Children with aggressive blood cancer offered new treatment cure hope

Children with aggressive blood cancer could benefit from a new treatment which experts hope will cure the disease.

The treatment, known as CAR T-cell therapy, is targeted at a specific protein identified by researchers to be present only on cancerous white blood cells. This therapy being launched at Great Ormond Street,, which involves genetically modifying the body’s immune cells to recognise and kill cancer cells, has shown success in other cancers but not in T-cell acute lymphoblastic leukaemia (T-ALL).

However, experts now believe they have a clearer target for attacking this deadly cancer due to the identification of the protein CCR9 on cancerous T cells. As part of a new study, Dr Sara Ghorashian, a consultant haematologist at Great Ormond Street Hospital, and her team are recruiting 12 children who have T-ALL that relapses or is resistant to conventional treatments. The study will commence around April next year at both Great Ormond Street Hospital and University College London Hospital, with the CAR T-cell therapy created at UCL.

The Great Ormond Street Hospital Charity has donated £2.4m to support the study. The research will also test a new approach to clinical trials by running a child and adult study simultaneously.

According to GOSH, dedicated research projects for children’s cancers are rare, with paediatric clinical trials traditionally starting much later than for adults and taking an average of 6.5 years longer to complete. This innovative method could save time and money, and would help ensure children and adults had access to targeted therapies on the at the same time, rather than children being forced to wait.

Researchers believe the therapy could work – it has been shown to clear leukaemia in the lab and in animal studies – and it is known that children tend to tolerate CAR T-cell therapy better than adults. Despite cancer being the biggest killer of children aged 14 and under in the UK, only 12 anti-cancer medicines have been authorised for paediatric cancer specifically in the last decade, compared to more than 150 for adult cancers, according to GOSH.

Dr Ghorashian SAID there was a "perception that there shouldn’t be early-phase clinical studies in paediatrics" but that this created problems for children in accessing new drugs and therapies. She added: "Often things like the specifics of how a drug is delivered are just borrowed from adults and not necessarily tailored to children."

"We don’t have as many new drugs for cancer in childhood cancers as we do for adult cancers, and the drugs come later to children. They come with dosing that’s borrowed from adults, and what we should be doing is testing them in parallel – making sure they’re safe in the first instance – but not preventing access to effective treatments for children."

She noted that no CAR T-cell therapies had been successful for T-ALL so far, but there had been success in treating another type of leukaemia known as B cell acute lymphoblastic leukaemia. Dr Ghorashian explained: "Our target, the CCR9 target, is only present on a very, very small proportion – around one to 2% of T cells in total – which means that when we treat with CAR T-cell therapy, hopefully, we won’t be eliminating healthy T cells in any significant numbers."

"This means that the patient’s leukemia will be eliminated if we’re lucky, but the patient’s healthy T cells will remain and will be able to continue fighting infection. If we can deliver a CAR T-cell therapy that doesn’t have to be consolidated with a rescue transplant, that is beneficial," and concluded: "That’s why we’re particularly excited to test this and see if it’s going to be effective."

Dr Ghorashian acknowledged that while CAR T-cell therapy can have side effects, they are generally more manageable than those associated with chemotherapy and bone marrow transplants. Dr Ghorashian added: "Too often, children wait unacceptable amounts of time to access new cancer treatment which could make all the difference."

"This study will pave the way for research to always include children, and make it a matter of course that both paediatric and adult patients are incorporated within clinical trials at the same time. Our goal is to never have a situation where children are left behind and we hope that we can prove the benefit of this novel approach to influence a change in the law in the future."

Maris Hanson, 47, lost her two-year-old son Frank to T-ALL in 2019. As the group chief legal and people officer at Giant Group, she's now championing the GOSH Charity. She said: "Frank was an incredibly happy child, very inquisitive and always looking out for new experiences. He was very active as a boy, he always wanted to be out and about."

Frank's illness became apparent shortly before his second birthday in January 2019 as his parents observed an unusual persistent infection accompanied by a low-grade fever. Although there was a short period of recovery, his condition severely deteriorated during a flight to Estonia, necessitating a medical plane to return him to the UK for treatment at GOSH.

Mrs Hanson said: "When Frank was diagnosed, I felt like my legs were taken out from under me. Even when the leukaemia spread to his brain, we still had hope. We hoped there would be a miracle; something would click and Frank would get better."

"But there comes a point when you can no longer treat the child if it means they’ll have no quality of life ..." "After three-and-a-half months, it was on the Mother’s Day weekend, we were basically told ‘there isn’t anything else that we can do, because ... his form of leukemia doesn’t respond’."

"So within four months, this journey basically ended for us in a way that I would never want any other parent to go through and let alone the child themselves, because it’s cruel. I was in a situation that I’ve lost my son. And I thought what can I do that would still, in a way, benefit him as well? That’s one way of me being able to continue to live my life."

GOSH Charity is spearheading its largest fundraising campaign ever to construct a new Children’s Cancer Centre. Dr Aoife Regan, from GOSH Charity, highlighted the significance of the initiative: "In line with our new cancer research strategy, we are really proud to be funding this important study which will hopefully, not only provide a potential new treatment option for children with a particularly aggressive form of cancer, but also lay the foundations for a new, more efficient clinical trial design that would benefit even more seriously ill children in the future."