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Primary myelofibrosis is one of several disorders in the spectrum of clonal myeloid diseases, malignant diseases that originate in the clonal expansion of a single neoplastic hematopoietic multipotential cell. Approximately 50 percent of cases have a mutation in the Janus kinase 2 (JAK2) gene. It is characterized, classically, by anemia, mild neutrophilia, thrombocytosis, and splenomegaly. Occasional cases may present with bi- or tricytopenias (~10%). Immature myeloid and erythroid precursors, teardrop-shaped erythrocytes, and large platelets are constant features of the blood film. The marrow contains an increased number of pathologic megakaryocytes and increased reticulin fibers and, often later, collagen fibrosis. This reactive, polyclonal fibroplasia is the result of cytokines (e.g., transforming growth factor [TGF]-β) released locally by the numerous abnormal megakaryocytes. The disease may be complicated by portal hypertension as a result of a very large splenic blood flow and loss of compliance of hepatic vessels and by fibrohematopoietic tumors that can develop in any tissue and lead to symptoms by compression of vital structures. Treatment may include hydroxyurea for thrombocytosis and massive splenomegaly, androgens, erythropoietin, or red cell transfusions for severe anemia, local irradiation of fibrohematopoietic tumors or of the spleen, and splenectomy. Trials of newly developed JAK2 inhibitors show beneficial effects but require further study. Portosystemic shunt surgery may be required for gastroesophageal variceal bleeding. In younger patients, allogeneic hematopoietic stem cell transplantation can be curative and nonmyeloablative transplantation has been successful, at least up to age 65 years, and may become the approach of choice at any age. The disease may remain indolent for years or may progress rapidly by further deterioration in hematopoiesis, by massive splenic enlargement and its sequelae, or by transformation to acute myelogenous leukemia. Overall median survival is approximately 5 years.

Acronyms and Abbreviations

Acronyms and abbreviations that appear in this chapter include: AML, acute myelogenous leukemia; bFGF, basic fibroblast growth factor; CD, cluster of differentiation; CML, chronic myelogenous leukemia; FISH, fluorescence in situ hybridization; G-6-PD, glucose-6-phosphate dehydrogenase; G-CSF, granulocyte colony-stimulating factor; IL, interleukin; MRI, magnetic resonance imaging; PDGF, platelet-derived growth factor; TGF, transforming growth factor; TNF-R, tumor necrosis factor-receptor.

Primary myelofibrosis is a chronic clonal myeloid disorder characterized by (1) anemia; (2) splenomegaly; (3) immature granulocytes, increased CD34+ cells, erythroblasts, and teardrop-shaped red cells in the blood; (4) marrow fibrosis; and (5) osteosclerosis. The disorder originally was described by Heuck1 in 1879 under the title “Two Cases of Leukemia and Peculiar Blood and Bone Marrow Findings.” In his monograph, Silverstein traced the history of the concepts set forth during the first half of the 20th century to explain the pathogenesis of this disease, including its origin in the marrow, the appearance of extramedullary hematopoiesis, and the relationship of fibrosis to hematopoietic changes.2 More than 20 designations for the disease have been proposed or used, and different designations were preferred in different countries.3Primary myelofibrosis has been designated the most recent “official” name of the ...

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