Primary myelofibrosis

Primary myelofibrosis (PMF), previously known as osteomyelofibrosis, is a myeloproliferative neoplasm characterised by proliferation of granulocyte and megakaryocyte lineages, as well as eventual deposition of fibrous connective tissue in the bone marrow.

PMF has two phases. In the prefibrotic phase, the bone marrow is hypercellular, while in the fibrotic phase, the bone marrow undergoes fibrosis.

50% of PMF cases are associated with JAK2 mutation. The remaining cases are caused by CALR or MPL mutations.

Clinical features

Asymptomatic presentations are rare. Patients have:

Hepatosplenomegaly (especially spleen, can grow very large)
Anaemia
Thrombosis
Bleedings
Extramedullary haematopoiesis – because of myelofibrosis

Diagnosis and evaluation

Labs show:

Decreased Hct
Decreased RBC
Elevated WBC
Elevated thrombocytes

Blood smear shows teardrop RBCs and other immature/abnormal cells. Bone marrow biopsy shows a hypercellular bone marrow with megakaryocytic proliferation in the prefibrotic stage, and fibrotic bone marrow in the fibrotic stage. Genetic testing for driver mutations confirms the diagnosis.

Treatment

There are many treatment options, depending on the patient’s symptoms and risk:

Interferon
JAK inhibitor (ruxolitinib)
Erythropoiesis-stimulating agents (ESA)
Allogeneic HSCT