TY - JOUR

T1 - Personalization of chronic myelogenous leukemia treatment - Prognostic value of the individual rate of BCR-ABL level decline

AU - Fominykh, M. S.

AU - Abdulkadyrov, K. M.

AU - Turkina, A. G.

AU - Shuvaev, V. A.

AU - Martynkevich, I. S.

AU - Tsaur, G. A.

AU - Bederak, N. V.

AU - Chelysheva, E. Yu

AU - Shukhov, O. A.

AU - Abdullaev, A. O.

AU - Udaleva, V. Yu

AU - Zotova, I. I.

AU - Shikhbabaeva, D. I.

AU - Polushkina, L. B.

AU - Ivanovo, M. P.

AU - Petrova, E. V.

AU - Martynenko, L. S.

AU - Kleina, E. V.

AU - Tsybakova, N. Yu

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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 Imatinîb 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).

AB - 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 Imatinîb 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).

KW - BCR-ABL

KW - Chronic myeloid leukemia

KW - Individualization of therapy

KW - Major molecular response

KW - Tyrosine kinase inhibitors

UR - http://www.scopus.com/inward/record.url?scp=84981163505&partnerID=8YFLogxK

U2 - 10.18821/0234-5730-2016-61-1-4-10

DO - 10.18821/0234-5730-2016-61-1-4-10

M3 - Article

AN - SCOPUS:84981163505

VL - 61

SP - 4

EP - 10

JO - ГЕМАТОЛОГИЯ И ТРАНСФУЗИОЛОГИЯ

JF - ГЕМАТОЛОГИЯ И ТРАНСФУЗИОЛОГИЯ

SN - 0234-5730

IS - 1

ER -