Childhood leukaemia: developing a new treatment to overcome drug resistance

Leukaemia is the most common cancer in children with around 500 children each year diagnosed with a type of leukaemia called acute lymphoblastic leukaemia (ALL).¹ Up to one in five of these children will have a fast-developing form of the disease called T-cell acute lymphoblastic leukaemia (T-ALL).² Thankfully, most are cured after treatment – but for those children where the disease returns or who don’t respond to existing treatments, the outlook is not as positive and many will lose their lives. Dr Frederik van Delft of Newcastle University is carrying out laboratory investigations to find out if combining two existing drugs could offer an effective new treatment option. His results could pave the way for a future clinical trial, providing hope for children and young adults if T-ALL comes back.

How are children’s lives affected now?

T-cell acute lymphoblastic leukaemia (T-ALL) is a form of blood cancer that mainly affects children, teenagers and young adults. The disease occurs when white blood cells called T-cells grow too fast, stopping the bone marrow from producing healthy blood cells.

Children with T-ALL will initially receive six months of intensive chemotherapy treatment, including steroid drugs – followed by lower-dose chemotherapy. Radiotherapy and/or a bone marrow transplantation is reserved for patients with drug-resistant disease.

“Thankfully, most children are cured – although they may be left with lifelong, sometimes serious, side-effects,” says Dr van Delft.

But sadly, the outlook is worse for children whose T-ALL doesn’t respond well to initial treatment, or if their cancer comes back and has become resistant to drugs.

“It is very difficult to successfully treat children with drug-resistant T-ALL,” says Dr van Delft. “We desperately need to find effective new treatments, so we can save more young lives from being cut tragically short.”

How could this research help?

“Our aim is to develop a new treatment approach that will improve survival for children and young people with T-ALL that has come back,” says Dr van Delft.

Dr van Delft is building on his previous laboratory work, which found that a combination of two existing drugs used to treat leukaemia – dasatinib (DAS) and dexamethasone (DEX) – could be an effective way to reverse drug resistance and kill T-ALL cells.

The team will now carry out more laboratory experiments to find out if and why these drugs might work better together for treating drug-resistant cancers. They will also search for specific characteristics of a child’s cancer cells that can help predict how well their disease will respond to this treatment.

“If our results look promising, we aim to test this drug combination in an international trial – selecting the children with relapsed T-ALL who are most likely to benefit,” says Dr van Delft.

References

1.Cancer Research UK Statistics: http://www.cancerresearchuk.org/health-professional/cancer-statistics/st... [website accessed 26 August 2018]

2.American Cancer Society: https://www.cancer.org/cancer/leukemia-in-children/detection-diagnosis-s... [website accessed 26 August 2018]