Changes to BCR-ABL Quantitation; Modification to test method and
Calibration to the WHO Internation Standard Result Reporting

Effective Monday, February 19, 2018, BCR-ABL quantitation by reverse transcription quantitative droplet digital polymerase chain reaction (RT-ddPCR) will be provided by the Molecular Pathology Laboratory at the Department of Pathology to replace the current test methods.

The BCR-ABL translocation [t(9;22)(q34;q11)] is present in greater than 95% of chronic myelogenous leukemia (CML), 20-40% of adult acute lymphoblastic leukemia (ALL) and a subset of pediatric ALL. Molecular assessment for the BCR-ABL RNA fusion transcript has become the standard for monitoring CML patients undergoing tyrosine kinase inhibitor therapy and translocation positive ALL.

A major molecular response (MMR) is equivalent to a three log10 reduction from a standardized baseline value as determined from the International Randomized Interferon versus STI571 (IRIS) study or 0.1% per International Scale (IS). MMR is reported when a patient shows an IS% value less than or equal to 0.1% IS.

A complete molecular response has been variably reported. It can be defined as the assay's limit of detection or four and a half log10 reduction (MR4.5) which for this assay is reported when a patient shows an IS% value less than or equal to 0.0032% IS.

Investigation for disease relapse should be considered if the IS% value increases by one log10 (ten-fold) or greater.

Specimen Type: Whole blood (EDTA anti-coagulated; pink or lavender top tube) or bone marrow aspirates (EDTA anti-coagulated; pink or lavender top tube).

Method: The BCR-ABL1 RNA Quantitation assay uses multiplex reverse transcription in combination with droplet digital PCR technology. The major and minor BCR/ABL1 translocations b2a2 (e13a2), b3a2 (e14a2) and e1a2 along with the ABL1 normalization control are simultaneously detected and quantified. A correction factor of 0.89 was determined by calibration to the International Scale. The assay can reliably detect 1 tumor cell in a background of 45,000 normal cells. The limit of quantitation is 0.003% IS. Positive values less than 0.003% will be reported as Trace Positive.

Results Reported: International Scale Percent Ratio (IS%) of BCR-ABL fusion transcript to ABL1 copies

Please use EPIC order code LAB 7393.

Questions concerning testing can be directed to Aaron Bossler, MD, PhD (ext. 4-9566).