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San Diego News Icon Don Bauder Gives His Heart to Ideal Candidate Bloomberg – Times of San Diego

Share This Article:Mike Bloomberg has a new fan in retired San Diego business journalist and columnist Don Bauder (inset). Photos by Chris Stone, Ellen BauderAt 83, San Diego journalism legend Don Bauder is guarding his health playing hermit at home (to avoid the flu) and venturing out only for doctor visits.

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Bauder, a Colorado resident since 2003, was forced by heart issues to retire in 2018 as a San Diego Reader columnist. But now he admits hell be questioned about his mental health.

Hes backing Mike Bloomberg for president.

Here I am finally making headway against the heart problems and now I am considered a candidate for the loony bin, Bauder said by email Wednesday.

If exercise and multiple trips to doctors and hospitals will repair my brain as they seem to have helped my heart, I feel I can thwart oncoming dementia, although I have never claimed that I am either stable or a genius as President Donald Trump has. I am at least stable enough to hope that my candidate will not choke on verbal borscht, as Trump does almost every day.

Bauder isnt wearing rose-colored glasses, though.

He concedes that the former New York City mayor once stated that if women wanted to be known for their intelligence, they would spend less time at Bloomingdales and more time at the library.

Bloomberg called the remark a Borscht Belt joke, Bauder said.

The former San Diego Union-Tribune financial editor also noted that Bloomberg once stated that 95% of murderers are male minorities, 15 to 25 who deserve to be pushed up against the wall.

Bauder adds: Democrats desperately need the votes of women, African-Americans and Latinos. New Yorkers have told me that those minorities will never forget, although Bloomberg has renounced his widely criticized stop-and-frisk policy that clearly discriminated against minorities while he was mayor of New York.

But it wasnt until former U-T colleague Logan Jenkins outed himself as a Bloomberg fan that Bauder also emerged from the closet at least locally.

Bauder wrote Times of San Diego:

As a former newspaper columnist and magazine writer, I agree wholeheartedly with Logan Jenkins. After a lot of pondering, I have concluded that Bloomberg is the ideal Democratic candidate. I started out backing Biden, but have become quite disenchanted. Unlike Trump, Bloomberg is a self-made billionaire.

Unlike Trump, who is clearly a sociopath on steroids, as well as a pathological liar and malignant psychotic narcissist, Bloomberg is eminently stable and also brilliant, as he proved in his business career and as mayor of New York City. I would add one thing to what Logan says: we desperately need a female on the ticket. As shown in 2018, females can see through Trump.

I would suggest Kamala Harris; her minority status would help balance the ticket. I worry that Bloombergs stop and frisk mistake will continue to turn off minorities.

Like Bloomberg, Bauder is a former Republican. (From 1960 to 1964, when he was in advertising and PR, Bauder voted for Richard Nixon.)

Since 2004, he says, hes voted for Democratic presidential candidates.

This year, however, I had problems, he wrote Wednesday. I feared that both Bernie Sanders and Elizabeth Warren had gone too far. I dont like Medicare for All. Those who want to keep their private plans should be able to do so. I cant see free higher education for all. Frankly, I think too many students are in college now.

Bauder calls student debt a cancerous problem, but cant see canceling it out.

Should we reimburse those who have already paid off their debt? I cant see giving stipends to families descended from slaves, he said. If anybody deserves to be paid off, its Native Americans, from whom we stole our country.

He said his cautious views left him with moderate choices.

I originally favored Joe Biden, but became disenchanted quickly. I liked Amy Klobuchar from the beginning, and I am happy to see her rising fast, he said. Pete Buttigieg is quite intelligent but needs seasoning. Ditto Tom Steyer.

Bauder considers the 2020 election critical.

Four more years of Trump would be disastrous, he said. Yes, I am concerned about more Russian hacking. Given the close 2016 races in Wisconsin, Michigan and Pennsylvania, we should all worry about Russian hacking this year.

Climate change is the most critical issue for Bauder because if the world doesnt do more to curb greenhouse gases, the world as we know it may suffocate by the end of the century.

This interview was conducted via email.

Times of San Diego: What does Mike Bloomberg offer?

Don Bauder: First: money. Lots of it. Hes worth close to $60 billion, making him 14th-richest in the world, according to Forbes. Unlike Trump, Bloomberg made the money himself. And he is ACTUALLY worth that.

Trump may not even be a billionaire, despite his claims to be worth $10 billion. The biggest advantage of Bloombergs wealth is that he can flood the nation with ads showing that Trump is a phony. Indeed, Bloomberg is already doing that, but you aint seen nuthin yet.

The Democratic Party is hurting for money. Bloomberg is NEEDED. He has not alienated the business community. Right now, money is flowing to Republican coffers because big business particularly pharmaceuticals, insurance, oil and the like is terrified of Sanders and Warren. That river of cash will slow down if the leftists are out of the picture.

As he has proved as New York mayor, Bloomberg is socially liberal and progressive. He supports abortion rights, government-funded stem cell research, same-sex marriage, gun control, environmentalism and routes to citizenship for illegal immigrants.

He is strong on public welfare and is a national leader in the battle against climate change. He wants to enhance the earned income tax credit. But unlike the other candidates, he has support from many in the business community. He is in favor of free trade. He is a fiscal conservative. He balanced New York Citys budget. Facing a crisis, he talked a Republican state Senate into passing a tax increase rather than slashing jobs.

He opposes wealth inequality proposing, for example, that his own taxes should go up. He says generally that taxes for the rich should rise. He would raise corporate taxes from 21% to 28% percent not enough in my judgment, but a good start.

He dislikes the fact that taxes on stock and bond gains are lower than income taxes. He would enhance worker rights and benefits although he has never been considered pro-union. He wants a $15 an hour minimum wage. He favors government-financed welfare projects. He believes rural communities should be more closely connected with urban centers.

During his political career, he has been a Republican, an independent and a Democrat. He knows his way around politics, having been mayor of New York City from 2002 to 2013.

He cracked one time that a short Jew would never be elected president, but I question that. He will absolutely eat up Trump in a debate. It will be obvious that he is 10 times smarter than Trump.

(Bauder cites the same metric in the San Diego mayors race, saying he favors Barbara Bry because of her intelligence.)

Your journalism career is marked by major investigations into scam artists and political boondoggles. What gives you confidence that Bloomberg has genuine concern for the common good and not himself and his affluent cohort?

He favors corporate welfare corporate projects partly funded by government. I consider most such projects to be scams, although few others do. As mayor of New York, he has warned the citizenry of scam artists on the loose. But early in his mayoral term he vetoed a bill against predatory lending.

Why should Sen. Kamala Harris be Bloombergs running mate?

First, the Democrats must have a female on the ticket on the top of the ticket or the vice president. If Bloomberg is at the top, a female must run for the second slot. A minority female would be greatly preferred. Kamala Harris fills that bill. Stacey Abrams or Oprah Winfrey (who says she doesnt want it) would also be excellent.

If Bloomberg doesnt break out in Super Tuesday voting, will he have a shot at winning enough delegates to prevail at Milwaukee Democratic National Convention?

If Bloomberg does poorly, he will have to consider dropping out. If he does drop out, he should continue giving his planned donations to the Democratic Party. Ditto Tom Steyer. Both must continue to give if they are no longer candidates. The Democratic Party is not in good financial shape. If Bloomberg loses, I would hope Sherrod Brown, senator of Ohio, would get in the race.

Bloomberg has credibility from his mayor terms and gun-control and climate-change work. But he was elected in a very liberal environment. Could he challenge Trump in red states?

You make a good point that Bloomberg might not go over well in red states where uneducated voters are abundant. Many Americans hate New Yorkers unfortunately, often for good reasons. But although Bloomberg is short in stature, many voters will realize that he would be the real alpha male in the race. He is tough and knowledgeable. He would take hard stands on many issues.

Handicap a Trump vs. Sanders contest.

Trump has already called Sanders a communist not a socialist, which he is. So we would have a rerun of Joe McCarthy. If Trump continues to call Sanders a communist, Democrats should call Trump and his ilk fascists. Down and dirty. I think Sanders would take the West Coast and most of the East Coast, including Florida.

But Trump would take states where education levels are low the South, and Northern states such as Montana, Wyoming, Idaho, North and South Dakota, Kansas, Nebraska and other traditionally red (redneck?) states. Colorado, New Mexico and even possibly Arizona could go for Sanders.

Ohio, Indiana and Iowa could go red and Wisconsin and Minnesota might go blue. Illinois could stay blue. Much depends on whether Americans realize that Trump is a pathological liar, sociopath, malignant psychotic narcissist. He seems totally out of control now.

Critics like Paul Heideman call Bloomberg a classic oligarch using his wealth to tilt the economic and political playing field in his favor. Can voters trust someone who uses vast wealth to gain support? How is billionaire Bloomberg better suited to the Oval Office than billionaire Steyer (or anyone else)?

Paul Heideman has a point. You are correct that some voters will see how many ads he spreads around and hold his wealth against him. But these people could be swayed by the wave of advertising.

What Bloomberg can do is massively sponsor ads that emphasize that Trump is a liar showing him saying one thing one day and the opposite the next day. Also, such ads could show that Trumps claims about the economy on his watch are false.

For example, Trump keeps repeating that the economy has done better under him than at other times. This is laughably false. GDP is growing a little over 2% now and there have been many times when it grew 3% and even 4%. Trump says unemployment is the lowest ever, and that is also false. These ads can also show Trump at his most vulgar. That might even go over well in redneck territory, however. Trumps racism through his dog whistles could be emphasized in certain markets but not in redneck areas.

Would Bloomberg address wealth inequality?

Bloomberg is strongly opposed to wealth inequality and says his own taxes should go up. However, he would only raise the corporate tax rate to 28% from 21%. Thats not enough, in my judgment. He believes income taxes for the rich should be boosted. He is also disgusted that taxes on stock and bond profits are lower than taxes on incomes.

He complains that economic growth is concentrated in a small number of regions. He would enhance worker rights and benefits although he has never been known as pro-union a possible negative. He wants a $15 minimum wage. He favors government-financed welfare projects. He would like to see rural communities better connected to urban growth centers. He wants to see research and development in regions needing development.

How is your health?

I saw my cardiologist just two weeks ago. I asked him if I was a candidate for a stent in my two arteries that are only moderately good. He said no. (Background: I have had two quadruple-bypass surgeries. The last one was in 1990. On average, the grafts last 30 years.) But cardiologists (I have had several) say this does not mean I have only two years to go.

The heart itself seems to be OK, but the concern is arteries or grafts from previous surgeries filling up. I will be 84 in May. I dont expect to make it to 90, but with lots of luck I may get half or a third of the way there.

San Diego News Icon Don Bauder Gives His Heart to Ideal Candidate Bloomberg was last modified: February 14th, 2020 by Ken Stone

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San Diego News Icon Don Bauder Gives His Heart to Ideal Candidate Bloomberg - Times of San Diego

5 Aesthetic Clinics To Know In The Klang Valley & Their Signature Treatments – Malaysia Tatler

Flawless skin and more beauty fixes at these top aesthetic clinics around town

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Located at The Shoppes at Four Seasons Place, La Jung is Kuala Lumpurs newest anti-aging and aesthetic clinic, offering anti-aging solutions from Switzerland in partnership with leading Swiss medical clinics.

Helmed by Cardiff-trained aesthetic medical practitioner Dr Nicholas Lim, La Jung spans 5,275sf and comprises five plush treatment rooms, two VIP waiting rooms, a VIP lounge, a VVIP waiting and treatment room, and even a discrete alternative entrance leading directly to the carpark.

Signature treatments: The Sylfirm treatment helps to suppress a common type of skin pigmentation among Asians known as melasma, according Dr. Nicholas. This sophisticated procedure uses technology developed in Silicon Valley, and is typically used to treat melasma in addition to laser treatment in more stubborn cases.

PicoPlus is another specialty of La Jung. It refers to the use of a second-generation pico and nano-second laser to tackle blotchy pigmentation with minimal damage to the surrounding tissue.

Call 03-2856 7616 for more information.

Photos: The Glitz Of La Jung Malaysia's Grand Opening

Beverley Wilshire Medical Centre offers medical aesthetic treatments, anti-ageing medicine, cosmetic surgery, dental aesthetics and hair restoration at its main branch in Jalan Tun Razak. The clinic is known for its non-surgical treatments including V-shape face and nose reshaping.

Signature treatments: A trusted name in cosmetic tourism packages, Beverley Wilshire Medical Centres cosmetic vacation is an all-in-one deal, pairing treatments with an overnight stay at one of its luxury suites or a partner hotel nearby, plus meals, post-op follow-ups and even airport transfers.

Call 03-2118 2888 for more information.

The art of aging gracefully is yours to explore at the Bangsar-based M.A.C Clinic, which specialises in non-invasive or minimally invasive treatments that require little to no downtime.

Offering treatments in body slimming, breast enhancements and laser treatments to preventive age management that targets health risk factors in ones lifestyle, M.A.C clinic is helmed by Dr Hew Yin Keat, a founding member of the Malaysian Society of Aesthetic Medicine.

Signature treatments: Dubbed The Liquid Face Lift, this procedure uses injectable fillers to minimise sagging skin and fine lines without the downtime of plastic surgery, according to Dr Hew. The Picosure Laser treatment is another highly sought-after treatment to improve the appearance of acne, scars and other pigmentation. Other signatures include regenerative medicine, stem cell treatments, the Infini Scar Treatment, and CoolSculpting by Zeltiq.

Call 03-2283 1212 for more information.

Related: MAC Clinic Unveils First PicoSure Laser Treatment in Malaysia In An Exclusive Party At Marinis On 57

Helmed by medical director Prof Dr Edmond Ng (also assistant professor and consultant at the Faculty of Medicine & Health Sciences at UCSI University), Xeoul Clinic boasts a team of full-time consultant aesthetic doctors with more than 10 years of experience.

A beauty clinic under the umbrella of the Xeoul Global brand, Xeoul Clinic specialises in face and skin, weight loss and hair treatments.

Signature treatments: Q-switch NdYag Laser treatment, Fractional CO2 Laser treatment, chemical peels and Regenera Activa for hair enhancement. Weight loss treatments include the BTL Vanquish Me and BTL Vanquish Flex procedures.

Call 03-5613 0023 for more information.

Dr Park Wonjin of Wonjin Beauty Medical Group: Achieving A More Beautiful You

Did you know that Da Vinci Clinic is regularly patronised by one of the cast members of the Netflix series Ghost Bride and feature film The Garden of Evening Mists?

This upscale clinic can be found at The Boulevard Office, Mid Valley City as well as in Cheras and Kepong. It offers face, skin, body and hair treatments in addition to holistic wellness programmes. From dimples creation, lip enhancements and breast augmentation to Botulinum Toxin injections to reduce oversized calves, Da Vinci Clinic operates on the philosophy of helping patients improve on the "minute elements" to unleash the true potential of beauty.

Signature treatments: The Da Vinci Double Eyelid Creation Treatment and Thermage, a non-invasive cosmetic procedure that eases the appearance of stretch marks, wrinkles, fine lines and sagging or uneven skin.

Call 03-2283 2888 for more information.

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5 Aesthetic Clinics To Know In The Klang Valley & Their Signature Treatments - Malaysia Tatler

Tech Ventures kicks off series dedicated to supporting female inventors and entrepreneurs at Johns Hopkins – The Hub at Johns Hopkins

BySaralyn Cruickshank

Of all the things that helped Barb Slusher on her path to becoming a leader in the field of drug discovery and an inventor with more than 70 patents to her name, the relationships she built with her peers, and particularly her female peers, were the most influential. By building relationships, she said, she was able to secure funding for her pharmaceutical ventures while still working in the industry, and the bonds she built with other women in pharma help ensure her voice is heard, even in a room full of men.

"If I look at the people who have invested money in the companies we've started, I've usually started a relationship with that person before. I've consulted for them, I've been to conferences with them, I've been on panels or boards with them. They get to know me and trust me, and that ultimately leads to them investing in my companies. It takes time," said Slusher, a Johns Hopkins alum who now directs the Johns Hopkins Drug Discovery Program. "I'm also used to being the only woman in the room, but when I'm with other women, we team up to make sure that each other's opinions are heard."

Slusher was one of three panelists to share insights about being a woman in innovation during an invitational breakfast event held Wednesday at FastForward U near the Johns Hopkins Homewood campus. Alongside stem cell researcher Sharon Gerecht and biomedical engineer Natalia Trayanova, Slusher spoke to 40 of the university's most prominent women in technology and entrepreneurshipfaculty, staff, and studentswho had gathered to network and share their experiences.

Image credit: Will Kirk / Johns Hopkins University

"I hope that 2020 is a year we acknowledge the lengths that female entrepreneurs go," said Christy Wyskiel, senior advisor to the president of Johns Hopkins University for innovation and entrepreneurship and executive director of Johns Hopkins Technology Ventures. "For Johns Hopkins women, in particular, I am committed to helping them find the sponsorship they need in the form of mentors, investors, board members, and believers in a more equal way."

Hosted by Johns Hopkins Technology Ventures, the event kicked off the AccelHERator event series, a collection of workshops and talks focused on supporting female inventors and entrepreneurs at Johns Hopkins. The series, funded by a grant from the Small Business Association, aims to address the barriers to success experienced by women in tech and business, and to support them and their work. Attendees of the launch event were largely those known by or already working with Tech Ventures, but organizers say they hope more members of the Johns Hopkins community will participate in the program by nominating women entrepreneurs and innovators to join the movement through an online form.

Image credit: Will Kirk / Johns Hopkins University

"The work of bringing research to the market is really difficult, in that it requires both cutting-edge science and a keen understanding of customers and how markets function," said Liz Burger, senior director of strategic initiatives at Tech Ventures. "We need all the talent we can get; we cannot afford to have women participate less. So today is a celebration of the vast potential of women at Johns Hopkins, and the rest of the events in the series are about equipping women with the tools to take action and move ideas forward."

Casey Overby Taylor, an assistant professor of medicine and an expert in biomedical informatics, attended the event to learn more about Tech Ventures and to network with other female entrepreneurs.

"I wanted to explore what it would take to build my own private, commercial business, so this is a good way to get exposed to this topic," Overby Taylor said.

Another attendee, Bailey Surtees, graduated from Johns Hopkins in 2017 and now heads a startup that operates out of FastForward U, the student-focused accelerator and makerspace where the breakfast event was held. She said she was interested in the event because she was looking for an opportunity to connect with other entrepreneurial women.

"The female professors that I had as a student at Hopkins made a big impact on my experience," Surtees said. "Seeing how they balanced being a professional woman at the top of their field and other goals I share with them, like being part of a family, was really cool and helped prepare me for what it's like to be a woman in business."

The next AccelHERator event will be a workshop about creating successful value propositions that help capture potential startup customers and clients. It takes place from 11 a.m. to 1 p.m. on Wednesday, April 1, at FastForward 1812 on the East Baltimore campus. Those interested in attending can register online. Additional events will be held in May and June.

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Tech Ventures kicks off series dedicated to supporting female inventors and entrepreneurs at Johns Hopkins - The Hub at Johns Hopkins

Study shows how a tiny and strange marine animal produces unlimited eggs and sperm over its lifetime – National Human Genome Research Institute

A little-known ocean-dwelling creature most commonly found growing on dead hermit crab shells may sound like an unlikely study subject for researchers, but this animal has a rare ability it can make eggs and sperm for the duration of its lifetime. This animal, called Hydractinia, does so because it produces germ cells, which are precursors to eggs and sperm, nonstop throughout its life. Studying this unique ability could provide insight into the development of human reproductive system and the formation of reproductive-based conditions and diseases in humans.

By sequencing and studying the genomes of simpler organisms that are easier to manipulate in the lab, we have been able to tease out important insights regarding the biology underlying germ cell fate determination knowledge that may ultimately help us better understand the processes underlying reproductive disorders in humans, Dr. Andy Baxevanis, director of the National Human Genome Research Institutes (NHGRI) Computational Genomics Unit and co-author of the paper. NHGRI is part of the National Institutes of Health.

In a study published in the journal Science, collaborators at NHGRI, the National University of Ireland, Galway, and the Whitney Laboratory for Marine Bioscience at the University of Florida, Augustine, reported that activation of the gene Tfap2 in adult stem cells in Hydractinia can turn those cells into germ cells in a cycle that can repeat endlessly.

In comparison, humans and most other mammals generate a specific number of germ cells only once in their lifetime. Therefore, for such species, eggs and sperm from the predetermined number of germ cells may be formed over a long period of time, but their amount is restricted. An international team of researchers have been studying Hydractinias genome to understand how it comes by this special reproductive ability.

Hydractinia lives in colonies and is closely related to jellyfish and corals. Although Hydractinia is dissimilar to humans physiologically, its genome contains a surprisingly large number of genes that are like human disease genes, making it a useful animal model for studying questions related to human biology and health.

Hydractinia colonies possess feeding polyps and sexual polyps as a part of their anatomy. The specialized sexual polyps produce eggs and sperm, making them functionally similar to gonads in species like humans.

During human embryonic development, a small pool of germ cells that will eventually become gametes is set aside, and all sperm or eggs that humans produce during their lives are the descendants of those original few germ cells. Loss of these germ cells for any reason results in sterility, as humans do not have the ability to replenish their original pool of germ cells.

In a separate study, Dr. Baxevanis at NHGRI and Dr. Christine Schnitzler at the Whitney Lab have completed the first-ever sequencing of the Hydractinia genome. In this study, researchers used this information to scrutinize the organisms genome for clues as to why there are such marked differences in reproductive capacity between one of our most distant animal relatives and ourselves.

Having this kind of high-quality, whole-genome sequence data in hand allowed us to quickly narrow down the search for the specific gene or genes that tell Hydractinias stem cells to become germ cells, said Dr. Baxevanis.

The researchers compared the behavior of genes in the feeding and sexual structures of Hydractinia. They found that the Tfap2 gene was much more active in the sexual polyps than in the feeding polyps in both males and females. This was a clue that the gene might be important in generating germ cells.

The scientists next confirmed that Tfap2 was indeed the switch that controls the process of perpetual germ cell production. The researchers used the CRISPR-Cas9 gene-editing technique to remove Tfap2 from Hydractinia and measured the resulting effects on germ cell production. They found that removing Tfap2 from Hydractinia stops germ cells from forming, bolstering the theory that Tfap2 controls the process.

The researchers also wanted to know if Tfap2 was influencing specific cells to turn into germ cells. Their analysis revealed that Tfap2 only causes adult stem cells in Hydractinia to turn into germ cells.

Interestingly, the Tfap2 gene also regulates germ cell production in humans, in addition to its involvement in myriad other processes. However, in humans, the germ cells are separated from non-germ cells early in development. Still, despite the vast evolutionary distance between Hydractinia and humans, both share a key gene that changes stem cells into germ cells.

This press release describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and better ways to prevent, diagnose and treat disease. Science is an unpredictable and incremental process each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of fundamental basic research.

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Study shows how a tiny and strange marine animal produces unlimited eggs and sperm over its lifetime - National Human Genome Research Institute

Actinium to Highlight Targeted Conditioning Portfolio at 2020 Transplantation & Cellular Therapy Annual Meeting; Phase 3 SIERRA Trial Preliminary…

NEW YORK, Feb. 13, 2020 /PRNewswire/ --Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium") announced today that presentations from its targeted conditioning portfolio have been accepted for presentation at the 2020 Transplantation & Cellular Therapy (TCT) Meetings, which brings together thousands of transplant professionals from over 500 transplant centers worldwide. TCT is being held February 19-23, 2020 at the Marriott World Center in Orlando, Florida. Notably, data from the pivotal Phase 3 SIERRA trial of Iomab-B have been selected for an oral presentation.

"We are excited that Iomab-B and the SIERRA trial have once again been selected as an oral presentation at TCT," said Dr. Mark Berger, Chief Medical Officer of Actinium. "We look forward to highlighting the potential benefit that Iomab-B can provide to a patient population with active disease who are otherwise ineligible for BMT. We are confident these findings will be received with great enthusiasm. TCT, which assembles leading transplant physicians from top centers in the United States and worldwide, is the ideal venue to showcase the extremely encouraging findings from the SIERRA trial thus far. In addition, our other conference activities are expected to provide significant exposure for this important trial and invaluable interactions with BMT thought leaders. Through the SIERRA trial, we aspire to change the treatment paradigm for older patients with relapsed or refractory AML to make potentially curative BMT via Iomab-B the standard of care for this patient population that continues to have poor outcomes."

Actinium's TCT Presentations:

Late Breaking Oral Presentation:

Poster Presentation:

About the SIERRA TrialThe SIERRA trial (Study ofIomab-B inElderlyRelapse/RefractoryAcute Myeloid Leukemia) is the only randomized Phase 3 trial that offers BMT (Bone Marrow Transplant) as an option for older patients with active, relapsed or refractory AML or acute myeloid leukemia. BMT is the only potentially curative treatment option for older patients with active relapsed or refractory AML and there is no standard of care for this indication other than salvage therapies. Iomab-B is an ARC (Antibody Radiation-Conjugate) comprised of the anti-CD45 antibody apamistamab and the radioisotope I-131 (Iodine-131). The 20 active SIERRA trial sites in the U.S. and Canada represent many of the leading bone marrow transplant centers by volume. For more information, visit http://www.sierratrial.com.

About Transplantation & Cellular Therapy Meetings (TCT) TCT, formerly known as the BMT Tandem Meetings, are the combined annual meetings of the American Society for Blood and Marrow Transplantation (ASBMT) and the Center for International Blood & Marrow Transplant Research (CIBMTR).Each year the conference brings together several thousand investigators, clinicians, researchers, nurses and other allied health professionals from over 500 transplant centers from over 50 countries around a full scientific program focused on bone marrow transplant and cellular therapies.

About Actinium Pharmaceuticals, Inc. (NYSE: ATNM)Actinium Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company developing ARCs or Antibody Radiation-Conjugates, which combine the targeting ability of antibodies with the cell killing ability of radiation. Actinium's lead application for our ARCs is targeted conditioning, which is intended to selectively deplete a patient's disease or cancer cells and certain immune cells prior to a BMT or Bone Marrow Transplant, Gene Therapy or Adoptive Cell Therapy (ACT) such as CAR-T to enable engraftment of these transplanted cells with minimal toxicities. With our ARC approach, we seek to improve patient outcomes and access to these potentially curative treatments by eliminating or reducing the non-targeted chemotherapy that is used for conditioning in standard practice currently. Our lead product candidate, I-131 apamistamab (Iomab-B) is being studied in the ongoing pivotal Phase 3Study ofIomab-B inElderlyRelapsed orRefractoryAcute Myeloid Leukemia (SIERRA) trial for BMT conditioning. The SIERRA trial is over fifty percent enrolled and promising single-agent, feasibility and safety data has been highlighted at ASH, TCT, ASCO and SOHO annual meetings. I-131 apamistamab will also be studied as a targeted conditioning agent in a Phase 1/2 anti-HIV stem cell gene therapy with UC Davis and is expected to be studied with a CAR-T therapy in 2020. In addition, we are developing a multi-disease, multi-target pipeline of clinical-stage ARCs targeting the antigens CD45 and CD33 for targeted conditioning and as a therapeutic either in combination with other therapeutic modalities or as a single agent for patients with a broad range of hematologic malignancies including acute myeloid leukemia, myelodysplastic syndrome and multiple myeloma. Ongoing combination trials include our CD33 alpha ARC, Actimab-A, in combination with the salvage chemotherapy CLAG-M and the Bcl-2 targeted therapy venetoclax. Underpinning our clinical programs is our proprietary AWE (Antibody Warhead Enabling) technology platform. This is where our intellectual property portfolio of over 100 patents, know-how, collective research and expertise in the field are being leveraged to construct and study novel ARCs and ARC combinations to bolster our pipeline for strategic purposes. Our AWE technology platform is currently being utilized in a collaborative research partnership with Astellas Pharma, Inc. Website: https://www.actiniumpharma.com/

Forward-Looking Statements for Actinium Pharmaceuticals, Inc.

This press release may contain projections or other "forward-looking statements" within the meaning of the "safe-harbor" provisions of the private securities litigation reform act of 1995 regarding future events or the future financial performance of the Company which the Company undertakes no obligation to update. These statements are based on management's current expectations and are subject to risks and uncertainties that may cause actual results to differ materially from the anticipated or estimated future results, including the risks and uncertainties associated with preliminary study results varying from final results, estimates of potential markets for drugs under development, clinical trials, actions by the FDA and other governmental agencies, regulatory clearances, responses to regulatory matters, the market demand for and acceptance of Actinium's products and services, performance of clinical research organizations and other risks detailed from time to time in Actinium's filings with the Securities and Exchange Commission (the "SEC"), including without limitation its most recent annual report on form 10-K, subsequent quarterly reports on Forms 10-Q and Forms 8-K, each as amended and supplemented from time to time.

Contacts:

Investors:Hans Vitzthum LifeSci Advisors, LLCHans@LifeSciAdvisors.com(617) 535-7743

Media:Alisa Steinberg, Director, IR & Corp Commsasteinberg@actiniumpharma.com(646) 237-4087

SOURCE Actinium Pharmaceuticals, Inc.

http://www.actiniumpharma.com/

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Actinium to Highlight Targeted Conditioning Portfolio at 2020 Transplantation & Cellular Therapy Annual Meeting; Phase 3 SIERRA Trial Preliminary...

This veteran-backed NASCAR team is heading to Daytona – We Are The Mighty

It's shake and bake, veteran style. NASCAR is well known for being military friendly. When the green flag waves at Daytona this weekend, it will usher in the new NASCAR season with a really special story. The crown jewel event is the Daytona 500. On Saturday, the day before the 500, there is a race called the NASCAR Racing Experience 300 which ushers in the Xfinity Series season. One of the cars racing to win the 300 should be the favorite of all military supporters around the country.

The Our America Dream Team car won't have the familiar sponsors you see on all the other race cars. Instead, they will feature veteran-owned businesses as the car trades rubber with all the cars on the track.

How is this possible? The team crowdfunded to raise money so they could race. In return for donations, veteran-owned businesses will be featured on the car racing around one of the world's most famous race tracks during one of racings marquee weekends.

The car will be driven by Colin Garrett. Garrett said, "I'm so grateful for the support from everyone who's backed the team. We're excited that fans and military-owned small businesses will be able to see the car on the track and feel proud, knowing they had a hand in us racing. When I started racing, my dad said he wanted me to find a way to use it to make a difference, so I could look back on it and know I helped someone. I wasn't quite 15 at the time and didn't really get it, but now I do. Working with the military community is the perfect fit, and it's cool that it ties in with my brothers' Army careers."

Team owner Sam Hunt added, "It feels good to know we're racing for something bigger than ourselves. We love racing, but the National Awareness Campaign makes it mean so much more."

Lisa Kipps-Brown, the marketing strategist behind the team who took time to answer questions about the team.

WATM: Where did the idea of "Our American Dream Team" come from?

Kipps-Brown: Two ideas converged to create "Our American Dream Team:"

We realized that the American Dream that we believe in and are chasing is often hard for those in the military community to achieve. Since we wanted to expand our National Awareness Campaign for 2020, helping those who have given so much achieve their own American Dream was the perfect fit to complement what we were already doing with Racing For Heroes. We decided to take a leap of faith and commit to crowdfunding the team to replace as much corporate sponsorship money as possible, which would free us up to promote issues important to the military community and companies owned by Veterans and military spouses.

WATM: Tell us a little about the team owner?

Kipps-Brown: 26-year-old Sam Hunt dreamed of starting a NASCAR team after racing throughout his childhood. After he graduated from college, the late J.D. Gibbs, whom Sam knew through his family, gave Sam his first two cars to help him get started. Sam started his team in 2018, living in his van behind the shop and couch surfing with friends to be able to afford the business. He and driver Colin Garrett started racing together that year in the K&N Pro Series, and realized they had something special working together.

WATM: Tell us about your driver?

Kipps-Brown: Unlike most NASCAR drivers, 19-year-old Colin Garrett didn't grow up racing karts or in a racing family. Yet, in just his third season of racing, he was historic South Boston (VA) Speedway's 2017 Limited Sportsman Division Champion and broke the track's qualifying speed record twice. In 2018 he started racing with team owner Sam Hunt in the K&N Pro Series and continued racing Super Late Model. What started out as a 3-race deal with Sam turned into a great fit, and they raced K&N together the rest of the 2018 season and all of 2019. In the fall of 2019, they decided they wanted to make the leap to the Xfinity Series.

WATM: Do you have any connections to the military? Why did they partake in this endeavor?

Kipps-Brown: Both of Colin's brothers are Active Duty Army, one currently deployed to Korea. One of Sam's best friends is a Navy SEAL. I am a milspouse whose husband is retired Navy with 26 years of service, 3 of which were in the Vietnam War. Combating Veteran suicide and helping service members transition back to civilian life is an issue that's personally important to them. Colin knows it could be his brothers who need help, and I have experienced how difficult the transition can be for Veterans and military families.

WATM: How hard was it to raise money?

Kipps-Brown: We knew it was a long shot, but we also had faith that we could do it. We believed in the loyalty of grassroots NASCAR fans and the power of large numbers of people who could give any amount. Nothing was too small. Our friends, family, and existing fans kicked it off for us, backing the team because they believed in us and our dream. We ended up raising enough to not only race in Daytona, but also pay for stem cell treatments for a Veteran through Racing For Heroes. Crowdfunding needs a crowd, though, and we're really just now tapping into the power of the military community.

WATM: What were the biggest obstacles?

Kipps-Brown: Connecting with the crowd was by far our biggest obstacle. People are jaded, and for good reason. They've seen too many people use Veterans' issues to further their own cause without giving anything back to the community. The most important connection so far has been when Stephanie Brown, founder of The Rosie Network, introduced us to Marine veteran Greg Boudah, founder of The Jewelry Network. The Jewelry Network, where Veterans buy jewelry, became a sponsor on the car for Daytona, and Greg has been instrumental in getting the grassroots movement going. He's activated his network of vetrepreneurs like Chris (Smurf) McPhee (retired Green Beret - Green Beret Media) and Michael Whitlow (Marine veteran - Vetbuilder) to help us get the word out. Once people get to know us, they realize we're part of the military family, that we're not just asking for money, and we really do want to make a difference. When we get over that hurdle, everyone responds with excitement.

WATM: How many veteran businesses donated?

Kipps-Brown: We have about 50 Veteran Business Advocates so far. When a vet- or milspouse-owned business gives and provides their logo, we promote them on our website, tell their story on our Facebook page, and provide a Veteran Business Advocate badge for their website. It's an opportunity for them to participate in a national NASCAR marketing campaign, something that would normally never be available to small businesses. There's never been anything like this done before, and we have plans in the works for other ways of helping grow military-owned businesses. Stay tuned 🙂

WATM: How did you get involved with this? What other outside help did they get.

Kipps-Brown: It's really been me, Colin's dad, and the staff of my web & marketing strategy company, Glerin Business Resources. I started working with Colin and his dad in November of 2018. A couple of months after that Racing For Heroes happened to contact me, wanting to hire me to develop a National Awareness Campaign for them.

When I visited them at Virginia International Raceway and saw all they do, I was literally in tears. I couldn't believe the extent of their free services, and the fact that they were holistic was even better. I remembered how hard it was for my husband when he retired, losing that sense of mission and knowing he was part of something that made a difference. I just couldn't bear the thought of taking money away from their programs. I called Colin's dad, Ryan, as soon as I left, and he readily agreed to roll Racing For Heroes into the work I was doing with them.

Just after that, he and I began working with Steve Sims, author of Bluefishing: The Art of Making Things Happen, as our business coach. Steve's encouragement, input, and challenging us to think differently were instrumental in the evolution of the team.

I think the fact that this whole campaign started with a call from Racing For Heroes is so cool; it's really an organic effort that was constantly changing throughout the season. We're proud that a movement that started in a small, rural town in Virginia has gone national and is becoming a disrupter in the racing industry.

WATM: Tell us about the race the car will be in?

Kipps-Brown: The NASCAR Racing Experience 300 is the most prestigious NASCAR Xfinity Series of the year. The 300-mile race is held at Daytona International Speedway the day before the Daytona 500, and is broadcast live on TV and radio.

WATM: Are there future plans for any other races?

Kipps-Brown: We intend to race as many Xfinity races on the national stage this year as we can fund, and we plan to be prepared to run the full 2021 season. Colin will also be running NASCAR Super Late Model and Late Model at the grassroots level, like his home track South Boston Speedway. The smaller tracks actually give him a better opportunity to interact directly with fans, which is great for helping communicate the free services available.

The NASCAR Racing Experience 300 rolls out at 2:30 p.m. EST this Saturday, February 15th. Tune in and cheer on the Our America Dream Team!

More information on the team and its cause can be found here.

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Breakthrough in Stem Cell Research: First Image of Niche Environment | Newsroom – UC Merced University News

By Lorena Anderson, UC Merced

Professor Joel Spencer and his lab have made a huge breakthrough in stem cell research.

Professor Joel Spencer was a rising star in college soccer and now he is an emerging scientist in the world of biomedical engineering, capturing for the first time an image of a hematopoietic stem cell (HSC) within the bone marrow of a living organism.

Everyone knew black holes existed, but it took until last year to directly capture an image of one due to the complexity of their environment, Spencer said. Its analogous with stem cells in the bone marrow. Until now, our understanding of HSCs has been limited by the inability to directly visualize them in their native environment until now.

This work brings an advancement that will open doors to understanding how these cells work which may lead to better therapeutics for hematologic disorders including cancer.

Understanding how HSCs interact within their local environments might help researchers understand how cancers use this same environment in the bone marrow to evade treatment.

Spencer studied biological sciences at UC Irvine where he was the captain of the mens Division 1 soccer team. He initially planned to pursue a career in professional soccer until faculty mentors opened doors for research and introduced Spencer to biophotonics the science that deals with the interactions of light with biological matter.

UC faculty were a big part of my research experience; they became mentors and friends, Spencer said. My first foray into research was as a lab tech, and that is where I met people who were doing biomedical imaging, and it just caught my wonder.

An image of a stem cell in its natural niche

Spencer left his native California to earn his Ph.D. in bioengineering at Tufts University in Boston and took a postdoctoral research position in the Wellman Center for Photomedicine at Massachusetts General Hospital and Harvard Medical School. In Boston, he learned about live-animal imaging and his wonder became a passion.

Now his emphasis is on biomedical optics: building new microscopes and new imaging techniques to visualize and study biological molecules, cells and tissue in their natural niches in living, fully intact small animals.

I work at the interface of engineering and biology. My lab is seeking to answer biological questions that were impossible until the advancements in technology we have seen in the past couple decades, he said. You need to be able to peer inside an organ inside a live animal and see whats happening as it happens.

Based on work conducted at UC Merced and in Boston, he and his collaborators including his grad student Negar Tehrani visualized stem cells inside the bone marrow of live, intact mice.

He and his collaborators have a new paper published in the journal Nature detailing the work they conducted to study HSCs in their native environment in the bone marrow.

We can see how the cells behave in their native niches and how they respond to injuries or stresses which seems to be connected to the constant process of bone remodeling, Tehrani said. Researchers have been trying to answer questions that have gone unanswered for lack of technology, and they have turned to engineering to solve those puzzles.

Its important for researchers to understand the mechanics of stem cells because of the cells potential to regenerate and repair damaged tissue.

Spencer, left, and students from his lab

Spencer returned to California three years ago, joining the Department of Bioengineering in the School of Engineering at UC Merced. Hes also an affiliate of the Health Sciences Research Institute and the NSF CREST Center for Cellular and Biomolecular Machines . This is his third paper in Nature, but the first stemming from work conducted in his current lab.

He didnt come to UC Merced just because he loves biology Spencer also joined the campus because of the students.

Now Im back in the UC system Im a homegrown UC student whos now faculty, Spencer said. As a student within the system I was able to participate in myriad opportunities, including mentorships that advanced my career. Now I try to encourage graduate and undergrad students to follow their dreams. I love being able to give them opportunities its something I really want to do for the next generation.

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Breakthrough in Stem Cell Research: First Image of Niche Environment | Newsroom - UC Merced University News

University of Delaware researcher receives $250K grant for new biotherapies – Technical.ly Brooklyn

As part of a pilot search for new medical breakthroughs, the partnership of King of Prussia-based plasma-based biotech company CSL Behring and the University City Science Center in Philadelphia has awarded $250,000, plus the opportunity to work alongside CSL Behring experts, to Eleftherios (Terry) Papoutsakis, Ph.D., of the University of Delaware, for his exploration of cell derived micro-particles and vesicles (MkMPs) for the treatment of thrombocytopenias and in stem-cell targeted gene therapies.

Papoutsakis is one of two researchers to receive the award, called the CSL Behring-Science Center Research Acceleration Initiative. The other, Cecelia Yates, Ph.D. of the University of Pittsburgh, uses biomimetic peptides as potential targeted therapeutic treatment of pulmonary fibrosis.

This initiative is another example of the strength of our partnership with the Philadelphia-based University City Science Center as we look in our backyard for innovative scientific advancements that have the potential to help rare disease patients lead full lives, said Dr. Bill Mezzanotte, EVP and head of research and development for CSL Behring, in a press release. Our growing R&D organization looks forward to working with Dr. Yates and Dr. Papoutsakis in the years ahead to advance their scientific research.

The therapy that Dr. Papoutsakis is developing involves gene editing of stem cells that may potentially benefit to patients for a variety of genetic blood disorders such as Wiskott-Aldrich syndrome.

The CSL Behring Science Center Research Initiative is currently accepting applications from researchers in the region developing therapeutic biotechnologies in immunology, neurology, haematology, thrombosis, transplant, respiratory and cardiovascular/metabolic to receive one of up to three grants in 2020 of up to $400,000 each. The deadline is April 13.

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Scientists Think They Know How Stress Causes Gray Hair – Thrive Global

Sorry Mom and Dad: It turns out you might not have been exaggerating when you told us your children made your hair turn gray.

Stress may play a key role in just how quickly hair goes from colored to ashen, astudyTrusted Sourcepublished this past week in the journal Nature suggests.

Scientists have long understood some link is possible between stress and gray hair, but this new research from Harvard University in Massachusetts more deeply probes the exact mechanisms at play.

The researchers initial tests looked closely at cortisol, the stress hormone that surges in the body when a person experiences a fight or flight response.

Its an important bodily function, but the long-term presence of heightened cortisol is linked to a host ofnegative health outcomes.

But the culprit ended up being a different part of the bodys fight or flight response the sympathetic nervous system.

These nerves are all over the body, including making inroads to each hair follicle, the researchers reported.

Chemicals released during the stress response specifically norepinephrine causes pigment producing stem cells to activate prematurely, depleting the hairs reserves of color.

The detrimental impact of stress that we discovered was beyond what I imagined,Ya-Chieh Hsu, PhD, a lead study author and an associate professor of stem cell and regenerative biology at Harvard, said in apress release. After just a few days, all of the pigment-regenerating stem cells were lost. Once theyre gone, you cant regenerate pigments anymore. The damage is permanent.

But stress isnt the only or even the primary reason that most people get gray hair.

In most cases, its simple genetics.

Gray hair is caused by loss of melanocytes (pigment cells) in the hair follicle. This happens as we age and, unfortunately, there is no treatment that can restore these cells and the pigment they produce, melanin,Dr. Lindsey A. Bordone, a dermatologist at ColumbiaDoctors and an assistant professor of dermatology at Columbia University Medical Center in New York, told Healthline. Genetic factors determine when you go gray. There is nothing that can be done medically to prevent this from happening when it is genetically predetermined to happen.

That doesnt mean environmental factors such as stress dont play a role.

Smoking, for instance, is a known risk factor for premature graying, according to a2013 studyTrusted Source. So kick the habit if you want to keep that color a little longer.

Other contributing factors to premature graying include deficiencies in protein, vitamin B-12, copper, and iron as well as aging due in part to an accumulation of oxidative stress.

That stress is prompted by an imbalance between free radicals and antioxidants in your body that can damage tissue, proteins, and DNA,Kasey Nichols, NMD, an Arizona physician and a health expert atRave Reviews, told Healthline.

And some degree of oxidative stress is a natural part of life.

We would expect increasing gray hair as we advance in age, and we see about a 10 percent increase in the chance of developing gray hair for every decade after age 30, Nichols said.

Changes you can pursueto delay premature grays include eating a diet high in omega-3 fatty acids such as walnuts and fatty fish, not spending too much time in the skin-damaging and hair-damaging ultraviolet light of the sun, and taking vitamin B-12 and vitamin B-6 supplements.

That said, if you are going gray prematurely, it wouldnt hurt to go have a checkup just in case natural genetic factors arent the sole culprit.

The new Harvard research is only a mouse study, so replicating the same results in a human study would be necessary to strengthen the findings.

But the Harvard research has implications far beyond graying hair, with the hair color change merely one obvious sign of other internal changes as a result of prolonged stress.

By understanding precisely how stress affects stem cells that regenerate pigment, weve laid the groundwork for understanding how stress affects other tissues and organs in the body, said Hsu. Understanding how our tissues change under stress is the first critical step towards eventual treatment that can halt or revert the detrimental impact of stress.

Might that also mean someday halting and reverting the march of premature gray hair? Its too soon to tell.

We still have a lot to learn in this area, Hsu said.

Originally published on Healthline.

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Isolated Extramedullary Relapse in Acute Lymphoblastic Leukemia: What Can We Do Before and After Transplant? – Cancer Network

Santiago Riviello-Goya, MD1; Aldo A. Acosta-Medina, MD2; Sergio I. Inclan-Alarcon, MD3; Sofa Garcia-Miranda, MD2; and Christianne Bourlon, MD, MHSc2

1Department of Medicine, Instituto Nacional de Ciencias Mdicas y Nutricin Salvador Zubirn, Mexico City, Mexico; 2Department of Hematology, Instituto Nacional de Ciencias Mdicas y Nutricin Salvador Zubirn, Mexico City, Mexico; 3Cancer Center, Centro Mdico ABC, Mexico City, Mexico

A 43-year-old male with a history of B-cell acute lymphoblastic leukemia (ALL), who underwent allogeneic hematopoietic stem cell transplantation (HSCT) 5 months prior, presented to the emergency department with a 5-day history of progressive bilateral lower extremity weakness. On physical examination, there were no additional neurologic findings; sensory function and urethral and anal sphincter tone were preserved.

Initial clinical laboratory testing showed peripheral blood cell counts, a peripheral blood smear, and a comprehensive metabolic panel within normal limits. Neuroimaging by computed tomography (CT) and magnetic resonance showed no evidence of acute intracranial processes or lesions suggestive of leukemic relapse. A lumbar puncture for cerebrospinal fluid (CSF) analysis was performed and documented the presence of lymphoid-appearing blasts (Figure 1). Flow cytometry (FC) confirmed central nervous system (CNS) infiltration by B-lineage lymphoid blasts (CD34+, CD45+, CD22+, CD19+, and CD10+) (Figure 2). Bone marrow aspirate and biopsy, including FC evaluation, were negative for systemic relapse. Bone marrow chimerism was 98%.

With a diagnosis of isolated extramedullary leukemic relapse (iEMR), the patient was initiated on weekly intrathecal chemotherapy and was weaned off graft-versus-host disease (GVHD) prophylaxis, achieving CSF clearance after 4 weeks of therapy. Against Hematology service recommendations, the patient declined systemic therapy and received only whole brain radiation therapy (24 Gy in 12 fractions).

The patient experienced remission of neurologic symptoms; however, after 5 months, he developed bilateral testicular tenderness and enlargement. An ultrasound was performed and was suggestive of leukemic infiltration (Figure 3). Chemotherapy with methotrexate and L-asparaginase in addition to radiotherapy to the testes (24 Gy in 12 fractions) was given without complications.

One year after initial CNS iEMR, the patient developed overt bone marrow relapse (BMR), as evidenced by development of bone pain throughout the lumbosacral region, and the appearance of multiple blastic and lytic lesions throughout the appendicular and axial skeleton. A positron emission tomography-CT scan documented abdominal lymphadenopathy (Figure 4). With this rapidly progressive picture, the patient was transitioned to supportive care and died 2 months later.

Is the risk of iEMR following HSCT modified by the choice of conditioning regimen? If so, which of the following approaches would have been the best choice to prevent iEMR in this patient?

A. There is no role of conditioning therapy in preventing iEMRB. Reduced intensity of regimen to favor graft-versus-leukemia (GVL) effectC. Nonmieloablative regimens including fludarabineD. Mieloablative regimens including total body irradiation (TBI)

CORRECT ANSWER: D. Mieloablative regimens including total body irradiation (TBI).

Allogeneic HSCT is an effective treatment for ALL, which can achieve long-term remission and even a potential cure.1 Antineoplastic activity is dependent on both high-dose chemotherapy and graft alloreactivity, with the latter manifested in the GVL effect, and undesirably yet inherently, in GVHD.2 Despite recent advances in allogeneic HSCT strategies, disease relapse is common and remains the most important cause of death in this population. Relapse is reported in 30% to 40% of patients but can increase to 60% in patients who are in a second complete remission (CR) at time of HSCT.2,3

Risk factors for relapse in patients with ALL who have undergone HSCT include disease- and transplant-related features. Reported high-risk disease characteristics include: hyperleukocytosis at diagnosis (white blood cell count >30 x109/L for B-lineage ALL and >100 x109/L for T-lineage ALL); cytogenetics associated with poor outcomes, including chromosome 11 translocations and t(9;22); a short remission timespan; more than a first CR; and a failed or delayed remission after induction therapy.4 In the HSCT population, transplant-related factors should be considered, including alternative donors other than those who are matched related and matched unrelated, the type of conditioning regimen, and the development of GVHD.2

ALL relapse following HSCT most commonly involves the medullary compartment, with a cumulative incidence of 41% at 5 years. Conversely, extramedullary relapse (EMR) is uncommon, with a 5-year cumulative incidence of 11.0% and 5.8% for EMR and iEMR, respectively.5 Due to the rarity of EMR, its prognostic impact remains controversial and the ideal management strategies are a subject of active study.

EMR is associated with poor clinical outcomes; however, the subgroup of patients with iEMR (as presented in this patient case) is gaining attention due to its increasing frequency, its role heralding a systemic relapse, and its clinical behavior showing better survival outcomes compared with BMR and EMR.6-8

Isolated EMR is defined as the presence of clonal blasts in any tissue other than the medullary compartment; bone marrow evaluation must show less than 5% of clonal blasts and a full donor chimerism. Most commonly affected sites include the skin, soft tissues, lymph nodes, and immune sanctuaries including the CNS and testes.1,5,9 Because prevention rather than treatment of relapse is related to improved survival outcomes, it is important to define subgroups of patients who may benefit fromearly intervention with a personalized transplant strategy.

Higher rates of iEMR have been linked to patients of younger age. This is thought to be secondary to: (1) a higher incidence of ALL compared with acute myeloid leukemia (AML) in this age subgroup, the former of which is most associated with EMR; (2) the relative overrepresentation of myelomonocytic/monocytic phenotypes in AML presenting in young individuals; and (3) the higher likelihood of a history of EMR in children compared with adults.1,10

A history of extramedullary (EM) disease, which has consistently been found to impact the development of iEMR, is preexistent in up to half of patients. In 2 out of 3 cases of EMR, disease affects the site of original EM involvement, possibly due to low efficacy of both high-dose chemotherapy and the GVL effect.1,5 An exception to this is CNS involvement, despite being a risk factor for subsequent CNS iEMR, which is commonly reported de novo, reflecting the protective effect of regularly administered prophylaxis to patients at high risk of CNS infiltration.11

The effect of GVHD on risk of iEMR is highly nuanced. Despite its well-known role as a protective factor for BMR, the same effect does not appear to hold true for iEMR.12 Initial reports in this population showed no differences in relapse-free survival regardless of acute or chronic GVHD (cGVHD) or a positive association between extensive cGVHD and iEMR development.10,13 This has led to investigators to postulate that the underlying physiopathology differs among different types of relapse, with decreased expression of human leukocyte antigen (HLA) minor histocompatibility antigens and adhesion molecules and decreased penetration of both immune cells and high-dose chemotherapy to EM sites.14 These mechanisms lead to decreased effectivness of T-cell dependent cytotoxicity of donor lymphocytes as compared with the medullary compartment, with subsequent clone selection and escape, enabling the development of iEMR.6

With the increased use of alternative donors, this has been contested in the haploidentical setting, with a recent report showing significantly increased rates of iEMR in patients who do not develop cGVHD. It is suggested that the role of GVL, coupled with GVHD, in this HLA-mismatched setting could partially explain the added benefit of GVHD in this subgroup. This report also evidenced increased tumor chemosensitivity in patients with EMR compared with BMR, possibly explained by reduced concentrations of conditioning therapy at EM sites.9

Cytogenetics associated with poor outcomes and advanced disease at the time of HSCT were described as risk factors for iEMR in initial cohort studies.1,5,10,15,16 However, recent publications that include alternative-donor HSCT recipients have reported that a haploidentical source could overcome this negative impact.9

The influence of type of conditioning regimen on likelihood of iEMR has been studied only retrospectively, mainly comparing TBI-based versus chemotherapy-based approaches. The landmark paper by Simpson et al showed a significantly elevated rate of iEMR in patients receiving busulfan-based conditioning. This finding has been related to the lack of penetration of drugs into the immune sanctuaries with chemotherapy-only regimens.17

Multiple approaches, including combination and single treatment for iEMR, have been described. Combination therapy including systemic chemotherapy plus local radiotherapy (or in CNS disease, radiation to the craniospinal axis, intrathecal chemotherapy, and systemic chemotherapy) has been associated with higher response rates than single-treatment strategies.9 Nonetheless, the best responses have been observed when combination therapy is followed by a cellular therapy (eg, second allogeneic HSCT, donor leukocyte infusion, and donor stem cell infusion), leading to CR rates of greater than 80%.5,13 Whether this increase in CR rate translates to an increase in survival outcomes remains debatable due to conflicting results in the current literature for iEMR.

Financial Disclosure: The authors have no significant financial interest in or other relationship with the manufacturer of any product or provider of any service mentioned in this article.

Corresponding author:

Christianne Bourlon, MD, MHScVasco de Quiroga No. 15.Belisario Domnguez Seccin XVI

Tlalpan, C.P. 14080, Ciudad de Mxico, Mxico

E-mail: chrisbourlon@hotmail.com

References:

1. Ge L, Ye F, Mao X, et al. Extramedullary relapse of acute leukemia after allogeneic hematopoietic stem cell transplantation: different characteristics between acute myelogenous leukemia and acute lymphoblastic leukemia. Biol Blood Marrow Transplant. 2014;20(7):1040-1047. doi: 10.1016/j.bbmt.2014.03.030.

2. Pavletic SZ, Kumar S, Mohty M, et al. NCI First International Workshop on the Biology, Prevention, and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation: report from the Committee on the Epidemiology and Natural History of Relapse following Allogeneic Cell Transplantation. Biol Blood Marrow Transplant. 2010;16(7):871-890. doi: 10.1016/j.bbmt.2010.04.004.

3. Devillier R, Crocchiolo R, Etienne A, et al. Outcome of relapse after allogeneic stem cell transplant in patients with acute myeloid leukemia. Leuk Lymphoma. 2013;54(6):1228-1234. doi: 10.3109/10428194.2012.741230.

4. Hoelzer D, Bassan R, Dombret H, Fielding A, Ribera JM, Buske C; ESMO Guidelines Committee. Acute lymphoblastic leukaemia in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;27(suppl 5):v69-v82. doi: 10.1093/annonc/mdw025.

5. Shem-Tov N, Saraceni F, Danylesko I, et al. Isolated extramedullary relapse of acute leukemia after allogeneic stem cell transplantation: different kinetics and better prognosis than systemic relapse. Biol Blood Marrow Transplant. 2017;23(7):1087-1094. doi: 10.1016/j.bbmt.2017.03.023.

6. Lee JH, Choi SJ, Lee JH, et al. Anti-leukemic effect of graft-versus-host disease on bone marrow and extramedullary relapses in acute leukemia. Haematologica. 2005;90(10):1380-1388.

7. Xie N, Zhou J, Zhang Y, Yu F, Song Y. Extramedullary relapse of leukemia after allogeneic hematopoietic stem cell transplantation. Medicine (Baltimore). 2019;98(19):e15584. doi: 10.1097/MD.0000000000015584.

8. Shi JM, Meng XJ, Luo Y, et al. Clinical characteristics and outcome of isolated extramedullary relapse in acute leukemia after allogeneic stem cell transplantation: a single-center analysis. Leuk Res. 2013;37(4):372-377. doi: 10.1016/j.leukres.2012.12.002.

9. Mo XD, Kong J, Zhao T, et al. Extramedullary relapse of acute leukemia after haploidentical hematopoietic stem cell transplantation: incidence, risk factors, treatment, and clinical outcomes. Biol Blood Marrow Transplant. 2014;20(12):2023-2028. doi:10.1016/j.bbmt.2014.08.023.

10. Harris AC, Kitko CL, Couriel DR, et al. Extramedullary relapse of acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation: incidence, risk factors and outcomes. Haematologica. 2013;98(2):179-184. doi: 10.3324/haematol.2012.073189.

11. Hamdi A, Mawad R, Bassett R, et al. Central nervous system relapse in adults with acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2014;20(11):1767-1771. doi: 10.1016/j.bbmt.2014.07.005.

12. Giralt SA, Champlin RE. Leukemia relapse after allogeneic bone marrow transplantation: a review. Blood. 1994;84(11):3603-3612.

13. Solh M, DeFor TE, Weisdorf DJ, Kaufman DS. Extramedullary relapse of acute myelogenous leukemia after allogeneic hematopoietic stem cell transplantation: better prognosis than systemic relapse. Biol Blood Marrow Transplant. 2012;18(1):106-112. doi: 10.1016/j.bbmt.2011.05.023.

14. Kolb HJ. Graft-versus-leukemia effects of transplantation and donor lymphocytes. Blood. 2008;112(12):4371-4383. doi: 10.1182/blood-2008-03-077974.

15. Lee KH, Lee JH, Choi SJ, et al. Bone marrow vs extramedullary relapse of acute leukemia after allogeneic hematopoietic cell transplantation: risk factors and clinical course. Bone Marrow Transplant. 2003;32(8):835-842. doi: 10.1038/sj.bmt.1704223.

16. Clark WB, Strickland SA, Barrett AJ, Savani BN. Extramedullary relapses after allogeneic stem cell transplantation for acute myeloid leukemia and myelodysplastic syndrome. Haematologica. 2010;95(6):860-863.

17. Simpson DR, Nevill T, Shepherd JD, et al. High incidence of extramedullary relapse of AML after busulfan/cyclophosphamide conditioning and allogeneic stem cell transplantation. Bone Marrow Transplant. 1998;22(3):259-264. doi: 10.1038/sj.bmt.1701319.

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Isolated Extramedullary Relapse in Acute Lymphoblastic Leukemia: What Can We Do Before and After Transplant? - Cancer Network