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Mayo prognostic model for WHO-defined chronic myelomonocytic leukemia: ASXL1 and spliceosome component mutations and
M M Patnaik1, E Padron, R R LaBorde
1Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Insights
A new prognostic model for chronic myelomonocytic leukemia (CMML) identifies key risk factors for survival. This model, using absolute monocyte count, circulating immature myeloid cells, hemoglobin, and platelet count, improves patient outcome prediction.
Area of Science:
- Hematology
- Oncology
- Clinical Pathology
Background:
- Chronic myelomonocytic leukemia (CMML) is a heterogeneous myeloid neoplasm with variable prognosis.
- Accurate prognostic models are crucial for guiding treatment decisions and patient management in CMML.
Purpose of the Study:
- To evaluate the prognostic relevance of clinical and laboratory parameters in CMML patients.
- To develop and validate a novel prognostic model for overall and leukemia-free survival in CMML.
Main Methods:
- Retrospective analysis of 226 Mayo Clinic patients with CMML.
- Univariate and multivariable analyses to identify significant prognostic factors.
- Development and validation of a new prognostic model using key identified risk factors.
Main Results:
- Increased absolute monocyte count (AMC), circulating immature myeloid cells (IMCs), decreased hemoglobin, and decreased platelet count were significant independent predictors of poor survival.
- Spliceosome component and ASXL1 mutations did not impact survival in this cohort.
- The novel prognostic model demonstrated superior performance in predicting overall and leukemia-free survival compared to conventional models, validated in an independent cohort.
Conclusions:
- A refined prognostic model incorporating AMC, IMCs, hemoglobin, and platelet count offers improved risk stratification for CMML patients.
- This model can aid in clinical decision-making and patient counseling regarding prognosis.
- Further validation in larger, diverse cohorts is warranted to solidify its clinical utility.
Abstract:
We evaluated the prognostic relevance of several clinical and laboratory parameters in 226 Mayo Clinic patients with chronic myelomonocytic leukemia (CMML): 152 (67%) males and median age 71 years. At a median follow-up of 15 months, 166 (73%) deaths and 33 (14.5%) leukemic transformations were documented. In univariate analysis, significant risk factors for survival included anemia, thrombocytopenia, increased levels of white blood cells, absolute neutrophils, absolute monocyte count (AMC), absolute lymphocytes, peripheral blood and bone marrow blasts, and presence of circulating immature myeloid cells (IMCs). Spliceosome component (P=0.4) and ASXL1 mutations (P=0.37) had no impact survival. On multivariable analysis, increased AMC (>10 × 10(9)/l, relative risk (RR) 2.5, 95% confidence interval (CI) 1.7-3.8), presence of circulating IMC (RR 2.0, 95% CI 1.4-2.7), decreased hemoglobin (<10 g/dl, RR 1.6, 99% CI 1.2-2.2) and decreased platelet count (<100 × 10(9)/l, RR 1.4, 99% CI 1.0-1.9) remained significant. Using these four risk factors, a new prognostic model for overall (high risk, RR 4.4, 95% CI 2.9-6.7; intermediate risk, RR 2.0, 95% CI 1.4-2.9) and leukemia-free survival (high risk, RR 4.9, 95% CI 1.9-12.8; intermediate risk, RR 2.6, 95% CI 1.1-5.9) performed better than other conventional risk models and was validated in an independent cohort of 268 CMML patients.
