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Classification and defining features of myelodysplastic neoplasms²²⁶

Classification and defining features of myelodysplastic neoplasms (MDS)
	Blasts	Cytogenetic	Mutations
MDS with defining genetic abnormalities
MDS with low blasts and isolated 5q deletion (MDS-5q)	<5% BM and <2% PB	5q deletion alone, or with 1 other abnormality other than monosomy 7 or 7q deletion
MDS with low blasts and SF3B1 mutation^a (MDS-SF3B1)	<5% BM and <2% PB	Absence of 5q deletion, monosomy 7, or complex karyotype	SF3B1
MDS with biallelic TP53 inactivation (MDS-biTP53)	<20% BM and PB	Usually complex	Two or more TP53 mutations, or 1 mutation with evidence of TP53 copy number loss or cnLOH
MDS, morphologically defined
MDS with low blasts (MDS-LB)	<5% BM and <2% PB
MDS, hypoplastic^b (MDS-h)	<5% BM and <2% PB
MDS with increased blasts (MDS-IB)
MDS-IB1	5-9% BM or 2-4% PB
MDS-IB2	10-19% BM or 5-19% PB or Auer rods
MDS with fibrosis (MDS-f)	5-19% BM; 2-19% PB

Diagnostic criteria for chronic myelomonocytic leukemia (CMML)
Prerequisite criteria
1. Persistent absolute (≥0.5 x 10⁹/L) and relative (≥10%) peripheral blood monocytosis
2. Blasts constitute <20% of the cells in the peripheral blood and bone marrow^c
3. Not meeting diagnostic criteria of chronic myeloid leukaemia or other myeloproliferative neoplasms^d
4. Not meeting diagnostic criteria of myeloid/lymphoid neoplasms with tyrosine kinase fusions^e
Supporting criteria
1. Dysplasia involving ≥1 myeloid lineages^f
2. Acquired clonal cytogenetic or molecular abnormality
3. Abnormal partitioning of peripheral blood monocyte subsets^g
Requirements for diagnosis
Prerequisite criteria must be present in all cases
If monocytosis is ≥ 1 x 10⁹/L: one or more supporting criteria must be met
If monocytosis is ≥0.5 and < 1 x 10⁹/L: supporting criteria 1 and 2 must be met
Subtyping criteria
Myelodysplastic CMML (MD-CMML): WBC < 13 x 10⁹/L
Myeloproliferative CMML (MP-CMML): WBC ≥ 13 x 10⁹/L
Subgrouping criteria (based on percentage of blasts and promonocytes)
CMML-1: <5% in peripheral blood and <10% in bone marrow
CMML-2: 5-19% in peripheral blood and 10-19% in bone marrow

Summary of MDS/MPN WHO 2022²²⁶

CMML criteria – major revision
- Lower cut-off for monocytosis
- MD-CMML vs MP=CMML subtypes
- CMML-0 eliminated
Atypical CML renamed MDS/MPN with neutrophilia
MDS/MPN-RS-t now MDS/MPN with SF3B1 mutation & thrombocytosis

^aDetection of ≥15% ring sideroblasts may substitute for SF3B1 mutation. Acceptable related terminology: MDS with low blasts and ring sideroblasts; ^bBy definition, ≤25% bone marrow cellularity, age adjusted; ^cBlasts and blast equivalents incude myeloblasts, monoblasts and promonocytes; ^d neoplasms (MPN) can be associated with monocytosis at presentation or during the course of the disease; such cases can mimic CMML. In these instances, a documented history of MPN excludes CMML. The presence of MPN features in the bone marrow and/or high burden of MPN-associated mutations (JAK2, CALR or MPL) tends to support MPN with monocytosis rather than CMML; ^eCriteria for myeloid/lymphoid neoplasms with tyrosine kinase fusions should be specifically excluded in cases with eosinophilia; ^fMorphologic dysplasia should be present in ≥10% of cells of a haematopoietic lineage in the bone marrow; ^gBased on detection of increased classical monocytes (>94%) in the absence of known active autoimmune diseases and/or systemic inflammatory syndromes.
BM bone marrow, PB peripheral blood, cnLOH copy neutral loss of heterozygosity