INFO PANEL

Diagnostic criteria for chronic myelomonocytic leukemia (CMML)
Monocytosis defined as monocytes ≥ 0.5 x 10⁹/L and ≥ 10% of the WBC
Cytopenia (thresholds the same as MDS)^*
Blasts (including promonocytes) < 20% of the cells in blood and bone marrow
Presence of clonality: abnormal cytogenetics and/or presence of at least one myeloid neoplasm associated mutation of at least 10% allele frequency^†
In cases without evidence of clonality, Monocytes ≥ 1.0 x 10⁹/L and > 10% of the WBC, and Increased blasts (including promonocytes),^‡ or morphologic dysplasia, or An abnormal immunophenotype consistent with CMML would be required for its diagnosis
Bone marrow examination with morphologic findings consistent with CMML (hypercellularity due to myeloid proliferation often with increased monocytes), and lacking diagnostic features of acute myeloid leukemia, MPN or other conditions associated with monocytosis^§
No BCR::ABL1 or genetic abnormalities of myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions

Diagnostic criteria for clonal monocytosis of undetermined significance (CMUS)
Persistent monocytosis defined as monocytes 0.5 x 10⁹/L and ≥ 10% of the WBC
Absence or presence of cytopenia (thresholds same as for MDS)^¶
Presence of at least one myeloid neoplasm associated mutation of appropriate allele frequency (i.e., ≥ 2%)^#
No significant dysplasia, increased blasts (including promonocytes) or morphological findings of CMML on bone marrow examination^\|\|
No criteria for a myeloid or other hematopoietic neoplasm are fulfilled
No reactive condition that would explain a monocytosis is detected

*Diagnostic criteria for myelodysplastic/myeloproliferative neoplasm with SF3B1* mutation and thrombocytosis (MDS/MPN-T-SF3B1)**
Thrombocytosis, with platelet count ≥ 450 x 10⁹/L
Anemia (threshold same as MDS)
Blasts < 1% in blood and < 5% in bone marrow
Presence of SF3B1 mutation (VAF > 10%), isolated or associated with abnormal cytogenetics and/or other myeloid neoplasm associated mutations
No history of recent cytotoxic or growth factor therapy that could explain the myelodysplastic/myeloproliferative features
No BCR:ABL1 or genetic abnormalities of myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions; no t(3;3)(q21.3;q26.2), inv(3)(q21.3q26.2), or del(5q)^**
No history of MPN, MDS, or other myelodysplastic/myeloproliferative neoplasm

Diagnostic criteria for myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis, not otherwise specified (MDS/MPN-RS-T, NOS)
Thrombocytosis, with platelet count ≥ 450 x 10⁹/L
Anemia associated with erythroid-lineage dysplasia, with or without multilineage dysplasia, and ≥ 15% ring sideroblasts
Blasts < 1% in blood and < 5% in bone marrow
Presence of clonality: demonstration of a clonal cytogenetic abnormality and/or somatic mutation(s). In their absence, no history of recent cytotoxic or growth factor therapy that could explain the myelodysplastic/myeloproliferative features
Absence of SF3B1 mutation; no BCR::ABL1 or genetic abnormalities of myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions; no t(3;3)(q21.3;q26.2), inv(3)(q21.3q26.2), or del(5q)^**
No history of MPN, MDS, or other MDS/MPN

Diagnostic criteria for myelodysplastic/myeloproliferative neoplasm, not otherwise specified (MDS/MPN, NOS)
Myeloid neoplasm with mixed myeloproliferative and myelodysplastic features, not meeting the criteria for any other MDS/MPN, MDS, MPN^††
Cytopenia (thresholds same as for MDS)
Blasts < 20% of the cells in blood and bone marrow
A platelet count of ≥ 450 x 10⁹/L and/or a white blood cell count of ≥ 13 x 10⁹/L
Presence of clonality: demonstration of a clonal cytogenetic abnormality and/or somatic mutation(s). If clonality cannot be determined, the findings have persisted and all other causes (e.g., history of cytotoxic or growth factor therapy or other primary cause that could explain the myelodysplastic/myeloproliferative features) have been excluded.
No BCR::ABL1 or genetic abnormalities of myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions; no t(3;3)(q21.3;q26.2), inv(3)(q21.3q26.2)^‡‡ or del(5q)^§§

^*A small proportion of cases may show only borderline or no cytopenia usually in early phase disease; ^† Based on International Consensus Group Conference, Vienna, 2018²²⁸; ^‡ Increased blasts: ≥5% in the bone marrow and/or ≥2% in the peripheral blood; ^§ For cases lacking bone marrow findings of SMML, a diagnosis of CMUS could be considered. If cytopenia is present, a diagnosis of CCMUS could be entertained. In these diagnostic settings, however, an alternative cause for the observed monocytosis would have to be excluded based on appropriate clinicopathological correlations; ^¶ If cytopenia is present the nomenclature of CCMUS is suggested; ^# VAF threshold based on International Consensus Group Conference, Vienna, 2018.²⁶⁰; ^|| Bone marrow findings of CMML include hypercellularity with myeloid predominance, often with increased monocytes and in a proportion of cases monoblasts and/or blast equivalents (ie, promonocytes) and/or dysplasia in at least 1 lineage; ^**In a case that otherwise meets the diagnostic criteria for myelodysplastic syndrome with del(5q); ^†† MPNs, in particular those in accelerated phase and/or in post-PV or post-EV myelofibrotic stage, may simulate MDS/MPN, NOS. A history of MPN and/or the presence of MPN-associated mutations (in JAK2, CALR, or MPL) particularly if associated with a high VAF, tend to exclude a diagnosis of MDS/MPN, NOS. The presence of hypereosinophilia would favor a diagnosis of CEL, NOS; ^‡‡ In a case that otherwise meets criteria for MDS-NOS; ^§§ In a case that otherwise meets the diagnostic criteria for MDS with isolated del(5q).