Prefibrotic primary myelofibrosis

Prefibrotic Primary Myelofibrosis (pre-PMF) is a bone marrow disorder characterized by the clonal proliferation of hematopoietic stem cells leading to the fibrotic thickening of the bone marrow matrix, which can precede the development of overt primary myelofibrosis (PMF). This condition falls under the category of myeloproliferative neoplasms (MPNs), a group of diseases that also includes polycythemia vera (PV), essential thrombocythemia (ET), and PMF. Pre-PMF is distinguished from overt PMF by its early stage of fibrosis, less pronounced symptoms, and a different prognosis.

Symptoms and Diagnosis

The symptoms of pre-PMF are often nonspecific and may include fatigue, anemia, splenomegaly (enlargement of the spleen), and a feeling of fullness or discomfort in the left upper abdomen due to splenic enlargement. Unlike overt PMF, the symptoms in pre-PMF are usually less severe.

Diagnosis of pre-PMF involves a combination of clinical evaluation, blood tests, and bone marrow examination. Blood tests may show abnormalities such as anemia or an elevated platelet count. A definitive diagnosis requires a bone marrow biopsy, which shows increased fibrosis compared to normal bone marrow but not to the extent seen in overt PMF.

Pathophysiology

The pathophysiology of pre-PMF involves the abnormal proliferation of hematopoietic stem cells that carry mutations in genes such as JAK2, CALR, or MPL. These mutations lead to the activation of signaling pathways that promote cell proliferation and resistance to apoptosis (programmed cell death), contributing to the accumulation of fibrous tissue in the bone marrow.

Treatment

Treatment for pre-PMF is primarily aimed at managing symptoms and preventing the progression to overt PMF. Therapeutic strategies may include the use of aspirin to reduce the risk of thrombosis, cytoreductive therapy to control blood counts, and treatment of anemia with erythropoiesis-stimulating agents or blood transfusions. In selected cases, especially for patients with significant symptoms or a high risk of progression, more aggressive treatments such as JAK inhibitors or allogeneic stem cell transplantation may be considered.

Prognosis

The prognosis of pre-PMF varies widely among individuals. Some patients may remain stable for years without progressing to overt PMF, while others may experience rapid progression. Factors that can influence prognosis include age, blood counts, and the presence of certain genetic mutations.

Epidemiology

Pre-PMF is less common than other MPNs such as PV and ET. The exact incidence and prevalence of the condition are difficult to determine due to its overlapping features with other MPNs and the evolving criteria for diagnosis.