The role of interferon-alpha in the treatment of idiopathic myelofibrosis

Idiopathic myelofibrosis (IMF) is se chronic myeloproliferative disorder ch aracterized by fibrosis of the bone marrow, varying degrees of extramedulla ry hematopoiesis, splenomegaly, anemia, and a leukoerythroblastic periphera l blood smear. Bone marrow fibrosis develops as a secondary phenomenon and is caused by increased intramedullary activity of mitogens such as platelet -derived growth factor (PDGF), transforming growth factor-beta (TGF-beta), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and c almodulin. Because, of the variable clinical course of IMF, attempts have b een made to define prognostic parameters that can be helpful in detecting p atients with a shortened life expectancy. The most important adverse progno stic parameters that have been reported are hemoglobin concentration, age, leukocyte count, number of thrombocytes, and cytogenetic abnormalities. How ever, no standardized prognostic score for IMF has yet been established. Th erapeutic strategies in IMF remain predominantly supportive. The most commo n are blood transfusions, androgens, and cytoreductive agents such as hydro xyurea. Bone marrow transplantation is increasingly being taken into consid eration, but it still has to be regarded as an experimental approach. Inter feron-alpha (IFN-alpha) has shown promising results in early hyperprolifera tive stages of IMF but has no or only very little effect in more advanced s tages of the disease. Whether IFN-alpha is able to postpone marrow fibrosis if administered in early disease stages remains to be determined in future clinical trials.