2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

CLASSIFICATION AND PROGNOSIS OF MPNs
Table 1. Classification of Chronic Myeloid Neoplasms According to the World Health Organization in 2008
Diseases Main criteria
Chronic myelogenous leukemia, BCR-
ABL1-positive
Positivity for the BCR-ABL1 fusion gene
Myeloproliferative Neoplasms
Chronic neutrophilic leukemia PB leukocytosis, WBC �25 � 10 9 /L
- Segmented PMNs and band forms are � 80% of WBCs
- Immature granulocytes � 10% of WBCs
- Myeloblasts � 1% of WBCs
Hypercellular BM biopsy (myeloblasts � 5% of NMCs)
Hepatosplenomegaly
No evidence of reactive neutrophila
No Philadelphia chromosome or BCR-ABL1 fusion gene; no rearrangement of PDGFRA, PDGFRB, or FGFR1; no evidence of PV, ET, or PMF;
no evidence of MDS or MDS/MPN
Polycythemia vera See Table 2
Primary myelofibrosis See Table 4
Essential thrombocythemia See Table 5
Chronic eosinophilic leukemia, NOS Eosinophils �1.5 � 10 9 /L
No Philadelphia chromosome or BCR-ABL1 fusion gene or other MPN (PV, ET, or PMF) or MDS/MPN (CMML or aCML)
No t(5;12)(q31-35;p13) or other rearrangement of PDGFRB
No FIP1L1-PDGFRA fusion gene or other rearrangement of PDGFRA
No rearrangement of FGFR1
PB and BM blasts � 20%, no inv(16)(p13.1;q22) or t(16;16)(p13.1;q22) or other feature diagnostic of AML
Presence of a clonal cytogenetic or molecular genetic abnormality, or blast cells � 2% in the PB or � 5% in the BM
Mastocytosis Cutaneous mastocytosis: mast cell infiltrate in the skin (criteria for SM not met)
SM: mast cell infiltrate in BM and/or other extracutaneous organs (minor diagnostic criteria include mast cell atypia in � 25% of cells,
detection of a mutation at codon 816 of KIT, an aberrant mast cell immunophenotype and elevated serum triptase levels)
MPN, unclassifiable Clinical, laboratory, and morphologic features of an MPN without meeting the diagnostic criteria for one specific MPN
Myeloid and lymphoid neoplasms
associated with eosinophilia and
abnormalities of PDGFRA, PDGFRB,
or FGFR1
Myeloid and lymphoid neoplasms associated with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1
An MPN with prominent eosinophilia (cases presenting with AML or ALL with eosinophilia are also included) AND presence of a FIP1L1-
PDGFRA fusion gene or presence of t(5;12)(q31�q33;p12) or a variant translocation or demonstration of PDGFRB fusion gene or of
rearrangement of PDGFRB or presence of t(8;13)(p11;q12) or a variant translocation leading to FGFR1 rearrangement
MDS/MPN
Chronic myelomonocytic leukemia Persistent PB monocytosis � 1 � 10 9 /L
No Philadelphia chromosome or BCR-ABL1 fusion gene
No rearrangement of PDGFRA or PDGFRB
� 20% blasts (including myeloblasts, monoblasts, and promonocytes) in PB and BM
Dysplasia in �1 myeloid lineage–if no/minimal myelodysplasia:
- Presence of an acquired clonal cytogenetic or molecular genetic abnormality OR
- Persistent monocytosis (�3 mo) and exclusion of all other causes of monocytosis
Juvenile myelomonocytic leukemia Persistent PB monocytosis � 1 � 10 9 /L
No Philadelphia chromosome or BCR-ABL1 fusion gene
� 20% blasts (including promonocytes) in PB and BM
Two of the following: hemoglobin F increased for age; immature granulocytes in PB; WBC count � 10 � 10 9 /L, clonal chromosomal
abnormality (may be monosomy 7); GM-CSF hypersensitivity of myeloid progenitors in vitro
Atypical chronic myeloid leukemia, BCR-
ABL1-negative
PB leukocytosis (WBCs �13 � 10 9 /L) because of increased numbers of neutrophils and their precursors (which constitute �10% of leukocytes)
with prominent dysgranulopoiesis
No Philadelphia chromosome or BCR-ABL1 fusion gene
No rearrangement of PDGFRA or PDGFRB
Minimal absolute basophilia; basophils usually � 2% of leukocytes
No or minimal absolute monocytosis; monocytes � 10% of WBCs
Hypercellular BM with granulocytic proliferation and dysplasia, � dysplasia in the other lineages
� 20% blasts in PB and BM
MDS/MPN, unclassifiable Clinical, laboratory and morphologic features of an MDS AND
- Provisional entity: refractory anemia
with ring sideroblasts associated with
marked thrombocytosis
Prominent myeloproliferative features, e.g., platelet count �450 � 10 9 /L associated with megakaryocytic proliferation, or WBC count �13 �
10 9 /L, � splenomegaly AND
No preceding MDS or MPN, no history of cytotoxic or growth factor therapy, no Philadelphia chromosome or BCR-ABL1 fusion gene, no
rearrangement of PDGFRA, PDGFRB or FGFR1, and no isolated del(5q), t(3;3)(q21;q26) or inv(3)(q21;q26) OR
De novo disease with mixed myeloproliferative and myelodysplastic features that cannot be assigned to any of the MDS, MPN, or MDS/MPN
categories
RARS-T: anemia, ring sideroblasts �15% of erythroid precursors, platelet count �450 � 10 9 /L, large and atypical BM megakaryocytes, no PB
blasts, �5% BM blasts AND NO BCR-ABL1 fusion gene, isolated del(5q), t(3;3)(q21;q26), inv(3)(q21;q26)
Myelodysplastic syndromes
Myelodysplastic syndrome PB cytopenia(s), dysplasia in �1 myeloid cell line, PB and BM blasts � 20%, � BM ring sideroblasts—several MDS categories exist: refractory
cytopenias with unilineage dysplasia (refractory anemia, refractory neutropenia, refractory thrombocytopenia), refractory anemia with ring
sideroblasts, refractory cytopenia with multilineage dysplasia, refractory anemia with excess blasts type 1 or 2, myelodysplastic syndrome
unclassified, MDS associated with isolated del(5q)
Abbreviations: PB, peripheral blood; WBCs, white blood cells; PMNs, polymorphonucleated cells; BM, bone marrow; NMCs, nucleated marrow cells; PV: polycythemia
vera; ET, essential thrombocythemia; PMF, primary myelofibrosis; MDS, myelodysplastic syndrome; MDS/MPN: myelodysplastic/myeloproliferative neoplasm; NOS, not
otherwise specified; MPN, myeloproliferative neoplasms; CMML, chronic myelomonocytic leukemia; aCML, atypical chronic myeloid leukemia; AML, acute myeloid
leukemia; SM, systematic mastocytosis; ALL, acute lymphoblastic leukemia; GM-CSF, granulocyte macrophage colony-stimulating factor; RARS-T, refractory anemia
with ring sideroblasts associated with marked thrombocytosis.
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