Personalised genetic management of chronic myeloid leukaemia

Dr Alistair Reid, Imperial College

Recent studies show that 40% of chronic myeloid leukaemia (CML) patients in remission will remain disease-free after treatment. Therapy withdrawal is an attractive strategy to eliminate side effects and cost of lifelong treatments. However, the safe withdrawal of drugs would require the exclusion of patients at highest risk of relapse. The causes of relapse are unknown but it is possible that patients relapse when they still have disease undetectable by the current technique of measurement. Dr Reid and his team aim to devise an improved means of detecting and measuring the level of dormant disease and to investigate the value of this measurement in safely selecting patients for withdrawal.

Dr Reid's team have developed a new technique that measures leukaemic DNA rather than its product, RNA (the conventional method). The procedure, which they have optimised for use in a clinical laboratory, uses two cutting-edge techniques: “next generation sequencing” and “digital PCR”. Importantly, their new DNA-based method detects leukaemia in about half of the patients whose disease is undetectable using the RNA method.

The team have been granted approval to apply this technique to patients enrolled in the DESTINY study, a large national drug discontinuation trial for CML. This will allow us to assess the relationship between the presence of low levels of disease and outcome after therapy withdrawal. Ultimately we hope that this patient-tailored investigation may enable us to identify patients who can safely stop treatment and/or predict relapse at a very early and treatable stage.