Chronic Monomyelocytic Leukemia (CMML)

 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 

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