Leukemia is an abnormal rise in the number of white blood cells. The white blood cells crowd out other blood cell elements such as red blood cells and platelets. The elevated white blood cells are immature and do not function properly.
Leukemia -- the term derives from the Greek words for "white" and "blood" -- is often considered a disease of children, yet it actually affects far more adults. It is more common in men than women and in Caucasians than African-Americans. There will be more than...
A trial randomly assigning 1,106 previously untreated patients to imatinib mesylate or to interferon plus cytarabine documented a 76% complete cytogenetic response rate with imatinib mesylate versus 14% for interferon plus cytarabine at a median follow-up of 19 months.[1,2][Level of evidence: 1iiDiii] At 18 months, 96.7% of the imatinib group had avoided progression to accelerated-phase CML or blast crisis compared with 91.5% of the interferon plus cytarabine group (P < .001). Because 90% of the combination group had switched to imatinib by 18 months (mostly because of intolerance of side effects), a survival difference may never be observed. By the 5-year median follow-up of this trial, imatinib mesylate induced complete cytogenetic response in more than 80% of the participants, with the annual rate of progression to accelerated-phase CML or blast crisis dropping from 2% in the first year to less than 1% in the fourth year. In addition, the overall survival (OS) rate for all patients at 5 years is 89%, with fewer than 50% of all deaths (4.5%) caused by CML. More than 90% of completely responding patients still show detectable evidence of the BCR/ABL translocation, usually by reverse transcription-polymerase chain reaction (RT-PCR) or by fluorescence in situ hybridization of progenitor cell cultures.[3,4,5] The clinical implication of this finding after 10 years or more is unknown, but these results have changed clinical practice. Poor compliance is the predominant reason for inadequate molecular response to imatinib.
Tyrosine kinase inhibitors with greater potency and selectivity for BCR/ABL than imatinib have been evaluated in newly diagnosed patients with CML. In a randomized, prospective study of 846 patients that compared nilotinib with imatinib, the rate of major molecular response at 24 months was 71% and 67% for two-dose schedules of nilotinib and 44% for imatinib (P < .0001 for both comparisons).[Level of evidence: 1iiDiv] Progression to accelerated-phase CML or blast crisis occurred in 17 patients on imatinib (14%), but this progression only occurred in two patients (<1%, P = .0003) and in five patients (1.8%, P = .0089), respectively, for those patients on two-dose schedules of nilotinib. Nilotinib-treated patients had a lower rate of treatment-emergent BCR/ABL mutations than did imatinib-treated patients.