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2016 Update of WHO Classification of Tumours of Haematopoietic and Lymphoid
Tissues
Dr Ankit RaiyaniDept of Hematology
SSH, Pune
What changes to expect in myeloid neoplasm
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Introduction
• Actual classification is yet to be published• Some of the particulars may change in the
published copy• Sources:
– WHO update: Myeloproliferative neoplasms, Atilio Orazi
– WHO update: Acute Leukemia, Deniel Arber– WHO update: MDS, Robert Hasserjian– LEUKEMIA CLASSIFICATION 2016: WHAT, WHEN,
“WHO”, Kathryn Foucar
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Myeloid Neoplasms- WHO 2016• AML:
– 25 subtypes; 3 new genetic entities – (numerous prognostic “types”) – (new criteria for blast enumeration) – (new familial category)
• MDS: – 7 subtypes – (all new names; some integration of molecular)
• MDS/MPN:– 5 subtypes; 1 new entity (RARS-T new entity) – (new molecular genetic criteria)
• MPN: – 8 subtypes – (new molecular genetic criteria)
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Acute Myeloid Leukemia
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Acute Myeloid Leukemia
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New Acute Myeloid Leukemia subtypes 2016
• AML with RUNX1 mutation (provisional)– Elderly male, poor prognosis
• AML with BCR-ABL 1 (provisional) – Antigen receptor deletion (IGH)
• AML with biallelic CEBPA mutations (CEBPAdm) • Familial AML/MDS (multiple types)• Promoted to full entity (No longer provisional)
– Acute Myeloid Leukemia with NPM1 mutation– Acute Myeloid Leukemia with CEBPAdm
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Reason to include AML RUNX1 mutation as separate entity
Jason H. Mendler et al. JCO 2012;30:3109-3118
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Reason for including “Biallelic” to CEBPA mutation
Kaplan-Meier curves for overall survival stratified by (A) CEBPA–wild-type (WT) or CEBPA-mutant status, (B) CEBPA-WT, CEBPA-single, or CEBPA-double mutant status
Claire L. Green et al. JCO 2010;28:2739-2747
• 7-20% AML has CEBPA mutation• 12-47% are monoallelic, rest biallelic
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AML-Required studies and key information in reports
Clinical Hx of chemo/MDS
Morphology Blast %, Dysplastic %
Flow Cytometry/ Cytochemistry
Confirm myeloid (CD 33, CD13, MPO)
Cytogenetics AML-defining vs other (many karyotypic subtypes)
Molecular: (selected)*
FLT3, NPM1, CEBPA, RUNX1, BCR-ABL1, other prognostic factors, KIT
*Only FLT3 mutation analysis required for all AML
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New Acute Myeloid Leukemia Criteria
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Revised criteria for AML -MRC • No prognostic significance of multilineage dysplasia
(MLD), IF-– No prior h/o Myelodysplastic Syndrome– NPM1 or CEBPAdm positive– Normal karyotype
• Classified under AML with NPM1m/ CEBPAdm
• Del9q is an MDS related entity only in the absence of NPM1 mutations– NPM1 commonly associated with del9q and is likely not adverse
in this setting• If prior h/o MDS, MDS/MPN, MPN or tMDS/AML or
cytogenetic abnormalities (other than del9q)- – No survival benefit of NPM1– Considered as AML -MRC
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Acute Erythroleukemia (AML M6a)
• Blast percentage to be calculated from total nucleated cells on BMA. (not from nonerythroid cells)
• Many cases of AML M6a (by older classification) will fall into MDS RAEB group
• Rest will be considered AML (probably AML MRC)• Pure Erythroid leukemia will remain a separate subclass• This is done to maintain consistency in the blast counting
in MDS/AML spectrum– Avoid abrupt change in blasts% when erythroids reach >50%– Erythroids may fluctuate due to therapy, metabolic changes,
EPO levels• This will link AML M6a with MDS, with which it shares
morphologic and genetic features
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Myelodysplastic Syndromes
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Assessment of dysplasia
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New handling of MDS with ring sideroblasts
• MDS with multilineage dysplasia and ring sideroblast will be reinstated (MLD-RS)
• MDS with SF3B1 mutation can be classified as SLD- RS/ MLD-RS if >5% ring sideroblasts are present– Will not require >15% RS
• SF3B1 mutation will not affect MDS –EB or isolated del(5q)
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Changes in MDS del(5q)
• Allow one additional cytogenetic abnormality– Excluding high risk abnormalities
• TP53 mutation study or p53 immunostain• Exclusions
– >5% blasts in PB/BM– Significant granulocytic dysplasia
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MDS/MPN
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RARS-T
• Promoted to full entity under MDS/MPN
MDS like MPN like
Clinical • Macrocytic anemia• Transfusion requirement
• Thrombocytosis• Need for cytoreduction
Morphological • Erythroid dysplasia• Ring sideroblasts
• Large megakaryocytes with bulbous nuclei
Genetic SF3B1 mutation (80-90%) JAK2 mutation (50-60%)Rarely CALR/MPL
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Updates to CMML
• Common pattern of co-mutations in epigenetic modifier and RNA splicing gene
• TET2+SRSF4 in 30-35% CMML• Either TET2, SRSF4, or ASXL1 in 90%• ASXL1 a/w poor prognosis• Presence of NPM1 or 11q23
rearrangement a/w rapid progression to AML
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aCML
• No changes in criteria• Assess for CSF3R mutation (If positive
strongly consider CNL)
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Myeloproliferative Neoplasms
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CNL
• Integration of CSF3R mutations in diagnosis (present in 90% CNL)
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THANK YOU!!!