Published online before print August 9, 2007

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Copyright © 2007 American Society for Investigative Pathology
Journal of Molecular Diagnostics, doi:10.2353/jmoldx.2007.060134

Accepted for publication April 25, 2007.

Special Article

Inter-Laboratory Comparison of Chronic Myeloid Leukemia Minimal Residual Disease Monitoring. Summary and Recommendations

Tong Zhang^*, Sylvie Grenier^*, Bevoline Nwachukwu^*, Cuihong Wei^*, Jeffrey H. Lipton, Suzanne Kamel-Reid^*, and ^@

From the Department of Pathology,* Molecular Diagnostics, and the Department of Medicine, Princess Margaret Hospital, The University Health Network, Toronto, Ontario; and the Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada

^@ To whom correspondence should be addressed. E-mail: amp{at}asip.org.

	Abstract

In patients with chronic myeloid leukemia, the use of real-time quantitative reverse transcription-polymerase chain reaction (RQ-PCR) for measuring BCR-ABL1 transcripts has become standard methodology for the diagnosis and monitoring of minimal residual disease. In 2004 and 2005, 38 different laboratories from North America participated in three separate sample exchanges using RQ-PCR to measure RNA transcript levels in unknown diluents of a BCR-ABL1-positive cell line, K562. In this study we compared results of quantitative testing for BCR-ABL1 from laboratories using different platforms, internal controls, reagents, and calculation methods. Our data showed that there can be considerable variability of results from laboratory to laboratory, with log reduction calculations varying from 1.6 to 3 log between laboratories at the same dilution. We found that none of the variables tested had a significant impact on the results reported, except for the use of ABL1 as the internal control (P < 0.001). Laboratories that used ABL1 consistently underreported their log reduction values. Regardless of the specific methodology and platform used for RQ-PCR testing, it is important for laboratories to participate in proficiency testing to ensure consistent and acceptable test accuracy and sensitivity. Our study emphasizes the need for optimization of RQ-PCR before offering clinical testing and the need for widely available universal standards that can be used for test calibration.