Projects we fund

Overview

Acute lymphoblastic leukaemia (ALL) is the most common childhood cancer. We’ve achieved a survival rate of more than 90%, but this takes two to three years of toxic chemotherapy for each child, and some also need radiotherapy and stem cell transplant. The drug Vincristine is an essential part of treating childhood ALL, and other childhood cancers, but, like most chemotherapy drugs, it has side effects and can cause nerve damage (known as peripheral neuropathy) leading to pain, numbness, difficulties with walking and handwriting and impact on long-term dexterity. If this shows up during treatment, doctors may have to reduce or even stop treatment – which can make the child more likely to relapse. We don’t yet have the specific and sensitive measurement tools to study vincristine-induced peripheral neuropathy (VIPN), in children. This project aims to develop new ways of assessing how this drug affects children so we can improve their treatment and minimise side-effects.

What difference will this project make?

This study will significantly improve our understanding of what influences both the effectiveness and the side-effects of Vincristine therapy for children with ALL and certain other cancers. In the current national childhood ALL clinical trial (UKALL 2011) some children are receiving Vincristine and some are not. The team will use an adapted version of a scale developed to assess neuropathy in adults to establish how the children with ALL are affected by Vincristine treatment. They’ll also explore the impact of genetic variations in Vincristine pathways. Genetic variation means that some children metabolise the drug faster and are less likely to develop neuropathy. However, because they break down the drug faster this might increase the risk of relapse. For other children, who metabolise the drug more slowly, it might treat their cancer more effectively, but they’re potentially at greater risk of neuropathy. By examining the relationship between genetic variants, Vincristine exposure and outcome (in terms of both neuropathy and response to therapy) the team expects to provide important new information on the optimal dosing of this essential drug in children. This will help doctors to personalise doses, so that each child can be given an optimal dose to treat their cancer with minimal risk of side-effects.