Chronic idiopathic myelofibrosis

Chronic Idiopathic Myelofibrosis

Chronic Idiopathic Myelofibrosis (CIMF), also known as Primary Myelofibrosis, is a rare type of bone marrow cancer that disrupts the body's normal production of blood cells. It is classified as a myeloproliferative neoplasm (MPN), a group of diseases that cause blood cells to grow abnormally in the bone marrow.

Pathophysiology

CIMF is characterized by the replacement of bone marrow with fibrous tissue, a process known as fibrosis. This fibrosis impairs the bone marrow's ability to produce blood cells, leading to anemia, thrombocytopenia, and leukopenia. The exact cause of the fibrosis is not well understood, but it is believed to be related to abnormal signaling pathways in hematopoietic stem cells.

The disease is often associated with mutations in the Janus kinase 2 (JAK2), calreticulin (CALR), or myeloproliferative leukemia virus oncogene (MPL) genes. These mutations lead to the constitutive activation of signaling pathways that promote cell proliferation and survival.

Clinical Presentation

Patients with CIMF may present with a variety of symptoms, including:

• Fatigue and weakness due to anemia
• Splenomegaly (enlarged spleen), which can cause abdominal discomfort
• Hepatomegaly (enlarged liver)
• Easy bruising or bleeding due to low platelet counts
• Night sweats and fever
• Bone pain

Diagnosis

The diagnosis of CIMF is based on a combination of clinical findings, laboratory tests, and bone marrow biopsy. Key diagnostic criteria include:

• Presence of bone marrow fibrosis
• Absence of the Philadelphia chromosome (to rule out chronic myeloid leukemia)
• Presence of JAK2, CALR, or MPL mutations

A bone marrow biopsy is essential to confirm the diagnosis and assess the degree of fibrosis.

Treatment

There is no cure for CIMF, but treatment focuses on managing symptoms and complications. Options include:

• JAK inhibitors, such as ruxolitinib, which can reduce splenomegaly and improve symptoms
• Blood transfusions to manage anemia
• Hydroxyurea to control high blood cell counts
• Allogeneic stem cell transplantation, which may be considered in younger patients with severe disease

Prognosis

The prognosis for patients with CIMF varies widely. Factors influencing prognosis include age, degree of anemia, white blood cell count, and the presence of certain genetic mutations. The disease can progress to acute myeloid leukemia in some cases.

Also see

• Myeloproliferative neoplasm
• Polycythemia vera
• Essential thrombocythemia
• Chronic myeloid leukemia