SOHO 2024 | Guidance on mutational testing for diagnosing and monitoring CML

Last year we have published specific ELN recommendations on current best practices for diagnosis and monitoring of CML and this document also includes a specific section about when and how we should be looking for mutations in CML. So the current recommendations are to look for mutations whenever we have a response classified as failure or warning according to the current clinical ELN recommendations. And there is also a nice flowchart in the document where we can decide based on the BCR-ABL transcript levels and the treatment time point whether the patient is in need of a mutation test. As far as the technology is concerned, we are currently at a turning point because Sanger sequencing is being replaced by next generation sequencing. Implementation of NGS for BCR-ABL mechanism mutations is a bit challenging because there are no commercial kits and the MyLab gene panel, although they include ABL1 among the target genes, are not recommended to that purpose. So each laboratory has to implement its own assay in an [unintelligible] way. But if possible, NGS has several advantages over single sequencing in terms of sensitivity. And in several cases, greater sensitivity may be beneficial. However, it is also important to let the physicians know how to best interpret NGS results, not to misinterpret or overinterpret. And again, in our ELN recommendation document, we provide some guidance in this regard and a sort of, again, flow chart to decide whether a mutation is clinically relevant and whether treatment change is recommended or not based on NGS mutation status.