The reduced osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is the typical characteristics of pediatric aplastic anemia (AA) pathogenesis. Long non-coding RNA MEG3 is reported to promote osteogenic differentiation of BMSCs via inducing BMP4 expression.This study aims to investigate the mechanism of DNMT1/MEG3/BMP4 pathway in osteogenic differentiation of BMSCs in pediatric AA.BMSCs were isolated and purified from bone marrows of pediatric AA patients (n=5) and non-AA patients (n=5). The expression of DNMT1, MEG3, and BMP4 in isolated BMSCs was detected using quantitative real-time PCR and western blot analysis. Osteogenic differentiation was determined using Alizarin red staining. The methylation of MEG3 promoter and the interaction between DNMT1 and MEG3 promoter were detected using methylation-specific PCR and chromatin immunoprecipitation assay, respectively.Lowly expressed MEG3 and BMP4 and highly expressed DNMT1 were observed in BMSCs of pediatric AA patients. The overexpression of MEG3 promoted osteogenic differentiation of BMSCs. Luciferase reporter assay showed that MEG3 overexpression increased transcriptional activity of BMP4. The inhibitor of methylation, 5-azacytidine, suppressed DNMT1 expression and reduced methylation of MEG3 promoter. Overexpression of DNMT1 increased the binding between DNMT1 and MEG3 promoter. The simultaneous overexpression of DNMT1 and MEG3 restored the inhibition of osteogenic differentiation caused by DNMT1 overexpression alone.Our findings indicated that DNMT1 mediated the hypermethylation of MEG3 promoter in BMSCs, and DNMT1/MEG3/BMP4 pathway modulated osteogenic differentiation of BMSCs in pediatric AA.

PubMed

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Hypermethylation-mediated downregulation of long non-coding RNA MEG3 inhibits osteogenic differentiation of bone marrow mesenchymal stem cells and...

Bone Marrow Stem Cells Comments Off on Hypermethylation-mediated downregulation of long non-coding RNA MEG3 inhibits osteogenic differentiation of bone marrow mesenchymal stem cells and… | February 6th, 2021

The mum of a Stockton toddler says time is running out to find a match for her son who is battling a rare blood cancer.

Little Mason Arrowsmith, one, was diagnosed with Juvenile Myelomonocytic Leukaemia (JMML) on Christmas Eve last year.

The condition is a rare type of slowly developing blood cancer that occurs in young children.

Although it was discovered at an early stage, doctors say Mason needs a stem cell or bone marrow transplant for the best chance of survival.

In a desperate attempted to help, his mum Katie Jordan will donate her own bone marrow later this month, but a full match is urgently needed.

"The hospital has been absolutely amazing, but unfortunately after searching worldwide there is no match for Mason due to his bone marrow being so rare," Katie said.

"We need to get him to transplant as soon as, the hospital is looking at the end of February, using me as his first donor in the hope that this will help him until we find a better match.

"I would give my life for Mason but unfortunately, I can only donate my bone marrow three times in a lifetime and Im not a full match for him.

"Children with JMML live around 12 months after diagnosis, we need to find mason a better match. Twelve months is not long enough for us to have with our boy, we are living the worst possible nightmare."

As Mason does not have a close enough match within his family - the only potential cure is through a stem cell transplant from an unrelated donor.

The family has now launched a 'Masons Mission' to encourage people to support blood cancer charity Anthony Nolan in raising urgent funds to add more donors to the stem cells register.

There is currently a blacklog of around 25,000 potential donors due to the impact of the coronavirus pandemic and the charity needs to raise up to an extra 500,000 to add people to the register, from ordering more swab packs to analysing completed swabs in its laboratory.

Any one of the 25,000 people who have applied to join the Anthony Nolan could be a match for Mason or one of the 2,300 patients in the UK, who need a stem cell transplant from a donor each year.

Katie added: "We have set our target at 10,000 which does seem a lot but this would help to cover 250 registrations and kits and allow us to continue our search for my baby."

Henny Braund, Chief Executive of Anthony Nolan said: "Were doing all we can to find a stem cell donor to give Mason a second chance of life.

"A perfect storm of the coronavirus pandemic, and a surge of 40,000 incredible people who have been inspired to join the Anthony Nolan register in the last month by patients, like Mason means that were in urgent need.

"The best thing people can do is support Anthony Nolans work financially. By giving anything, together we can add all potential lifesavers to the register, and give patients like Mason hope."

Anthony Nolan recruits people aged 16-30 to the stem cell register as research has shown younger people are more likely to be chosen to donate.

They also carry out ground-breaking research to save more lives and provide information and support to patients after a stem cell transplant, through its clinical nurse specialists and psychologists, who help guide patients through their recovery.

It costs 40 to recruit each potential donor to the register, so Anthony Nolan relies on financial support.

You can support Masons Mission here.

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Family 'living worst nightmare' as they desperately seek donor for tot with rare blood cancer - Teesside Live

Bone Marrow Stem Cells Comments Off on Family ‘living worst nightmare’ as they desperately seek donor for tot with rare blood cancer – Teesside Live | February 6th, 2021

Researchers at the Catholic University of Korea St. Marys Hospital have recently proved the efficacy of bone marrow-derived stem cells to treat ototoxicity hearing loss, the hospital said Thursday.

The team, led by Professor Park Kyoung-ho of the Department of Otolaryngology, conducted an experiment on animal models with ototoxic sensorineural hearing, or sudden hearing loss.

They utilized Catholic MASTER cells, bone marrow stem cells developed by the Catholic Institute of Cell Therapy, to compare the stem cell injection group with the controlled group.

The result showed that animals started to recover their hearing after three weeks. Five weeks later, they recovered normal hearing at 8000Hz, 16000Hz and 32000Hz frequency.

Ototoxic hearing loss is caused when a person ingests chemicals or certain medications that adversely affect the inner ear functions. Major symptoms related to the illness are dizziness, false hearing, and hearing loss, which permanently defects hearing functions. Elders with such symptoms should have medical consultations as they are a high-risk group, the hospital said.

We have proved the efficacy of our bone marrow stem cells in recovering hearing, said Professor Park, who doubles as the director of the Stem Cell Institute. Through the results, we expect to provide new treatment opportunities for patients with hearing loss.

The test results were published in the Korean Journal of Otorhinolaryngology-Head and Neck Surgery.

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Stem cells efficacy confirmed in treating ototoxic hearing loss - Korea Biomedical Review

Bone Marrow Stem Cells Comments Off on Stem cells efficacy confirmed in treating ototoxic hearing loss – Korea Biomedical Review | February 4th, 2021

The outbreak of the Covidpandemic has made many patients reluctantto undergotreatments. While their apprehension seems to overpower them, doctors need to ensure thatstrict guidelines and protocols which assure the best quality service are followed.

Among elective surgeries andtransplants, bone marrow transplant cases have increased substantially in the past few months. Adhering to guidelines for pre-transplant evaluation and the management of a common complication, graft versus host disease (GVHD)is essential.

With the diversity of practice and expertise, the following guidelines will provide a pivotal tool for learning about the rapidly updated therapy landscape in Hematopoietic stem cell transplantation (HSCT).

The guidelines intended to provide a systematic approach for transplantation and help streamline clinical practices and educate new generations of physicians-in-training. Additionally, guidelines can help to evaluate a potential transplant recipient anddetermine if the patient is an eligible candidate for the procedure.

Types and selection of transplantation:

Selection of the type of transplantation for a patient depends on factors such as the type of malignancy, availability of a suitable donor, age of the recipient, the ability to collect a tumor-free autograft, the stage, the malignancy's susceptibility to the GVM effect, and status of disease -- bone marrow involvement, the bulk of disease, chemosensitivity to conventional chemotherapy. This method is particularly applicable for Autologous or Allogeneic Transplantation where one can have a sibling donor or a matched unrelated donor. In the case of a matched unrelated donor, ensure that the collection is adequate and stem cells are available well in time especially if they are imported from countries in Europe.

A haploidentical transplant is another type of transplant that uses healthy, blood-forming cells from a half-matched donor to replace the unhealthy ones. The ideal donor in this case is a family member.

That said, for bone marrow transplant blood products are the backbone and it is important to ensure to have adequate supply before you begin with the transplant.

What are the guidelines and protocols that can be adopted in current times?

Some measures for consideration are: Minimize face-to-face visits including monitoring and consider shifting to telehealth where feasible. Some adaptive community measures like the hospital in the home services, community practices for blood collection, imaging, and support services. For radiation oncology treatment, consider reducing fractions when supported by evidence Consider alternative and less resource-intensive treatment regimes. Minimize unnecessary visitors to cancer centers, for instance, limiting to only patients and their essential caregivers based on frailty and language needs Screen for possible symptoms of COVID-19 and triage patients for admission. If necessary, the admission has to be directed to oncology/hematology departments rather than emergency departments. Immunocompromised patients are likely to have atypical presentations of COVID-19 For suspected checkpoint inhibitor-related pneumonitis prioritizes COVID-19 testing for an early decision regarding corticosteroid therapy.

These are some guidelines that you should heed during a bone marrow transplant. While it is imperative to be updated about the guidelines, timely intervention can reduce the other possible complications during the process.

(The author is the Director, Medical Oncology and Hemato Oncology, atFortis Cancer Institute, Bangalore)

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Understanding bone marrow transplant: The guidelines and the protocols - The New Indian Express

Bone Marrow Stem Cells Comments Off on Understanding bone marrow transplant: The guidelines and the protocols – The New Indian Express | February 4th, 2021

Dave Asprey  |  Photo Credit: Twitter

A man who is determined to live until he is 180 years old says that his bizarre methods will soon be as popular as mobile phones. American millionaire tech entrepreneur Dave Asprey, 47, believes he will live to the year 2153 'at least' by using techniques such as sitting in a cold cryotherapy chamber and intermittent-fasting.

Dave coined the term 'Biohacking' to describe his methods of turning back the biological clock.

He got parts of his bone marrow removed to have the stem cells injected back into his body for $25,000 (Rs 18 lakh).

He speculated that people who are under 40 years of age will be "happy and highly functional" at 100 after applying his methods.

When This Morning's Holly Willoughby asked him why he wants to live so long, he replied, "I'm curious, I think there's a lot of things we can fix and improve in the world and I don't feel like I'm at all done yet."

Dave believes that he won't be the only one to be live for so long.

"The things I am working to pioneer, some of them are expensive, some of them are free like fasting. This will be like cell phones, everyone has cell phones - everyone will have anti-ageing. Change can happen rapidly in society," he said. "There will be many people who are under 40 right now who [will be] walking around under their own power, perfectly happy, highly functional, who are more than 100 years old."

Dave has spent an estimated $1 million on techniques and hacks to try and improve his body's overall functioning.

He added, "I set myself up to have much less inflammation than most people do, by controlling what I eat and how I sleep and a lot of other anti-ageing treatments."

He explained why he re-introduced his stem cells in his body, saying, "When we're young, we have a ton of stem cells and we heal like young people. As we age our stem cells get exhausted, so I do things like intermittent fasting which give me more stem cells and then I take my own stem cells and move them around the body so I heal and move like a young person."

Dave also believes in the benefits of cryotherapy, also known as cold therapy, which is the use of low temperatures in medical therapy to treat a variety of tissue lesions. He has been having cold showers for over ten years.

Another technique that Dave uses to live a long life is intermittent fasting, which involves restricting times that you eat meals to create periods of fasting over a certain period.

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Man who wants to live for 180 years spends Rs 18 lakh to re-inject his own stem cells - Times Now

Bone Marrow Stem Cells Comments Off on Man who wants to live for 180 years spends Rs 18 lakh to re-inject his own stem cells – Times Now | February 4th, 2021

- DKMS-BMST continues to urge Indians to step up to be a potential lifesaver!

BENGALURU, India, Feb. 4, 2021 /PRNewswire/ -- February 4th is marked as World Cancer day every year. This day is observed to spread awareness about the disease and its increasing burden. In line with the theme for this year "Create a futurewithout cancer. The time to act isnow", DKMS BMST Foundation India, a non-profit organization with a mission to provide a second chance at life to blood cancer and blood disorder patients in India makes an appeal to people to come forward and register as potential blood stem cell donors.

On World Cancer Day 2021, DKMS is also celebrating a milestone of providing more than 90,000 blood cancer patients across 57 countries with a second chance at life, since it was founded almost 30 years ago in 1991. DKMS is an international non-profit organization that helps provide patients with lifesaving blood stem cell transplants. DKMS has presence in India, Germany, USA, Poland, UK, Chile, and South Africa.

Patrick Paul, CEO, DKMS BMST Foundation India, says, "DKMS is proud to be the world's leading donor center, accounting for nearly 30% of the total donor pool. While, this is a global milestone, when it comes to India, the fact is that the Indian donors are highly underrepresented in the global database. This is why it becomes difficult for doctors to find a matching blood stem cell donor for Indian patients. While DKMS has registered over 10.5 million donors and has provided over 90,000 patients with a second chance at life globally, it is critical to highlight that only over 43,000 Indian donors are part of this donor pool."

In India, every year, over one lakh people are diagnosed with a form of blood cancer and it remains one of the leading causes of cancer-related deaths among children. Most people are unaware that a life-threatening disease like blood cancer can be treated and in most of the cases, a stem cell transplant is the patient's only chance for survival. For instance, 15-year-old Maheer from Gujarat, India, is one of the blood cancer survivors who had received a lifesaving blood stem cell donation in 2012. He was able to find his matching blood stem cell donor, Dr. Sita, who hails from Germany. Today, he leads a normal, healthy and happy life. He is in grade 9 and loves to travel, read and swim.

Today, more than 37 million potential unrelated donors are listed worldwide with stem cell donor centers and registries, of which only 0.03% are Indians. Currently, in India, the biggest challenge is the lack of awareness about blood stem cell transplant and the importance of registering as a potential blood stem cell donor. The entire procedure is safe and secure. Once the blood stem cells are collected from a donor, they are infused into the patient through a transplant process which then moves through the bloodstream and settles in the bone marrow. These new blood stem cells begin to increase in numbers and produce red blood cells, white blood cells, and platelets, resulting in the replacement of the patient's diseased cells and that's how a blood cancer patient gets a second chance at life. This situation can only be improved by recruiting many more potential stem cell donors from India.

This World Cancer Day, one can take a pledge to become a potential lifesaver. Registration takes only 5 minutes. If one between 18 and 50 years and in good health, the first step to register as a blood stem cell donor by ordering the home swab kit at http://www.dkms-bmst.org/register.

SOURCE DKMS BMST Foundation India

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World Cancer Day 2021: DKMS Announces The Milestone Of Giving 90,000 Blood Cancer Patients Worldwide A Second Chance At Life - PR Newswire India

Bone Marrow Stem Cells Comments Off on World Cancer Day 2021: DKMS Announces The Milestone Of Giving 90,000 Blood Cancer Patients Worldwide A Second Chance At Life – PR Newswire India | February 4th, 2021

Up Market Research (UMR) recently published a report entitled, the Hematopoietic Stem Cell Transplantation (HSCT) Market, describing the crucial aspects of the market by conducting an in-depth analysis of the current trend, emerging threats, and future market assessment. This report takes into account the adverse impact of the COVID-19 pandemic on the market for the period of 2020-2020 and provides a detailed information about how the market will perform during the forecast period, 2020-2027. Our research team presents the report in a simplistic manner supported by fact and actual figures that will assist clients to arrive an informed decision about their investment plans and business strategies.

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The report provides a holistic view of the market offering key insights of the market behavior over last four years and key assessment of the future market performance. It includes a systematic analysis of historical data for the period, 2015-2020 and draws upon assessment of the market performance for the forecast period, 2020-2027 by observing 2020 as the base year. With the reference to the available data, it provides vital insights on key factors such as drivers, restrains, trends, challenges, and opportunities of the Hematopoietic Stem Cell Transplantation (HSCT) market growth.

This report provides a comprehensive outlook on the key segments and sub-segmentations that includes the complete information about the product types, applications, end-users and regions. It offers latest information regarding the growth rate, volume, and size of the market in respect to each segment and also explains the market performance of these segments in the respective five regions. Moreover, it discusses a wide range of the emerging market scope and potential drawbacks present in the segments.

Hematopoietic Stem Cell Transplantation (HSCT) Market Report Includes:

The Global Hematopoietic Stem Cell Transplantation (HSCT) Market Report is segmented into:

By Types:

AllogeneicAutologous

By Applications:

Peripheral Blood Stem Cells Transplant (PBSCT)Bone Marrow Transplant (BMT)Cord Blood Transplant (CBT)

By Regions:

For More Information on This Report Visit: https://www.upmarketresearch.com/home/enquiry_before_buying/30593

The report covers the competitive landscape of various major global players, their current market positions, and key business strategies adopted to mark their major footprint in the market. This includes information about the product launch, expansion of the production facilities or plants, adoption of new technologies, latest merger & acquisition, partnership, and collaboration of the key players. It furthers provides concrete information about the existing market scope for the new entrants and the current competitive levels and scenario for the emerging players in the global market.

The Hematopoietic Stem Cell Transplantation (HSCT) Market Report Covers the Following Companies:

Regen Biopharma IncChina Cord Blood CorpCBR Systems IncEscape Therapeutics IncCryo-Save AGLonza Group LtdPluristem Therapeutics IncViaCord I

Up Market Research (UMR) also offers customized report for a particular product, application, and region as per the requirement of clients and provides additional companies profiles as per the clients request.

Regarding the methodology, the report is prepared by relying on primary and secondary sources including interviews of the company executives & representatives and accessing official documents, websites, and press release of the companies related to the Hematopoietic Stem Cell Transplantation (HSCT) market. It also includes comments and suggestions from the experts in the market especially the representatives from government and public organizations as well as international NGOs. The report prepared by Up Market Research (UMR) is known for its data accuracy and precise style, which relies on genuine information and reliable data source. Moreover, customized report can be available as per the clients wishes or specific needs. It takes into account of various research tools and methods including predictive analysis, Porters 5 force analysis, SWOT analysis, and real-time analytics.

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Hematopoietic Stem Cell Transplantation (HSCT) Market Incredible Possibilities, Growth With Industry Study, Detailed Analysis And Forecast To 2027 ...

Bone Marrow Stem Cells Comments Off on Hematopoietic Stem Cell Transplantation (HSCT) Market Incredible Possibilities, Growth With Industry Study, Detailed Analysis And Forecast To 2027 … | February 4th, 2021

Regenerative therapies such as stem cells and platelet-rich plasma already play an important role in managing osteoarthritis (OA). Nonetheless, veterinarians have found that response to even these therapies is less than ideal in many cases, prompting researchers to continuously seek novel therapies for this all-too-common musculoskeletal disorder. One of the newest to be unveiled is called bone marrow mononuclear cell (BMNC) therapy. One researcher who presented at the 2020 American Association of Equine Practitioners Convention, held virtually, reported that the equine industry is in critical need for therapies that resolve joint inflammation but preserve tissue healing, and BMNC appears a promising candidate.

Much more than stem cells classically sought for cartilage healing, bone marrow is rich in macrophage progenitor cells, explained James B. Everett, DVM, MS, previously of the Virginia-Maryland College of Veterinary Medicine, who now works at the Equine Surgical Center at ThorSport Farm,in Murfreesboro, Tennessee. Macrophages are a type of white blood cell that play a role in tissue repair and cartilage integrity, and produce the anti-inflammatory mediators, including interleukin-10 (IL-10).

Everett said macrophages in the synovial (joint) membrane are essential for joint health, clearing aggressors, secreting key molecules required for optimal joint function, and forming a shield that protects tissues undergoing repair, similar to a wound scab. However, when the amount of tissue damage overwhelms these housekeeping functions, macrophages stimulate inflammation as a means of recruiting more cells, especially more macrophages, to cope with increased demands for repair.

If this response is efficiently accomplished, macrophages then produce, among other things, high concentrations of IL-10 and resolve the inflammatory process, returning the joint to a healthy state, he said.

Everett emphasized that not all inflammation is bad. This acute inflammation is essential to establish a resolving response, and anti-inflammatory therapies can negatively interfere.

As presented by Everetts colleague Bruno Menarim, DVM, PhD, in a separate session, studies show that BMNCs promote the endogenous resolution of experimentally induced inflammation. To see if these promising features translated to naturally occurring inflammation in live horses, Everetts research team studied 19 horses, dividing them into three treatment groups:

The selected horses were diagnosed with OA in a single joint, and the team injected those joints once with the saline, triamcinolone, or BMNCs. The BMNCs were autologous, meaning veterinarians collected them from each patients own bone marrow aspirate. They processed the aspirate in-house, and the isolated mononuclear cells, composed predominantly of macrophages, were ready to inject into the affected joint within three hours of aspiration.

We found that while objectively assessed lameness (via Lameness Locator) decreased in all three groups, it was only significant in the BMNC-treated horses, said Everett. Further, the treatment was well-tolerated with no adverse events appreciated in this study.

He said that using BMNCs can help reduce the need for chronic use of non-steroidal anti-inflammatory drugs and corticosteroids, which produces potentially harmful consequences. Further, BMNCs preserve the production of molecules such as interleukins and cytokines that are essential for restoring joint homeostasis. Corticosteroids often inhibit these molecules.

The researchers noted that these results support a larger clinical trial using BMNCs in clinical cases of equine OA.

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Novel Bone Marrow 'Ingredient' To Help Arthritic Horses The Horse - TheHorse.com

Bone Marrow Stem Cells Comments Off on Novel Bone Marrow ‘Ingredient’ To Help Arthritic Horses The Horse – TheHorse.com | February 3rd, 2021

EDMONTON -- A little girl with leukemia in northern Alberta is in desperate need of a bone marrow transplant.

Friends and family of 10-year-old Ameilia Powder have set up a stem cell drive to find a match.

"Asking for help is probably one of the most difficult things to do when you're in this situation and really opening your story up to everyone is really hard. but at the end of the day Ameilia needs a bone marrow match," Ameilia's grandmother Jaime Harpe said. "I'll do whatever it takes to get her that match."

Ameilia was diagnosed in March 2020 and went through five months of treatment at the Stollery Children's Hospital before returning home to Fort McKay First Nation in August.

The cancer returned late last month and this time, a bone marrow transplant is the only option to save her life.

"All people have to do is go blood.ca/stemcells and they can register online, and a kit gets sent to you in the mail," organizer Amanda Main said. "You just swab your cheek, pop it back in and you get entered in the data base, that's all you have to do."

Potential matches need to be between the ages of 17 and 35.

A GoFundMe page has already raised more than $11,000.

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'Whatever it takes': Stem cell drive underway to find bone marrow match for girl on Alta. First Nation - CTV Edmonton

Bone Marrow Stem Cells Comments Off on ‘Whatever it takes’: Stem cell drive underway to find bone marrow match for girl on Alta. First Nation – CTV Edmonton | February 3rd, 2021

Cynata Therapeutics (ASX: CYP), founded by two clever stem cell researchers and one wise Australian techpreneur, is in the process of developing a treatment for COVID-19.

Using its in-house stem cell technology Cymerus, the ASX-listed biotech hopes to treat one of the deadliest complications of COVID-19 -acute respiratory distress syndrome (ARDS).

In doing so Cynata would achieve what competitor Mesoblast (ASX: MSB) couldn't with FDA approval.

By deploying an industrialised approach to stem cell therapeutics, Cynata CEO Ross Macdonald (pictured) is confident the clinical trial process won't leave the company hamstrung.

In 1981 scientists discovered a way to derive embryonic stem cells from early mouse embryos.

The discovery thrilled scientists, and eventually led to the development of a method to do the same in lab-grown human embryos by 1998.

While there have been plenty of discussions surrounding the ethics of using of embryonic stem cells, these major scientific movements have pushed researchers to discover new and inventive ways of treating a whole raft of diseases and infections.

One such researcher, Dr Ian Dixon, saw potential for the use of mesenschymal stem cells (MSCs) - a type of stem cell that can differentiate into a variety of cell types enabling the treatment of many diseases and infections.

However there was still an obstacle to overcome: how do you mass produce enough cells needed to commercialise a treatment?

Luckily, two researchers at the University of Wisconson, Professor Igor Slukvin and Dr Maksym Vodyanik, had invented a biotechnological breakthrough called Cymerus.

The technology was able to do exactly what Dixon needed: the consistent manufacture of MSCs on an ultra-large scale; basically what Henry Ford did to the industrialisation of the auto industry, but for stem cells.

So in 2003 Dixon partnered with the two researchers to start Cynata - now an ASX-listed biotechnology company trialing a number of different treatments for a wide variety of ailments.

Most recently, Cynata's focus has been on developing a treatment for a complication of COVID-19 called acute respiratory distress syndrome (ARDS).

The complication ravages COVID-19 infected patients, destroying their organs through what is known as a cytokine storm. The complication is estimated to kill up to half of COVID-19 patients that suffer from it.

Melbourne-based Cynata is currently in the very early stages of its investigation into whether its MSCs will be able to treat the coronavirus complication overwhelming hospitals globally.

If this all sounds familiar, you might be thinking of another ASX-listed biotech called Mesoblast (ASX: MSB).

In March last year Mesoblast, also based in Melbourne, saw its shares surge after announcing plans to evaluate its stem cell treatment solutions on COVID-19 patients.

The group commenced the arduous clinical trial process to see if its remestemcel-L therapy could treat ARDS by using bone marrow aspirate from healthy donors - a similar approach the company had already taken to treat a condition many suffer from after receiving bone marrow transplants.

Mesoblast was riding high on the ASX following positive announcements surrounding the clinical traila process, especially back in April 2020 when a trial at New York City's Mt Sinai hospital found its remestemcel-L therpay achieved "remarkable" results.

Serious attention gathered around Mesoblast, with the company even securing $138 in funds from investors to continue its important research.

The company went so far as to sign a commercialisation deal for the COVID-19 treatment with Novartis, and the US Food and Drugs Administration (FDA) fast tracked the approvals process for the potential game-changing treatment.

However, in December 2020, Mesoblast hit a stumbling block.

Mesoblast's COVID-19 treatment flunked the test - its remestemcel-L therapy failed to show a lower mortality rate for patients in the prescribed 30-day timeframe of treatment.

At that point Cynata had commenced research into its own ARDS treatment. But did Mesoblast's failure unnerve Cynata CEO Ross Macdonald? Not a chance.

"I'm more confident that our trial will be successful where theirs was a failure," Macdonald said.

"If you use a process like we have developed - we don't rely on multiple different [stem cell] donations. You start with exactly the same material every time."

To explain, Macdonald used the analogy of a local caf; you normally expect a coffee from one caf to taste more or less exactly the same every time you go there - the same beans are used every time.

Whereas Macdonald said Mesoblast's process is like going to the same caf every day, but each visit they use different beans from a different supplier which leads to inconsistency in taste and flavour.

Cynata's approach with its MSCs is in line with the first example - what you get the first time from them will be replicated in each and every dose of the drug - while MSB's is like the latter.

"Yes, you still got the coffee, but the experience of the taste is totally different than it was yesterday," he said.

"The FDA said to Mesoblast, well you've got a manufacturing problem that is reliant upon multiple donors prepared to donate bone marrow and that is flawed.

"So with that in mind it's perhaps not surprising that they had a pretty disappointing result in the clinical trials."

Additionally, Macdonald said the initial investor reactions to MSB's early COVID-19 trail results were overblown.

"The initial data from their trial that got everybody excited was, in my view, quite flawed, because they said "look at how many patients are dying in intensive care units with COVID compared the patients that we treated," he said.

"But the reality of the situation was quite different. The control group at that time - the death rate was way, way higher than you would typically see for ARDS, whether its COVID or anything else. And it was simply because of the chaos that existed in intensive care units in New York in the first wave.

"So we think that the initial enthusiasm was perhaps a little misguided."

When asked why Mesoblast is receiving so much attention compared to Cynata, especially considering the above, Macdonald said it was simply because MSB is bigger and has been around for longer. For context, MSB has a market capitalisation of $1.46 billion, whereas Cynata's is just $94.56 million.

"I'd love to know why there is less attention, and how we can get our market cap above a billion dollars," joked Macdonald.

"I think the answer though is that they've been around for a lot longer than we have, they have spent a hell of a lot more money than we've spent - their monthly spend is more than we've spent for pretty much our entire existence.

"But I think the fundamental reason why is that data drives value in biotech, so the more clinical data you generate that shows your product works, the more attention you attract from investors."

That's not to say Cynata is being totally ignored in favour of the larger Mesoblast.

The company secured a $15 million placement led by $10 million from healthcare investor BioScience Managers in December.

The funds will be used to expand Cynata's clinical development pipeline and scale their operations in Australia.

As such, the company is preparing to expand its clinical development pipeline to include idiopathic pulmonary fibrosis, renal transplantation, and diabetic foot ulcers.

"So we're starting to garner that attention now that says two things - one, cell therapies are definitely a medical revolution and two, Cynata is part of that new generation of companies," Macdonald said.

As for the company's pipeline, in addition to the COVID treatment trials, Cynata is planning on launching three new clinical candidates that will get under way this year.

There's also Cynata's osteoarthritis trial, which Macdonald describes as significant for the biotech company; with 2 million patients in Australia and 30 million in the United States the company is hoping to tap into an $11 billion plus addressable market.

"It will ultimately show whether MSCs are useful in that particularly devastating condition," he said.

"It doesn't just affect people who want to go and play golf or tennis, it affects, particularly manual labourers who can no longer work.

"So the cost to the economy of osteoarthritis is quite significant, which is of course one of the reasons why the Australian Government is funding this trial."

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As an athlete, Courtlynn Havard has always set goals for herself to improve her game whether on the soccer or softball field. She has worked toward those goals through hard work and perseverance.

Now her goals have shifted slightly.

Courtlynn, a sophomore at Franklin Parish High School, currently has two main goals: to beat aplastic anemia and paroxysmal nocturnal hemoglobinuria (PNH) and to help others.

Helping others for Courtlynn brightens her day, strengthens her and gives her hope for a better tomorrow.

From that desire to help others, the Havard family is sponsoring a bone marrow drive at Life Church in Winnsboro Feb. 20 from 10 a.m. until 2 p.m.

The drive will be administered by DKMS, an international nonprofit organization, whose goal is to find bone marrow donors for people like Havard.

It is simple as a swab in your cheek, said Jaimie Havard, Courtlynns mother. That could save a life. It only takes a minute and is so easy for you to give somebody a second chance on life.

Anyone 18-55 with good health can participate in the drive. Participates stay in their car, watch a video on their phone and fill out a short form, said Amy Roseman of DMKS.

They are given a kit with a swap for their cheeks. The whole process takes 7-10 minutes.

Interested people can also go to dkms.org to order a free kit.

In October, Courtlynn went to the doctor with kidney stones. When doctors took her blood, they found her blood count was low.

Her mother and Courtlynn met with an oncologist who gave them disturbing news.

At first the oncologist thought it was leukemia, Jaimie said. You feel like your whole world is collapsing. I didnt know what to say or do. Courtlynn was devastated and crying. I was trying to be strong for her.

The Havards were then sent to LSU Health Shreveport. The medical professionals there performed a bone marrow biopsy and found she had aplastic anemia and PNH.

You never think it can be your child, Jaimie said. It is really an unbelievable, indescribable feeling.

Aplastic anemia is a condition that occurs when your body stops producing enough new blood cells, according to the Mayo Clinic. The condition leaves a person fatigued and more prone to infections and uncontrolled bleeding.

A rare and serious condition, aplastic anemia can develop at any age. It can occur suddenly, or it can come on slowly and worsen over time and can be mild or severe.

Treatment for aplastic anemia might include medications, blood transfusions or a stem cell transplant, also known as a bone marrow transplant.

PNH is a rare acquired, life-threatening disease of the blood. The disease is characterized by destruction of red blood cells (hemolytic anemia), blood clots (thrombosis), and impaired bone marrow function (not making enough of the three blood components).

PNH affects 1-1.5 persons per million of the population and is primarily a disease of younger adults. The median age of diagnosis is 35-40 years of age, with occasional cases diagnosed in childhood or adolescence. PNH is closely related to aplastic anemia.

Courtynns world use to evolve around sports, mud riding with her friends and being very social.

Now because of her weak immune system, she has to be careful and stay at home with her English Spaniel, Old Mack, and go to school virtually. Courtlynn talks to her friends via cell phone, computer and occasionally gets a visit from one that sits on her porch while she socially distances.

I missed my friends the most, Courtlynn said. I am one of those people that get up and go. I dont stay still.

She also goes to doctors whether it be locally to get her blood count tested, or Shreveport to receive platelets and blood or Memphis to St. Judes.

Saving people around the world

One thing that drives Courtlynn through this situation is keeping up with other kids situations, Jaimie said. There are so many stories out there of kids looking for bone marrow transplants.

The Feb. 20 bone marrow drive is a way Courtlynn and her family can help others.

DKMS has been finding matching bone marrow donors for 30 years. They are now in the United States, Germany, Poland, India and South Africa.

Sadly, only 2 percent of Americans have signed up as potential donors, Roseman said. We are hoping we will have really nice support for Courtlynn and the other patients looking for donors.

Reasons vary for the low percentage of potential donors, but Roseman attributes not knowing the need and ease of the process.

You fill out contact information, swap your cheeks and you are put in a data base that is only seen by medical teams searching for donors, Roseman said. We call it, youre a hero in waiting.

The biggest misconception is the donation of bone marrow if you are a match.

You are asked to donate stem cells from the blood stream, Roseman said. It is a very easy process. It is very similar to donating plasma or platelets and takes a morning or afternoon.

Blood is taken from one arm, and the blood is put back into the other arm, Roseman, said. Stem cells lost in the process will regenerate.

You have given someone a second chance in life, Roseman said.

A person may be asked to donate actual bone marrow if he or she is matched to a three year old or younger. This procedure is done in a hospital and takes less than an hour. DKMS pays for the hospital visit and time loss from work.

It is amazing to think about giving someone a second chance on life by giving up a just morning of your time, Roseman said.

A community comes together

The Franklin Parish community has come together in support of Courtlynn and the Havard family.

Boutique shops, individuals and restaurants have come together to raise money for her cause.

During the Feb. 20 bone marrow drive at Life Church a BBQ chicken plate lunch will be on sale for $10. T-shirts will also be on sale at the event. Keep up with all drives and Courtlynns journey on her Facebook page: Courtlynns Compass.

We have a really amazing group of friends and family that have come together, Jaimie said. Our local community has stepped up big time. Complete strangers are showing so much love and support for my baby. It speaks volumes for our little town we live in.

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The anti-emetic agent metoclopramide blocked CD93 signaling in cell culture and delayed leukemia development in mice, according to data from a preclinical study published in Cell Reports. The results indicate that CD93 signaling, which is an important regulator of self-renewal and proliferation of murine and human leukemia stem cells (LSCs), could be a potential therapeutic target for the elimination of LSCs in chronic myeloid leukemia (CML).

To characterize the function of CD93 in CML, the researchers first demonstrated that all subsets of LSCs expressed CD93 while more differentiated leukemia granulocytes did not. Though CD93 was shown to encourage self-renewal and proliferation of murine and human LSCs, it notably had no such effect on hematopoietic stem cells.

In an experiment, the investigators injected mice with LSCs that were either proficient or deficient in CD93. Mice with CD93-deficient LSCs were found to incorporate bromodeoxyuridine, which is used to detect proliferating cells, at a lower rate than mice with CD93-proficient LSCs. The finding suggests that proliferation of LSCs is impaired when CD93 is absent.

Next, a drug library was used to screen for compounds that could block CD93 signaling. Among the 240 compounds evaluated in vitro, 10 blocked CD93 signaling; one of the compounds was the anti-emetic agent metoclopramide.

Mice were then treated with either vehicle or metoclopramide. Notably, metoclopramide-treated mice had delayed leukemia development and lived longer than vehicle-treated mice. Among the metoclopramide-receiving mice, most genes were downregulated in the LSCs, particularly genes that promote stem cell maintenance and myeloid differentiation, cell proliferation and survival, response to cytokine signaling, and gene expression.

In vitro exposure to metoclopramide was found to disrupt colony formation in human bone marrow CML stem/progenitor cells. A control experiment showed that metoclopramide had no effect on hematopoietic stem/progenitor cells from humans with healthy bone marrow.

The study authors reasoned that because metoclopramide is a very well-tolerated and cheap anti-emetic drug, its LSC-eradicating activity in patients with CML can be directly tested in clinical drug repurposing studies.

Reference

Riether C, Radpour B, Kallen NM, et al. Metoclopramide treatment blocks CD93-signaling-mediated self-renewal of chronic myeloid leukemia stem cells. Cell Rep. 2021;34(4):108663. doi:10.1016/j.celrep.2020.108663

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Introduction

Osteonecrosis of the femoral head is a progressive disorder that causes pain and often progresses to hip joint collapse, finally resulting in disabling arthritis.1,2 It occurs between 30 to 50 years of age, and prevails at a relatively younger age in Asians compared to their western counterparts.3 It is estimated that approximately 20,00030,000 new cases of osteonecrosis are diagnosed in the United States each year, accounting for 10% of total hip arthroplasties performed.4 The Indian Society of Hip and Knee Surgeons has reported that more than 50% of all hip replacements in India are performed for osteonecrosis.5 Many studies have reported osteonecrosis to be more prevalent in men compared to women (3 or 5:1).3 The underlying pathophysiology of osteonecrosis remains unclear; however, it is multifactorial and several traumatic and nontraumatic etiological factors may contribute to its development. Traumatic events that may cause osteonecrosis include femoral neck/head fracture, hip dislocation, or slipped capital femoral epiphysis. Nontraumatic factors include use of steroids, alcoholism, metabolic disorders such as Cushings syndrome, and inherited disorders such as sickle cell disease.6,7 Besides the known traumatic and nontraumatic causes, some cases of osteonecrosis are idiopathic.1,8

Osteonecrosis of the femoral head may progress to secondary arthritis, and degeneration of articulating surface from advanced osteonecrosis necessitates total hip arthroplasty (THA). A primary treatment target of osteonecrosis of femoral head is to delay/prevent progression to osteoarthritis. Core decompression (CD) is the most widely used procedure in clinical practice; however, it has shown poor clinical outcomes, with up to 40% of patients having to undergo THA despite undergoing core decompression procedure.8 Therefore, a more pathophysiological approach may be required to treat osteonecrosis of femoral head. Osteonecrosis is characterized by a reduction in the osteogenic progenitor cells, an increase in osteoblast death, and altered intramedullary vascular supply due to trauma.1 It was observed that the number and function of mesenchymal cells in hematopoietic tissue and stroma of the bone marrow decreased in osteonecrosis patients.2 This observation indicated potential for using bone marrow stromal cells for the treatment of osteonecrosis, and consequently, several clinical studies have demonstrated encouraging results.2 A meta-analysis also showed that treatment with cell therapy compared to core decompression alone increased Harris hip score, decreased necrotic area of femoral head and collapse of femoral head, and reduced THA conversion rate.9 However, a recent randomized study has shown that bone marrow cell implantation in addition to core decompression did not improve THA conversion rate in patients with grade 3 osteonecrosis.10 The ideal treatment goal for osteonecrosis is to facilitate new bone formation in the place of dead bone that can provide pain relief, cease disease progression, prevent joint collapse, and preserve the joint. The fact thatbone marrow aspirate consists of mesenchymal stem cells raised a possibility if bone marrow cells could be differentiated into bone forming cells or osteoblasts and characterized by bone alkaline phosphatase. In a randomized trial, autologous osteoblast implantation was shown to significantly delay the evolution to subchondral fracture and reduce pain compared to bone marrow aspirate.11

OSSGROW (Regrow Biosciences Pvt Ltd., Mumbai, India) is a commercially available technology that involves implantation of autologous adult live-cultured osteoblasts (AALCO) derived from mesenchymal stem cells sourced from the bone marrow aspirate for osteonecrosis of the hip that received conditional marketing approval in India in March 2017.12 Here, we evaluated the efficacy of OSSGROW implantation technique by assessing retrospective data from patients with osteonecrosis who underwent the procedure. We also evaluated the correlation between Ficat-Arlet stages of osteonecrosis and clinical outcomes of the AALCO implantation procedure.

This retrospective, observational, non-comparative study was conducted at 37 centers in India. We retrospectively reviewed the data of patients with osteonecrosis of the femoral head who had undergone OSSGROW (AALCO) from 2010 to 2015. Key inclusion criteria were patients aged 12 years with a confirmed diagnosis of osteonecrosis in one or both hip joints who had undergone AALCO implantation. Diagnosis, analysis, and classification of osteonecrosis were done according to Ficat-Arlet based on radiography, computed tomography (CT) scans, and magnetic resonance imaging (MRI) findings. Patients whose medical records were not complete or were lost to follow-up were excluded from the study.

The protocol was approved by the Institutional Ethics Committee - Regrow Biosciences Pvt Ltd. and as this study was a retrospective study, informed consent was not required to review medical records. We also sought permission from the head of the institutes/departments before data collection. Patient data confidentiality was maintained in this study.

All the patients had undergone AALCO implantation on the recommendation of their consulting orthopedic surgeon after having received an explanation of the complications of osteonecrosis, the therapeutic options available, and the risks involved with the implantation procedure. Osteoblasts from patients were obtained from bone marrow aspiration from the posterior/superior iliac crest. Mesenchymal stem cells from the bone marrow were isolated and differentiated ex vivo into osteoblasts. Osteoblasts were then cultured for approximately 4 weeks under stringent laboratory conditions and multiplied up to 48 million osteoblasts (Figure 1). The cultured cells were implanted using a gel (Tisseel kit from Baxter) at the site of osteonecrosis through a minimally invasive surgery in a 3-step procedure: core decompression, curettage, and injection of osteoblasts (Figure 2).

Figure 1 Microscopic image of osteoblast in culture used for the final cell product before cell implantation.

Figure 2 Steps of osteoblasts implantation. (A) Step 1 Insertion of guide wire in center of lesion as identified on the MRI. (B) Step 2 Guide wire and 8mm cannulated drill for core decompression. The entry point of the guide wire is near the vastus ridge, to prevent a fracture due to stress-riser, greater width of femur and faster healing due to cancellous bone. (C) Step 3 Curettage: a variety of angulated curettes is used to do forage (curettage to remove necrotic bone). This bone is sent for biopsy.

Patients were operated on under spinal anesthesia. Core decompression tunnels were created into the subchondral necrotic lesion of the femoral head, approximately 23 mm away from the joint cartilage, by using 2.0-mm K-wires under fluoroscopic guidance through the greater trochanter and the femoral neck, and over drilled using trephine was performed by the centrally positioned K-wire. Cultured osteoblasts were injected following the curettage, and necrotic tissues were removed.

The patients had to undergo appropriate rehabilitation therapy after the implantation, which included complete bed-rest for 4 weeks post-implantation. After 4 weeks, passive lower limb exercises were performed for 2 weeks following post-implantation. Accordingly, non-weight bearing, partial weight bearing, and full weight bearing exercises were suggested as per the study protocol. Descriptive demographic and clinical data recorded before and after the procedure were collected from patient records. Past medical history, concomitant medications, and surgical treatments undertaken before and after the AALCO were recorded. Pre-existing risk factors for osteonecrosis such as steroid intake, alcohol consumption, comorbid conditions, or trauma were also noted.

Improvement in functional capacity and pain reduction were evaluated using Harris Hip Score (HHS) and visual analog scale (VAS) respectively at the time of pre- and post-operative consultations. Continued use of steroids or alcohol consumption after undergoing the AALCO implantation was recorded. The main outcome of the study was the need for THA (THA conversion rate). Based on these parameters, the treatment outcome was determined to be either improved (better score after AALCO implantation), stable (same condition as before AALCO implantation), or progressive (worse scores following AALCO implantation).

Continuous and quantitative variables were summarized using descriptive statistics and compared using Students t-test or nonparametric test, as applicable. Categorical data were presented as frequency count (n) and percentages (%) and were compared using the 2 test or Fishers exact test. P-values <0.05 were considered significant. All analyses were performed using the SPSS version 10.0.

Data from 64 patients were collected and analyzed as per the study protocol, and 101 hip joints were assessed. The age of patients ranged from 1270 years and BMI ranged from 20.632 kg/m2. The majority of the patients were men (79.7%). The mean duration since diagnosis of osteonecrosis was 7.4 1.6 years and the mean duration of AALCO treatment was 6.3 1.4 years (Table 1). Unilateral involvement of the hip joint was seen in 42.2% of cases. Bilateral involvement of hip joints was seen in 57.8% of patients. The majority of hips diagnosed were grade III (42.1%) and grade IV osteonecrosis (10.5%). While the exact cause for osteonecrosis was not known (idiopathic) in 25% of patients, 35.9% of cases were linked to steroid use and 26.6% to alcohol abuse. Records of concomitant medications revealed that 91.9% of patients were on analgesics, 8.1% were on ayurvedic treatment, and 1 patient took bisphosphonate.

Table 1 Demographic Characteristics

A total of 98 hip joints were assessed as data of 3 patients were not available for changes in mean VAS scores (improvement in pain), before and after the AALCO implantation. As shown in Figure 3A, the mean VAS score reduced significantly after a mean 6.3 years of AALCO treatment compared to the baseline (32.2 32.1 vs 58.8 13.8; mean difference: 26.5 35.2, p = 0.001) indicating significant improvement in pain. Similarly, HHS also improved post-operatively (47.1 12.3 vs 63.7 27.7; mean difference: 16.7 28.7, p = 0.001) showing functional improvement of patients. We categorized patients based on their HSS score (<70: poor, 7080: fair, 8090: good, 90100: excellent). At baseline, 96 hips (98%) had HSS score of <70, each of the two remaining hips had scores of <80 and <90, respectively. Improvement in HSS scores was seen at follow-up with 42 hips (43.3%) with HSS <70, 11 (11.3%) with 7080, 26 (26.8%) with 8090, and 18 (18.6%) with HSS scores of 90100.

Figure 3 (A) Changes in visual analog scale (VAS) and Harris hip scores. (B) Need for hip replacement surgery in different grades of osteonecrosis. (Osteonecrosis graded according to Association Research Circulation Osseous criteria).

The mean follow-up period since diagnosis of osteonecrosis was 6.3 years (range 49 years). Following AALCO treatment, 29 (28.7%) hips underwent THA, indicating that AALCO treatment could prevent and delay THA for 71.3% of hips. The mean time to THA was 3.2 2.0 years (range: 19 years). A total of 9 (39.1%) grade II, 11 (47.8%) grade III, and 3 (13%) grade IV hip joints required THA surgery (Figure 3B). In other words, AALCO treatment could delay THA for up to 3 years in 80% of hips in early stage osteonecrosis (Grades I and II) and 72% of hips in late stage osteonecrosis (Grades III and IV). Univariate analysis showed that the age of the patient, BMI, gender of patients, the side of osteonecrosis, and duration of disease had no effect on the clinical success of the procedure. Following AALCO treatment, 35.9% of patients continued using steroids and 29.7% continued with alcohol consumption. Of the total 29 hip joints that required surgery at follow-up, 20.7% and 41.4% had an associated etiology of alcohol consumption and steroid intake, respectively (Figure 4A). Overall, a significantly greater number of patients with underlying etiologies of alcohol consumption, smoking, or taking steroids required THA compared to those without these etiologies (14 [37.8%] vs 3 [11.1%], p = 0.017).

Figure 4 (A) Need for hip replacement stratified as per etiology of osteonecrosis. (B) Overall outcome stratified as per the grades of osteonecrosis.

Abbreviations: RA, rheumatoid arthritis; SLE, systemic lupus erythematous.

Based on the pre- and post-operative data, the condition of 65.6% of patients improved and 1.6% remained stable following AALCO treatment. Overall, the condition of 65.9% of hips (56/85) in grade I to grade III improved (Figure 4B). For quick reference, the pre- and post-operative radiograph images for a given patient are presented in Figure 5.

Figure 5 Pre- and posttransplantation MRI and X-ray images (A): pre-operative MRI (male patient [35 years]): Ficat and Arlet Stage II B with a subchondral fracture of right hip with a large anterolateral lesion(arrow) involving more than 40% of femoral head and less than 2mm depression at high risk of collapse. Etiology is post steroid AVN. (B) Post-operative MRI at 5 months post-surgery. (C) Post-operative X-ray at 4 years after surgery; anteroposterior (AP) view and lateral view.

We retrospectively studied the clinical outcomes of AALCO treatment. Our results showed that there was a reduction in pain and improvement in joint function following AALCO implantation, as was evident from a statistically significant reduction in the mean VAS score and increase in the HHS score. Of all the hips that underwent the AALCO implantation, 60% improved and 38% worsened with a THA conversion rate of 28%.

AALCO is a minimally invasive, surgical 3-step procedure with each step contributing significantly to the overall effectiveness of the treatment. The first step is core decompression that reduces pressure allowing increased blood flow. In the second step, the necrotic bone is debrided by a curette that promotes new bone formation. The third and most important step is implantation of osteoblasts that form new bone. The THA conversion rate is reported lower with core decompression compared to natural progression of disease, but approximately 40% of patients still required THA.8 Bone marrow cell therapy was shown to improve the THA conversion rate further.9 In a recent randomized trial, implantation of autologous bone marrow aspirate concentrate did not show any improvement in patients with grade 3 osteonecrosis.10 In our study, AALCO implantation avoided THA in 72% of hips in late grade osteonecrosis, suggesting that the technique may even benefit patients in advanced stages of disease; however, our results are limited by the relatively small numbers of patients belonging to each stage.

The differences in the THA conversion may not be directly comparable to those with others may be due to the diversity in the presentation of patients, differences in the follow-up period, or the AALCO technique.13,14 The THA conversion rate certainly remains low with AALCO treatment compared to 75% THA conversion rate reported in patients with natural progression to osteoarthritis resulting from osteonecrosis of the femoral head.15,16 A randomized study found autologous osteoblastic cells implantation to be more efficacious than bone marrow implantation as an adjunct to core decompression. The disease progression rate was found to be 20% in patients who had undergone autologous osteoblasts implantation vs 47% in patients in the bone marrow implantation group.11 Bone alkaline phosphatase-characterized osteoblasts have better regenerative potential compared to heterogeneous bone marrow cells.17,18 Use of these characterized cells could explain the favorable outcomes of AALCO implantation in our study.

Intake of alcohol and/or steroids is known to adversely affect bone renewal by causing an imbalance between the normal progenitor cells and the fat-storing bone marrow progenitor cells.1,19,20 The latter phenotype also leads to fat embolism and arteriosclerosis reducing the blood supply to necrotic tissues.1,19,20 In our study, alcohol and steroid intake were associated with occurrence of osteonecrosis of the femoral head in more than a quarter of patients. These results highlight the adverse impact of alcohol and steroid intake on the progression of osteonecrosis that is already evident in the literature in the pathogenesis of osteonecrosis.2125 As expected, THA conversion rate was also higher among patients who consumed alcohol and/or used steroids compared to those who did not in our study, signifying the adverse impact of alcohol and steroids on the AALCO treatment outcomes. However, a consensus on the specific mechanisms leading to these observations is yet to be reached.

A major limitation of our study was the retrospective data collection, and the lack of assessments of radiographic progression of the affected hips.

The results of this study substantiate the therapeutic potential for AALCO in improving clinical outcomes in terms of pain and functional activity, and reducing the risk of disease progression and the need for THA in patients with osteonecrosis. However, this study was limited by the small sample size and the retrospective data collection limiting the power of study for some subgroup comparisons. Further, clinical studies and long-term trials are warranted to confirm the findings of this study.

Authors acknowledge CBCC Global Research for providing medical writing and submission support funded by Regrow Biosciences Pvt. Ltd.

The authors report no conflicts of interest in this work.

1. Hernigou P, Poignard A, Zilber S, Rouard H. Cell therapy of hip osteonecrosis with autologous bone marrow grafting. Indian J Orthop. 2009;43(1):4045. doi:10.4103/0019-5413.45322

2. Gangji V, Hauzeur J-P, Matos C, De Maertelaer V, Toungouz M, Lambermont M. Treatment of osteonecrosis of the femoral head with implantation of autologous bone-marrow cells: a pilot study. J Bone Joint Surg Am. 2004;86(6):11531160. doi:10.2106/00004623-200406000-00006

3. Vardhan H, Tripathy SK, Sen RK, Aggarwal S, Goyal T. Epidemiological profile of femoral head osteonecrosis in the North Indian population. Indian J Orthop. 2018;52(2):140146. doi:10.4103/ortho.IJOrtho_292_16

4. Moya-Angeler J, Gianakos AL, Villa JC, Ni A, Lane JM. Current concepts on osteonecrosis of the femoral head. World J Orthop. 2015;6(8):590601. doi:10.5312/wjo.v6.i8.590

5. ISHKS registry. Available from: http://www.ishks.com/pdf/ISHKS-registry-2019.pdf. Accessed December 17, 2020. 2019.

6. Xie XH, Wang XL, Yang HL, Zhao DW, Qin L. Steroid-associated osteonecrosis: epidemiology, pathophysiology, animal model, prevention, and potential treatments (an overview). J Orthop Translat. 2015;3(2):5870. doi:10.1016/j.jot.2014.12.002

7. Jaffr C, Rochefort GY. Alcohol-induced Osteonecrosisdose and duration effects. Int J Exp Pathol. 2012;93(1):7879. doi:10.1111/j.1365-2613.2011.00798_1.x

8. Houdek MT, Wyles CC, Martin JR, Sierra RJ. Stem cell treatment for avascular necrosis of the femoral head: current perspectives. Stem Cells Cloning. 2014;7:6570. doi:10.2147/SCCAA.S36584

9. Xu S, Zhang L, Jin H, et al. Autologous stem cells combined core decompression for treatment of avascular necrosis of the femoral head: a systematic meta-analysis. Biomed Res Int. 2017;2017:6136205. doi:10.1155/2017/6136205

10. Hauzeur JP, De Maertelaer V, Baudoux E, Malaise M, Beguin Y, Gangji V. Inefficacy of autologous bone marrow concentrate in stage three osteonecrosis: a randomized controlled double-blind trial. Int Orthop. 2018;42(7):14291435. doi:10.1007/s00264-017-3650-8

11. Hauzeur JP, Toungouz M, Lechanteur C, et al. Autologous osteoblastic cells (PREOBy) versus concentrated bone marrow implantation in osteonecrosis of the femoral head: a randomized study. Revue de Chirurgie Orthopdique et Traumatologique. 2016;102(7):S73. doi:10.1016/j.rcot.2016.08.002

12. Cuende N, Rasko JEJ, Koh MB, Dominici M, Ikonomou L. Cell, tissue and gene products with marketing authorization in 2018 worldwide. Cytotherapy. 2018;20(11):14011413. doi:10.1016/j.jcyt.2018.09.010

13. Pepke W, Kasten P, Beckmann NA, Janicki P, Egermann M. Core decompression and autologous bone marrow concentrate for treatment of femoral head osteonecrosis: a randomized prospective study. Orthop Rev (Pavia). 2016;8(1):6162. doi:10.4081/or.2016.6162

14. Zhao D, Cui D, Wang B, et al. Treatment of early stage osteonecrosis of the femoral head with autologous implantation of bone marrow-derived and cultured mesenchymal stem cells. Bone. 2012;50(1):325330. doi:10.1016/j.bone.2011.11.002

15. Hernigou P, Habibi A, Bachir D, Galacteros F. The natural history of asymptomatic osteonecrosis of the femoral head in adults with sickle cell disease. J Bone Joint Surg Am. 2006;88(12):25652572. doi:10.2106/00004623-200612000-00002

16. Tomaru Y, Yoshioka T, Sugaya H, et al. Ten-year results of concentrated autologous bone marrow aspirate transplantation for osteonecrosis of the femoral head: a retrospective study. BMC Musculoskelet Disord. 2019;20(1):410. doi:10.1186/s12891-019-2797-4

17. Birmingham E, Niebur G, McHugh PE. Osteogenic differentiation of mesenchymal stem cells is regulated by osteocyte and osteoblast cells in a simplified bone niche. Eur Cell Mater. 2012;23:1327. doi:10.22203/eCM.v023a02

18. Prins H-J, Braat AK, Gawlitta D, et al. In vitro induction of alkaline phosphatase levels predicts in vivo bone forming capacity of human bone marrow stromal cells. Stem Cell Res. 2014;12(2):428440. doi:10.1016/j.scr.2013.12.001

19. Cui Q, Wang GJ, Balian G. Steroid-induced adipogenesis in a pluripotential cell line from bone marrow. J Bone Joint Surg Am. 1997;79(7):10541063. doi:10.2106/00004623-199707000-00012

20. Hernigou P, Beaujean F, Lambotte J. Decrease in the mesenchymal stem-cell pool in the proximal femur in corticosteroid-induced osteonecrosis. J Bone Joint Surg Br. 1999;81(2):349355. doi:10.1302/0301-620X.81B2.0810349

21. Sakaguchi M, Tanaka T, Fukushima W, Kubo T, Hirota Y. Impact of oral corticosteroid use for idiopathic osteonecrosis of the femoral head: a nationwide multicenter case-control study in Japan. J Orthop Sci. 2010;15(2):185191. doi:10.1007/s00776-009-1439-3

22. Kubo T, Ueshima K, Saito M, Ishida M, Arai Y, Fujiwara H. Clinical and basic research on steroid-induced osteonecrosis of the femoral head in Japan. J Orthop Sci. 2016;21(4):407413. doi:10.1016/j.jos.2016.03.008

23. Cooper C, Steinbuch M, Stevenson R, Miday R, Watts N. The epidemiology of osteonecrosis: findings from the GPRD and THIN databases in the UK. Osteoporos Int. 2010;21(4):569577. doi:10.1007/s00198-009-1003-1

24. Fukushima W, Fujioka M, Kubo T, Tamakoshi A, Nagai M, Hirota Y. Nationwide epidemiologic survey of idiopathic osteonecrosis of the femoral head. Clin Orthop Relat Res. 2010;468(10):27152724. doi:10.1007/s11999-010-1292-x

25. Kang JS, Park S, Song JH, Jung YY, Cho MR, Rhyu KH. Prevalence of osteonecrosis of the femoral head: a nationwide epidemiologic analysis in Korea. J Arthroplasty. 2009;24(8):11781183. doi:10.1016/j.arth.2009.05.022

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[Full text] Retrospective Study on Implantation of Autologous-Cultured Osteoblasts | ORR - Dove Medical Press

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India Stem Cell Market to surpass huge revenue of USD 1.27 Billion at CAGR +13% by 2028.

Stem cell therapy in India helps in treating several diseases, including leukaemia, lymphoma, thalassemia, Parkinsons, Alzheimers, stroke, cerebral palsy, spinal cord injury, muscular dystrophy, etc. Stem cell therapy in India has shown promising results in India and as well as all over the world.

In comparison, in India it costs INR 10-20 lakh in private hospitals, while in government hospitals it is much cheaper INR 3-6 lakh depending on the type of procedure, he said

On average, private banking of stem cells derived from cord blood costs INR 50,000-70,000. Banks claim to freeze the cells in liquid nitrogen so that it can be used up to 20 years from the date of preservation.

Researchers hope stem cells will one day be effective in the treatment of many medical conditions and diseases. But unproven stem cell treatments can be unsafe so get all of the facts if youre considering any treatment. Stem cells have been called everything from cure-alls to miracle treatments.

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Key players profiled in the report includes:

Thermofisher Scientific India Pvt. Ltd., Pluristem Technologies Ltd., Becton Dickinson Private Limited, Stem Cell Technologies India Pvt. Ltd., Merck Lifescience Pvt. Ltd., Cordlife India Pvt. Ltd., LifeCell International Pvt. Ltd., StemCyte India Therapeutics Private Limited, Stempeutics Research Private Limited, ReeLabs Private Limited, CryoSave, Indu Stem Cell Bank, Path Care Labs Pvt

The aim of the report is to equip relevant players in deciphering essential cues about the various real-time market based developments, also drawing significant references from historical data, to eventually present a highly effective market forecast and prediction, favoring sustainable stance and impeccable revenue flow despite challenges such as sudden pandemic, interrupted production and disrupted sales channel in the India Stem Cell market.

Market segments on the basis of:

This research report is an amalgamation of all relevant data pertaining to historic and current market specific information that systematically decide the future growth prospects of the India Stem Cell market. This section of the report further aims to enlighten report readers about the decisive developments and catastrophic implications caused by an unprecedented incident such as the pandemic that has visibly rendered unparalleled implications across the market.

This report is well documented to present crucial analytical review affecting the India Stem Cell market amidst COVID-19 outrage. The report is so designed to lend versatile understanding about various market influencers encompassing a thorough barrier analysis as well as an opportunity mapping that together decide the upcoming growth trajectory of the market. In the light of the lingering COVID-19 pandemic, this mindfully drafted research offering is in complete sync with the current ongoing market developments as well as challenges that together render tangible influence upon the holistic growth trajectory of the India Stem Cell market.

Besides presenting a discerning overview of the historical and current market specific developments, inclined to aid a future-ready business decision, this well-compiled research report on the India Stem Cell market also presents vital details on various industry best practices comprising SWOT and PESTEL analysis to adequately locate and maneuver profit scope. Therefore, to enable and influence a flawless market-specific business decision, aligning with the best industry practices, this specific research report on the market also lends a systematic rundown on vital growth triggering elements comprising market opportunities, persistent market obstacles and challenges, also featuring a comprehensive outlook of various drivers and threats that eventually influence the growth trajectory in the India Stem Cell market.

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India Stem Cell Geographical Segmentation Includes:

North America (U.S., Canada, Mexico)

Europe (U.K., France, Germany, Spain, Italy, Central & Eastern Europe, CIS)

Asia Pacific (China, Japan, South Korea, ASEAN, India, Rest of Asia Pacific)

Latin America (Brazil, Rest of L.A.)

Middle East and Africa (Turkey, GCC, Rest of Middle East)

Some Major TOC Points:

Chapter 1. Report Overview

Chapter 2. Growth Trends

Chapter 3. Market Share by Key Players

Chapter 4. Breakdown Data by Type and Application

Chapter 5. Market by End Users/Application

Chapter 6. COVID-19 Outbreak: India Stem Cell Industry Impact

Chapter 7. Opportunity Analysis in Covid-19 Crisis

Chapter 9. Market Driving Force

And More

In this latest research publication a thorough overview of the current market scenario has been portrayed, in a bid to aid market participants, stakeholders, research analysts, industry veterans and the like to borrow insightful cues from this ready-to-use market research report, thus influencing a definitive business discretion. The report in its subsequent sections also portrays a detailed overview of competition spectrum, profiling leading players and their mindful business decisions, influencing growth in the India Stem Cell market.

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Report Consultant A worldwide pacesetter in analytics, research and advisory that can assist you to renovate your business and modify your approach. With us, you will learn to take decisions intrepidly by taking calculative risks leading to lucrative business in the ever-changing market. We make sense of drawbacks, opportunities, circumstances, estimations and information using our experienced skills and verified methodologies.

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India Stem Cell Market speedy growth at US$ 1.27 Bn by 2028 with Thermofisher Scientific India, Pluristem Technologies, Becton Dickinson Private...

Bone Marrow Stem Cells Comments Off on India Stem Cell Market speedy growth at US$ 1.27 Bn by 2028 with Thermofisher Scientific India, Pluristem Technologies, Becton Dickinson Private… | February 3rd, 2021

World Cancer Day: Blood cancer can be managed with treatments such as chemotherapy, radiation therapy

World Cancer Day 2021: This day is observed on February 4. Blood cancer originates in the blood forming tissues when abnormal blood cells start growing out of control, thereby interrupting the functioning of the normal blood cells. The normal blood cells help strengthen the immune system by fighting infection and producing new blood cells. Most blood cancers begin in the bone marrow where blood is produced. The three most common blood cancers are lymphoma, leukaemia and multiple myeloma. The common symptoms include weakness, shortness of breath, minimal injury resulting in fractures, excessive or easy bruising, bleeding gums, recurrent infections and frequent vomiting sensations. Blood cancer can be managed with treatments such as chemotherapy, radiation therapy and stem cell transplant.

Multiple myeloma

Multiple Myeloma develops in the bone marrow and affects plasma cells of the body. Plasma cells are responsible for producing antibodies that attack infections and diseases. When these cells become cancerous, they collect in the bone marrow and weaken the bones, causing pain on movement. They also produce antibodies that are useless and make the body weaker. Some common symptoms for multiple myeloma include low blood count, high calcium levels, kidney problems and spinal cord compression due to weakened bones.

Also read:Cervical Cancer During Pregnancy: Here's All You Need To Know

Lymphoma

Lymphoma affects the lymphatic system, which is responsible for getting rid of toxins in the body. When the immune cells, or lymphocytes, grow out of control, they collect in the lymph nodes, spleen and in other tissues, and organs. The main types are Hodgkins and non-Hodgkin lymphoma. Some common symptoms for lymphomas include painful swelling in the neck, groin, and armpits, fever and drenching sweats, fatigue, unexplained weight loss and shortness of breath.

Leukaemia

Leukaemia is cancer in the bone marrow that gradually spreads to the bloodstream. It is the most common cause of death due to cancer in India. In Leukaemia, the bone marrow produces metamorphosed cells, that outgrow the healthy blood cells gradually. There are multiple forms of leukaemia, but the diagnosis is determined based on speed of symptom development and the type of blood cells that accumulate. Some common symptoms for leukaemia include severe and frequent infections, recurrent nosebleeds, tiny red spots on the skin and excessive sweating and pain in the bones and joints.

While lymphomas and leukaemia affect both children and adults, Myeloma is more prevalent among adults.

Also read:What To Do When A Cancer Patient Tests Positive For COVID-19?

There are several therapies that can be used for treating the different kinds of blood cancer such as:

While there have been developments and advancement in therapies and treatments available for cancer, a significant portion of the future cancer burden can be prevented if we take necessary precautionary measures in the early stages. Better control on tobacco sale and consumption, dietary changes, expansion and equitable distribution of medical facilities, awareness about education programs and risks, prevention, and knowing the benefits of bone marrow donation can go a long way in reducing the burden of blood cancer.

Also read:Alarming Cancer Symptoms Men Should Not Ignore

(Dr Nitin Sood, Director, Hemato Oncology and Stem Cell Transplant Medical and Haemato Oncology, Cancer Institute, Medanta)

Disclaimer: The opinions expressed within this article are the personal opinions of the author. NDTV is not responsible for the accuracy, completeness, suitability, or validity of any information on this article. All information is provided on an as-is basis. The information, facts or opinions appearing in the article do not reflect the views of NDTV and NDTV does not assume any responsibility or liability for the same.

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World Cancer Day 2021: Know All About The Different Types Of Blood Cancer From Expert - NDTV Doctor

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Combinations of JAK inhibitors and novel agents, such as epigenetic regulators, could help prolong survival in patients with myeloproliferative neoplasms (MPNs), providing patients with more than a reduction in spleen size and symptomatic relief, explained Shella Saint Fleur-Lominy, MD, PhD, who added that for patients who have already progressed on ruxolitinib (Jakafi), fedratinib (Inrebic), momelotinib, and pacritinib could be potential second-line options.

A lot of these agents will probably be used in combination with ruxolitinib for the most optimal response. Its very promising to see all those different agents emerge that have an effect on disease outcome and modulation of the bone marrow, said Saint Fleur-Lominy. For every symptomatic patient who gets diagnosed with myelofibrosis, polycythemia vera [PV], or essential thrombocythemia [ET], we need to determine if theyre a candidate for a clinical trial, because thats how we advance the treatment landscape.

In an interview with OncLiveduring a 2020 Institutional Perspectives in Cancer webinar on hematologic malignancies, Saint Fleur-Lominy, an assistant professor, Department of Medicine, at NYU Langone Healths Perlmutter Cancer Center, discussed the current landscape of MPNs and the importance of addressing disease burden and progression.

Saint Fleur-Lominy: Downstream of JAK, there are STAT dependent and independent pathways that are involved in disease modulation. A number of newer agents target those signals downstream of JAK. For example, theres the oral kinase inhibitor alisertib, which is downstream of cNeT, which is downstream of JAK. Its one of the molecules that is upregulated in this disease. The phase 1 study was very small, but when they analyzed bone marrow samples pre- and posttreatment, they saw that there was improvement in the degree of fibrosis, and preclinical data showed the same thing.

Other agents include epigenetic regulators. We have an ALS21 inhibitor. We have BT inhibitors. One was studied in combination with ruxolitinib in [JAK-inhibitor nave patients] and patients who didnt have a good response to ruxolitinib. One of the themes among these different agents is that that they modulate the disease. One of the key findings, particularly for the LSD1 inhibitor was that the bone marrow fibrosis and variant allele frequency was reduced significantly. Those diseases dont just have the JAK mutation, they have a lot of other genes that could be mutated and that have [an effect on] survival, disease progression, and response to treatment. Having drugs that target those repeated clones is very significant. Theres also a telomerase inhibitor, and there is a phase 3 trial that is being planned.

Patients can have thrombotic events like clots, and we see that across the different subtypes of PV, ET, and myelofibrosis. Patients who have a low level of fibrosis can have those complications. It doesnt matter how much fibrosis you have in the bone marrow. The risk is usually lower in younger people, but as you age, you see [patients at greater] risk.

There is also a risk of bleeding events as well, especially in ET when people have a very high platelet count. There is also a risk of leukemic transformation because MPN is a disease that has mutations in hematopoietic stem cells, and those stem cells can transform [and] acquire new high-risk mutations and other chromosomal abnormalities and transform into acute leukemia.

In terms of symptom burden, a very large study looked at the symptomatic manifestation of MPNs [and found that] the burden is really high. Approximately 80% of patients have a really high symptomatic burden, [ranging] from fatigue to other symptoms like reduced appetite, early satiety because of big spleen, or the big spleen causing abdominal discomfort. As high as 60% of patients have abdominal discomfort, or early satiety. Up to 80% of patients reported fatigue.

Other symptoms like itching and night sweats [were also common]. Itching you see more with PV. Weight loss, fever, and bone pain [are additional symptoms that patients may experience]. The severity varies, so some patients have mild symptoms, and some patients have more severe symptoms. The main thing is that patients with MPNs have a very high symptomatic burden. Thats one of the reasons [a lot of studies] evaluating drugs in this disease usually use spleen reduction size and symptomatic relief as end points.

One of the most common mutations is JAK2. These are diseases of abnormal JAK signaling. About 95% of patients with PV have the classic JAK2 V617F mutation, and the rest usually have [a JAK exon 12 or exon 14 mutation]. The JAK V617F mutation is found in up to 60% of patients with ET or myelofibrosis. MPL and CALR mutations are found in up to 30% [of patients].

Ruxolitinib was the first JAK inhibitor that was approved for the treatment of higher-risk myelofibrosis, and then later on was approved for the treatment of patients with PV who are intolerant to hydroxyurea or have not responded to hydroxyurea and are symptomatic.

[The end point that was evaluated in the pivotal trial] in myelofibrosis was reduction of spleen volume and symptomatic relief. The COMFORT-I and COMFORT-II trials were both randomized controlled trials. The COMFORT-I trial had a placebo [control] and the COMFORT-II trial had best available therapy [as the control]. Both of these studies also had significant crossover. Once the investigators realized that ruxolitinib [led to a significant improvement in] patient outcomes and symptom relief, and that there was a signal for overall survival [OS], [patients were] allowed crossover [to receive ruxolitinib]. In COMFORT-II, there wasnt really a significant [improvement in] OS, but the crossover [probably] affected that.

In terms of PV, patients were higher risk and were not responding to hydroxyurea or were intolerant to hydroxyurea. These patients were phlebotomy dependent. A significant number of patients achieved phlebotomy independence and had a reduction in spleen volume and symptoms.

Fedratinib [Inrebic] is a selective JAK2 inhibitor compared with ruxolitinib, which is a JAK1/2 inhibitor. The thought is that [fedratinib] will be better tolerated than [ruxolitinib. When the investigators did the randomized placebo-controlled trial for fedratinib, they evaluated 2 different doses of fedratinib. At the higher dose, they saw a rare but serious complication of Wernicke encephalopathy. Because of that, were using the lower dose of 400 [mg].

In terms of the decrease in spleen size and symptoms, there didnt seem to be a difference between the 400 [-mg] and the 500 [-mg] dose. Therefore, it makes sense that the 400 [-mg dose] is the one that were using. [Although fedratinib] results in less thrombocytopenia, ruxolitinib is the go-to drug for patients who can tolerate it. You can still use fedratinib post-ruxolitinib, but I dont know about the reverse [sequence].

We saw updated data [for momelotinib from the SIMPLIFY-1 and -2 studies] at the 2020 ASH Annual Meeting and Exposition. [Momelotinib] inhibits JAK1/2 and Activin receptor 1. One of the studies was a noninferiority study that randomized JAK-inhibitor nave patients to ruxolitinib or momelotinib. The outcome was about the same. The other study was designed to be a superiority trial that was against best available therapy in patients who were post-ruxolitinib. The primary end point was clinical response rate, and it met the end point. [We also saw an improvement in] the total symptom scores and transfusion independence. The sustained responses and the survival benefit [for momelotinib] makes it a very promising [agent], especially for patients post-ruxolitinib compared with best available therapy.

A lot of those patients are older, and they may not be candidates for transplant. Therefore, having something that can prolong survival and make them feel better, post-ruxolitinib, is really important. When you withdraw ruxolitinib, patients can have symptoms rebound, which also seems to have an effect on survival, so if you have another JAK inhibitor that can keep them going, thats very helpful. Im hopeful for momelotinib and pacritinib.

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MPN Efforts Set Sights on Improved Survival and Symptom Burden - OncLive

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World Cancer Day 2021: Leukemia is a type of blood cancer

World Cancer Day: It is true that most of the cancers get diagnosed at a later stage and the precious time is lost to give a patient a quality life ahead. But effective screening methods implemented in the early diagnosis of blood cancer can help save lives. India ranks third highest in reporting blood cancer cases, after US and China. Almost a lakh of new cases of blood disorder are reported each year. There are several different types of blood cancer depending upon the type of blood cells it affects primarily.

There are three types of blood cancers - leukemia, lymphoma and myeloma. Leukemia occurs when one can suffers from rapid production of abnormal cancer cells in the bone marrow. Thus, due to the abnormal cancer cells, the bone marrow's ability of the production of red blood cells and platelets gets affected. Leukemia occurs most often in adults older than 55, but it is also the most common cancer in children younger than 15.

Having a risk factor, or even several risk factors, does not always mean that a person will get the disease, and many people get cancer without having any known risk factors.

While, in most of the cases, the exact cause of Leukemia is not known, but certain risk factors can attribute to the risk of Leukemia, like:

a. Radiation exposure - High-dose radiation exposure (such as being a survivor of an atomic bomb blast or nuclear reactor accident) increases the risk of developing acute myeloid leukemia (AML). Radiation treatment for cancer has also been linked to an increased risk of AML. The risk varies based on the amount of radiation given and what area is treated.

b. Previous chemotherapy for cancer

c. Smoking and drinking

Family history of leukemia - Although most cases of AML are not thought to have a strong genetic link, having a close relative (such as a parent, brother, or sister) with AML increases your risk of getting the disease. Someone who has an identical twin who got AML before they were a year old has a very high risk of also getting AML.

Genetic Disorder - e.g. Down syndrome, Fanconi anaemia

Exposure to certain chemicals - For example, long-term exposure to benzene is a risk factor for acute myeloid leukemia, a type of blood cancer. Benzene is a solvent used in the rubber industry, oil refineries, chemical plants, shoe manufacturing, and gasoline-related industries, and is also found in cigarette smoke, gasoline and motor vehicle exhaust, and some glues, cleaning products, detergents, art supplies, and paints.

World Cancer Day 2021: Leukemia can lead to shortness of breathPhoto Credit: iStock

Awareness, early diagnosis and treatment are the key:

Early diagnosis and awareness of symptoms allows for more treatment options and can improve survival rates in Leukemia. Some early cancers may show signs and symptoms but that may not always be the case. Initially, doctors make a note of family history and conduct a complete physical examination of the patient. Blood tests may include complete blood count with evaluations of liver and kidney function tests. Bone marrow examination is eventually done to diagnose blood cancers. Diagnostic imaging tests such as CT scan, PET scan, MRI, and/or X-rays may be performed to assess the extent of the disease at diagnosis, and also to assess response after treatment. There is no way to prevent Leukemia at large, but avoiding tobacco and exposure to pesticides and industrial chemicals might help in reducing the risk of Cancer. It is important to also ensure that people with cancer have access to safe and effective treatment that also includes pain relief.

There are several treatment options for blood cancer. The type of treatment depends upon the type and stage of blood cancer, age of the patients and the other underlying medical conditions. Most blood cancers generally include chemotherapy, radiation therapy, stem cell transplant (bone marrow and cord blood transplant), and immunotherapy.

Symptoms to watch for:

To spread awareness on early diagnosis, people need to be educated on various symptoms of blood cancer and seek timely intervention

(Dr. Sunil Bhat, MBBS, MD (Pediatrics) Mazumdar Shaw Cancer Centre, Narayana Health City, Bengaluru)

Disclaimer: The opinions expressed within this article are the personal opinions of the author. NDTV is not responsible for the accuracy, completeness, suitability, or validity of any information on this article. All information is provided on an as-is basis. The information, facts or opinions appearing in the article do not reflect the views of NDTV and NDTV does not assume any responsibility or liability for the same.

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World Cancer Day 2021: Know The Symptoms And Risk Factors Of Leukemia - NDTV Doctor

Bone Marrow Stem Cells Comments Off on World Cancer Day 2021: Know The Symptoms And Risk Factors Of Leukemia – NDTV Doctor | February 3rd, 2021

DRESDEN, Germany, Feb. 3, 2021 /PRNewswire/ -- GEMoaB, a biopharmaceutical company focused on the development of next-generation immunotherapies for hard-to-treat cancers, today announced interim data from the ongoing Phase I study of their lead asset UniCAR-T-CD123 in relapsed/refractory acute myeloid leukemia (rrAML) at the Virtual 3rd EHA-EBMT European CAR-T-Cell Meeting, which is held from February 04-06, 2021. The data are being presented as oral presentation by Dr. Martin Wermke, University Hospital Dresden, Germany (February 05, 12:20 CET) and as a poster presentation by Dr. Sabrina Kraus, University Hospital Wrzburg, Germany (Abstract 68).

"These clinical results present a promising step forward as we continue to evaluate the safety and efficacy of UniCAR-T-CD123," said Professor Gerhard Ehninger, Chief Medical Officer of GEMoaB. "We are highly encouraged by the fact that UniCAR-T-CD123 has demonstrated a favorable safety and efficacy profile in rrAML. The clinical data nicely confirm our UniCAR key platform claims and provide the clinical proof of UniCAR's rapid switch on/off and re-activation capability. We look forward to progressing our study and positioning UniCAR as a potentially superior cellular immunotherapy platform for patients with hard-to-treat advanced hematologic malignancies and solid tumors."

Data highlights for the oral presentation titled: "Proof-of-Concept for Rapidly Switchable Universal CAR-T Platform with UniCAR-T-CD123 in Relapsed/Refractory AML" include:

The poster named "Re-activation of UniCAR-T-Cells with 2nd Cycle of Targeting Module TM123 in a Patient with Relapsed/Refractory AML" is summarizing data obtained on re-activation and re-expansion of UniCAR-T cells, leading to a CRi in the respective patient.

Both presentations will be available on the GEMoaB website following the congress.

About the UniCAR-T-CD123 Phase IA Study

This first-in-human phase I study is an open-label, non-randomized, dose-finding study designed to evaluate the safety and activity of UniCAR-T-CD123 in up to 16 CD123 positive patients with relapsed/refractory AML. Its purpose is to determine the maximum tolerated dose (MTD) as well as Dose limiting toxicities (DLT) of the combined application of a single dose of UniCAR-T and the continuous infusion of TM123 over 25 days. Application follows post bridging therapy and lymphodepletion. The study also investigates response rates, response duration, persistence of UniCAR-T cells over time as well as the ability to rapidly switch UniCAR-T cells on and off in case of side effects through stopping TM infusion. The study takes place at selected Phase I, Acute Leukemia and CAR-T experienced University centers in Germany. The study is supported by a grant from the German Federal Ministry for Education and Research (project "TurbiCAR"). To learn more about the trial, please visit clinicaltrials.gov.

About UniCAR

GEMoaB is developing a rapidly switchable universal CAR-T platform, UniCAR, to improve the therapeutic window and increase efficacy and safety of CAR-T cell therapies in challenging cancers, including acute leukemias and solid tumors. Conventional CAR-T cells depend on the presence and direct binding of cancer antigens for activation and proliferation. An inherent key feature of the UniCAR platform is a rapidly switchable on/off mechanism (less than 4 hours after interruption of TM supply) enabled by the short pharmacokinetic half-life and fast internalization of soluble adaptors termed TMs. These TMs provide the antigen-specificity to activate UniCAR gene-modified T-cells (UniCAR-T) and consist of a highly flexible antigen binding moiety, linked to a small peptide motif recognized by UniCAR-T.

About GEMoaB

GEMoaB is a privately-owned, clinical-stage biopharmaceutical company that is aiming to become a fully integrated biopharmaceutical company. By advancing its proprietary UniCAR, RevCAR and ATAC platforms, the company will discover, develop, manufacture and commercialize next-generation immunotherapies for the treatment of cancer patients with a high unmet medical need.

GEMoaB has a broad pipeline of product candidates in pre-clinical and clinical development for the treatment of hematological malignancies as well as solid tumors. Its clinical stage assets GEM333, an Affinity-Tailored Adaptor for T-Cells (ATAC) with binding specificity to CD33 in relapsed/refractory AML, and GEM3PSCA, an ATAC with binding specificity to PSCA for the treatment of castrate-resistant metastatic prostate cancer and other PSCA expressing late stage solid tumors, are currently investigated in Phase I studies and globally partnered with Bristol-Myers Squibb. Phase IA dose-finding studies of the first UniCAR assets UniCAR-T-CD123 in hematological malignancies and UniCAR-T-PSMA in solid tumors are currently recruiting patients.

Manufacturing expertise, capability and capacity are key for developing cellular immunotherapies for cancer patients. GEMoaB has established a preferred partnership with its sister company Cellex in Cologne, a world leader in manufacturing hematopoietic blood stem cell products and a leading European CMO for CAR-T cells, co-operating in that area with several large biotech companies. More information can be found at http://www.gemoab.com.

For further information please contact Jana Fiebiger [emailprotected] Tel.: +49 351 4466-45012

Investor Contact Michael Pehl [emailprotected] Tel.: +49 351 4466-45030

Forward-looking Statements. This announcement includes forward-looking statements that involve risks, uncertainties and other factors, many of which are outside of our control, that could cause actual results to differ materially from the results and matters discussed in the forward looking statements. Forward looking statements include statements concerning our plans, goals, future events and or other information that is not historical information. The Company does not assume any liability whatsoever for forward-looking statements. The Company assumes that potential partners will perform and rely on their own independent analyses as the case may be. The Company will be under no obligation to update the Information.

SOURCE GEMoaB

https://www.gemoab.com/

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GEMoaB Announces UniCAR-T-CD123 Data from its Ongoing Phase I Study in Patients with Relapsed/Refractory AML (rrAML) to be Presented at Virtual 3rd...

Bone Marrow Stem Cells Comments Off on GEMoaB Announces UniCAR-T-CD123 Data from its Ongoing Phase I Study in Patients with Relapsed/Refractory AML (rrAML) to be Presented at Virtual 3rd… | February 3rd, 2021

The SA Bone Marrow Registry (SABMR) says their ability to recruit new donors has been severely limited by the outbreak of the second Covid-19 wave.

SABMR head of donor recruitment Nadia Chalkley said they typically recruit a few hundred new donors each year from the Eastern Cape.

The shrinking pool of donors has had a material impact on our ability to match patients suffering from life threatening blood diseases with suitable donors, she said.

At any given time, there are more than 200 patients in SA that need a bone marrow transplant. The fewer donors we have, the lesser the chance of finding a match. For patients with leukemia, thalassemia and other blood disorders, a bone marrow transplant is their only hope of survival.

Chalkley said the the current odds of finding a successful match is about one in 100,000 and will only get worse as the donor pool continues to shrink.

Sadly, more than 70% of patients struggle to find a stem cell match within their own families, which means many rely on strangers for a second chance at life.

If local donors are not forthcoming, we have to look overseas for potential matches, which is costly.

She said SABMR was working hard to ensure the safety of donors and patients by allowing online registration.

We also offer at-home sampling kits, which only requires a cheek swab. These kits can be delivered and collected free of charge from anywhere in the country.

Once new donors have completed the online registration form, they will be contacted by one of our consultants to discuss the easiest way of dispatching and collecting the kits.

One of the biggest misconceptions with regards to bone marrow donation, according to Chalkley, is that it involves large needles being pushed into ones spine.

However, the most common form of donation is whats called peripheral blood stem cell collection, since the same blood-forming cells found in bone marrow are also present in circulating blood.

The process is similar to donating plasma and doesnt require surgery.

In order to register as a bone marrow donor, you must be between the ages of 16 and 45 and meet the required standards listed by the SABMR.

A full list of the criteria can be found at https://sabmr.co.za/.

Each of us have a role to play. This new year, put away frivolous resolutions and rather direct your energy into making a difference by signing up as a donor. The simple act could just make someones new years wish come true, Chalkley said.

Visit the SABMR website, call 021-447-8638 or email donors@sabmr.co.za

Related

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Covid-19 leads to shortage of bone marrow donors - GO! and Express

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Leukemia is the cancer of blood cells, usually white blood cells which fight and clears infections. It is also known as cancer of blood-forming tissues i.e lymphatic system and bone marrow. It is usually characterized by greatly increased numbers of abnormal white blood cells in circulating blood. It is a very serious disorder and the patient needs to change the blood regularly with normal blood from donors.

By Aysha Bibi

How does leukemia develop?

Our blood contains many different types of cells. These include red blood cells, white blood cells, and platelets. These cells are made on daily basis in the bone marrow. Leukemia happens when the body starts making white blood cells beyond its need. Immature white blood cells are released in the blood and these are non-functional. Moreover, as white blood cells increase in number, the number of red blood cells and platelets are not enough to maintain a healthy life and perform their normal functions.

Types of Leukemia

Leukemia has four main types

In the acute form of leukemia, cells multiply quickly in the bone marrow and enter the circulatory system too early but these cells are immature and non-functional. Chronic leukemia occurs when marrow produces mature cells and it progresses more slowly than other forms.

Lymphocytic leukemia is a type with an accumulation of apparently mature dysfunctional lymphocytes. Normally lymphocytes differentiate to form B-cells, T-cells, and natural killer cells which are the backbone of the immune system.

Myelogenous leukemia is a cancer of white blood cells usually granulocytes and monocytes. Either it is lymphocytic or myeloid, leukemia results in a compromised immune system, and the body cannot protect itself from different infections.

Acute lymphocytic leukemia(ALL) It is most common in children. It can spread to the central nervous system.

Acute myelogenous leukemia(AML) It is the second most common type of leukemia in children and also common in adults.

Chronic lymphocytic leukemia It is common in adults. This remains stable for many years but in some types, patients need treatment.

Chronic myelogenous leukemia(CML) Older people may are at higher risk for this type of leukemia.

Risk Factors

Some significant risk factors that can cause leukemia

Symptoms of Leukemia

Various types of leukemia can cause different symptoms. These symptoms usually not appear in the early stages, but they may include;

Diagnosis of Leukemia

CBC: with a blood test doctor looks at several different blood cells and their maturity. Immature cells may appear in the blood.

Bone marrow biopsy is done by taking bone marrow. With help of this doctor check the type and severity of leukemia.

CT scan and MRI are also done for the diagnosis of leukemia.

Treatment of Leukemia

Depending on the type of leukemia and its spreading, a doctor may look for the following options:

In a radiation treatment, high energy X-rays are used to kill leukemic cells. But normal cells are also affected.

In chemotherapy, different drugs are given to kill leukemic cells in blood and bone marrow. This may include a pill or injection in muscle or vein.

Targeted therapy is done to block the expression of some genes or proteins that are involved in the production of cancerous cells.

A Stem cell transplant involves a bone marrow transplant from a healthy donor. In this method, high-dose chemotherapy is done to destroy the leukemic cells of a patient. The healthy stems cells of donor are then injected to body.

Splenectomy is the removal of spleen and doctor may look for this option if spleen becomes fills with cancer cell and start affecting other body organs.

Preventing or reducing the risk of leukemia

Unfortunately, there is currently no cure for leukemia. Minimum exposure to pesticides and radiations may help to reduce the risk of leukemia. Leukemia can also be prevented by avoiding tobacco.

One can lower the risk of developing leukemia by following:

It is the best way to lower the risk of leukemia.

Studies have shown that overweight and obesity are also contributing factors to increasing the risk of developing leukemia.

Pollution, gasoline, car exhaust contains low levels of benzene. It is also found in offices and homes and found in paint, glue, etc. wearing a mask while using these may help you lower the risk of exposure.

Medical radiations like x-rays increase the risk of leukemia. Try to avoid unnecessary radiation exposure.

Your body and mind function at their best with a healthy diet. Proper nutrition provides energy fuel for body functioning, it also strengthens the immune system.

References:

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What Is Leukemia: And How To Prevent It? - Technology Times Pakistan

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