Improving infection prevention with drug optimisation
After a decade in the transplant-pharmacology field, pharmacist Julian Lindsay’s goal is to set up an international study aimed at improving survival and quality of life through drug optimisation.
Mr Lindsay is a senior bone marrow transplant pharmacist at the Royal North Shore Hospital (RNSH) in Sydney.
He was awarded a PhD scholarship from the Leukaemia Foundation and the Haematology Society of Australia and New Zealand (HSANZ) in early-2020 and is taking a three-year break from his pharmacy position to undertake his PhD at the world-leading Fred Hutchinson Cancer Research Centre in Seattle (U.S.) in conjunction with the Peter MacCallum Cancer Centre in Melbourne.
“I entered the field as I could see the great benefit in having specialist knowledge in all medications used to treat blood cancers and during bone marrow transplantation,” said Mr Lindsay
“The entire process essentially uses medications now, not surgery or any other physical intervention like in other fields of medicine.”
The title of his research is Preventing Infection in Haematological Malignancy and Bone Marrow Transplantation.
His project focuses on addressing critical knowledge gaps related to specific patient risk factors in developing infections such as Epstein-Barr virus*, cytomegalovirus** and invasive fungal infections.
He is investigating how the optimisation of antimicrobial therapies could prevent these infections, thereby improving survival and patients’ quality of life.
Drug optimisation focuses on the individual patient and their experience. The goal is to improve their outcomes through increased safety, reduced toxicity, and the accurate prescription and dosage of medications.
“To achieve better cure rates, chemotherapy and transplantation techniques are now highly immune suppressing,” explained Mr Lindsay.
“This has led to infections becoming a major cause of morbidity and mortality in these patients.
“While many drugs are registered to prevent or treat infections in patients, we need to better understand if these drugs are the right ones for each individual.”
“Not everyone fits into the same shoe, especially in haematology, with the vast array of malignancies, co-morbidities, and genetics also affecting how well someone can break down these drugs.”
Mr Lindsay’s research project centres on bone marrow transplantation, a procedure where patients have the highest risk of developing a fatal infection.
“While a 10% mortality rate might not seem like a large number, with over 50,000 transplants a year worldwide, resulting in 5000 lives lost, it is just unacceptable to me,” said Mr Lindsay.
In his clinical role at the RNSH, during his daily ward rounds, Mr Lindsay would help treat blood cancer patients who often needed to remain in hospital for up to six months.
“I’ve seen many patients succumb to infection that may have been avoided with more knowledge of these drugs,” he said.
“Some patients you see more than your friends or family – that’s what has really motivated me over the years to want to improve the current treatment standards.”
Mr Lindsay believes this project has remarkable potential due to the successful reformulations of similar therapies in the past.
“The first mould-active antifungal drug on the market was thought to be a huge breakthrough as it prevented most moulds from growing,” he said.
“This was a liquid medicine which people drank.
“Unfortunately, over half of patients experienced horrible gastrointestinal side effects and weren’t able to absorb enough of the drug.”
An Australian drug company has since reformulated this drug as a capsule and now almost 90% of patients achieve good levels in their blood and are no longer nauseated.
“And, after two years, they have almost no fungal infection at all,” said Mr Lindsay.
“That’s really exciting to me and the type of outcome I hope to achieve with this project.”
“The Fred Hutchinson Cancer Research Centre is considered the pioneer of allogeneic transplantation in the world. They do almost as many transplants every year as all of Australia combined,” said Mr Lindsay.
He travelled to the centre in February 2020, but the COVID-19 outbreak made it too difficult for him to remain in the U.S.
“Luckily, I was able to set up a virtual private network (VPN)*** to my computer while I was there, so I can still connect in from Australia,” he said.
“That was a huge relief, otherwise the project may have been put on hold completely.”
His days are currently spent at the computer, reviewing medical records, having video meetings with treating specialists, statisticians and data managers, and coordinating the project across centres.
So far, the results have been promising, with the optimisation of an anti-fungal drug called itraconazole resulting in less than 2% of patients affected by a mould infection.
The project is also utilising a new genetic test, undertaken prior to transplant, to understand whether a patient will effectively metabolise an anti-fungal drug called voriconazole.
“It’s metabolised by a liver enzyme which people have three common variants of,” he explained.
Some people with a particular variant can’t metabolise the drug well, which can result in terrible side-effects including hallucinations and visual disturbance as soon as the drug levels rise in their blood.
“Long-term, it can actually cause a severe, almost irreversible bone pain from fluoride building up in the bones,” he said.
This new test can determine whether the dosage needs to be adjusted or whether the patient needs to be given a different drug altogether.
Mr Lindsay is grateful for the opportunity to contribute to his field and improve outcomes for patients.
“I’m so thankful to the Leukaemia Foundation and HSANZ for seeing the value in this project and putting faith in a pharmacist,” said Mr Lindsay.
“The work I’m doing now is a culmination of several years of planning and is informed by the wealth of experience I have with real patient scenarios.
“My PhD is really different to others as I’m not in a lab, using a cell line or novel agent, I’m actually looking at real-world data.
“My established connection with Fred Hutchinson Cancer Research Centre was really important, as it means I will have enough patient data to have a meaningful outcome and a chance to change current practice.”
Mr Lindsay is keen to see the results of the project translated into patient care as soon as possible and is working on the updated Australian Antifungal Prophylaxis Guidelines.
“I don’t believe there’s a point in doing research if you don’t disseminate the information so everyone can benefit.”
Mr Lindsay is looking forward to returning to the U.S. this year, COVID-19 depending, to commence clinical learning for the project.
“The current situation with the pandemic has given me a lot of time to look at the bigger picture,” said Mr Lindsay
“But I am keen to get back into the clinical setting, doing the ward rounds and meeting face-to-face with patients, to really immerse myself in the individual patient’s experience again.”
This PhD is kindly supported by the Frederiks Foundation in honour of Cor and Helene Frederiks.
The Leukaemia Foundation’s National Research Program
More than 5600 Australians lose their life to a blood cancer each year and more than 186,000 people are expected to die from blood cancers by 2035. The Leukaemia Foundation’s increased and sustained investment in the National Research Program, including Julian Lindsay’s research project, is a key to driving down these figures and saving lives.
In the last 20 years, the Leukaemia Foundation has invested more than $54.5 million into research, which includes supporting more than 370 researchers across 290 research projects, through PhD scholarships and research grants at over 50 hospitals, research institutes, and universities.
The Leukaemia Foundation is committed to funding research the drives rapid advancements in treatments, diagnostics and novel therapies and gives Australians access to the latest treatments through clinical trials.
*Epstein-Barr virus (EPV) also known as human herpes virus 4, is a type of herpes virus that can spread through saliva. Most people will get EBV as a child and have it for the rest of their life. The virus infects B-cells that are part of our immune system, which protect the body against disease. It can interfere with the cells, causing them to grow and divide out of control and has been linked to cases of Hodgkin lymphoma and Burkitt’s lymphoma.
**Cytomegalovirus (CMV) is a member of the herpes virus family transmitted by contact with saliva, urine or genital secretions. Most people who acquire the virus after birth experience few or no symptoms but it can be fatal in patients with suppressed immune systems.
***A virtual private network (VPN) is an encrypted connection over the internet from a device to a network. The encrypted connection helps ensure that sensitive data is safely transmitted.