Technical standardization and development of the International Scale (IS) for reporting Philadelphia chromosome BCR-ABL1 fusion gene expression has improved consistency for sequential testing in disease monitoring for patients with chronic myeloid leukemia (CML), but greater standardization among testing laboratories is still needed, according to a study published in the British Journal of Haematology.1

The study team reviewed external quality assessment trial data for reverse transcription quantitative polymerase chain reaction (RT-qPCR) assessments of BCR-ABL1 mRNA collected between 2007 and 2015.

“Comparison of participant results identified considerable variability at both high and low levels of disease, including therapeutically-important decision points,” the authors reported. But variability dropped when results were converted to the IS.

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Methods used by different centers for converting RT-qPCR results to IS scores yield “consistently different median results,” they noted. Despite IS scores’ role in improving the comparability of results, the authors concluded that further improvements are still needed to “fully realize the benefits of molecular monitoring of CML.”

It is unclear, however, whether RT-qPCR can reliably determine deep molecular response at any given point in a patient’s treatment. Greater interlaboratory standardization or the adoption of newer PCR platforms might be needed.

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“Clearly, there is a risk of misclassifying the success or failure of any treatment at a particular time point, and in practice most hematologists consider trends of residual disease over time in addition to levels of disease at fixed points,” they reported. “It is likely therefore that the eligibility of criteria for consideration of treatment cessation will require the demonstration of deep molecular response over multiple time-points in order to minimize the effects of intrinsically inaccurate measurement.”


  1. Scott S, Travis D, Whitby L, Bainbridge J, Cross NC, Barnett D. Measurement of BCR-ABL1 by RT-qPCR in chronic myeloid leukaemia: findings from an International EQA Programme. Br J Haematol. 2017 Mar 14. doi: 10.1111/bjh.14557 [Epub ahead of print]