Stem Cell Clinic

Improving blood stem cell transplantation outcomes by treating donors – Fred Hutch News Service

Are you a good bone marrow donor and if not, can you become one? There are 55,000-60,000 blood stem cell transplantations also known as bone marrow transplants performed across the globe each year. A serious complication known as graft-versus-host disease (GVHD) is diagnosed for over half of these patients and occurs due to donor cells attacking healthy cells in the recipient. GVHD can be present in an acute or chronic form. While donor cells in GVHD are in attack mode, there may be ways to re-program them to be better resident cells in their new host. This idea comes from a body of literature that suggests statins, a common class of cholesterol-lowering drugs, can alter immune function. To evaluate this, a handful of studies have looked at either long-term or short-term statin treatment of donors and found differing results, but even so some findings from retrospective studies indicated that treatment of donors reduced the incidence of GVHD when recipients were also taking specific types of immunosuppressive drugs. Continuing investigation of this topic, Dr. Marco Mielcarek, a Professor in the Clinical Research Division at Fred Hutchinson Cancer Center and his team performed two prospective studies. Like the previous study on long-term statin treatment, they observed a reduction in GVHD incidence for cases in which donors received long-term statin treatment and recipients were taking the specific immunosuppressant cyclosporine (CSP), but not for those recipients who did not take CSP. These studies were published recently in Transplantation Cellular Therapy.

To prevent incidence and severity of GVHD, and thereby make allogeneic transplantation safer, transplant recipients typically receive prophylaxis consisting of several immunosuppressive medications, commented Dr. Mielcarek. Most of the time, these medications have to be taken for months (sometimes years). These drugs that suppress the immune system also make the person more susceptible to infection and other toxicities. Dr. Mielcarek continued, Therefore, using a medication that could be given to allogeneic stem cell donors for a limited time before they donate stem cell products for transplantation would be an innovative way of preventing GVHD without causing the toxicity of immunosuppressive drugs given to recipients. Pre-clinical studies support the use of statin treatment of donors to alter T cell function and reduce inflammatory effects, both of which would be beneficial to reducing the probability of developing GVHD in the recipient. Two large retrospective studies from the Mielcarek group suggested that donor statin use reduced the risk of severe acute GVHD in patients who were also taking CSP, added Dr. Mielcarek. Since these studies were performed as retrospective analyses, the researchers set out to perform prospective studies to investigate the outcome of short- or long-term statin treatment of donors on the occurrence of GVHD in two recipient groups, those taking CSP and those that were not.

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Improving blood stem cell transplantation outcomes by treating donors - Fred Hutch News Service

The salvage role of allogeneic hematopoietic stem-cell … – Nature.com

Baseline characteristics

A total of 52 adult patients with R/R DLBCL were identified and enrolled. The median age at diagnosis was 45years (range, 1763), with marginal male predominance (n=30, 57.7%). 36 patients (69.2%) were identified as having an advanced-stage disease (Ann Arbor stage IIIIV), whereas 15 (28.8%) suffered from B symptoms. Thirteen patients (25.0%) had BM involvement of DLBCL at the time of diagnosis, and 8 of 13 (61.5%) had complex karyotypes. All enrolled patients were classified as low (n=15, 28.8%), low-intermediate (n=13, 25.0%), high-intermediate (n=14, 26.9%), and high (n=10, 19.2%) risks based on international prognostic index (IPI) risk classification. Four patients had a double-hit mutation (7.7%), and according to Hans criteria, 32 and 13 patients were categorized as ABC type (61.5%) and GCB type (25.0%), respectively. The baseline characteristics at the time of diagnosis are summarized in Table 1.

Notably, most enrolled patients had previously undergone intensive treatments, and the median number of chemotherapy lines before allo-HSCT was 4 (range, 26). Sixteen patients (30.8%) had previously undergone auto-HSCT, and the median time from diagnosis and auto-HSCT to allo-HSCT was 27.1months (range, 6.2117.7months) and 18.5months (range, 6.544.8months), respectively. The disease status at the time of transplantation was CR (n=14, 26.9%), PR (n=16, 30.8%), and active disease (n=22, 42.3%). Donor types included matched sibling (n=18, 34.6%), haploidentical (n=18, 34.6%), matched unrelated (n=11, 21.2%), and unrelated donors with one allele mismatch (n=5, 9.6%). The conditioning regimen comprised MAC (n=2, 3.9%) and RIC (n=50, 96.1%). Half of the enrolled patients were ABO-type matched (n=26, 50.0%), 27 (51.9%) were in donor-to-recipient sex mismatch, and 44 (84.6%) were both donor and recipient cytomegalovirus (CMV) IgG seropositive. Table 2 presents the demographic information of the patients who underwent allo-HSCT.

Over a median follow-up period of 38.3months (range, 1.9112.0), the estimated 5-year OS and EFS were 38.4% (95% CI, 24.751.8) and 30.6% (95% CI, 18.843.3), respectively. The estimated 5-year CIR, NRM, and GRFS were 36.7% (95% CI, 23.649.8), 32.7% (95% CI, 20.345.6), and 15.1% (95% CI, 6.926.2), respectively. Figure1 shows the 1-year (100days outcomes in CIR and NRM) and 5-year survival outcomes. Compared to the active-disease group, the remission-achieved group showed a significantly superior rate of CR in the first 3months after allo-HSCT (76.7% vs. 36.4%, p=0.003) and at the last follow-up (50.0% vs. 13.6%, p=0.006) (Fig.2). Moreover, except for NRM (26.7% vs. 40.9%, p=0.217), the clinical outcomes of OS (54.1% vs. 15.6%, p=0.001), EFS (46.4% vs. 9.1%, p<0.001), and GRFS (22.9% vs. 4.6%, p=0.002) were significantly superior in the remission-achieved group with lower CIR (26.9% vs. 50.0%, p=0.047). In detail (Fig.3), among patients in the remission-achieved group before allo-HSCT (n=30), 23 achieved CR, one achieved PR, four experienced disease relapse after allo-HSCT and died due to disease progression, and three died after engraftment (two from bacterial septic shock and one from veno-occlusive disease [VOD]) without relapse. In contrast, among patients in the active-disease group before allo-HSCT (n=22), eight achieved CR. However, only two remained in CR, four experienced disease relapse, and two died due to septic shock during disease remission. All eight of the remaining patients who achieved PR eventually relapsed, and six died after engraftment either due to allo-HSCT-related complications (one with grade IV hemorrhagic cystitis combined with renal failure, one with VOD, and two with grade IV acute hepatic GVHD complicated with liver failure) or infection (two with CMV pneumonia).

Survival outcomes of patients with relapsed/refractory diffuse large B-cell lymphoma after undergoing allogeneic hematopoietic stem-cell transplantation. The estimated 1- and 5-year (A) OS is 45.0% (95% CI, 30.758.3) and 38.4% (95% CI, 24.751.8). The estimated 1- and 5-year (B) EFS is 32.7% (95% CI, 20.545.4%) and 30.6% (95% CI, 18.843.3). The CIR and NRM at day 100 after allo-HSCT is (C) 15.4% (95% CI, 7.126.5) and (D) 17.3% (95% CI, 8.528.8). Furthermore, the estimated 5-year CIR and NRM are 36.7% (95% CI, 23.649.8) and 32.7% (95% CI, 20.345.6), respectively. The estimated 1- and 5-year (E) GRFS is 17.3% (95% CI, 8.528.6) and 15.1% (95% CI, 7.026.2). CI, confidence interval; CIR, cumulative incidence of relapse; EFS, event-free survival; GRFS, graft-versus-host disease-free, relapse-free survival; HSCT, hematopoietic stem-cell transplantation; NRM, non-relapsed mortality; OS, overall survival; R/R DLBCL, relapsed/refractory diffuse large B-cell lymphoma.

Response rate and clinical course of patients with diffuse relapsed/refractory large B-cell lymphoma after undergoing allogenic hematopoietic stem-cell transplantation. (A) Remission-achieved group: Among 30 patients in the remission-achieved group, the overall response rate (23 CR and 1 PR) was 80.0% (n=24) at 3months after allo-HSCT. At the last follow-up, 15 patients remained CR (including 1 PR patient who achieved CR after donor leukocyte infusion), but three died after engraftment without relapse, and six experienced DLBCL relapse. (B) Active-disease group: Among 22 active-disease group patients, the overall response rate (8 CR and 8 PR) was 72.7% (n=16) at 3months after allo-HSCT. However, at the last follow-up, only two patients remained CR, two died after engraftment without relapse, and 12 (4 CR and 6 PR) experienced DLBCL relapse. CMV, cytomegalovirus; CR, complete remission; GVHD, graft-versus-host disease; HSCT, hematopoietic stem-cell transplantation; NRM, non-relapsed mortality; PD, progression of disease; PR, partial remission.

Comparison of survival outcomes between the remission-achieved and active-disease groups in patients with diffuse large B-cell lymphoma who underwent allogeneic hematopoietic stem-cell transplantation. The clinical outcomes of (A) OS (54.1% vs. 15.6%, p=0.001), (B) EFS (46.4% vs. 9.1%, p<0.001), and (E) GRFS (22.9% vs. 4.6%, p=0.002) were significantly superior in the remission-achieved group with (C) lower CIR (26.9% vs. 50.0%, p=0.047), except for (D) NRM (26.7% vs. 40.9%, p=0.217). CI, confidence interval; CIR, cumulative incidence of relapse; EFS, event-free survival; GRFS, graft-versus-host disease-free, relapse-free survival; HSCT, hematopoietic stem-cell transplantation; NRM, non-relapsed mortality; OS, overall survival; R/R DLBCL, relapsed/refractory diffuse large B-cell lymphoma.

The overall cumulative incidence of grade 3 to 4 acute GVHD and moderate-to-severe chronic GVHD that required steroid pulse therapy was 17.3% (95% CI, 8.528.8%) and 29.1% (95% CI, 17.242.0%), respectively. The active-disease group had a significantly higher incidence of grade 34 acute GVHD than the remission-achieved group before allo-HSCT (6.7% vs. 31.8%, p=0.023). However, no significant differences in moderate-to-severe chronic GVHD incidence (37.1% vs. 18.2%, p=0.172) were observed between the two groups. The allo-HSCT-related complication incidence, response rate, and survival outcomes in the remission-achieved and active-disease groups before allo-HSCT are presented in Table 3.

The results of the univariate analysis for OS, EFS, CIR, NRM, and GFRS are presented in Supplementary Tables 1 and 2. In the multivariate analysis, a shorter interval from diagnosis to allo-HSCT (median of<27.1months), which reflects relatively rapid disease progression, showed significantly poor OS (hazard ratio [HR], 3.92; 95% CI, 1.838.43; p<0.001) and EFS (HR, 2.65; 95% CI, 1.285.46; p=0.008). Complex karyotypes in BM involving DLBCL were also associated with poor OS (HR, 1.42; 95% CI, 1.061.90; p=0.018) and NRM (HR, 1.41; 95% CI, 1.021.94; p=0.040). Active disease before allo-HSCT was associated with significantly lower EFS (HR. 2.50; 95% CI, 1.215.17; p=0.014), GFRS (HR, 2.54; 95% CI, 1.374.72; p=0.003), and higher CIR (HR, 3.03; 95% CI, 1.148.02; p=0.026). The MAC regimen for allo-HSCT was associated with significantly higher CIR (HR, 11.3; 95% CI, 3.3338.1; p<0.001), and patients with previous autologous stem-cell transplantation (ASCT) had significantly better GRFS (HR, 0.50; 95% CI, 0.260.98; p=0.043). The results of the multivariate analysis are presented in Fig.4.

Multivariable analysis of survival outcomes related to allogeneic hematopoietic stem-cell transplantation in patients with relapsed/refractory diffuse large B-cell lymphoma. (A) The multivariable analysis for each survival outcome shows that a shorter interval of the median of<27.1months from diagnosis to allo-HSCT (HR, 3.92; 95% CI, 1.838.43; p<0.001) and complex karyotype presenting bone marrow (HR, 1.42; 95% CI, 1.061.90; p=0.018) are significantly related to poor OS. In the case of EFS, a shorter interval compared to the median of<27.1months from diagnosis to allo-HSCT (HR, 2.65; 95% CI, 1.285.46; p=0.008) and active disease before allo-HSCT (HR, 2.50; 95% CI, 1.215.17; p=0.014) are significantly related to poor EFS. Previous ASCT are significantly related to better GRFS (HR, 0.50; 95% CI, 0.260.98; p=0.043), but active disease before allo-HSCT are significantly related to poor GRFS (HR, 2.54; 95% CI, 1.374.72; p=0.003). (B) Active disease before allo-HSCT (HR, 3.03; 95% CI, 1.148.02; p=0.026) is also significantly related to higher CIR with MAC conditioning (HR, 11.3; 95% CI, 3.3338.1; p<0.01). Complex karyotype presenting bone marrow is also related to higher NRM (HR, 1.41; 95% CI, 1.021.94; p=0.040). CI, confidence interval; ASCT, autologous stem-cell transplantation; CIR, cumulative incidence of relapse; EFS, event-free survival; GRFS, graft-versus-host disease free, relapse-free survival; HR, hazard ratio; HSCT, hematopoietic stem-cell transplantation; MAC, myeloablative conditioning; NRM, non-relapsed mortality; OS, overall survival; R/R DLBCL, relapsed/refractory diffuse large B-cell lymphoma.

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The salvage role of allogeneic hematopoietic stem-cell ... - Nature.com

Patients could have faster access to ground-breaking stem cell … – GOV.UK

The safe manufacture of potentially life-saving stem cells through innovative automation and machine learning, could give patients faster access to stem cell treatments in the future.

Today, experts and UKSCB alumni are meeting for a special event at the Medicines and Healthcare products Regulatory Agencys South Mimms Laboratories to celebrate two decades of supporting innovation in research and in the clinic, and to look to the future of advanced therapeutics.

Human embryonic stem cells have the potential to help parts of the human body repair and regenerate following illness and disease. They could have applications in a vast range of diseases such as blindness, blood cancer and heart disease.

With support from national partners at the Medical Research Council (MRC), Biotechnology and Biological Sciences Research Council (BBSRC) and National Institute for Health Research (NIHR), the UKSCB provides high quality stem cells for world-leading research, with 30 stem cell lines available for clinical application. This makes the UKSCB the largest source of clinical grade human embryonic stem cells in the world.

Globally, the UKSCB has supplied stem cells to 25 different countries for research and clinical applications, with 54% of the stem cell lines requested in 2022 being of clinical grade, which has risen year on year.

Dr Lee Carpenter, Head of the UK Stem Cell Bank, said:

Stem cell treatments are difficult to manufacture because its labour intensive and expensive, making their availability to help patients limited.

As we celebrate 20 years of the UK Stem Cell Bank, we look to automation to alleviate the manual aspects of laboratory working with stem cells and to scale up manufacturing, without compromising on our safety and quality standards.

This ultimately means patients could get faster access to more cost-effective, safer stem cell therapies to treat or prevent their condition or disease.

Dr Marc Bailey, MHRA Chief Science and Innovation Officer, said:

This isnt the stuff of science fiction. Our unique asset at the MHRA, the UKSCB, means we will continue to be at the forefront of the latest scientific developments so that we can help bring safe and effective treatments to the people who need them most.

At a time where medicines to slow or stop degenerative diseases, such as Parkinsons disease, are becoming a reality, our work is helping research go even further, curating and supplying the foundation of cell-based therapeutics, which have the potential to treat, and one day, even cure these diseases.

The UKSCBs future is diverse and exciting and, much like the cells we curate, there are endless possibilities for us to support research and clinical advances in the UK and around the world.

Twenty years ago, the MHRAs UKSCB was established to curate and distribute all human embryonic stem cells created in the UK.

Over the past two decades, the UKSCB has become renowned for being at the centre of advanced therapeutics - medicines for human use based on genes, tissues, or cells - in the UK, as well as globally.

It is recognised around the world as a leading repository, with over 180 different human embryonic stem cell lines used for research and development, with many of these that could be used for treating patients.

The UKSCB has recently completed a trial using a robot that grows stem cells to see whether they meet the standards needed for use in the manufacture of potentially life-saving treatments compared with our highly skilled experts.

The CellQualiaIntelligent Cell Processing System at the MHRA South Mimms Laboratories was, at the time, the only one in the world outside of Japan, where it was developed. This was a successful trial that demonstrated automation of stem cell production is possible, and now other automation systems are being considered in future studies comparing automation and manual production.

The UKSCB is the UKs repository for the storage and regulation of stem cells. Further information about the UKSCB can be found here.

A stem cell line is a population of cells that all descend from a single donor and are grown in a lab. Under appropriate conditions, cells in a stem cell line keep growing but dont differentiate into specialised cells. Ideally, they remain free of genetic defects and continue to expand, which can be frozen for storage or shared with other researchers.

Stem cell derived therapies, also known as regenerative medicine, promotes the repair of diseased, dysfunctional or injured tissue by providing specialised cells that can be derived from stem cells i.e. neurons, cardiac and immune cells.

The Medicines and Healthcare products Regulatory Agency (MHRA) is responsible for regulating all medicines and medical devices in the UK by ensuring they work and are acceptably safe. All our work is underpinned by robust and fact-based judgements to ensure that the benefits justify any risks.

The MHRA is an executive agency of the Department of Health and Social Care.

For media enquiries, please contact the newscentre@mhra.gov.uk or call 020 3080 7651.

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Patients could have faster access to ground-breaking stem cell ... - GOV.UK

NIH researchers work to preserve fertility for people undergoing … – National Institutes of Health (.gov)

Media Advisory

Thursday, October 12, 2023

Novel conditioning agent shows promise in animal models of sickle cell disease.

Researchers at the National Institutes of Health have created a novel gene therapy procedure that could preserve fertility in people with sickle cell disease and other genetic blood conditions. Infertility is a high-risk and long-term side effect associated with current bone marrow transplantation and gene therapy approaches to treat sickle cell disease. It is a common reason people of reproductive age give for not pursuing these therapies.

The study, which appears in Nature Communications, describes the successful testing in animals of an antibody-drug conjugate, or conditioning agent, that exclusively targets blood-forming stem cells in the bone marrow. Conditioning agents are used in gene therapy to remove diseased stem cells and allow healthy stem cells to form. This new agent, called CD117-ADC, does not appear to damage other organs during the conditioning process. It is less toxic than the conventional agent now used for gene therapy in humans, called busulfan, which may cause ovarian failure in women and may stop sperm production in men, resulting in infertility.

Researchers found that CD117-ADC allowed robust engraftment of gene-modified cells to increase fetal hemoglobin, a type of oxygen-carrying blood protein present at birth. When used in adults with sickle cell disease, fetal hemoglobin can reduce complications associated with the disease, and reactivating and increasing its production is a promising goal for gene therapy. Unlike busulfan, the new conditioning agent also was shown to preserve fertility in females and males.

The paper, Fertility-preserving myeloablative conditioning using single dose CD117 antibody-drug conjugate in a rhesus gene therapy model, published Oct. 12 in the Nature Communications.

John F. Tisdale, M.D., chief of the Cellular and Molecular Therapeutics Branch of the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, and Naoya Uchida, M.D., Ph.D., a staff scientist in the branch, are available to discuss this study.

To request an interview with Drs. Tisdale and Uchida, please email nhlbi_news@nhlbi.nih.gov

About the National Heart, Lung, and Blood Institute (NHLBI): NHLBI is the global leader in conducting and supporting research in heart, lung, and blood diseases and sleep disorders that advances scientific knowledge, improves public health, and saves lives. For more information, visit http://www.nhlbi.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

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NIH researchers work to preserve fertility for people undergoing ... - National Institutes of Health (.gov)

Cellstory Liquid Microneedling Treatment Review – Coveteur

For many of us, the thought of needles jabbing into our bodylet alone our facecan make even the bravest of us wince from the mere thought, making many viable aesthetic treatments out of the question. This is not unusualneedle phobia or trypanophobia, if you want to get fancy, is super prevalent, affecting up to 30% of adults. While I dont have a debilitating fear of needles, I love stumbling upon treatments that all of us, if not most, can experience without having, you know, a panic attack. Case in point: liquid microneedling. Dont let the name fool youthere are zero needles involved, but it offers similar benefits that one sees from needle-based treatments.

I happened upon Cellstory during my beauty travels, and I was fascinated by this non-invasive treatment (with little to no downtime) that boasts similar results to a non-ablative laser treatment. Cellstory, the professional treatment in question from Beyond Miracles, is patented with microspears containing 50,000 microneedles derived from freshwater-grown sponges that are applied to the skin (by a professional) through an 8-step facial treatment. ...[S]tep 5 contains the patented Microspear technology, which can be described as liquid microneedles. With the application of medium pressure, the Microspear[s] are delivered into the lower epidermis of the skin, creating tiny microchannels, which allows for better ingredient penetration, explains Dr. Dendy Engelman, MD, FACMA, FAAD, a board-certified cosmetic dermatologist and Mohs surgeon at Shafer Clinic in New York City. In other words, these microspears are small enough to penetrate the skin and work their magic.

Cellstory eliminates the pain, bleeding, swelling and irritation often associated with microneedling. Cellstory helps minimize the appearance of fine lines and wrinkles (specifically around the mouth, eyes, and forehead), acne, pigmentation, and uneven texture. It gives an overall healthy, supple, [and] bouncy glow, adds Dr. Engelman.

I was excited for the opportunity to try Cellstory, especially after waiting some time to schedule it, as I had to make sure that it did not interfere with any treatments or injectables I had previously scheduled. You should avoid Botox and fillers for 14 days before the treatment, and avoid lasers, chemical peels, microneedling and mesotherapy for seven days before, says Dr. Engelman. When the time came, I visited esthetician and founder Taylor Worden at her eponymous skincare oasiswhich I can confirm isin SoHo, New York City, for my Cellstory treatment.

Like any relaxing facial treatment I have gone for, I slipped into something a little more comfortable, wrapped my hair into a top bun, and laid on the esthetician bed. The start of the 8-step treatment was extremely relaxing. First, she applied an amino acid-infused cleanser; second, she swiped a cotton round drenched with a mixture of ginkgo biloba and niacinamide across my face; third, Worden applied an Awake Essense with a brush and let sit on my face for a few minutes; and fourth, she applied an activator ampoule packed with stem cell extract and three growth factors with a brush to my face.

Before I describe step five, the bread and butter of the whole treatment, I want to stress how relaxed and unready I was for what was to come. Worden applied the actual liquid microneedle creampacked with those 50,000 microscopic microneedles (or microspears), yellow calming complex, and growth factors topically through a syringe. She placed small dot-like shapes all over my face.

During step five of the treatment.

My skin immediately following the last step of the treatment.

Then, I vaguely remember her asking me if I was ready. Quickly and in precise circular motions, she massaged it into my skin, and it felt like she was shaving my skin down using sandpaper. The microspears are meant to have a prickly, tingly, and warming effect, but my skin screamed. This continued for several minutes until the cream was completely absorbed into my skin. Though I was very uncomfortable, I knew the cream was working its magic.

The following morning, when I finally touched my face to wash it, I felt the liquid microneedles. It was a sensation I had never experienced before. It almost felt like little pieces of glass lodged into my skin. While this sounds dramatic, its the best way I can describe it; however, it was not painful -just weird. This sensation lasted three days and decreased in intensity with each passing day.

You're advised to cleanse your face lightly after the treatment or until the sensation disappears completely. Following the treatment, for 72 hours, you should avoid retinol, exfoliants (physical or chemical), face oils or oil-based products, heavy sweating (i.e., saunas, heavy exercise), and sun exposure. Additionally, for one week after the treatment, you should avoid chemical peels or lasers, says Dr. Engelman.

My face immediately following the treatment.

My skin the morning after the treatment.

Cellstory is not a one-and-done treatment. We recommend that you initially have four treatments, one week apart," says Dr. Engleman. "After that, we suggest one time per month for maintenance. However, you can see results after just one treatment." There are also two at-home versions of Cellstory, each packed with 10,000 microneedles, compared to the 50,000 in the professional version. The at-home is a great alternative if you dont have access to a provider or want to maintain your treatment results from home.

Id be lying to you if I said I didnt look like a tomato after the treatment. I became the living, breathing version of #tomatogirlsummer. Despite that, my skin looked, in the best way I can describe it, WOW. It was the cleanest and smoothest it has ever looked after a treatment. It was something beyond a miracle (Im sorry - I couldnt resist the pun). In the hours following the treatment, the redness faded. The next morning, my skin looked healthy, glowy, and there wasn't a pore in sight. I was stunned by how a facial gave me better resultsalmost immediatelythan any laser treatment I had ever had.

In the days following the treatment, my skin looked plump and hydrated. Though my skin looked like the perfect canvas for makeup, I opted to go sans cosmetics and take full advantage of my perfect-looking skin.

If youre pregnant or breastfeeding or have any open wounds on your face, you should avoid the treatment. The only skin type that should completely avoid Cellstory altogether, says Dr. Engelman, is someone with severe melasma.

Just an FYI, in case you have a nut allergy: There is a small percentage of macadamia seed oil in step five. The allergy risk is very low, but we recommend spot testing if you have a severe nut allergy, says Dr. Engelman.

Depending on who you see and where you are, the cost of Cellstory can range from $350 to $500. (You can find a full list of providers, here.)

I cannot recommend this treatment enough. It is safe for almost everyone, and the results speak for themselves. Having gone through numerous sessions of both microneedling and radio frequency microneedling, and experiencing post-treatment swelling, redness, and blood, there is absolutely no downside to this treatment. And a reminderzero needles. Just some manageable discomfort. Lets just say Im ready to book my next appointment now.

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Cellstory Liquid Microneedling Treatment Review - Coveteur

Selecting and Sequencing Ruxolitinib, Other Treatments in Chronic … – Cancer Network

Nelson J. Chao, MD, MBA, and his colleagues discussed the use of ruxolitinib as treatment for patients with graft-vs-host disease.

At an Around the Practice program hosted by CancerNetwork,a panel of experts discussed symptom assessment and the selection of treatment options in patients with chronic graft-vs-host disease (GVHD). They reviewed these topics in the context of a clinical scenario involving a patient with acute GVHD. The panel was led by Nelson J. Chao, MD, MBA, a cellular therapy specialist and stem cell transplant specialist at the Duke Adult Blood and Marrow Transplant Clinic in Durham, North Carolina.

The panelists included Hana Safah, MD, a professor of clinical medicine in the Section of Hematology and Stem Cell Transplantation Program and the Leukemia and Lymphoma Programs at Tulane University School of Medicine in New Orleans, Louisiana; Erin Kopp, NP, the directorof advanced practice and a nurse practitioner at City of Hope Comprehensive Cancer Center in Duarte, California; and Catherine J. Lee, MD, MS, an associate professor in the Clinical Research Division at the Fred Hutchinson Cancer Center in Seattle, Washington.

Chao: Ruxolitinib [Jakafi] is approved as a second-line treatment for GVHD based on the phase 3 REACH3 study [NCT03112603].1,2 If treatment with ruxolitinib fails, what would you do?

Safah: There are options that may also help patients if ruxolitinib fails. Some of my colleagues use ibrutinib [Imbruvica]. Im not as much of a fan of ibrutinib, though it is an option. It has been studied in patients, and it did show benefits, especially if a patient has only skin GVHD. ROCK2 inhibitors are a good third-line option in patients with disease progression following JAK inhibitors. I also continue extracorporeal photopheresis [ECP] in these patients, especially those with skin GVHD.

Kopp: If a patient is starting to show that they may become steroid refractory or dependent, we work them up for clinical trials before we get [to the treatment phase], because clinical trials are an important option to observe. For centers outside of that space, the referral process should start early because clinical trials require screening, slots, and time. We start that concurrently. If we are in a situation where ruxolitinib or any other second-line options are not panning out, we already have the clinical trial potentially available.

Chao: Does anybody have a favorite treatment option?

Lee: Ill still use rituximab [Rituxan] or low-dose weekly methotrexate to see [whether] it helps. Ive seen rituximab work in the very refractory setting, particularly for oral chronic GVHD. I have not had much luck with very advanced ocular or sclerotic chronic GVHD, although there are reports of rituximab having activity in the setting.

Safah: Rituximab can be helpful. I sometimes add rituximab early in patients with severe skin GVHD. Thats one option. Targeting the plasma cells in patients with progression is another. Ive used proteasome inhibitors with minor success. They do not work by themselves, but they can add to the treatments available, whether its rituximab, [ECP], or antithymocyte globulin. However, there is nothing that will always work. Clinical trials are always important to have. [However], when they fail, it becomes a question of: What is available for us, and what can the patient receive? [At this point], it depends on the clinical status, the comorbidities, and the toxicities from the options available.

Chao: Theres the phase 2 AGAVE-201 trial [NCT04710576] with axatilimab that is targeting the monocytes, which is potentially another mechanism.3

Chao: What do you think about this situation?

Lee: I feel horrible for the patient. This is an unfortunate situation, and it is an example of when patients are released back to their homes, they may not be under close supervision before returning with these severe symptoms. The case study brings up a couple questions. When the patient developed acute GVHD, it was treated successfully with corticosteroids. The first questions that come up in my mind are: What was going on with the tacrolimus and sirolimus [Rapamune] at this time? Did the patient just stop taking her medications, or had she been weaned off? Regardless, she does present around month 6 with these GI symptoms, elevated liver function tests, and signs of chronic GVHD as shes reporting tightness around the mouth. This needs to be treated urgently.

At this point, I would have admitted the patient into the hospital and started high-dose steroids, as what was done here. I would have started at 1 mg/kg per day, thinking that this might be acute or chronic GVHD and knowing that some other treatment options take a little longer to take effect. I would have started corticosteroid equivalent at 2 mg/kg per day and watched her carefully. If she had not responded by day 5, I would have added a second-line agent and started tapering off the corticosteroids. I dont find a reason here to increase the steroids to 2 mg/kg after someone doesnt respond to 1.5 mg/kg. The patient was left too long on this 1.5-mg/kg per day dose.

Safah: I agree. I would have been giving the higher dose earlier compared with what was done here. I evaluate these patients very early on. If there is no evidence of response by day 5, or if theyre progressing by day 5 and there is no evidence of response by day 7, I elect to go to a second-line treatment rather than increasing the dose of steroids as such.

Kopp: This is an excellent representation of the type of patients we receive and the questions that often come with them. If theyre not continuing to receive care in the institution in which they underwent a transplant and there are changes to their immunosuppressive regimens, steroids, or presentation of symptoms, we dont always get the full report of what happened. So, patients do show up on my doorstep presenting like this. One thing we need to focus on is how often were monitoring our patients at critical milestones. When you initiate steroids, the concept is that the patient needs to be closely followed for 3,5, or 7 days because we can identifysometimes as early as 3 dayswhether a patient is responding to the corticosteroid dose.

Im hoping this illustrates the challenges that many physicians and other health care professionals have when working with a patient like this. The onus is on everyone who interacts with the patients to say when theres a new symptom and where theres a change in something that we do. Additionally, the patient sometimes must advocate for themselves and say, How can I see you in another week? Or call their transplant physician or the long-term care clinic so were aware of it sooner rather than later.

Organ Involvement With Ruxolitinib and Using Steroids

Chao: Given our earlier discussion, this patients condition is not getting better, and ruxolitinib is the drug we would probably all pick to treat her.

Safah: I agree with you. Ruxolitinib is approved as a second-line therapy in patients who are refractory to steroids. This patient would be a very appropriate candidate for such a treatment.

Chao: Does it matter which organ is involved in terms of outcomes?

Safah: When you look at ruxolitinib in the REACH3 trial, the benefit was seen across all organs. We might combine it with other drugs. We can add rituximab, but we need to be careful [because] it may cause immunosuppression. We need to be careful of the risk of infection, especially when were adding JAK inhibitors. The risk of whether there may be viral reactivation or other infections should be considered when combining ruxolitinib with other immunosuppressants. I prefer to take it slowly. Again, I know benefits have been seen across all organs on the trial.

Lee: We know that in the REACH3 trial for acute GVHD, the responses and the duration of response [DOR] were not so great among those who had severe gastrointestinal involvement. This leads to the unmet need that we are still facing, which is understanding what therapy may fit best for a particular organ. This is an area of research that will help guide treatment for different manifestations of GVHD if we can identify and develop biomarkers.

Chao: Do you taper patients off steroids if you have ruxolitinib as an option? What would you do if someone is refractory?

Lee: We would taper off the steroids in someone who is refractory. This is also very dependent on the institution. Fred [Hutchinson Cancer Center] has a long history of using steroids and being a little slower on the taper, but other institutions may feel comfortable in terms of rapidly tapering off the steroids.

Kopp: My experience is that we are less excited about tapering the steroids even when it seems that patients are refractory. Theres the fear that if you see some effect and then take the steroids away, the disease will flare even more. Theres a reliance on keeping those steroids as you add ruxolitinib or any other agent on top of them. With any oral agent like ruxolitinib, there has been hesitancy to use it with patients who have GI presentations. With the REACH studies, there doesnt seem to be an issue with absorption and utilization unless we know theres a significant issue with a patients absorption. However, there is efficacy to a certain level. Thats where I think we start combining steroids with ruxolitinib, which may give the effect but not the DOR. We may then add another agent if were talking about different organs.

What I have noticed in the [past] 5 years is that the addition of agents has become more intentional. People are looking at the etiology, the drugs mechanism of action, the affected organs, and the research involved. Its a complex process. Before, I would describe practice as a dartboard where you just throw everything at it and see what sticks. Now, there are a lot of ingredients, and were all more experienced with how it will affect the overall outcome.

Chao: Are there any drugs coming down the pipeline that youre excited about?

Lee: The field is exciting to look forward to when it comes to more combinational therapies, as we are seeing that combinations of drugs with different mechanisms of action may help control GVHD and perhaps improve it by targeting different biological pathways. I have used a combination of ruxolitinib and belumosudil [Rezurock], and I know some centers have initiated clinical trials of using these 2 drugs in refractory chronic GVHD.

Safah: In practice, many of us have used ruxolitinib and [belumosudil] together. Some of us have used it in patients who are refractory to one or the other. Ive also used them in patients who have severe chronic GVHD and were not going to be maintained on only 1 drug. Im asking my colleagues now, and Ive requested that we start publishing the data on patients who have received the combination and have done well so that our other colleagues can do the same. Belumosudils safety profile is not bad. On the other hand, the JAK inhibitors do very well, and they have a nice mechanism for controlling inflammation and potentially fibrosis. Adding them together can benefit patients. We can do it in the refractory setting. Maybe we should start looking at earlier lines, and maybe we can skip steroids. Other than that, I think clinical trials will be best, but we dont have many other options at this point.

Kopp: For GVHD, the seeds are planted for early settings in transplant. For posttransplant regimens that include cyclophosphamide, there is a lot of focus on identifying [whether] a patient has acute GVHD or multiple risk factors. Theres been a foundation set with biomarkers. What we do with them next may involve the concept of precision medicine in acute and chronic GVHD to meet the needs of the patient systemically.

Ive also seen a growth in supportive therapy. For the patient, the fact that we can manage these symptoms while were treating the underlying process is probably the biggest development that patients are excited about. If patients have skin that feels like its peeling off and you have 5 more agents now that may treat them topically, thats a huge win as a patient. The same thing applies to oral sloughing. The inability to brush your teeth with toothpaste is something that patients bring to us, as well as needing to wear sunglasses outside at night because their eyes are so dry. The growth in supportive therapy regimens is also something that needs more research because its important to the patients alongside treating the underlying cause.

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Selecting and Sequencing Ruxolitinib, Other Treatments in Chronic ... - Cancer Network

Molecule discovered that grows bigger and stronger muscles – Earth.com

Over the years, scientists have embarked on anti-aging research to provide drugs and treatments that can slow or reverse aging and treat age-related diseases.Now, scientists at Stanford University have discovered an aging-related protein that can stimulate growth of stronger and larger muscles.

The 15-PGDH protein is the latest discovery by the Stanford scientists, who are working on possible treatments for diminished strength and paralysis due to trauma, heritable neuromuscular diseases, or aging.

Using a mouse model, the researchers injected a 15-PGDH-blocking molecule in older mice. They followed the simulated injuries to the sciatic nerves of the injected mice with treatments.

This led to more prostaglandin E2 (PGE2) production, followed by the growth of stronger and larger muscle fibers in the mice.

By inhibiting the 15-PGDH, also known as gerozyme, the researchers significantly improved the endurance and strength of the muscles grown in the lab.

The researchers found that 15-prostaglandin dehydrogenase (15-PGDH), which accumulates with age and promotes muscle atrophy, markedly increased in denervated mouse myofibers and aggregated in target fibers, hallmarks of chronic nerve damage in human myogenic neuropathies, noted Melissa L. Norton, the editor of the published study.

Treating older mice with chronic muscle denervation with the 15-PGDH inhibitor enhanced the motor neurons and rejuvenated the neuromuscular junctions and function.

This could potentially help older adults who experience increasingly weaker muscles with age and people dealing with muscle-wasting diseases like amyotrophic lateral sclerosis (ALS).

Our data suggests that inhibition of 15-PGDH may constitute a therapeutic strategy to physiologically boost prostaglandin E2, restore neuromuscular connectivity, and promote recovery of strength after acute or chronic denervation due to injury, disease or aging, the researchers noted in their report.

Although this latest study expands on existing evidence of protein regulating muscle function during aging in mice, the researchers have described it as unique.

Study co-author Dr. Helen Blau is the director of the Baxter Laboratory for Stem Cell Biology at Stanford.

This is the first time a drug treatment has been shown to affect both muscle fibers and the motor neurons that stimulate them to contract, speeding up healing and restoring strength and muscle mass, said Dr. Blau.

The Stanford scientists want to build on their findings to see if this mechanism can be transitioned into real-life treatments and therapy.

Our next steps will be to examine whether blocking 15-PGDH function in people with conditions like spinal muscular atrophy, in combination with gene therapy or other treatments, can increase lost muscle strength, said Dr. Blau.

We are also looking at ALS to see if something like this might help these patients. Its really exciting that we are able to affect both muscle function and motor neuron growth.

Weak muscle strength is a huge problem among elders. According to a study by the Centers for Disease Control and Prevention (CDC), five percent of adults aged 60 and over have weak muscle strength, while 13 percent have intermediate muscle strength.

But muscle weakness isnt just a concern for older people. It starts creeping in as early as your 50s and comes with a great economic cost. Weaker muscles reduce the ability to move around, work, and care for oneself. This condition also increases the risk of injuries.

The good news is that science is making promising strides toward addressing this widespread problem. With continued research and advancement, a lasting solution for muscle weakness may be on the horizon.

The study can be found in the journal Science Translational Medicine.

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Molecule discovered that grows bigger and stronger muscles - Earth.com

Knight Therapeutics Announces CMED Price Approval of Minjuvi … – GlobeNewswire

MONTREAL, Oct. 16, 2023 (GLOBE NEWSWIRE) -- Knight Therapeutics Inc., (TSX: GUD) ("Knight") a pan-American (ex-USA) specialty pharmaceutical company, announced today that its Brazilian affiliate, United Medical Ltd., has received pricing approval for Minjuvi (tafasitamab) from the Drugs Market Regulation Chamber (CMED). As a result, Knight expects to launch Minjuvi in Brazil in the second quarter of 2024.

In July 2023, ANVISA (Agncia Nacional de Vigilncia Sanitria) granted Market Authorization under their rare disease designation according to Resolution RDC 205/2017 for Minjuvi in combination with lenalidomide followed by Minjuvi monotherapy for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplantation (ASCT).

Diffuse large B-cell lymphoma is a type of aggressive non-Hodgkin lymphoma, with suboptimal efficacy results with standard available therapies for patients who have failed to previous treatments and are not candidates for transplant.

Considering the nature of the disease and the current unmet medical need, there is still space to improve the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma in Brazil, said Dr. Danielle Leo, Head of the Hematology Department from Beneficncia Portuguesa Hospital in So Paulo. Minjuvi is an innovative therapy with proven efficacy and safety profile. There is no other effective alternative approved in the country in the second line of treatment for relapsed or refractory DLBCL.

The approval is based on the data from L-MIND, an open label, multicenter, single arm Phase 2 study, that evaluated Minjuvi in combination with lenalidomide for the treatment of adult patients with relapsed or refractory DLBCL. The study primary analysis results showed an objective response rate (ORR, primary endpoint) of 60%, including a complete response rate (CR) of 43% and a disease control rate (DCR) of 75%.

Were excited to continue to advance the approval of Minjuvi in Brazil, a new treatment option for a current unmet need. We look forward to launching Minjuvi in Brazil and obtaining approval in other key markets in Latin America, said Samira Sakhia, Knight Therapeutics President and CEO.

In September 2021, Knight entered into a supply and distribution agreement with Incyte (NASDAQ: INCY), for the exclusive rights to distribute pemigatinib (Pemazyre) as well as tafasitamab (sold as Monjuvi in the United States and Minjuvi in Europe) in Latin America.

With the price approval Minjuvi will be available for commercialization in the Brazilian market. Knights team is working diligently with physicians, key institutions and payors to ensure patients have access to Minjuvi, said Cristiane Coelho, Knight Therapeutics Brazil General Manager.

About Minjuvi (tafasitamab)

Minjuvi (tafasitamab) is a humanized Fc-modified cytolytic CD19 targeting immunotherapy. In 2010, MorphoSys licensed exclusive worldwide rights to develop and commercialize tafasitamab from Xencor, Inc. Tafasitamab incorporates an XmAbengineered Fc domain, which mediates B-cell lysis through apoptosis and immune effector mechanism including Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) and Antibody-Dependent Cellular Phagocytosis (ADCP).

In the United States, Monjuvi(tafasitamab-cxix) is approved by the U.S. Food and Drug Administration in combination with lenalidomide for the treatment of adult patients with relapsed or refractory DLBCL not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplantation (ASCT). This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). Please see the U.S. full Prescribing Information for Monjuvi for important safety information.

In Europe, Minjuvi(tafasitamab) received conditional approval, in combination with lenalidomide, followed by Minjuvi monotherapy, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for autologous stem cell transplantation (ASCT).

Tafasitamab is being clinically investigated as a therapeutic option in B-cell malignancies in several ongoing combination trials. Its safety and efficacy for these investigational uses have not been established in pivotal trials.

Minjuviand Monjuviare registered trademarks of MorphoSys AG. Tafasitamab is co-marketed by Incyte and MorphoSys under the brand name Monjuviin the U.S., and marketed by Incyte under the brand name Minjuviin Region Europe, the United Kingdom and Canada. As part of its agreement with MorphoSys, Incyte received exclusive commercialization rights for tafasitamab outside the United States.

XmAbis a registered trademark of Xencor, Inc.

About Pemigatinib (Pemazyre)

Pemigatinib is a kinase inhibitor indicated inthe United Statesfor the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

The FDA approval in the USA is based on a multicenter, open-label, single-arm, multicohort, phase 2 study (FIGHT-202), that evaluated the safety and antitumor activity of pemigatinib in patients with previously treated, locally advanced or metastatic intrahepatic cholangiocarcinoma with and without FGFR2 fusions or rearrangements, in patients aged 18 years or older with disease progression following at least one previous treatment.

The overall response rate was 36%, with 2.8% of patients having a complete response and 34% having a partial response. Median duration of response was 9.1 months. The most common adverse reactions occurring in 20% or more of patients who received pemigatinib are hyperphosphatemia, alopecia, diarrhea, fatigue, dysgeusia, nausea and stomatitis.

Pemigatinib is also the first targeted treatment approved for use inthe United Statesfor treatment of adults with relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with FGFR1 rearrangement.

InJapan, pemigatinib is approved for the treatment of patients with unresectable biliary tract cancer (BTC) with a fibroblast growth factor receptor 2 (FGFR2) fusion gene, worsening after cancer chemotherapy.

InEurope, pemigatinib is approved for the treatment of adults with locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement that have progressed after at least one prior line of systemic therapy.

Pemazyre is marketed byIncyteinthe United States,EuropeandJapan.

Pemazyre is a trademark ofIncyte Corporation.

About Knight Therapeutics Inc.

Knight Therapeutics Inc., headquartered in Montreal, Canada, is a specialty pharmaceutical company focused on acquiring or in-licensing and commercializing pharmaceutical products for Canada and Latin America. Knight's Latin American subsidiaries operate under United Medical, Biotoscana Farma and Laboratorio LKM. Knight Therapeutics Inc.'s shares trade on TSX under the symbol GUD. For more information about Knight Therapeutics Inc., please visit the company's web site at http://www.knighttx.com or http://www.sedar.com.

Forward-Looking Statement

This document contains forward-looking statements for Knight Therapeutics Inc. and its subsidiaries. These forward-looking statements, by their nature, necessarily involve risks and uncertainties that could cause actual results to differ materially from those contemplated by the forward-looking statements. Knight Therapeutics Inc. considers the assumptions on which these forward-looking statements are based to be reasonable at the time they were prepared but cautions the reader that these assumptions regarding future events, many of which are beyond the control of Knight Therapeutics Inc. and its subsidiaries, may ultimately prove to be incorrect. Factors and risks, which could cause actual results to differ materially from current expectations are discussed in Knight Therapeutics Inc.'s Annual Report and in Knight Therapeutics Inc.'s Annual Information Form for the year ended December 31, 2022 as filed on http://www.sedar.com. Knight Therapeutics Inc. disclaims any intention or obligation to update or revise any forward-looking statements whether because of new information or future events, except as required by law.

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Knight Therapeutics Announces CMED Price Approval of Minjuvi ... - GlobeNewswire