SINGAPORE – Two-year-old Mathias kept coming down with high fever. Then his family noticed bruises on his inner thighs.

"We thought he was being punished in childcare," said his father, Mr Michael Teo, 39, a civil servant.

Following a second visit to a general practitioner, the family was advised to take the toddler to KK Women's and Children's Hospital (KKH).

By then, tiny blood spots resembling pinpricks started appearing on his legs, said the boy's mother, Ms Adriana Koh, 34, who works in the talent acquisition field.

Mathias was taken to KKH on a Sunday in April 2022 as his parents were afraid he might have caught dengue fever.

A blood test revealed the toddler had an alarmingly elevated white blood cell count, and he was promptly admitted to the Children's Intensive Care Unit (ICU).

Two days later, the doctors told his parents that Mathias has leukaemia – a cancer that starts in the cells of the bone marrow where blood cells are made – and recommended chemotherapy.

"It was a shock. We have no family history (of leukaemia), and he was born healthy and had been healthy since," said Mr Teo.

Leukaemia is the most common childhood cancer in the world. In Singapore, about 150 children are diagnosed with cancer every year. About two-thirds are leukaemia cases, according to KKH.

In the ICU, Mathias would scream in fear each time the doctors came to draw his blood for various tests. He also screamed for his parents when they had to leave the ward for the team to perform a bone marrow biopsy.

Mr Teo said they wanted so much to elevate the pain their son was feeling but felt completely helpless.

"We broke down outside the ICU. We hugged each other," he added.

The toddler did not respond to the first round of chemotherapy and was put on a stronger dose in the second stage of the treatment. He was constantly hungry and asking his grandmother for food every half-hour.

Said Mr Teo: "He had to eat very fresh food... so she had to make the fresh food, and he was still whining and whining."

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Mathias became weak and bloated until "we almost couldn't recognise him", Mr Teo added.

When the doctors assessed the boy's response to the first five weeks of chemotherapy, they confirmed he had an aggressive form of leukaemia – pre-B acute lymphoblastic leukaemia involving the KMT2A gene.

"In Mathias' case, the genetic changes found in the leukaemia cells are known to be high-risk and not as responsive to conventional chemotherapy," said Associate Professor Joyce Lam, a senior consultant at KKH's haematology/oncology service and medical director of the hospital's cell processing laboratory.

Worldwide, such patients have poor prognosis, with up to 80 per cent succumbing to the disease.

As Mathias did not respond to chemotherapy, his doctors decided on a new and promising treatment known as CAR-T therapy, followed by a stem cell or bone marrow transplant.

Car-T, or chimeric antigen receptor T-cell therapy, uses the body's own immune system to help fight the cancer.

It was approved in Singapore in March 2021. In the therapy, a type of white blood cells that help fight infections – T cells – are genetically altered in a lab and infused back into the patient.

The re-engineered T cells – now known as Car-T cells – acquire a new receptor that enables them to locate and destroy the cancer cells.

These Car-T cells were manufactured by the Cell & Gene Therapy Facility at the Health Sciences Authority.

Following the Car-T treatment, KKH's Teo Sok Yong and Goh Cheng Liang childhood cancer lab, which opened in early 2022, processed the healthy donor cells for Mathias' stem cell transplant in August 2022.

About 10 to 15 per cent of leukaemia cases require "extraordinary efforts to treat", said Dr Michaela Seng, a senior consultant at KKH's haematology/oncology service, and one of the doctors caring for Mathias.

"So Car-T is now the new tool, which basically spares the (patient) a lot of the toxicities, either by replacing a whole chunk of strong chemo or even replacing transplant completely – but in his case, we had to do both."

Still, Mathias was spared from more months of high-dose chemotherapy, Dr Seng added.

The strategy also meant he could avoid radiotherapy exposure to his whole body, reducing the risk of acute and chronic conditions in his later life, including earlier onset of these conditions when compared to his peers in adulthood, she said.

Such radiation exposure would have been necessary in his case in a traditional transplant situation, Dr Seng added.

"Now we can differentiate which cancer needs less treatment, which one needs more, and for those that need more, (we ask ourselves), do we have better-designed therapies to avoid some of the side effects?" she said.

Mathias became the youngest patient at KKH to have undergone Car-T treatment. The one-time treatment is generally known to be costly. The Kymriah Car-T therapy, for instance, comes with a reported price tag of US$475,000 (S$640,000).

As for the type of Car-T treatment that Mathias had, it is currently only available to the hospital's patients as part of research.

When Mathias was ready for the transplant one month after the Car-T therapy, his father went to the Singapore General Hospital to donate his stem cells. After his cells were harvested, they were quickly sent to the KKH lab for processing before they were transplanted into Mathias.

After the transplant, Mathias suffered from intense vomiting and diarrhoea for about a week, his father said. "He would vomit and then immediately start eating. If he was eating, it was a good sign."

For some six months till earlier this year, Mathias was back at the hospital every week for the doctors to monitor his cancer. It is now in complete remission, and the frequency of the monitoring will gradually decrease with time.

The couple, who have an older daughter, continue to worry about their son but after that ICU episode, they have resolved to be more positive for his sake, said Mr Teo.

"We put aside our sadness… and focused on his treatment," he added.

"At least, there is a solution. After coming here (to KKH) and talking to other parents, we learnt that as long as the doctors tell us there is a solution, it's good news."

This article was first published in The Straits Times. Permission required for reproduction.