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INTRODUCTION

Myeloproliferative neoplasms (MPN) are clonal disorders of hematopoietic stem cells that manifest clinically as overproduction of cells that contribute to the myeloid lineage

Classification WHO Myeloproliferative Neoplasm (MPN) Categories

  1. 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

  2. “Nonclassic” MPNs

    • Chronic neutrophilic leukemia (CNL)

    • Chronic eosinophilic leukemia not otherwise specified (CEL-NOS)

    • “MPN unclassifiable”

 

BCR-ABL–negative classic MPN (PV, ET, and PMF)

Arber DA et al. Blood 2016;127:2391

Epidemiology

 

BCR-ABL–negative classic MPN

Polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF)

 

Polycythemia vera (PV)

  1. Incidence: 0.8–2.6/100,000

  2. Median age at diagnosis: ~60 years

  3. Median survival: >15 years

  4. 10-year risk of myelofibrosis: <4%

  5. 10-year risk of AML: <2%

Note: longer disease duration and evolution into myelofibrosis significantly increase the risk of leukemic transformation

 

Essential thrombocythemia (ET)

  1. Incidence: 0.2–2.5/100,000

  2. Median age at diagnosis: ~60 years

  3. Median survival: >15 years

  4. 10-year risk of myelofibrosis: ~10%

  5. 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)

  1. Incidence: 0.4–1.5/100,000

  2. Median age at diagnosis: ~60 years

  3. Median survival: <3 years to >10 years

  4. 10-year risk of myelofibrosis: N/A

  5. 10-year risk of AML: ~20% based on the presence or absence of well-defined prognostic determinants

  6. 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

  7. 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

  8. High-molecular-risk (HMR) genetic abnormalities encompass ASXL1, EZH2, SRSF2, IDH1/2, and U2AF1Q157 mutations and absence of type 1 CALR mutation

 

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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

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 ...

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