28 January 2010

University research to improve treatment of childhood leukemia

Children with leukaemia could be offered tailored treatment to avoid unnecessary side-effects from chemotherapy, thanks to research carried out at the University of Sheffield.

Researchers in the University´s Academic Unit of Clinical Pharmacology in the Department of Human Metabolism, have been awarded £77,260 from the blood cancer charity Leukaemia & Lymphoma Research, to continue their investigations into how a child´s genetic code can affect his or her response to drugs when treated for leukaemia.

Acute lymphoblastic leukaemia (ALL) affects around 450 children a year in the UK. It is a highly aggressive cancer and is fatal without effective treatment. The main treatment for ALL is chemotherapy with toxic drugs. Once a child has achieved remission they must undergo `maintenance´ therapy for at least two years with lower doses of drugs, including one called 6-mercaptopurine (6-MP).

The team at the University, led by Dr Lynne Lennard, is studying how each child´s genetic code determines how he or she will react to this drug.

Currently, daily oral doses of 6-MP are taken during the years of long-term maintenance chemotherapy. Attempts to reduce the duration of 6-MP maintenance to less than two years have resulted in more disease relapse in those that took the shorter course of treatment, so it is important that the child receives the optimal amount of 6-MP throughout maintenance chemotherapy.

Research has shown that an enzyme in the liver called TPMT has been identified as playing a major role in handling this drug. Some children appear to have a particularly active form of the enzyme and this means they digest the drug very quickly and the body does not receive enough 6-MP. In these children, unless action is taken and the 6-MP dose increased, the drug is not very effective against the leukaemia. On the contrary, other children have a less active form of TPMT which means the body received too much 6-MP and the drug has toxic side effects.

Dr Lennard and her team are developing a genetic test for TPMT that can be used to tell doctors exactly how much of the drug they should give to each child.

Dr Lennard, from the University´s Academic Unit of Clinical Pharmacology, said: "Our aim is to measure the TPMT status of each child so that they can be given the correct dose of 6-MP to increase the effectiveness of the drug whilst reducing the toxic side affects. There are very rare cases where even standard doses of 6-MP are lethal because the TPMT enzyme is completely inactive. For these children a much reduced dose of 6-MP is required.
"We are investigating whether a quick screening test at diagnosis can predict subsequent TPMT enzyme activity during chemotherapy."

Dr David Grant, Scientific Director at Leukaemia & Lymphoma Research, said: "Our University of Sheffield team has a record of world-class research in the field of childhood leukaemia. This is contributing to the continued improvement in the cure rate for children with this blood cancer. We are confident that further work by Dr Lennard´s team will bring even more benefit for these children."

Notes for Editors: Leukaemia & Lymphoma Research currently has £2,885,000 invested in blood cancer research in Sheffield.
Leukaemia & Lymphoma Research is the only UK charity solely dedicated to research into blood cancers, including leukaemia, lymphoma and myeloma. Leukaemia & Lymphoma Research was previously known as Leukaemia Research and has changed its name to raise awareness of its longstanding commitment to research into all the blood cancers - not just leukaemia. Leukaemia & Lymphoma Research needs to raise £120 million in the next five years to continue its life-saving research. For more information, visit the link below or call 020 7405 0101.

For further information please contact: Shemina Davis, Media Relations Officer, on 0114 2225339 or email shemina.davis@sheffield.ac.uk or Henry Winter at the Leukaemia & Lymphoma Research Press Office on 020 7269 9019, 07824 375880 or email hwinter@llresearch.org.uk.

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