Chronic idiopathic myelofibrosis

Neoplasms. In this chapter we refer to patients with myelofibrosis, whether primary or secondary, and to ET or PV, as patients with CIMF. CIMF is a heterogeneous disorder with variable age of onset, presenting features, phe notypic manifestations, and prognosis. It is estimated that 701 patients were diagnosed with myelofibrosis in 2003 in the US, the only year for which statistics are available to date. 3 However, it is widely believed that this represents an underestimation of the actual incidence. The incidence increases with age, with the median age at diagnosis being 67 years, 4 although patients may present in the 3rd to 5th decades of life. 5 Average life expectancy is approximately 5 - 7 years, although younger patients with good prognostic features may have a life expectancy of 15 years or more. 4,5 Clinical presentation of patients diagnosed with CIMF may range from being asymptomatic, with their disease discovered on inve stigation for occult causes of leukocytosis or splenomegaly, to being severely debilitating. Myeloproliferation is one of the major fea tu resofthediseaseandcanleadtoa spectrum of clinical problems ranging from asymptomatic mild leukocytosis and/or thrombocytosis to severe organ damage. Clinical consequen cesofmyeloproliferationcan lead to morbidity and mortality from either a direct effect owing to increases in circulating cells or indirectly owing to organ damage resulting from sequestration of immature cells and production of blood cells in sites other as extramedullary hematopoiesis (EMH). This is commonly manifested as marked hepatosplenomegaly, with associated pain, early satiety, sequestration of erythrocytes and platelets, and portal hypertension. 6 In addition, nonhepatosplenic EMH might cause symptoms in various other organs including the lungs (e.g. respiratory distress and pulmonary hypertension), peritoneum (e.g. ascites), spine (e.g. paralysis), and pericardium (e.g. tamponade). 7 Current evidence suggests that sequestration of circulating myeloid progenitors is the underlying cause of EMH in CIMF. 8 Although most frequently leukocytosis by itself is asymptomatic, extreme elevations of leukocytes (i.e. > 100 × 10 9 /l), particularly when a large percentage of them are immature (increasing myeloblasts as oppo sed to mature neutrophils), may be associated with leukostasis. This latter phenomenon is not common in CIMF and when it occurs is more likely in the setting of leukemic transformation. Thrombocytosis is more common and may lead to vascular events (i.e. thrombosis or bleeding).