Myelofibrosis Risk, Prognosis, and Survival

Risk

In myelofibrosis, the presence of any of the following risk factors* indicates that a patient is already at intermediate risk1,2:
  • Hemoglobin level <10 g/dL
  • Leukocyte count >25 × 109/L
  • Age >65 years
  • Red cell transfusion dependency
  • Circulating blast cells ≥1%
  • Platelet count <100 × 109/L
  • Constitutional symptoms
  • Unfavorable karyotype
New or increasing splenomegaly is considered to be a marker of disease progression in myelofibrosis.3

IWG-MRT and ELN response criteria state that appearance of a new splenomegaly that is palpable at least 5 cm below the left costal margin constitutes progressive disease.3†

Splenomegaly can cause/exacerbate cytopenias due to splenic sequestration.4

Splenomegaly may cause pain, early satiety, abdominal discomfort, and other symptoms.4,5

In a study of 428 patients with primary myelofibrosis, 90% were considered to be intermediate or high risk within one year of diagnosis.2
In a study of 1,054 patients with primary myelofibrosis, approximately 90% of patients had palpable splenomegaly at diagnosis.1
ELN = European LeukemiaNet IWG-MRT = International Working Group-Myeloproliferative Neoplasms Research and Treatment
*As included in the Dynamic International Prognostic Scoring System Plus tool. Progressive disease assignment for splenomegaly requires confirmation by CT or MRI showing a ≥25% increase in spleen volume from baseline. Baseline values for both physical examination and imaging studies refer to pretreatment baseline and not to posttreatment measurements.3

Prognosis

Because myelofibrosis has a heterogeneous presentation, determining a patient’s prognosis can be difficult.6 However, progress in understanding the clinical variables associated with myelofibrosis has led to the development of several prognostic scoring systems.1,6

Prognosis based on risk factors at diagnosis

Early prognostic models, such as the International Prognostic Scoring System (IPSS) developed by the IWG-MRT, estimate prognosis based on risk factors present at diagnosis.1 The IPSS and similar models are therefore appropriate for newly diagnosed cases.7 The 5 adverse prognostic factors included in IPSS are1:

  • Age >65 years
  • Constitutional symptoms
  • Hemoglobin <10 g/dL
  • WBC count >25 × 109/L
  • Blood blasts ≥1%

Patients are assigned into 1 of 4 risk categories based on the number of risk factors present.1

Prognosis based on disease progression

The Dynamic International Prognostic Scoring System (DIPSS), also developed by the IWG-MRT, takes into account progression of disease over time and can be used to evaluate prognosis as a patient’s condition evolves.6

DIPSS uses the same adverse prognostic factors as IPSS but weights them differently. In determining the risk categories, hemoglobin below 10 g/dL is given a score of 2, while the other risk factors are counted as 1.6

IPSS risk and survival1
Risk category
Number of risk factors
Median survival, years
Low
0
11.3
Intermediate-1
1
7.9
Intermediate-2
2
4.0
High
≥3
2.3
DIPSS risk and survival6
Risk category
Number of risk factors
Median survival, years
Low
0
Not Reached
Intermediate-1
1–2
14.2
Intermediate-2
3–4
4
High
5–6
1.5
Myelofibrosis is a progressive disease

Myelofibrosis is associated with progressive constitutional symptoms, increasing splenomegaly, and worsening cytopenias. PV or ET may progress to a myelofibrotic stage8 and myelofibrosis itself can transform to secondary acute myelogenous leukemia.9 Leukemic transformation occurs in 8% to 23% of patients with myelofibrosis during the first decade after diagnosis.9

Transformation Rates to Myelofibrosis
image of chart that shows transformation rates of PV and ET to myelofibrosis
AML = acute myelogenous leukemia EMH = extramedullary hematopoiesis ET = essential thrombocythemia PMF = primary myelofibrosis PET-MF = post–essential thrombocythemia myelofibrosis PPV-MF = post–polycythemia vera myelofibrosis PV = polycythemia vera

Survival

Myelofibrosis, similar to other malignancies, is a serious disease.7

Published estimates of median survival in primary myelofibrosis range from 2.25 to 11.25 years, depending on risk level.1

Cancer 5-Year Overall Survival Rates11a
shows chart of percentage of cancer 5 year survival rate by type of cancer
aFive-year overall survival rates were estimated using SEER data obtained from population-based cancer registries of the US population and SEER Stat Software version 8.3.2. The analysis included patients with initial/primary site diagnosis between years 2007–2011. Overall survival is defined as the time from diagnosis until death from any cause.11,12
Causes of Mortality in PMF
shows pie chart of the percentage of mortality in primary myelofibrosis
A study of 1,054 patients with PMF examined the causes of mortality in patients with myelofibrosis. The results are shown in the graph above. The most common cause of death was transformation to acute leukemia.1
References

1. Cervantes F, Dupriez B, Pereira A, et al. Blood. 2009;113:2895-2901. 2. Gangat N, Caramazza D, Vaidya R, et al. J Clin Oncol. 2011;29(4):392-397. 3. Tefferi A, Cervantes F, Mesa R, et al. Blood. 2013;122(8):1395-1398. 4. Mesa RA. Blood. 2009;113(22):5394-5400. 5. Scherber RM, Geyer HL, Mesa RA. Curr Hematol Malig Rep. 2014;9(4):324-330. 6. Passamonti F, Cervantes F, Vannucchi AM, et al. Blood. 2010;115:1703-1708. 7. Barbui T, Barosi G, Birgegard G, et al. J Clin Oncol. 2011;29:761-770. 8. Tefferi A. Am J Hematol. 2008;83:491-497. 9. Mesa RA, Li CY, Ketterling RP, Schroeder GS, Knudson RA, Tefferi A. Blood. 2005;105:973-977. 10. Abdel-Wahab OI, Levine RL. Annu Rev Med. 2009;60:233-245. 11. Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) SEER*Stat Database: Incidence - SEER 18 Regs Research Data + Hurricane Katrina Impacted Louisiana Cases, November 2015 Submission (1973-2013 varying) - Linked To County Attributes - Total U.S., 1969-2014 Counties. Accessed January 4, 2017. 12. Howlader N, Noone AM, Krapcho M, et al (eds). SEER Cancer Statistics Review, 1975-2012, National Cancer Institute. Bethesda, MD. Available at: http://seer.cancer.gov/csr/1975_2012/, based on November 2014 SEER data submission, posted to the SEER web site, April 2015. Accessed November 7, 2016.

 
Resources
By: World Health Organization (WHO)
A diagnostic worksheet from the WHO for primary MF, PV, and ET.
By: International Working Group for Myeloproliferative Neoplasms Research and Treatment (IWG-MRT)
Diagnostic criteria from the IWG-MRT.