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Life Expectancy

Myelofibrosis (MF) is a rare, chronic, aggressive hematologic malignancy that is classified as one of 3 classic myeloproliferative neoplasms, along with polycythemia vera (PV) and essential thrombocythemia (ET). MF is characterized by clonal proliferation of affected hematopoietic stem cells, bone marrow failure due to excessive fibrosis, anemia, significant splenomegaly, extramedullary hematopoiesis, constitutional symptoms, and leukoerythroblastosis.¹

In most cases, MF is caused by somatic driver mutations in the JAK2, CALR, and MPL genes. Genetic mutations in ASXL1, TET2, SRSF2, IDH-1/2, and U2AF1 may also be associated with MF.²

MF may be primary or secondary.³ Most cases of MF are primary, occurring without a known underlying condition; however, approximately one-third of patients with MF have a previous diagnosis of either PV or ET, which may progress to secondary MF.⁴

Factors Affecting Life Expectancy

During the past few decades, advancements in treatments for MF have increased patient survival.¹ Life expectancy depends on several factors, including patient age, biological sex, comorbidities, type of MF, disease progression, MF risk stratification, patient genetics, and patient response to treatment. Several sources report that the median survival for patients with primary MF is between 3.5 and 5.5 years.^2,5

The most common causes of death in patients with MF include infection, hemorrhage, cardiac failure, mortality following splenectomy, and transformation of MF to acute myeloid leukemia (AML). Other reported causes of mortality include renal failure, hepatic failure, and thrombosis. Many of the causes of death are disease- or treatment-related; however, others are comorbidities.⁵

Life Expectancy Relative to Age

Although MF can occur at any age, it primarily affects individuals older than 50 years, with a median age at diagnosis of approximately 65 years.^2,6 Older age correlates with shorter survival in patients with MF.⁵

Researchers in a study published in 2018 analyzed the clinical and genetic markers predicting short-term (≤5 years) or long-term (20+ years) survival in patients with primary MF. They reported that age older than 70 years independently predicted 5-year mortality, whereas patients age 70 or younger were more likely to survive beyond 20 years.²

The Dynamic International Prognostic Scoring System-plus (DIPSS-plus), a risk stratification system for patients with MF, includes age older than 65 years as one of 8 risk factors adversely affecting survival.⁵

Read more about MF epidemiology

Life Expectancy Relative to Sex

Women with MF are more likely than men to survive longer than 20 years after a diagnosis of MF.² Fewer than 20% of patients with MF are predicted to survive longer than 10 years.⁵

Read more about MF diagnosis

Life Expectancy Relative to Comorbidities

Because MF affects primarily an older population, chronic comorbidities are often present, including hypertension, cardiovascular disease, dyslipidemia, other malignancies, diabetes, renal dysfunction, pulmonary disease, and hepatic disease.⁷

Researchers in a 2022 study involving 668 patients with MF identified the comorbidities linked with the greatest adverse effect on overall survival. These included hypertension, dyslipidemia, smoking, and hepatitis C. Diabetes, renal dysfunction, and pulmonary disease also increased risk of death.⁷

Read more about MF comorbidities

Life Expectancy Relative to Myelofibrosis Type and Disease Progression

The risk for mortality in patients with PV and ET that progresses to secondary MF is higher than the risk for patients with primary MF.³

PV and ET are generally considered to be less aggressive myeloproliferative neoplasms than primary MF; however, genetic mutational differences have been noted between patients with MF secondary to PV or ET and those with primary MF. These mutational differences may affect disease progression to more aggressive forms, such as secondary MF or even AML.⁸

Leukemic transformation occurs in 10% to 20% of patients with primary MF within the first 10 years.^4,5 Progression to blast phase disease correlates with patient mortality.¹ Increased density of the bone marrow microvasculature, which occurs in approximately 70% of patients with primary MF, is an independent risk factor for poor survival.⁵

Read more about MF types

Life Expectancy Relative to Risk Stratification and Genetics

Several scoring systems are used for the risk stratification of patients with MF: the DIPSS-plus; the Mutation-Enhanced International Prognostic Scoring System (MIPSS-70), used to evaluate potential candidates for allogeneic stem cell transplant; and the Genetically Inspired Prognostic Scoring System (GIPSS).⁵

Life Expectancy According to DIPSS-plus

DIPSS-plus classifies patients with MF into 4 risk categories^3,5:

Low risk (0 points), with a median survival of 15.4 years
Intermediate-1 risk (1 point), with a median survival of 6.5 years
Intermediate-2 risk (2-3 points), with a median survival of 35 months (2.9 years)
High risk (4-6 points), with a median survival of 16 months (1.3 years)

DIPSS points are assigned on the basis of 8 possible adverse factors⁵:

Age older than 65 years
Hemoglobin level below 10 g/dL
Platelet count below 100 x 10⁹/L
Leukocyte count higher than 25 x 10⁹/L
Constitutional symptoms
Percentage of circulating blasts in the peripheral blood of 1% or higher
Red blood cell transfusion dependency
Unfavorable karyotype

Life Expectancy According to MIPSS70

MIPSS70 classifies patients with MF as being at low, intermediate, or high risk according to the following 3 genetic and 6 clinical risk factors⁵:

Absence of CALR type 1/like mutations
Presence of any high-molecular-risk mutation, such as in ASXL1, SRSF2, EZH2, or IDH1/2
Presence of 2 or more high-molecular-risk mutations
Hemoglobin level below 10 g/dL
Leukocyte count above 25 × 10 ⁹/L
Platelet count below 100 × 10 ⁹/L
Percentage of circulating blasts of 2% or higher
Bone marrow fibrosis grade 2 or higher
Constitutional symptoms

The MIPSS70+ scoring system adds an unfavorable karyotype as a fourth genetic risk factor and includes only 4 clinical risk factors: hemoglobin level, leukocyte count, circulating blast level, and constitutional symptoms. MIPSS70+ classifies patients with MF into 4 risk categories (low, intermediate, high, and very high).⁵

Life Expectancy According to GIPSS

GIPSS classifies patients with MF into 4 risk categories⁵:

Low (0 points), with a median survival of 26.2 years (94%)
Intermediate-1 risk (1 point), with a median survival of 8 years (73%)
Intermediate-2 risk (2 points), with a median survival of 4.2 years (40%)
High (3 or more points) with a median survival time of 2 years (14%)

The GIPSS is based exclusively on genetic risk factors⁵:

VHR karyotype
Unfavorable karyotype
Absence of CALR type 1/like mutation
Presence of ASXL1, SRSF2, and U2AF1 Q157 mutations

Some experts strongly suggest using GIPSS to predict patient prognosis and guide treatment decisions. Patients at low risk may be managed with long-term observation, whereas allogeneic stem cell transplant (HSCT) may be considered for transplant-age patients at high risk.⁸

Read more about MF genetics

Life Expectancy Relative to Treatment Response

The only potentially curative treatment for MF is HSCT.³ The cure rate with this treatment has been reported to be between 30% to 65%,³ but this comes at an increased risk of mortality.⁹ Studies indicate that the 3- to 5- year survival rate after HSCT ranges from 45% to 70%; relapse and transplant-related mortality typically occur within the first 2 years after treatment.⁹

A study conducted by the European Society for Blood and Marrow Transplantation analyzed risk factors for 2- and 5-year mortality in patients with primary MF (n=1906), secondary MF (n=421), or MF transformed to AML (n=134) who underwent HSCT between 1995 and 2014.⁹ The researchers found that risk of mortality was lower in younger patients and women. The 5-year survival rate for patients in this study was 84%; relapse and non-relapse mortality occurred in 13% and 8% of patients, respectively. Primary causes of death in this cohort included progression of primary MF (24), other malignancies (13), infection (13), unknown causes (17), graft-vs-host disease (GVHD; 12), and toxicity (1).⁹

Another study showed that older age, male biological sex, history of secondary MF, and absence of GVHD before 2 years increased risk of mortality following HSCT. GVHD before 2 years decreased risk of primary disease relapse, which was the leading cause of mortality.^3.

Read more about MF treatment

References

Vaidya R, Siragusa S, Huang J, et al. Mature survival data for 176 patients younger than 60 years with primary myelofibrosis diagnosed between 1976 and 2005: Evidence for survival gains in recent years. Mayo Clin Proc. 2009;84(12):1114-1119. doi:10.4065/mcp.2009.0543
Penna D, Lasho TL, Finke CM, et al. 20+ Years and alive with primary myelofibrosis: phenotypic signature of very long-lived patients. Am J Hematol. 2019;94(3):286-290. doi:10.1002/ajh.25351
Robin M, Wreede LC de, Wolschke C, et al. Long-term outcome after allogeneic hematopoietic cell transplantation for myelofibrosis. Haematologica. 2019;104(9):1782-1788. doi:10.3324/haematol.2018.205211
Primary myelofibrosis. Leukaemia Foundation. Accessed December 22, 2022.
Lal A. Primary myelofibrosis: prognosis. Medscape. Updated September 21, 2022. Accessed December 22, 2022.
Primary myelofibrosis. NORD. Accessed December 22, 2022.
García-Fortes M, Hernández-Boluda JC, Álvarez-Larrán A, et al. Impact of individual comorbidities on survival of patients with myelofibrosis. Cancers (Basel). 2022;14(9):2331. doi:10.3390/cancers14092331
Tefferi A, Guglielmelli P, Pardanani A, Vannucchi AM. Myelofibrosis treatment algorithm 2018. Blood Cancer J. 2018;8(8):1-7. doi:10.1038/s41408-018-0109-0
Robin M, Eikema DJ, de Wreede LC, et al. Life expectancy in long-term survivors transplanted for myelofibrosis: a registry study from the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation. Blood. 2017;130(Suppl 1):3307. doi:10.1182/blood.V130.Suppl_1.3307.3307

Reviewed by Harshi Dhingra, MD, on 12/30/2022.

Maria Arini Lopez, PT, DPT, CSCS, CMTPT, CIMT

Maria Arini Lopez, PT, DPT, CSCS, CMTPT, CIMT is a freelance medical writer and Doctor of Physical Therapy from Maryland. She has expertise in the therapeutic areas of orthopedics, neurology, chronic pain, gastrointestinal dysfunctions, and rare diseases especially Ehlers Danlos Syndrome.

Myelofibrosis (MF)