Chronic Myelomonocytic leukemia: 2020 update on diagnosis, risk stratification and management

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Abstract

Disease overview: Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder with overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms, with an inherent risk for leukemic transformation (~15% over 3-5 years). Diagnosis: Diagnosis is based on the presence of sustained (>3 months) peripheral blood monocytosis (≥1 × 109/L; monocytes ≥10%), along with bone marrow dysplasia. Clonal cytogenetic abnormalities occur in ~ 30% of patients, while >90% have gene mutations. Mutations involving TET2 (~60%), SRSF2 (~50%), ASXL1 (~40%) and the oncogenic RAS pathway (~30%) are frequent; while the presence of ASXL1 and DNMT3A mutations and the absence of TET2 mutations negatively impact over-all survival. Risk stratification: Molecularly integrated prognostic models include; the Groupe Français des Myélodysplasies (GFM), Mayo Molecular Model (MMM) and the CMML specific prognostic model (CPSS-Mol). Risk factors incorporated into the MMM include presence of nonsense or frameshift ASXL1 mutations, absolute monocyte count>10 × 109/L, hemoglobin <10 g/dL, platelet count <100 × 109/L and the presence of circulating immature myeloid cells. The MMM stratifies CMML patients into four groups; high (≥3 risk factors), intermediate-2 (2 risk factors), intermediate-1 (1 risk factor) and low (no risk factors), with median survivals of 16, 31, 59 and 97 months, respectively. Risk-adapted therapy: Hypomethylating agents such as 5-azacitidine and decitabine are commonly used, with overall response rates of ~40%-50% and complete remission rates of ~7%-17%; with no impact on mutational allele burdens. Allogeneic stem cell transplant is the only potentially curative option, but is associated with significant morbidity and mortality.

Original languageEnglish (US)
Pages (from-to)97-115
Number of pages19
JournalAmerican journal of hematology
Volume95
Issue number1
DOIs
StatePublished - Jan 1 2020

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Leukemia, Myelomonocytic, Chronic
Risk Management
Molecular Models
Mutation
decitabine
Monocytes
Developmental Bone Disease
Azacitidine
Frameshift Mutation
Survival
Myelodysplastic Syndromes
Myeloid Cells
Hematopoietic Stem Cells
Platelet Count
Chromosome Aberrations
Hemoglobins
Stem Cells
Bone Marrow
Alleles
Morbidity

ASJC Scopus subject areas

  • Hematology

Cite this

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title = "Chronic Myelomonocytic leukemia: 2020 update on diagnosis, risk stratification and management",
abstract = "Disease overview: Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder with overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms, with an inherent risk for leukemic transformation (~15{\%} over 3-5 years). Diagnosis: Diagnosis is based on the presence of sustained (>3 months) peripheral blood monocytosis (≥1 × 109/L; monocytes ≥10{\%}), along with bone marrow dysplasia. Clonal cytogenetic abnormalities occur in ~ 30{\%} of patients, while >90{\%} have gene mutations. Mutations involving TET2 (~60{\%}), SRSF2 (~50{\%}), ASXL1 (~40{\%}) and the oncogenic RAS pathway (~30{\%}) are frequent; while the presence of ASXL1 and DNMT3A mutations and the absence of TET2 mutations negatively impact over-all survival. Risk stratification: Molecularly integrated prognostic models include; the Groupe Fran{\cc}ais des My{\'e}lodysplasies (GFM), Mayo Molecular Model (MMM) and the CMML specific prognostic model (CPSS-Mol). Risk factors incorporated into the MMM include presence of nonsense or frameshift ASXL1 mutations, absolute monocyte count>10 × 109/L, hemoglobin <10 g/dL, platelet count <100 × 109/L and the presence of circulating immature myeloid cells. The MMM stratifies CMML patients into four groups; high (≥3 risk factors), intermediate-2 (2 risk factors), intermediate-1 (1 risk factor) and low (no risk factors), with median survivals of 16, 31, 59 and 97 months, respectively. Risk-adapted therapy: Hypomethylating agents such as 5-azacitidine and decitabine are commonly used, with overall response rates of ~40{\%}-50{\%} and complete remission rates of ~7{\%}-17{\%}; with no impact on mutational allele burdens. Allogeneic stem cell transplant is the only potentially curative option, but is associated with significant morbidity and mortality.",
author = "Patnaik, {Mrinal M.} and Ayalew Tefferi",
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AU - Patnaik, Mrinal M.

AU - Tefferi, Ayalew

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N2 - Disease overview: Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder with overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms, with an inherent risk for leukemic transformation (~15% over 3-5 years). Diagnosis: Diagnosis is based on the presence of sustained (>3 months) peripheral blood monocytosis (≥1 × 109/L; monocytes ≥10%), along with bone marrow dysplasia. Clonal cytogenetic abnormalities occur in ~ 30% of patients, while >90% have gene mutations. Mutations involving TET2 (~60%), SRSF2 (~50%), ASXL1 (~40%) and the oncogenic RAS pathway (~30%) are frequent; while the presence of ASXL1 and DNMT3A mutations and the absence of TET2 mutations negatively impact over-all survival. Risk stratification: Molecularly integrated prognostic models include; the Groupe Français des Myélodysplasies (GFM), Mayo Molecular Model (MMM) and the CMML specific prognostic model (CPSS-Mol). Risk factors incorporated into the MMM include presence of nonsense or frameshift ASXL1 mutations, absolute monocyte count>10 × 109/L, hemoglobin <10 g/dL, platelet count <100 × 109/L and the presence of circulating immature myeloid cells. The MMM stratifies CMML patients into four groups; high (≥3 risk factors), intermediate-2 (2 risk factors), intermediate-1 (1 risk factor) and low (no risk factors), with median survivals of 16, 31, 59 and 97 months, respectively. Risk-adapted therapy: Hypomethylating agents such as 5-azacitidine and decitabine are commonly used, with overall response rates of ~40%-50% and complete remission rates of ~7%-17%; with no impact on mutational allele burdens. Allogeneic stem cell transplant is the only potentially curative option, but is associated with significant morbidity and mortality.

AB - Disease overview: Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder with overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms, with an inherent risk for leukemic transformation (~15% over 3-5 years). Diagnosis: Diagnosis is based on the presence of sustained (>3 months) peripheral blood monocytosis (≥1 × 109/L; monocytes ≥10%), along with bone marrow dysplasia. Clonal cytogenetic abnormalities occur in ~ 30% of patients, while >90% have gene mutations. Mutations involving TET2 (~60%), SRSF2 (~50%), ASXL1 (~40%) and the oncogenic RAS pathway (~30%) are frequent; while the presence of ASXL1 and DNMT3A mutations and the absence of TET2 mutations negatively impact over-all survival. Risk stratification: Molecularly integrated prognostic models include; the Groupe Français des Myélodysplasies (GFM), Mayo Molecular Model (MMM) and the CMML specific prognostic model (CPSS-Mol). Risk factors incorporated into the MMM include presence of nonsense or frameshift ASXL1 mutations, absolute monocyte count>10 × 109/L, hemoglobin <10 g/dL, platelet count <100 × 109/L and the presence of circulating immature myeloid cells. The MMM stratifies CMML patients into four groups; high (≥3 risk factors), intermediate-2 (2 risk factors), intermediate-1 (1 risk factor) and low (no risk factors), with median survivals of 16, 31, 59 and 97 months, respectively. Risk-adapted therapy: Hypomethylating agents such as 5-azacitidine and decitabine are commonly used, with overall response rates of ~40%-50% and complete remission rates of ~7%-17%; with no impact on mutational allele burdens. Allogeneic stem cell transplant is the only potentially curative option, but is associated with significant morbidity and mortality.

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