Use of thrombopoietin receptor agonists for thrombocytopenia in pediatric malignancies: A retrospective cohort study

Abstract Background: Thrombocytopenia is a common and clinically significant complication in pediatric patients undergoing treatment for both hematologic and solid malignancies. Thrombopoietin receptor agonists (TPO-RAs), including eltrombopag and romiplostim, have demonstrated efficacy in adults and in chemotherapy induced thrombocytopeniaHowever, their use in pediatric oncology remains off-label and poorly characterized. We describe our institutional experience using TPO-RAs in pediatric patients with malignancies who developed chemotherapy induced thrombocytopenia. Methods: We conducted a retrospective cohort study of pediatric patients with chemotherapy induced thrombocytopenia treated at Mayo Clinic between May 1, 2018, and February 6, 2025. Eligible patients received eltrombopag or romiplostim for chemotherapy induced thrombocytopenia. Clinical and treatment characteristics were extracted from the electronic medical record. Primary outcomes included platelet count response and changes in transfusion requirements. Secondary outcomes included bleeding events, time to hematopoietic recovery, and treatment-related adverse events. Results: Six patients (50% male; median age 14 years) with diagnoses including neuroblastoma, Ewing sarcoma, hepatoblastoma, and CNS malignancies received TPO-RA therapy (eltrombopag n=3; romiplostim n=3). Four patients (67%) were treated in the setting of relapsed disease. The median duration of therapy was 6 weeks (range, 3–12). The median starting and ending doses were 75 mg daily for eltrombopag and 3 mcg/kg and 5 mcg/kg, respectively, for romiplostim. Baseline platelet counts increased from a mean of 54 ×10⁹/L to 109 ×10⁹/L by week 4. The median time to a platelet count >50 ×10⁹/L was 4.9 weeks. Platelet transfusion requirements decreased from a mean of 9.8 units pre-treatment to 3.0 units post-treatment. No grade ≥3 bleeding events, thrombotic complications, or clonal evolution were observed. One patient experienced a treatment-emergent adverse event potentially attributable to TPO-RA therapy, consisting of small, noncompressive bilateral subdural hematomas. The event occurred in the context of previously unreported aspirin use and did not require neurosurgical intervention. Discontinuation occurred due to either achievement of platelet goals or underlying disease progression. Conclusions: TPO-RAs may offer a viable adjunctive strategy for managing chemotherapy induced thrombocytopenia in pediatric patients with solid malignancies. In this small cohort, TPO-RA therapy was associated with improved platelet counts, reduced transfusion burden, and a favorable safety profile. These findings support further prospective investigation into the safety, efficacy, and optimal use of TPO-RAs in pediatric oncology.