In:
Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 4049-4049
Kurzfassung:
Background The approval of second-generation tyrosine kinase inhibitors (TKIs) for the first line treatment of Chronic Myeloid Leukemia (CML) has generated a need for early molecular parameters associated with inadequate responses to Imatinib Mesylate (IM). Objective We correlated quantitative determination of BCR-ABL transcripts at diagnosis with the outcome (defined according to the 2013 European Leukemia Net recommendations) of 272 newly diagnosed CML patients receiving IM 400 mg/die. Methods BCR-ABL transcripts were measured from peripheral blood samples drawn at diagnosis before patients received any pharmacological treatment using Real-Time Quantitative PCR (RQ-PCR). All molecular determinations were performed twice (in triplicates) on the same sample using either ABL or glucuronidase-beta (GUS) as reference genes. BCR-ABL values were then reported on the international scale (IS). Results With a median follow-up of 60 months, 65.4% of patients achieved an optimal response, 5.6% presented a response currently defined as "warning", 22.4% failed IM treatment and 6.6% switched to a different tyrosine kinase inhibitor because of intolerance to the drug. We recorded 19 deaths (6.9%), 7 (2.5%) attributable to disease progression. We applied Receiver Operating Characteristic (ROC) curves to define BCR-ABL/GUSIS expression levels that would separate patients likely (i.e. below the threshold) or unlikely (i.e. above the threshold) to achieve multiple endpoints, namely: optimal response (OR), failure-free survival (FFS), event-free survival (EFS), transformation-free survival (TFS) and overall survival (OS). Employing the specific threshold calculated for each endpoint we found that high BCR-ABL/GUSIS levels at diagnosis were associated with inferior probabilities of OR (p 〈 0.001), FFS (p 〈 0.001) and EFS (p 〈 0.001). Elevated BCR-ABL/GUSIS levels were also associated with higher rates of disease transformation to the accelerated phase or blast crisis (p=0.029) but not with OS (p=0.132). Conclusions High BCR-ABL transcripts at diagnosis measured by RQ-PCR employing GUS as a reference gene allow the identification of CML patients unlikely to benefit from standard dose IM that should be considered for alternative forms of treatment. Disclosures Hochhaus: Novartis: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; ARIAD: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding.
Materialart:
Online-Ressource
ISSN:
0006-4971
,
1528-0020
DOI:
10.1182/blood.V126.23.4049.4049
Sprache:
Englisch
Verlag:
American Society of Hematology
Publikationsdatum:
2015
ZDB Id:
1468538-3
ZDB Id:
80069-7
