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Sophie (5) lit up a room and was a little inspiration – New Ross Standard

By Stem Cell Doctors

Sophie Walsh, who left this world on Tuesday (18th) aged five, was a ray of sunshine who brightened up the lives of everyone who was fortunate enough to meet her.

Sophie, like most children her age, was due to start school this week. After a long, courageous battle with cancer, she succumbed to the illness that afflicted her over three years at Crumlin Children's Hospital on Tuesday.

Born a perfectly healthy child on July 3, 2015, into a loving home, her parents Sandra and Thomas were overjoyed to bring her back to her freshly decorated room in Lacken Valley.

Sophie met all her milestones but just before her second birthday, Thomas and Sandra sensed there was something wrong.

'She was going off her food. We went to doctors, hospitals a couple of times, both in Waterford and Wexford. Then back to the GP and CareDoc. They were all putting it down as a viral thing that would run its course but nothing seemed to be getting any better,' Thomas said.

They brought Sophie to CareDoc one Sunday evening and a doctor noticed a lump which was examined at University Hospital Waterford and the next day Sophie, Thomas and Sandra left for Crumlin, the first of many visits.

'Our lives changed overnight,' Sandra said. 'Our consultant sat us down and laid out a treatment plan which was going to be up to two years. The doctors said it was going to be an intensive time.'

Sophie was diagnosed with neuroblastoma, a cancer of the central nervous system.

The prognosis was 50/50 as Sophie had an amplified version of the illness which made it harder to treat. Thankfully Sophie responded very well to treatment and after a few weeks her energy levels started improving.

'She was back to being normal, except without the hair. She completed ten rounds of chemotherapy and had a break over Christmas and had surgery for her tumour, from which she recovered well. She had her own stem cell transplant in March,' Thomas said.

Throughout, Sandra and Thomas were staying in the Ronald McDonald House near Crumlin on and off, their every waking moment by her side as Sophie recovered from the transplant and had 14 rounds of radiotherapy in St Luke's, being administered a general anaesthetic every day.

She recovered from her treatment and had five rounds, once a month of immune-therapy.

'She finished that in January 2019 and then she was finished. There was no evidence of disease.'

Throughout Sophie couldn't enjoy the social interactions other children take for granted.

'She couldn't have a normal childhood as she was susceptible to infections. She could have cousins and friends around (sometimes). When we could, we did. She was in isolation for 100 days after her bone marrow transplant. Sophie made loads of friends at Crumlin. There were families from throughout Ireland we met up there and became good friends with. She was in Tir na ng playschool (when she could). She was looking forward to starting school.'

Throughout the spring of 2019 Sophie was in great health. 'Everything was going good. She loved her dolls. She loved watching Youtube. Watching kids playing with toys. She loved to play. When she was feeling up to it she wanted to play and when she wasn't she watched TV.'

Recalling a really happy child, an old soul in a child's body, her parents said she was ahead of her years in terms of her conversations and speech. 'She was around adults a lot between nurses and doctors. She had a great imagination. She could pick up a book and even if she couldn't understand the words she'd make up a story from the pictures.'

Sandra said: 'She was very witty; very quick off the mark. She was stubborn as well. If she didn't want to do anything you couldn't change her mind; it was set and that was it.

'We often said she was an old person wrapped up in a small person's body.'

Sophie enjoyed a magical trip to Disneyland with her parents, revelling in meeting Mickey Mouse and all the Disney characters she had seen on TV.

'She loved it!' they said.

Having enjoyed great health all spring of last year, something showed up in a routine scan midway during the summer.

'It was very small and they couldn't be 100 per cent. We had to wait and see what happened. She did a biopsy in September which confirmed she had relapsed and, at that stage, we knew she would have a very poor prognosis of five or six per cent. But we didn't give up hope because she had such a good response the first time around so we thought she could do it again. She had a tough road.'

Due to the location of the cancer within the femur and her tender age, the bone broke the day after the biopsy.

Undeterred Sophie went around in her buggy to trick or treat that Hallowe'en, totally embracing the chance to get dressed up.

'She adapted so well to every challenge. She had a nice Christmas.'

Sophie continued getting treatments after Christmas. 'The treatment she was on wasn't working as well as they liked and there was more progression on it. They switched her onto a different treatment again in February. We were running out of options at this stage.'

Sophie's condition was being kept at bay with the chemotherapy. She still had a good quality of life, but less energy.

'We had been told that the chemo would only work for so long and the cancer can find ways around it and gets used to it. We were always hoping for a miracle and that something would come along.'

Sophie enjoyed a great fifth birthday with friends and family in the garden.

A few weeks later, Aoibhinn's Pink Tie charity staff arranged a princess party at the Horse & Hound for her.

'She had wanted to meet Elsa and Anna. She had her cousins and there was face painting. That was her last good day.'

That evening Sophie started complaining of pain and her leg became more and more swollen.

She was admitted to University Hospital Waterford the following week and a CT scan showed quick progression of the tumour.

Sophie was transferred to Crumlin to help her pain management.

She died on Tuesday, August 18.

'It happened so suddenly. She was tired from treatment. There was one of us with her at all times; we took it in turns.'

Both Thomas and Sandra, who have been out of work since the diagnosis to care for Sophie, said: 'Everything changed so quickly and with the diagnosis and the prognosis we didn't want to wait a second. We didn't want to be looking back in five or ten years time that we had missed out. We had three amazing years. It was just the three of us, especially during lockdown it was nice just to have that time, the three of us.'

They praised the nursing staff of the hospitals Sophie as cared in.

Thomas said: 'Throughout, the whole community were amazing; especially neighbours and local businesses. Even just in terms of support. She was treated like a mini celebrity in The Bakehouse and O'Briens. Everywhere she went on the town everybody knew her and was so good to her. She was a little character as well. Every day she'd say something that made you laugh. She wasn't always in good form but she could change so quick. She would never dwell on things and never left her illness define her; she just kinda got on with it and never talked about it.'

Some of the nurses attended Sophie's funeral, as did staff members from McDonald's in Waterford, a favourite destination for Sophie.

'The nurses left off balloons outside for her. They were so good to her. If she wanted a dance party they held a dance party, copying her moves. The Dunbrody ship was lit up gold for Sophie, ahead of cancer awareness month in September. She would have been starting school this week. We had picked a school and she was looking forward to starting big school.'

Sandra and Thomas left the house on Friday morning for their daughter's funeral.

'All of the neighbours were lined up on either side of the road. We had a garda escort down. Fr Tom Orr gave a lovely, personal eulogy. He was excellent to us and even called to Crumlin to see her. Members of the United Striders stood as guards of honour, as did Urban Gym and Tr na Ng staff.'

'You Are My Sunshine' rang out from the speakers at her funeral Mass, where not a dry eye could be found.

Sophie was laid to rest in St Stephen's Cemetery, not far from her home.

The family want to thank everyone involved in sharing their love of Sophie on Friday, from the guards of honour to their neighbours and the wider community.

Sandra and Thomas said the Ronald McDonald House and Aoibhinn's Pink Tie charities were tremendously supportive throughout the three years.

'When a diagnosis comes, it's rushed and people arrive at John's Ward [in Crumlin] with just the clothes on their back. Even to have a toothpaste and brush.'

They recall in hushed tones, five years of happy memories with Sophie. 'Just being so happy; a family - the three of us. She could just light up a room; she had a presence about her. She would make anybody laugh and left a lasting impression on people who were just drawn to her. She could come out with anything. She told it as it was.'

They spoke of a child who inspired them to have a positive outlook on life and cherish each day as it comes, no matter what.

'For a five-year-old she was so happy go lucky. She inspired us. One day in the hospital she was colouring for the nurses and started colouring squiggles. I said why aren't you doing it properly and she said "life is too boring to just stay between the lines". There is a lot you can learn from a five-year-old, about outlook on life and how to deal with adversity. If Sophie spiked a temperature it means a few days in hospital and there was never any complaining.'

Sophie is dearly missed by Thomas and Sandra, her grandfathers Pat and Billy, aunts, uncles, cousins, extended family and friends.

New Ross Standard

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Sophie (5) lit up a room and was a little inspiration - New Ross Standard

Rare group of HIV patients don’t need drugs to suppress virus due to way it integrates in their DNA – Brinkwire

By Stem Cell Doctors

A woman diagnosed with HIV almost 30 years ago may have been cured of the virus without taking drugs or having a bone marrow transplant.

Scientists have studied Loreen Willenberg for decades, with the 66-year-old insisting she has never taken medication to keep the virus at bay. Doctors say her body fights the infection naturally.

But now academics claim she can be added to the list of cured HIV patients, next to theBerlin patient Timothy Ray Brown and the London patientAdam Castillejo.

Both Mr Brown, 54, and Mr Castillejo, 40, had cancer and were given a bone marrow transplant from adonor with HIV-resistant genes to wipe out their disease and the AIDS-causing virus in one fell swoop.

Ms Willenberg who was diagnosed in 1992 and is considered an elite controller because she possesses the rare ability to suppress the virus by itself never had the risky treatment.

Researchers at the Ragon Institute of MGH, MIT and Harvard found no traces of HIV in the Californian woman through standard tests.

Advanced technology that analysed 1.5billion of Ms Willenbergs blood cells found tiny quantities of the virus, meaning she isnt HIV-free. But the doctors revealed her immune system had rendered the leftover traces incapable of reproducing.

Dr Sharon Lewin, director of The Peter Doherty Institute for Infection and Immunity in Australia, told the New York Times: She could be added to the list of what I think is a cure, through a very different path.

Another 63 patients not on anti-retroviral drugs were also found to have traces of HIV that were unable to reproduce.

The team, whose work was published in the journal Nature, say the findings provide evidence that these people have achieved a functional cure.

Elite controllers are only believed to account for 0.5 per cent of the 37million people living with HIV across the world.

Researchers found that, because of where these patients have the virus encoded in their DNA, the pathogen is unable to make copies of itself. Thiskeeps the virus below detectable levels, which makes it untransmissible.

Once a person contracts HIV, the virus sets about attacking and destroying immune cells that normally protect the body from infection.

In the last decade, doctors have gained a much improved understanding of how to control HIV. The rate of deaths from the disease has plummeted since the peak of the AIDS epidemic in the early 1980s.

It is treatable and doctors recommend taking a combination or cocktail of drugs known as antiretroviral therapy, or ART.

Within six months of taking the medication once a day, a persons viral load will be virtually undetectable, but the body wont be completely rid of it.

This is because the virus hides in the body by integrating its genetic material into DNA and forming whats known as a latent reservoir.

But ART which can cause nausea, diarrhoea, headaches and fatigue isnt able to destroy these reservoirs but if an HIV patient ceases taking the cocktail, the virus can start making copies of itself again.

Elite controllers have latent reservoirs, but they dont need to take drugs to stop the virus from spreading throughout the body.

They naturally maintain what other people need ART to do, co-author Dr Mathias Lichterfeld, an infectious disease physician at Ragon, told HealthDay.

For the study, the team looked at blood samples from 64 elite controllers and 41 HIV patients taking ART.

Results showed that, in elite controllers, HIV genetic material was found in so-called gene deserts of the DNA. These are where there is little gene activity so the virus is unable to make copies of itself and instead remain in a blocked and locked state.

Lead author Dr Xu Yu, an associate professor of medicine at Harvard Medical School, said: This positioning of viral genomes in elite controllers is highly atypical.

In the vast majority of people living with HIV-1, HIV is located in the active human genes where viruses can be readily produced.

Dr Yu calls this a functional cure, which occurs when a virus is still in the body but can be controlled without medication.

The researchers believe this is because, in the early days of infection, the immune systems of elite controllers killed the virus after it integrated into DNA regions with a great deal of gene activity.

The team says the findings could lead to a cure, either by creating drugs that replicate the phenomenon of elite controllers or that eliminate HIV thats integrated in parts of the DNA that have substantial gene activity.

Elite controllers carry a mutation of CCR5, which prevents it from expressing, which essentially blocks the gene altogether. Experts say the genetic quirk has descended from northern Europeans.

The study comes after a Brazilian man in his mid-30s with HIV went into long-term remission after treatment with drugs and vitamin B3.

Doctors last month revealed the case of the Sao Paolo patient, who is understood to be the first HIV patient in the world to go into remission following pharmaceutical treatment.

And scientists last year revealed that a third HIV-positive patient in Germany may be free of the virus after undergoing the risky bone-marrow transplant.

But neither the Sao Paolo patient orthe Dsseldorf patient had been free of the virus for long enough to be considered cured.

For example, cancer patients have to be in remission for five years before they are labelled as cured.

Unfortunately, the Berlin and London patients cases do not change the reality much for the millions of people living with HIV.

The treatment is unlikely to have potential on a wider scale because both Mr Castillejo and Mr Ray Brown were given stem cells to treat cancer, not HIV.

Stem cell and bone marrow transplants are life-threatening operations with huge risks. Dangers lie in the patient suffering a fatal reaction if substitute immune cells dont take.

Mr Ray Brown, who is from Seattle but was treated in Germany, has been HIV-free for 12 years without medication.

But Mr Castillejo, whose mental health had spiralled drastically over the years and even led him to consider ending his life, was only treated in 2016.

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Rare group of HIV patients don't need drugs to suppress virus due to way it integrates in their DNA - Brinkwire

Hematopoietic Stem Cell Transplantation (HSCT) Market boosting the growth Worldwide: Market dynamics and trends, efficiencies Forecast 2022 -…

By Stell Cell Research

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Hematopoietic Stem Cell Transplantation (HSCT) Market boosting the growth Worldwide: Market dynamics and trends, efficiencies Forecast 2022 -...

Global Cell Proliferation Kit Market Insights And Extensive Research (2020-2025) : Biological Industries, Thermo Fisher – The Daily Chronicle

By Stell Cell Research

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Global Cell Proliferation Kit Market Insights And Extensive Research (2020-2025) : Biological Industries, Thermo Fisher - The Daily Chronicle

Foetal cells are used to make the Oxford coronavirus vaccine. But they came from a foetus in 1973 – ABC News

By Stell Cell Research

Religious leaders have raised ethical doubts over one of Australia's primary coronavirus vaccine hopes because scientists have used foetal cells in its development.

Developers at Oxford University and pharmaceutical firm AstraZeneca are using cell lines from an electively aborted foetus in the vaccine candidate, with Anglican, Catholic and Greek Orthodox leaders questioning the practice.

But using foetal cells in vaccine development isn't new and the Catholic Church has previously expressed qualified support for the use of vaccines derived from these cells under certain circumstances.

We spoke to Bill Lott, a virologist at QUT's Institute of Health and biomedical innovation, to understand the role of foetal cells in vaccine development.

The foetal cells used in vaccine development are derived from a small number of foetuses which were legally terminated decades ago.

The Oxford vaccine uses HEK (human embryonic kidney) 293 cell lines, obtained from a female foetus in the Netherlands in 1973.

"We're using tissues that were from foetuses that were aborted 40, 50, 60 years ago," Dr Lott said.

"It doesn't require newly aborted foetuses."

While living human cells can only divide around 50 times, those foetal cells have been genetically modified so they can divide an infinite number of times.

"That's why we can use the cells that we harvested [decades ago] today," Dr Lott said.

"They're not the actual original cells, they've been immortalised and then propagated over the decades."

This means we'll never need to replace specimens used in development.

"Just by analogy, buying ivory is illegal [because] if you create a market for ivory, then it creates the demand to kill more elephants," Dr Lott said.

"In this case, that's not happening because these foetuses were aborted 60 years ago, 50 years ago, and using these immortalised tissues now is not going to create a need to go and get new ones."

In fact, scientists would prefer to keep using HEK 293 cell lines because they have been repeatedly tried and tested in a laboratory setting and found to be safe.

"When you're making a vaccine you require safety testing," Dr Lott said.

"If we went back and used a different cell type, you're throwing an unknown into the consideration.

"So that will severely slow down your ability to make these things.

"Using HEK 293, we've used it for decades and we know that it's safe."

This week, Australia's Deputy Chief Medical Officer Nick Coatsworth pointed out the use of foetal cells had been a "reality" in past vaccine development.

"The reality for vaccines is that they need cell cultures in order for us to grow them," he said.

"The human cell is a really important part of their development.

"There are strong ethical regulations surrounding the use of any type of human cell, particularly foetal human cells.

"This is a very professional, highly powered research unit at Oxford University.

"I think we can have every faith that the way they have manufactured the vaccine has been against the highest of ethical standards internationally."

Breaking down the latest news and research to understand how the world is living through an epidemic, this is the ABC's Coronacast podcast.

So, how do foetal cells help with vaccine development? Dr Lott explained they operate like a "vaccine factory".

First, scientists need to develop the vaccine candidate and then combine it with an adenovirus vector.

An adenovirus is a particular type of common virus that causes illnesses like bronchitis, pneumonia and a sore throat.

For instance, when you get a cold, you may be infected with an adenovirus, a coronavirus or a rhinovirus.

A vector is an organism that spreads infection by moving pathogens from one host to another.

So an adenovirus vector? "That's an adenovirus that has been sort of emptied out and then you put a different kind of genome in there to make protein," Dr Lott said.

The next step is to put the vaccine/adenovirus vector combination into a big vat of foetal cells.

"The viral vector infects these HEK 293 cells really, really efficiently," Dr Lott said.

"One reason why you use the HEK 293 is because you get essentially 100 per cent infection with the adenoviral vector.

"And what it does is it turns the HEK 293 cells into a vaccine factory."

What do we mean by "vaccine factory"? Dr Lott explains foetal cells begin producing "tons and tons of that modified adenovirus" which they then "spit out into the liquid bit of the cells" called the cell culture media.

"[The foetal cells] start cranking out this massive amount of modified adenovirus, and then you purify those things away from the cell tissue," he said.

"You pull the [cell] media off, and it's just going to be full of the vaccine and essentially no tissue.

"And that's what your vaccine is."

The foetal cells will operate as this "vaccine factory" regardless of whether the vaccine is effective or not so the next step generally involves animal and then human trials of varying scale.

Inherent in the whole process is stripping away the conditioned cell media, where the foetal cells are contained.

The head of the World Health Organization has warned we may never get a silver bullet for COVID-19. What could that future look like in Australia?

That means a successful vaccine developed using foetal cells will have no remnants of those cells in the final product.

"You purify the vaccine away from the cells that they were grown in, and then you destroy all the cells," Dr Lott said.

"So then you're going to take that liquid and you'll purify it some more, but there are not going to be any [foetal] cells in there.

"There's nothing left when it becomes the vaccine that gets delivered."

Foetal tissue has been used with innovative effect in various strands of medical research.

The difference is some of those processes require fresh foetal cells not the "immortalised" cells vaccine developers can use.

"The vaccine work is pretty straightforward," Dr Lott said.

"But cancer research, the research into the mechanisms of various things cystic fibrosis, haemophilia, rheumatoid arthritis that all required fresh foetal tissue."

Scientists studying Zika virus used foetal cells to discover that the virus crossed the placental membrane and caused brain damage in unborn foetuses.

"[That research] brought out a whole raft of therapies and protections for unborn foetuses [and] "saved a lot of lives, including [the lives of] unborn foetuses," Dr Lott said.

Foetal cell lines have been used in the development of various vaccines, including for chicken pox, Ebola, polio, rubella, shingles, Hepatitis A, and rabies.

Foetal tissue has also facilitated breakthroughs in the treatment of various medical issues including cystic fibrosis, haemophilia, IVF, Parkinson's and Alzheimer's diseases, AIDS, and spinal cord injuries.

Scientists have many different methodologies for developing vaccines and there are a variety of reasons why foetal cells aren't always used.

Billions are being poured into the race to find a coronavirus vaccine, with the winner owning a powerful political tool. During the last pandemic an Australian company got there first.

"Some of them don't use it because of ethical issues," Dr Lott said.

"Some of them don't use it because they're not using an adenovirus [vector], so they don't really need the HEK 293.

"And there are other [development] strategies.

"There's an mRNA strategy that's very popular.

"So some of them don't require it."

The development of a coronavirus vaccine was time critical because of the virus' devastating public health and economic impacts, Dr Lott said.

Therefore, it was important for scientists to diversify their methodologies in order to develop a vaccine as quickly as possible.

Both stem cells and foetal cells are critical to innovations in medical research but what's the difference between the two?

Dr Lott explains stem cells are basically the earliest iteration of a foetal cell before the cell differentiates itself into, for example, a hair cell, liver cell, eye cell or skin cells.

"A stem cell is simply a cell that can turn into a different cell types," Dr Lott said.

"That first embryonic stem cell can eventually turn into any kind of cell in your body.

"So you've got embryonic stem cells, and then you've got adult stem cells, and in between are the foetal stem cells [which] are partially differentiated.

"So foetal cells contain not only stem cells some of the foetal cells have already differentiated into their final cell type."

In 2005 and again in 2017, the Catholic Church expressed qualified support for the use of foetal-cell-derived vaccines but only if there was no available alternative.

A 2005 "moral reflection" issued by Pope Benedict XVI specifically addressed the issue.

"As regards the diseases against which there are no alternative vaccines which are available and ethically acceptable, it is right to abstain from using these vaccines if it can be done without causing children, and indirectly the population as a whole, to undergo significant risks to their health," the Pope wrote.

"However, if the latter are exposed to considerable dangers to their health, vaccines with moral problems pertaining to them may also be used on a temporary basis.

"We find a proportional reason, in order to accept the use of these vaccines in the presence of the danger of favouring the spread of the pathological agent."

In 2017, the life ethics arm of the Catholic Church issued a statement that: Catholic parents could vaccinate their children with a "clear conscience" that "the use of such vaccines does not signify some sort of cooperation in voluntary abortion".

Earlier this year and in the context of the coronavirus vaccine race, John Di Camillo, an ethicist with the National Catholic Bioethics Center, confirmed: "One is allowed to make use of [vaccine derived from foetal tissue] where there's a serious threat to the health or life of the individual, or of the greater population.

"This does not amount to a strictobligationto use it, but it certainly can be a legitimate choice in conscience if theres that serious reason, and there's no other reasonable alternative."

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Foetal cells are used to make the Oxford coronavirus vaccine. But they came from a foetus in 1973 - ABC News

Impact Of Covid-19 Outbreak On Global Automated Cell Culture Market Segment Analysis and 2020-2024 Future Projection Level – The Daily Chronicle

By Stell Cell Research

The research study Automated Cell Culture market 2020 available by ABRReports.com provides the detailed insights about factors affecting the market growth as well as detailed analysis of the market structure along with forecast of the various segments and sub-segments of the global market

Access the PDF Sample Copy of the report at https://www.abrreports.com/industry-insights/global-automated-cell-culture-industry-market-research-2019?form=request-report-sample

The objective of the Study:

The key purpose of the study to track and analyze competitive developments such as joint ventures, strategic alliances, mergers and acquisitions, new product developments, and research and developments in the global Automated Cell Culture market. The report provides historical and forecast revenue of the market segments and sub-segments with respect to four main geographies and their countries- North America, Europe, Asia, Latin America and the Rest of the World. The study delivers country-level analysis of the market with respect to the current market size and future perspective as well as country-level analysis of the market for segment by application, product type, and sub-segments country-level analysis of the market for segment by application, product type, and sub-segments

Access full research report with Table of Content at https://www.abrreports.com/industry-insights/global-automated-cell-culture-industry-market-research-2019

Key market segmentation as below:

Key players in global Automated Cell Culture market include: BD Tecan Trading Sartorius TAP Biosystems Cell Culture Company Eppendorf Merck KGaA Hamilton Company Thermo Fisher Scientific OCTANE BIOTECH

Market segmentation, by product types: Automated Cell Culture Storage Equipment Automated Cell Culture Vessels Automated Cell Culture Supporting Instruments Bioreactors

Market segmentation, by applications: Drug Development Stem Cell Research Cancer Research

Market segmentation, by regions: North America Europe Asia Pacific Middle East & Africa Latin America

In this report, we analyze the Automated Cell Culture industry from two aspects. One part is about its production and the other part is about its consumption. In terms of its production, we analyze the production, revenue, gross margin of its main manufacturers and the unit price that they offer in different regions from 2014 to 2019. In terms of its consumption, we analyze the consumption volume, consumption value, sale price, import and export in different regions from 2014 to 2019. We also make a prediction of its production and consumption in coming 2019-2024.

At the same time, we classify different Automated Cell Culture based on their definitions. Upstream raw materials, equipment and downstream consumers analysis is also carried out. What is more, the Automated Cell Culture industry development trends and marketing channels are analyzed. Finally, the feasibility of new investment projects is assessed, and overall research conclusions are offered.

The report can answer the following questions: 1. What is the global (North America, South America, Europe, Africa, Middle East, Asia, China, Japan) production, production value, consumption, consumption value, import and export of Automated Cell Culture? 2. Who are the global key manufacturers of Automated Cell Culture industry? How are their operating situation (capacity, production, price, cost, gross and revenue)? 3. What are the types and applications of Automated Cell Culture? What is the market share of each type and application? 4. What are the upstream raw materials and manufacturing equipment of Automated Cell Culture? What is the manufacturing process of Automated Cell Culture? 5. Economic impact on Automated Cell Culture industry and development trend of Automated Cell Culture industry. 6. What will the Automated Cell Culture market size and the growth rate be in 2024? 7. What are the key factors driving the global Automated Cell Culture industry? 8. What are the key market trends impacting the growth of the Automated Cell Culture market? 9. What are the Automated Cell Culture market challenges to market growth? 10. What are the Automated Cell Culture market opportunities and threats faced by the vendors in the global Automated Cell Culture market?

Purchase the research report @ https://www.abrreports.com/industry-insights/global-automated-cell-culture-industry-market-research-2019/checkout?option=one

Table of Contents 1 Industry Overview of Automated Cell Culture 2 Industry Chain Analysis of Automated Cell Culture 3 Manufacturing Technology of Automated Cell Culture 4 Major Manufacturers Analysis of Automated Cell Culture 5 Global Productions, Revenue and Price Analysis of Automated Cell Culture by Regions, Manufacturers, Types and Applications 6 Global and Major Regions Capacity, Production, Revenue and Growth Rate of Automated Cell Culture 2014-2019 7 Consumption Volumes, Consumption Value, Import, Export and Sale Price Analysis of Automated Cell Culture by Regions 8 Gross and Gross Margin Analysis of Automated Cell Culture 9 Marketing Traders or Distributor Analysis of Automated Cell Culture 10 Global and Chinese Economic Impacts on Automated Cell Culture Industry 11 Development Trend Analysis of Automated Cell Culture 12 Contact information of Automated Cell Culture 13 New Project Investment Feasibility Analysis of Automated Cell Culture 14 Conclusion of the Global Automated Cell Culture Industry 2019 Market Research Report

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Impact Of Covid-19 Outbreak On Global Automated Cell Culture Market Segment Analysis and 2020-2024 Future Projection Level - The Daily Chronicle

Genetic mutations may be linked to infertility, early menopause – Washington University School of Medicine in St. Louis

By Stell Cell Research

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Gene in fruit flies, worms, zebrafish, mice and people may help explain some fertility issues

Researchers at Washington University School of Medicine in St. Louis have identified a gene that plays an important role in fertility across multiple species. Pictured is a normal fruit fly ovary (left) and a fruit fly ovary with this gene dialed down (right). Male and female animals missing this gene had substantially defective reproductive organs. The study could have implications for understanding human infertility and early menopause.

A new study from Washington University School of Medicine in St. Louis identifies a specific genes previously unknown role in fertility. When the gene is missing in fruit flies, roundworms, zebrafish and mice, the animals are infertile or lose their fertility unusually early but appear otherwise healthy. Analyzing genetic data in people, the researchers found an association between mutations in this gene and early menopause.

The study appears Aug. 28 in the journal Science Advances.

The human gene called nuclear envelope membrane protein 1 (NEMP1) is not widely studied. In animals, mutations in the equivalent gene had been linked to impaired eye development in frogs.

The researchers who made the new discovery were not trying to study fertility at all. Rather, they were using genetic techniques to find genes involved with eye development in the early embryos of fruit flies.

We blocked some gene expression in fruit flies but found that their eyes were fine, said senior author Helen McNeill, PhD, the Larry J. Shapiro and Carol-Ann Uetake-Shapiro Professor and a BJC Investigator at the School of Medicine. So, we started trying to figure out what other problems these animals might have. They appeared healthy, but to our surprise, it turned out they were completely sterile. We found they had substantially defective reproductive organs.

Though it varied a bit by species, males and females both had fertility problems when missing this gene. And in females, the researchers found that the envelope that contains the eggs nucleus the vital compartment that holds half of an organisms chromosomes looked like a floppy balloon.

This gene is expressed throughout the body, but we didnt see this floppy balloon structure in the nuclei of any other cells, said McNeill, also a professor of developmental biology. That was a hint wed stumbled across a gene that has a specific role in fertility. We saw the impact first in flies, but we knew the proteins are shared across species. With a group of wonderful collaborators, we also knocked this gene out in worms, zebrafish and mice. Its so exciting to see that this protein that is present in many cells throughout the body has such a specific role in fertility. Its not a huge leap to suspect it has a role in people as well.

To study this floppy balloon-like nuclear envelope, the researchers used a technique called atomic force microscopy to poke a needle into the cells, first penetrating the outer membrane and then the nucleuss membrane. The amount of force required to penetrate the membranes gives scientists a measure of their stiffness. While the outer membrane was of normal stiffness, the nucleuss membrane was much softer.

Its interesting to ask whether stiffness of the nuclear envelope of the egg is also important for fertility in people, McNeill said. We know there are variants in this gene associated with early menopause. And when we studied this defect in mice, we see that their ovaries have lost the pool of egg cells that theyre born with, which determines fertility over the lifespan. So, this finding provides a potential explanation for why women with mutations in this gene might have early menopause. When you lose your stock of eggs, you go into menopause.

On the left is a normal fruit fly ovary with hundreds of developing eggs. On the right is a fruit fly ovary that is totally missing the NEMP gene. It is poorly developed and no eggs are visible.

McNeill and her colleagues suspect that the nuclear envelope has to find a balance between being pliant enough to allow the chromosomes to align as they should for reproductive purposes but stiff enough to protect them from the ovarys stressful environment. With age, ovaries develop strands of collagen with potential to create mechanical stress not present in embryonic ovaries.

If you have a softer nucleus, maybe it cant handle that environment, McNeill said. This could be the cue that triggers the death of eggs. We dont know yet, but were planning studies to address this question.

Over the course of these studies, McNeill said they found only one other problem with the mice missing this specific gene: They were anemic, meaning they lacked red blood cells.

Normal adult red blood cells lack a nucleus, McNeill said. Theres a stage when the nuclear envelope has to condense and get expelled from the young red blood cell as it develops in the bone marrow. The red blood cells in these mice arent doing this properly and die at this stage. With a floppy nuclear envelope, we think young red blood cells are not surviving in another mechanically stressful situation.

The researchers would like to investigate whether women with fertility problems have mutations in NEMP1. To help establish whether such a link is causal, they have developed human embryonic stem cells that, using CRISPR gene-editing technology, were given specific mutations in NEMP1 listed in genetic databases as associated with infertility.

We can direct these stem cells to become eggs and see what effect these mutations have on the nuclear envelope, McNeill said. Its possible there are perfectly healthy women walking around who lack the NEMP protein. If this proves to cause infertility, at the very least this knowledge could offer an explanation. If it turns out that women who lack NEMP are infertile, more research must be done before we could start asking if there are ways to fix these mutations restore NEMP, for example, or find some other way to support nuclear envelope stiffness.

This work was supported by the Canadian Institutes of Health, research grant numbers 143319, MOP-42462, PJT-148658, 153128, 156081, MOP-102546, MOP-130437, 143301, and 167279. This work also was supported, in part, by the Krembil Foundation; the Canada Research Chair program; the National Institutes of Health (NIH), grant number R01 GM100756; and NSERC Discovery grant; and the Medical Research Council, unit programme MC_UU_12015/2. Financial support also was provided by the Wellcome Senior Research Fellowship, number 095209; Core funding 092076 to the Wellcome Centre for Cell Biology; a Wellcome studentship; the Ontario Research FundsResearch Excellence Program. Proteomics work was performed at the Network Biology Collaborative Centre at the Lunenfeld-Tanenbaum Research Institute, a facility supported by Canada Foundation for Innovation funding, by the Ontarian Government, and by the Genome Canada and Ontario Genomics, grant numbers OGI-097 and OGI-139.

Tsatskis Y, et al. The NEMP family supports metazoan fertility and nuclear envelope stiffness. Science Advances. Aug. 28, 2020.

Washington University School of Medicines 1,500 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is a leader in medical research, teaching and patient care, ranking among the top 10 medical schools in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

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Genetic mutations may be linked to infertility, early menopause - Washington University School of Medicine in St. Louis

Equipping the Immune System to Fight Against COVID-19 – BioSpace

By Stem Cell Treatment

The coronavirus that causes COVID-19 has one major advantage over us it is a new human virus. Most people have not encountered the virus before, meaning their immune system is not primed and ready to fight it. When someone gets sick with COVID-19, there is a lag in an efficient immune response, giving the virus time to do significant damage before the immune system can reign in the infection.

It essentially becomes a race between how fast your immune system can clear the virus and how quickly the virus can replicate and induce damage, Agustin Melian, MD, Chief Medical Officer and Head of Global Medical Sciences at AlloVir, told BioSpace.

To develop an effective treatment or vaccine for COVID-19, scientists must understand how the immune system is impacted during the disease. One type of immune cell that is particularly important in the bodys response to COVID-19 is T-cells. T-cells perform many functions, including recognizing invading viruses such as the coronavirus that causes COVID-19.

Multiple studies from Wuhan, China reported that COVID-19 patients had very low T-cell counts; the sicker the patient, the lower their T-cell count. Lower T-cell counts were correlated with poorer outcomes (including higher risk of death) and T-cells isolated from COVID-19 patients also showed signs of exhaustion.

The elderly, patients with low T-cell numbers, and patients who express exhaustion markers on their T-cells are high risk groups in which nave cell responses (responses against a virus they have never seen before) may be deficient or delayed, thus allowing the virus to induce a large amount of damage, Dr. Melian explained. These patients may, therefore, benefit from AlloVirs approach which is designed to restore natural T-cell immunity in high risk patients.

Could giving high-risk COVID-19 patients functional T-cells against the coronavirus boost their immune system and help them recover? This is the question AlloVir aims to answer.

AlloVir creates allogeneic (off-the-shelf) virus-specific T-cells designed to treat common and devastating viral-associated diseases in vulnerable patients, such as those who are immunocompromised or patients who received an organ or stem cell transplant. Now, they are expanding their anti-viral T-cell arsenal and taking aim at COVID-19.

We believe AlloVirs technology is well positioned to treat patients with COVID-19 because our technology is designed to provide SARS-CoV-2 specific T-cell immunity while leaving non-infected cells intact, Dr. Melian commented. Our virus-specific T-cell candidates have been used to treat more than 275 immunocompromised patients with life-threatening viral infections and diseases and we believe it our approach may also have promise in treating COVID-19.

Fighting viruses with T-cells in immunocompromised patients

When you get infected with a virus, your immune system responds to the foreign threat by making specific T-cells that can recognize the virus. These specific T-cells prompt your immune system to destroy any cells infected by the virus.

However, if you have a T-cell deficiency, your immune system cannot robustly protect you. This is a major problem because an otherwise innocuous virus can become a serious infection, causing complications, and possibly even be life-threatening.

That is where AlloVir comes in. They address the underlying problem the weakened immune system. A weakened immune system can be beefed up by giving patients with T-cell deficiencies off-the-shelf virus-specific T-cells (VSTs) originally taken from healthy people. This restores their natural T-cell immunity and helps their immune system fight off the viruses.

At AlloVir, we are a leading innovator in discovering and developing allogeneic, virus-specific T-cell immunotherapies, Dr. Melian said. We are now excited to be applying our capabilities in discovering and developing SARS-CoV-2 specific T-cells to join the fight in developing a COVID-19 program for patients at high risk of severe and devastating disease.

AlloVirs virus-specific T-cell platform

To create AlloVirs T-cell therapies, the target virus is first studied carefully to identify its specific antigens (unique molecules on the outside of each virus that are specific to the virus and alert the immune system). The best antigens those that induce a strong T-cell response are used to create the therapy.

Next, blood is taken from healthy donors who have been exposed to the virus of interest and T-cells are isolated from the blood. The T-cells are activated in the lab they are trained to recognize the identified viral antigens, enabling the T-cells to selectively recognize only the desired virus.

After the T-cells have learned to recognize the specific virus, they are expanded to generate multitudes of cells. Once the activated, specific T-cells are created, they can be cryopreserved and kept for a long time, making them readily available as soon as a patient needs them. The entire process, from antigen selection to donor to ready-to-go T-cell treatment, can be completed in a matter of weeks. This process can be seen in the visual below.

Source: AlloVir

Patients are matched using the companys proprietary human leukocyte antigen (HLA)-matching formula. HLAs are proteins on the surface of cells that regulate the immune system.

Our proprietary donor selection algorithm, known as Cytokin enables us to cover >95 percent of patients in our target population from cells derived from a small number of donors, Dr. Melian said. This proprietary process of prospectively manufacturing cells for off-the-shelf use enables us to study our allogeneic cell therapies in large numbers of patients that suffer from global health crises, like seasonal influenza and, as we are discussing, the COVID-19 pandemic.

These T-cells are advantageous because they are active against a single virus or multiple viruses, are not patient-specific (so they are readily available) and are a single treatment that provides lasting protection. The biggest bonus is the immediate off-the-shelf use for time-sensitive infections in vulnerable populations, added Dr. Melian.

In addition to developing their COVID-19 therapy (called ALVR109), AlloVir has two other multi-virus specific T-cell therapies in development: Viralym-M (ALVR105) and ALVR106. Both therapies focus on treating viral diseases common to stem cell and solid organ transplant patients and other vulnerable populations.

Viralym-M targets six common viruses: BK virus (BKV), cytomegalovirus (CMV), adenovirus (AdV), Epstein-Barr virus (EBV, also called human herpesvirus 4), human herpesvirus 6, and JC virus (also called human polyomavirus 2). Although these viruses are widespread and infect most people, they only cause severe problems in people with weakened immune systems due to age, organ or stem cell transplant, or disease (such as diabetes or AIDS). In a Phase 2 study, 93 percent of 38 allogeneic stem cell transplant patients had a clinical response to Viralym-M treatment and functional Viralym-M cells lasted up to 12 weeks in the patients.

ALVR106 targets four common respiratory viruses: influenza, parainfluenza virus, respiratory syncytial virus (RSV), and human meta-pneumovirus (HMPV). While these viruses tend to cause mild to moderate respiratory illnesses, they can cause severe, life-threatening illness, especially in people with weakened immune systems. ALVR106 is still in preclinical development but clinical trials are expected to begin this year. Overall, AlloVir expects to have three new proof-of-concept (POC) Phase 1b/2 and three pivotal Phase 3 studies started over the next 6-18 months.

Off-the-shelf T-cells against COVID-19

While AlloVir originally designed their T-cell therapies for transplant patients, their platform can potentially be applied to any virus to create virus-specific T-cells. This versatility allowed AlloVir to pivot and create T-cells against SARS-CoV-2, the virus that causes COVID-19. This new investigational therapy, called ALVR109, is being developed as a stand-alone treatment, though it may also be incorporated into their ALVR106 respiratory virus therapy at some point in the future.

Normally, the body would make virus-specific T-cells on their own and these would clear the virus, commented Dr. Melian. We enable that process in patients who otherwise would be T-cell deficient to restore T-cell immunity by giving ex vivo expanded cells that come from patients who already have demonstrated a potent immune response and have cleared the infection.

The process of creating coronavirus-specific T-cells is the same as creating their other virus-specific T-cell therapies. First, blood is taken from people who have recovered from COVID-19 and the T-cells are isolated. Then, the cells are stimulated with viral antigens in the lab, expanded, and cryopreserved.

We purposely choose a broad range of viral antigens to stimulate the T-cells to ensure the virus cant circumvent the virus-specific T-cell therapy by mutating or developing resistance, Dr. Melian said. Working with a wide spectrum of viral activity is different than other approaches that just focus on one viral antigen.

An open-label Phase 1 trial (called BAT IT) is anticipated to start within the next few months. Initial clinical studies of ALVR109 aim to treat high-risk COVID-19 patients, such as the elderly, to prevent organ damage. Prophylaxis studies, where the T-cells could be given to high-risk or immunocompromised patients who are not currently sick with COVID-19, may be considered later.

Coronavirus-specific T-cells vs. COVID-19 convalescent plasma

You may be wondering if another treatment that uses blood from COVID-19 survivors, called convalescent plasma therapy, is similar to AlloVirs T-cell therapy. In convalescent plasma treatment, antibodies from COVID-19 survivors are isolated from their blood by separating out their plasma (the liquid part of the blood). The plasma is given to COVID-19 patients to help their immune system fight off the infection.

Although convalescent plasma and AlloVirs coronavirus-specific T-cell treatments are both derived from COVID-19 survivors blood, the two treatments are fundamentally different.

Antibodies and T-cells work in different areas of the immune system, explained Dr. Melian. Antibodies can go after viruses in circulating blood but cant necessarily see viruses in infected cells. On the other hand, T-cells are pleotropic and directly attack virally infected cells, turning off the viral factories. T-cells are interesting because it is a live therapy they can home to virally-infected cells and direct the immune system.

Dr. Melian went on to explain that T-cell approach may be more comprehensive because they can support other immune cells that work against viruses, such as B-cells that make viral-specific antibodies. T-cells can also stimulate cytokines including interferon (a group of signaling proteins the immune system uses to respond to viruses), which further activates the bodys antiviral response.

Providing virus-specific antibodies may be beneficial and protective for some viral infections, Dr. Melian added. We dont know how these antibodies affect COVID-19 patients yet, but COVID-19 has a high mortality rate despite standard of care treatment. In this respect, it is important that all viable approaches to treatment be evaluated and I am very pleased to see these therapies have entered clinical testing.

Convalescent plasma and AlloVirs coronavirus-specific T-cell therapies are not mutually exclusive, so they could even be used together.

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Equipping the Immune System to Fight Against COVID-19 - BioSpace

CAR T-Cell Therapies Continue to Raise the Bar in Lymphoma Management – OncLive

By Stem Cell Treatment

CAR T-cell therapies continue to elicit encouraging responses with manageable toxicity in older patients with lymphomas who may be unable to tolerate more intensive approaches, according to Pashna N. Munshi, MD.

In July 2020, the FDA approved brexucabtagene autoleucel (Tecartus; formerly KTE-X19)for the treatment of adult patients with relapsed/refractory mantle cell lymphoma (MCL) based on data from the ZUMA-2 trial. In 60 patients evaluable for efficacy based on a minimum duration of follow-up for response of 6 months, results showed that a single infusion of the product resulted in an 87% objective response rate (ORR), with a 62% complete remission (CR) rate.1

Brexucabtagene autoleucel is going to provide patients with MCL with another treatment option. MCL is a very heterogeneous disorder; it can behave indolently in some patients, but in others, it's a very aggressive disease, said Munshi, associate clinical director of the Stem Cell Transplant and Cellular Immunotherapy Program at MedStar Georgetown University Hospital. Patients who relapse early often don't do very well and cannot get into remission. Having an option like CAR T-cell therapy gives these patients a chance to receive [a treatment] that is targeted, with manageable toxicities.

The ZUMA-5 trial with axicabtagene ciloleucel (axi-cel; Yescarta) showed similarly impressive response rates, according to Munshi. Results from an interim analysis revealed that at a median follow-up of 15.3 months, patients with follicular lymphoma and marginal zone lymphoma (MZL) who received treatment with the CAR T-cell product experienced an ORR of 93% and a CR rate of 80%.2

In an interview withOncLive during the 2020 Institutional Perspectives in Cancer webinar on Leukemia/Lymphoma, Munshi, who is also an assistant professor of medicine at Georgetown University, discussed the CAR T-cell therapies that have emerged in the lymphoma space and highlighted the next steps for research with these products.

OncLive: Could you highlight some of the CAR T-cell products that are generating excitement in lymphoma?

Munshi: The most recently approved therapy was brexucabtagene autoleucel, which was evaluated in the ZUMA-2 trial; this was a phase 2, single-arm, open-label, multicenter trial done in patients with relapsed/refractory MCL. This product is similar to the CD19-targeted CAR T-cell product axicabtagene ciloleucel, although some differences exist.[Results showed] an ORR of 93%, with CR rates of 67% in a total of 68 patients. The ORR and the durability of those responses resulted in the approval of the product.

Another important clinical trial that is currently underway is ZUMA-5, which is being done in patients with relapsed/refractory indolent non-Hodgkin lymphoma. This trial had 2 cohorts: patients with follicular lymphoma and those with MZL. The follicular lymphoma cohort is now closed to enrollment and the results were [presented during] the 2020 ASCO Virtual Scientific Program and those results will be presented at the 2020 ASH Annual Meeting.

Ninety-six patients were evaluable for efficacy. [The ORR] was 95% in the follicular lymphoma arm and 81% for the MZL arm. At the time of data cutoff, 68% of patients had ongoing responses, so this is a very exciting therapy. We hope this will be a new indication for the treatment of patients with relapsed/refractory indolent lymphoma, especially follicular lymphoma.

What is the clinical significance of the brexucabtagene autoleucel approval?

One type of treatment approach that patients with MCL are offered is a high-dose chemotherapy with autologous stem cell transplantation. However, many patients may not be eligible for such high-intensity chemotherapy. Patients may be older, frail, and not in good enough shape to receive high-intensity treatment. CAR T-cell therapy may be given to these patients.

[In the ZUMA-2] trial, there was a substantial number of older patients [who achieved] very good responses [with the therapy]. The ORR was 87% at a median follow-up of about 8.6 months; this was later updated because 4 patients in the initial study were deemed as nonresponders by an independent radiology review. This therapy can potentially be given more up front for patients with MCL who have progressed on 2 or more lines of therapy.

Many older patients were also included on the ZUMA-5 trial. Could you expand on this? What does the safety look like with this product?

The median age range of participants was vast; the trial included patients who were as young as 34 years up to those who were 79 years. Many of these patients were older; they were over 60 years and yet, they could tolerate this therapy with really impressive ORRs.

Even though these therapies do have toxicities, such as cytokine release syndrome (CRS) and neurological effects, they are well [managed] by experts. We use therapies, such as the IL-6 inhibitor tocilizumab(Actemra) up front to treat CRS, as well as up-front steroids, in patients who may have some level of neurological involvement. In terms of the ZUMA-5 trial, it is important to note the age range and the fact that at least 73% of these patients were refractory to the last therapy they had received.

What are some of the updates that have been reported with tisagenlecleucel (tisa-cel; Kymriah)?

The [manufacturers of] tisa-cel presented real-world data with their commercial product and compared it with clinical trial results. They saw, if not similar, an almost improved toxicity profile and similar response rates which were reflective of their clinical trial.

Based on the initial JULIET study, 92% of patients were allowed bridging therapy. Only 72% to 75% of patientsreceived bridging therapy on the commercial side. The real-world data showed a median ORR of approximately 60%, with approximately 40% achieving a CR; [this] is similar to the 40% best responses observed on the clinical trial.

The grade 3 or higher toxicities were very low; only 4.3% of patients experienced CRS; that is remarkable. More patients are increasingly being given up-front tocilizumab or steroid use, which is mitigating the toxicity of these therapies and making it safer for patients.

What are the next steps for research with this modality?

A Pandora's box has been opened. Were not limited to CAR T-cell therapies; many, many targets are now being explored. There are CAR natural killer cell therapies; there are specific targets in leukemia that are being studied. CD33-targeted CAR T-cell trials are being done, and investigators are also exploring a combination of CD33-targeted and CD123-targeted products.

[Additionally], there are bispecific CAR T-cell engagers. Different methods are being used to try to see why relapse happens with CAR T-cell therapy. Maybe 1 antigen is lost and, therefore, you need a second antigen to be targeted, [hence] the CD19/CD22 combinations being examined in acute lymphoblastic leukemia. Many different forms of therapies are under exploration.

The next step is to find a way to [minimize] toxicities and relapse in the CAR T-cell world.The final stage is to look at off-the-shelf or allogeneic CAR T products. With these options, patients may not have to wait for their own cells to be processed as CAR T cells; the product will be readily available. That will really change how quickly these patients receive treatment, and it also potentially shifts the bar for many diseases.

For example, if this [approach] is successful in acute myeloid leukemia, many patients may get this therapy when they were not otherwise eligible for allogeneic stem cell therapy. If this therapy were to put them in remission, they could potentially make it to an allogeneic stem cell transplant or may not even need to undergo a transplant if these therapies prove durable. It's a very exciting future for CAR T cells.

What is your take-home message to your colleagues?

What I'd like to tell all the providers out there who are seeing patients with lymphoma and myeloma, especially with regard to refractory lymphomas, early referral is key. This is an autologous product, so it can take anywhere from 2 weeks to 3 weeks [to manufacture], depending on the type of product. When patients have an active malignancy, they're really waiting with active disease and it's hard to treat them with new therapy in between while they wait to receive CAR T-cells.

There is an aspect of overcoming insurance hurdles with some of these patients, as these are expensive products. Many milestones need to be achieved before patients can [receive] these therapies. Family members need education about the care that patients need once they're sent home. Also, referring providers may need to see these patients more frequently after they're treated with CAR T-cells, depending on their need.

There is some education that goes into this and we are armed as specialized, authorized treatment centers to arm patients and their caregivers with the knowledge about these therapies, the adverse effects of these approaches, and potentially provide them with a therapy that would make a change to the cancer in their body.

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CAR T-Cell Therapies Continue to Raise the Bar in Lymphoma Management - OncLive

Determining Who Has Early Myelofibrosis Involves a Broad Look at Patient Factors – Targeted Oncology

By Stem Cell Treatment

Patients considered to have early myelofibrosis are a heterogeneous group for whom disease risk, best treatment strategies, and the probability of mortality are best determined individually by looking at patients clinical characteristics and molecular markers together.

The burden of myelofibrosis is variable. Risk in terms of survival is a factor, but not the only factor in treatment, Ruben Mesa, MD, said in a presentation during the Texas Virtual MPN (Myeloproliferative Neoplasm) Workshop.1 It is looking at the entire clinical picture for a patient as well as understanding their wishes [about how aggressive they want to be with the disease] that is important.

Regarding the term early myelofibrosis, Mesa, who is the director of the University of Texas Health San Antonio MD Anderson Cancer Center, said that this term may apply to a case of mild anemia, splenomegaly, or other myelofibrosis symptoms. But, he said that multiple patient factors are involved in determining who it should apply to, such as burden of vascular events, risk of progression, splenomegaly, and baseline health or comorbidities. Generally, he discussed the treatment of patients with low- or intermediate 1risk disease, as those who typically present with more favorable prognosis.

Management of all patients with myelofibrosis should progress through the same steps of evaluating survival and disease burden; developing a treatment plan of either observation, stem cell transplant, or frontline systemic therapy; and creating strategies for eventual disease progression.

Patient-reported symptom assessment tools are valuable and may help calculate symptom burden. Mesa cited using versions of both the MPN-Symptom Assessment Form (SAF) and the MPN-SAF Total Symptom Score (TSS) to look at effects such as fatigue, satiety, and pruritis.

Just as we think of different prognostic scores, so too can there be different quartiles in terms of the severity and intensity of symptoms, Mesa said. These things are not necessarily linked to their risk score, which is predictive of survival, he said, noting that disease burden and disease risk scores are not interchangeable.

Risk scores, such as the Dynamic International Prognostic Scoring System (DIPSS)Plus, take constitutional symptoms as well as clinical features like age, degree of cytopenia, and karyotype into account when evaluating patients for prognosis. Using this risk scoring system, one study of 520 patients estimated that the median time spent in the low-risk category was 4.9 years (range, 0-26.7). Mesa noted that as patients progressed through intermediate 1risk to high-risk disease stages, time spent in each category decreased. Therefore, patients considered to have early myelofibrosis, whether it be low- or intermediate 1risk disease, still had progressive disease.2

Molecular phenotypes have also been instrumental in the current era of decision making for treatment of myelofibrosis. Based on an unfavorable molecular marker, patients otherwise considered to have intermediate-risk disease might now have a poorer prognosis and require more aggressive therapy in hopes of extending survival.

New molecular phenotypes have clearly helped augment and refine prognosis, but they dont fully give us a sense of disease burden, said Mesa. Issues can arise in which patients with very high-risk disease dont have severe symptom burden; conversely, individuals with severe symptoms may actually have lower-risk disease.

We all know patients are much more complex than just the status of their clone or their molecular phenotype, although that is critically important, Mesa said.

Patients with intermediate-risk disease are the most heterogenous group who stand to benefit greatly from information obtained by next-generation sequencing. Results obtains from molecular profiling may better inform a patients prognosis, and incorporation of this information may upgrade disease risk and suggest benefit of transplant or clinical trial.

Based on the National Comprehensive Cancer Network (NCCN) guidelines for MPNs, patients should first be assessed using either the DIPSS or DIPSS-plus. Patients who are asymptomatic by the MPN-SAF TSS can be observed or referred for clinical trial. Symptomatic patients can be treated with ruxolitinib (Jakafi), another available systemic agent, or be referred for clinical trial.3

For patients considered to have intermediate 1risk disease by the NCCN guidelines, observation, ruxolitinib, clinical trial, and allogeneic hematopoietic stem cell transplantation are all considered acceptable forms of myelofibrosis management.

The indication for ruxolitinib was based on the COMFORT-I (NCT00952289) and COMFORT-II (NCT00934544) studies,4 both of which examined the use of the JAK2 inhibitor in patients with intermediate or high-risk disease. Mesa said these patients were included in the trial because they represented the greatest need. However, approval based on this evidence should not be interpreted as meaning that ruxolitinib is unsuitable for use in patients with intermediate 1 or low-risk disease.

In fact, data from the phase 2 ROBUST trial that were released after the FDA issued its frontline approval supported the use of ruxolitinib more broadly in patients with myelofibrosis, including 19 patients with intermediate 1risk disease.5 Similarly, the global, expanded-access phase 3b JUMP trial included the largest cohort to date of patients with intermediate 1risk myelofibrosis and supported the safety and efficacy of ruxolitinib in this group.6

Mesa also added that fedratinib (Inrebic) is approved as frontline therapy for myelofibrosis,7 but data are lacking to support its use in patients with low-risk disease. As that becomes available, it can be considered in this group, he said.

Revisiting the NCCN Guidelines, Mesa reviewed the Evidence Blocks to determine interventions for low-risk disease, including hydroxyurea (Hydrea), interferon, and ruxolitinib. For intermediate 1risk disease, he said most evidence at this point supports the use of ruxolitinib but he expects that other agents will be added to the list as more data emerge.4 However, studies of real-world evidence and investigator-initiated trials will likely be needed since trials supporting approval typical involve patients in higher-risk categories.

Concluding the discussion, Mesa said understanding why patients progress will be important in the selection of novel therapies for patients with early myelofibrosis. Earlier patients all have areas in which they might benefit [from therapy], but as is natural, that evolution occurs as we develop more efficacy and safety data for these medicationsOnce we understand the mechanism of progression and have suitable markers of progression, then we might be in a better position to have progression-free survival be a viable end point for these individuals.

References:

1. Mesa R. To JAKi or not to JAKi How I treat Early MF. Presented at: Texas Virtual MPN Workshop; August 27-28, 2020; Virtual.

2. DIPSS-Plus: a refined Dynamic International Prognostic Scoring System (DIPSS) for primary myelofibrosis that incorporates karyotype, platelet count and transfusion status. Blood. 2010;116(21):4104. doi:10.1182/blood.V116.21.4104.4104

3. NCCN. Clinical Practice Guidelines in Oncology (Evidence Blocks). Myeloproliferative neoplasms, version 1.2020. Accessed August 27, 2020.

4. FDA approves Incytes Jakafi (ruxolitinib) for patients with myelofibrosis. News release. November 11, 2011. Accessed August 27, 2020. https://bit.ly/2ED5yP8

5. Mead AJ, Milojkovic D, Knapper S, et al. Response to ruxolitinib in patients with intermediate-1-, intermediate-2-, and high-risk myelofibrosis: results of the UK ROBUST Trial.Br J Haematol. 2015;170(1):29-39. doi:10.1111/bjh.13379

6. Giraldo P, Palandri F, Palumbo GA, et al. Safety and efficacy of ruxolitinib (Rux) in patients with intermediate-1risk myelofibrosis (MF) from an open-label, multicenter, single-arm expanded-access study. Presented at: 20th Annual Congress of European Hematology Association; June 11-14, 2015; Vienna, Austria. Abstract P675. https://bit.ly/2D3Nvkv

7. FDA approves fedratinib for myelofibrosis. FDA. August 16, 2019. Accessed August 27, 2020. https://bit.ly/2EJOU0k

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Determining Who Has Early Myelofibrosis Involves a Broad Look at Patient Factors - Targeted Oncology

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