Myelofibrosis is a rare blood cancer originating in the bone marrow, where the buildup of scar tissue disrupts the normal production of blood cells. This disruption leads to various symptoms and complications. To manage the disease, clinicians use risk stratification to predict the likely course and aggressiveness of the disease for a patient.
This risk assessment is a foundational step in developing a personalized management plan. It allows for a more accurate prognosis and helps guide conversations about the most appropriate therapeutic path. The clinical journey with myelofibrosis is highly variable, so risk assessment provides a framework for navigating this uncertainty.
The Purpose of Myelofibrosis Risk Assessment
The purpose of risk stratification is to provide a clearer picture of an individual’s prognosis. Because the disease behaves differently from person to person, a standardized assessment is needed to anticipate the likely trajectory. This information sets realistic expectations and informs the urgency of potential interventions.
This assessment is also a tool for tailoring treatment strategies. It helps determine whether a patient might be managed with observation, requires medication, or needs more aggressive therapies. For example, a lower-risk patient might not need immediate treatment, while a higher-risk patient may be considered for more definitive procedures.
Risk stratification also facilitates shared decision-making between the healthcare team and the patient. By categorizing the disease’s potential aggressiveness, doctors can have more structured conversations about the risks and benefits of various treatment options. These risk scores are also used in clinical trials to ensure study populations are comparable for evaluating new therapies.
Elements Considered in Myelofibrosis Risk
A comprehensive risk assessment in myelofibrosis involves evaluating clinical observations, blood test results, and genetic markers. One of the most consistently used clinical factors is the patient’s age, with individuals over 65 facing a higher risk. Another element is the presence of constitutional symptoms, including significant unexplained weight loss, persistent fevers, and drenching night sweats. The size of the spleen is also measured, as an enlarged spleen is a common feature of the disease.
Blood parameters provide objective data for risk stratification. Key measurements include hemoglobin levels, with low levels (anemia) indicating a worse prognosis. The white blood cell count is also important, as a significantly elevated count is an adverse factor. The platelet count is assessed, with very low numbers being a negative prognostic indicator. Clinicians also look for the percentage of circulating blasts (immature blood cells) in the blood; a level of 1% or higher points to a more aggressive disease.
The degree of fibrosis, or scarring, within the bone marrow is a direct measure of the disease’s physical impact. In addition, cytogenetic analysis, which examines chromosomes, can reveal abnormalities associated with a poorer outcome.
Genetic analysis has become central to risk assessment. Clinicians test for “driver” mutations in genes like JAK2, CALR, and MPL, which are found in about 90% of patients. The specific type of mutation matters; a type 1 CALR mutation is often associated with a better prognosis compared to a JAK2 or MPL mutation. The presence of other, non-driver mutations are considered high-risk molecular markers that signal a greater likelihood of disease progression. These include mutations in genes such as:
- ASXL1
- SRSF2
- EZH2
- IDH1/2
Interpreting Myelofibrosis Risk Scores
Individual risk factors are integrated into formal scoring systems to produce a standardized risk category. These models use the collected clinical, blood, and genetic data to generate a score that places a patient into a specific risk group. This systematic approach allows for more consistent prognostication and helps guide treatment decisions.
Several prognostic scoring systems have been developed and refined over time.
- The International Prognostic Scoring System (IPSS) was an early model relying on five clinical variables: age, symptoms, hemoglobin, white blood cell count, and blast percentage.
- The Dynamic IPSS (DIPSS) can be applied at any point during the disease course.
- The DIPSS-Plus model further incorporates transfusion dependency, platelet count, and unfavorable chromosome analysis.
- The Genetically Inspired Prognostic Scoring System (GIPSS) is based on genetic markers, including karyotype and mutations like CALR, ASXL1, and SRSF2.
- The Myelofibrosis Prognostic Scoring System 70 (MIPSS70) and its updates integrate both clinical and genetic information for patients under 70.
The output of these scoring systems is a risk category, such as low, intermediate-1, intermediate-2, or high risk. Newer models have further refined these into very low or very high risk. Each category corresponds to a different median survival expectation, providing a general outlook on the disease’s aggressiveness.
Treatment Decisions Based on Risk Level
The risk category assigned to a patient is a major driver of the management strategy. For individuals classified as low-risk without significant symptoms, the recommended approach is often active monitoring. This involves regular check-ups and blood tests to monitor for disease progression without immediate treatment.
Patients in the intermediate-1 risk category may also be observed if they are asymptomatic, but treatment is often considered if symptoms affect quality of life. For this group, therapies might include manufactured interferon to help control blood counts or JAK inhibitors. The decision to start treatment is individualized based on the clinical picture and patient preferences.
For those in the intermediate-2 and high-risk categories, more immediate and intensive therapy is required. JAK inhibitors are a standard treatment for managing symptoms and reducing spleen size in these patients. The choice of a specific JAK inhibitor may depend on factors like the patient’s platelet count or anemia. These medications include:
- Ruxolitinib
- Fedratinib
- Pacritinib
- Momelotinib
Eligible patients with higher-risk disease are also considered for allogeneic stem cell transplantation. This procedure, which replaces the patient’s diseased bone marrow with healthy donor stem cells, is the only potentially curative treatment. Due to its significant risks, it is generally reserved for younger, fitter patients. Participation in clinical trials is also an important option for patients at all risk levels.
The Evolving Landscape of Myelofibrosis Risk
The field of myelofibrosis risk assessment is continuously evolving. A patient’s risk status is not fixed at diagnosis. As the disease progresses, clinical features can worsen, blood counts can change, and new genetic mutations can be acquired, all of which can alter a patient’s risk profile. This means that risk must be reassessed periodically to ensure the management strategy remains appropriate.
Research is constantly uncovering new insights that refine how risk is calculated. The identification of new prognostic markers, both genetic and clinical, is a key area of focus. Scientists are working to understand the complex interplay between different mutations and how they influence the disease’s behavior. This is leading to the development of more sophisticated and personalized risk models.
The goal of this research is to move beyond predicting outcomes and toward modifying the disease’s course. By identifying patients at the highest risk of progression earlier and with greater accuracy, clinicians can intervene with more effective therapies. Advancements in molecular profiling and risk-adaptive therapies are steadily transforming the management of myelofibrosis into a more personalized and proactive discipline.