Clinicopathologic characteristics and outcomes of patients with clonal hematopoiesis who progress to myeloid neoplasms

Clonal hematopoiesis (CH) is a non-malignant clonal expansion of a hematopoietic stem cell population due to the acquisition of somatic mutation(s) that confer advantages in self-renewal and proliferation. These mutations have been detected in healthy individuals and rise in frequency with normal aging [1]. The increase in prevalence of CH with age may reflect the cumulative effect of exposures to environmental stressors, such as radiation, tobacco, and mutagenic drugs, that provide selective pressure for particular hematopoietic stem cells and consequent clonal expansion [2]. Although its presence does not directly lead to oncologic disease, CH has been associated with an increased risk of hematologic malignancies and myeloid neoplasms (MNs), chronic inflammation, and cardiovascular complications [3].

The Clonal Hematopoiesis Risk Score (CHRS) is a personalized prediction tool incorporating age, peripheral blood laboratory values, specific mutations, and variant allele frequency (VAF) to assess the risk of progression to MNs in healthy adults with CH [4]. The impact of medical histories, especially prior cancer diagnosis and exposure to antineoplastic therapy, is not included. Additionally, although it is well established that CH increases risk of MN transformation, the dynamics of disease evolution in patients with CH who progress to MNs remain unknown. Thus, we aimed to evaluate the clinicopathologic characteristics and survival outcomes of patients with MN with known antecedent CH, with a particular focus on patients with prior non-myeloid malignancies.