Treatment of patients with chronic myelogenous leukemia (CML) is usually initiated when the diagnosis is established, which is done by the presence of an elevated white blood cell (WBC) count, splenomegaly, thrombocytosis, and identification of the BCR/ABL (breakpoint cluster region/Abelson) translocation. The optimal frontline treatment for patients with chronic-phase CML is the subject of active clinical evaluation but involves specific inhibitors of the BCR/ABL tyrosine kinase.
In a randomized trial comparing imatinib mesylate with interferon plus cytarabine, with 5 years' median follow-up, imatinib mesylate induced complete cytogenetic responses in more than 80% of newly diagnosed patients; in addition, the annual rate of progression to accelerated phase or blast crisis dropped from 2% to less than 1% in the fourth year on the imatinib arm.[Level of evidence: 1iiDiii] However, most of these continually responding patients still showed detectable evidence of the BCR/ABL translocation by the most sensitive measurement of reverse transcriptase-polymerase chain reaction (RT-PCR).[3,4,5] The clinical implication of this finding after 10 years or more is unknown, but these results have changed clinical practice. Although evidence-based survival advantages are unavailable because of crossover in randomized trials, the overall survival rate for all patients at 5 years is 89%, with fewer than 50% of all deaths (4.5%) caused by CML.
ALL (also called acute lymphocytic leukemia) is an aggressive type of leukemia characterized by the presence of too many lymphoblasts or lymphocytes in the bone marrow and peripheral blood. It can spread to the lymph nodes, spleen, liver, central nervous system (CNS), and other organs. Without treatment, ALL usually progresses quickly.
Signs and symptoms of ALL may include the following:
Weakness or fatigue.
Fever or night sweats.
Bruises or bleeds easily (i.e., bleeding gums,...
Tyrosine kinase inhibitors with greater potency and selectivity than imatinib for BCR/ABL have been evaluated in newly diagnosed patients with CML. In a randomized, prospective study of 846 patients comparing 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, on two-dose schedules of nilotinib.
Similarly, in a randomized, prospective study of 519 patients comparing dasatinib with imatinib, the rate of major molecular response at 12 months was 46% for dasatinib and 28% for imatinib (P < .0001). The rate of major molecular response at 24 months was 64% for dasatinib and 46% for imatinib (P < .0001).[Level of evidence: 1iiDiv] Progression to accelerated-phase CML or blast crisis occurred in 13 patients (5%) on imatinib and in six patients (2.3%) on dasatinib (not statistically different).