Inferior Survival in Therapy-Related Chronic Myelomonocytic Leukemia: A Population-Based Analysis

The prognostic impact of therapy-related chronic myelomonocytic leukemia (t-CMML) compared with de novo CMML (dnCMML) remains uncertain, in part due to the absence of therapy-related designations in cancer registries.

Using the Surveillance, Epidemiology, and End Results (SEER) database, we compared outcomes between de novo CMML (dnCMML) and therapy-related CMML (t-CMML), operationally defined by antecedent chemotherapy and/or radiotherapy and diagnosis as a subsequent primary malignancy. Survival was evaluated by antecedent treatment exposure and within major antecedent malignancy groups. Additional operational definitions of t-CMML were evaluated to assess the robustness of findings.

Among 8,432 patients diagnosed with CMML between 2000 and 2022 after exclusion of antecedent myeloid malignancies, 594 (7.0%) met criteria for the primary definition of t-CMML. Median overall survival (OS) for the entire CMML cohort was 18 months, with shorter median OS observed for t-CMML compared with de novo CMML (14 vs 19 months). On multivariable Cox regression adjusted for age, sex, race, and era of diagnosis, t-CMML was associated with an increased risk of death (hazard ratio 1.20, 95% CI 1.09-1.32). Compared with dnCMML, inferior OS was observed among patients with recorded chemotherapy exposure but not among those treated with radiotherapy alone. Direct comparisons between chemotherapy-exposed and radiotherapy-only patients showed no significant difference in OS in the pooled adjusted analysis or within individual antecedent malignancy groups. Increasing definitional stringency was associated with stepwise worsening OS.

Registry-defined t-CMML was associated with inferior survival compared with de novo disease. Although chemotherapy-exposed t-CMML was associated with poorer outcomes relative to dnCMML, OS did not differ significantly between chemotherapy-exposed and radiotherapy-only patients in direct pooled or malignancy-specific comparisons. Studies integrating detailed treatment histories with molecular and cytogenetic data are needed to clarify the biology and prognostic significance of t-CMML.