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Drug discovery has remarkable potential for high-risk childhood leukaemia

Drug discovery has remarkable potential for high-risk childhood leukaemia

Exciting research is laying the groundwork to develop a promising new targeted therapy for aggressive subtypes of childhood leukaemia including infant acute lymphoblastic leukaemia (ALL).

Dr Michelle Henderson in the lab
Dr Michelle Henderson: “It’s going to become a reality that across the country every child’s cancer will be sequenced

Lead investigator, Dr Michelle Henderson is a senior scientist, project leader and joint Research Manager of Molecular Diagnostics at Sydney’s Children’s Cancer Institute.

Before moving to the Children’s Cancer Institute, Dr Henderson spent 10 years working on the genetics and molecular biology of breast cancers at the Garvan Institute of Medical Research.

“Fourteen years ago, the opportunity to move to the Children’s Cancer Institute came up,” explained Dr Henderson.

“After spending years studying individual genes involved in cancer, I wanted to take a step closer to the clinic where I could potentially discover new treatments and have a more direct impact on people with cancer.”

While major research advancements have significantly improved survival rates in childhood leukaemia, Dr Henderson and her team are working to target certain subtypes of childhood leukaemia that still have very poor prognoses.

These include children who fail induction treatment, relapse during treatment or whose leukaemia harbours chromosomal rearrangement of the Mixed Lineage Leukaemia (MLL) gene*, an abnormality that occurs in 90% of infant ALL, with a survival rate of less than 50%.

“It can be an extra challenge with children as their bodies are still developing and these chemotherapeutic agents that work so well for leukaemia can still be very harmful to the patient,” said Dr Henderson.

“If it’s a more aggressive cancer then that child will receive more aggressive treatment and that can affect them later in life, leading to physical problems such as heart disease, osteoporosis, infertility, obesity, or even the risk of a second cancer.

“This presents an urgent need for the development of novel treatment strategies incorporating more selective, targeted therapies, allowing for a reduction in chemotherapy dosage and toxicity.”

For the past 10 years, Dr Henderson’s lab has collaborated with a lab in Buffalo, New York, conducting ‘screens’ with the aim of finding new drugs which specifically kill cancer cells without affecting normal cells.

Together they have discovered a new drug, OT-82, which has ‘remarkable’ potential to improve treatment in aggressive childhood leukaemia.

Dr Henderson’s research was awarded a Priority-driven Collaborative Cancer Research Scheme (PdCCRS) grant in 2019 to further develop this therapy.

This grant was co-funded by the Leukaemia Foundation, The Kid’s Cancer Project and Cancer Australia.

“This drug, OT-82, blocks the production of a cellular biochemical called nicotinamide adenine dinucleotide (NAD) which rapidly dividing cancer cells can be dependent on for energy,” said Dr Henderson.

“NAD is also a co-factor for a number of enzymes that help the cell repair itself and so leukaemia cells can require a lot of it because they’re continually growing and need to repair themselves all the time.

“Based on the knowledge that cancer cells depend on NAD more than normal cells, researchers have tried for many years to design a compound that actively targets and inhibits production of NAD. But a suitable compound was yet to be found.”

Although not looking to target this pathway in particular, Dr Henderson and her collaborators in the U.S. came upon such a compound through a screening strategy aimed directly at blood cancer cells.

“We were surprised when the compound that came out of the search appeared to be an inhibitor of an enzyme called NAMPT (nicotinamide phosphoribosyltransferase), which is necessary for producing NAD in the cell but whose association with blood cancers was unknown,” she explained.

“This particular compound universally kills blood cancer cells, but the normal blood cells just go into a pause.

“The normal blood cells don’t die, they are just in pause and then when you stop treating them, they rejuvenate again, whereas the cancer cells don’t.

“It’s interesting that we’ve come across it through a completely blind approach of just screening thousands and thousands of compounds and found one that targets blood cancer cells.

“This compound seems to be very well tolerated so far in adult trials and is earmarked for going further into paediatric trials.”

With this grant, Dr Henderson and her team are laying the groundwork for these paediatric trials, by determining which children could be most responsive.

“Part of our research is to determine exactly which subtypes of leukemia will respond, both on a broad, phenotype level, and at a molecular level, to find which genes are expressed in that particular cancer,” said Dr Henderson.

“We want to have a set of biomarkers, or subtype markers, that say if a patient has this cancer and it expresses this gene or mutation, they are more likely to respond to OT-82.

“So far, we have found a set of very responsive patient samples that each have mutations in DNA repair genes.

“We think that when they have a weakness in their DNA repair, with the cancer cell having to grow so rapidly and requiring NAD for repair, that’s when they are particularly responsive to OT-82.

“We are also looking at how OT-82 can be used in combination therapy to promote the response to other drugs currently being used for leukaemia treatment.”

The impact of this project is further enhanced by a collaborative grant recently awarded to the Children’s Cancer Institute to deliver personalised medicine to every child in Australia.

“It’s going to become a reality that across the country every child’s cancer will be sequenced,” said Dr Henderson.

“Such a completely individualised approach to treatment means that OT-82 could have an incredible impact on patient survival outcomes.”

Inhibiting NAD also appears to be relevant to some other cancers that depend on the same pathway.

“They might be solid tumours like sarcoma or brain tumours with certain genetic mutations you can screen for that cause dependence on this particular pathway,” said Dr Henderson.

The next big challenge for the research team will be gearing up for a paediatric leukaemia clinical trial.

“That’s why this funding from the Leukemia Foundation, The Kid’s Cancer Project and Cancer Australia is so important,” said Dr Henderson.

“Even though a relatively small number of children may have these high-risk leukaemia subtypes, it will have a significant impact on survival outcomes for this group and may be applied across other cancer types.

“The whole team is so thankful to have the opportunity to gather this supporting evidence and make a real case for OT-82 to be taken to clinical trial stage for these deadly childhood leukaemias.”

*Also referred to as Mixed Lineage Leukaemia Gene Rearrangement (MLL-r). This occurs when a piece of DNA is swapped with another chromosome which results in two different genes being abnormally joined together. The resulting protein can no longer control the development of the blood system and blood cells grow out of control, resulting in leukaemia.

From PhD in Melbourne to postdoc in New York

From PhD in Melbourne to postdoc in New York

The Leukaemia Foundation’s National Research program has supported the careers of the brightest researchers and clinicians, like Matthew Witkowski, for almost 20 years.

Matthew Witkowski
Matt Witkowski is investigating what drives ALL cells to be resistant to therapy and how their environment influences relapse

His research is a prime example of how critical research funding is to understand the biology and genetics of blood cancers and to developing new treatments.

A young Matt with medals and trophies he and his two brothers had won, including the under 11s footy grand final for Diamond Creek in 2001.
Matt with medals and trophies he and his two brothers had won, including the under 11s footy grand final for Diamond Creek in 2001

Matt’s career trajectory was kick-started when he won the under 11s footy grand final for Diamond Creek in Victoria! He has since moved from sport to science and, after completing his Honours at the Walter and Eliza Hall Institute (WEHI) in Melbourne, was awarded a PhD scholarship from the Leukaemia Foundation.

Now he’s working as a postdoc scientist at the New York University School of Medicine in the U.S. and his sights are focused on improving the effectiveness of CAR T-cell therapy.

When ALL News spoke to Matt, he had just presented on The relapsed B-cell acute lymphoblastic leukaemia immune microenvironment and won the first prize post-doctoral Eugene Cronkite 2019 New Investigator Award at the International Society for Experimental Haematology conference in Australia.

Matt Witkowski and mum Tina
Matt Witkowski with his mum, Tina Witkowski, at the Walter and Eliza Hall Institute during his PhD scholarship

He explained that back in 2011, when he applied for a PhD scholarship, “the Leukaemia Foundation was very competitive, but I was lucky enough to receive it”.

Matt’s PhD, from January 2012 to December 2014, was valued at $120,000.

“It was my first scholarship. It was a big deal for me, and relieved a lot of the stress,” said Matt.

“You knew someone cared about what you were doing as a student and that it was worth investing in. That’s critical at the point when you are learning the lay of the land in science.”

Matt did his PhD in lab of Dr Ross Dickins which was then at WEHI*.

“The Leukaemia Foundation was a big supporter of our lab and was a constant support and funding stream. Our lab thrived on that bit of stability,” said Matt.

“You do a lot of work all the time, in science. You’re constantly working, so you don’t want to worry about funding, especially when the Australian government can swing around in terms of how much they are investing in science.

Matt Witkowski, right, with from left, Grace Liu, Ross Dickins* and Mark McKenzie** from Dr Dickins’ lab at the Walter and Eliza Hall Institute
Matt Witkowski, right, with from left, Grace Liu, Ross Dickins* and Mark McKenzie** from Dr Dickins’ lab at the Walter and Eliza Hall Institute

“We were a small lab with one post doc, two students, and Ross as well. It was one of the few acute lymphoblastic leukaemia labs at WEHI at that time,” explained Matt.

“We were working on ALL because it is the most common cancer in kids and the most common cause of cancer-related death in children. I work on B-cell leukaemia, which is the most prevalent form of ALL.

“Students are the powerhouse of a lot of labs, especially ours.

“The other student in the lab, Grace Liu [also a Leukaemia Foundation three-year PhD scholarship recipient (2010-2012)] and I were producing a lot of the data.

“We both got meaningful papers out of it, which put us in good stead for building a career in the field” said Matt, and this was important for his career going forward.

Matt was investigating genes defective in leukaemia patients who showed resistance to chemotherapy, which would suggest that these particular genes dictated a patient’s ability to respond to chemotherapy.

“My work has focused on the Ikaros gene and defining how Ikaros interacts with other genes in a leukaemia cell to drive chemotherapy resistance and cancer development,” he said.

“By understanding these interactions, explanations for why patients who lack the Ikaros gene do not respond to therapy may become clear.

“Ultimately, this may lead to alternative therapy for ALL patients who would otherwise not respond to common chemotherapeutics.”

Matt had papers published in both Leukemia and The Journal of Experimental Medicine, and prior to completing his PhD, he went to a conference in Colorado in the U.S. where he met his current boss, Iannis Aifantis, an internationally recognised immunologist and cancer biologist, who heads a laboratory at New York University (NYU).

“He had read our papers and said, ‘do you want to come to New York for an interview in the lab?’.

“To be honest, New York wasn’t on my list. It seemed a little daunting. However, Luisa Cimmino, a previous postdoc with Ross Dickins, who was in the Aifantis lab, said ‘come to New York, it is really nice here’.

And so Matt went to further his career and research in New York. He went from a lab of four people to being a postdoc in a lab of 29! He’s still there now, continuing his work in ALL, “and it has been great ever since, just working away”, he says.

“I was able to extend on what I did in Ross’ lab. I worked in the same disease, ALL, but new technologies were coming out from the States and I could use them straight away.

“Leukaemia is a very complicated disease. You have a cell that is abnormal and it grows and grows in your bone marrow and spreads.

“What we did in Ross’ lab during my PhD, was provide really valuable information about what the genetic changes were in cells that made them transform into leukaemia. We used very novel tools to do that.

“Ross had brought that back from America and we took advantage of that to understand what underpinned leukaemia emerging and causing disease, and treatment resistance.

“When I went to America, I thought; how does the bone marrow itself influence the leukaemia? It obviously doesn’t grow on its own. It grows by interacting with everything around it.

‘When a patient presents with the disease that is throughout their bone marrow, then they get treatment, a small amount of leukaemic cells will just hang around and eventually the patient may relapse with the disease.

“My question was, ‘is there something that actually drives that small population of cells that are resistant to therapy to hang around, and what is the influence of the environment on these cells that would mean they would eventually not respond to therapy and inevitably cause relapse in these patients’.

“I was able to do a lot of that in the U.S. where we had new technologies where we could look not only at the leukaemic cell, but also everything surrounding it.

“We could deconstruct and pull apart the whole landscape of the bone marrow and understand all of the components and how they were talking to the leukaemia to keep it alive.

“What we have been able to do at NYU is use novel technologies to understand the whole system and how it evolves over time. We think we might be able to intervene with how the environment keeps the leukaemia alive, as a means of improving therapy,” said Matt, first author on a paper about this work that was published in Cancer Cell in June 2020.

“If you just stop these populations of cells from supporting leukaemic cells, you might be able to improve therapies that are already quite good in leukaemia.

“By just taking into consideration that you don’t just treat the leukaemia, sometimes you have to treat the things around it that would potentially support it surviving. This is a new paradigm in a lot of therapies.”

Matt has continued to keep in touch with an Australian ALL patient, India Papas, who he met through the Leukaemia Foundation when she was young.

“Every so often I ask Jodie [her mum] how India is going, and she seems to be doing really well…she has grown up.”

Matt said, looking to the future, his holy grail was to understand why some patients fail CAR T-cell therapy.

“This therapy harnesses a patient’s own immune cells to kill their tumour. It was originally utilised at the Children’s Hospital of Philadelphia and St. Jude Children’s Research Hospital (Memphis) as a way to treat B-cell leukaemia.

“Initially, it looked great. It looked like taking T-cells out of a patient and repurposing their own cells to kill tumour cells was going to be a really nice curative treatment.

“But it turns out that now we are a few years out from those initial trials, they [CAR T-cells] are not as effective as we thought. There are patients relapsing.

“It is an expensive therapy as well. In the U.S., it costs USD500,000 for a single treatment with this drug.

“There have to be ways to mitigate the relapsing that emerges from this. Not all of them are because of the drugs or because the B-cells they are targeting are naturally resistant. Sometimes there are other mechanisms.

“My goal is to start a group that tries to understand why patients fail this therapy.

“My initial work, in understanding how the bone marrow is composed, provides a good platform to understand how the environment informs how these new immune therapies are working.

“That is the goal in my immediate future, to start my own group where I can do this… to be around these therapies and take advantage of the fact that patients get biopsies which lets us see how they perform over time and why they don’t respond or why they do.

“There is also something called Bi-specific T-cell engagers. They hook leukaemic cells up to cells in the body that, if activated, kill leukaemia cells.

“There is a drug, called blinatumomab, that has done pretty well in this kind of field, where you are depending on the environment to kill the cells by using CAR T-cells and blinatumomab.

Matt Witkowski holding up a fish and fishing line
During a vacation in Maine, Matt threw in a line and came up trumps

“Once we understand what the environment is and how it influences the leukaemia cells, it might inform us which patients may not respond to these drugs. We have made the assumption that the environment is going to allow these drugs to work, but we don’t know that,” said Matt.

Matt said he was open to potentially moving back to Australia to start his own lab or to do that somewhere in America.

“I may come back to Australia but I’m not definitive about anything at the moment,” he said.

* Dr Ross Dickins subsequently moved to the Australian Centre for Blood Diseases at Monash University.

** Mark McKenzie was supported by a three-year Leukaemia Foundation Postdoctoral Fellowship (2010-2012).

Research aims to improve QOL by decreasing treatment toxicity

Research aims to improve QOL by decreasing treatment toxicity

Research aims to improve QOL by decreasing treatment toxicity 

Kate van Dyke
Lead investigator, Dr Kate Vandyke is motivated by people living with myeloma whose quality of life could be improved significantly by her research work

Exciting research is examining whether a new inhibitor can be used to prepare myeloma patients for bortezomib and other myeloma therapies, to increase the efficacy and potentially decrease toxicity of these therapies.

Lead investigator, Dr Kate Vandyke is a Research Fellow in Professor Andrew Zannettino’s Myeloma Research Laboratory at the South Australian Health and Medical Research Institute, Cancer Theme.

“We’re a pretty big lab of 25 and we mainly work on factors that are associated with poor prognosis in myeloma and working out ways of targeting these factors,” said Dr Vandyke.

“We also investigate the interaction between the cancer cells and the microenvironment and pre-malignant myeloma conditions like monoclonal gammopathy of undetermined significance (MGUS) that can convert to myeloma.”

Dr Vandyke was awarded a Priority-driven Collaborative Cancer Research Scheme grant in 2019 to build on her finding that the novel N-cadherin inhibitor, LCRF-0006, can dramatically increase the antitumour efficacy of low dose bortezomib (Velcade®) treatment. This grant was co-funded by the Leukaemia Foundation, Cure Cancer Australia, and Cancer Australia.

“The project has been a long time in the making,” said Dr Vandyke.

“We’ve been working on a N-cadherin inhibitor (LCRF-0006) as a potential target for myeloma for almost 10 years.

Myeloma lab
Professor Andrew Zannettino, front right, with his Myeloma Research Laboratory staff, including Dr Vandyke, at the South Australian Health and Medical Research Institute, Cancer Theme

In this project, Dr Vandyke is looking at one particular drug (bortezomib) that’s used in the majority of myeloma patients and which causes peripheral neuropathy in about a third of these patients.

“This is a really horrible side-effect affecting the nerves in the extremities. It causes pain in the hands and feet, pins and needles, numbness, and burning sensations – it’s really nasty,” she said.

“Bortezomib, as well as targeting the myeloma tumour cells, also targets some of the long nerve fibres that go into the hands and feet. It targets the long axons of these nerve fibres and causes damage.”

Dr Vandyke’s project will look to increase the way the drug is delivered intravenously from the bloodstream to the cancer cells.

“The way bortezomib moves out of the blood and into the cancer cell is limited by the blood vessels as they’ve got a strong boundary around them that stops the blood from seeping out,” said Dr Vandyke.

“We think that this N-cadherin inhibitor is just opening up that barrier a little bit to allow the drug to get through more efficiently. It’s working more on blood vessels in cancer rather than normal blood vessels.

“You’re getting more of the drug into the cancer and can decrease the amount that’s going elsewhere in the body which should decrease those side-effects.”

Kate Vandyke in the lab
Dr Kate Vandyke: “We’ve been working on a N-cadherin inhibitor as a potential target for myeloma for almost 10 years”

The research team has just published a paper in the medical journal, FASEB BioAdvances, using a pre-clinical model showing that using LCRF-0006 effectively increases the effect of the bortezomib.

“This means we can actually use a lower dose of bortezomib and therefore we hope side-effects will stop because you’ll get a better anti-cancer effect with a lower-dose drug,” said Dr Vandyke.

The next steps will be to see if the side-effects are actually decreased and to optimise the drug to be ready for human clinical trials.

“Because this drug hasn’t been used in patients before, it would have to go through Phase I trials and safety studies before going on to larger clinical trials,” said Dr Vandyke.

“Also, because we don’t have a pharmaceutical company that’s making the drug, the next big hurdle would be funding – always a challenge.”

Dr Vandyke is motivated by the people who are living with myeloma and whose quality of life could be improved significantly by her work.

“As a scientist, you can get bogged down in the finer details of what you’re doing and you forget the big picture,” she said.

“We have a lot of engagement with patient groups that come for tours and education sessions at the lab.

“While advancements in myeloma therapies have improved survival rates significantly, toxic side-effects and treatment-related quality of life (QOL) have become increasingly important factors for patients.

“Many patients won’t want to take the drug if it’s going to have such a detrimental effect on their quality of life, regardless of the long-term survival outcome.”

Dr Vandyke is also passionate about fostering the next generation of researchers.

“I really enjoy the teaching and supervision side of things. I’ve got quite a few PhD students that I co-supervise with Prof. Zannettino and I’m mentoring a couple of junior researchers as well,” she said.

“One of them, Dr Krzysztof Mrozik, has been a real driver for this project – we couldn’t have done it without him.

“It’s also great for them to be able to talk to the patients and their carers and families and see this is why we’re doing what we’re doing.”

Dr Vandyke said she was, “incredibly grateful to Leukaemia Foundation supporters for enabling me, and my team, to do the work we do”.

“They have made this project possible.”

Dr Vandyke has used this funding support to expand her research group; to hire a technical support staff member, and support the research of a junior researcher.

“These grants are given to some of the very best emerging talent from around Australia, and I am proud to be included in this group.”

Lymphoma rates jump 37% in past decade, with further significant increase still to come

Lymphoma rates jump 37% in past decade, with further significant increase still to come

Tuesday September 15, 2020

Today is World Lymphoma Awareness Day and the Leukaemia Foundation is highlighting the rising incidence of one of Australia’s most common blood cancers.

Over the past 10 years, incidence of lymphoma have risen by 37%, leading to close to 7000 people being diagnosed with this blood cancer each year in 2020[1]. Sadly, projections also show the number of Australians diagnosed with a lymphoma will jump a further 147 per cent by 2035 – making for an extra 10,000 Australians being told they have lymphoma every year[2].

Leukaemia Foundation Acting CEO Alex Struthers said with more people being diagnosed with lymphoma every year, it is a priority for the Leukaemia Foundation to ensure that each and every person will have access to the right treatment, care and information they need to survive their blood cancer and live well with their diagnosis.

“We welcome improved diagnostics to inform new targeted treatment approaches and we strongly support emergence of innovative therapies, like CAR T-cell therapy, which is now available on the Pharmaceutical Benefits Scheme (PBS) for some lymphoma patients – but not all,” Ms Struthers said.

“We need better access to genetic testing and more investment in research and clinical trials in Australia to help make new cellular and immunotherapies more accessible to all people living with any one the diverse set of lymphoma cancers.”

Leukaemia Foundation research shows that less than 30% of Australians living with blood cancer have access to genetic and genomic testing to inform their diagnosis and treatment planning. It also shows that less than 20% of Australians living with this disease have participated in a clinical trial, and only 1 in 5 who want to enroll in a clinical trial have access to one[3].

Improving access to diagnostics, clinical trials and new therapies forms part of what the Blood Cancer Taskforce has been considering in their development of the first National Strategic Action Plan for Blood Cancer, due for release soon.

The Blood Cancer Taskforce – a unique collaboration of some of the country’s top blood cancer experts and leaders – has now delivered the National Action Plan to the Federal Government and will continue to work alongside the Government to support the launch of the Plan soon.

“The National Action Plan will be a blueprint to not only save lives, but to improve these statistics and bridge these gaps to better meet the diagnosis and treatment needs of every Australian who is told they have a blood cancer,” Ms Struthers said.

The Leukaemia Foundation will today launch two webinars to help increase awareness, celebrate breakthroughs in treatment and acknowledge what still needs to be done to conquer the disease.

Speakers will include Dr Glenn Kennedy, Executive Director of Cancer Services at the Royal Brisbane and Women’s Hospital, who will present on CAR-T therapy including an overview of CAR-T and its relevance to the lymphoma patient population.

Physiotherapist and lymphoma survivor Ms Julie Allen will also present from a patient perspective and talk about the importance of exercise as treatment for lymphoma patients.

Both webinars can be accessed here.

For more information about lymphoma, and to register for the Leukaemia Foundation’s disease specific newsletter Lymphoma News, go to https://www.leukaemia.org.au/disease-information/lymphomas/

– ENDS –

What is Lymphoma?

  • There are more than 50 different sub-types of lymphoma, divided into two primary disease groups – Hodgkin lymphoma and Non-Hodgkin lymphoma.
  • Lymphoma is the general term for cancers that develop in the lymphatic system. The lymphatic system is made up of a vast network of vessels (similar to blood vessels) that branch out into all the tissues of the body.
  • These vessels contain lymph, a colourless watery fluid that carries lymphocytes, which are specialised white blood cells that fight infection.
  • There are two types of lymphocytes, B-lymphocytes and T-lymphocytes (also called B-cells and T-cells). These cells protect us by making antibodies and destroying harmful microorganisms such as bacteria and viruses.
  • Lymphoma originates in developing B-lymphocytes and T-lymphocytes, which have undergone a malignant change. This means that they multiply without any proper order, forming tumours which are collections of cancer cells. These tumours cause swelling in the lymph nodes and other parts of the body.
  • Over time, malignant lymphocytes (called lymphoma cells) crowd out normal lymphocytes and eventually the immune system becomes weakened and can no longer function properly.

Lymphoma incidence, prevalence and mortality

  • Every day, 19 people are diagnosed with lymphoma in Australia and sadly 4 people lose their life from the disease[4]
  • Currently 6,932 are diagnosed with lymphoma each year in Australia, and more than 1,731 Australians lose their life to lymphoma each year[5].
  • The average 5-year survival rate for people diagnosed with lymphoma is 76%[6].
  • The number of Australians diagnosed with lymphoma annually is expected to more than double to reach 17,171 people per year by 2035[7].
  • The number of Australians losing their life to lymphoma each year is also projected to more than double to reach 5,082 people per year by 2035[8].

Leukaemia Foundation advocacy: Lymphoma
Medicine which the Leukaemia Foundation has actively advocated for increased access to in the past year includes:

  • Ibrutinib – in both capsule and tablet form as first-line treatment of patients with small lymphocytic lymphoma
  • Polatuzumab vedotin – as treatment for relapsed or refractory diffuse large B-cell lymphoma patients who are ineligible for stem cell transplantation.
  • Acalabrutinib – for treatment of patients with relapsed or refractory small lymphocytic lymphoma not suited for treatment or second-line treatment.
  • Acalabrutinib – for use as monotherapy or in combination with obinutuzumab, for the first-line treatment of patients with small lymphocytic lymphoma who harbour a 17p deletion.
  • Pembrolizumab – as a treatment for patients with relapsed or refractory primary mediastinal large B-cell lymphoma
  • Venetoclax – as a combination treatment with obinutuzumab for the first-line treatment of patients with CLL who have coexisting conditions and are unsuitable for fludarabine based chemoimmunotherapy.
  • Mogamulizumab – as a treatment for relapsed or refractory cutaneous T cell lymphoma for the treatment of patients with relapsed or refractory CTCL following at least one prior systemic treatment for this condition.

Leukaemia Foundation National Research Program: Lymphoma
A number of clinical trials, research grants and PhD scholarships are funded under the Leukaemia Foundation’s lymphoma program with the aim to better understand the biology and genetics of the disease, develop new and improved treatments and treatment protocols and improving quality of life for Australians living with lymphoma. These projects include:

  • Two international clinical trials funded through the Leukaemia Foundation’s Trials Enabling Program in collaboration with the Australasian Leukaemia and Lymphoma Group (ALLG):
    • Hodgkin Lymphoma trial, led in Australia by Professor Mark Hertzberg, in collaboration with the German High-Grade Lymphoma Group – looking at optimisation for first -line treatment of advanced stage Hodgkin lymphoma.
    • Follicular Lymphoma trial, led in Australia by Professor Judith Trotman, in collaboration with the UK Liverpool Trials group – looking at using PET scans to determine the response to therapy and inform treatment duration in patients with previously untreated high tumour burden follicular lymphoma
  • A cancer genomics clinical trial designed to bring precision medicine to blood cancer patients who have exhausted all other therapy options, with the first phase targeting high grade B-cell lymphoma patients.
  • A series of projects across the lymphoma diagnosis and treatment spectrum through the Leukaemia Foundation’s PhD scholarship program in collaboration with the Haematology Society of Australia and New Zealand (HSANZ) and the Strategic Ecosystem Research Partnership program:
    • Development of a new class of small ‘drug-like’ molecules that kill B-cell blood cancers
    • Development of a new genetic, immune and clinical prognostic score to assess the best treatment pathway and supporting informed decision making for follicular lymphoma patients,
    • Epigenetic pre-treatment therapy to sensitise diffuse large B-cell lymphoma cells to subsequent chemotherapy.
    • Investigating the mechanism by which the tumour suppressor gene TP53 prevents the development of Leukaemia and Lymphoma
    • A series of projects and clinical trials aimed at developing new treatment approaches for blood cancers, and the prevention and treatment of Graft Versus Host Disease through the Centre for Blood Transplant and Cell Therapy.
    • Testing clinical efficiency of CAR T-cells in the treatment of diffuse large B-cell lymphoma.

Research in Action: Blood Cancer Genomics Trial

Research in Action: Blood Cancer Genomics Trial

  • When?
    13 October 2020, 3pm-4pm AEST/4pm – 5pm AEDT
  • Where?
    Online – Webex meeting

In this live seminar, you will learn how your continuing support is set to revolutionise the way people with blood cancer are treated today and in the future.

Every person’s blood cancer is unique; the therapies used to treat them should be unique as well. That is the power of precision medicine.

Today we will hear from Dr Peter Diamond, Head of Research at the Leukaemia Foundation, and Associate Professor Steven Lane of QIMR Berghofer about precision medicine based clinical trials and the new Blood Cancer Genomics Trial which is scheduled to open later this year.

3pm-4pm AEST/4pm – 5pm AEDT
Online (Webex meeting)

Fill out the form here to register. If you have any questions about our seminars, please contact Julia Eyles, Leukaemia Foundation Supporters Coordinator, on jeyles@leukaemia.org.au or (07) 3318 4448.

Davina’s selfless generosity could spark research breakthrough

Davina’s selfless generosity could spark research breakthrough

Before tragically losing her life to incurable blood cancer in 2018, Davina Sickerdick made a lasting commitment to others facing this devastating disease.

Davina Sickerdick standing outside Buckingham Palace in London
Davina Sickerdick pictured in London

Davina was diagnosed with myeloma after persistent back pain raised concern with her GP.

Myeloma, also known as multiple myeloma, affects more than 140,000 people worldwide each year – last year more than 2,000 Australians were diagnosed.

Davina’s partner of 22 years, John, remembers the relentless radiation, chemotherapy and stem cell harvesting that followed her diagnosis.

“There was never really a break with it,” said John. “When you have myeloma you are permanently on chemotherapy, meaning hospital visits every month and blood tests at least twice a week.

“She really had a terrible time with it, various complications along the way and she was allergic to some of the drugs.”

With her health getting worse and faced with the reality she may not survive, Davina decided she wanted to help others.

“Davina was that sort of person,” remembers John.

“She couldn’t do enough for anyone, and nothing was too much trouble.”

Davina always considered herself to be an ordinary person but her family and friends thought of her as extraordinary, full of life, colourful and loved anything that had a little “sparkle”.

“She was the one who took the initiative and contacted the Leukaemia Foundation to discuss the process [of leaving a Gift in Will].

“They armed us with the correct wording and made sure we were well supported to make our wishes clear and formalised.

“My Will reflects the same thing as Davina’s – I will be directing money towards helping more people battling blood cancer through the work of the Leukaemia Foundation.”

Professor Andrew Zannettino will work to eliminate the disease with Davina’s kind gift

Davina’s kind gift has funded strategic research projects looking to better understand myeloma and why so many patients relapse after initial treatment.

With Davina’s gift, Professor Andrew Zannettino from the University of Adelaide has embarked on a three-year study to target certain cells which could eliminate this disease.

“The impact of this gift cannot be underestimated,” said Professor Zannettino.

“Davina’s generosity means we can look for new ways of beating blood cancer and hopefully ensure no one else has to experience the same struggle.”

John is looking forward to seeing real outcomes for families battling blood cancer and encourages others to consider updating their Will.

“I just hope more research can be done, and not just in myeloma, I know there are many other blood cancers needing the same type of support,” said John.

“I feel very proud and happy to think that her gift could spark a real breakthrough, we always spoke about making a difference with our estates and I hope this can make a really positive change for society.”

More than 50% of Australians over 18 don’t have a Will in place (Moneymag, Feb, 2019). Make 2020 your year to double check your Will is sorted and consider leaving a lasting impact for people living with blood cancer. If you would like to know more about leaving a gift to the Leukaemia Foundation, please contact Emma Quigley, Gifts in Wills Officer on 1800 620 420 or email GiftinWill@leukaemia.org.au.

Talk to Emma now

You’re investing in the researchers of tomorrow, today

You’re investing in the researchers of tomorrow, today

Thanks to our supporters, Dr Khai Li Chai was recently awarded a Leukaemia Foundation PhD Scholarship, through the Haematology Society of Australia and New Zealand (HSANZ).

Dr Chai is a specialist clinical and laboratory haematologist at Monash University undertaking vital research into blood cancer.

Your generosity will support Dr Chai over the next three years to investigate people living with a range of blood cancers: chronic lymphocytic leukaemia (CLL), non-Hodgkin’s lymphoma (NHL), multiple myeloma, and individuals who have undergone stem cell transplants.

Khai Li Chai
Dr Khai Li Chai

Her research will focus on hypogammaglobulinemia – a condition where the body does not produce enough antibodies and is linked with serious infections. Sadly, it is a major cause of mortality and illness in affected patients.

Her work will explore antibody therapy to prevent and treat infections in patients, to ultimately lead to a better standard of care.

You can read more about her project and the other bright young minds our supporters are helping here.

Supporter briefing: National Action Plan for Blood Cancer

Research in Action: Blood Cancer Genomics Trial

  • When?
    13 October 2020, 3pm-4pm AEST/4pm – 5pm AEDT
  • Where?
    Online – Webex meeting

In this live seminar, you will learn how your continuing support is set to revolutionise the way people with blood cancer are treated today and in the future.

Every person’s blood cancer is unique; the therapies used to treat them should be unique as well. That is the power of precision medicine.

Today we will hear from Dr Peter Diamond, Head of Research at the Leukaemia Foundation, and Associate Professor Steven Lane of QIMR Berghofer about precision medicine based clinical trials and the new Blood Cancer Genomics Trial which is scheduled to open later this year.

3pm-4pm AEST/4pm – 5pm AEDT
Online (Webex meeting)

Fill out the form here to register. If you have any questions about our seminars, please contact Julia Eyles, Leukaemia Foundation Supporters Coordinator, on jeyles@leukaemia.org.au or (07) 3318 4448.

Clinical trials critical to finding curative therapies for MPN

Clinical trials critical to finding curative therapies for MPN

Dr David Ross and others in Tokyo
Associate Professor David Ross, centre, at a conference in Tokyo

Associate Professor David Ross is a clinical and laboratory haematologist who has always had an interest in MPN.  His clinical PhD scholarship in CML, monitoring residual disease, was funded by the Leukaemia Foundation. He is Head of the Clinical Trials Unit at the Royal Adelaide Hospital and Director of the South Australian Cancer Research Bio Bank. In this comprehensive interview he discusses everything from research, current therapies, clinical trials, diagnosis, prognosis, incidence, and more, and says, “it’s a very exciting time in MPN”.

After “almost nothing” by way of new treatments for 20 or 30 years, “there’s just been this massive explosion of clinical trial activity in MPN, said Associate Professor David Ross.

“We’ve gone from a situation where there were basically no new treatments, to one where a dozen drugs have been in clinical trials over the past few years.”

But one of the big issues in MPN remains.

“In CML, we have drugs like imatinib that essentially turn the disease off and, for most patients, ensure that it will never transform to a more aggressive phase, and the patient will never die from leukaemia,” explained Dr Ross.

“Therapies have improved some of the clinical manifestations in MPN, but the drug treatments available don’t change the long-term outcome of the disease.”

Does he see this changing?

“Look, I think it will. There’s been a huge amount of research on MPN in the last 10 or 20 years.”

Dr Ross said his holy grail is “to have a treatment for MPN that is curative, to be able to give someone a course of treatment that completely gets rid of the disease, gets rid of future risk, gets rid of any current symptoms or problems”.

Dr David Ross
Dr David Ross

JAK2 mutation – the key discovery

The JAK2 mutation is found in almost everyone with polycythaemia (rubra) vera (PV) and more than half of people with essential thrombocythaemia (ET) and myelofibrosis (MF).

“That key discovery, first published in 2005, has given scientific insights into these diseases that has spurred a lot of research and development,” said Dr Ross.

“Then there’s the calreticulin (CALR) mutation, found in about a third of patients with ET and MF. This second most common mutation was only discovered in 2013.

“That extra scientific information is a clue for academic researchers and drug companies to start understanding the disease and looking for drugs that can target those particular pathways.

“That’s where the JAK inhibitors came from, like ruxolitinib (Jakavi®), but as people better understand what CALR does, and what JAK2 does, and what MPL [another MPN mutation] does, they may find other targets that might be more effective.”

Next generation sequencing

Another important development was ‘next generation’ sequencing (NGS). Traditional sequencing looks at one small section of a single gene. NGS looks at many different sequences, often in many different genes, all at the same time.

“NGS panels are available for various blood diseases with lots of different mutations. These may test five or six genes, sometimes 30 or 40 genes, so a single test will give you a large amount of information,” said Dr Ross.

“There’s an increased use of sequencing panels to look for not only JAK2, MPL, and CALR, but also other mutations that may be associated with higher risk disease and that currently are most relevant for MF. They are IDH1, IDH2, ASXL1, EZH2, U2AF1, and SRSF2.

“The presence of a mutation in one of those genes increases the risk of MF, and for a small group of patients that’s really essential information, used in guiding transplant decisions.

Sequencing panels may also be useful to clarify the diagnosis.

Dr Ross went on to explain that if someone is intermediate risk, but doesn’t have any bad mutations, that might downgrade that person to being low-risk. Whereas, if someone is intermediate risk and has one or two of those mutations, that might push that person up into a high-risk group where the life expectancy might be only two or three years, and convert them from a watch and wait approach to going straight to a bone marrow transplant.

Dr Ross said this panel test was not currently funded by the Federal government.

“As is usually the case, the Medicare rebate for the test lags years behind research and clinical practice, so individual hospitals are paying for it, or sometimes individual patients pay to have it done privately.”

He said the cost varied from $400 for a small panel looking at the most common mutations in a particular gene, up to $1500 for a more extensive panel that sequenced 30-40 genes.

“But when you think that a bone marrow transplant might cost quarter of a million or half a million dollars, this is a trivial amount of money.”

Each state has different rules about getting tests done.

“In South Australia, everyone with MF who’s been discussed for transplantation would get this done; that’s a small number of patients out of the total MPN population, because MF is the rarest of the MPNs and only 25% or less of MF patients will be transplant-eligible.”

Clinical trials in MPN

Most recent studies have been for myelofibrosis, reflecting it being the MPN with the highest need.

Ruxolitinib was the original JAK inhibitor. Several studies have explored other JAK inhibitors (fedratinib, pacritinib, and momelotinib) on their own, or comparing them to ruxolitinib.

“Different companies are looking to see if one of the newer JAK inhibitors works after ruxolitinib has failed, or offers advantages over ruxolitinib in certain patients,” said Dr Ross.

“For instance, there is some hope that pacritinib might be better in people with a low platelet count, and momelotinib might be better in people with a low haemoglobin.

“Neither has been proven, but these are the questions that are being looked at in clinical trials.

“We currently have a momelotinib study [called Momentum] that is recruiting patients with myelofibrosis who are anaemic.

“The ‘mel’ in the name is because it was originally developed in Melbourne,” he explained.

“It’s already been used in hundreds of patients, so we know that it works.

“Most people on ruxolitinib have a modest drop in haemoglobin; they become more anaemic. It’s been observed that with momelotinib, the drop in haemoglobin is less, and some patients have an improvement in anaemia.

“So, whether momelotinib will offer an advantage specifically in the subgroup of people with myelofibrosis who are anaemic is being explored,” said Dr Ross.

Momelotinib and ruxolitinib both inhibit JAK1 and JAK2. Another study testing fedratinib will try to answer the question of whether there is some advantage to a pure JAK2 inhibitor [it doesn’t inhibit JAK1]. This study will recruit MF patients who have a had a suboptimal response on ruxolitinib, but  is currently on hold due to COVID-19.

The Kartos study opened recently. KRT-232 is an MDM2 inhibitor being tested in MF patients who have failed on ruxolitinib therapy. Dr Ross said MDM2 was involved in the P53 pathway, which is important in lots of different cancers. It’s a quality control pathway within the cell that senses DNA damage and causes the cell to undergo apoptosis [cell death] if there has been DNA damage.

“These are all international studies that include Australian sites,” said Dr Ross.

And there are other drugs in completely different classes that have different mechanisms of action that have been tried in early phase studies.

Australians were among the first patients enrolled on an ongoing study of bomedemstat that inhibits an epigenetic enzyme involved in controlling blood cell production.

“It’s a tablet and it’s shown some improvements in symptoms and spleen size and is generally quite well tolerated,” said Dr Ross.

An initial study of ruxolitinib combined with another class of drugs, called BET inhibitors, showed some encouraging responses. Now a larger study is in the planning stage and may open in Australia in the next six months.

Experimental data suggests navitoclax, which is related to venetoclax, and inhibits another member of the BCL-2 family, may be useful in MF, and luspatercept is being explored to see if it improves anaemia in MF.

The ADORE study is open at several sites for Australian MF patients who are on ruxolitinib and are anaemic. It is a Phase I platform study looking at a series of experimental drugs being added to ruxolitinib. A small number of patients will try each combination and then the results will be reviewed to decide which combination is the most promising, to take it to a bigger study.

“So, it’s a ‘pick a winner’ study,” said Dr Ross.

Studies in PV and ET

Dr Ross said that the first clinical trial in Adelaide for PV closed recently. It was using another MDM2 inhibitor called idasanutlin, “and it definitely works in some people who failed standard treatment”. The study closed due to toxicity concerns.

“The main issue was nausea. You can imagine that if you’ve got PV and you’re going to live with the disease for 10 or 20 years, having a drug that causes nausea for a week every month is not very good for quality of life.”

He also is “quite excited” about an upcoming ET study, also using bomedemstat. The opening of this study has also been delayed by COVID-19 but is expected in late-2020.

“It will be our first ever ET study in Adelaide.”  

“Because we’ve already had experience with that drug, we know that its safety profile is pretty good, so I’m optimistic about that.

“It will be for people who have been resistant to, or intolerant of hydroxyurea, which is the standard treatment for most people with ET.”

Ask about studies for you

“There are many studies for myelofibrosis at the moment – we’ve currently got four in South Australia – and a lot of the time they’re competing for the same rare patient population,” said Dr Ross.

“For companies to test their drugs, they need more patients.

“If we can’t enrol patients in clinical trials, it slows down the development of a drug and means that our patients won’t get normal access to the drugs because it takes longer to do the study properly.

“This is the problem of a rare disease.”

Dr Ross urged patients with MF to be proactive in asking their clinicians about clinical trial options in their city.

“A lot of these studies are open in only one hospital or maybe two hospitals in a bigger city. We need people to be referred to sites where a study is open, so we can put people on them,” he said.

“And they can look on the ClinTrial Refer app or website to see whether there’s anything that meets their particular circumstances.

“A lot of these studies are looking for only a few patients in each hospital, who meet very specific criteria, but if there are five or six studies, there is room for a lot of patients,” said Dr Ross.

The prime target population in MF are those patients on ruxolitinib or who have been on ruxolitinib and have not had an optimal response, and the main focus of these studies is to improve on the benefits already seen with ruxolitinib.

MPN is different from other blood cancers

MPN is a blood cancer, said Dr Ross, “but the way it behaves is completely different from lymphoma or leukaemia, so many people with MPN can go undiagnosed”.

“What sets ET and PV apart from other diseases, is that many people have either no symptoms or vague symptoms, like tiredness, together with blood count abnormalities, which means they may go undiagnosed for some time,” he explained.

“They’re often overlooked for a long period of time. That’s one of the standout features of ET and PV, and the main risk is bleeding and clotting (venous or arterial thrombosis) that can come out of the blue in people who didn’t know that they had an MPN.

“That makes it quite different from most other cancers. You’re not treating a tumour or trying to clear out the leukaemic cells, you’re mostly trying to protect the patient from having a clotting or bleeding episode.

“And the longer you leave it, the more chance there is of having a clot.

“What we know is that some people turn up and they have a clot that could potentially have been prevented if the diagnosis had been made earlier. So, a significant fraction of people with MPN will first be diagnosed when they present with a blood clot or a stroke or a heart attack.

“Sometimes, in those cases, we see someone who comes in having had a high platelet count for three years, and nobody’s done anything about it. So possibly, if that person had received appropriate treatment, he or she might never have had that clot,” said Dr Ross.

He cited the findings of a colleague with a long-standing interest in MPN, Dr Cecily Forsyth. She went back through the records at her centre, at Gosford (NSW), looking at people with a diagnosis of MPN and tracked their haemoglobin, white blood cell, and platelet counts.

“One of the patients had a high platelet count for 20 years before a diagnosis was made,” said Dr Ross.

“The estimated risk of having a clot is about 2% per year for ET, and maybe about five or 10% for PV. Many people, just by chance, will go years without having any problems, but someone’s got to be the one who’s unlucky.

“If someone has blood tests for other reasons and a mildly elevated platelet count is noted, it would often be disregarded if the person is otherwise well.

“In most laboratories, a normal platelet count is 150-450. In fact, your platelet count might be 300 or 200, but the top of the normal range is commonly close to 450.”

What complicates things is that if you are unwell, for instance if you have a chest infection, or if you are iron deficient, your platelet count might go up.

“In young women, in particular, it’s quite common to be iron deficient due to periods or pregnancy, so a slightly high blood count may be disregarded.

“And in an older person who’s got arthritis or other chronic health problems, a slightly high platelet count might be put down to inflammation.

“It’s when there’s a sustained elevation, with no obvious cause, that someone needs to think, ‘well, actually, this has been present two or three times. It needs to be looked into’.”

Myelofibrosis and stem cell transplantation

Dr Ross said myelofibrosis (MF) is completely different from ET and PV.

“Most people with MF feel unwell. They often have severe tiredness, itching, sometimes night sweats, and discomfort from enlargement of the spleen,” he said.

“The main aim of treatment is to lessen the severity of those symptoms, improve quality of life, and make people feel better.

“And, because MF is a more serious disease with a shorter life expectancy, we do bone marrow transplantation for higher risk MF patients who are young and fit, in whom the risks of transplantation are warranted.

“The age limit for transplantation has been continually creeping up over the past decades. Now, for most sites around the country, it’s up to age 70.

“Unfortunately, the risks associated with the transplant rise steeply once you’re above 50 [years old], and the chances of dying from the transplant if you’re nearly 70 are pretty high. The average age at diagnosis of MF is also around 70, so we don’t do very many transplants for myelofibrosis, but it is a potentially curative treatment,” said A/Prof. Ross.

Transplantation is not used for ET or PV because the risk is rarely justified. The treatments for those diseases are about controlling the blood counts and reducing the risk of clotting, but they’re not eradicating the disease or reducing the risk of future progression.

Diagnosis of MPN and its importance

MPN diagnoses are currently based on blood counts, bone marrow appearance, and clinical features, such as itching, sweating and spleen enlargement, said Dr Ross.

“It’s an old-fashioned classification system.”

He said Professor Tony Green’s group in the UK published a “highly influential” paper in the New England Journal on the results a large group of 2000 patients whose MPN was classified based on the results of genomic sequencing.

“They looked at patterns of mutation and showed that the behaviour of the disease and long-term survival could be predicted with some accuracy just by looking at the genes without the traditional pathological classification,” said Dr Ross.

“This hasn’t yet changed the way that we diagnose MPN, but it has emphasised the fact that you can get a lot of useful clinical and biological information from extended sequencing that may add to our old-fashioned classification system.

“And, in some cases where the bone marrow appearance is difficult to interpret, and one pathologist might think it’s ET, and another thinks it’s early myelofibrosis, looking at the sequencing for these difficult-to-classify cases might tell you, well, actually this is more likely to be MF, or actually, this is more likely to be PV.

“The biggest distinction is to identify early myelofibrosis and that’s important because the life expectancy is much shorter, and transplantation might be an option.

“And drug access is determined by having a biopsy that says you have myelofibrosis. You can only get ruxolitinib on the Pharmaceutical Benefits Scheme (PBS) if you have myelofibrosis; you can’t get if you’ve got PV or ET.

“It has been proven that ruxolitinib is effective in hydroxyurea-resistant and -intolerant PV, but it hasn’t been funded [by the PBS] because of the cost.”

“At the moment ET and PV are treated similarly. They both usually get hydroxyurea or interferon plus aspirin.

“The difference is that in PV, we aim to keep the hematocrit, which is a measure of haemoglobin, below 45%, as well as the platelet count and white cell count in the normal range. Whereas in ET, we only look at the platelet and white cell counts.

“Lots of drugs are being investigated at the moment and if any of those make it to clinical practice, the implication of making an accurate diagnosis will become more important,” said Dr Ross.

Incidence and prevalence of MPN

A paper published last year in the American Journal of Hematology based on epidemiology work by Professor Peter Baade reported on the latest available statistics on incidence, prevalence, and survival of MPN in Australia.

“This showed there are 23 cases of MPN per million population per year, so it’s a pretty uncommon disease, but because many people with MPN will live for many years, the prevalence is relatively higher, considering the low frequency of diagnosis,” explained Dr Ross.

“For instance, somebody with ET might live for 20-30 years, whereas for many cancers the survival will be much shorter.

“According to that study, new diagnoses of PV and ET were roughly equal; at about nine per million per year, and primary myelofibrosis is the rarest at about five per million per year.”

Regarding age at diagnosis, Dr Ross said the average age of diagnosis for all MPNs was 68. The oldest cohort, with an average age of 72 years, were those with primary myelofibrosis, and the youngest was ET at 66 years, closely followed by PV at 67.

However, he said, “there’s a tail of younger patients”.

“We see people in their 20s with ET, whereas myelofibrosis is rare below the age of 40.”

“The cause of MPN in most cases is unknown. If you have a family member with MPN, your risk of getting an MPN is increased about five-fold compared to the general population.

“Although it’s not an inherited disease, there’s an inherited risk component. We do occasionally see brothers and sisters or parents and children that both have MPN.”

Dr Ross said there weren’t any known strong risk factors, although there is an increased risk with exposure to radiation and, rarely, to industrial chemicals.

“No-one has ever done a proper, large epidemiological study of MPN risk factors.”

Disease progression and risk

Dr Ross said ET and PV can both turn into MF.

“It’s generally estimated to be something like 20-30% lifetime risk, but that might depend on the age at diagnosis.

“If you’re diagnosed [with ET or PV] at 75, you may never get myelofibrosis. But if you are diagnosed at 30, your risk of getting myelofibrosis might be substantially higher because you’re potentially going to live for another 50 years.

“All three diseases can turn into acute myeloid leukaemia (AML).”

However, Dr Ross said the risk of AML for ET patients is very low, around 2%, and 5% for PV, so it is rare.

“Every now and again it happens, and it is a shock for those people.”

For MF, the risk of AML is 20-30%.

*  Dr David Ross received a Leukaemia Foundation clinical PhD scholarship (January 2006-January 2009, $120,000) for his research project, Characterisation of persistent CML cells in patients treated with ABL kinase inhibitors.

For information about any of the studies mentioned, download the Clinical Refer app on your smartphone and search using the name of a drug or study. 

Improving outcomes for Australians with an MPN 

Improving outcomes for Australians with an MPN 

Photo of Dr Leisl Butler in her lab

Dr Liesl Butler is investigating the gene mutations and biological pathways that lead to the development of MPN and hopes to make significant advances in blood cancer research.

The junior haematologist, based at the Australian Centre for Blood Diseases at Monash University (Melbourne), has a strong interest in molecular pathology and is looking to improve outcomes for Australians living with an MPN.

She is undertaking translational research and was awarded a 2020 Leukaemia Foundation of Australia PhD Scholarship, through the Haematology Society of Australia and New Zealand (HSANZ).

This provides funding of $120,000 from 2020 to 2023 and her project title is Development of improved biomarkers and targeted therapies for MPN.

Dr Butler is working under the supervision of Professor Andrew Perkins, a leading haematologist and group leader at the Australian Centre for Blood Diseases at Monash University.

Working as a clinician, Dr Butler appreciates that research is pivotal to successfully treating the blood cancers and she is excited at the prospect of her research being translated into meaningful outcomes for patients.

“Molecular pathology has had a considerable impact on diagnostic and therapeutic approaches in blood cancer,” she said.

“The area is rapidly expanding and its integration into standard practice is drastically improving clinical outcomes.

“I will study the gene mutations and biological pathways that lead to the development of the MPNs by undertaking tests in patient samples and mouse models,” said Dr Butler.

“Molecular techniques are now critical in the detection, classification and monitoring of many blood cancers, and are essential in the development of new treatment strategies and predicting disease response.

“The MPNs are a challenging disease group which causes significant morbidity and can limit life expectancy; the overall biology of these cancers remains elusive and new therapies are desperately needed.

“Additional research in the field will further our understanding of these cancers and lead to developments in treatment, hopefully improving the lives of patients,” said Dr Butler who is in the early stages of her PhD project.

“I have studied the current literature in the field extensively and begun preliminary experiments. Thus far, the results are very encouraging.”

She was “thrilled” to discover that she had been offered the PhD scholarship, overcoming what she considers the biggest hurdle for researchers; funding.

“I feel privileged to have the support of the Leukaemia Foundation and Haematology Society of Australia and New Zealand for my project,” said Dr Butler.

“And I am incredibly grateful to the Leukaemia Foundation supporters aiding my project.

“I look forward to what I can achieve over the next three years with the assistance of the scholarship and hope to make significant advances in blood cancer research.”