Velocity of early BCR-ABL transcript elimination as an optimized predictor of outcome in chronic myeloid leukemia (CML) patients in chronic phase on treatment with imatinib

Hanfstein B, Shlyakhto V, Lauseker M, Hehlmann R, Saussele S, Dietz C, Erben P, Fabarius A, Proetel U, Schnittger S, Krause S, Schubert J, Einsele H, Hanel M, Dengler J, Falge C, Kanz L, Neubauer A, Kneba M, Stegelmann F, Pfreundschuh M, Waller CF, Spiekermann K, Baerlocher GM, Pfirrmann M, Hasford J, Hofmann WK, Hochhaus A, Mueller MC (2014)

Publication Type: Journal article

Publication year: 2014

Journal

Leukemia Springer Nature

Publisher: Nature Publishing Group: Open Access Hybrid Model Option B

Book Volume: 28

Pages Range: 1988-92

Journal Issue: 10

DOI: 10.1038/leu.2014.153

Abstract

Early assessment of response at 3 months of tyrosine kinase inhibitor treatment has become an important tool to predict favorable outcome. We sought to investigate the impact of relative changes of BCR-ABL transcript levels within the initial 3 months of therapy. In order to achieve accurate data for high BCR-ABL levels at diagnosis, beta glucuronidase (GUS) was used as a reference gene. Within the German CML-Study IV, samples of 408 imatinib-treated patients were available in a single laboratory for both times, diagnosis and 3 months on treatment. In total, 301 of these were treatment-naïve at sample collection.(i) with regard to absolute transcript levels at diagnosis, no predictive cutoff could be identified; (ii) at 3 months, an individual reduction of BCR-ABL transcripts to the 0.35-fold of baseline level (0.46-log reduction, that is, roughly half-log) separated best (high risk: 16% of patients, 5-year overall survival (OS) 83% vs 98%, hazard ratio (HR) 6.3, P=0.001); (iii) at 3 months, a 6% BCR-ABL(IS) cutoff derived from BCR-ABL/GUS yielded a good and sensitive discrimination (high risk: 22% of patients, 5-year OS 85% vs 98%, HR 6.1, P=0.002). Patients at risk of disease progression can be identified precisely by the lack of a half-log reduction of BCR-ABL transcripts at 3 months.

Authors with CRIS profile

Stefan Krause Department of Medicine 5 – Haematology and Oncology

Involved external institutions

Ruprecht-Karls-Universität Heidelberg DE Germany (DE) MLL Münchner Leukämielabor GmbH DE Germany (DE) Universitätsklinikum Würzburg DE Germany (DE) Klinikum Chemnitz DE Germany (DE) Klinikum Nürnberg DE Germany (DE) Universitätsklinikum Tübingen DE Germany (DE) Universitätsklinikum Gießen und Marburg (UKGM) DE Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) DE Germany (DE) Universitätsklinikum Ulm DE Germany (DE) Universitätsklinikum des Saarlandes (UKS) DE Germany (DE) Universitätsklinikum Freiburg DE Germany (DE) Ludwig-Maximilians-Universität (LMU) DE Germany (DE) Inselspital, Universitätsspital Bern CH Switzerland (CH) Universitätsklinikum Jena DE Germany (DE)

How to cite

APA:

Hanfstein, B., Shlyakhto, V., Lauseker, M., Hehlmann, R., Saussele, S., Dietz, C.,... Mueller, M.C. (2014). Velocity of early BCR-ABL transcript elimination as an optimized predictor of outcome in chronic myeloid leukemia (CML) patients in chronic phase on treatment with imatinib. Leukemia, 28(10), 1988-92. https://doi.org/10.1038/leu.2014.153

MLA:

Hanfstein, B., et al. "Velocity of early BCR-ABL transcript elimination as an optimized predictor of outcome in chronic myeloid leukemia (CML) patients in chronic phase on treatment with imatinib." Leukemia 28.10 (2014): 1988-92.

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