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Christine has a rare genetic predisposition to MDS

Christine has a rare genetic predisposition to MDS

Christine and Greg at Ashleigh's end of year school service Nov 2018

Christine (left) and husband Greg (right) at their daughter Ashleigh’s end of year school service in November 2018.

After losing her dad to MDS, and her brothers diagnosis just a month before hers, Christine Heath’s family underwent genetic testing to understand whether their MDS could be hereditary.  

Christine, a high school maths teacher, fell suddenly, back in 2015, when walking up the stairs to class, then fainted while lining her students up.

“It was just for a split second and I only dropped my books,” said the now 53-year-old from Port Lincoln, South Australia.

But she thought to herself, “that’s not right”, and went to the doctor to be checked out. Her blood tests returned some “funny results” and her doctor was particularly concerned about her haemoglobin level.

Christine's daughter, Ashleigh and dad, Geoff, Christmas 2010
Christine’s daughter, Ashleigh and dad, Geoff, Christmas 2010

She was given the option of redoing the test in three months or going straight to a specialist.

“Given my dad, Geoff, had died from MDS in 2011, I opted to go to the specialist,” said Christine.

She saw the same haematologist who had treated her father, and he assured her any blood issues could not possibly be hereditary, that it was unlikely to be MDS, but he would monitor her over the coming years.

A ‘double-whammy’ diagnosis

After being closely monitored for several months, Christine was formally diagnosed in April 2016 with myelodysplastic syndrome/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T)*.

“This was just a month after my older brother, Stephen, who was also going to our dad’s haematologist, received the same diagnosis – a double whammy,” said Christine.

“My daughter, Ashleigh, was in year 10 at the time and I really wanted to be actively involved in her life, see her graduate, and live with my husband, Greg a lot longer.

“To begin with, I was put on ‘watch and wait’ with tissue and blood samples taken to find a stem cell donor.”

Genetic testing

Even after her diagnosis, her haematologist was still reluctant to class her MDS as hereditary.

It wasn’t until Christine, Stephen, and their partners attended a Leukaemia Foundation MDS workshop in September 2016 that they started to find some answers.

“The workshop was in Adelaide and there was a geneticist there, Professor Hamish Scott, who we approached after his session, and told him about our situation,” said Christine.

“He said straight away, ‘oh I definitely want your genes… let us do some testing’.”

Christine and her mum and dad, 2010
Christine and her mum and dad, 2010

Another haematologist arranged for samples from Christine and Stephen to be shared with Prof. Scott and extra information about their dad and grandmother was provided.

The researchers asked her mum, Gill, for permission to use Christine’s dad’s blood samples. These had been stored as they looked different, but Geoff’s medical team was unable to understand why at the time.

“My mum also remembered that other family members had experienced blood issues and so they did a family tree and tracked it back a couple of generations,” explained Christine.

“It was then confirmed that we do indeed have a genetic predisposition to MDS!”

Read about the Blood Cancer Genomics Clinical Trial headed by Professor Hamish Scott in Adelaide and supported by the Leukaemia Foundation.

Christine’s brother, Stephen and her Dad in 2010
Christine’s brother, Stephen and her Dad in 2010

Ashleigh also has provided hair and blood samples, but she chose not to ask for information about any findings.

“She said she might when she has a family one day, but right now she’s focused on living for every day and doesn’t want that hanging over her head,” said Christine.

“She has just begun studying science at the University of Adelaide, majoring in immunology and genetics.

“We are really proud of her and the interest she has in the science behind all this. She could be the one who makes a difference for us in the future.”

Navigating treatment

In October 2016, Christine flew to the Peter MacCallum Cancer Centre in Melbourne to get a second opinion.

“I learnt there that there were no clinical trials suitable for me and to just continue to maintain a balanced diet and consider part-time work.”

Early the following year, Christine needed to begin having blood transfusions and erythropoietin (EPO) injections every two months.

In 2018, as her condition worsened, she stopped work altogether.

“I’ve been on income protection ever since,” she said.

“I strongly encourage people to check whether their super gives them the option.”

Christine in hospital during her transplant
Christine in hospital during her transplant

Time for transplant

After living with Ashleigh in Adelaide for 12 years while she completed her schooling, Christine moved back to Port Lincoln to be with her husband in early-2019. Greg had stayed at Port Lincoln to support his parents as his father was battling leukaemia at the time.

When Christine’s transfusions got closer and closer together, her haematologist said, ‘time’s up, we’re going to transplant’.

“A sudden drop in two of the blood lines had appeared, which was the marker he was waiting for,” she said.

“I was a bit scared, but I knew that’s what I wanted to do.

“I felt far too young to die and I didn’t want to have to deteriorate like my dad had done before he passed.”

Ashleigh had produced a booklet for her senior school research project on the associated benefits and risks of transplants.

“Her project question was, ‘do the positive outcomes of getting a stem cell transplant to treat blood cancer outweigh the risk factors?’” said Christine.

“She interviewed a number of haematologists, ran a patient survey, and did a heap of research.

“She did an amazing job, and I think it really helped her to understand the process and cope with what I was going through.”

Christine and her family were given the time to take a holiday together before her transplant.

“We went up to Queensland and did ‘the worlds’,” said Christine.

“We were able to visit Ashleigh’s cousins there, and I didn’t want to take the risk of going overseas in case something went wrong.

“It was such a great trip. I’m not a big ride person but I was chief bag holder and took all the photos while they went on the rides.”

On 16 August 2019, Christine had her transplant with stem cells donated from the umbilical cord blood of two baby girls, after a previous donor match was no longer viable due to age.

“When I got to the hospital everything happened very quickly. I was started on chemotherapy and then I had full body radiation.

“On transplant day, I had Greg and my mum there, as well as Stephen and his wife, as he was about to have his own transplant and wanted to see the whole process.

“My niece, Stephen’s daughter, was also there. She had just finished her honours degree in science, supervised by haematologist, Dr David Yeung.

“Shortly after, she was employed to work with the transplant team doing all the data collection for transplant patients and looking for trends in treatment.

“It was feeling a little bit like a party, but it was kind of a letdown as the transplant itself is like having a transfusion.”

Christine needed to stay in hospital for seven weeks after the transplant.

“I consider myself extremely lucky as I didn’t have any long-term issues with graft versus host disease (GVHD) and didn’t go into intensive care once,” she said.

“I did go off my food for a bit and had to have a feeding tube, which I hated. I had a bad reaction to cyclosporine**, and they put me on steroids for suspected GVHD which caused me to develop steroid-induced diabetes.

“That was only temporary for about three months and by the time they had taught me to do the injections myself, it was time to stop.”

Christine "hanging" at the village post transplant
Christine “hanging” at the village post transplant

Leukaemia Foundation support

Christine and Greg stayed at the Leukaemia Foundation patient and family accommodation village in Adelaide for six months during her transplant and recovery.

“It was really important to stay close to the hospital as Port Lincoln is a seven-hour drive from Adelaide,” said Christine.

“We loved it there and we made quite a few friends around the village. We all kept an eye out for each other.

“There’s morning teas and the staff put on a Christmas lunch for everyone. There’s also a nice little games room where my husband and I would play a bit of ping pong or table tennis when I was feeling better.

“I cannot thank everyone from the Leukaemia Foundation enough – they were brilliant.”

Christine was kept busy during her recovery, with regular appointments and blood tests.

“These were weekly to begin with, then steadily decreased to fortnightly and monthly appointments,” said Christine.

“I also had lots of physio to build my muscle as I had lost about 15 kilos while in hospital.”

Although the Heaths had hoped to return home in February 2020, the COVID-19 outbreak meant they had to remain in Adelaide until the situation stabilised.

“I actually think I would’ve struggled being away from a major hospital during that time. You want that peace-of-mind that help is just down the road should you need it,” she said.

Focused on the future

Eventually returning to Port Lincoln in April 2020, Christine has been focusing on slowly settling back into everyday life.

Christine's 1st rebirthday breakfast
Christine’s 1st rebirthday breakfast

“Life is looking really good and I’m now even talking about when I can return to work,” she said.

“I try to exercise every day and do what housework I can. I keep busy with people dropping in, and I’m really looking forward to summer so I can get back to the beach.

“But I’m always conscious of not overdoing it as I can still get really tired some days.”

Christine has regular tele-health appointments with her haematologist and travels back to Adelaide every two months for a face-to-face check-up.

“I can have my blood tests in Port Lincoln and I need to have a venesection fortnightly because my iron levels are too high from all the transfusions,” explained Christine.

“I also have an immunoglobulin infusion once a week which is a subcutaneous injection, two little needles into my stomach which I’ve been taught to self-administer.”

Now she is firmly focused on living for every day and is confident that with medical advancements, outcomes for people with genetic diseases will improve.

“I’m still in contact with Prof. Scott and serve as a consumer advocate whenever the opportunity arises,” said Christine, who together with two other women, started an MDS/MPN-RS-T Facebook support group.

“I also want to stress that our family is an extremely rare case and MDS is not typically a hereditary disease,” said Christine.

*MDS/MPN-RS-T is a rare subtype of MDS/MPN characterised by anaemia, bone marrow dysplasia with ring sideroblasts and persistent thrombocytosis ≥450 × 109/L with proliferation of large and morphologically atypical megakaryocytes.

**Cyclosporine is an immunosuppressant used to prevent rejection, following allogeneic bone marrow transplantation.

PhD scholarships focused on improving outcomes for people with AML and MPN

PhD scholarships focused on improving outcomes for people with AML and MPN

The Leukaemia Foundation and the Haematology Society of Australia and New Zealand (HSANZ) are proud to announce the successful recipients of the 2021 round of PhD Scholarships Basit Salik and Dr Julian Grabek. The work of these recipients will help improve the understanding and treatment for acute myeloid leukaemia (AML) and myeloproliferative neoplasms (MPN).

The Leukaemia Foundation has been supporting Australian blood cancer research and the careers of promising scientists and clinicians for over 20 years. These PhD Scholarships, valued at $130,000 each, are part of the Leukaemia Foundation’s National Research Program which has invested more than $54.5 million into research since 2000. To date that funding has supported over 370 researchers across 290 research projects, through PhD scholarships and research grants, at over 50 hospitals, research institutes and universities.

Accelerating research and providing access to best practice treatments are two key research priorities of the Leukaemia Foundation and were identified as key priority areas in the State of the Nation: Blood Cancer in Australia report and recently released National Strategic Action Plan for Blood Cancer. These reports show us while significant gains have been made, it is projected that more than 186,000 Australians may die from blood cancers by 2035. These reports highlight that research has the potential to reduce blood cancers mortality rates and the associated economic costs but to do so will required increased and sustained investment in research. That is why 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.

The Leukaemia Foundation thanks Brydens Lawyers and the Bourne Foundation for their generous contribution and support to the PhD Scholarship program.

 

Details of the research projects include:

Dr. Julian GrabekDr. Julian Grabek – Clinician researcher, Queensland Institute of Medical Research (QIMR) Berghofer, Brisbane

Myeloproliferative neoplasms (MPN) are clonal haematological disorders of stem cells.  These stem cells undergo a mutation that drives an overproduction of blood cells. Throughout the course of the disease the stem cells are driven by specific mutations (JAK2, CALR and MPL) but over time additional genetic mutations are acquired leading to progression of the disease to either secondary myelofibrosis and bone marrow failure or acute myeloid leukaemia. These outcomes have limited treatment options and have a poor prognosis.

High risk stem cells with the potential to develop into leukaemia can be identified early in the disease but are often a “needle in a haystack” when compared to the rest of the MPN stem cells.  By using cutting edge single cell technology, the aim of Dr Grabek’s project is to separate each individual cell of the MPN stem cells. Through a combination of mutational analysis by novel nanopore technology and assessment of downstream gene signalling they will be able to determine the early stages of leukaemia development in these disorders. In future, it is hoped to establish which treatments have the potential to arrest these early changes and prevent transformation to leukaemia.

 

Basit Salik - Research scientistBasit Salik – Research scientist

Over the last 4 decades, chemotherapy-directed management of acute myeloid leukaemia (AML) patients has remained largely unchanged. While most patients achieve complete remission after chemotherapy, most patients with AML relapse and ultimately die of the disease.

A high relapse rate in AML suggests that current standard therapies do not target these highly self-renewing leukaemia cells and that immune subversion by the primary tumour leads to an ineffective anti-tumour response. Cancer cells including leukaemias can adapt to oncogenic and/or environmental stressors such as chemotherapy, hypoxia, and metabolic stress. Indeed, several stress-induced molecules augment pro-survival signalling and aggressiveness in cancer cells. By contrast, either by direct recognition of stress-induced molecules on cancer cells or by exposure to environmental stress factors, immune cells also undergo functional impairment.

Basit and his team will investigate biological pathways that regulate cancer cell-intrinsic adaptation/aggressiveness as well as immune dysfunction by utilising patient samples and mouse models of AML. The team is hopeful that this research will lead to improved therapeutics that can effectively inhibit leukaemia growth with the potential of harnessing anti-leukaemia immune responses for durable disease control.

This PhD scholarship is kindly supported by Brydens Lawyers.

The Leukaemia Foundation receives no ongoing government funding, and the National Research Program relies on the continued support of generous donations. Donations allow us to continue to invest in Australian blood cancer research and to support the next generation of researchers, driving this type of innovative research for better treatments, better care and ultimately a cure for blood cancer. To find out how to support the Leukaemia Foundation’s National Research Program call 1800 620 420.

Leukaemia Foundation to host virtual seminars for National MPN Awareness Day today

Leukaemia Foundation to host virtual seminars for National MPN Awareness Day today

Thursday September 10, 2020

Australians living with the rare blood cancer Myeloproliferative Neoplasms (MPN) will today be able to connect through a new virtual seminar being hosted by the Leukaemia Foundation as part of National MPN Awareness Day.

Working in partnership with MPN Alliance Australia, the free live seminar will include four speakers from Monash University, The University of Western Australia, Cancer Council Queensland and a patient advocate from Sydney.

Leukaemia Foundation Acting CEO Alex Struthers encouraged those Australians and their families living with MPN to sign up to the free live event and unite with other Australians experiencing the blood disorder.

“This event will be streamed live, enabling attendees to gather together virtually to hear some of the latest insights into the disease to better inform their diagnosis and treatment, and break down some of the barriers they may face in accessing this information,” Ms Struthers said.

Myeloproliferative neoplasms (MPN) are cancers that start in the bone marrow, where blood cells are made. In MPN, the bone marrow makes too many of one or more types of blood cells (red blood cells, white blood cells and/or platelets). These cells change the thickness of the blood. They also crowd the bone marrow and then it can’t make enough healthy blood cells.

There are seven types of MPN, diagnosed using blood tests and a bone marrow biopsy. Some forms can transform into other types of MPN or into acute myeloid leukaemia (AML) – one of Australia’s deadliest blood cancers with a  five-year survival rate of just 28 per cent1.

The Leukaemia Foundation has invested nearly $700,000 into research of MPNs as part of its $50 million National Research Program and continues to advocate and support all Australians living with more than 120 different blood cancers across the nation.

Currently, the Leukaemia Foundation is funding the research of Dr Liesl Butler – a junior haematologist based at the Centre for Blood Diseases at Monash University in Melbourne. Find out more about Dr Butler’s research here.

Virtual Seminar Details

Date: September 10, 2020

Time: 12 noon AEST

Where: Online via Microsoft Teams Live

Register here

Speakers:

Prof. Andrew Perkins from Monash University. Topic: Current clinical and research interests – rundown on how diagnosis and treatment is progressing and emerging therapies.

Prof. Wendy Erber from University of Western Australia. Topic: Why do Myeloproliferative Neoplasms Progress to Fibrosis?.

Prof. Peter Baade from Cancer Council QLD. Topic: How does the burden of MPN in Australia vary by where people live.

Helen Williams from Sydney. Helen is newly diagnosed with PV and will be discussing her experience from a patient perspective.

More about MPN

Myeloproliferative neoplasms (MPN) are a rare group of blood cancers.

The MPN Polycythaemia vera is diagnosed in an estimated 250 Australians each year, essential thrombocythaemia around 200 and myelofibrosis an estimated 150. Rarer sub types are diagnosed in less than 50 Australians each year.

MPN is more commonly diagnosed in people over 50, although it can rarely occur in younger people, every rarely in in children.

Many people have no symptoms when they are first diagnosed with an MPN and the disease is often picked up accidently during a routine blood test or physical examination.

When symptoms do occur, the develop gradually over time and can include headaches, blurred vision, fatigue, weakness. Dizziness, itchiness, night sweats and raised blood pressure.

Most people with an MPN have no family history of the disease.

Find out more about MPN here.

– ENDS –

Jennie’s had baby George since her MPN diagnosis

Jennie’s had baby George since her MPN diagnosis

Jennie Wigginton and her family on holiday at Wilson’s Promontory in September 2017
Jennie Wigginton and her family on holiday at Wilson’s Promontory in September 2017

Jennie and Russell Wigginton had to put their plans to have a second child on hold when Jennie was diagnosed “out of the blue” with essential thrombocythaemia (ET) in May 2015. 

Their son, Austin, was two at the time, and the Wiggintons had been trying for a second child for six months.

“We got pregnant quite quickly with our first,” said Jennie, now 39, a social worker who also runs her own business as a fitness instructor and personal trainer.

Jennie Wigginton in the park
Jennie Wigginton: “I do what I can to stay healthy, and ultimately my family is my inspiration”

In the build-up to her diagnosis, Jennie had been getting severe headaches.

“Really painful headaches, where you could take Panadol and Nurofen and it wouldn’t even touch the sides,” she explained.

Russell, concerned she may be diabetic, suggested she go to the doctor, and three days after having blood tests, Jennie got a call saying she needed to see the doctor again, straight away.

“My results showed my blood platelet count was up near the two million mark, and when I asked what the usual range was, it was 450, so it was massively out of the normal range.

“They said, ‘look, it’s in line with essential thrombocythaemia’ and sent me to the emergency department, to see whether I needed to see someone urgently about it.”

Jennie was told there was nothing they could do at that time, and to go home, take some aspirin and the haematology department would be in touch.

“Within a week, they did some very thorough work and checked all my levels. I had an ultrasound of my spleen, a CT scan of my brain, and a bone marrow biopsy, before I started any medication.

“Then I went on hydroxyurea, initially, to help control my platelet count.

“The bone marrow biopsy actually revealed the early stages of myelofibrosis (MF). I’ve got some scarring on my bone marrow,” said Jennie.

Her diagnosis was a combination of MF and ET and she began seeing her haematologist every fortnight and had regular blood tests.

“The platelets started responding straight away and they’ve gradually come down, but not ever to within the normal range.

“When I first found out I had this condition, I was told MPN normally affected people in their 60s or older,” said Jennie who was 35 at the time.

“I wondered what it meant for me as a younger person and somebody who wanted to continue with having more children. I didn’t know what the impact was going to be, so obviously it was a little bit scary.

“I remember that day coming back from the doctors and just being in shock and thinking, gosh, what does this all mean? You think about your own immortality… am I going to be around to watch my children grow up, or my child at that point, and am I going to be able to have more children? You just don’t know.

Jennie Wiggington and her sons
Jennie and her sons, George and Austin, wearing her Metafit Footscray business hoodies

“And I’d never heard of it [MPN] before and didn’t know anything about the condition.

“So, you’re just really shocked by it because it took me out of the blue. Suddenly I’m being told I’ve got a blood cancer, and not knowing what the future held,” said Jennie.

“I’m someone who likes to keep fit but I had to balance that as I was concerned because I was at risk of blood clots because of my high platelets.

“Once my blood platelets came down more into range, I felt more comfortable. I was taking aspirin to thin the blood, and the doctor said it was good to keep exercising and moving.”

When first diagnosed, Jennie mentioned to her haematologist that she had been unsuccessful in falling pregnant again. She was told it might be due to her blood condition and to stop trying for the moment.

“I went to a fertility specialist who talked about having cancer as a young person and the implications of different treatments and how they can impact on your fertility,” said Jennie.

“We talked through options about the possibility of freezing eggs, or IVF, stuff like that, but as we were not at that point, we would go down the natural route if we could and see how things go.”

Hydroxyurea successfully reduced Jennie’s platelet count over six months, from May to October 2015. Then, in November, she transitioned to interferon over three months before stopping hydroxyurea because of the implications that can have on a developing baby.

She initially injected herself with the interferon three times a week before the dosage was increased to five times a week.

“When you start that medication, often you get flu-like symptoms and start to feel quite groggy, but luckily it only lasted for the first few days. Your body adjusts and gets used to it. I was advised to take Panadol to help with any kind of aches.

“It was Roferon-A, not the pegylated one, I didn’t move on to that until later,” said Jennie.

“Before we could start trying to fall pregnant again, I had to be clear of the hydroxyurea for three months, so it had all got out of my system.

Jennie Wiggington with her medal for Melbourne Marathon
Jennie competed in the Melbourne Marathon (Half) in October 2019

“I remember the doctors saying not much is known about pregnancy and MPN because not that many people of childbearing age have the condition.

“So it was kind of, ‘we know that you can’t have children on hydroxyurea and we believe interferon is the safest option for you, and the research shows that there’s not an impact on the baby’.

“I guess they don’t know 100 per cent, but it’s the safest form of treatment whilst you’re pregnant.

“But there were still risks of clotting and haemorrhaging and the placenta coming away from the womb. I was told that those were the inherent risks around having another baby.

“It was hard because we’d had our son. Did we just say, ‘that’s it, we’re done, and we’re not going to risk it?’ because the risks weren’t just for the baby, but potentially for me as well because of the blood clotting.

“We just took each step at a time and listened to the advice from the specialist doctors,” said Jennie.

“We got pregnant again in August 2016. Because of my blood condition, it was deemed as a high-risk pregnancy and I was under the care of specialist doctors.

“I was getting the best advice and care with lots of support, regular appointments, and monitoring.

“They picked up very early on, when I was about six weeks pregnant, that my thyroid levels were through the floor and in the danger zone for the baby developmentally.

“I had to go on thyroxine. They don’t know if the interferon had impacted my thyroid and damaged it, which it can apparently do, or whether I got Hashimoto’s disease, which is hereditary – my sister and my aunty both have it. Or it could have been brought on by pregnancy,” said Jennie, who continues to take thyroxine.

Mid-way through her pregnancy, with the blessing of her doctors, the Wiggintons went back to England for a month and a family Christmas. Jennie and Russell had migrated to Australia in 2010.

“I just had to make sure I had all the medications with me,” said Jennie.

She took an anticoagulant (blood thinner) before, during and after each flight, to minimise the risk of blood clots, and she drank lots of water.

Wiggington Family in New Zealand
Holidaying in New Zealand in July 2018 – Russell and Jennie with George and Austin

All in all, Jennie’s pregnancy went well, and her obstetrician said she had done ‘amazingly well’. To minimise the risks during labour, the decision was made to induce her in the 39th week.

“Then nothing happened for 24 hours and, as I wasn’t dilated enough and the baby’s heart rate dropped, they did an emergency caesarean.

“He had some low blood sugar, because he was quite little when he was born, and had to go into special care for a few days until his blood sugar stabilised.”

George was born in May 2017, “a fine, healthy baby boy”, and Jennie and Russell, who had always hoped to have two children, and feeling lucky nothing major had happened, decided “enough’s enough, we’ll finish on a good note”.

Jennie continued her interferon medication until she heard that pegylated interferon [Pegasys®] become available on the Pharmaceutical Benefits Scheme.

“I went straight to my haematologist saying, ‘I’d like to try this’. I started on a low dose and that’s what I’ve been on since.

“It’s been great because it means now I only have to inject once a week rather than five days a week and have no ill effects from it. It’s just been a revelation, really, in terms of treatment for the illness.

“I never had any horrible side-effects on Roferon-A,” said Jennie, but she used to have “really bad itching” which was worse in winter when her skin was dry.

“I’d scratch so bad I’d bleed on my legs and on my tummy, but that’s gone for me now. I don’t know if it’s the pegylated interferon, or if it’s changing hormones or the environment.”

Jennie self-injects the pegylated interferon into the fatty subcutaneous area around her stomach.

“Sometimes, I inject into my leg, just to give my tummy a bit of a rest.”

Over the course of Jennie’s experience with MPN she has gone from seeing her haematologist every two weeks, to once a month, then six-weekly, and now it’s every three months.

When she spoke to MPN News Jennie had just received her latest results.

“My platelets were the lowest since I was diagnosed and only very slightly above the normal range which is really good.”

In June, Jennie asked to have her bone marrow tested again even though this is not usually done unless there is a change in presentation or bloods.

“Overall, it looks like the scarring has got worse since five years ago, but he [her haematologist] said it’s hard to decipher if it’s the progression of the disease or the impact of the interferon.

“As everything else looks good and there are no blast cells present, the decision was to carry on as normal.

“The only other options would be to go on ruxolitinib [Jakavi®] or a stem cell transplant but we decided, neither at this point.”

Jennie said she had been affected by “really bad headaches again”.

“Automatically, I go back to the worse-case scenario in my head, what’s wrong, something’s happening. Am I going to have a stroke because I have a blood clot or is the condition getting worse?”

“I’ve got a really good GP. She’s really thorough. She sent me for MRIs and referred me to the neurologist.

“I think it’s just about trying to keep a level head and also listening to your body.

“We’ve recently moved and had a lot of changes and I think it’s also about being kind to yourself and taking a bit of time out.”

In early-July, the family moved from Melbourne to rural Woodend where they have a “massive garden and a view of Mt Macedon”, and there’s been a new addition to the family, Monty, a kelpie puppy.

Since COVID-19, Jennie has worked her three days of social work a week from home rather than driving the hour into Melbourne, and she has moved her fitness business online and is training her clients from a distance. She keeps fit by running most days “for fitness and to clear your head”.

“I don’t let it [MPN] control me or dictate who I am or what I am, but sometimes I need to remember that I have this condition, and I do need to listen to my body and just slow down and rest, if my body’s telling me to,” she said.

But, as a mum with two young kids, running a family, and working, Jennie said, “it’s a necessity to keep going”.

“I do what I can to stay healthy, and ultimately my family is my inspiration.

“I want to be here for as long as I can to be with them and look after them and watch them grow up.

“It’s good to know that support is there if I need it.”

Jennie has joined the Leukaemia Foundation’s coffee mornings and been to the blood cancer conference in Melbourne a couple of times, although with a young family that’s not always easy.

“It takes quite a lot of effort for me to get to those meetings. I need to take time off work and find childcare,” she said.

“I’m on a few of the Facebook support groups. There are people in a similar situation to me, young, and wanting to talk about having babies with the condition. I’ve been able to share my knowledge and experience.

“It’s nice to know that you’re not out there on your own, especially when initially diagnosed, and that there are other people experiencing similar difficulties and that there are great support networks available to help and reassure each other.”

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.”

Tereena goes to her “happy place” when she’s in pain or discomfort

Tereena goes to her “happy place” when she’s in pain or discomfort

Tereena with alpacas

Tereena Cocks, 52, has practised meditation and visualisation almost as long as she’s been living with blood cancer, and that’s more than half her life.

She was 24 when she was diagnosed with essential thrombocythaemia (an MPN) and has had many different therapies over the years on watch and wait.

“My disease was ‘recalcitrant’,” said Tereena, “I’d constantly swing between really high counts and really low counts, with episodes of extremely painful clots or nasty bleeds.

“My maintenance therapy was a knife’s edge; it was very difficult for my haematology team to manage,” said Tereena, who lives with husband, Craig, on acreage, an hour south of Adelaide, with their two German shepherds and two alpacas.

Learning to manage pain

“When I was first diagnosed, I had a lot of bone pain. At a pain unit, I learnt self-hypnosis and autogenic relaxation*.

“Back in those days, I was an ambulance paramedic and didn’t want to have anything that would interfere with my cognition.

“So, I learnt other ways to cope with the discomfort, by natural means, rather than by taking opiate-type drugs,” she said.

“I’m an hour away from the nearest major hospital which means I’d have at least an hour of severe pain, and meditation helps a lot with that.

“And during admission, when I’d have tests like having a needle stuck into a joint, I’d just go off to my happy place.”

Benefits of relaxing deeply

“When you’ve got a bad illness and the doctors are all fluffing over you, your life is in a bit of a spin and you tend to lose control,” said Tereena.

“This whole relaxation thing helps when you’re out of your comfort zone and there’s nothing you can do about it. You just calm your whole body down. I find that to be absolutely wonderful.”

Relaxation technique

“I mainly do visualisation and autogenic relaxation,” she said.

“It involves finding a comfortable, relaxed position, and having a mantra that you go through in your mind.

“You think about your toes first, give your toes a bit of a wriggle, and internally say, ‘my toes are warm and relaxed’, and you wriggle them and let them relax.

“Then you give your calves a bit of a flex and say to yourself, ‘my calves are warm and relaxed’.

“You work your way up and through lots of different areas of your body and it’s amazing where you’ll find you’re holding on to tension.

“There’s a breathing part and when you get to your lungs, you take nice deep breaths in and out. It’s a really relaxing thing to do.”

Tereena said the amount of time she devotes to this practice depends on how much time she’s got and what she’s using it for.

“You can do it very quickly when you need to, but you can also take as much time as you like when you’ve got no other things to do. It’s just a matter of training.”

Myelofibrosis and leukaemia

In October last year, Tereena found out her disease had transformed to an aggressive form of myelofibrosis. Then two weeks later, she was diagnosed with acute myeloid leukaemia.

When Tereena spoke to our Living Well e-News, she was Day 60 after having an allogeneic bone marrow transplant in April.

She used visualisation a lot while she was away from home for her transplant. And she had “a bit of assistance”.

“I’ve got external security cameras at my house and I can use my telephone to access my cameras when I’m away, in hospital.

“I have that in the background, and when I’m lying in the hospital room, I can picture myself at home and being well – it’s such a comfort.

“I can hear all the familiar noises of home and the sounds of the animals outside and the birds flying over.”

For people without home security cameras, Tereena suggests they record the sounds of home to listen to during lengthy periods of time in hospital.

“I was in a really bad state when I was in hospital. I had Grade 4 mucositis – the worst it can possibly get.

‘I couldn’t eat or drink a single thing and had TPN nutrition. It was really painful, and that’s when I’d go into my happy place, to get me through all of that.”

Coping with cancer

Having worked in the health industry all her life, Tereena knows the benefits of a good mental state.

During challenging times in hospital, she thinks to herself… “each minute is a minute I don’t have to have again”, “I don’t have to do the last five minutes again”, and “today’s a different day and one day closer [to recovering]”.

“I just plod on, one foot in front of the other, always steps forward,” said Tereena.

“And I live each day to the best of my capabilities, enjoying the little things and not worrying about what I can’t change.”

Soon after her diagnosis, Tereena read a book about living in the moment, written by Vietnamese Buddhist monk, Thich Nhat Hanh. She’s still got The Miracle of Mindfulness on her bedside table.

“You can learn some amazing things from it,” said Tereena, who practises mindfulness daily, usually in the morning.

“It puts you in a really good mental attitude. You feel good about the day, before it starts.

“I honestly think that if you put all this positive stuff in and around you then that’s what happens in your day… it comes back to you.

“It’s not just for when you’re in pain or unwell, it’s something good to use in life every single day.”

September is Blood Cancer Awareness Month, helping to raise awareness of every blood cancer. Learn more.

* A technique that involves progressive relaxation of the body’s extremities, heartbeat stabilisation, and maintenance of slow, deep breaths.

Haemo-globetrotter Bryan has blood tranfusions on his travels

Haemo-globetrotter Bryan has blood tranfusions on his travels

Bryan and Winona Mitchell visiting a winery in Croatia
Bryan and Winona Mitchell visiting a winery in Croatia

When veteran traveller Bryan Mitchell, 74, journeys from country to country, he gets treatment for his MDS along the way… that is until COVID-19 put a stop to his travels.  

His last overseas transfusions were in Marseille and Paris during a six-week trip to France last September which he described as “very good and very expensive”. 

“If you can afford a holiday overseas you can afford the medication” he said.

Since his diagnosis with MDS, he hasn’t let his fortnightly blood transfusions stop him from travelling the world with his wife of 38 years, Winona. It just requires some extra planning.

“I need to ensure that I have enough blood in my body to get me from A to B,” said the Shepparton (Victoria) resident.

Bryan sitting in a boat, with the Murray cod caught on a fishing trip at Lake Mulwala
Bryan with the Murray cod caught on a fishing trip at Lake Mulwala

The couple has three adult children and four grandchildren and has tackled Bryan’s illness for a third of the time they have been together.

“Until the age of 55, I was in excellent health. I was still playing cricket and participating in long-distance running and down-hill skiing.”

But his heart health was faltering. Bryan developed angina, had stents put in and then bypass surgery in 2005.

“My life changed from that time.”

In 2007, a routine blood test prompted the beginning of what Bryan felt was a “long-term downturn in health”.

He was initially diagnosed with MDS which he said, “was something I had never heard of”.

Bryan’s condition is now categorised as an MDS-type chronic myelomonocytic leukaemia (CMML); a rare blood cancer that has characteristics of both MDS and myeloproliferative neoplasms (MPN).

Until this diagnosis, he had been “active and enjoying life” and, impressively, Bryan didn’t retire from the Public Service until 2014, aged 68, when he was quick to take up contract work.

“I was flippant to begin with. I went to see a respected oncologist in Melbourne who fully explained the illness. At the time, it seemed to have no impact on my life.

“However, my coexistent ischaemic heart disease is impacted if my haemoglobin drops too low (80-85),” Bryan explained.

“Recently, I have been as low as 74 and once I was 55 which was pretty scary.”

Having been transfusion-dependent since 2011, he currently has two to three units of transfused blood every two weeks.

“There is no treatment available to me other than blood transfusions, and deferasirox [Jadenu®, an iron overload medication] to help regulate my iron levels,” said Bryan, and this ongoing regimen is a frustrating reality for him.

Winona and Bryan on the Champs Elysees during their trip to Paris in 2019
Winona and Bryan on the Champs Elysees during their trip to Paris in 2019

“MDS and ever-increasing iron levels have a significant impact, and anaemia is also a real problem,” he said.

“I have overcome heart disease and two strokes, one of which left me blind in my right eye.

“I am a true one-eyed Magpies’ supporter,” joked Bryan, but his struggles don’t stop there.

“As a result of a carcinoma, I have had plastic surgery to repair a crater in my scalp that wouldn’t heal.

“During the four operations I have had on my head, infection has caused many problems and MDS has had a big impact with my body’s ability to fight the infection,” he said.

“The last six months have been quite an adventure, but we’re getting there.”

But Bryan’s dreams along with encouragement from his family and friends have inspired him to continue his MDS journey.

“As well as my ambition to see the world and a desire to see my grandchildren grow up,” he added.

And these motivations have seen Bryan accomplish many feats.

“Three years ago, we decided to realise a dream and travel to India. We organised a two-week small group tour of three major areas, including the Taj Mahal,” said Bryan.

“I am so glad we did. Many travellers would not attempt a trip to India.

“We love to travel overseas but I need blood every two weeks. In 2018, we went on a three-week cruise through the Baltic counties. To achieve this, we needed to organise a blood transfusion somewhere,” Bryan explained.

“We found that at the major hospital in Stockholm [Sweden]. I was able to have two units of blood, enough to enable us to finish our holiday.

“There is a charge, but it’s worth it.”

Beside the Ganges in India which Bryan described as “one of life’s most amazing places” to visit
Beside the Ganges in India which Bryan described as “one of life’s most amazing places” to visit

Years ago, the pair had met an old veteran on a cruise from Turkey to Amsterdam. The man, in his 80s, had been escorted to a hospital when they stopped in Vienna, to receive a blood transfusion.

“We had thought that was pretty good, but then we forgot about it. Now, here we are, doing the same thing,” said Bryan.

The amount of travelling Bryan does is impressive, blood cancer or not.

In 2020, the couple had planned four trips, but Bryan’s doctor said ‘no’ to him going on a family holiday to Bali with Winona and their daughter in late-January.

“They went without me as I was susceptible to infection.”

Then their Mekong River cruise in March was cancelled as the COVID-19 pandemic intensified.

“We have one planned to Portugal and Spain in July. We won’t be going, that won’t happen. And later, in August, Canada and there’s a real prospect that won’t happen either.

“Winona is my rock,” said Bryan about the help his wife provides so he stays on top of his medical regimen.

Bryan explained how, through all her own struggles, Winona has stayed strong and continues to make chasing their dreams possible.

“With the assistance of Mr Google and my wife’s persistence, we were able to organise transfusions at major hospitals in Marseille and Paris last year. The hospitals were modern and clean and English was spoken. Payment was upfront, and there was a 24-hour aftercare service.

“Some of the procedures are different, but don’t be alarmed, the lunches are great,” joked Bryan.

He has few regrets, except one – not participating in a new clinical trial, but hefty expenses and extensive travel due to living in a regional area made the trial seem inaccessible.

“I would jump at the opportunity now,” he said.

A regular at the oncology unit in Shepparton, Bryan feels that being surrounded by a support system, including others living with MDS, has made all the difference.

“The staff there are fantastic. They make attending so much easier, and happy. I admire their sense of humour and professionalism,” said Bryan.

Despite desperate struggles with severe anaemia and angina, Bryan still considers himself lucky.

“At least I know that if I get into trouble, I can get blood from someone like you,” said Brian when he spoke to MDS News.

“I see people in much worse situations than me. It makes me feel very humbled.”

Bryan wants to see MDS better understood as an illness.

“I’ve got close friends, one of 25 years and one of 40 years, who don’t understand,” he said.

“At times, I look terrific to my friends and family, but feel terrible. That is the nature of the beast.”

“I’ve gone from being as fit as a Mallee bull to nowhere near that person.”

Travel gives Bryan “something to really look forward to” but he also understands that “eventually the travelling will have to stop”.

Although physical activity is limited by his condition, Bryan keeps himself busy with many hobbies and he continues to play lawn bowls.

One of Bryan’s award-winning photographs of a tree
One of Bryan’s award-winning photographs

“I am also into photography and gardening; the environment is very important to me,” said Bryan. He has taken lots of travel shots over the years, and last year he won seven photography awards at the Shepparton Agricultural Show.

To others living with blood cancer, Bryan says, “enjoy what you can and do not be put off. Look for alternatives to help you achieve your dreams”.

Through everything, he assures others, “you can do it”.

Some of his friends tell him he pushes the boundaries too much, but he knows better.

“It can be done… just be positive and sensible.”

Ken isn’t ruled by his MPN and is optimistic about his future

Ken isn’t ruled by his MPN and is optimistic about his future

Ken at a Fluro Friday mental health promotion at Phillip Island in 2016 at which he was a speaker.
Ken at a Fluro Friday mental health promotion at Phillip Island in 2016 at which he was a speaker.

Had Ken Young been home, rather than in Melbourne’s CBD when his spleen spontaneously ruptured, he mightn’t have lived to tell us about his 20+ years living with an MPN.

“I nearly died,” said Ken, 64, describing the life and death incident in December 2005.

“I was travelling on the train when I had this incredible pain on my left side and shoulder. I thought I was having a heart attack.”

This happened on his way to the city to buy clothes for his first grandchild. He got off at Flinders Street Station, hailed a guard, explained he was unwell and to call an ambulance, which took him straight to hospital.

“Had I been home having a snooze, I probably wouldn’t have woken up. It was very confronting,” he said.

Seven years prior, Ken, was diagnosed with polycythaemia vera (PV), aged 43, after going to his GP about a sore foot. It turned out to be an ischaemic toe that was pre-gangrenous, and he was told to go straight to hospital. That’s where he spent Easter 1998, not camping as planned!

“I was very lucky to find, quite early in my journey, someone who said, ‘yeah I think I know what it is’,” said Ken.

But first, he “fell into the hands of surgeons” who looked at how to remove his toe. They tried to find the cause and thinking there may be a blockage, Ken had an angiogram. He was also told, ‘your blood is like jam’.

“It never clicked…why it was like jam?” said Ken.

Ken and two of his rescue dogs
Ken and two of his rescue dogs

“When they couldn’t work out what the problem was, I was sent to a hospital physician. She took one look at me and my blood results and said, ‘I think I know exactly what the situation is’.

“I had that classic ruddy complexion of polycythaemia,” said Ken, and his haematocrit “was quite high”.

She referred him to a specialist professor but when the result of a bone marrow biopsy was ‘MPD unspecified’, Ken went back to the physician.

“She said, ‘I’m pretty sure it’s polycythaemia’ and referred me to a specialist haematologist,” said Ken, who was originally diagnosed with an MPD.

“I was told I had a myeloproliferative disorder and said, ‘how do you spell that’? It wasn’t named a neoplasm until a few years later.

“When I was first diagnosed, I was quite shocked,” said Ken, because his haematologist had no information to give him and he was strongly advised against looking on the internet.

“I was working in IT at the time, so I went on what was then Alta Vista (before Google) and it came up with the backend of an insurance company that basically said, ‘do not insure – dead within five years of diagnosis’, so I thought, okay this is serious.”

Not much online support was available either, but there were online email lists in the UK and U.S.

“Because I was in the tech industry, I quickly joined up,” said Ken, who came across a fellow Australian with the disease “who was very knowledgeable”.

“He helped me with the ins and outs of the MPDs and as there was no Australian email list, he encouraged me to set one up,” said Ken, which he did in September 1998.

“That’s how I got to be an advocate in MPDs.”

Ken has since run the Australian MPN email list “in various forms and on various platforms”. It started with 10 subscribers and at the last count had 233 Australians and New Zealanders.

Over the intervening years, Ken has had a strong connection to people with MPN and has been very active with the MPN Alliance Australia which is a Leukaemia Foundation-associated patient group.

“A lot of people just don’t know what’s available to them and many say, ‘I’m not happy with my specialist’.

“I refer people to the Leukaemia Foundation’s support services, and talk about advocacy and what their rights are as patients. A lot of them have absolutely no idea that you can actually ask for a second opinion and simple things like asking a doctor to write things down.”

Ken’s professional background is secondary teaching and he’s worked in youth homelessness and disability. Now he works part-time – four days a week – for a primary care partnership in Victoria in the area of patient advocacy within health services.

“Because I’ve got the lived experience, I’ve got a lot to contribute in that area.”

Ken’s treatment protocols

After being diagnosed, Ken had a venesection every two to three months until the spleen incident in 2005, when his medication was changed to hydroxyurea (Hydrea®), which Ken reacted to “very badly”.

“Within four months, I had massive ulceration from my lips down through my trachea into my upper respiratory area, and incredible ulceration on my legs.

“They quickly took me off Hydrea and put me on interferon. For six to seven years I was on quite a high dose, which I self-injected at night five times a week.

“I felt incredibly exhausted, and I think it was the cause of peripheral neuropathy in my feet.”

Ken was on interferon from 2006 until January 2019 when he went on pegylated interferon alfa-2a (Pegasys®).

“I worked closely with Nathalie Cook [a fellow MPN advocate] to get pegylated interferon on the Pharmaceutical Benefits Scheme,” he said.

“Now I’m on 45mg of Pegasys once a week. My bloods are controlled, I’ve got a lot more energy, I don’t feel tired, and I find it much easier to take than Roferon®-A [interferon alfa-2a].

“I’ve got a routine. Every Saturday night I do my injection; subcutaneously either into my stomach or thighs, where there’s a bit of meat, and it’s very straight forward.”

Over his 20 years with MPN, Ken has had three bone marrow biopsies; in 1998, 2001 and 2018.

“There’s been very little progress of fibrosis. It’s still polycythaemia and it’s still controlled,” he said.

Ken Young with his wife, Claire, standing near the ocean.
Ken Young with his wife, Claire.

Living with an MPN 

“I’ve had MPN for a significant chunk of my life. It’s just part of who I am, and I just get on with it,” said Ken.

“In retrospect, having the diagnosis hasn’t limited my enjoyment in life. It’s extended it in a way that makes me want to be part of a wider community of people, and it’s quite a sharing and positive experience.

“You get to a point in life where different things are important and for me it’s being able to make a difference.

“Part of the problem with getting a blood cancer is the sense of helplessness,” said Ken.

“I can’t change the diagnosis – that’s happened. I can’t change the treatment – that’s just going to happen, but I can change other things for other people… making sure there’s information and support services.

“For me it’s working out what you can change and focusing on that. There’s so much of life you can’t control – it’s about being active where you can.

Ken’s advice

“Educate yourself,” said Ken.

“It’s not about becoming an academic and reading scientific papers. There are ways of getting information that are quite accessible and there are some wonderful YouTube presentations from MPN specialists that you can sit and listen to.

Here’s Ken’s ‘go-to’ list:

www.patientpower.info
www.mpnallianceaustralia.org.au
www.mpnvoice.org.uk
www.mpnadvocacy.com

“And this may be a blokey comment… but a lot of males won’t address health issues and tend to have a ‘she’ll be right’ attitude.

“It’s really important to share when you’re not feeling well, and things change.

“I know a lot of people, myself included in some respects, who tend to be a bit stoic.

“The important thing is to know your changes, notice what’s happening to your body and to yourself, and share this with the people around you.

“There’s probably a reason that you should investigate.”

How the MPN field has progressed

“When I was first diagnosed no one knew what caused MPN,” said Ken.

“The whole thing has changed. Understanding at the genetic level has changed dramatically and the understanding of the JAK2 and other genetic mutations has opened up all sorts of treatment options, particularly with the JAK2 inhibitor drugs.

“There are discoveries that MPNs have links to inflammation. There’s the development of immunotherapies, and the potential for targeted treatment in the CAR T-cell area is something that is completely revolutionary.

“None of that was around 20 years ago. Where we’ve come from, to where we are now, is quite amazing,” he said.

“Now in Australia there are dedicated MPN research groups like the work Steven Lane is doing in Brisbane and Kate Burbury at Walter and Eliza Hall Institute and Peter McCallum Cancer Centre, Andrew Perkins at Monash, David Ross in Adelaide, and Wendy Erber and her team in Perth.

“And there’s more research in the U.S. and UK looking at the whole notion of what’s driving these diseases that offers a whole new way of looking at them and new treatment patterns.

“The main treatment option for people at the moment – if you can do it – is a bone marrow transplant, which has incredible risks.

“There may well be different treatment options. Who knows where it’s all heading. It’s an exciting time,” said Ken.

Where Ken is at with his MPN

“My disease is stable, and I’ll probably live my three score and ten years,” he said.

“I’m quite optimistic about my future actually. I’m not ruled by my disease or defined by it.

“I do other things that are positive contributions to the community,” said Ken, who with his wife, Claire, are foster carers.

New classifications of MPN mean better diagnostics and more definitive prognoses

New classifications of MPN mean better diagnostics and more definitive prognoses

How the MPNs are classified is set to change with eight new classifications based on the underlying mechanisms that drive the mutations, according to international MPN expert, Professor Tony Green.

His Green lab at Cambridge University has been pivotal in identifying the new genetic groups that are expected to replace the “conventional way” of categorising people with MPN used “for 100 years or more”.

Professor Tony Green
Professor Tony Green

Early in his career, Professor Green found haematology “fascinating” because it allowed him to do research that he couldn’t have done in other areas of medicine.

“You get blood cancer in the blood and in the bone marrow, where the action is. You can’t do that [research] in the brain very easily… patients tend to complain!” he said.

Although a consultant haematologist and “clinician by trade”, Prof. Green has spent 80% of his 30-year career in research leadership roles.

He heads his own research group, is the Head of the University of Cambridge Department of Haematology, Professor of Haemato-Oncology at the University of Cambridge, and Director of the Cambridge Stem Cell Institute. He also is a recent president of the European Hematology Association.

Research at the Green laboratory at Cambridge

The driver for most scientists, he says, is understanding how things work.

“Once you understand how things work, or how things have gone wrong in the case of a blood cancer, you can use that knowledge to manage patients with those diseases better. Whether it’s to diagnose them better, treat them better, or give them better information about their prognosis,” said Prof. Green whose lab works in three broad areas.

One uses information “we now have” to make a difference in the clinic, and the second is “more biological” – trying to understand how mutations cause the changes they do.

“How does a mutation in a particular gene, like JAK2, result in the sort of diseases that it does? How does it cause the stem cells to go wrong or the red blood cell progenitors to increase?” said Prof. Green.

“There’s a lot we don’t understand about the mechanisms there.

“Quite often, when you study something abnormal, you learn stuff about the normal, and vice versa,” said Prof. Green about the third area – the unexpected insights that are stumbled across, “such as discovering how the normal regulation of blood cell formation works while trying to understand how the mutations work and the pathways they are part of”.

Referring to the clinical impact of his research, Prof. Green highlighted two messages he thought MPN News readers might want to know from a paper titled Classification and Personalized Prognosis in Myeloproliferative Neoplasms, published in the New England Journal, in October 2018.

A new classification system for MPNs

The first was a new way of classifying the MPNs.

“Until now, we have used the old-fashioned terms to describe patients. We put them into categories – polycythaemia vera (ET), essential thrombocythaemia (ET), myelofibrosis (MF)… based on describing what we see in the patient… too many red cells, too many platelets. It’s a phenotype*-based classification,” Prof. Green explained.

“There are lots of different causes of too many red blood cells and lots of different causes of too many platelets.

“What you really want is a classification based on the underlying mechanisms. The mechanisms that drive these diseases are all the different mutations.

“We’ve looked at 2000 patients with many, many different mutations,” he said.

Based on genome classification, eight separate genomic groups were identified according to the mutations each patient had and covering the gamut of MPNs. And each of those eight groups included some people with what would have been called PV, some with what would have been called ET, and some with what would have been called MF.

“Those eight groups are defined by the real biological causes of these diseases,” said Prof. Green.

“I think this is going to be a much more robust and objective way of categorising patients, which will make it easier when it comes to doing clinical trials, which will have patients stratified into those eight groups rather than the rather subjective names that we give these diseases at the moment.”

The second aspect of the paper was the result of using the “very large database” of 2000 people and “all our clinical and molecular data to generate a way of giving an individual patient a personal prognosis, which is something we couldn’t do”.

“Because what tends to happen is… we put people into groups. We say you are low-risk or high-risk. But low-risk has a whole mixture of people in it and high-risk has a whole mixture of people in it. So, we didn’t know where an individual person fitted in.

“Now we have been able to do that,” said Prof. Green.

“Comparing data from a patient in the clinic to the 2000-patient data bank, we can say with some sort of confidence, ‘well Mrs Jones, you have approximately a 20% chance of developing AML five years from now’.”

Prof. Green expects patients would have polygenic tests** and those results would be combined with their age, gender, laboratory data, blood counts, etc.

“Put that all together and you can give somebody a much more personal idea of what their outlook might be,” he said.

The question now, Prof. Green said, was how this new form of classification would be implemented by individual clinicians and applied in clinical trials.

“It will take a little time for change to occur, and it will be interesting to see how quickly this is picked up and how rapidly it is used,” he said.

“I suspect it will be used more in clinical trials to begin with because you can stratify your patients going into a clinical trial into these eight groups.”

He also expects, initially, that this genomic approach will be compared with the conventional way of categorising patients in a controlled, clinical setting.

Prof. Green said applying the genomic classifications in the clinic would mean genomic sequencing of all MPN patients.

“There are quite a few steps that need to be put in place before this can be set up and run routinely in the clinic.”

World-leading MPN research

In 1995, the Green lab set up “the largest randomised clinical trial ever in any MPN” – the PT1 study.

“The group in Cambridge is unusual. We span everything from large clinical trials through to identifying the mutations, through to understanding what the mutations do,” said Prof. Green.

“Our main strength is trying to understand the disease, and the diagnosis and prognosis stage, which I think is really essential.

“I don’t work at the bench anymore,” said Prof. Green, who has up to 15 researchers in his lab – a mixture of a PhD students, technicians and post-docs.

“I try to sit down with them as a group once a week, and individually, which is variable but ideally is once a week.

“My role is to provide a bit of strategic direction and help keep the focus in the right place, rather than going off on tangents.”

He said some people on his team were good at making mouse models. One post-doc was “absolutely superb” at all the protein signaling-type approaches and transcription regulation – the molecular biology, and others have expertise in methylation changes – the cell biology of what’s going on.

“To understand a disease properly, you really need people to understand the cell biology,” said Prof. Green.

“Sometimes you get taken into apoptosis, or cell death. Sometimes you get taken down into mechanisms of receptor signaling, and other times you are down in the nucleus asking questions about transcription and chromatin.

“And, depending on where our results lead us and the sort of question we are trying to answer, the group evolves.”

What a difference 20 years makes

Prof. Green said the field “had moved fantastically over the last 20 years”.

“If you look across the blood cancers, the number of advances that have made an enormous difference to patients has been very exciting.

“One can point to several diseases where, 20 years ago, a patient with a particular cancer, would almost invariably be dead within five years.

“Now, they are alive and well 20 years later. They may not be completely cured, but what we have achieved has made an enormous difference.”

A word of advice

Prof. Green offered people with MPN some advice.

“This is so easy to say and very difficult to do… those with a very positive approach to their disease, who are just getting on with it and letting it interfere with their lives as little as possible – that has got to be the way to go.

“There is a lot of life to live out there, family to spend time with, all that stuff. Don’t let it [an MPN] get in the way. Easy to say, difficult to do.

“MPN has a relatively slow and long trajectory. They do progress; ET and PV slowly but surely over many years,” he said.

“If you follow somebody for sufficiently long, many will develop either MF, or the unlucky ones will develop acute myeloid leukaemia. But it is such a long trajectory that a large proportion of them will die from something else.

“Most come with chronic phase PV, or ET, and one of the things I absolutely say up front is… if you have got to have a disease, this is the one to have, because most people with chronic phase disease will die of something else, not their disease. They will die with their disease, but not from it.

“I try and give them the information we have about what their personal outlook might be. It’s too easy for people to think they have got a blood cancer and they are going to die, it’s not like that for MPNs,” said Prof. Green.

Professor Green’s holy grail

Prof. Green has two holy grails which he would like to see achieved during his career, and the first is “a targeted therapy that works”.

“The JAK2 inhibitors are not targeted to the mutation,” he said.

“We need a better way of targeting. What we want is a JAK2 inhibitor that only hits the mutant. That is a long way off, but it would be nice.

“And, then, in terms of the consequences, I’d like to really understand in humans how this mutation [JAK2] arises. We are starting to get this information. We can now do lineage tracing in man, so we can look at a patient and we can say ‘your JAK2 mutation arose when you were five’.

“But what we don’t know is how that mutation changed your stem cells back then. So, getting a better understanding of what is going on in the patient looking back is the second holy grail.”

The physical appearance or biochemical characteristic of an organism as a result of the interaction of its genotype and the environment.

** A polygenic score, also called a polygenic risk score, genetic risk score, or genome-wide score, is a number based on variation in multiple genetic loci and their associated weights.