Finding new ways of treating leukaemia in children

Decades ago, acute lymphoblastic leukaemia (ALL) in children was considered a death sentence.

Today, the cure rates are much higher, with more than four in five young patients here being cured of the most common form of childhood cancer.

And for the one in five who does not respond well to chemotherapy, scientists are looking at other ways of killing the cancer cells.

ALL is a cancer of the bone marrow and affects about 30 children in Singapore every year.

Doctors are today able to use different combinations of chemotherapy drugs in optimal doses to maximise the chance of a cure and minimise side effects, building on various breakthroughs in the past decades, said Associate Professor Allen Yeoh, senior consultant in the Division of Paediatric Haematology-Oncology, National University Cancer Institute, Singapore (NCIS).

Until 1972, the blood cancer was considered incurable.

Then scientists led by Dr Donald Pinkel at the St Jude Children's Research Hospital in Tennessee developed the first successful protocol that cured 50 per cent of children with ALL using a combination of chemotherapy and radiation.

While this treatment was subsequently adopted for use here and achieved a 38 per cent cure rate between 1972 and 1988, radiation often left patients with long-term side effects, said Prof Yeoh.

"As leukaemia hides in the brain, as well (as) in (the) testes in males, we had to radiate their brains and testes," he added.

This caused the children to have a poorer memory and IQ compared with their siblings. They also suffered from hormonal deficiencies which caused them to be shorter than their siblings. Boys became infertile, their sperm-producing cells destroyed by the radiation.

But clinician scientists in Singapore found ways to overcome that.

First, they were able to replace radiation with more chemotherapy in the late 1980s and 90s. They then experiemented with different combinations of the drugs, and found that they worked better in groups of three to four at each time.

Patients who had a low risk of relapse also received lower doses of chemotherapy while those who had high amounts of residual leukaemia cells after initial treatment were given more aggressive chemotherapy, and even a bone marrow transplant from the start, said Prof Yeoh. He added: "We are still using the nine drugs that were available 30 years ago."

"About 85 per cent of our patients receive the lowest doses of chemotherapy among developed countries and yet have the same or even superior cure rates."

A patient is considered cured of the disease if he does not suffer a relapse and lives more than five years. Chances of the cancer coming back after this are rare, Prof Yeoh said.

TREATMENT BY OTHER MEANS

We have reached the limits of chemotherapy, so immunotherapy, harnessing the immune system to try to kill leukaemia cells, is an alternative.

ASSOCIATE PROFESSOR ALLEN YEOH, senior consultant in the Division of Paediatric Haematology-Oncology, National University Cancer Institute, Singapore.

Despite their success, scientists are not resting on their laurels.

For the remaining 15 per cent of children who do not respond well to chemotherapy, immunotherapy could one day be a viable alternative.

Scientists in other parts of the world are studying how the body's T-cells, a type of white blood cell, may be reprogrammed to target an antigen called CD19 found on the surface of many leukaemia cells.

"We have reached the limits of chemotherapy, so immunotherapy, harnessing the immune system to try to kill leukaemia cells, is an alternative," said Prof Yeoh.

Immunotherapy can take the form of injections or drugs that restore the natural ability of the immune system lost during cancer development, added Dr Wang Cheng-I, Principal Investigator Technologist at the Therapeutic Antibody Engineering Lab in A*Star's Singapore Immunology Network.

Dr Wang noted: "Chemotherapy drugs sometimes cannot kill a sub-population of cancer cells called cancer stem cells. The consequence is that while patients may experience an initial shrinkage or disappearance of a cancerous tumour, cancer cells can reappear in a matter of months."

A version of this article appeared in the print edition of The Straits Times on August 31, 2016, with the headline 'Finding new ways of treating leukaemia in children'. Print Edition | Subscribe