Please cite this article in press as: Tiribelli M, et al. EUTOS score predicts long-term outcome but not optimal response to imatinib in patients with chronic myeloid leukaemia. Leuk Res (2013), http://dx.doi.org/10.1016/j.leukres.2013.07.037 ARTICLE IN PRESS G Model LR-4974; No. of Pages 4 Leukemia Research xxx (2013) xxx–xxx Contents lists available at ScienceDirect Leukemia Research j o ur nal ho me page: www.elsevier.com/locate/leukres EUTOS score predicts long-term outcome but not optimal response to imatinib in patients with chronic myeloid leukaemia Mario Tiribelli ∗ , Massimiliano Bonifacio, Elisabetta Calistri, Gianni Binotto, Elena Maino, Luciana Marin, Emanuele Guardalben, Antonio Branca, Filippo Gherlinzoni, Gianpietro Semenzato, Rosaria Sancetta, Giovanni Pizzolo, Renato Fanin Division of Hematology and Bone Marrow Transplantation, Azienda Ospedaliero – Universitaria di Udine, Italy a r t i c l e i n f o Article history: Received 3 June 2013 Accepted 29 July 2013 Available online xxx Keywords: Chronic myeloid leukaemia Imatinib EUTOS score Prognosis a b s t r a c t To test the recently developed EUTOS score in predicting optimal response to imatinib and the long-term outcome, 265 patients with early chronic phase chronic myeloid leukaemia treated with standard dose imatinib were analysed. Achievement of optimal response endpoints were higher in low-risk patients, though the difference was not statistically significant: PCyR at 6th month 86% vs 67% (p = 0.06), CCyR at 12th month 80% vs 63% (p = 0.09), MMR at 18th month 61% vs 36% (p = 0.11). However, EUTOS score was predictive for the long-term response. With a median follow-up of 61 months, 53% high-risk patients experienced imatinib failure, compared to 23% in the low-risk group (p = 0.013). Among high-risk patients, 4/17 (23%) progressed to accelerated/blastic phase or died, compared to 11/248 (5%) low-risk patients, with 5-year progression-free survival rates of 84 ± 10% and 96 ± 1%, respectively (p = 0.04). Our data confirm that EUTOS score envisions the long-term outcome of imatinib therapy. © 2013 Elsevier Ltd. All rights reserved. 1. Introduction The introduction of imatinib and, subsequently, second- generation tyrosine kinase inhibitors (2G-TKIs) has dramatically changed the prognosis of patients with chronic myeloid leukaemia (CML). Long-term results of the IRIS study reported rates of esti- mated progression free survival (PFS) and overall survival (OS) at 6 years around 90% [1]. However, CML patients display hetero- geneous response to therapy and, therefore, survival depending on baseline clinical characteristics. Until recently, the stratifica- tion was made according to two scores developed in CML patients treated with chemotherapy (Sokal) [2], and interferon (Euro) [3]. In 2011 the European LeukemiaNet (ELN) evaluated more than 2000 patients with early chronic phase (ECP) CML treated with front-line imatinib to develop a new prognostic scoring system, the Euro- pean Treatment and Outcome Study (EUTOS) score [4]. EUTOS score uses only two clinical variables, the percentage of basophils and the spleen size, thus dividing patients in 2 groups of low- and high-risk, with different rates of 18-month complete cytogenetic response (CCyR) and five-year PFS. Since its publication, however, there have been conflicting reports about the efficacy of the EUTOS score [5–8]. ∗ Corresponding author at: Division of Hematology and Bone Marrow Transplan- tation, Azienda Ospedaliero – Universitaria di Udine, P.le S. M. Misericordia, 15, 33100 Udine, Italy. Tel.: +39 0432 559666; fax: +39 0432 559661. E-mail address: mario.tiribelli@uniud.it (M. Tiribelli). Moreover, scanty data are available on the power of this system in predicting the optimal response to imatinib in terms of cytogenetic and molecular response at specific time-points, as defined by 2009 ELN recommendations [9]. To contribute in clarifying this point, we evaluated 265 ECP CML patients treated with front-line standard dose imatinib. 2. Methods All evaluable patients with newly diagnosed CP CML treated with standard dose (i.e. 400 mg daily) imatinib as initial therapy from April 2000 and August 2011 were included in this retrospective analysis. Individual charts were reviewed, and clinical data were extracted. Patients who received any cytoreductive treatment except for hydroxyurea before imatinib were excluded from the study. Informed consent was obtained in accordance with the Declaration of Helsinki before the start of therapy. The EUTOS score was calculated according to the published formula, i.e. 7× basophil percentage in peripheral blood plus 4 x spleen size in centimetres below the costal margin, both evaluated at the time of diagnosis and before any cytoreductive therapy. A score ≤87 identifies low-risk patients while >87 identifies high-risk cases [4]. Cytogenetic analysis was performed in bone marrow cells with conventional G-banding technique. Partial cytogenetic response (PCyR) and CCyR were defined as 1–35% and 0% Ph+ metaphases, respectively. Molecular response was assessed by quantitative polymerase chain reaction (Q-PCR); results were expressed as BCR/ABL transcript logarithmic reduction until 2006, and as the BCR-ABL/ABL transcript ratio (International Scale–IS) thereafter. A major molecular response (MMR) was defined as a 3-log reduction or as BCR-ABL/ABL ratio ≤0.1%. Cytogenetic assessment was performed at least at 3, 6 and 12 months after imatinib therapy, than every 6 months until CCyR was attained, then every 1–2 years. Molecular response was assessed every 3 months for the first year or until achievement of MMR, than every 3–6 months. 0145-2126/$ – see front matter © 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.leukres.2013.07.037