Chronic MyeloMonocytic Leukemia (not CML)
Persistently high monocyte count- 3 months
Most frequent MDS/Myeloproliferative neoplasms – a cross between the two
Median age 72
Median survival 20-40 months
Transformation to AML (15-30%)
WHO definition of CMML:
1. Excess monocytes- persistent over 3 months, ≥ 1
- Monocytes 10% of total WC count
2. Dysplasia: morphological difference (blood film on BMBx)
OR
3. Genetic abnormalites ( on cytogenetics or molecular)
WHO Addition in 2022:
Persistent 3 months Monocytes ≥ 0.5 over 10% of WC count
AND Dysplasia
AND Genetic Abnormalities
No single diagnostic test
- Exclude MPNs: CML, MF, pre-fibrotic MF, PRV and ET
- Exclude Genetics: PDFGR A and B, FGFR 1, JAK-2 rearrangement
- Ensure less than 20% blasts
Common Presentation:
- Constitutional Sx
- Cytopenias and sequelae
- Effusions pericardial or pleural (inflammation and infiltration)
- Skin deposits
- Autoimmune disorders (higher incidence of CMML)
Classification:
-Myelodysplastic CMML- WC<13
o Cytopenias**
- Myeloproliferative CMML – WC ≥ 13
o Activate RAS pathway mutations
o Leukostasis**(*brain and lung*)
o More adverse clinical outcomes
o More splenomegaly and extra-medullary (infiltrative)
PROGNOSTIC CLASSIFICATION: Blast Count
- CMML-1: BMBx <10% blasts
- CMML-2: BMBx <20% blasts OR Presence of Auer Rods (trumps blast %)
OTHER:
o CPSS-Mol: cytogenetics, "NARS”, blast count, WBC count, transfusion dependence
Investigations
- R/O infection
- FBC and trend
- Blood film
- Flow of Peripheral blood (immunophenotyping): Chronic Panel
o Classical Monocyte MO1: CD14 +ve and CD16 -ve
- If >=94% MO1 on flow specific and sensitive for malignant
- Can help differentiate reactive monocytes MO3 (CD14 weak +ve, CD16 +ve)
-BMBx if appropriate as per age and fitness
o Aspirate: Dysplasia, Excess monocytes
o Flow: Acute panel (check blasts percentage)
o Cytogenetics:
- Poor cytogenetics: Trisomy 8, Chrom. 7 abnormalities, complex cytogenetics (3 or more cytogenetic abnormalities)
-Good cytogenetics: Isolated loss of chromosome Y
o Molecular: PCR in EDTA- “NARS”.....NRAS, ASXL1, RUNX1, SETBP1
Treatment decisions:
- High risk (AML risk) + Tx eligible -> Intensive chemo (AML style) and Tx
- Transplant outcomes: Overall survival approx. 30% but curable
- Low risk and not transplant eligible: QOL improvement
o Watch and wait
o Cytopenia supportive treatment w/ transfusions
o CMML-1 with raised WC count:
->Hydroxycarbimide as long as it provides benefit but can worsen cytopenias in patients with stable counts
o CMML-1 with significant cytopenias MML-2 with WC <13 with high risk of AML
-> Azacytidine (hypomethylating agent) Subcutaneous
Chronic MyeloMonocytic Leukemia (not CML)
Persistently high monocyte count- 3 months
Most frequent MDS/Myeloproliferative neoplasms – a cross between the two
Median age 72
Median survival 20-40 months
Transformation to AML (15-30%)
WHO definition of CMML:
1. Excess monocytes- persistent over 3 months, ≥ 1
- Monocytes 10% of total WC count
2. Dysplasia: morphological difference (blood film on BMBx)
OR
3. Genetic abnormalites ( on cytogenetics or molecular)
WHO Addition in 2022:
Persistent 3 months Monocytes ≥ 0.5 over 10% of WC count
AND Dysplasia
AND Genetic Abnormalities
No single diagnostic test
- Exclude MPNs: CML, MF, pre-fibrotic MF, PRV and ET
- Exclude Genetics: PDFGR A and B, FGFR 1, JAK-2 rearrangement
- Ensure less than 20% blasts
Common Presentation:
- Constitutional Sx
- Cytopenias and sequelae
- Effusions pericardial or pleural (inflammation and infiltration)
- Skin deposits
- Autoimmune disorders (higher incidence of CMML)
Classification:
-Myelodysplastic CMML- WC<13
o Cytopenias**
- Myeloproliferative CMML – WC ≥ 13
o Activate RAS pathway mutations
o Leukostasis**(*brain and lung*)
o More adverse clinical outcomes
o More splenomegaly and extra-medullary (infiltrative)
PROGNOSTIC CLASSIFICATION: Blast Count
- CMML-1: BMBx <10% blasts
- CMML-2: BMBx <20% blasts OR Presence of Auer Rods (trumps blast %)
OTHER:
o CPSS-Mol: cytogenetics, "NARS”, blast count, WBC count, transfusion dependence
Investigations
- R/O infection
- FBC and trend
- Blood film
- Flow of Peripheral blood (immunophenotyping): Chronic Panel
o Classical Monocyte MO1: CD14 +ve and CD16 -ve
- If >=94% MO1 on flow specific and sensitive for malignant
- Can help differentiate reactive monocytes MO3 (CD14 weak +ve, CD16 +ve)
-BMBx if appropriate as per age and fitness
o Aspirate: Dysplasia, Excess monocytes
o Flow: Acute panel (check blasts percentage)
o Cytogenetics:
- Poor cytogenetics: Trisomy 8, Chrom. 7 abnormalities, complex cytogenetics (3 or more cytogenetic abnormalities)
-Good cytogenetics: Isolated loss of chromosome Y
o Molecular: PCR in EDTA- “NARS”.....NRAS, ASXL1, RUNX1, SETBP1
Treatment decisions:
- High risk (AML risk) + Tx eligible -> Intensive chemo (AML style) and Tx
- Transplant outcomes: Overall survival approx. 30% but curable
- Low risk and not transplant eligible: QOL improvement
o Watch and wait
o Cytopenia supportive treatment w/ transfusions
o CMML-1 with raised WC count:
->Hydroxycarbimide as long as it provides benefit but can worsen cytopenias in patients with stable counts
o CMML-1 with significant cytopenias MML-2 with WC <13 with high risk of AML
-> Azacytidine (hypomethylating agent) Subcutaneous