Myelofibrosis with myeloid metaplasia: new developments in pathogenesis and treatment.

Myeloid metaplasia with myelofibrosis (MMM) is a chronic myeloproliferative disorder (CMPD) characterized by progressive anemia, massive splenomegaly, both hepatosplenic and non-hepatosplenic extramedullary hematopoiesis (EMH), a leukoerythroblastic blood smear, circulating progenitor cells, and marked bone marrow stromal reaction including collagen fibrosis, osteosclerosis and angiogenesis. The overall median survival is 5 years although it might range from 2 to 15 years depending on the presence or absence of clinically defined prognostic factors. Death is often due to leukemic transformation, portal hypertension or infection. In addition to shortened survival, quality of life is often affected by frequent red blood cell transfusions, profound constitutional symptoms, and cachexia. Drug therapy and autologous hematopoietic stem cell transplantation (HSCT) are of only palliative value and have not been shown to improve survival. The role of allogeneic HSCT, both myeloablative and non-myeloablative, is actively being investigated. Both splenectomy and radiation therapy have defined therapeutic roles to control EMH-associated symptoms. Analysis of the molecular biology of the disease is underway with the aid of animal models leading to the identification of novel therapeutic targets. Among the novel agents tested, thalidomide seems the most promising although newer agents are on the horizon.