From the Guidelines
The diagnostic workup for Chronic Myelomonocytic Leukemia (CMML) should include a patient's history, physical examination, complete blood count, peripheral blood smear examination, bone marrow aspiration and biopsy, conventional cytogenetic analysis, and molecular assays to exclude other conditions, as recommended by the SIE, SIES, and GITMO groups 1. The initial evaluation should focus on excluding reactive causes of monocytosis, such as infectious diseases and solid tumors.
- Key components of the diagnostic workup include:
- Patient's history and physical examination to assess spleen size and search for cutaneous lesions
- Complete blood count and peripheral blood smear examination with differential leukocyte count to identify monocyte count, dysgranulopoiesis, and presence of promonocytes, blasts, and neutrophil precursors
- Bone marrow aspiration and biopsy to evaluate marrow cellularity, dysplasia, and hyperplasia of megakaryocyte compartment, blast count, and bone marrow fibrosis
- Conventional cytogenetic analysis to detect acquired clonal chromosomal abnormalities and exclude t(9;22) and t(5;12) translocations
- Molecular assays to exclude bcr/abl fusion gene and rearrangement of PDGFRA and PDGFRB, and to validate potential diagnostic molecular biomarkers, such as SRSF2, TET2, JAK2, or RAS mutations 1. The diagnostic workup should also include staining of bone marrow biopsy sections with hematoxylin-eosin, immunostaining for CD34+ and monocytic cells, and Gomori's silver impregnation for fibrosis.
- Additional tests, such as serum chemistry panel, LDH, iron studies, vitamin B12, and folate levels, may be necessary to rule out other conditions that can cause monocytosis. A comprehensive diagnostic approach is essential to ensure accurate diagnosis and appropriate risk stratification for treatment planning, as recommended by the SIE, SIES, and GITMO groups 1.
From the Research
Diagnostic Workup for Chronic Myelomonocytic Leukemia (CMML)
The diagnostic workup for CMML involves several key components, including:
- Bone marrow biopsy and aspirate with thorough evaluation 2
- Morphologic criteria, including monocyte-dominant leukocytosis, dysplastic changes, and increased blasts in the bone marrow 3
- Identification of monocyte subtypes in peripheral blood using multiparameter flow cytometry 3
- Cytogenetic abnormalities, which occur in approximately 30% of patients 4, 5
- Molecular evidence of clonality, with over 95% of patients harboring somatic mutations 4
Key Diagnostic Criteria
The diagnosis of CMML is based on the presence of:
- Sustained (>3 months) peripheral blood monocytosis (≥0.5 × 10^9/L; monocytes ≥10% of leukocyte count) 4
- Consistent bone marrow morphology 4
- <20% bone marrow or peripheral blood blasts (including promonocytes) 4
- Cytogenetic or molecular evidence of clonality 4
Risk Stratification
Several risk models are used to stratify CMML patients, including:
- The Mayo Molecular Model (MMM), which incorporates factors such as ASXL1 mutations, absolute monocyte count, hemoglobin, platelet count, and circulating immature myeloid cells 4, 5
- The Groupe Français des Myélodysplasies (GFM) and CMML-specific prognostic model (CPSS-Mol) 5 These models help identify high-risk patients who may benefit from allogeneic stem cell transplantation 4, 5