Charles A. Schiffer, MD

I am very comfortable in using imatinib as initial therapy in most patients who present in chronic phase, with the possible exception of patients with more advanced disease and higher Sokal scores.

Resistance due to new mutations in the genes coding for the targeted proteins, as well as to changes in other signaling pathways, often develops, and newer drugs and perhaps combination approaches may be needed.

Chronic myelogeneous leukemia (CML) is a biologically unique neoplasm resulting from a mutation producing a single abnormal protein that induces unregulated proliferation of myelopoiesis. Imatinib mesylate (Gleevec) profoundly inhibits the chimeric bcr/abl tyrosine kinase, and has dramatically improved the outlook for patients with CML in chronic phase.

As comprehensively described by Drs. Prow and Vadhan-Raj, lineage-specific preparations of thrombopoietin are now in clinical development: pegylated recombinant human megakaryocyte growth and develop- ment factor (PEG-rHuMGDF) and recombinant human thrombopoietin (rhTPO). These preparations produce marked increases in megakaryocyte mass and platelet count after SC dosing.