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Tsaur et al. (Abstract)

Cellular Therapy and Transplantation (CTT), Vol. 3, No. 9
doi: 10.3205/ctt-2010-No9-abstract48
© The Authors. This abstract is provided under the following license: Creative Commons Attribution 3.0 Unported

Abstract accepted for "4th Raisa Gorbacheva Memorial Meeting on Hematopoietic Stem Cell Transplantation",
Saint Petersburg, Russia, September 18–20, 2010

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Determination of BCR-ABL elevation level that corresponds to mutation detection in chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors

Grigory A. Tsaur1,2, Anna S. Ivanova1,2, Yulia A. Yakovleva1,2,  Tatyana O. Riger1,2, Olga M. Plekhanova1, Alexander M. Popov1,2,3, Andrey V. Misyurin4, Marina V. Suchkova4, Leonid I. Saveliev1,2,3, Larisa G. Fechina1,2

1Regional Children Hospital No. #1, Ekaterinburg, Russian Federation; 2Institute of medical cell technologies, Ekaterinburg, Russian Federation; 3Ural state medical academy, Ekaterinburg, Russian Federation; 4National research center for Hematology, Moscow, Russian Federation

Correspondence: Grigory A. Tsaur, Regional Children Hospital No. 1, Pediatric Oncology / Hematology Center, 32, S. Deryabina str., 620149 Ekaterinburg, Russia, E-mail: grigory.tsaur@spam is badgmail.com

Abstract

Aim: To evaluate the threshold level of BCR-ABL/ABL elevation that predicts the presence of BCR-ABL mutation.

Methods: In the current study 48 patients (pts) with suboptimal response or treatment failure according to the European LeukemiaNet criteria (M. Baccarani et al, JCO 2009) were investigated. Point mutations in BCR-ABL tyrosine kinase domain (TKD) were analyzed by reverse transcription–PCR and direct sequencing on an ABI Prism 3130 genetic analyzer. BCR-ABL and ABL copy numbers were assessed using real-time quantitative PCR. The elevation of BCR-ABL/ABL was calculated by subtraction of BCR-ABL/ABL value at the time point (TP) prior to mutation screening from the BCR-ABL/ABL value at the TP where a mutation was detected. The threshold level was defined by ROC curve analysis. Positive and negative predictive values (PPV, NPV), sensitivity, specificity, overall correct prediction (OCP) were calculated.

Results: patients were divided into two groups based on mutation status. They were as follows: with (n=18) and without (n=29) TKD point mutations. The groups did not differ in age, sex, presence and duration of pre-imatinib therapy, cumulative achievement of CHR, CCyR, MMR, or BCR-ABL/ABL level increase. ROC curve analysis determined that a 5.5 times BCR-ABL/ABL level increase corresponded to 92.9% of NPV for mutation detection. The odds ratio was 8.89 (95% CI 1.03–76.58). Despite a high specificity (93.0%), other parameters of diagnostic performance such as sensitivity, PPV, and OCP were relatively low (40.6%, 40.6%, 56.5%, respectively).

Conclusions:
Mutation detection can be used as screening method where the NPV is the most valuable parameter. Thus BCR-ABL/ABL elevation of 5.5 times allows detection of every single patient with BCR-ABL mutations.

Keywords: chronic myeloid leukemia, mutation analysis, BCR-ABL

 

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