Background. The availability of three TKIs approved for the front-line treatment of Chronic Myeloid Leukemia (CML) raises questions about the optimal treatment strategy in individual patients. Two risk factors at diagnosis, spleen volume and basophils percentage (the EUTOS score), and one dynamic risk factor, reduction ≤10% of BCR-ABL transcript level after 3 months of imatinib, have been separately proved able to predict the long-term outcome of treatment. Aims and Methods. To identify patients with greater probability of good response to imatinib, we retrospectively tested the combination of EUTOS score and 3-month BCR-ABL transcript level in 169 consecutive CML patients treated front-line with standard dose (400 mg daily) imatinib. Patients were stratified into “good” (low EUTOS score and 3-months BCR-ABL ≤10%); “intermediate” (high EUTOS score or 3-months BCR-ABL >10%) and “poor” (high EUTOS score and 3-months BCR-ABL >10%) risk groups. Optimal responses were defined according to the European LeukemiaNet recommendations. Time to treatment failure (TTF) was measured from the start of imatinib to any of the followings: progression to accelerated or blastic phase (AP/BP), death for any cause at any time, hematologic or cytogenetic resistance leading to imatinib discontinuation. Progression free survival (PFS) was measured from the diagnosis to AP/BP or death for any cause at any time.Results. Median age of patients was 55 years (range 19–84). According to the EUTOS score there were 150 low risk (88.8%) and 19 high risk patients (11.2%); 3-month BCR-ABL transcript was ≤10% in 133 (78.7%) and >10% in 36 patients (21.3%). Patients with “good”, “intermediate” and “poor risk” profiles were 71.6%, 24.3% and 4.1%, respectively. Patients in the “good risk” group had a significantly higher probability of achieving optimal response to imatinib: 6-month PCyR rates were 91.3%, 78.4% and 42.9% for good, intermediate and poor risk, respectively (p=0.0042), 12-month CCyR rates were 91.2%, 69.7% and 20% (p=0.0001), 18-month MMR rates were 77.9%, 26.1% and 0%, (p<0.0001). After a median follow-up of 43.2 months (range 11–108), the probabilities of imatinib failure were 18.2%, 36.6% and 85.7% respectively. Also TTF and PFS were significantly different. Conclusions. The combination of EUTOS score and 3-month BCR-ABL level identifies a group of about two thirds of CML patients with a very good outcome on imatinib front-line treatment.

Combination of EUTOS score and 3-month BCR-ABL transcript level identifies a group of good-risk CML patients with favourable response to imatinib front-line.

BONIFACIO, Massimiliano;
2013-01-01

Abstract

Background. The availability of three TKIs approved for the front-line treatment of Chronic Myeloid Leukemia (CML) raises questions about the optimal treatment strategy in individual patients. Two risk factors at diagnosis, spleen volume and basophils percentage (the EUTOS score), and one dynamic risk factor, reduction ≤10% of BCR-ABL transcript level after 3 months of imatinib, have been separately proved able to predict the long-term outcome of treatment. Aims and Methods. To identify patients with greater probability of good response to imatinib, we retrospectively tested the combination of EUTOS score and 3-month BCR-ABL transcript level in 169 consecutive CML patients treated front-line with standard dose (400 mg daily) imatinib. Patients were stratified into “good” (low EUTOS score and 3-months BCR-ABL ≤10%); “intermediate” (high EUTOS score or 3-months BCR-ABL >10%) and “poor” (high EUTOS score and 3-months BCR-ABL >10%) risk groups. Optimal responses were defined according to the European LeukemiaNet recommendations. Time to treatment failure (TTF) was measured from the start of imatinib to any of the followings: progression to accelerated or blastic phase (AP/BP), death for any cause at any time, hematologic or cytogenetic resistance leading to imatinib discontinuation. Progression free survival (PFS) was measured from the diagnosis to AP/BP or death for any cause at any time.Results. Median age of patients was 55 years (range 19–84). According to the EUTOS score there were 150 low risk (88.8%) and 19 high risk patients (11.2%); 3-month BCR-ABL transcript was ≤10% in 133 (78.7%) and >10% in 36 patients (21.3%). Patients with “good”, “intermediate” and “poor risk” profiles were 71.6%, 24.3% and 4.1%, respectively. Patients in the “good risk” group had a significantly higher probability of achieving optimal response to imatinib: 6-month PCyR rates were 91.3%, 78.4% and 42.9% for good, intermediate and poor risk, respectively (p=0.0042), 12-month CCyR rates were 91.2%, 69.7% and 20% (p=0.0001), 18-month MMR rates were 77.9%, 26.1% and 0%, (p<0.0001). After a median follow-up of 43.2 months (range 11–108), the probabilities of imatinib failure were 18.2%, 36.6% and 85.7% respectively. Also TTF and PFS were significantly different. Conclusions. The combination of EUTOS score and 3-month BCR-ABL level identifies a group of about two thirds of CML patients with a very good outcome on imatinib front-line treatment.
2013
chronic myeloid leukemia; imatinib; BCR/ABL; EUTOS score
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/893603
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