Disease Overview for Primary Myelofibrosis (PMF)

PMF (also known as agnogenic myeloid metaplasia, chronic idiopathic 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 myeloid leukemia (CML), PMF usually presents as follows:[2]

In addition to the clonal proliferation of a multipotent hematopoietic progenitor cell, an event common to all chronic myeloproliferative neoplasms, myeloid metaplasia is characterized by colonization of extramedullary sites such as the spleen or liver.[6,7]

Most patients are older than 60 years at diagnosis, and 33% of patients are asymptomatic at presentation. Splenomegaly, sometimes massive, is a characteristic finding. Patients younger than 40 years have a more indolent course, with fewer thrombotic events or transformation to acute leukemia.[8]

Symptoms of PMF include:

For more information about the symptoms listed above, see Fatigue, Hot Flashes and Night Sweats, and Nutrition in Cancer Care.

To establish a diagnosis of PMF, the World Health Organization classification requires that the patient meet all three major criteria and two minor criteria.[9]

Major Criteria

Minor Criteria

The major causes of death include:[13]

Fatal and nonfatal thrombosis was associated with age older than 60 years and JAK2 V617F positivity in a multivariable analysis of 707 patients followed from 1973 to 2008.[16] Bone marrow examination including cytogenetic testing may exclude other causes of myelophthisis, such as CML, myelodysplastic syndrome, metastatic cancer, lymphomas, and plasma cell disorders.[7] 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:[17-21]

Patients without any of the adverse features, excluding age, have a median survival of more than 10 to 15 years, but the presence of any two of the adverse features lowers the median survival to less than 4 years.[22,23] International prognostic scoring systems incorporate the aforementioned prognostic factors.[22,24] Thrombocytopenia (platelet count <50 × 109/L) is a very poor prognostic factor for PMF and for myelofibrosis following thrombocythemia or PV.[25]

Karyotype abnormalities can also affect prognosis. In a retrospective series, the 13q and 20q deletions and trisomy 9 correlated with improved survival and no leukemia transformation in comparison with the worse prognosis with trisomy 8, complex karyotype, -7/7q-, i(17q), inv(3), -5/5q-, 12p-, or 11q23 rearrangement.[16,26]