Study Assesses Genetic Precursors in Childhood Chronic Thrombocytopenia

In patients with childhood-onset chronic thrombocytopenia, a study has used molecular analysis to determine the prevalence of inherited thrombocytopenia (IT), a set of conditions that increase risk for myelodysplastic syndrome and cancers. Slightly more than half of these patients have genetic precursors for IT, according to the study’s data, which were presented at the Society of Hematologic Oncology 2024 Annual Meeting in Houston, Texas.

“A significant group includes mutations predisposing to myelodysplastic syndrome and malignancies, primarily leukemias and lymphomas, such as Wiskott-Aldrich syndrome or RUNX1 familial platelet disorder,” the investigators wrote.

The study cohort included 156 patients with childhood-onset chronic thrombocytopenia. They had a median age of 8.99 years, and 92% of the cohort was pediatric patients. Each patient was evaluated with targeted next-generation sequencing using a panel of 750 genes which focused on IT. The study found that 84 patients, or 54% of the total cohort, had a molecular background for IT.

Among the patients with a molecular background for IT, 18 had backgrounds associated with IT syndrome types that predispose patients to cancer or bone marrow aplasia. They had a median age of 3.82 years and median platelet count upon referral of 44×109/L. Of those patients, 17 were pediatric.

Regarding which cancer-predisposing genetic defects were most common, five patients had defects in the WAS gene, four had defects in the RUNX1 gene, and three had defects in the ETV6 gene. Over a median follow-up of 3.69 years, malignancies developed in three patients in the form of acute lymphoblastic leukemia or acute myeloid leukemia, and there was one mortality due to leukemia progression.

“In our cohort, there is a notable predominance of pediatric patients with an early age of molecular evaluation, for whom prompt diagnosis enables appropriate oncological surveillance and genetic counseling, thereby acquiring crucial prognostic significance,” the investigators observed.

Reference

Urbański B, Bąbol-Pokora K, Janczar S, et al. Inherited thrombocytopenia syndromes may predispose to childhood malignancies – experiences from a Polish cohort. Abstract #MDS-325. Presented at the Society of Hematologic Oncology 2024 Annual Meeting; September 4-7, 2024; Houston, Texas.