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

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

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)

Acute Myeloid Leukemia

Acute Myeloid Leukemia

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

Reason to include AML RUNX1 mutation as separate entity

Jason H. Mendler et al. JCO 2012;30:3109-3118

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

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

New Acute Myeloid Leukemia Criteria

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

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

Myelodysplastic Syndromes

Assessment of dysplasia

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)

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

MDS/MPN

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

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

aCML

• No changes in criteria• Assess for CSF3R mutation (If positive

strongly consider CNL)

Myeloproliferative Neoplasms

CNL

• Integration of CSF3R mutations in diagnosis (present in 90% CNL)

THANK YOU!!!