New research led by Children’s Cancer Institute and published this week in the British Journal of Cancer suggests there may be a new way to reliably monitor cancer in some children, thanks to next generation sequencing technology.
Since 2002, a method known as ‘minimal residual disease (MRD) testing’ has been used in the Institute’s lab, and labs worldwide, to measure disease levels in children diagnosed with acute lymphoblastic leukaemia (ALL), the most common cancer in children. This methodology − which uses a sensitive technique called ‘PCR’ to detect low levels of leukaemia cells that persist during treatment, thereby giving an indication of how well the cancer is responding – has been found to dramatically improve treatment success, and is now used routinely to help guide treatment decisions for children and adults with ALL.
In the newly published study, whole genome sequencing and targeted next generation sequencing were used to develop a new type of MRD test for monitoring disease in children with a particularly difficult-to-treat subtype of ALL, which features a gene alteration known as an ABL-class fusion. Children with this gene fusion generally do not respond well to standard chemotherapy and are at high risk of relapse and death.
In recent years, the availability of a new therapy called tyrosine kinase inhibitors has improved the outlook for many children with this subtype of leukaemia. However, some children do not have an optimal response to this therapy and need further treatment in the form of a stem cell transplant. To identify these children, MRD testing is needed.
While a conventional MRD test – one which uses disease markers based on immunoglobulin and T-cell receptor rearrangements – may fail to detect or may underestimate the level of cancer in these children, the new MRD test, based on genomic data collected from the leukaemia cells, is likely to provide a more reliable measurement, the researchers found. Further, the new MRD test could enable earlier recognition of the gene fusions, which may lead to improved clinical outcomes.
“This is a very important paper describing new ways of approaching MRD monitoring for children with ALL,” said Dr Michelle Henderson, Research Manager in the Minimal Residual Disease Group at Children’s Cancer Institute, and an author on the study. “Excitingly, adaptation of this new approach for MRD marker development opens the way for disease monitoring in children with other cancers, for which conventional tests have not been possible.”