AG Ferguson wins $500000 for individuals impacted by US Stemology’s unproven claims that its stem cell injections could treat COVID-19 and other…

Attorney Generals Office shuts down US Stemologys deceptive marketing, including claims that stem cell injections could treat COVID-19

SEATTLE Attorney General Bob Ferguson today announced that, as a result of his lawsuit against the company, Seattle-based US Stemology and its owner, Dr. Tami Meraglia, cannot advertise, market or receive any payment for unproven stem cell treatments. US Stemology must also pay $500,000 to the Attorney Generals Office, which will be used to provide restitution for those who paid for stem cell procedures. 107 individuals paid for the procedures and are eligible for restitution.

In March, Ferguson filed a lawsuit against the company, asserting it claimed in its marketing that stem cell injections could treat COVID-19 and dozens of other serious medical conditions, including asthma, lupus, Parkinsons disease, congestive heart failure and multiple sclerosis. There is no reliable clinical evidence stem cell therapy can effectively treat these conditions.

After the Attorney Generals Office began its investigation, US Stemology stopped performing stem procedures in June 2021, and has not performed any procedures since.

Some people paid up to $10,000 for the unproven treatments. Due to medical privacy laws, the Attorney Generals Office cannot obtain information about US Stemologys clients unless those clients provide a waiver. All 107 people eligible for restitution will receive a letter from US Stemology in the mail in the next two months, which asks them to provide some information to the Attorney Generals Office for the purpose of providing the refunds. Individuals must complete this form to receive their refund.

Dr. Meraglia and US Stemology advertised stem cells as a life-changing miracle cure that could treat almost anything even COVID, Ferguson said. They preyed on peoples fears and frustrations about their health to sell hundreds of thousands of dollars in unproven treatments. Our work put a stop to US Stemologys modern day snake-oil scheme.

Under the consent decree, filed in King County Superior Court, the company must pay $500,000 to the Attorney Generals Office, whichwill be used as restitution for those who paid for Dr. Meraglias stem cell treatments. The company must pay $300,000 in suspended penaltiesif they violate the terms of the consent decree.

The Attorney Generals Office has independently verified that US Stemology lacks the funds to pay the full judgment amount immediately. The company is required to pay the $500,000 within 24 months, at a 6 percent interest rate. The Attorney Generals Office will provide restitution before utilizing any remainder to cover the cost of the case and future enforcement of the Consumer Protection Act.

Under the consent decree, the company also cannot claim its treatments are part of a clinical trial without proper FDA approval. In its marketing to consumers, the company claimed it was treating patients as part of clinical trials. In reality, the trials did not follow generally accepted standards of scientific research and the researchers themselves led the independent review of the trials.

Details of the case

US Stemology owns the Seattle Stem Cell Center in lower Queen Anne. The Attorney Generals Office was first alerted to this case when a concerned Washingtonian reported the companys false claims that it could treat and prevent COVID-19. The company made these claims for at least three months in the early stages of the pandemic.

For example, an ad from the company claimed that a critically ill COVID patient got better from stem cell treatments. In spring 2020, the company posted a downloadable Free Coronavirus Thriving Guide, that called stem cell treatment your personalized vaccine against getting sick with COVID-19.

After the Attorney Generals Office sent a cease and desist letter, the company removed from its website the claims that stem cells are effective against COVID-19.

While looking into the consumer complaint, investigators at the Attorney Generals Office discovered that the company claimed it could treat dozens of other conditions including serious heart, autoimmune and neurological conditions without reliable scientific evidence that stem cell treatments are effective in treating them.

US Stemology began marketing that it could treat these conditions starting as early as 2018. Meraglia began the stem cell clinic out of the basement of the medispa she owned, which mostly performed aesthetic and cosmetic treatments at the time.

The Seattle Stem Cell Center performed its stem cell treatments on over 100patients for a host of serious, chronic conditions, including asthma, muscular dystrophy, stroke, diabetes and Crohns disease.

The Food and Drug Administration (FDA) has only approved stem cell treatments for some blood disorders, but these procedures use a different cell type than what US Stemology used. The FDA has not approved stem cell treatments for any other condition. Health insurance plans generally do not cover stem cell treatments.

Assistant Attorneys General Daniel Davies and Logan Starr, investigators Anton Forbes and Eric Peters, paralegal Rosa Hernandez and legal assistant Michelle Paules are working on the case.

If you see suspicious or unproven claims about health treatments, report it to the Attorney Generals Office by filing a complaint at https://www.atg.wa.gov/file-complaint.

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Washingtons Attorney General serves the people and the state of Washington. As the states largest law firm, the Attorney Generals Office provides legal representation to every state agency, board, and commission in Washington. Additionally, the Office serves the people directly by enforcing consumer protection, civil rights, and environmental protection laws. The Office also prosecutes elder abuse, Medicaid fraud, and handles sexually violent predator cases in 38 of Washingtons 39 counties. Visit http://www.atg.wa.gov to learn more.

Media Contact:

Brionna Aho, Communications Director, (360) 753-2727; Brionna.aho@atg.wa.gov

General contacts: Click here

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AG Ferguson wins $500000 for individuals impacted by US Stemology's unproven claims that its stem cell injections could treat COVID-19 and other...

Tafasitamab Plus Lenalidomide Superior to Standard Therapies in Key Subgroups of High-Risk R/R DLBCL – Cancer Network

Subgroup analysis of the RE-MIND trial support use of tafasitamab plus lenalidomide to treat high-risk diffuse large B-cell lymphoma.

A subgroup analysis of the observational RE-MIND2 study (NCT04697160) in patients with stem cell transplantineligible high-risk diffuse large B-cell lymphoma (DLBCL) suggests improved overall survival (OS) with tafasitamab (Monjuvi) plus lenalidomide (Revlimid) treatment vs selected systemic therapies, according to data presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.1

Using matched cohorts of patients in subgroups based on the number of extranodal sites and presence or absence of elevated lactate dehydrogenase (LDH) level, the hazard ratio for OS suggests a trend toward favoring tafasitamab plus lenalidomide in each matched analysis set overall, and in most patient subgroups, said lead investigator Grzegorz S. Nowakowski, MD, of the Division of Hematology at the Mayo Clinic in Rochester, Minnesota.

In each subgroup examined, there was a trend favoring enhanced OS with tafasitamab plus lenalidomide when compared with systemic therapies pooled, rituximab [Rituxan] plus lenalidomide [Revlimid; R2], and polatuzumab [Polivy] plus bendamustine and rituximab [pola-BR].1

For the tafasitamab plus lenalidomide versus systemic therapies pooled matched cohort comparison, median OS was:

For the tafasitamab plus lenalidomide versus pola-BR matched cohort comparison, median OS was:

For the tafasitamab plus lenalidomide vs R2 matched cohort comparison, median OS was:

For the tafasitamab plus lenalidomide versus CD19-directed CAR-T cell therapy matched cohort comparison, median OS was:

The observed trend of shorter OS duration of CAR-T cells versus tafasitamab plus lenalidomide in high-risk patients warrants further investigation, said Dr. Nowakowski. We note that analyses between tafasitamb and comparator therapies are not powered for statistical comparison. Small sample size resulted in wide confidence intervals; therefore, those results must be interpreted with caution.

RE-MIND2 compared patient outcomes from the phase 2 L-MIND study (NCT02399085)2 with those from closely matched real-world cohorts, including patients treated with other systemic therapies for DLBCL pooled in a single cohort and cohorts comprising patients treated with common regimens.

Patients from L-MIND were closely matched with patients from 4 RE-MIND2 cohorts using estimated propensity score based one-to-one nearest neighbor matching balanced for up to 9 baseline covariates according to clinical relevance and other available patient records.

A total of 3454 patients were enrolled in RE-MIND2 from 200 study sites. The 1:1 matching methodology resulted in 76 pairs for tafasitamab plus lenalidomide versus systemic therapies pooled, 24 pairs versus pola-BR, 33 pairs versus R2, and 37 pairs versus CAR T-cell therapy.

The differences in cohort sizes reflects availability of baseline covariate data in hospital databases for therapies of interest, Nowakowski said.

Despite small sample sizes, these results may aid in contextualizing therapy options for treating patients with R/R DBCL, Nowakowski concluded.

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Tafasitamab Plus Lenalidomide Superior to Standard Therapies in Key Subgroups of High-Risk R/R DLBCL - Cancer Network

Understanding CAR T-Cell Therapy Utilization Patterns Among the Community Oncology Setting – Targeted Oncology

Thirty-nine percent of oncologists working in the community setting refer 2 out of 5 patients to receive chimeric antigen receptor (CAR) T-cell therapy at hospitals, according to data from a surveydisseminated by Cardinal Health Specialty Solutions.1

The research also showed that a decent portion of oncologists (27%), do not refer or administer CAR T-cell therapy at all, and a small proportion, 6%, perform in-office infusions. The survey raises questions about how to improve CAR T-cell availability for patients treated at community clinics. The recommendation born from the survey was to align stakeholders to address the concerns of the oncology population

In an interview with Targeted Oncology, Bruce Feinberg, DO, vice president, chief medical officer Cardinal Health Specialty Solutions, discussed the use of CAR T-cell therapy in the community oncology setting, the challenges oncologist face, and the next wave of innovation to improve CAR T-cell administration for patients.

TARGETED ONCOLOGY: Can you discuss CAR T-cell therapies that are FDA-approved in hematologic malignancies? How have these therapies impacted treatment?

Feinberg: The story of CAR T goes back a little before the drugs were approved. The recognition that our view of cancer in general was thinking of cancer as an invader. The way we thought about bacteria or viruses so that they were the enemy that we are going to then destroy.The recognition that changed all that was rather than thinking about cancer as the external alien enemy, because cancer was created by cells, and they are human cells that are transforming, should we be thinking about how to then look at the problem a little bit differently and see it as a failure of the host, as opposed to the invader.The story really begins as we think about empowering the immune system. The first aspects of that go back to the 1980s with interferons, interleukins, and tumor-infiltrating lymphocytes, and that was the first round.

The second way begins as we started to now think about the mid-2000 teams with the immune checkpoint inhibitors and start to look at manipulating T cells. The T-cell manipulation that begins with CART is not stopping with CAR T. It is going to be developing into bispecific antibodies, and natural killer cells that are then manipulated, so we are going to be seeing a rapid expansion of this host empowerment, how we really trigger the immune system to do its job, and then control this process, which really is a process of self as opposed to the external enemy.

Now that we have CAR T cells, what are the key challenges community oncologists facewith giving this treatment to patients?

The good news regarding these challenges is that we have had these challenges before. I mentioned that we think back in the early first phase of empowering the immune system with treatments like interleukin-2, we have the same kind of problem intensive treatment performed in hospital patients in ICU environments. We have also had that same world-specific to hematologic malignancies when we think about transplant, initially allogeneic transplant and then with autologous transplant, but similarly intensive complex programs, and multi-step approaches to patient care often done in tertiary care academic environments. There has been a background that really helps this field move forward quickly, based on that prior experience.

But the barriers that we have witnessed are those barriers we have seen before. Having an educated community workforce of healthcare providers who are knowledgeable about these treatments, an academic, tertiary care environment, where they remove all the barriers to those patient referrals, and hopefully patients who understand to some degree that complexity of the program will be willing to undergo consent for those procedures. Each of those barriers exist, but each of those barriers has been seen before, and we can rely on past experiences to help guide us forward.

Cardinal Health conducted a survey around in-office infusion and referrals for CAR T-cell therapy. How did community oncologists respond?

The research has been focused on both understanding physician perceptions. Are these therapies ready for primetime? Do they adopt and support these therapies? If they do support and adopt, what are the barriers to being able to refer patients for these treatments? Then lastly, what are the outcomes of these patients by getting into the chart itself and understanding the outcomes of patients? We have done all that in recent years, and some of that work was just recently presented at iSPOR.

At iSPOR, particularly regarding diffuse large B-cell lymphoma, there were 2 observational research studies that were done. One looked at the feasibility of being able to use that electronic health record in the community oncologist office to be able to understand the full journey of the patient who undergoes CAR T therapy, and can it understandthe scope and quality of the data that is housed within that medical record?

The second aspect of it was understanding. Could you be able to assess outcomes from the data within that medical record? So,2 parallel studies that were done specifically in diffuse large B-cell lymphoma, and also studies that have been done trying to look at new areas like multiple myeloma and understanding what physicians' perceptions about another hematologic malignancyin which there will be CAR T therapy available.

How do you interpret the findings from this survey?

For the community oncologist's electronic health record as a data source for conducting research on patients who are undergoing CAR T and other therapies, what we found is that the data source was rich and robust. For almost every major benchmark, in terms of the patient journey for CAR T,prior therapy, the timing of that prior therapy, the nature of that prior therapy, the referral to the tertiary center for consideration for CAR T, the actual evaluation for CAR T, the pheresis procedure, the site of the lympho-depletion procedure, chemotherapy, the actual administration of CAR T, the subsequent adverse event tracking, and the ER visits and hospitalizations, as well as the return to the community oncology clinic, all of that data was available within the community oncologist health record. That is a treasure trove of data that we can use as we start to expand the CAR T arsenal to understand the patient experience with CAR T in the real-world setting.

As we know, patients and clinical trials are often not representative of what is happening in real-world patients and clinical trials. First, less than 3% of adults with cancer participate in oncologic clinical trials, and those that do are healthier, they are less diverse, they are younger, they often are more health literate, and they have a higher socioeconomic status. That lack of representation becomes a problem that we start to extrapolate to all comers. Understanding what is happening in the real world to these patients is critical, and our data demonstrates that using the community oncologists to abstract the records is giving us that data that is necessary to understand the patient's experience. That is1 key outcome is that in the feasibility study, we saw as a strong positive for a new data source that can evaluate the real-world experience of patients undergoing CAR T-cell therapy.

The second outcome is that based on the feasibility of that data, could we find interesting details and insights about those patients being treated?We saw some interesting patterns of care that seemed to be geographically different. The timing of referrals and the nature of the CAR T-cell treatmentwere different as we looked across the major geographic regions of the country. Trying to understand that is going to be critical as the research continues, so are these trends and patterns related to Centers of Excellence and the KOLs, who often speak from those centers of excellence within a region?

Memorial Sloan Kettering often influences what happens in the Mid Atlantic, MD Anderson influences what happens in the South and the Southwest, and a center like UCLA influenceswhat's happens on the West Coast. As the Centers of Excellence have an influence, are we going to see differences in patterns of care in these different regions? Then, what were the outcome differences between those patterns of care?

Can you provide background on your study of CAR T-cell utilization patterns for relapsed/refractory diffuse large B-cell lymphoma in the US-based community hematologists/oncologists?

It has been almost 7 years since we first started to evaluate and publish on the broader world of empowering the host through immunologic therapies in the treatment of cancer. Our CAR T work now is 5 years, there have been a half dozen publications, similar tothe ones that we are talking about now, over the course of the past 5 years. We are trending that rate of adoption, that perceptions of physicians, the perceived barriers they find, and we are not just doing that assessment of physicians in the community, but we are also gathering experts from the major tertiary care centers to understand what they are perceiving as barriers and a general sense that CAR T therapy currently is under-utilized for those reasons and those barriers. What we find is there are still problems. The patients undergoing CAR T therapy have advanced disease, and are not clinically stable. The current timeline for CAR T, which can take 6 weeks from point of referral to point of CAR T-cell administration, often is problematic because of that patient instability.

Then, there are a host of new therapies which entered the armamentarium of treating physicians, which are making it confusing as to which is the appropriate second-line, third-line treatment. Recent data from ZUMA-7 [NCT03391466]trial has demonstrated that CAR T is a more effective therapythan autologous stem cell transplant as the first salvage treatment. That also adds a dynamic so that when we are doing this research, it can't be viewed as static. We have to be viewing it as a need for recurrent evaluations, as therapy indications change, and as new therapies come alive. Part of the basis for this research is really to be able to constantly trend what's happening in the field of newer therapies and how physicians perceive those new therapies and what are the outcomes of the patients. They're referring for those therapies. That was the focus of the work we've recently have done in diffuse large B-cell lymphoma.

Based on these 2 studies, how do you think the challenges that oncologists are experiencing with CAR T cells are impacting patient care?

I think overall, it is a good story. I think all physicians who treat cancer, particularly patients who have refractory or relapsed disease, for whom cure has been elusive, are looking for new therapeutic options. CAR T came with a tremendous amount of enthusiasm and excitement, but also with some concern about itstoxicity. Now, we are seeing second- and third-generation CAR T therapies, we're seeing expanded indications for earlier line of treatment. I think that excitement continues, and I think reservations are decreasing.

I think communication between tertiary care centers and community oncologists is improving, and we're getting closer to that point where patients will not have to leave home and leave their communities for this treatment, but we are not there yet.We are still testing and trying to understand what it will take for community physicians to participate in this aspect of care. I think that is going to be the next wave of innovation, and it will be operational innovation, rather than just drug development innovation, on how we can get these therapies to be done closer to the time of need.

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Understanding CAR T-Cell Therapy Utilization Patterns Among the Community Oncology Setting - Targeted Oncology

Eagles Club will host Hengeveld benefit | News – nwestiowa.com

REGIONALA benefit will be held Saturday at the Sheldon Eagles Club for a Hartley man facing a second bout with cancer at the age of 26.

Branden Hengeveld was diagnosed in February of 2021 with Hodgkin lymphoma and went through six months of chemotherapy. After this treatment, he was given the all-clear in August.

In December, he had a follow-up scan, and the doctors noticed some concerning things. They did a biopsy, but it came back negative. Hengeveld went back for another scan in March and enlarged lymph nodes prompted another biopsy which this time came back positive for Hodgkin lymphoma.

When it was discovered, the cancer already was between stages 2 and 3.

Hengeveld has started doing chemotherapy treatment again in Sioux Falls, SD, to shrink his cancer and then at the end of June, he will be headed to Mayo Clinic in Rochester, MN, for around six weeks.

Six to eight weeks is the usual, but they said just prepare for a 100-day stay, he said.

Hengeveld will be undergoing a stem cell transplant treatment at Mayo. The treatment consists of three weeks of tests, then six days of strong chemotherapy followed by the stem cell transplant which will take three weeks of recovery.

He will have to stay in Rochester during the entire process.

Funds raised by Saturdays benefit will go toward travel, rent and any other expenses for Hengeveld during his treatment.

Hengeveld grew up in Sanborn and lives in Hartley. He has worked for the last few years at Den Hartog Industries in Hospers, where he became friends with Vanessa Harig who is hosting the event.

Pretty much everyone at Den Hartog knows Branden, Harig said. Hes a very great guy and is always very happy and bubbly. It is going to be hard when he is away in Rochester.

Hengevelds father and brother knew they wanted to hold a benefit for him but were unsure how to organize it, so they sought out Harigs assistance.

Me being crazy like I am, said, Yea, I can organize a benefit, Harig said.

She is no stranger to organizing events and helping others. Harig is the director of the Awakening Grace Foundation in Orange City, which helps those who have lost a child during pregnancy or infancy.

Although she has a lot going on, Harig felt up to the task and the cause worthy.

A lot of people get caught off guard when the realize how young Branden is and that he has already had cancer twice, she said. Hes fighting hard and doing everything he can.

Despite all that has happened, Hengeveld remains positive.

Its been a process for sure, he said. But Ive met a lot of people and made some good friends throughout it.

Hengeveld has a GoFundMe page as well as a Facebook page where he posts updates.

Saturdays fundraising event will consist of a spaghetti supper with garlic bread and homemade desserts starting at 5 p.m. until it is gone as well as a silent auction 5-7 p.m. There also will be a raffle for a Traeger smoker grill which will be drawn for at 7:30 p.m. Tickets for the raffle are $20 each and 100 tickets will be sold. Participants need not be present to win.

Text Vanessa Harig at 712-344-2149 to enter the raffle or for any questions.

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Eagles Club will host Hengeveld benefit | News - nwestiowa.com

The Oncology Institute set to join the Russell 2000 and Russell 3000 Indexes – StreetInsider.com

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CERRITOS, Calif., June 07, 2022 (GLOBE NEWSWIRE) -- The Oncology Institute, Inc. (NASDAQ: TOI), one of the largest value-based oncology groups in the United States, today announced thatit will join the Russell 2000 and Russell 3000 Indexes after the 2022 Russell indexes annual reconstitution, effective after the US market opens on June 27, according to a preliminary list of additions posted June 3.

Annual Russell indexes reconstitution captures the 4,000 largest US stocks as of May 6, ranking them by total market capitalization. Membership in the US all-cap Russell 3000 Index, which remains in place for one year, means automatic inclusion in the large-cap Russell 1000 Index or small-cap Russell 2000 Index and the appropriate growth and value style indexes. FTSE Russell determines membership for its Russell indexes primarily by objective, market-capitalization rankings, and style attributes.

We are excited to be joining the Russell indexes as this represents another important milestone since becoming a public company in November of 2021, said Brad Hively, CEO of TOI. As we grow our business and execute our strategic objectives, we look forward to educating key stakeholders about TOIs innovative oncology care and our continued progress.

Russell indexes are widely used by investment managers and institutional investors for index funds and as benchmarks for active investment strategies. Approximately $12 trillion in assets are benchmarked against Russells US indexes. Russell indexes are part of FTSE Russell, a leading global index provider.

For more information on the Russell 3000 Index and the Russell indexes reconstitution, go to the Russell Reconstitution section on the FTSE Russell website.

About The Oncology Institute, Inc.

Founded in 2007, TOI is advancing oncology by delivering highly specialized, value-based cancer care in the community setting. TOI offers cutting-edge, evidence-based cancer care to a population of approximately 1.5 million patients including clinical trials, stem cell transplants, transfusions, and other care delivery models traditionally associated with the most advanced care delivery organizations. With 80+ employed clinicians and more than 600 teammates in over 50 clinic locations and growing, TOI is changing oncology for the better. For more information visitwww.theoncologyinstitute.com.

Contacts

Media

The Oncology Institute Julie Korinke [emailprotected](562) 735-3226 x 88806

Revive Michael Petrone [emailprotected](615) 760-4542

Investors

Solebury Trout Maria Lycouris [emailprotected]

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The Oncology Institute set to join the Russell 2000 and Russell 3000 Indexes - StreetInsider.com

The path to least resistance: How our researchers are outsmarting cancers survival skills – Cancer Research UK News

Breast cancer cells Credit: NCI

Drug resistance is one of biomedicines biggest threats, standing in the way of cures for all manner of viruses, infections and diseases, including cancer. But our scientists across the country are working hard to tackle it.

After a shock breast cancer diagnosis in January 2021 at the age of 48, doctor and mother Tina* underwent six months of chemotherapy, which for many people with early-diagnosed breast cancer can be curative. But a test following treatment confirmed the presence of residual cancer cells. Cells that had somehow survived the treatment onslaught. Cells that indicate the cancer could return. When I was told that my treatment hadnt been entirely successful, I initially felt very upset, Tina recalls. Id had a difficult time through chemo, needing multiple blood transfusions and experiencing multiple delays in treatment due to low blood counts. To then be told that there seemed to be residual disease due to chemo resistance was very hard to hear.

To be told after treatment that there seemed to be residual disease due to chemo resistance was very hard to hear Tina, breast cancer patient

Despite the huge progress weve made in breast cancer survival which has doubled in the UK over the past 40 years Tinas is a reality for many women with triple negative breast cancer, a subtype that can be harder to treat. For these women, when cancer does recur its more difficult to get on top of, explains Cancer Research UK clinician scientist Dr Sheeba Irshad. Dr Irshad is part of a growing cohort across our institutes and centres who are working to expose and exploit the mechanisms that allow some cancer cells to resist treatment (from chemotherapy to targeted treatments and even immunotherapies), lay dormant and then re-emerge later, when theyre harder to eradicate.

Drug resistance is a major reason why cancer regrows after treatment, so its also a significant contributor to people not surviving their disease, confirms Professor Dan Tennant, a Cancer Research UK biochemist at the University of Birmingham. Hes setting his sights on hypoxia a low-oxygen state in cells that occurs in most solid cancers and is a leading cause of drug resistance. Like all cells, cancer cells need oxygen to survive and multiply. When oxygen is scarce, theyre forced to adapt, finding compensatory ways to complete fundamental processes. Whats left is a cancer cell with a markedly different metabolism than a cancer cell with a normal oxygen supply. And one that stands out to someone like Professor Tennant, whos investigating how cancer cells survive such hostile conditions.

I dont think its a coincidence that, for example, glioblastoma an aggressive brain tumour is one of the most hypoxic tumour types and also incredibly resistant to treatments, he reasons. Given that hypoxic cells are some of the most drug-resistant cells within a tumour, by targeting them, we can directly alleviate resistance. And because the rest of the body has a normal oxygen supply, going after just the hypoxic cancer cells means patients should experience fewer negative side effects. Thinking about long-term therapy and a persons quality of life, thats a huge bonus, he adds.

Earlier this year, Professor Tennants team landed on a promising drug target. By feeding hypoxic cells nutrients such as sugars and watching how they use them compared to cancer cells with normal oxygen levels, they identified an enzyme that plays a critical role in hypoxic cells. When they removed the enzyme from cancer cells in mice, it caused the hypoxic tumour cells to die.

Despite this focus on the most fundamental elements of biology, Professor Tennant and his team are making steady progress toward the clinic not least because just 50 metres away, Cancer Research UK neurosurgeon Professor Colin Watts is collecting tissue samples from volunteer patients and passing them to the team so they can check their lab-based models against the real thing. The data generated on each side quickens the pace of progress. As Professor Tennant explains, Now, when we take our discovery science and try to translate it into new therapies, it has a better chance of working.

Its an attitude shared by Professor Stephen Tait at the Cancer Research UK Beatson Institute in Glasgow, whos also eager to use our vast clinical network to translate lab discoveries swiftly. He and his team are examining what happens when treatments do their job well but cause harmful unintended consequences. They found that when chemotherapy successfully kills a cancer cell, the dying cell can emit a protein that acts as a protector to neighbouring cancer cells, shrouding them from chemotherapy and allowing them to emerge unscathed. Professor Tait now hopes to test this by combining chemotherapy with a drug to inhibit this protein.

Its promising work, but perhaps more exciting is some of the teams earlier research, which is now flying towards the clinic thanks to an alliance set up by Cancer Research UK. Its based on their discovery that by blocking a class of proteins called caspases before a cancer cell is killed, the dying cell releases signals to the immune system. In normal circumstances, the immune system ignores cell death if it didnt, it would constantly be responding to the billions of cells that die within us each day. But with the immune system alerted, any leftover cancer cells can be ambushed and killed. Professor Tait is modest about the discovery: Like a lot of things in research, if you just stay alert, you see exciting stuff going on, he says. But their findings could lead to a new class of treatments that combine the strength of chemotherapy with the bodys perceptive immune response.

Back in Birmingham, Cancer Research UK cell biologist Dr Clare Davies is also making clinically relevant fundamental discoveries. Shes studying breast cancer stem cells, which initiate breast tumours. These cells are inherently chemo-resistant because they can repair the DNA damage that chemotherapy induces, she explains. They manage to do this because they have enhanced genes and mechanisms that control DNA repair pathways. These cells also multiply slower than other cancer cells, and because chemotherapy actively targets rapidly dividing cells, they face less bombardment.

We often think that science is a slow burn, but this shows it can really fly when people invest the time and money Dr Clare Davies

Developing drugs that specifically target the pathways enhanced in cancer stem cells would provide a new way to tackle chemo-resistant breast cancer. And Dr Davies and her team have identified an enzyme that they believe helps keep cancer stem cells alive by increasing these pathways. If we can inhibit this enzyme while also delivering chemotherapy, we can block the repair mechanisms and push the cancer stem cell over the edge, she explains, suggesting that we could cut cancer recurrence off at the source. Cancer is clever. It evolves, she says. We must understand the mechanisms underlying this evolution by studying cancer stem cells.

Dr Davies is now working with a pharmaceutical company to progress this work to patients through a clinical trial. We often think that science is a slow burn, but this shows it can really fly when people invest the time and money.

While these steps forward are cause for enthusiasm, they must also be met by innovation and resource in the clinic. Thats why Dr Irshad is leading a clinical trial platform named PHOENIX, which aims to accelerate the drug development pipeline for hard-to-treat breast cancers. Biopsies taken before and after treatment help the team understand the chemo-resistant disease in each individual patient and monitor the efficacy of specific drugs. These short-term efficacy trials allow us to design better trials with a higher likelihood of success, Dr Irshad explains.

Its then that the progress made in breast cancer survival really begins to count. Were lucky in breast cancer care that if secondary cancer is likely, we do have options for our patients, she adds. We can be proactive and that really matters.

With so many advances in drug discovery over the past few decades from improving chemotherapy and radiotherapy, to delivering targeted treatments and immunotherapies drug resistance deals a cruel blow. Only by bridging the biomedical and clinical worlds, and working in partnership with health systems and philanthropic partners, can we create the infrastructure and funding required to support our researchers and clinicians as they strive to remain one step ahead and ensure people like Tina arent left in limbo, waiting to be told whether their cancer has returned.

Researcher images from top to bottom: Dr Sheeba Irshad, Professor Dan Tennant, Professor Stephen Tait, Dr Clare Davies

I found out I had breast cancer on Wednesday 13 January, 2021. I remember the day well.

When I was told that my treatment hadnt been entirely successful, I initially felt very upset. Id had a difficult time through chemo, needing multiple blood transfusions and experiencing multiple delays in treatment due to low blood counts. To then be told that there seemed to be residual disease due to chemo resistance was very hard to hear.

From the outset, my hospital team have been fantastic. The oncologists always had a positive approach. As a mother of young children, I felt that this was essential. And when Dr Irshad told me that I would be entered into the trial, I felt hopeful and grateful that it was possible.

Its incredibly important that researchers like Dr Irshad continue vital research in this area. I never thought I would get breast cancer. I have become friends with a lot of women with breast cancer since my diagnosis. Were all so different. I would give anything to know what caused it. Im hoping that, with research, not only will we find treatments but also causes. I have a daughter and would not want her to go through what I have been through. Currently, Im doing really well. I have returned to work fully and lead a normal life. Lots of good things have happened as a result of my diagnosis. Ive realised how many people care for me and my family and I now lead a healthier lifestyle.

*Name has been changed at the request of the contributor.

Were tremendously grateful for funding weve received from supporters including Gonzalo and Maria Garca, Garfield Weston Foundation, Denise Leffman Trust and Mike Jackson, which has helped facilitate the work featured in this article.

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The path to least resistance: How our researchers are outsmarting cancers survival skills - Cancer Research UK News

The Foundation of Hope and Innovation Partners with Venice Family Clinic to Provide Free Mammograms – GlobeNewswire

CERRITOS, Calif., May 24, 2022 (GLOBE NEWSWIRE) -- The Foundation of Hope and Innovation, a charity supported by The Oncology Institute, Inc. (NASDAQ: TOI), announced a $40,000 donation to Venice Family Clinic to fund mammography services to women in Los Angeles. The donation will fund 10 free mammography days throughout greater Los Angeles.

The Foundation of Hope and Innovation selected Venice Family Clinic to be the first grant recipient of 2022 because of its 50-year history of providing primary care, specialty care, dental care, and mental health services to their community. Venice Family Clinics services align closely with The Foundation of Hope and Innovations founding principles: advance treatment options for patients and fill the gaps in healthcare delivery, including early detection of cancer and mental health support for patients.

Early detection of cancer is critically important to ensure prompt treatment and optimal outcomes, shared Dr. Daniel Virnich, Board President for The Foundation of Hope and Innovation. By partnering with a well-respected non-profit healthcare provider like Venice Family Clinic, we can ensure that more people have access to affordable cancer screening services and timely cancer treatment.

Venice Family Clinic provides high-quality, comprehensive health care to families and individuals who might otherwise go without the care they need. With 17 locations serving nearly 45,000 patients, Venice Family Clinic increases access to quality healthcare for Angelinos in need and helps ensure more people have access to early cancer screenings.

The generous donation by The Foundation of Hope and Innovation will ensure 200 patients access mammograms they may not have otherwise been able to access, added Rigoberto Garcia, Director of Health Education at Venice Family Clinic. We are thrilled to be able to extend these services to more patients.

About The Foundation of Hope and InnovationThe Foundation of Hope and Innovation believes that every patient, and their family, deserves access to high quality care and support services. They are committed to filling gaps in healthcare delivery, including early detection and mental health support. For more information visit http://www.foundationofhopeandinnovation.org.

About The Oncology Institute, Inc.Founded in 2007, The Oncology Institute of Hope and Innovation (TOI) is advancing oncology by delivering highly specialized, value-based cancer care in the community setting. TOI offers cutting-edge, evidence-based cancer care to a population of approximately 1.5 million patients including clinical trials, stem cell transplants, transfusions, and other care delivery models traditionally associated with the most advanced care delivery organizations. With 80+ employed clinicians and more than 600 teammates in 50 clinic locations and growing, TOI is changing oncology for the better. For more information visit http://www.theoncologyinstitute.com.

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The Foundation of Hope and Innovation Partners with Venice Family Clinic to Provide Free Mammograms - GlobeNewswire

Stem Cell Concentration System Market Research Report Contains Key Players, Industry Overview, Supply Chain, Analysis And Forecast To 2021- 2026 The…

New York, United States: The global Stem Cell Concentration System Market research is an intelligence report with meticulous efforts undertaken to check the proper and valuable information by Decisive Markets insights. The info which has been looked upon is completed considering both, the prevailing top players and therefore the upcoming competitors. Business strategies of the key players and therefore the new entering market industries are studied very well. Well explained SWOT analysis, revenue share and call information are shared during this report analysis. It also provides market information in terms of development and its capacities.

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Stem Cell Concentration System Market Segmentation- By Type : Syringes Bone Marrow Collection Needles Anticoagulant and Concentrating Devices Others By Application : Hospital Clinic Diagnostic Laboratories Key Players : EmCyte Terumo Perkin Elmer Zimmer Biomet Teleflex Argos Technologies Avita Medical Arthrex

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The cost analysis of the worldwide market has been performed while keeping in sight manufacturing expenses, labour cost, and raw materials and their market concentration rate, suppliers, and price trend. Other factors like Supply chain, downstream buyers, and sourcing strategy are assessed to supply an entire and in-depth view of the market. Buyers of the report will be exposed to a study on market positioning with factors like target client, brand strategy, and price strategy taken into consideration.

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Stem Cell Concentration System Market Research Report Contains Key Players, Industry Overview, Supply Chain, Analysis And Forecast To 2021- 2026 The...

Google Reverses Ban on Ads for All Stem Cell Therapies, Will Allow FDA-Approved Ones – Gizmodo Australia

Google announced Monday it will allow ads for stem cell treatments approved by the Food and Drug Administration to appear in search results starting in July. The tech giant previously banned any ads for stem cell therapies, FDA-approved or otherwise.

In an update to its policies page first spotted by Gizmodo, the company said that, starting July 11, it will permit search engine ads for stem cell therapies given the thumbs up from the FDA, a very small list of just 23 companies that treat some blood disorders and cancers, according to the FDAs website.

At the same time, Google is clarifying its policy language on stem cell therapy ads, which would allow a global cell or gene therapy company to advertise if the ads are are exclusively educational or informational in nature, regardless of regulatory approval status. Google did not clarify what would constitute educational or informational, nor did the company respond to a request for comment how it will restrict less-than-reputable products from being advertised with its technology going forward. We will update the story if we hear more.

The search engine said it banned all advertising for stem cell treatments back in 2019, proclaiming at the time it was restricting ads that have no established biomedical or scientific basis. In 2021, the company clarified that it was restricting ads for experimental treatments meant for so-called biohacking or other DIY genetic engineering, as well as any cell or gene therapies like stem cell therapy.

Despite the pledge to ban such ads or Mondays announced change, a simple Google search reveals just how easily bad actors can get around the restrictions. Searching for stem cells for neuropathy reveals several misleading ad results for stem cell treatments that are not FDA approved, though at least one maker claims it is FDA registered and another says its treatment is supported by FDA master files.

Paul Knoepfler, a professor at the University of California Davis School of Medicine who researches stem cells and cancer, has written before about Googles problematic search engine ad policies that allow stem cell companies to easily advertise their products in spite of the tech giants rules. In an email, he told Gizmodo he is concerned How effectively the new rule for strictly educational ads would be maintained, particularly given the context of Google Search now so often highly ranking promotional clinic websites arguably presented as educational material.

Stem cells as an industry have grown rapidly in recent years and are expected to continue doing so, with MarketWatch reporting in February the $US2.75 ($4) billion industry is expected to more than double to $US5.72 ($8) billion by 2028.

Stem cell treatments are approved by the FDAs Cellular, Tissue and Gene Therapies Advisory Committee. Though some companies claim in advertising they have FDA approval, being listed on clinicaltrials.gov database or being registered with the FDA isnt full-on approval, according to the agencys guidelines. The fact that companies regularly run around Googles existing policies leaves even more questions on the table. Knoepfler asked whether clinical trial recruitment be allowed, when hes often seen such trials already claiming their treatment already works.

Perhaps good citizens in the regenerative medicine world want the opportunity to run such ads related to clinical trial recruitment, but even exclusively educational ads of that type with good intentions could run into ethical issues, Knoepfler added.

Shoshana Wodinsky contributed reporting.

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Google Reverses Ban on Ads for All Stem Cell Therapies, Will Allow FDA-Approved Ones - Gizmodo Australia

Supporting the gastrointestinal microenvironment during high-dose chemotherapy and stem cell transplantation by inhibiting IL-1 signaling with…

Mucosal barrier injury (MBI) in the gastrointestinal tract remains a major clinical obstacle in the effective treatment of hematological malignancies, driving local and systemic complications that negatively impact treatment outcomes. Here, we provide the first evidence of hyper-activation of the IL-1/CXCL1/neutrophil axis as a major driver of MBI (induced by melphalan), which supports evaluating the IL-1RA anakinra, both preclinically and clinically. Our data reinforce that strengthening the mucosal barrier with anakinra is safe and effective in controlling MBI which in turn, stabilises the host microbiota and minimises febrile events. Together, these findings represent a significant advance in prompting new therapeutic initiatives that prioritise maintenance of the gut microenvironment.

The IL-1/CXCL1/neutrophil axis is documented to drive intestinal mucosal inflammation, activated by ligation of intestinal pattern recognition receptors, including toll-like receptors (TLRs)31. In the context of MBI, TLR4 activation is known to drive intestinal toxicity32, 33, however targeting TLR4 directly is challenging due to emerging regulation of tumour response34,35,36,37. As such, we selected anakinra as our intervention to inhibit inflammatory mechanisms downstream of TLR4. While anakinra was able to minimise the intensity and duration of MBI, it did not completely prevent it with comparable citrulline dynamics across animal groups in the first 48h after melphalan treatment. This reflects the core pathobiological understanding of MBI which is initiated by direct cytotoxic events which activate a cascade of inflammatory signalling that serve to exacerbate mucosal injury and the subsequent breakdown of the mucosal barrier33. By preventing this self-perpetuating circle of injury with anakinra, we were able to effectively minimise the duration of MBI and thus have a profound impact on the clinical symptomology associated with MBI including weight loss and anorexia. These findings firstly highlight the cluster of (pre-)clinical symptoms related to MBI (malnutrition, anorexia, diarrhea)38 and suggest that the mucoprotective properties of anakinra will provide broader benefits to the host, mitigating the need for intensive supportive care interventions (e.g. parenteral nutrition).

In line with our hypothesised approach, minimising the duration of MBI reduced secondary events including enteric pathobiont expansion and fever. This again reiterates that changes in the host microbiome and associated complications can be controlled by strengthening the mucosal barrier39. It can be postulated that by minimising the intensity of mucosal injury, the hostility of the microbial environment is reduced ensuring populations of commensal microbes to be maintained. This is supported by our results with the abundance of Faecalibaculum maintained throughout the time course of MBI. Faecalibaculum is a potent butyrate-producing bacterial genus documented to control pathogen expansion by acidification of the luminal environment. Administration of Faecalibacteria prausnitzii has been shown to reduce infection load in a model of antibiotic-induced Clostridioides difficile infection, whilst also showing mucoprotective benefits in models of MBI40, 41. Furthermore, it is documented to cross feed other commensal microbes increasing colonization resistance. Together, these underscore the luminal benefits of strengthening the mucosal barrier and suggest that maintenance of commensal microbes is central to minimizing translocation events and subsequent BSI.

In our clinical Phase IIA study with 3+3 design, we have shown that treatment with anakinra, up until a dose of 300mg, appears to be safe, feasible, and tolerated well. Of course, the sample size of this study was relatively small. However, anakinra was previously evaluated for its efficacy in the treatment of acute and chronic GvHD in patients allogeneic HSCT. In these studies, patients were treated for a similar time period (with higher doses of anakinra). No differences were seen between the anakinra and placebo group regarding (S)AEs, including infections and time to neutrophil recovery. There were no significant changes in our exploratory analyses, however, it was of note to see marked increase in IL-10 in patients that received 300mg anakinra. This may reflect anakinras capacity to promote anti-inflammatory signaling as observed in COVID-19 related respiratory events42. However, with our sample size it is not possible to make any conclusions on this mechanism. Our conclusion is that the recommended dose (RP2D) for anakinra is 300mg QD, which will be investigated in Phase IIB trial (AFFECT-2 study: Anakinra: Efficacy in the Management of Fever During Neutropenia and Mucositis in ASCT; clinicaltrials.gov identifier NCT04099901)43.

While encouraging, our data must be viewed in light of some limitations. Most importantly, our animal model purposely did not include any antimicrobials as we aimed to dissect the true contribution of MBI in pathogen expansion and subsequent febrility. While it is unclear if melphalan has a direct cytotoxic effect on the microbiota, it is likely that MBI drives dysbiosis with antibiotics serving to exacerbate these changes, with previous data demonstrating no direct impact of specific chemotherapeutic agents on microbial viability44. As such, assuming dysbiosis is secondary to mucosal injury as recently demonstrated45, we anticipate that anakinra will still have an appreciable impact on the severity of dysbiosis and may even prompt more protocolised/limited antibiotic use. Similarly, while we used body temperature as an indicator of BSI, we did not culture peripheral blood or mesenteric lymph nodes as was performed in our animal model development. The ability of anakinra to prevent BSI and thus minimise antibiotic use will be best evaluated in AFFECT-2 where routine blood culture is performed. It is also important to consider that we detected episodes of bacteremia in our participants that were likely caused by skin colonizing organisms; a mechanism anakinra will not influence. While these are expected in HSCT recipients, the majority of infectious cases originate from the gut, and we therefore anticipate anakinras capacity to strengthen the mucosal barrier will be clinically impactful in our next study. It must also be acknowledged that limited mechanistic investigations were conducted to identify the way in which anakinra provided mucoprotection. It is well documented that MBI is highly multifactorial, involving mucosal, microbial and metabolic dysfunction33, 46; each of which is mediated through aberrant cytokine production. It is therefore unlikely that anakinra will affect distinct pathways, instead dampening multiple mechanisms. In translating this evidence to the clinic, the impact of anakinra on symptom control is of greater significance than mechanistic insight.

In conclusion, we have demonstrated that not only is anakinra safe in HSCT recipients treated with HDM, but may also be an effective strategy to prevent acute MBI. Our data are critical in supporting new antibiotic stewardship efforts directed at mitigating the emerging consequences of antibiotic use. We suggest that minimizing the severity and duration of MBI is an important aspect of infection control that may optimize the efficacy of anti-cancer treatment, decreasing its impact on antibiotic resistance and the long-term complications associated with microbial disruption.

This study is reported using the ARRIVE guidelines for the accurate and reproducible reporting of animal research.

All animal studies were approved by the Dutch Centrale Commissie Dierproeven (CCD) and the Institutional Animal Care and Use Committee of the University Medical Centre Groningen, University of Groningen (RUG), under the license number 171325-01(-002). The procedures were carried out in accordance with the Dutch Experiments on Animals (Wet op de Dierproeven) and the EU Directive 2010/63/EU. All animals were individually housed in conventional, open cages at the Centrale Dienst Proefdieren (CDP; Central Animal Facility) at the University Medical Centre Groningen. Rats (single housed) were housed under 12h light/dark cycles with ad libitum access to autoclaved AIN93G rodent chow and sterile water. All rats acclimatised for 10days and randomised to their treatment groups via a random number sequence generated in Excel. Small adjustments were made to ensure comparable body weight at the time of treatment and cages were equally distributed across racks to minimise confounding factors. HRW was responsible for animal allocation and assessments while RH/ARDSF performed treatments. Softened chow and subcutaneous saline were provided to rats to reduce suffering/distress and were humanely euthanised if a clinical toxicity score>/=12 was observed. This score was calculated based on weight loss, diarrhea, reluctance to move, coat condition and food intake; each of which were assessed 03. At completion of the study, rats were anaesthetised with 5% isoflurane in an induction chamber, followed by cardiac puncture and cervical dislocation (isoflurane provided by a facemask).

We have previously reported on the development and validation of our HDM model of MBI, which exhibits both clinical and molecular consistency with patients undergoing HDM treatment21. During model development, plasma (isolated from whole blood) was collected and stored for cytokine analysis to inform the selection of our intervention. Repeated whole blood samples (75l) were collected from the tail vein into EDTA-treated haematocrit capillary tubes on day 0, 4, 7 and 10.

Cytokines (IFN-, IL-1, IL-4, IL-5, IL-6, IL-10, IL-13, KC/GRO and TNF-) using the Meso Scale Discovery V-Plex Proinflammatory Panel Rat 2 following manufacturers guidelines. On the day of analysis, all reagents were brought to room temperature, samples were centrifuged to remove any particulate matter and diluted 1:4. Data analysis was performed using the Meso Scale Discovery Workbench.

Male albino Wistar rats (150180g) were randomized (Excel number generator) to one of four experimental groups (N=16/group): (1) controls (phosphate buffered saline (PBS)+0.9% NaCl), (2) anakinra+0.9% NaCl, (3) PBS+melphalan, and (4) anakinra+melphalan. Melphalan was administered as a single, intravenous dose on day 0 (5mg/kg, 10mg/ml) via the penile vein under 3% isoflurane anaesthetic. Anakinra was administered subcutaneously (100mg/kg, 150mg/ml) twice daily from day 1 to+4 (8 am and 5pm). N=4 rats per group were terminated at the exploratory time points (day 4, and 7) and N=8 on day 10 (recovery phase) by isoflurane inhalation (3%) and cervical dislocation. The primary endpoint for the intervention study was plasma citrulline, a validated biomarker of MBI19, 47, which was used for all power calculations (N=8 required, alpha=0.05, beta=0.8).

Clinical manifestations of MBI were assessed using validated parameters of body weight, food intake and water intake, as well as routine welfare indicators (movement, posture, coat condition). Rats were weighed daily, and water/food intake monitored by manual weighing of chow and water bottles.

Plasma citrulline is an indicator of intestinal enterocyte mass48, and a validated biomarker of intestinal MBI. Repeated blood samples (75l) were collected from the tail vein into EDTA-treated haematocrit capillary tubes on day 0, 2, 4, 6, 7, 8 and 10. Citrulline was determined in 30l of plasma (isolated from whole blood via centrifugation at 4000g for 10min) using automated ion exchange column chromatography as previously described49.

Whole blood samples (200l) were collected from the tail vein into MiniCollect EDTA tubes on day 0, 4, 7 and 10 for differential morphological analysis which included: white blood cell count (WBC, 109/L), red blood cell count (RBC, 109/L), haemoglobin (HGB, mmol/L), haematocrit (HCT, L/L), mean corpuscular volume (MCV, fL), mean corpuscular haemoglobin (MCH, amol), mean corpuscular hemoglobin concentration (MCHC, mmol/L), platelet count (PLT, 109/L), red blood cell distribution width (RDW-SD/-CV, fL/%), mean platelet volume (fL), mean platelet volume (MPV, fL), platelet large cell ratio (P-LCR, %), procalcitonin (PCT, %), nucleated red blood cell (NRBC, 109/L and %), neutrophils (109/L and %), lymphocytes (109/L and %), monocytes (109/L and %), eosinophils (109/L and %), basophils (109/L and %) and immunoglobulins (IG, 109/L and %). For the purpose of the current study only neutrophils, lymphocytes and monocytes were evaluated.

Core body temperature was used as an indicator of fever. Body temperature was assessed daily using the Plexx B.V. DAS-7007R handheld reader and IPT programmable transponders. Transponders were inserted subcutaneously under mild 2% isoflurane anaesthesia on day 4. Average values from day 4 to 1 were considered as baseline body temperature.

The microbiota composition was assessed using 16S rRNA sequencing in N=8 rats/group. Repeated faecal samples were collected on day 0, 4, 7 and 10 and stored at 80C until analysis. Sample preparation (including DNA extraction, PCR amplification, library preparation), quality control, sequencing and analyses were all performed by Novogene (please see supplementary methods for full description).

All data (excluding 16S data) were analysed in GraphPad Prism (v8.0. Repeated measures across multiple groups were assessed by mixed-effect models with appropriate post-hoc analyses. Terminal data analyses were assessed by one-way ANOVA. Statistical analyses are outlined in figure legends and P<0.05 was considered significant.

This Phase IIA trial (AFFECT-1: NCT03233776, 17/6/2017) aimed to i) assess the safety of anakinra in autologous HSCT recipients undergoing conditioning with HDM, and ii) determine the maximum tolerated dose of anakina (100, 200 or 300mg).

This study was approved by the ethical committee Nijmegen-Arnhem (NL59679.091.16; EudraCT 2016-004,419-11) and performed in accordance with (a) theDeclaration of Helsinki (1964, amended October 2013), (b) Medical Research Involving Human Subjects Act and c) Good Clinical Practice guidelines.We enrolled patients from Radboud University Medical Centre who were at least 18years of age and were scheduled to undergo an autologous HSCT after receiving conditioning with HDM (200mg/m2) for multiple myeloma. All participants provided informed consent. Important exclusion criteria were active infections, a history of tuberculosis or positive Quantiferon, glomular filtration rate<40ml/min, and colonization with highly resistant micro-organisms or with gram-negative bacteria resistant to ciprofloxacin.

Patients were involved in the design of the AFFECT trials, through involvement of Hematon, a patient organization for patients with hemato-oncological diseases in the Netherlands. The project plan, including trial materials, have been presented to patient experts from Hematon. They have given their advice on the project, and provided input on the design of the study as well as on patient information. Patients will also be involved in the dissemination of the results of the AFFECT trials. Information on both the design as well as the outcome of the AFFECT trials is and/or will be available on websites specifically aimed at patients, such as the Dutch website kanker.nl.

Conforming with routine clinical practice and care, study participants were admitted at day 3, treated with melphalan 200mg/m2 at day 2, and received their autologous HSCT at day 0. They were treated with IL-1RA anakinra (Kineret, SOBI) intravenously once daily from day 2 up until day+12.

A traditional 3+3 design was used (Fig. S1), in which the first cohort of patients was treated with 100mg, the next cohort with 200mg and the third cohort with 300mg of anakinra. In this study design, the cohort is expanded when dose limiting toxicities (DLTs) occur. The primary study endpoint was safety, using the common toxicity criteria (CTCAE) version 4.050, as well as the maximum tolerated dose of anakinra (MTD; 100, 200 or 300mg). DLTs were defined as the occurrence of (1) an infection due to an opportunistic pathogen (including Pneumocystis jirovecii pneumonia, mycobacterial infections and invasive mould disease), (2) a suspected unexpected serious adverse reaction (SUSAR), (3) severe non-hematological toxicity grade 34 (meaning toxicity that does not commonly occur in the treatment with HDM and HSCT, or that is more severe than is to be expected with standard treatment) and (4) primary graft failure or prolonged neutropenia (neutrophils have not been>0.5109/l on one single day, assessed on day+21, and counting from day 0).

Secondary endpoints included: incidence of fever during neutropenia (defined as a tympanic temperature38.5C and an absolute neutrophil count (ANC)<0.5109/l, or expected to fall below 0.5109/l in the next 48h), CRP levels, intestinal mucositis as measured by (the AUC of) citrulline, clinical mucositis as determined by daily mouth and gut scores, incidence and type of BSI, short term overall survival (100days and 1year after HSCT), length of hospital stay in days and use of systemic antimicrobial agents, analgesic drugs and total parenteral nutrition (incidence and duration).

Patients received standard antimicrobial prophylaxis including ciprofloxacin and valacyclovir, as well as antifungal prophylaxis (fluconazole) on indication; i.e. established mucosal colonization. Upon occurrence of fever during neutropenia, empirical treatment with ceftazidime was started. The use of therapies to prevent or treat mucositis (i.e. oral cryotherapy) was prohibited. Also, treatment with acetaminophen or non-steroidal anti-inflammatory drugs was not allowed during hospital admission. All other supportive care treatments (i.e. morphine, antiemetics, transfusions, TPN) were allowed.

Laboratory analysis was performed three times a week, which included hematological and chemistry panels and plasma collection for citrulline analysis. Blood cultures were drawn daily from day+4 up until day+12, which was halted upon occurrence of fever. Outside this period, conforming to standard of care, blood cultures were drawn twice weekly and in occurrence of fever. Conforming standard of care, surveillance cultures of mucosal barriers were obtained twice weekly.

Plasma was longitudinally collected from participants throughout the study period for the evaluation of cytokines using the Meso Scale Discovery Customised U-Plex 9-analyte panel following manufacturers guidelines (IL-1/, IL-1RA, CXCL1, TNF, IL-10, IL-17, IL-6, GM-CSF). 16S sequencing was performed by Novogene (as per preclinical analysis methodology).

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Supporting the gastrointestinal microenvironment during high-dose chemotherapy and stem cell transplantation by inhibiting IL-1 signaling with...