Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)
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.
Milk thistle has been used for more than 2,000 years, primarily as a treatment for liver dysfunction. The oldest reported use of milk thistle was by Dioscorides, who recommended the herb as a treatment for serpent bites. Pliny the Elder (A.D. 23-79) reported that the juice of the plant mixed with honey is indicated for "carrying off bile."[1,2] In the Middle Ages, milk thistle was revered as an antidote for liver toxins.[1,2] The British herbalist Culpepper reported it to be effective for relieving...
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.
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 comparing nilotinib with imatinib, the rate of major molecular response at 12 months was 43% and 44% for 2-dose schedules of nilotinib and 22% for imatinib (P < .001 for both comparisons). The rate of complete cytogenetic response at 12 months was 80% and 78% for 2-dose schedules of nilotinib and 65% for imatinib (P < .001 for both comparisons).[Level of evidence: 1iiDiv] Progression to accelerated phase or blast crisis occurred in 11 patients on imatinib (4%) but only occurred in 2 patients (<1%, P = . 01) and 1 patient (<1%, P = .004) for the patients on 2-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 complete cytogenetic response at 12 months was 77% for dasatinib and 66% for imatinib (P = .007).[Level of evidence: 1iiDiv] Progression to accelerated phase or blast crisis occurred in nine patients (3.5%) on imatinib and in five patients (1.9%) on dasatinib (not statistically different).