Prefibrotic primary myelofibrosis
A rare blood cancer distinct from overt myelofibrosis.
Prefibrotic primary myelofibrosis (Pre-PMF) is a rare blood cancer. The World Health Organization first recognized it as a separate type of myeloproliferative neoplasm in 2016. The disease can progress to overt primary myelofibrosis, but the speed of progression varies, and not everyone with Pre-PMF will develop the overt form. Its symptoms and presentation often look like those of essential thrombocythemia; the key difference is that Pre-PMF involves fibrosis in the bone marrow.
To diagnose Pre-PMF, a bone marrow biopsy is necessary. The major diagnostic criteria from the bone marrow include: abnormal growth and atypia of megakaryocytes (the cells that make platelets); reticulin fibrosis that is no more than grade 1 (grades 2 or 3 point to primary myelofibrosis); cellularity adjusted for the patient’s age; an increase in granulocytes (a type of white blood cell); reduced red blood cell production; and the presence of a clonal marker such as a mutation in JAK2, CALR, or MPL. At least one minor criterion must also be met: anemia not due to another condition; a high white blood cell count (leukocytosis); an enlarged spleen (splenomegaly); or LDH levels above the normal range.
In primary myelofibrosis, the diagnostic criteria include reticulin or collagen fibrosis of grade 2 or 3. Pre-PMF and essential thrombocythemia can look similar, both showing megakaryocyte proliferation and a mutation. The presence of reticulin fibrosis in Pre-PMF is what most clearly separates the two.
Treatment depends on risk. Patients considered low risk for thrombosis or major bleeding are simply monitored. Low-dose aspirin is recommended for those without a history of thrombosis. For intermediate-risk patients, treatment focuses on symptoms like anemia or constitutional issues. High-risk patients, or those with a history of thrombosis, receive oral anticoagulants and cytoreductive drugs such as hydroxycarbamide, and are managed like patients with primary myelofibrosis.
Prognosis for Pre-PMF is hard to pin down due to a lack of multi-center data and biases from the disease being newly classified in 2016. The 10-year rate of progression to overt PMF ranges from 9.7% to 31.5%. The 10-year risk of transformation into acute myeloid leukemia is between 5.8% and 12%.
Quick Facts
- Field
- Hematology and oncology
Facts from the source article.
Lore & Background
Prefibrotic primary myelofibrosis was first described in 1976, but was not introduced into the WHO classification of tumors until 2001, and not formally classified as a distinct entity until the 2016 revision. Diagnosis requires a bone marrow examination demonstrating proliferation and atypia of megakaryocytes, reticulin fibrosis not exceeding grade 1, age-adjusted cellularity, proliferation of granulocytes, decreased red blood cell production, and presence of a clonal marker such as JAK2, CALR, or MPL. At least one minor criterion—anemia, leukocytosis, splenomegaly, or elevated LDH—must also be present.
Reader's Guide
Prefibrotic primary myelofibrosis represents a significant refinement in the classification of myeloproliferative neoplasms, allowing for earlier and more accurate diagnosis compared to essential thrombocythemia or overt primary myelofibrosis. Its recognition as a distinct entity in 2016 has improved prognostic stratification, though a dedicated prognostic scoring model does not yet exist. Treatment varies by risk: low-risk patients may be observed or given low-dose aspirin, intermediate-risk patients receive symptom-driven therapy, and high-risk patients are treated with oral anticoagulants and cytoreductive drugs similarly to overt primary myelofibrosis. Prognosis is notably better than overt PMF, with median survival estimated at 17.6 years in one study, though data remain limited by the disease's recent reclassification and lack of multi-center studies.
Did You Know?
- The 10-year cumulative incidence of progression to overt primary myelofibrosis ranges from 9.7% to 31.5%.
- The 10-year incidence of transformation into acute myeloid leukemia ranges from 5.8% to 12%.
- One study showed 98% of pre-PMF patients were alive after 10 years from diagnosis.
- Reticulin fibrosis grade 2 or 3 is a diagnostic criterion for primary myelofibrosis, not pre-PMF.
More in Idiopathic diseases 1-24
Spotted an error? Know more?
Reader corrections go straight into our review queue. Suggest an edit · How this site is sourced