Chronic myeloid leukemia: current status and controversies.
Until recently, the standard treatment for newly diagnosed patients with chronic myeloid leukemia (CML) in chronic phase who were not eligible for allogeneic stem cell transplant was interferon-alfa alone or in combination with low-dose cytarabine. Moreover, about 20% to 25% of patients who were relatively young and had suitable HLA-matched donors have in recent years been offered treatment by allogeneic stem cell transplantation, a procedure that can cure CML but is associated with an appreciable risk of morbidity and mortality. However, following the recognition in the 1980s that the p210 oncoprotein encoded by the BCR-ABL fusion gene on the Philadelphia chromosome had greatly enhanced tyrosine kinase activity and was probably the initiating event in the chronic phase of CML, much effort was directed toward development of drugs that would selectively inhibit this kinase activity. In 1998 these efforts culminated in the first clinical use of imatinib mesylate (Gleevec), which has since been shown to produce impressive results in treatment of patients with CML in chronic phase. In previously untreated patients, the incidence of complete cytogenetic responses exceeds 80%, and the majority of responses appear thus far to be durable. Imatinib also proved active in patients with accelerated phase and blastic phase disease, but in most of these cases, the benefits have been relatively short-lived. The advent of imatinib has thus necessitated a fundamental reappraisal of the approach to the initial management of CML.
Mughal
Tariq I
TI
Department of Haematology, Hammersmith Hospital at the Imperial College London, London, United Kingdom. tmughal@freenet.co.uk
Goldman
John M
JM
D001549:Benzamides; D002986:Clinical Trials as Topic; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018579:Patient Selection; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000627:therapeutic use*; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000494:pharmacology; D011743:Pyrimidines / Q000627:therapeutic use*; D033581:Stem Cell Transplantation
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl