Yazarlar : White DL, Radich J, Soverini S, Saunders VA, Frede A, Dang P, Cilloni D, Lin P, Mongay L, Woodman R, Manley P, Slader C, Kim DW, Pane F, Martinelli G, Saglio G, Hughes TP.

Yayın : Haematologica.

Yayın Yılı : 2011

Pubmed Linki : http://www.ncbi.nlm.nih.gov/pubmed/22207690

Konu : Lösemi

Literatür İçeriği :  

Abstract

Background. The functional activity of the OCT-1 protein (OCT-1 activity) is an excellent predictor of molecular response and progression free survival in newly diagnosed chronic phase chronic myeloid leukaemia patients treated with imatinib as front-line therapy. Design and Methods. In this study the predictive value of OCT-1 activity in the setting of 400 and 800mg/day imatinib dosing, and trough imatinib plasma levels are assessed in 100 patients enrolled to the TOPS study. Results. Patients on 400mg/day imatinib with high OCT-1 activity achieve significantly higher rates of major molecular response by 24 months than those patients with low OCT-1 activity (low OCT-1 activity -57% of patients;high OCT-1 activity 100%;p<0.001), but this difference does not reach significance in patients receiving 800mg/day (low OCT-1 activity -68%;high OCT-1 activity -95%;p=0.073). In addition, the combination of low trough imatinib levels (<1200ng/ml) and low OCT-1 activity defines a group of patients who achieve the lowest rates of major molecular response (47%) by 24 months when compared to all other patients (81% p=0.009). These patients are also at the highest risk for imatinib failure when compared to all other patients (p<0.001).Conclusions. High dose imatinib leads to superior molecular responses in patients with low OCT-1 activity. In this group trough imatinib levels may define a group with inferior outcomes. For high OCT-1 activity patients higher imatinib dosing or monitoring of imatinib trough levels were not found to be of significant clinical value. Hence OCT-1 activity determined prior to the start of therapy in newly diagnosed CML patients provides a valuable prognostic tool to determine the optimal up-front dose of imatinib in newly diagnosed chronic phase chronic myeloid leukaemia patients.

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