When the immune system is weakened, even everyday microbes can become life-threatening. This is especially true for cancer patients undergoing bone marrow transplants such as blood cancer (leukemia) patients, where fungal infections can spread rapidly through the body. These infections affect up to 10% of patients receiving bone marrow transplants - a process where damaged and diseased cells are replaced with healthy cells from a donor.
A bone marrow transplant weakens the body's immune system for up to 12 months following the procedure, and this means that a serious fungal infection that invades the body at this time can result in death rate of up to 80% in those who suffer this complication.
What's more, in addition to distress caused to patients and families, managing and treating fungal infections in cancer patients is notoriously very costly, and drug resistance is emerging.
A world-first human trial
Professor David Gottlieb, a haematologist and bone marrow transplant physician at The University of Sydney, has been working on a world-first human clinical trial for patients with serious fungal infections that have developed following a bone marrow transplant.
Patients on this clinical trial receive the best available antifungal treatment but in addition are given a novel treatment known as adoptive T-cell immunotherapy (ACT). This early phase clinical trial was created to determine the safety of ACT, which was developed in Gottlieb's lab, for treating fungal infections in immunosuppressed patients.
ACT consists of white blood cells made in the laboratory and trained to identify and fight fungal infections. These treated immune cells are then given to patients to improve their immunity.
Madeline's light at the end of the tunnel
Madeline was diagnosed with leukemia in 2019. She underwent an intense regimen of chemotherapy before her bone marrow transplant, where she received cells donated by her older brother.
Following her transplant, Madeline was eager to return home, but it wasn't long before she was readmitted to hospital. In December 2020, Madeline found out she had developed graft vs. host disease (GvHD) of her stomach – a condition that occurs when the new immune system from the donor (the graft) attacks the patient's (host) tissues.
To treat the GvHD Madeline received treatment that made her susceptible to infection and as a result she developed a fungal infection in her brain which led to even more complications.
Professor David Gottlieb, Madeline's leading doctor, offered her a space on a clinical trial using ACT targeted to serious fungal infections occurring after a bone marrow transplant.
After much consideration and discussion with her parents, Madeline opted to join the trial, and she was the first person to receive the treatment. After receiving the trial treatment, Madeline made an excellent recovery and will never look back with regret.
To Professor Gottlieb, I have no words other than thank you for saving my life. I wouldn't be here today, living a semi-normal life again if it wasn't for you.
Looking to a more hopeful future
Professor David Gottlieb is incredibly excited about the trial, with data from the first six patients showing no safety concerns and highly encouraging anti-fungus effects. The trial has provided signs of positive outcomes for patients whose bodies have been invaded by fungal disease who are known to have poor prognoses.
"We are incredibly excited by the positive outcomes we have seen in the first patients treated on the trial and are looking forward to recruiting additional patients to the study," says Professor David Gottlieb.
This trial will be running until 2026 and continues to assess the effectiveness of fungus-specific immune cells in bone marrow transplant patients. If these results remain positive, the next step would be to do a randomised trial.
"If there is someone who has been given the opportunity to do a clinical trial, I would say don't hesitate! You've made it this far, there's no point in stopping, you can't go back. Fight for yourself and the life you can live you can gain back. There is light at the end of the tunnel," Madeline encourages.
This work could lead to pharmaceutical products being developed for fungal infections, which would reduce the duration, cost and complications of fungal infections, with an increase in cancer survival.
The Translational Program Grant
This project started 10 years ago with the support of a Cancer Council NSW's Project Grant supported by Susan and John Freeman. The outcomes laid foundation for a Translational Program Grant (TPG) which was funded through Cancer Council NSW and Cancer Institute NSW. TPG are prestigious awards aimed at supporting multi-disciplinary approaches to cancer research that will rapidly translate research discoveries into clinical programs and policy.
Cancer Council NSW awarded this TPG $3,750,000.00, which started in 2019 and will run up until 2026.
"I would like to thank the supporters of Cancer Council NSW for their consistent support of this project. Without your ongoing belief and support, the ideas and conviction of myself and my team to bring immunotherapy to a group of highly susceptible and vulnerable individuals would not have been possible," says Professor David Gottlieb.
To learn more about how Cancer Council NSW is funding breakthrough research, visit our research page.
All donations and funds raised through Daffodil Day will directly fund cancer research projects like this across Australia, helping save lives and bringing us closer to a cancer-free future. Visit daffodilday.com.au and give to Cancer Council's Daffodil Day to fund life-saving cancer research.
