Stem Cell Clinic

Improvements in Stem Cell Transplants for AML With CRISPR – Targeted Oncology

By Stem Cell Treatment

Guenther Koehne, MD, PhD, deputy director and chief of blood and marrow Transplant, hematologic oncology and benign hematology, Baptist Health Medical Group, discusses a phase 1/2 study (NCT04849910) where he served as the principal investigator. The abstract is being presented at this year's American Society of Hematology 2023 Annual Meeting.

The study is a first-in-human phase 1/2 open-label multicenter trial to establish the safety of trem-cel, a CRISPR/Cas9 gene-edited allograft lacking CD33, as a donor allograft for CD33-positive patients with acute myeloid leukemia at high risk of relapse.

Transcription:

Some patients with high-risk acute myeloid leukemia relapse earlier. And that is also, I think, a big step forward that we now don't consider a acute myeloid leukemia all the same. They are risk-stratified from the beginning : FLT3-positive AMLs, TD53-mutated AML, and some others we know are very high risk of relapse, so they will relapse despite of allogeneic transplants. So what's happening there is now we can certainly come in with post-transplantation maintenance treatments, as we do in multiple myeloma. But that's a little complicated, more complicated, because the markers that are expressed on the leukemia cell that can be targeted are also expressed on the normal healthy hematopoietic stem cell, and therefore, you would eliminate the healthy stem cells at the same time as you're trying to knock off the leukemia cell population. But now, I'm proud to say I'm a principal investigator of a clinical trial that uses CRISPR technology. That is gene editing of downregulating the expression of CD33 on the normal hematopoietic stem cells prior to the transplant. And with that, now we have a CD33 that is highly overexpressed on leukemia cell populations. So if we now have a CD33-negative stem cell product from the donor, and infuse this into the patient, then the patients have a normal reconstitution normal blood production, normal recovery of this white cells, platelets, but the cells are all CD33-negative. And now we can go in with treatments that target CD33.

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Improvements in Stem Cell Transplants for AML With CRISPR - Targeted Oncology

The Risks of Stem Cell and Exosome Treatments for Long COVID: A Call for Stricter Regulations – Medriva

By Stem Cell Treatment

In a recent study led by Leigh Turner, PhD, it was revealed that stem cell and exosome treatments are being marketed to patients suffering from long COVID by 36 businesses. These treatments, boasting claims of symptomatic relief, immune boosting, acute COVID infection treatment, and prevention of COVID, have an average cost of $11,322. However, despite their prevalence, these treatments lack extensive scientific evidence and pose potential risks, including serious injury and financial scams. This raises the need for stricter regulation by the Food and Drug Administration (FDA) and the Federal Trade Commission (FTC).

According to the study, the majority of these businesses offering stem cell and exosome treatments for long COVID are based in the U.S. and Mexico. The cost of these therapies ranges from $2,950 to $25,000. Despite the FDA and FTC issuing warning letters to such companies, the marketplace remains vast and largely unregulated. It is noteworthy that long COVID patients, in their desperation for relief, can easily fall prey to entities making appealing therapeutic claims without solid scientific evidence.

While the use of stem cell and exosome treatments for long COVID remains controversial, research has highlighted the potential of Mesenchymal stem cell-derived exosomes (MSC-Exos) in the treatment of lung diseases. They are considered a more stable and safer option than traditional cell therapies. MSC-Exos deliver non-coding RNAs (ncRNAs) to communicate with target cells, inhibiting inflammatory factors, reducing oxidative stress, promoting normal lung cell proliferation, and reducing apoptosis. Some researchers are exploring the detailed mechanisms of MSC-Exos in the clinical treatment of lung disease by developing standardized culture, isolation, purification, and administration strategies.

Its important to note that the link between stem cell treatments and COVID-19 isnt entirely new. A study conducted during the recent COVID-19 outbreak in China revealed that pediatric patients who had received hematopoietic stem cell transplants were more susceptible to COVID-19 infection. This vulnerability was particularly high in recipients over 100 days post-transplant. This study, while not directly connected to the stem cell and exosome treatments for long COVID, does provide some insight into the interaction between stem cell treatments and COVID-19.

While there are ongoing clinical trials and research exploring the use of stem cell and exosome treatments for long COVID, the current lack of substantial scientific evidence calls for caution. Potential benefits for managing long-term symptoms of COVID-19 are promising, but more rigorous scientific studies are needed to confirm these benefits and to understand the risks involved.

Given the potentially serious risks and the high cost of these treatments, there is an urgent need for stricter regulations to prevent financial scams and to ensure patient safety. It is crucial that the FDA and FTC take more robust actions to regulate this marketplace. Until then, patients and healthcare professionals should approach such treatments with caution, critically evaluating claims and seeking treatments that are backed by solid scientific evidence.

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The Risks of Stem Cell and Exosome Treatments for Long COVID: A Call for Stricter Regulations - Medriva

FDA approves CRISPRCas9 therapy for sickle cell disease – ASBMB Today

By Stem Cell Treatment

Officials at the U.S. Food and Drug Administration todayannouncedapproval ofthe first CRISPRCas9 therapeutic to treat sickle cell disease. The cell therapy is the only cure to date for patients who are not eligible for stem cell transplants. The FDA approved the therapy for patients age 12 to 35.

Casgevy uses CRISPRCas9 technology to edit a patients own hematopoietic stem cells to produce high levels of fetal hemoglobin, which is not normally expressed at adulthood and drowns out the damaging effects of sickle hemoglobin.

The therapeutic, exagamglogene autotemcel, sold as Casgevy, from CRISPR Therapeutics and Vertex Pharmaceuticals, uses CRISPRCas9 technology to edit a patients own hematopoietic stem cells to produce high levels of fetal hemoglobin, which is not normally expressed in adulthood and drowns out the damaging effects of their sickle hemoglobin. The therapy was approved in the United Kingdom in November.

Sickle cell disease is a debilitating, genetic disorder that causes abnormal red blood cell development. It affects approximately 7.74 million individuals worldwide. Red blood cells are normally disk-shaped and move easily throughout the blood, carrying oxygen to vital organs. In a patient with sickle cell disease, red blood cells are warped, or sickle-shaped, which can lead to impaired blood flow and cause stroke, infection, eye issues, severe pain crises and premature death.

The therapeutic specifically targets BCL11A, a repressor of the fetal hemoglobin gene, using a guide RNA. The precise target site is a residue within the BCL11A enhancer region, which, once modified by the Cas9 nuclease, takes the brakes off the fetal hemoglobin gene, leaving transcription and later translation free to occur.

Victoria Gray, a mother of four from Mississippi, was the first sickle cell patient to receive Casgevy in a 2019 clinical trial. Prior to the treatment, Gray said she had to rush to the emergency room at least once a month and often stay in the hospital for weeks at a time due to her painful crises. Since receiving Casgevy, she has had no emergency room visits, hospital stays or crises, she said.

I feel cured, Gray said. My life has changed dramatically with just a leap of faith.

Emmanuelle Charpentier is a biochemist, microbiologist and geneticist, recognized as an expert in regulatory mechanisms underlying processes of infection and immunity in bacterial pathogens.

Emmanuelle Charpentier is a cofounder of CRISPR Therapeutics and the director of and a scientific member at the Max Planck Unit for the Science of Pathogens. Charpentier shared the 2020 Nobel Prize in chemistry for the development of CRISPRCas9 with Jennifer Doudna, an RNA biochemist at the University of California, Berkeley.

Peter Marks, director of the FDAs Center for Biologics Evaluation and Research, commented on today's action.These approvals represent an important medical advance with the use of innovative cell-based gene therapies to target potentially devastating diseases and improve public health, Marks said. Todays actions follow rigorous evaluations of the scientific and clinical data needed to support approval, reflecting the FDAs commitment to facilitating development of safe and effective treatments for conditions with severe impacts on human health.

The FDA approved Casgevy based on three studies showing that the drug is a safe and effective treatment for sickle cell disease. In the most recent safety and efficacy clinical trial, patients like Gray who received the therapeutic sustained long-term high levels of total hemoglobin, similar to what is seen in healthy adults, and most were blood transfusionindependent and free of painful crises for at least one year after treatment.

Benjamin Oakes, CEO and cofounder of Scribe Therapeutics, said The approval is just the tip of the iceberg. It's a really beautiful proof of concept for what CRISPR genome editing can do. The real vision and mission for the whole CRISPR field should be to create safer, more effective therapies that can be brought more broadly to patients.

Benjamin Oakes is cofounder and CEOof Scribe Therapeutics.

Oakes said he and his colleagues are developing the next generation of CRISPR gene therapies using an engineered CasX protein that cuts DNA more precisely than Cas9.

According to the Institute for Clinical and Economic Review, Casgevy could be priced at up to $1.93 million to be cost-effective, a measure that estimates how much it costs to gain a unit of a health outcome, such as a life year gained or a death prevented. With this price tag, ICER estimated that 15% of eligible patients could be treated over a five-year period.

In 2022, patients with sickle cell disease incurred out-of-pocket medical costs totaling up to $44,000, with insurers covering approximately $1.7 million per patient. Economists predict that gene therapies like Casgevy could cost a single state Medicare program more than$30 million per year.

The FDA will evaluate a second gene therapy for sickle cell disease, bluebird bios lovo-cel, later this month. Unlike Casgevy, lovo-cel uses a lentiviral vector to introduce a modified beta globin gene into patient stem cells. This modified gene produces an antisickling hemoglobin protein, which is designed to inhibit the polymerization of mutant sickle hemoglobin, making it less likely to form blockages in the circulation.

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FDA approves CRISPRCas9 therapy for sickle cell disease - ASBMB Today

FDA Approves A CRISPR-Based Therapy for Sickle Cell Disease – geneonline

By Stem Cell Treatment

FDA Approves A CRISPR-Based Therapy for Sickle Cell Disease

After CASGEVY (exagamglogene autotemcel) passed the U.S. Food and Drug Administrations (FDA) Biologics License Application (BLA) in June this year (2023), Vertex Pharmaceuticals and CRISPR Therapeutics announced its FDA approval on December 8. CASGEVY is the first FDA-approved treatment utilizing the novel genome-editing technology CRISPR, marking an innovative advance in gene therapy and offering a glimmer of hope for patients with severe sickle cell disease (SCD). Approximately 16,000 patients aged 12 years and older with recurrent Vaso-Occlusive Crisis (VOC) are now eligible to receive this innovative one-time treatment.

Related article: Vertex and CRISPR Collaborate Again with $330 Million Diabetes Gene Editing Deal

The administration of CASGEVY requires specialized knowledge in stem cell transplantation. Vertex is actively collaborating with proficient hospitals to establish Authorized Treatment Centers (ATCs) throughout the United States. Notable institutions involved in this initiative include Boston Medical Center, Childrens National Hospital, and City of Hope Childrens Cancer Center, among others. These ATCs are set to play a pivotal role in facilitating the delivery of CASGEVY to eligible patients. The companies have outlined plans to introduce additional ATCs in the forthcoming weeks, expanding accessibility for patients in need.

CASGEVY, a genome-editing cell therapy, leverages CRISPR/Cas9 technology to edit autologous CD34+ hematopoietic stem cells. This targeted approach aims to diminish BCL11A expression, leading to an increased production of fetal hemoglobin (HbF). Through the reduction or elimination of vaso-occlusive crises, CASGEVY holds the promise of significantly enhancing the quality of life for individuals affected by sickle cell disease (SCD). The therapy has obtained conditional marketing authorization in the United Kingdom and Bahrain. Regulatory agencies in Europe and Saudi Arabia are actively reviewing CASGEVY, with ongoing assessments for its investigational use in treating transfusion-dependent thalassemia (TDT).

The approval marks a significant milestone, not just in the landscape of sickle cell disease (SCD) treatments but also in advancing the frontier of CRISPR-based therapies. The success of CASGEVY represents a noteworthy leap forward in the realm of genetic medicine, offering hope and potential therapeutic avenues for those who require them.

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Modified Stem Cell Transplant Procedure Shows Favorable Results in Adults Living with Severe Sickle Cell Disease – InvestorsObserver

By Stem Cell Treatment

Less Toxic Approach to Haploidentical Bone Marrow Transplantation in Adults Living with Severe Sickle Cell Disease Offers Promise

LBA-4 : Reduced Intensity Haploidentical Bone Marrow Transplantation in Adults with Severe Sickle Cell Disease: BMT CTN

SAN DIEGO , Dec. 12, 2023 /PRNewswire/ --Stem cell transplantation is a potentially curative treatment for sickle cell disease (SCD), but it is not feasible for most people, often due to a lack of suitable donors or the inability to tolerate the intensive chemotherapy required as part of the treatment. In a new study, presented during the 65th American Society of Hematology (ASH) Annual Meeting and Exposition, adults living with severe SCD saw good outcomes from a modified transplantation procedure that broadens the potential donor pool and includes a gentler conditioning regimen, suggesting a less toxic approach could allow a much broader array of people to benefit from the treatment.

"This is a pragmatic approach for adults with SCD, and the results are fantastic," said Adetola A. Kassim , MBBS, MS , professor of medicine at Vanderbilt University Medical Center, the study's lead author. "It actually beat our expectations. This study has clearly shown that you can take selected adult patients with significant comorbidities to transplant, and hopefully change the trajectory of their disease."

The trial is the largest multi-center study to date to test the modified approach in adults with SCD.

SCD is an inherited blood disorder in which red blood cells become misshapen, diminishing their ability to carry oxygen. It causes episodes of severe pain, called vaso-occlusive crises, as well as damage to tissues and organs that accrue over time and can lead to early death. A stem cell transplant can cure the disease by removing the stem cells that produce misshapen blood cells and replacing them with stem cells from a donor that will make healthy blood cells.

The standard transplantation procedure for SCD requires that the donor be a sibling with a high degree of genetic similarity and that the recipient be healthy enough to tolerate a high-intensity chemotherapy regimen as part of the procedure. In the modified procedure used for the study, called related, reduced intensity haploidentical bone marrow transplantation, the donor only needs to be "half-matched" genetically to the recipient, broadening the pool of potential donors to include not only siblings but parents, children, cousins, aunts, and uncles.

While fewer than one-quarter of people with SCD have a matched sibling who could potentially serve as a donor, about 90% have a relative who could serve as a half-matched donor. In addition, because it uses a lower intensity conditioning regimen, the modified approach is more easily tolerated by people with health problems such as organ damage, a complication of SCD that becomes more common with age.

As a result of these modifications, a much broader group of people living with SCD could be eligible for reduced intensity haploidentical bone marrow transplantation than for conventional matched-donor transplantation, including older individuals, those with more comorbidities, and those without a matched sibling donor.

For the study, researchers enrolled 54 individuals living with SCD with a history of stroke or reduced heart functioning, pain episodes, or frequent blood transfusions. Forty-two participants ultimately underwent the modified stem cell transplantation procedure. At two years, the overall rate of survival following the transplant was 95% and the estimated rate of event-free survival (defined as survival without graft failure or a second infusion of stem cells) was 88%.

At 100 days following the transplant, 4.8% of patients experienced a primary graft failure and 4.8% experienced adverse events of grade three or higher. Infections were common; 78.6% of patients experienced at least one hospital admission following their transplant, most due to infections. Two participants died within the first year after the transplant, one from organ failure and one from fluid buildup in the lungs associated with COVID-19 infection.

Most participants experienced significant improvements in markers of healthy blood functioning, a reduction in pain episodes and fatigue, and improved heart and lung functioning. Overall, researchers said that the results suggest the modified procedure can achieve results that are comparable to conventional stem cell transplantation and is tolerable even for people with health conditions that would make them ineligible for a conventional transplant.

In future studies, the researchers plan to focus on opportunities to reduce rates of infection, enhance supportive care, and preserve fertility among people undergoing the procedure. They also plan to continue to follow trial participants to track long-term outcomes.

"Some of these patients are really thriving and now getting back into the community," said Dr. Kassim. "Our hope is that long-term follow-up will be able to quantify the added value of curing patients of SCD." Dr. Kassim added that most patients were off immunosuppression therapy at both the one and two-year post-transplant timepoints with no significant chronic graft-versus-host disease, providing evidence that the study's cyclophosphamide-based post-transplant regimen helped to reduce the risk of this serious complication.

Researchers noted that for many people, the feasibility of this treatment will depend not only on the availability of family donors, but on costs and insurance coverage, the ability to take time off work and even temporarily relocate to undergo the procedure, and the availability of family and caregiver support.

This study was funded by the National Heart, Lung and Blood Institute and the National Cancer Institute.

Adetola Kassim , MBBS, MS, of Vanderbilt University , will discuss this study in the Late-Breaking Abstracts Session on Tuesday, Dec. 12, 2023 , at 9:00 a.m. Pacific time in Hall A ( San Diego Convention Center).

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The American Society of Hematology (ASH) ( hematology.org ) is the world's largest professional society of hematologists dedicated to furthering the understanding, diagnosis, treatment, and prevention of disorders affecting the blood. For more than 60 years, the Society has led the development of hematology as a discipline by promoting research, patient care, education, training, and advocacy in hematology.

ASH's flagship journal, Blood ( bloodjournal.org ) is the most cited peer-reviewed publication in the field, and Blood Advances ( bloodadvances.org ) is an open-access, online journal that publishes more peer-reviewed hematology research than any other academic journal worldwide. Two new journals will be joining the Blood Journals portfolio in 2024, Blood Neoplasia ( bloodneoplasia.org ) and Blood Vessels, Thrombosis & Hemostasis ( bloodvth.org ).

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Stem cell study reveals how infantile cystinosis causes kidney failure and how to cure it – EurekAlert

By Stem Cell Medicine

image:

This image, produced by a fluorescence microscope,shows a normal renal proximal tubule, the specific nephron segment in the kidney that is impaired in the rare disease infantile cystinosis. The red, green and yellow regions indicate the presence of different proteins in the tubule and the blue indicates the presence of nuclei. The UB researchers generated the tubule in the image from stem cells derived from an individual who does not have the disease.

Credit: Alexandra Kojac

BUFFALO, N.Y. University at Buffalo research has identified how a misstep in the genesis of a key component of the kidney causes infantile cystinosis, a rare disease that significantly shortens the lifespan of patients. Published Nov. 30 in theInternational Journal of Molecular Sciences, the work reveals that the mechanisms that cause the disease could be addressed and potentially cured through the genome-editing technique CRISPR. That could make kidney transplants, the most effective treatment currently available for these patients, unnecessary.

Infantile cystinosis, the most common and most severe type of cystinosis, occurs as the result of an accumulation in the bodys cells of cystine, an amino acid. The buildup damages cells throughout the body, especially the kidneys and the eyes. Treatment consists of medications that work to lower the level of cystine in the body, as well as therapies that address the impaired growth of these children due to the inability to properly absorb nutrients. Some children require feeding tubes. Eventually, patients with infantile cystinosis, also called nephropathic cystinosis, will require dialysis and a kidney transplant.

Promise of stem cells

Human-induced pluripotent stem cells (hiPSCs) are stem cells that can differentiate into many different cell types. They hold tremendous potential for studying genetic diseases; the drawback has been that differentiation into certain cell types has been problematic. Such is the case with many cell types found in the kidney.

But a new protocol developed by this research team was successful.

When our normal human-induced pluripotent stem cells were subjected to the differentiation protocol we developed, we were able to demonstrate extensive expression of physiologically important markers of the renal proximal tubule, the specific nephron segment that is altered in this disease, saysMary L. Taub, PhD, senior author on the paper and professor of biochemistry in the Jacobs School of Medicine and Biomedical Sciences at UB.

Ramkumar Thiyagarajan, PhD, assistant professor of geriatric studies at the University of Kansas and formerly a postdoctoral fellow at UB, is first author on the paper.

The protocol involved extracting stem cells from a healthy individual and an individual with infantile cystinosis. The researchers developed a culture medium to grow stem cells that included a small number of defined components present in blood, including insulin, specific proteins, growth factors and others. Conducting the differentiation protocol under these conditions occurred in a timely manner, says Taub, we didnt have to wait for weeks on end, and it occurred in a reproducible manner.

The researchers were able to efficiently differentiate the hiPSCs into the kidney proximal tubule, the type of nephron in the kidney that is impaired in infantile cystinosis, as well as in other kidney diseases.

Unlike in other studies, we were able to retain a number of markers in the tubule that are physiologically important in the kidneys reabsorptive functions, says Taub. Although these markers were expressed in both the normal and the cystinosis-derived hiPSCs, the genesis of the tubule was impaired in the cystinosis-derived cells, mimicking what happens in infantile cystinosis.

A potential cure

That finding means that the CRISPR genome-editing technique could be used to repair the defective genome and potentially cure the disease. The normal gene can be introduced in the genome of cystinotic hiPSCs, which can then be injected in the kidney to replace the defective proximal tubules of individuals with infantile cystinosis, Taub says.

In cystinotic individuals, it is the renal proximal tubule that degenerates, presumably due to programmed cell death, explains Taub, so the entire kidney would not need to be replaced. The defective renal proximal tubules of individuals with this disease can be replaced with normal tubules following the introduction of the normal gene into cystinotic hiPSCs obtained from the patient. And because these tubules are from cells derived from the patient, there should be no problem with tissue rejection.

The findings are applicable to other kidney diseases where the renal proximal tubule is damaged, including acute kidney injury that can lead to chronic kidney disease and renal failure, and can be fatal.

Initial studies will need to be conducted with animal models as well as with in vitro tissue culture cells.

The research was funded byUBs WNYSTEM and The Cystinosis Research Foundation.

International Journal of Molecular Sciences

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Stem cell study reveals how infantile cystinosis causes kidney failure and how to cure it - EurekAlert

Orca-Q Demonstrates Early Efficacy, Tolerable Safety in Haploidentical Stem Cell Transplant Without PTCy – Targeted Oncology

By Stem Cell Medicine

Bone marrow: 7activestudio - stock.adobe.com

The high-precision cellular product Orca-Q showcased early signals of clinical activity and an acceptable safety profile in patients receiving a haploidentical stem cell transplantation (haplo-SCT) without posttransplant cyclophosphamide (PTCy), according to findings from a phase 1 trial (NCT03802695) presented during the 2023 ASH Annual Meeting.1

Results showed that both the graft-vs-host disease (GVHD) relapse-free survival (GRFS) rate and overall survival (OS) rate at 1 year was 82% (95% CI, 65%-94%) with Orca-Q. This is in comparison to historical data with conventional PTCy for haplo-SCT, with recent 1-year GRFS rates of 46%.

These findings show promising safety and efficacy outcomes using Orca-Q cell therapy for haploidentical transplant, said Samer A. Srour, MB ChB, MS, lead study author and assistant professor in the Department of Stem Cell Transplantation, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center in Houston, in an oral presentation during the meeting. No safety signals in this haploidentical setting were identified.

Standard allogeneic SCT can be a curative approach for patients across many high-risk hematologic cancers, although access to this therapy was previously limited to those who have a fully matched donor. The introduction of PTCy as prophylaxis for GVHD increased the utility of haploidentical donors; however, it has also increased relapse rates and toxicity issues such as cytokine release syndrome (CRS), delayed engraftment and T-cell reconstitution, mucositis, infections, cardiac events, and non-relapse mortality, Srour added.

However, GRFS rates in this patient population remain low. Through allograft optimization, Orca-Q improves haplo-SCT with its fully defined stem and immune cells, which consist of hematopoietic stem and progenitor cells, invariant natural killer cells, regulatory T cells, and CD4+/CD8+ T-cell subsets.

Orca-Q is derived from granulocyte colony stimulating factor that is mobilized during peripheral blood apheresis and is manufactured centrally at a Current Good Manufacturing Practice Manufacturing Facility in Sacramento, California. Its administration involves a vein-to-vein time of less than 72 hours across the United States, Srour noted, adding that the vein-to-vein time was within 60 hours for most cases on the study.

The multicenter, dose-expansion trial enrolled patients aged 18 to 65 years with the following high-risk hematologic cancers: acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), very high or high-risk myelodysplastic syndrome, or myelofibrosis. Patients were required to be undergoing a haplo-SCT with negative donor-specific antibodies and were eligible for myeloablative chemotherapy with a Hematopoietic Cell Transplantation-specific Comorbidity Index 4 or lower, a Karnofsky performance score of at least 70, and adequate organ function.

Orca-Qs regimen begins with myeloablative conditioning on days -10 to -2, followed only by single-agent tacrolimus on day -1no PTCy or additional immunosuppressive therapies are administered. A fresh Orca-Q infusion is given on day 0, and tacrolimus is tapered on day +60 (posttransplant).

The studys primary end points are dose-limiting toxicities and primary graft failure.

Off the 33 patients enrolled onto the study, the median age is 43 years (range, 21-63) and 27% of patients were female; a total 30.3% of patients identified as Hispanic or Latino. Patients were Asian (15.2%), Black or African American (21.2%), White (42.4%), or other (21.2%). Their primary disease was ALL (30.3%), AML (63.3%), or chronic myeloid leukemia (6.1%). Additionally, patients had high-/very highrisk disease (18%), intermediate-risk disease (79%). Disease risk index was not applicable for 3% of patients.

Patients disease status at time of transplant encompassed those who achieved their first complete remission (CR1; 73%), second CR (CR2; 24%) and CML accel phase (3%). Patients either had a total body irradiation (TBI)-based conditioning regimen (51.5%) or busulfan-based one (48.5%). Donor characteristics showed that there were more male donors (73%) vs female donors (27%), and the CMV status was positive (30.3%), negative/not detected (36.3%), or not available (33.3%).

Rapid engraftment with Orca-Q was observed in the patients. The median engraftment time with neutrophils was 12.0 days (range, 8-25) and 15.5 days with platelets (range, 8-79). Two patients experienced secondary graft failure, and grade 1/2 CRS occurred in 3 patients (grade 1, n = 2; grade 2, n = 1).

Additional data showed a low incidence of severe Common Terminology Criteria for Adverse Events grade 2 (CTCAE; n = 9) and CTCAE grade 3 (n = 15) infections. There were 5 events (15%) of acute grade 2 to 4 GVHD and 1 event of grade 3 acute GVHD. At a median follow-up of 375 days (range, 73-1384), no patients have developed moderate to severe chronic GVHD. This in comparison to historical cohorts with PTCy, which show 1-year chronic GVHD rates of 24% to 33%.2

The phase 1 trial is continuing to enroll patients across the United States. Srour stated that there are plans to increase the age criteria to 75 years and provide less-intensive conditioning therapy.

Editors Note: Dr Srour disclosed research funding from Orca Bio for this study.

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Orca-Q Demonstrates Early Efficacy, Tolerable Safety in Haploidentical Stem Cell Transplant Without PTCy - Targeted Oncology

Stem Cell-Based Therapy: A Ray of Hope for Advanced Heart Failure Patients – Medriva

By Stem Cell Medicine

In a groundbreaking multinational clinical trial led by Mayo Clinic researchers and international collaborators, it was discovered that stem cell-based therapy significantly improved the quality of life for patients suffering from advanced heart failure. The study, one of the largest of its kind, involved 315 patients from 10 countries and revealed lower death and hospitalization rates among those treated with cell therapy. The research, funded by the Marriott Family Foundation and National Institutes of Health, was published in Stem Cells Translational Medicine.

The study demonstrated that patients who received stem cell therapy experienced a lessened daily hardship and a sustained benefit on both physical and emotional health. This promising form of biotherapy involves extracting stem cells from the patients own bone marrow and programming them to heal damaged heart tissue.

This trial stands out in the field of regenerative medicine, showcasing the potential of stem cell-based therapy in improving the quality of life for patients with advanced heart failure. The reduced daily hardship reported by patients, as well as the lower death and hospitalization rates, indicate the effectiveness of this therapy. Moreover, the sustained benefits on physical and emotional health emphasize the potential of biotherapy in the management of advanced heart disease.

The clinical trial was conducted in a double-blinded fashion, involving 315 patients from 39 hospitals across 10 countries. The results showed a significant improvement in the patients who received stem cell therapy, with lower death and hospitalization rates. The research was one of the largest studies of cell intervention after a heart attack, and patients reported a lessening of their daily hardship when stem cells optimized for heart repair were added to the standard of care.

The Mayo Clinic has long been at the forefront of regenerative medicine, seeking to harness the power of cells, tissue, and genes to provide first-of-their-kind therapeutics for patients in early-stage clinical trials. In other studies, Mayo Clinic researchers have demonstrated a nearly 20% increase in human papillomavirus (HPV) vaccination rates among adolescents through a combination intervention approach.

While the results of this clinical trial are promising, further independent clinical studies are needed to validate the findings and better understand the potential of stem cell-based therapy in treating advanced heart failure. As advancements in this field continue to emerge, the hope for patients suffering from heart diseases grows stronger.

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Mayo Clinic researchers say stem cell therapy improves quality of life for patients with advanced heart failure – KIMT 3

By Stem Cell Medicine

ROCHESTER, Minn. A multinational clinical trial involving Mayo Clinic researchers has found stem cell-based therapy improved quality of life for patients with advanced heart failure.

In the study, patients reported their daily hardship lessened when stem cells optimized for heart repair supplemented the standard of care, and the study further documented lower death and hospitalization rates among those treated with cell therapy.

"In this era of global aging, people live longer, yet are at risk of chronic disease imposing a poor quality of life. Heart failure is an emerging epidemic in need of new healing options," says Andre Terzic, M.D., Ph.D., a Mayo Clinic cardiovascular researcher and lead author of the paper. "The stem cell-based approach in the present study demonstrates sustained benefit on physical and emotional health in response to biotherapy."

Dr. Terzic is the Marriott Family Director, Comprehensive Cardiac Regenerative Medicine for the Center for Regenerative Biotherapeutics.

Approximately 800,000 people in the U.S. suffer heart attacks every year.

The study team recruited 315 patients from 39 hospitals in 10 countries who had advanced heart failure despite receiving standard of care. Mayo Clinic says patients were randomly divided into groups that would receive stem cell therapy versus those who would not. Patients assigned to cell treatment underwent cardiac catheterization. Then, stem cells taken from their own bone marrow and programmed to heal damaged heart tissue were delivered to the heart. Patients assigned not to receive stem cells had cardiac catheterization without cell delivery known as the sham treatment.

"Data from one of the largest cardiovascular cell therapy trials, testing a regenerative technology discovered at Mayo Clinic, indicate benefit in both quantity and quality of life in advanced heart disease," saysSatsuki Yamada, M.D., Ph.D., a Mayo Clinic cardiovascular researcher, and first author on the study. "The benefit of regenerative care has been typically evaluated on the basis of clinician-reported outcomes. What's unique in this study is that it was designed to listen to the patient's experience."

This research is published in Stem Cells Translational Medicine.

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Mayo Clinic researchers say stem cell therapy improves quality of life for patients with advanced heart failure - KIMT 3

Type 1 Diabetes Treatment Breakthrough with Stem Cells | Health News – Medriva

By Stem Cell Medicine

In a significant breakthrough for type 1 diabetes treatment, a new experimental device housing millions of stem cells has demonstrated promising results in reducing the need for insulin shots. This development could potentially revolutionize the management of type 1 diabetes and pave the way for advanced treatment options. However, a more comprehensive body of research and clinical trials are still required to confirm the effectiveness of this approach.

An experimental device containing millions of stem cells was tested on ten people with type 1 diabetes, a condition in which the immune system destroys insulin-making cells in the pancreas. After six months, three of the patients showed significant improvement. The device, developed by the biotech company ViaCyte, delivers a steady supply of insulin to the body, presenting hope for a potential cure for type 1 diabetes by 2024. While the trial has its limitations and failed to normalize blood glucose levels, it offers a promising start for cell replacement therapies for type 1 diabetes.

Cellular regenerative medicine approaches, particularly those involving the use of CRISPR/Cas-engineered cellular products, have been explored as potential therapies for type 1 diabetes. However, the use of CRISPR/Cas as a genome editing tool for the treatment of type 1 diabetes is not without its drawbacks and potential hidden threats.

Leading institutions around the world are accelerating their research efforts to develop new treatments for type 1 diabetes. One such initiative is the University of Oxfords RDM group, which was awarded 2.55 million for a diabetes research project as part of the Type 1 Diabetes Grand Challenge. Led by Professor David Hodson, the project aims to study insulin-boosting molecules on beta cells. These molecules could potentially be used to create better lab-grown beta cells, protect transplanted beta cells, or even stimulate the growth of new beta cells. This research is part of a larger 50 million pledge from the Steve Morgan Foundation to expedite research for new treatments for type 1 diabetes.

Recent studies have highlighted the potential of human pluripotent stem cells as an unlimited resource for generating functional cells, including pancreatic cells, for type 1 diabetes treatment. One such study focused on the role of circular RNA circRNA hsa_circ_0032449 in pancreatic specification and the differentiation of stem cells into functional cells. The deficiency of hsa_circ_0032449 resulted in a weakened progenitor state of pancreatic cells and inhibited the development of mature and glucose-responsive SC cells.

With these groundbreaking advancements in stem cell therapies, there is renewed hope for millions of people worldwide living with type 1 diabetes. However, medical researchers and healthcare professionals agree that extensive further research and clinical trials are vital to fully validate the effectiveness of these approaches.

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Type 1 Diabetes Treatment Breakthrough with Stem Cells | Health News - Medriva

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