Introduction
Thrombocytopenia in patients with hematologic malignancies often results from the disease itself or as a side effect of intensive chemotherapy. Persistent thrombocytopenia can lead to severe bleeding complications with associated morbidity and mortality.1 Current standard-of-care strategies, including platelet transfusions, chemotherapy dose reductions, and delays to allow spontaneous platelet recovery, are problematic for several reasons. Platelet transfusions provide only transient increases in platelet count, can cause multiple side effects, and are not effective in all patients. Additionally, chemotherapy dose reductions and delays can compromise antitumor efficacy, potentially leading to poorer outcomes. 2-4
Recombinant thrombopoietin receptor agonists (TPO-RAs) stimulate platelet production by binding to and activating the thrombopoietin receptor (c-MPL) on megakaryocyte progenitor cells, offering a pharmacologic approach to address thrombocytopenia in various clinical contexts. There are four currently available agents in the United States: the subcutaneous injectable drug romiplostim and the oral small-molecule agents eltrombopag, avatrombopag, and lusutrombopag. Romiplostim and eltrombopag are currently US Food and Drug Administration approved for pediatric and adult chronic immune thrombocytopenia (ITP)5,6, while the oral TPO-RAs have additional approvals for aplastic anemia7, periprocedural thrombocytopenia in patients with chronic liver disease8, and hepatitis-associated thrombocytopenia in adults9. TPO-RAs have been shown to effectively increase and sustain platelet counts with a favorable long-term safety profile across these clinical contexts5,10,11. Although TPO-RAs are not approved for chemotherapy-induced thrombocytopenia (CIT), studies in adults with predominantly solid tumors have shown that romiplostim improves platelet counts, leading to fewer chemotherapy delays and dose reductions without significant toxicities.3,12-15 Recent data also suggest eltrombopag is safe and effective for managing thrombocytopenia in adult patients with hematologic malignancies following chimeric antigen receptor (CAR)T-cell therapy. 16,17
Despite these promising data supporting the use of TPO-RAs across multiple clinical contexts in adults with cancer, the role of TPO-RAs in pediatric oncology is underexplored. Data on their safety and efficacy in children and young adults are limited, and the few available studies are focused primarily on solid malignancies in small cohorts.18-20 Although the National Comprehensive Cancer Network provides recommendations for managing thrombocytopenia in adults, including the use of TPO-RAs for CIT and ITP21, these guidelines do not extend to pediatric or adolescent and young adult (AYA) populations.
In light of these gaps, we report on our institutional experience of 15 pediatric and AYA patients with hematologic malignancies who received a TPO-RA between 2015 and 2023.