Abstract
BACKGROUND: Chronic myelomonocytic leukemia (CMML) is largely a disease of individuals older than 50 years; its occurrence in patients aged 50 years and younger is rare. The authors sought to characterize the clinicopathologic features and genetic profile of young-onset (age 50 years and younger) CMML (y-CMML) compared with older onset (older than 50 years) CMML (o-CMML). METHODS: The authors conducted a multi-institutional study of 32 patients with y-CMML and 119 patients with o-CMML, analyzing clinical, morphologic, cytogenetic, and molecular data. RESULTS: Patients who had y-CMML frequently presented with splenomegaly (59% vs. 11%; p < .001) and hepatomegaly (25% vs. 2%; p < .001) compared with those who had o-CMML. Although the overall incidence of cytogenetic abnormalities was similar, patients who had y-CMML exhibited distinct mutational patterns. PTPN11 mutations were significantly more common in y-CMML (13% vs. 3%; p = .034) than in o-CMML, whereas TET2 (6% vs. 57%; p < .001) and SRSF2 (16% vs. 46%; p = .002) mutations were significantly less frequent. In addition, multi-hit TET2 (6% vs. 34%; p = .002) and TET2-SRSF2 (3% vs. 29%; p = .003) co-mutations were rare in y-CMML. However, the molecular differences did not affect the CMML-specific risk-stratification categories because the clinical outcomes, including overall survival and leukemia-free survival, did not differ between the two groups. CONCLUSIONS: CMML in patients aged 50 years and younger is rare and presents with unique clinical and mutational features, suggesting a distinct pathogenesis.