How is Myelofibrosis Staged and Classified?

Myelofibrosis is a type of cancer that affects the bone marrow's ability to generate new blood cells caused by scar tissue within the marrow. Staging and classifying myelofibrosis is based on the severity of symptoms, complications, and the patient's overall health status. The International Prognostic Scoring System (IPSS) and the Dynamic International Prognostic Scoring System (DIPSS) are commonly used to stage and classify myelofibrosis.

International Prognostic Scoring System (IPSS)

Commonly referred to as IPSS, is used by doctors when first diagnosing myelofibrosis to predict the disease course and create the best treatment strategy for patients. This score is based on the following risk factors:

• Age over 65 years
• Presence of constitutional symptoms
• Hemoglobin level less than 10 g/dL
• Leukocyte count greater than 25 x 10^9/L
• Circulating blasts 1% or greater.

Each risk factor a patient has is assigned one point, and the total score determines the risk category: low (0 points), intermediate-1 (1 point), intermediate-2 (2 points), and high (3 or more points).

Dynamic International Prognostic Scoring System (DIPSS)

The DIPSS re-evaluates the myelofibrosis stage at any time after diagnosis. This is useful for patients monitoring their treatment outcomes and overall health. This scoring system includes the same risk factors as the IPSS but assigns two points for hemoglobin levels less than 10 g/dL and for circulating blasts 1% or greater.

DIPSS-plus classifies patients with myelofibrosis into 4 risk categories: 

• 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)

Besides IPSS and DIPSS other scoring systems help doctors stage a patient according to the genetic findings, allowing a more accurate prognosis and a better treatment strategy that focuses on a patient’s individual characteristics. 

Mutation-Enhanced International Prognostic Scoring System (MIPSS70)

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

• 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
• Symptoms like: fever, lack of appetite, headache and muscle or bone pain, general body discomfort

Genetically Inspired Prognostic Scoring System (GIPSS)

GIPSS is based exclusively on genetic risk factors:

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

GIPSS can help with prognosis and guide treatment decisions. Patients at low risk may be managed with long-term observation, whereas an allogeneic stem cell transplant may be considered for patients at high risk.

It classifies patients with myelofibrosis into 4 risk categories:

• 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%)

Myelofibrosis can be divided into three phases: prefibrotic, overtly fibrotic, and advanced phase.

How Does Myelofibrosis Develop?

Myelofibrosis typically develops in three stages, each with varying severity and associated symptoms. Understanding these stages—from the initial prefibrotic phase to advanced myelofibrosis—can help patients and caregivers better anticipate the progression of the disease and explore treatment options tailored to each phase

Prefibrotic Myelofibrosis 

In the prefibrotic phase, There is minimal or no noticeable bone marrow fibrosis (scarring). The bone marrow is hypercellular; patients may have mild anemia and splenomegaly. This phase can last for several years. 

Overtly Fibrotic Myelofibrosis

Sometimes referred to as primary myelofibrosis if there is no other cause attributing to scarring in the bone marrow. In this phase, the bone marrow becomes fibrotic, and the production of blood cells is impaired. Patients may have severe anemia, thrombocytopenia, and marked splenomegaly. This phase can last for several years to decades.

Advanced Myelofibrosis

In advanced myelofibrosis, the disease progresses to acute myeloid leukemia (AML). Patients may have severe anemia, thrombocytopenia, and leukocytosis. The survival rate is often low for these patients, but continuous research is required to offer them more treatment options to improve their survival.

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Expanding knowledge for all patients and discovering the best time to start treatment is possible thanks to research. This is why it is very important to continue active research on myelofibrosis so that patients’ outcomes can be improved.

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Sources:

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5013940/
• https://b-s-h.org.uk/media/psjlvrys/diagnosis-and-evaluation-of-prognosis-of-myelofibrosis-a-british-society-for-haematology.pdf?cf=638354657263300000 
• https://ashpublications.org/blood/article/141/16/1954/493326/Myelofibrosis
• https://onlinelibrary.wiley.com/doi/10.1111/bjh.19164