alexa Impact of early dose intensity on cytogenetic and molecular responses in chronic- phase CML patients receiving 600 mg day of imatinib as initial therapy.
Bioinformatics & Systems Biology

Bioinformatics & Systems Biology

Journal of Proteomics & Bioinformatics

Author(s): Hughes TP, Branford S, White DL, Reynolds J, Koelmeyer R,

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Abstract We conducted a trial in 103 patients with newly diagnosed chronic phase chronic myeloid leukemia (CP-CML) using imatinib 600 mg/day, with dose escalation to 800 mg/day for suboptimal response. The estimated cumulative incidences of complete cytogenetic response (CCR) by 12 and 24 months were 88\% and 90\%, and major molecular responses (MMRs) were 47\% and 73\%. In patients who maintained a daily average of 600 mg of imatinib for the first 6 months (n = 60), MMR rates by 12 and 24 months were 55\% and 77\% compared with 32\% and 53\% in patients averaging less than 600 mg (P = .037 and .016, respectively). Dose escalation was indicated for 17 patients before 12 months for failure to achieve, or maintain, major cytogenetic response at 6 months or CCR at 9 months but was only possible in 8 patients (47\%). Dose escalation was indicated for 73 patients after 12 months because their BCR-ABL level remained more than 0.01\% (international scale) and was possible in 45 of 73 (62\%). Superior responses achieved in patients able to tolerate imatinib at 600 mg suggests that early dose intensity may be critical to optimize response in CP-CML. The trial was registered at www.ANZCTR.org.au as #ACTRN12607000614493. This article was published in Blood and referenced in Journal of Proteomics & Bioinformatics

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