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
| Autor: | Joerg Hasford, Lothar Kanz, Susanne Saussele, Mathias Hänel, Markus Pfirrmann, Christian Dietz, C. Falge, Cornelius F. Waller, Wolf-K. Hofmann, Ulrike Proetel, Susanne Schnittger, Benjamin Hanfstein, Jolanta Dengler, H. Einsele, Philipp Erben, Andreas Neubauer, Michael Pfreundschuh, Michael Kneba, Gabriela M. Baerlocher, Rüdiger Hehlmann, J. Schubert, Martin C. Müller, Alice Fabarius, Andreas Hochhaus, Michael Lauseker, Karsten Spiekermann, Stefan W. Krause, Valeria Shlyakhto, Frank Stegelmann |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Adult
Male Risk Oncology Cancer Research medicine.medical_specialty Disease free survival Adolescent Treatment outcome Fusion Proteins bcr-abl Antineoplastic Agents Sensitivity and Specificity Disease-Free Survival Piperazines Young Adult Myelogenous Interferon Leukemia Myelogenous Chronic BCR-ABL Positive hemic and lymphatic diseases Internal medicine medicine Humans neoplasms Aged Glucuronidase Proportional Hazards Models Aged 80 and over business.industry Myeloid leukemia Imatinib Hematology Middle Aged Prognosis medicine.disease Leukemia Pyrimidines Treatment Outcome Imatinib mesylate Benzamides Immunology Imatinib Mesylate Female business medicine.drug |
| Zdroj: | Leukemia. 28:1988-1992 |
| ISSN: | 1476-5551 0887-6924 |
| DOI: | 10.1038/leu.2014.153 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|