WHO Diagnostic Criteria Flashcards
Primary myelofibrosis
PMF
Major
Megakaryocyte abnormality, reticulin grade 2+
Not meeting other mpn criteria
JAK2 MPL CALR
Other clinical marker (ASXL1, TET2, EZH1, SRSF2, SF3B1,)
Minor Leukoerythroblastic Leukocyte >11 Anaemia Palpable splenomegaly LDH
NB prePMF reticulin grade 1
Not leucoerythroblastic
CMML
CMML-0 <2%
CMML -1 2-4% PB 5-q10%BM
CMML 2 5-19 % PB 10-19% BM
CMML diagnostic criteria
• Persistent PB monocytosis ≥1 × 109/L, with monocytes accounting for ≥10% of the WBC count
• Not meeting WHO criteria for BCR-ABL1+ CML, PMF, PV, or ET*
- No evidence of PDGFRA, PDGFRB, or FGFR1 rearrangement or PCM1-JAK2 (should be specifically excluded in cases with eosinophilia)
- <20% blasts in the blood and BM†
• Dysplasia in 1 or more myeloid lineages. If myelodysplasia is absent or minimal, the diagnosis of CMML may still be made if the other requirements are met and
• An acquired clonal cytogenetic or molecular genetic abnormality is present in hemopoietic cells‡
or
• The monocytosis (as previously defined) has persisted for at least 3 mo and
• All other causes of monocytosis have been excluded
Eosinophilia plus myeloid/lymphoid neoplasm
PDGFRA Eosinophilia Cryptic deletion at 4q12 Respond to TKI
↑Serum tryptase
FIP1L1-PDGFRA, at least 66 other partners
↑Marrow mast cells
PDGFRB Eosinophilia t(5;12)(q32;p13.2)
ETV6-PDGFRB, at least 25 other partners Respond to TKI
Monocytosis mimicking CMML
FGFR1 Eosinophilia Translocations of 8p11.2 Poor prognosis; do not respond to TKI
Often presents with T-ALL or AML
FGFR1-various partners
PCM1-JAK2 Eosinophilia t(8;9)(p22;p24.1) PCM1-JAK2 May respond to JAK2 inhibitors
ET
WHO ET criteria
Major criteria
1. Platelet count ≥450 × 109/L
2. BM biopsy showing proliferation mainly of the megakaryocyte lineage with increased numbers of enlarged, mature megakaryocytes with hyperlobulated nuclei. No significant increase or left shift in neutrophil granulopoiesis or erythropoiesis and very rarely minor (grade 1) increase in reticulin fibers
3. Not meeting WHO criteria for BCR-ABL1+ CML, PV, PMF, myelodysplastic syndromes, or other myeloid neoplasms
4. Presence of JAK2, CALR, or MPL mutation
Minor criterion
Presence of a clonal marker or absence of evidence for reactive thrombocytosis
Diagnosis of ET requires meeting all 4 major criteria or the first 3 major criteria and the minor criterion
PV
Major criteria 1. Hemoglobin >16.5 g/dL in men Hemoglobin >16.0 g/dL in women or, Hematocrit >49% in men Hematocrit >48% in women or, increased red cell mass (RCM)* 2. BM biopsy showing hypercellularity for age with trilineage growth (panmyelosis) including prominent erythroid, granulocytic, and megakaryocytic proliferation with pleomorphic, mature megakaryocytes (differences in size) 3. Presence of JAK2V617F or JAK2 exon 12 mutation
Minor criterion
Subnormal serum erythropoietin level
Diagnosis of PV requires meeting either all 3 major criteria, or the first 2 major criteria and the minor criterion†
aCML
- PB leukocytosis due to increased numbers of neutrophils and their precursors (promyelocytes, myelocytes, metamyelocytes) comprising ≥10% of leukocytes)
- Dysgranulopoiesis, which may include abnormal chromatin clumping
- No or minimal absolute basophilia; basophils usually <2% of leukocytes
- No or minimal absolute monocytosis; monocytes <10% of leukocytes
- Hypercellular BM with granulocytic proliferation and granulocytic dysplasia, with or without dysplasia in the erythroid and megakaryocytic lineages
- <20% blasts in the blood and BM
- No evidence of PDGFRA, PDGFRB, or FGFR1 rearrangement, or PCM1-JAK2
- Not meeting WHO criteria for BCR-ABL1+ CML, PMF, PV, or ET*
MPS MPN RS and thrombocytosis
MDS/MPN diagnostic criteria
• Anemia associated with erythroid lineage dysplasia with or without multilineage dysplasia, ≥15% ring sideroblasts,* <1% blasts in PB and <5% blasts in the BM
• Persistent thrombocytosis with platelet count ≥450 × 109/L
• Presence of a SF3B1 mutation or, in the absence of SF3B1 mutation, no history of recent cytotoxic or growth factor therapy that could explain the myelodysplastic/myeloproliferative features†
• No BCR-ABL1 fusion gene, no rearrangement of PDGFRA, PDGFRB, or FGFR1; or PCM1-JAK2; no (3;3)(q21;q26), inv(3)(q21q26) or del(5q)‡
• No preceding history of MPN, MDS (except MDS-RS), or other type of MDS/MPN
*At least 15% ring sideroblasts required even if SF3B1 mutation is detected.†A diagnosis of MDS/MPN-RS-T is strongly supported by the presence of SF3B1 mutation together with a mutation in JAK2 V617F, CALR, or MPL genes.
‡In a case which otherwise fulfills the diagnostic criteria for MDS with isolated del(5q)-no or minimal absolute basophilia; basophils usually <2% of leukocytes.
Jmml
JMML diagnostic criteria
I. Clinical and hematologic features (all 4 features mandatory)
• PB monocyte count ≥1 × 109/L
• Blast percentage in PB and BM <20%
• Splenomegaly
• Absence of Philadelphia chromosome (BCR/ABL1 rearrangement)
II. Genetic studies (1 finding sufficient)
• Somatic mutation in PTPN11* or KRAS* or NRAS*
• Clinical diagnosis of NF1 or NF1 mutation
• Germ line CBL mutation and loss of heterozygosity of CBL†
III. For patients without genetic features, besides the clinical and hematologic features listed under I, the following criteria must be fulfilled:
• Monosomy 7 or any other chromosomal abnormality or at least 2 of the following criteria:
• Hemoglobin F increased for age
• Myeloid or erythroid precursors on PB smear
• GM-CSF hypersensitivity in colony assay
• Hyperphosphorylation of STAT5
Germline and myeloid
Myeloid neoplasm classification
Myeloid neoplasms with germ line predisposition without a preexisting disorder or organ dysfunction
AML with germ line CEBPA mutation
Myeloid neoplasms with germ line DDX41 mutation*
Myeloid neoplasms with germ line predisposition and preexisting platelet disorders
Myeloid neoplasms with germ line RUNX1 mutation*
Myeloid neoplasms with germ line ANKRD26 mutation*
Myeloid neoplasms with germ line ETV6 mutation*
Myeloid neoplasms with germ line predisposition and other organ dysfunction
Myeloid neoplasms with germ line GATA2 mutation
Myeloid neoplasms associated with BM failure syndromes
Myeloid neoplasms associated with telomere biology disorders
JMML associated with neurofibromatosis, Noonan syndrome or
Noonan syndrome-like disorders
Myeloid neoplasms associated with Down syndrome*
Acc CML
CML, accelerated phase
CML, accelerated phase criteria
Any 1 or more of the following hematologic/cytogenetic criteria or response-to-TKI criteria:
• Persistent or increasing WBC (>10 × 109/L), unresponsive to therapy “Provisional” response-to-TKI criteria
• Persistent or increasing splenomegaly, unresponsive to therapy • Hematologic resistance to the first TKI (or failure to achieve a complete hematologic response* to the first TKI) or
• Persistent thrombocytosis (>1000 × 109/L), unresponsive to therapy • Any hematological, cytogenetic, or molecular indications of resistance to 2 sequential TKIs or
• Persistent thrombocytopenia (<100 × 109/L) unrelated to therapy • Occurrence of 2 or more mutations in BCR-ABL1 during TKI therapy
• 20% or more basophils in the PB
• 10%-19% blasts† in the PB and/or BM
• Additional clonal chromosomal abnormalities in Ph+ cells at diagnosis that include “major route” abnormalities (second Ph, trisomy 8, isochromosome 17q, trisomy 19), complex karyotype, or abnormalities of 3q26.2
• Any new clonal chromosomal abnormality in Ph+ cells that occurs during therapy
