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Personalization of chronic myelogenous leukemia treatment - prognostic value of the individual rate of BCR-ABL level decline


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Abstract

Relevance. Chronic myelogenous leukemia (CML) patients represent the heterogeneous group. Several studies in recent years were aimed to personalize treatment based on individual patients characteristics. Aim of study. The aim of our study was to assess prognostic value of individual BCR-ABL decline rate in the first three months of CML therapy to predict optimal response. Patients and methods. Fifty-four patients with chronic phase CML were included in the study. Forty-one patients started treatment with Imatinib 400 mg/day, 12 patients started with Nilotinib 600 mg/day and 1 patient started with Dasatinib 100 mg/day. BCR-ABL level was determined by International Scale at the moment of diagnosis and after 3, 6 and 12 months with ITK therapy. The ratio of BCR-ABL levels at 3 months to baseline for each patient, frequency of the achievement of the early molecular response at 3 months (10% by IS) and MMR at 12 months were assessed; in addition, we calculated ratio of BCR-ABL levels at 3 months to BCR-ABL levels at 1 month. Twenty-six out of 34 patients (76.5%) with ratio of BCR-ABL levels at 3 months to baseline below than 0,1 achieved MMR at 12 months, while only 9 out of 20 patients (45%) with ratio more than 0,1 had optimal response (p = 0.02). Ratio of BCR-ABL levels at 3 months to BCR-ABL levels at 1 month showed much better results with the same (0.1) cut-off value - 5 out of 6 patients (83.3%) with ratio BCR-ABL levels at 3 months to BCR-ABL levels at 1 month below than 0.1, while only the 1 patient (16.7%) with ratio more than 0.1 achieved optimal response (p = 0.04), respectively. Application of early molecular response at 3 months (10% by IS) yielded worse discrimination results: 33 of 46 (71.7%) patients with BCR-ABL level ≤ 10% at 3 months, whereas 2 of 8 (25%) patients with BCR-ABL > 10% had MMR at 1 year (p = 0.02), respectively. Furthermore, application of our ratio cut-off value in patients with early molecular response (BCR-ABL level ≤ 10% at 3 months) allowed us to reveal additional 5 high-risk patients who have not reached MMR after 1 year of therapy. Conclusion. Our study showed that individual BCR-ABL level decline rate estimated in the first three months of CML therapy from the baseline to the level measured at 3 months might be useful as an optimal predictor of outcome for CML patients (MMR after 1 year of treatment).


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