Myelofibrosis is a serious bone marrow disorder that disrupts the body's normal production of blood cells. The staging and classification of myelofibrosis is based on the severity of symptoms, the presence of 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)

The IPSS is used at the time of diagnosis and includes five 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 is used to reassess the disease stage at any time after diagnosis. It includes the same risk factors as the IPSS, but assigns two points for hemoglobin level 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)

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%)

Understanding the Phases of Myelofibrosis

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

Prefibrotic Phase

In the prefibrotic phase, the bone marrow is hypercellular but fibrosis is not yet evident. Patients may have mild anemia and splenomegaly. This phase can last for several years.

Overtly Fibrotic Phase

In the overtly fibrotic 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 Phase

In the advanced phase, the disease progresses to acute myeloid leukemia (AML). Patients may have severe anemia, thrombocytopenia, and leukocytosis. The survival rate in this phase is often low.

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