Measurement of BCR-ABL1 transcripts on the International Scale in the United States: current status and best practices.

Chronic myeloid leukemia (CML) results from the Philadelphia chromosome (Ph) translocation and expression of its fusion oncoprotein BCR-ABL1. BCR-ABL1 tyrosine kinase inhibitors (TKIs) are the standard therapy for Ph-positive CML. Achievement of deep molecular responses (typically defined as ≥4-log reduction in BCR-ABL1 RNA levels) is an emerging treatment goal becoming attainable for more patients due to the availability of second-generation TKIs. Deep molecular responses are associated with improved long-term outcomes and are required prior to attempting cessation of treatment in treatment-free remission clinical trials. The National Comprehensive Cancer Network and European LeukemiaNet recommend regular monitoring of BCR-ABL1 RNA levels using real-time quantitative polymerase chain reaction (RQ-PCR). However, BCR-ABL1 RQ-PCR is a complex laboratory-developed test; routine quantitative results from clinical diagnostic laboratories may differ from those used to establish the recommendations. Although an International Scale (IS) was developed for standardized reporting of BCR-ABL1 RNA levels, IS adoption has been slow in the United States, but is now used by the vast majority of laboratories. Here, we discuss the importance of molecular monitoring in CML, gaps between current and best molecular monitoring practices in the United States, and challenges and potential solutions for universal IS adoption in the United States.