What is the prognosis for myelofibrosis?

Prognosis of Myelofibrosis

The prognosis for myelofibrosis varies significantly based on risk stratification, with median survival ranging from 135 months for low-risk patients to 27 months for high-risk patients according to the International Prognostic Scoring System (IPSS). 1

Risk Stratification Systems

International Prognostic Scoring System (IPSS)

• IPSS is the recommended prognostic system for myelofibrosis and should be scored in all patients at diagnosis 2
• IPSS adverse prognostic factors include: 2
  • Age > 65 years
  • Constitutional symptoms
  • Hemoglobin < 10 g/dL
  • WBC count > 25 × 10^9/L
  • Blood blasts ≥ 1%
• Based on these factors, patients are categorized into four risk groups: 1
  • Low risk (0 factors): median survival 135 months
  • Intermediate risk-1 (1 factor): median survival 95 months
  • Intermediate risk-2 (2 factors): median survival 48 months
  • High risk (≥3 factors): median survival 27 months

Dynamic IPSS (DIPSS)

• DIPSS allows prognostic assessment at any time during the disease course, not just at diagnosis 3
• Uses the same variables as IPSS but as time-dependent covariates 3
• When patients shift to the next risk category, the hazard ratio increases significantly (HR 4.13 for low risk, 4.61 for intermediate-1, and 2.54 for intermediate-2) 3

DIPSS-Plus

• DIPSS-Plus incorporates additional independent risk factors: 2
  • Unfavorable karyotype
  • Transfusion dependency
  • Platelet count < 100 × 10^9/L

Genetic Factors Affecting Prognosis

• Driver mutations (JAK2V617F, CALR, MPL) and their impact: 2

  • Longest overall survival observed in CALR+ASXL1− patients (median 10.4 years)
  • Shortest survival in CALR−ASXL1+ patients (median 2.3 years)
  • CALR+ASXL1+ and CALR−ASXL1− patients have intermediate survival (median 5.8 years)

• Additional high-risk mutations that adversely affect survival or leukemia-free survival: 2

  • ASXL1
  • SRSF2
  • CBL
  • KIT
  • RUNX1
  • SH2B3

Disease Progression and Complications

• Potential complications affecting survival include: 4, 5

  • Transformation to acute leukemia
  • Thrombotic events
  • Hemorrhagic episodes
  • Progressive cytopenias
  • Increasing transfusion dependence

• Transfusion need in the first year of diagnosis identifies patients with median survival of less than 5 years 2

• Cytogenetic abnormalities (other than sole 13q– or 20q–) are associated with median survival of less than 5 years 2

Treatment Impact on Survival

• The only curative therapy for myelofibrosis is allogeneic hematopoietic stem cell transplantation (alloSCT) 2, 4

• AlloSCT is recommended for all patients with intermediate-2 and high-risk disease, and for intermediate-1 patients with poor prognostic features 2

• JAK inhibitors (e.g., ruxolitinib) improve symptoms and splenomegaly but have not demonstrated disease-modifying potential or curative effects 5

• For patients who are not transplant candidates, treatment goals shift to symptom management and quality of life improvement 2

Monitoring and Disease Evolution

• Regular monitoring every 3-6 months is recommended to assess for disease progression 2

• Signs of disease progression include: 2, 6

  • Worsening cytopenias
  • Increasing blast percentage
  • Progressive splenomegaly
  • Worsening constitutional symptoms

• The evolution of myelofibrosis is highly variable, with some patients having indolent disease for many years while others progress rapidly 6

Special Considerations

• Comorbidities, particularly cardiovascular disease, can significantly impact overall survival in patients with myeloproliferative neoplasms 7

• Age-adjusted DIPSS may be more appropriate for patients younger than 65 years 3

• The presence of JAK2V617F mutation alone does not correlate with survival or IPSS score, but JAK2V617F allele burden may be relevant (lower quartile associated with shorter survival) 2