytopenia, which was terminated due to low patient accruement.

In our study, we aim to explore the feasibility of using romiplostim in children with sarcomas, receiving myelosuppressive chemotherapy and its role in preventing CIT, thereby which we aim more effective administration of intense chemotherapy and prevent treatment delays.