Epidemiology
Primary myelofibrosis is a rare disease. The annual incidence is approximately 0.5-1.5/100,000 in the U.S. The global incidence is unknown.
Primary myelofibrosis appears to be more common in Caucasians. In addition, the prevalence is higher in German Jews. It is slightly more common in males than in females. However, the prevalence in pediatric patients is twice as high in females as in males.
Primary myelofibrosis can develop in all age groups. The median age at diagnosis is 65 years. 22% of patients are younger than 56 years. Primary myelofibrosis in children usually occurs within 3 years of age.
Etiology
Patients with primary myelofibrosis have the most significant alterations in the hematopoietic system. Other organ systems can also be involved due to extramedullary hematopoiesis. Studies have shown that myeloid cells in patients with primary myelofibrosis are differentiated by clonal stem cells. However, bone marrow fibroblasts and T cells are polyclonal. The etiology of excessive myelofibrosis remains unclear. Platelets, megakaryocytes and monocytes are secreting a variety of cytokines, such as transforming growth factor beta (TGF -β), platelet-derived growth factor (PDGF), interleukin 1 (IL), epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). can lead to fibroblast production and proliferation of extracellular matrix. In addition, vascular endothelial cell proliferation and bone marrow microvascular growth may be due to TGF-β and bFGFβ.
Neovascularization is the main hallmark of chronic myeloproliferative disease. Microvessel density in the bone marrow is elevated in approximately 70% of patients with myelofibrosis. Neovascularization is present in both bone marrow and extramedullary hematopoietic sites in patients with primary myelofibrosis. Elevated levels of serum vascular endothelial growth factor are the main mechanism for increased neovascularization.
Risk factors
No specific causative factors are found in the vast majority of patients. Radiation, certain contrast agents, and industrial solvents (e.g., benzene, toluene) may increase the risk of disease.
Studies have found an increased incidence of secondary hematologic and non-hematologic tumors in patients with chronic myeloproliferative neoplasms. Compared to the general population incidence, the risk is 1.2 in patients with primary thrombocytosis; 1.6 in patients with true erythrocytosis; and 1.6 in patients with chronic granulocytic leukemia.
Prognosis
The median survival time for patients with primary myelofibrosis is 3.5-5.5 years. the 5-year survival rate is half that of the age- and sex-matched general population. the 10-year survival rate is less than 20% [6]. Common causes of death in patients with primary myelofibrosis are infection, bleeding, cardiac insufficiency, splenectomy-related complications, and leukemic transformation. 20% of patients with primary myelofibrosis will develop leukemic transformation within 10 years.
Advanced age and anemia are poor prognostic factors for survival. Renal insufficiency, hepatic insufficiency, and thrombosis are also common causes of death.
Other poor prognostic factors include hypermetabolic symptoms, leukocytosis (white blood cell count range 10,000-30,000 /μL), leukopenia, increased number of primitive cells and naive granulocytes visible in peripheral blood, thrombocytopenia (platelet count <100,000/μL), and abnormal karyotype.
Patients with primary myelofibrosis have significantly more blood vessels in the bone marrow. Studies have reported increased microvascular density in the bone marrow in approximately 70% of patients and is an independent poor prognostic factor for patient survival.
Risk score
Primary myelofibrosis is indicated by a scoring system to indicate prognosis [7]. This system uses 2 adverse prognostic factors: hemoglobin less than 10 g/dl and leukocytes less than 4000 /μL or greater than 30,000 /μL. Patients without risk factors are considered low risk, those with both factors are considered high risk, and the presence of a single risk factor is considered intermediate risk. Median survival times were 93, 26 and 13 months in the low-, intermediate- and high-risk groups, respectively.
Low-risk patients with karyotypic abnormalities had a worse prognosis than those with normal karyotypes (median survival of 50 and 112 months, respectively). Increased risk of transformation of acute myeloid leukemia (AML) has been reported with leukocytosis (>30,000 /μL) and abnormal karyotype.
The Dynamic International Prognostic Scoring System for Primary Myelofibrosis (DIPSS) contains 5 risk factors that are prognostic factors for overall survival.
Age greater than 65 years
Hemoglobin level below 10 g/dl
White blood cell count above 25 x109/L
Peripheral blood primitive cells ≥1 %
Systemic symptoms
A 2011 study evaluated the prognostic value of karyotype, platelet count and transfusion status in relation to DIPSS. The results found that either poor karyotype or thrombocytopenia was a poor prognostic indicator for disease-free survival.