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Disease Overview

Chronic idiopathic myelofibrosis (also known as agnogenic myeloid metaplasia, primary myelofibrosis, myelosclerosis with myeloid metaplasia, and idiopathic myelofibrosis) is characterized by splenomegaly, immature peripheral blood granulocytes and erythrocytes, and teardrop-shaped red blood cells.[1] In its early phase, the disease is characterized by elevated numbers of CD34-positive cells in the marrow, while the later phases involve marrow fibrosis with decreasing CD34 cells in the marrow and a corresponding increase in splenic and liver engorgement with CD34 cells. As distinguished from chronic myelogenous leukemia (CML), chronic idiopathic myelofibrosis usually presents with a white blood cell count smaller than 30,000/mm³, prominent teardrops on peripheral smear, normocellular or hypocellular marrow with moderate to marked fibrosis, an absence of the Philadelphia chromosome or the BCR/ABL translocation, and frequent positivity for the JAK2 mutation.[2] In addition to the clonal proliferation of a multipotent hematopoietic progenitor cell, an event common to all chronic myeloproliferative disorders, myeloid metaplasia is characterized by colonization of extramedullary sites such as the spleen or liver.[3,4]

Most patients are older than 60 years at diagnosis, and 33% of patients are asymptomatic at presentation. Splenomegaly, sometimes massive, is a characteristic finding.

Symptoms include:

• Splenic pain.
• Early satiety.
• Anemia.
• Bone pain.
• Fatigue.
• Fever.
• Night sweats.
• Weight loss.

The median survival is 3.5 to 5.5 years, but patients younger than 55 years have a median survival of 11 years.[3,4] The major causes of death include progressive marrow failure, transformation to acute nonlymphoblastic leukemia, infection, thrombohemorrhagic events, heart failure, and portal hypertension.[5]

Bone marrow examination including cytogenetic testing may exclude other causes of myelophthisis, such as CML, myelodysplastic syndrome, metastatic cancer, lymphomas, and plasma cell disorders.[4] In acute myelofibrosis, patients present with pancytopenia but no splenomegaly or peripheral blood myelophthisis. Peripheral blood or marrow monocytosis is suggestive for myelodysplasia in this setting.

There is no staging system for this disease.

Prognostic factors include:[6,7,8]

• Age.
• Anemia.
• Leukopenia.
• Leukocytosis.
• Circulating blasts.
• Karyotype abnormalities. In a retrospective series of 81 patients, 13q and 20q lesions correlated with improved survival and no leukemia transformation in comparison to the trisomy 8 or 12p lesions.[9]
• Systemic B symptoms (i.e., fever, night sweats, and weight loss).

Patients without any of these adverse features, excluding age, have a median survival of more than 10 years, while the presence of any two of these adverse features lowers the median survival to less than 3 years.[6]