Myelofibrosis types
Fact-checked by There are two main types of myelofibrosis — primary and secondary — differentiated by whether or not the disease is associated with another underlying condition. They share similar symptoms, such as an enlarged spleen, lack of healthy red blood cells (anemia), fatigue, and bone pain, and are usually treated similarly.
Myelofibrosis is a rare blood cancer wherein abnormal and immature blood cells are overproduced in the bone marrow, causing inflammation and scarring (fibrosis) that impede healthy blood cell production. It belongs to a group of blood cancers called myeloproliferative neoplasms (MPNs).
Beyond primary and secondary myelofibrosis classifications, a person’s doctor may also classify their myelofibrosis based on risk status, or on how likely the disease is to progress and affect survival. Understanding these myelofibrosis subtypes helps physicians make treatment decisions and inform patients of their long-term outlook.
Primary myelofibrosis
In primary myelofibrosis, the most common form of the blood cancer, there is no underlying condition associated with the disease. Scientists don’t know why primary myelofibrosis arises, but most cases are associated with disease-driving mutations in one of three genes:
- JAK2, accounting for 50%-60% of cases
- CALR, accounting for 25%-30% of cases
- MPL, accounting for 5%-10% of cases
These mutations are acquired during a person’s lifetime and are generally not inherited. In up to around 10% of cases, mutations are not found in any of these genes — called triple-negative — which tends to be linked to a more aggressive disease course.
Primary myelofibrosis is also classified into one of two myelofibrosis stages based on what’s happening in the bone marrow:
- Prefibrotic myelofibrosis: An early stage where there is a lot of excessive cell growth, but little or no bone marrow scarring. Often presents with less severe or no symptoms. Clinically, it can look similar to the MPN essential thrombocythemia (ET).
- Overt myelofibrosis: An advanced stage where significant scarring has accumulated in the bone marrow. Associated with more severe anemia, enlarged spleen, and other symptoms.
In general, prefibrotic myelofibrosis is associated with better long-term outcomes and longer survival than overt myelofibrosis, but the disease course can vary substantially based on genetic mutation and other factors.
Secondary myelofibrosis
Secondary myelofibrosis arises as a complication of other blood disorders, most often the MPNs ET or polycythemia vera (PV).
In post-ET myelofibrosis and post-PV myelofibrosis, bone marrow overactivity and stress eventually give rise to the bone marrow scarring that characterizes myelofibrosis. PV and ET are associated with mutations in the same genes that are linked to primary myelofibrosis, most commonly JAK2.
Less commonly, myelofibrosis may be associated with other underlying conditions, including different types of blood cancer or immune-mediated diseases:
- leukemia
- lymphoma
- multiple myeloma
- metastatic bone cancer
- autoimmune conditions, such as lupus or systemic sclerosis
- HIV infection
For secondary myelofibrosis to be diagnosed, a person must have a preexisting diagnosis of a precursor condition, obvious bone marrow fibrosis, and typical clinical signs of myelofibrosis.
The symptoms of secondary myelofibrosis are similar to those of primary myelofibrosis, although there may be the addition of symptoms associated with the underlying precursor condition.
How myelofibrosis is classified beyond ‘type’
After a myelofibrosis diagnosis, doctors also classify patients into risk groups — generally low, intermediate, or high. These myelofibrosis risk categories inform the likelihood of disease progression, survival outcomes, and treatment decision-making.
There are a few different risk stratification systems that are used for primary myelofibrosis, but broadly, they may consider factors such as:
- age
- blood cell counts
- numbers of immature blood cells
- symptoms
- genetic factors
- degree of bone marrow fibrosis
- need for blood transfusions
The standard systems used for primary myelofibrosis are the International Prognostic Scoring System (IPSS) and the Dynamic International Prognostic Scoring System (DIPSS), which don’t account for genetic factors. Newer systems, such as the Mutation-enhanced International Prognostic Scoring System (MIPSS70) and the Genetically inspired International Prognostic Scoring System (GIPSS), already incorporate genetic markers.
The main risk stratification system for secondary myelofibrosis is the Myelofibrosis Secondary to Polycythemia Vera and Essential Thrombocythemia (MYSEC-PM).
How MF type affects treatment and outlook
In general, primary and secondary myelofibrosis are treated similarly, with the management plan depending largely on a person’s risk score and their general health, more so than the specific disease type.
People with early-stage myelofibrosis and those at a lower risk of disease progression may not be treated right away, while those with more aggressive or advanced myelofibrosis might receive medications, surgery, or a stem cell transplant to help manage symptoms and slow disease progression.
In either of the two myelofibrosis types, survival and long-term outlook are influenced by several factors, including genetics, disease subtypes, and progression.
About 10%-20% of people with myelofibrosis will develop acute myeloid leukemia, a more aggressive blood cancer. This is called a blast phase transformation, and may occur more often in primary myelofibrosis than in secondary disease.
Myelofibrosis News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
