Fighting childhood cancer
“In October 1966, a first cousin of mine was taken to a Dublin Paediatric Hospital.” Professor Owen Smith said. “He was nine years of age. He was admitted and nursed in a back room for three weeks until he died of acute lymphoblastic leukaemia, the most common childhood cancer. There was no specific treatment in this country at that time and like all other children with acute leukaemia in 1966 the clinical care was purely a palliative one, namely, he was put on intravenous fluids, given morphine to keep him as comfortable as possible, but there was literally nothing else that could be done. In Ireland and indeed in most countries in Europe in 1966 a child diagnosed with leukaemia would live for approximately 6 to 12 weeks. His diagnosis, his rapid demise, and the negative impact it had on family life never left me and when I went to medical school, it was always at the back of my mind that I wanted to become a blood doctor, and working in leukaemia was always on my horizon. That’s why I dedicated my whole life to curing children who found themselves in similar circumstances.”
In Ireland there are on average around 210 children a year who are diagnosed with cancer. Around one third of those have acute leukaemia. The other two most common types are brain tumours and neuroblastoma.
“We’re curing over 90% of children with acute lymphoblastic leukaemia now.” Prof. Smith said, “But we’re doing this at a price, and that price is usually long term toxicities for these children. For the past 70 years, real efforts in curing childhood cancers have focused on the area of acute leukaemia because that’s the most accessible form of cancer that we have. If you stick a needle into a vein, you can get a cancer biopsy as opposed to going into a solid tumour which takes more time and is more invasive. I’m hugely interested in this area of research for two reasons – one is because we don’t cure all of these children, we cure approximately 90% and that means that unfortunately around 10% are not cured, so I’m interested in looking at ways to find treatments and cures for that other 10% so that we can cure 100% of these children. Secondly, the children that we do cure suffer the ravages of the treatments that we use, like long term toxicity, especially in the group of the young adolescents where they are a bit more prone to the side-effects, like bone disease secondary to steroids, and heart disease, like cardio myopathy, secondary to anthracyclines.”
Prof Smith spoke about one of the greatest moments and the worst moments in his career – “One of the greatest things that happened to me throughout my entire life was being stopped in Grafton Street by a lady pushing a pram saying ‘Professor Smith, do you remember me? I was one of your patients with leukaemia!’ Now she has her own children. It was the most uplifting and incredible moment. I was so privileged to be in that position. On the other side, I always remember the children who didn’t make it and who died of refractory or relapsed disease. That’s what drives me to keep going and to try get these children cured without toxicity and side effects.”
Jonathan Bond’s professorship was developed to advance research into paediatric and adolescent cancers of the blood, with the aim of improving survival rates for those affected. Based at the UCD School of Medicine, the professorship is supported under the NCRC Research Leadership Award Scheme, by a significant legacy donation from the late Mr Brendan McGonnell to CMRF Crumlin.
Professor Bond spoke about the opportunities this donation has left, not only the medical community, but the benefits to wider society – “My fellowship comes from a legacy donation from the late Brendan McGonnell who was interested in supporting a fellowship to help advance scientific knowledge in a medical area. It’s a huge investment in the future and in the wider society. It’s a wonderful thing to leave behind.”
Prof. Bond is researching blood cancers. He is using systems biology in his research, a combination of computer techniques with traditional experiments in the lab which allows him to analyse a cell to test what happens when the leukaemia cell has a mutation.
“The computer model allows us to do a lot of experiments before going into the lab, and can help us to target unexpected variations.” Bond explained. He said that leukaemia has a lot of different side effects, but that research has greatly improved outcomes for children with leukaemia today – “Leukaemia is a cancer of white blood cells and it starts with one cell mutating, which eventually goes out of control. It can fill up your bone marrow, and block normal blood cells from working, for example, it can affect your red blood cells to the point of making you anaemic, it can negatively affect your immune system which means you can’t fight infection as well as you normally could, and it can affect your platelets which means you can’t clot if you start to bleed. Up until the 50s, it was a fatal diagnosis. Now, we can cure about 90% of children with cancer. Research is vital because we can’t progress without it. Every single advancement so far is thanks to research and every single advancement we will make in the future will be because of research.”
Professor Bond said his aim is to find better treatments and better stratifications for children with leukaemia, based on understanding the mechanism of how the leukaemia comes about.
“This will allow us to identify what treatments will be better, which will ultimately improve the survival and reduce the toxicity.” Prof. Bond said. “Most children now do quite well, and generally the side effects are better than they were a couple of years ago. We’re better at dealing with the side effects and predicting how someone will react to treatment. There are still some side effects that are very debilitating. For example steroids can cause problems to the blood supply of the bones, particularly adolescents can get something called osteonecrosis, which means ‘bone death’. This means that sometimes teenagers can end up with hip replacements. Treatments like steroids do work, but they are not without their consequences or toxicity. Chemotherapy is a scattergun approach to curing the child of the cancer, you obviously want to kill the cancer but it has a negative aftermath for the child. It’s like using a sledgehammer to crack a nut. I want to target the treatment to just eliminate the leukaemia cell, without harming the child.”
Prof. Bond said the biggest step in research in recent years has been in immunotherapy – “We’re now using something called Car T cells, they are genetically engineered white blood cells extracted from the patients themselves to attack the leukaemia cells. In practice, you take out the patient’s white blood cells, you process them and make them express an antibody for the leukaemia cell. You then put them back into the patients and this has had really amazing results, particularly in children who have gone into remission. This form of treatment now has approval from the European Board of Medicine, so it should be used in Ireland very soon!”