title: Early BCR-ABL1 Reduction Is Predictive of Better Event-free Survival in Patients With Newly Diagnosed Chronic Myeloid Leukemia Treated With Any Tyrosine Kinase Inhibitor.
abstract: An early molecular response has a strong predictive value in chronic myeloid leukemia (CML). Recently, the halving time (velocity of early BCR-ABL1 transcript elimination) has been shown to represent an additional prognostic index. Our objective was the evaluation of the prognostic significance of the 3-month point in our population. We retrospectively collected BCR-ABL1 transcript data at different time points, events, and survival data of patients with CML treated at the Division of Hematology, San Luigi Hospital, University of Turin, Turin, Italy. Of 71 patients diagnosed from January 2005 to March 2015 in our center and treated with front-line tyrosine kinase inhibitors (imatinib, nilotinib and dasatinib), we selected those who had undergone a molecular evaluation at 3 months. The event-free survival (EFS) by the median follow-up time was the primary endpoint. The data from 50 patients with CML chronic phase were analyzed. Overall, 34 of the 50 patients (68%) had a transcript ≤ 10% at 3 months. Of those in the > 10% group, 63% had experienced an event compared with 12% in the ≤ 10% group by the median follow-up point (P < .001). The halving time threshold for discriminating between EFS was 17 days. None of the patients with a transcript > 10% at 3 months had a halving time of ≤ 17 days. Patients with BCR-ABL1 ≤ 10% and a halving time of ≤ 17 days had significantly better EFS than that of patients with BCR-ABL1 ≤ 10% and a halving time > 17 days and of patients with BCR-ABL1 > 10% (96% group 1 vs. 60% group 2 vs. 27% group 3; P < .001). Irrespective of the tyrosine kinase inhibitor used, the prognosis was significantly superior for patients with BCR-ABL1 ≤ 10% and halving time of ≤ 17 days. Our data revealed that the use of ABL1 as a control gene is reliable for the determination of the halving time in the clinical setting and highlight the importance of measuring the BCR-ABL1 transcript at CML diagnosis.
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Azienda Ospedaliero-Universitaria San Luigi Gonzaga, Orbassano (TO), Italy. Electronic address: carmen.fava@unito.it.
authors.forename: Carmen
authors.initials: C
authors.lastname: Fava
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Azienda Ospedaliero-Universitaria San Luigi Gonzaga, Orbassano (TO), Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Rege-Cambrin
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Azienda Ospedaliero-Universitaria San Luigi Gonzaga, Orbassano (TO), Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Dogliotti
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Azienda Ospedaliero-Universitaria San Luigi Gonzaga, Orbassano (TO), Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Gottardi
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Berchialla
authors.affiliation: Azienda Ospedaliero-Universitaria San Luigi Gonzaga, Orbassano (TO), Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Di Gioacchino
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Azienda Ospedaliero-Universitaria San Luigi Gonzaga, Orbassano (TO), Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Crasto
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Azienda Ospedaliero-Universitaria San Luigi Gonzaga, Orbassano (TO), Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Lorenzatti
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Azienda Ospedaliero-Universitaria San Luigi Gonzaga, Orbassano (TO), Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Volpengo
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Azienda Ospedaliero-Universitaria San Luigi Gonzaga, Orbassano (TO), Italy.
authors.forename: Filomena
authors.initials: F
authors.lastname: Daraio
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Azienda Ospedaliero-Universitaria San Luigi Gonzaga, Orbassano (TO), Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Fantino
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Azienda Ospedaliero-Universitaria San Luigi Gonzaga, Orbassano (TO), Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Saglio
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D012189:Retrospective Studies; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D016044:Fusion Proteins, bcr-abl
keywords: Chronic myeloid leukemia; Early molecular response; Halving time; Molecular monitoring; Prognostic factors