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Myeloproliferative neoplasms (MPN) are clonal disorders of hematopoietic stem cells that manifest clinically as overproduction of cells that contribute to the myeloid lineage
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Classification WHO Myeloproliferative Neoplasm (MPN) Categories
Classic MPN
Chronic myeloid leukemia (CML), BCRI-ABL1+; see Chapter 12
Polycythemia vera (PV)✫
Essential thrombocythemia (ET)✫
Primary myelofibrosis (PMF)✫
PMF, prefibrotic/early stage
PMF, overt fibrotic stage
“Nonclassic” MPNs
✫BCR-ABL–negative classic MPN (PV, ET, and PMF)
Arber DA et al. Blood 2016;127:2391
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Epidemiology
BCR-ABL–negative classic MPN
Polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF)
Polycythemia vera (PV)
Incidence: 0.8–2.6/100,000
Median age at diagnosis: ~60 years
Median survival: >15 years
10-year risk of myelofibrosis: <4%
10-year risk of AML: <2%
Note: longer disease duration and evolution into myelofibrosis significantly increase the risk of leukemic transformation
Essential thrombocythemia (ET)
Incidence: 0.2–2.5/100,000
Median age at diagnosis: ~60 years
Median survival: >15 years
10-year risk of myelofibrosis: ~10%
10-year risk of AML: ~6%
Note: longer disease duration and evolution into myelofibrosis significantly increase the risk of leukemic transformation
Ania BJ et al. Am J Hematol 1994;47:89–93
Gangat N et al. Br J Haematol 2007;138:354–358
Gangat N et al. Leukemia 2007;21:270–276
Mesa RA et al. Am J Hematol 1999;61:10–15
Tefferi A et al. Leukemia 2013;27:1874–1881
Tefferi A et al. Blood 2014;124:2507–2513
Primary myelofibrosis (PMF)
Incidence: 0.4–1.5/100,000
Median age at diagnosis: ~60 years
Median survival: <3 years to >10 years
10-year risk of myelofibrosis: N/A
10-year risk of AML: ~20% based on the presence or absence of well-defined prognostic determinants
Indicators of adverse prognosis as in Dynamic International Prognostic Scoring System (DIPSS-Plus):
Age >65 years
Hemoglobin <10 g/dL
Leukocyte count >25,000/mm3
Circulating blasts ≥1%
Constitutional symptoms
Unfavorable karyotype included complex karyotype or single or two abnormalities including +8, −7/7q-, i(17q), −5/5q-, 12p-, inv(3), or 11q23 rearrangement
Thrombocytopenia <100,000/mm3
Revised cytogenetic risk stratification: very high-risk (VHR) karyotype includes single/multiple abnormalities of –7, inv(3)/3q21, i(17q), 12p–/12p11.2 or 11q–/11q23, single/multiple autosomal trisomies other than +9 and +8, unfavorable karyotype comprises of any abnormal karyotype other than normal karyotype or sole abnormalities of 20q–, 13q–, +9, chromosome 1 translocation/duplication, –Y, or sex chromosome abnormality other than –Y
High-molecular-risk (HMR) genetic abnormalities encompass ASXL1, EZH2, SRSF2, IDH1/2, and U2AF1Q157 mutations and absence of type 1 CALR mutation
Cervantes F et al. Br J Haematol 1997;97:635–640
Dupriez B et al. Blood 1996;88:1013–1018
Gangat N et al. J Clin Oncol 2011;29:392–397
Passamonti F et al. Blood 2010;115:1703–1708
Tefferi A et al. Cancer 2007;109:2083–2088
Tefferi A et al. J Clin Oncol 2018;36:1769–1770
Tefferi A et al. Leukemia 2018;32:1189–1199
Tefferi A et al. Leukemia 2018;32:1631–1642
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Mutations in MPN
Chronology:
1951: CML, PV, ET, and PMF recognized to have significant overlap in both clinical and biological features and felt to be related diseases
1960: CML recognized as ...