Improving treatment for children with leukaemia

Lymphoblastic leukaemia

A routine test for a genetic defect that can lead to serious side effects is improving therapy for children and young adults with a common form of leukaemia.

Our scientists found that the detection of a deficiency of thiopurine methyltransferase (TPMT) prior to acute lymphoblastic leukaemia (ALL) treatment allows early identification of the one in 300 children or young adults predisposed to serious side effects from thiopurine drugs. Thiopurine-based drugs are an important group of drugs used to treat ALL.

Identifying a TPMT deficiency early spares children and young adult patients potentially life-threatening conditions, such as sepsis and myelosuppression, where the bone marrow fails to produce adequate numbers of red blood cells, white blood cells and platelets.

The work was carried out by Dr Lynne Lennard and Professor Ajay Vora from the University’s Medical School, and builds on work done by Dr Lennard and Professor Sir John Lilleyman in the 1980s and 1990s.

In the UK alone, around 450 children and young adults are diagnosed with acute lymphoblastic leukaemia per year, making it one of the most common forms of leukaemia in that age group. The conventional treatment includes a thiopurine drug called 6-mercaptopurine, which is so crucial to cancer treatment that it is on the World Health Organisation list of essential medicines.

Testing for a TPMT deficiency prior to the start of thiopurine treatment enables doctors to recognise whether a child needs a reduced dosage of 10 per cent.

The impact of this research is such that now every new ALL patient in the UK is tested for a TPMT deficiency prior to starting thiopurine-based treatment.

The dose reduction of 6-mercaptopurine allows the other chemotherapeutic drugs to be given at their maximum tolerated doses. It also prevents prolonged gaps in treatment chemotherapy, which could result in the re-emergence of the leukaemia. This can occur if the TPMT deficiency had not been recognised and the patient had been given the full dose.

The impact of this research is such that now every new ALL patient in the UK is tested for a TPMT deficiency prior to starting thiopurine-based treatment. This treatment has been guided by Dr Lennard, Professor Vora and Professor Lilleyman’s research since 1999.

Professor Vora said: "It's always very satisfying to apply research that translates into a clinical application and the fact it benefits patients makes it further rewarding."

Professor Vora and his team are now researching other genetic polymorphisms affecting ALL treatment and its outcome. This current research, as with that into TPMT, will potentially enable doctors to identify other genotypes and moderate treatment and dosage accordingly.