Clinical lymphoma, myeloma & leukemia · 2025
Characterization of Indolent Chronic Myelomonocytic Leukemia Phenotypes and Dynamic Features of Disease Progression.
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Aguirre Luis E, Ball Somedeb, Jain Akriti, Ali Najla Al, Sallman David A, Kuykendall Andrew, Sweet Kendra, Lancet Jeffrey E, Padron Eric, Komrokji Rami S
Аннотация
BACKGROUND: Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic disorder characterized by features of myeloproliferation and myelodysplasia. Various prognostic models incorporate clinical, cytogenetic, and molecular factors to assess risk and guide treatment decisions. However, there has been limited exploration of a subset of patients exhibiting more indolent disease behavior. Due to the significant heterogeneity in disease biology, clonal architecture, clinical presentation, and outcomes, identifying key markers is essential for predicting which patients may present with indolent disease and for recognizing those at greater risk of progression who may require early intervention.
PATIENTS AND METHODS: We analyzed baseline clinical and molecular parameters in 656 CMML patients, stratifying them into 2 groups: those observed for ≥ 3 years (indolent CMML) and those needing treatment within that period.
RESULTS: 14% of CMML patients exhibited indolent disease, correlating with superior outcomes (mOS: 78.5 months vs. 25 months in nonindolent cases). Indolent disease was associated with higher hemoglobin and platelet counts, JAK2 mutations, and fewer cytopenias. In contrast, features indicating the need for earlier treatment included leukocytosis, elevated lymphocyte/monocyte counts, higher percentage of circulating immature cells/blasts, increased marrow cellularity/blasts, and NRAS, ASXL1, and RUNX1 mutations. Changes in the M:E ratio, the presence of abnormally localized immature precursors (ALIP) and gain of mutations reflecting clonal evolution indicated clinical decline and need for timely treatment initiation.
CONCLUSION: A small proportion of CMML patients exhibit indolent features linked to better outcomes, contrasting with markers indicating earlier treatment initiation, which are associated with increased risk of progression; recognizing these markers aids in predicting disease aggressiveness.
PATIENTS AND METHODS: We analyzed baseline clinical and molecular parameters in 656 CMML patients, stratifying them into 2 groups: those observed for ≥ 3 years (indolent CMML) and those needing treatment within that period.
RESULTS: 14% of CMML patients exhibited indolent disease, correlating with superior outcomes (mOS: 78.5 months vs. 25 months in nonindolent cases). Indolent disease was associated with higher hemoglobin and platelet counts, JAK2 mutations, and fewer cytopenias. In contrast, features indicating the need for earlier treatment included leukocytosis, elevated lymphocyte/monocyte counts, higher percentage of circulating immature cells/blasts, increased marrow cellularity/blasts, and NRAS, ASXL1, and RUNX1 mutations. Changes in the M:E ratio, the presence of abnormally localized immature precursors (ALIP) and gain of mutations reflecting clonal evolution indicated clinical decline and need for timely treatment initiation.
CONCLUSION: A small proportion of CMML patients exhibit indolent features linked to better outcomes, contrasting with markers indicating earlier treatment initiation, which are associated with increased risk of progression; recognizing these markers aids in predicting disease aggressiveness.