therapy: drugs inhibiting JAK2 may improve symptoms rather than eradicating the neoplastic clone; further clinical trials are needed to clarify the role of these inhibitors.

•Approximately one-third of patients may have an asymptomatic or oligosymptomatic course

5.4.3Management

•Antithrombotic prophylaxis (e.g., acetic salicylic acid) is not established and is controversial

•Cytotoxic agents are not standardized. Symptoms of the disease must be weighed against adverse effects of drugs

•Anagrelide, a quinazoline derivate, decreases platelet count efficiently and has few adverse effects, which do not influence myelogenous cells. Its effect is based on its activity in reducing megakaryopoiesis

•Hydroxyurea is active in myeloproliferative disorders; however, it has been replaced by anagrelide

•Interferon-alpha and interferon-gamma inhibit megakaryopoiesis in vitro and inhibit stem cell proliferation and differentiation in the bone marrow

5.5Idiopathic Myelofibrosis

•Bone marrow fibrosis is well known in clonal hematological disorders: often seen in children in megakaryoblastic AML (FAB subtype M7) and in the preceding MDS phase of this disorder

•In adults, often associated with myeloproliferative disorders (CML, PV) and with MDS, particularly in secondary therapy associated with MDS, CMML, and unclassified MDS

•In childhood also in nonclonal disorders, e.g., systemic infectious diseases, hematological disorders such as sickle cell anemia, or hypereosinophilic syndrome

•Idiopathic myelofibrosis (IM) may precede malignant disorders for weeks and months

•IM should be regarded as a separate entity, but is a myeloproliferative disorder

•Although rare, IM is seen in children, with a possibly higher female to male incidence

5.5.1Clinical Manifestations

•Hepatosplenomegaly often seen

•Bone marrow may be hypocellular, but also hypercellular with increased reticulin fibers. Dysplastic signs may be present in erythroid cells, and less commonly in other lineages

•Extramedullary hematopoiesis may be observed