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.