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🌱 來自：Etiologies-of thrombocytopenia

myelofibrosis

hematology

• from primary myelofibrosis (PMF)

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Epidemiology

• Prevalence of 16–18,500 people in the United States
• Median age of onset mid-60s
• Includes 1° MF as well as post-PV & post-ET MF

Signs and symptoms

• Systemic sxs: Fatigue, fevers, night sweats, wt loss, pruritus, early satiety
• Organomegaly: Hepatomegaly & splenomegaly (may be massive)

Physical and laboratory findings

• CBC: Anemia, thrombocytopenia common, thrombocytosis may also be seen early in dz. Leukopenia or leukocytosis may be seen. WBC differential may show left shift
• Other labs: Elevated LDH, alkaline phosphatase, & uric acid common
• Blood smear: Leukoerythroblastosis (nucleated RBCs, dacrocytes, myeloid left shift)
• BMBx: Prefibrotic MF vs. overt MF (2016 WHO classification)

Differential diagnosis

• Other causes of BM fibrosis: Other myeloid neoplasms, lymphoid neoplasms, metastatic malignancy, infxn, connective tissue disorder (lupus)
• WHO criteria: Requires meeting all three major criteria & at least 1 minor criterion
  • WHO 2016 Criteria for the Diagnosis of Prefibrotic Myelofibrosis
  • WHO 2016 Criteria for the Diagnosis of Overt Myelofibrosis

Genetics

More than 90% of myelofibrosis patients harbor driver mutations in one of the 3 genes JAK2, CALR, and MPL,

• Driver muts: pts have mut in one of three
  • JAK2 (JAK2 V617F in ∼50%, JAK2 exon 12 in ∼15%),
  • CALR (∼25%), or
  • MPL (∼5%).
• Approx 10% of pts are “triple-negative” & have none of these muts. CALR muts are a/w improved survival relative to other muts
• Muts in ASXL1, EZH2, IDH1/2, SRSF2, Ras pathway are a/w worse prog (Leukemia 2013;27(9):1861; Leukemia 2020;34(3):799)

Disease sequelae

• Transformation to acute leukemia: Occurs in 20% of pts. Carries extremely poor prog w/ median survival of 2.7 mos. Factors a/w transformation include: Blasts ≥3%, plt <100, unfav karyotype (see DIPSS)
• Extramedullary hematopoiesis: May occur in areas such as near vertebral column, LNs, & can result in organomegaly, effusions, cord compression
• Thrombotic events: ↑ Risk of both arterial & venous thrombotic events
• Bone & joint alterations: May include osteosclerosis, gouty arthritis

Prognostication

• IPSS: Estimates survival from time of dx (Blood 2009;115:392)
• DIPSS: Can be used at any time DIPSS-plus additionally considers karyotype, transfusion, thrombocytopenia (JCO 2011;29(4):392)
• GIPSS
• Molecular IPSS (MIPSS)-70 & MIPSS70-plus include molecular data ie, high-risk muts (ASXL1, EZH2, IDH1/2, SRSF2) (JCO 2018;36(4):310)
• Lille system: Based on Hb levels & presence of leukopenia or leukocytosis
• MYSEC-PM, SMF

Greenfield G, McMullin MF, Mills K. Molecular pathogenesis of the myeloproliferative neoplasms. Journal of Hematology & Oncology. 2021;14(1):1-18. doi:10.1186/s13045-021-01116-z treatment-of-myelofibrosis