A pilot study to test the feasibility of delivering an integrated risk stratification algorithm for multi-centre trials in childhood leukaemia

Summary

Risk-stratified treatment of acute lymphoblastic leukaemia (ALL) cures >90% of children and young adults with ALL, but at the cost of significant toxicity for a high proportion of patients. Targeting aggressive novel therapies to patients destined to relapse, whilst reducing the burden of therapy for patients who can be cured with less chemotherapy, requires improvements to current risk stratification processes. Extending the genetic risk stratification algorithm through the integration of copy number alterations (CNA) offers one of the most promising avenues.
This study aims to develop a clinically applicable single nucleotide polymorphism (SNP) array method for CNA analysis of ALL. Initially, two platforms for CNA analysis (Illumina and Affymetrix) will be compared with Multiplex ligation-dependent probe amplification (MLPA). The best performing platform will be studied further to assess to the feasibility of its use in delivering clinically applicable CAN analysis in real time. This requires the development of both a workflow and an integrated analysis platform to ensure that the complex analysis of CNA, minimal residual disease and conventional genetic data correctly feeds into treatment decisions.
This work contributes to the development of the next international phase III trial in childhood ALL, due to open in late 2018/early 2019, of which the UK is a substantive partner. International collaborations are essential to recruit sufficient patients to answer the randomised questions that will further improve outcomes for children with ALL. This project will assist the development of that trial and preparation of further grant applications to CR-UK to fund its conduct.