Podcasts about allogeneic

In this week's episode of The Dr. Joy Kong Podcast, I sit down with a fellow expert, the amazing Dr. Scott Martin.Dr. Martin is a pioneer in regenerative medicine who has consulted for multiple biotech companies and advocates for holistic, patient-centered care.Together, he and I will be discussing the common misconceptions in the industry, including whether birth tissue products truly contain live cells, if some professionals in the field are exploiting patients for profit, and why these problems have gone unaddressed for far too long.We will also be talking about:The ethics behind using birth tissue in stem cell treatmentsThe personal attacks I have suffered as a regenerative medicine doctorWhy the future of regenerative medicine lies in patient outcomes, not product sales… and a lot more!Are you ready?Let's dive in.Key Takeaways:Introduction (00:00)Dr. Scott Martin's background and contributions (02:05)Challenges in regenerative medicine (03:37)Regulatory and market challenges (08:11)Autologous vs. Allogeneic biologics (15:50)Manipulation of scientific literature (22:05)Manipulated research methods in autologous biologic studies (37:57)Ethical discussion: providing all options in biologic treatments. (1:10:08)Closing remarks (1:26:30)Additional Resources: ✨ Learn more about how to live a long and pain-free life: https://joykongmd.com/ ✨ Follow me on Facebook: https://www.facebook.com/stemcelldrjoy/ ✨ Follow me on Instagram: https://www.instagram.com/dr_joy_kong/ —Dr. Joy Kong is a regenerative medicine and anti-aging expert. Her podcast is part of her mission to reduce suffering and elevate happiness. Join us every week for the latest holistic health insights that will help you live a long and pain-free life.

CAR T-cell therapy has revolutionized the lymphoma treatment landscape in recent years. In this episode, we delve into cutting-edge CAR... The post Novel CAR strategies being explored in lymphoma: allogeneic products, trispecific CARs & new manufacturing platforms appeared first on VJHemOnc.

Dr. John Sweetenham and Dr. James Foran discuss the evolving treatment landscape in acute myeloid leukemia, including new targeted therapies, advances in immunotherapy, and the current role for allogeneic transplantation. TRANSCRIPT Dr. John Sweetenham: Hello, I'm Dr. John Sweetenham, the host of the ASCO Daily News Podcast. There has been steady progress in the therapies for acute myeloid leukemia (AML) in recent years, largely based on an increasing understanding of the molecular mechanisms which underlie the disease. On today's episode, we'll be discussing the evolving treatment landscape in AML. We'll explore risk group stratification, new targeted therapies, advances in immunotherapy for AML, and also a little about the current role for allogenic transplantation in this disease.  I'm delighted to welcome Dr. James Foran to this discussion. Dr. Foran is a professor of medicine and chair of the Myeloid Malignancies and Blood and Marrow Transplant Disease Group at the Mayo Clinic Comprehensive Cancer Center. He's based in Jacksonville, Florida.  Our full disclosures are available in the transcript of this episode.  James, it's great to have you join us on the podcast today, and thanks so much for being here. Dr. James Foran: I'm delighted and thank you for the invitation. Thank you very much. Dr. John Sweetenham: Sure, James, let's get right into it. So, our understanding of the molecular mechanisms underlying AML has resulted not only in new methods for risk stratification in this disease, which have added refinement to cytogenetics, but also has resulted in the development of many new targeted agents. Understanding that this is a complex area of investigation, and our time is somewhat limited, can you give us a high-level update on the current state of the art in terms of how risk factors are being used for treatment selection now? Dr. James Foran: Absolutely. I think in the past, you know, we had things broken down pretty simply into make a diagnosis based on morphology, do cytogenetics, break patients into the groups of those who were more likely to benefit from therapy – so-called favorable risk – those where the intensive therapies were less likely to work – so-called poor adverse risk, and then this large intermediate group that really had variable outcomes, some better, some worse. And for a long time, the progress was in just identifying new subtle cytogenetic risk groups. And then, late 1990s, we began to understand that FLT3 mutations or NRAS mutations may be more adverse than others that came along. In the first part of this millennium, in the, you know, 2000-2010 range, a lot of work was being done to understand better or worse risk factors with single genes. The ability to do multiplex PCR, and then more recently NGS platforms, have allowed us to really look at many genes and identify many mutations in patients. At the beginning that was used just to sort of refine – who did a little better, who did a little worse with intensive therapy – helped us decide who may benefit more from an allogeneic transplanter for whom that would not be necessary.  But the good news is that really, we're now starting to target those mutations. One of the first molecularly targeted treatments in leukemia was FLT3 mutations, where we knew they were adverse. Then along came targeted treatments. I was involved in some of those early studies looking at sunitinib, sorafenib, more recently midostaurin, now quizartinib, FDA approved, and gilteritinib in the relapse refractory setting.  So we're moving into a state where we're not just refining prognosis, we're identifying targets. You know, it's been slow progress, but definite incremental progress in terms of outcomes by looking for FLT3 mutations, then looking for IDH mutations, and more recently, mutations involving NPM1 or rearrangement of what we used to call the MLL gene, now the lysine methyltransferase 2A or KMT2A rearrangement, where we now have targets. And it's not just for refinement of prognosis, but now we're identifying therapeutic targets for patients and ways to even look for measurable residual disease which is impacting our care. Dr. John Sweetenham: That's great, James. And I'm going to expand on that theme just a little bit and perhaps ask you to elaborate a little bit more on how the introduction of these new therapies have specifically impacted frontline therapy. And a couple of ancillary questions maybe to go along with that: First of all, is ‘7+3' a standard therapy for anybody in 2025? And maybe secondly, you know, could you comment also maybe briefly on older patients with AML and how you think maybe the treatment landscape is changing for them compared with, say, 5 or 10 years ago? Dr. James Foran: I'll start with the therapy and then work my way back. So we've had ‘7+3' cytarabine daunorubicin or cytarabine anthracycline since 1976, and we're still using it as the backbone of our intensive therapy. There is still an important role for it, particularly in younger or fitter patients, and particularly for those with intermediate or favorable risk genetic groups or cytogenetic risk groups just because we achieve high rates of remission. Our 30-day induction mortality rates are lower now than they were 10 and 20 years ago. Our supportive care is better. And we still have a busy inpatient hospital service here at Mayo Florida and my colleagues in Rochester and Arizona as well giving intensive therapy. So that remains the backbone of curative therapy for younger adults. We are trying to be a little more discriminating about who we administer that to. We are trying to add targeted agents. We know from, now, two different randomized trials that the addition of a FLT3 inhibitor, either midostaurin or more recently quizartinib, has a survival advantage in patients with a FLT3 mutation, or for quizartinib, a FLT3/ITD mutation. And so yes, ‘7+3' remains important.  Off protocol for somebody who just comes in with acute leukemia in a 40-year-old or 30-year-old or even early 60s and fit, we would still be considering ‘7+3' therapy and then waiting for an expedited gene mutation panel and an expedited cytogenetics panel to come back to help us discriminate is that a patient for whom we should be giving a FLT3 inhibitor? I think there's a little more nuance about when we do a day 14 bone marrow, do they really matter as much anymore? I still do them. Some of my colleagues find them less important. But we're still giving intensive therapy. We're still giving high-dose ARA-C consolidation for younger patients who achieve complete remission.  In older adults, it's a different story. You know, it was only in the early part of the 2000s – 2004, 2007 range – where we really got buy-in from randomized studies that low-dose therapy was better than no therapy. There was a lot of nihilism before then about therapy for older adults, especially over age 75. We know that low-dose ARA-C is better than nothing. It looked like azacitidine was better than ARA-C or at least equivalent or slightly better. But with the advent of venetoclax it was a game changer. I ran a national randomized study of intensive therapy in AML. It was the last national randomized study of intensive therapy in older patients right before venetoclax got approved. And we were very excited about our results, and we thought we had some really interesting clinical results. And suddenly that's a little bit obsolete in patients over 70 and particularly over age 75 because of the high remission rates with azacytidine venetoclax or hypomethylating agents, so-called HMAs and venetoclax and the survival advantage. Now, it's not a home run for everybody. We quote 60% to 70% remission rates, but it's a little different based on your cytogenetics and your mutation profile. You have to continue on therapy so it's continuous treatment. It's not with curative intent, although there are some people with long-term remission in it. And the median survival went from 10 months to 15 months. So home run? No, but definitely improved remissions, meaningful for patients off transfusions and better survival. So right now it's hard to find an older adult who you wouldn't give azacitidine and venetoclax or something similar, decitabine, for instance, and venetoclax, unless somebody really was moribund or had very poor performance status or some reason not to. And so ‘7+3' is still relevant in younger adults. We're trying to get better results with ‘7+3' by adding targeted agents and azacitine and venetoclax in older adults.  I think the area of controversy, I guess there are two of them, is what to do in that overlap age between 60 and 75. Should people in that age still get intensive therapy, which we've used for years – the VIALE-A trial of aza-venetoclax was age 75 plus – or with cardiac comorbidities? And I think if you're 68 or 72, many of us are starting to bias towards aza-venetoclax as generally being better tolerated, generally being more outpatient, generally being slow and steady way to get a remission. And it doesn't stop you from going to transplant for somebody who might still be a candidate.  The other area of controversy is somebody under 60 who has adverse cytogenetics where we don't do very well with ‘7+3,' we still give it and we might do just as well with decitabine venetoclax. A lot of us feel that there's equipoise in the 60 to 75 group where we really can ask a question of a randomized study. Retrospective studies might suggest that intensive therapy is a little better, but there are now a couple of randomized studies happening saying, “Can we replace ‘7+3' in that intermediate age with aza-venetoclax?” And for younger adults similarly, we're looking to see how we apply that technology. Those are the areas where we're really trying to investigate what's optimal for patients and that's going to require randomized trials. Dr. John Sweetenham: Oh, that's great, thank you. And I'll just extend that question a little bit more, particularly with respect to the new targeted therapies. How much are they impacting the treatment of these patients in the relapse and refractory setting now? Dr. James Foran: Oh, they're definitely impacting it. When I trained and probably when you trained, AML was still a medical emergency. But that was the thing that you admitted to the hospital immediately, you started therapy immediately. The rule was always that's the one thing that brings the fellow and the consultant in at night to see that new patient on a Friday or Saturday. Now, we'll still admit a patient for monitoring, but we try not to start therapy for the first three or five or seven days if they're stable, until we get those genetics and those genomics back, because it helps us discriminate what therapy to pursue. And certainly, with FLT3 mutations, especially FLT3/ITD mutations, we're adding FLT3 inhibitors and we're seeing a survival advantage. Now, on the surface, that survival advantage is in the range of 7% or 10%. But if you then pursue an allogeneic transplant in first remission, you're taking disease where we used to see 30%, 40% long-term survival, maybe less, and you're pushing that to 60%, 70% in some studies. And so we're now taking a disease that– I don't want to get off topic and talk about Ph+ ALL. But that's a disease where we're actually a little excited. We have a target now, and it used to be something really adverse and now we can do a lot for it and a lot about it.  The other mutations, it's a little more subtle. Now, who knew until 2010 that a mutation in a sugar metabolism gene, in isocitrate dehydrogenase, or IDH was going to be so important, or even that it existed. We know that IDH1 and IDH2 mutations are still a minority of AML, certainly less than 10% to 15%, maybe overall. But we're able to target those with specific IDH1 and IDH2 inhibitors. We get single-agent responses. There are now two approved IDH1 inhibitors on the market. We don't yet have the randomized data that adding those to intensive therapy is better, but we're getting a very strong hint that it might be better in older adults who have an IDH mutation, maybe adding those is helpful and maybe adding those to low-intensity therapy is helpful. Those studies are ongoing, and we're also trying with low-intensity treatments to add these agents and get higher remission rates, deeper remissions, longer remissions. I think a lot of work has to be done to delineate the safety of that and the long-term efficacy. But we're getting hints it's better, so I think it is impacting.  The other area it's impacting is when you pick up adverse mutations and those have crept into our classification systems like an ASXL1 mutation or RUNX1 mutation for instance, or some of the secondary AML mutations like BCOR and others, where that's helping us discriminate intermediate-risk patients who we think aren't going to do as well and really helping us select a group who's more likely to get benefit from allogeneic transplant or for whom at least our cure rates without allo transplant are low. And so I think it's impacting a lot. Dr. John Sweetenham: Great. And I'm going to pick up now, if I may, on a couple of things that you've just mentioned and continue the theme of the relapsed and refractory setting. We've started to see some reports which have looked at the role of immune strategies for patients with AML, in particular CAR T or NK cells. Can you comment a little on this and let us know whether you think either these two strategies or other immune strategies are likely to have a significant role in AML in the future? Dr. James Foran: They are, but I think we're still a step behind finding the right target or the right way to do it. If you think of allogeneic transplantation as the definitive immune therapy, and we know for adverse AML we can improve survival rates and cure rates with an allotransplant, then we know inherently that immune therapy matters. And so how do we do what they've done in large cell lymphoma or in CD19 targeting for B cell malignancies? How do we bring that to acute myeloid leukemia? There have been a number of efforts. There have been at least 50 trials looking at different targets. CD33, CD123, CD7, others, CLL-1. So, there have been a number of different trials looking at how to bind a CAR T or a CAR T construct that can be active. And we have hints of efficacy. There was kind of a provocative paper in the New England Journal of Medicine a year ago in April of last year from a Chinese group that looked at a CD7-based CAR T and it was 10 patients, but they used CD7 positive acute leukemia, AML or ALL and had a CD7-targeted CAR T and they actually incorporated that with a haploidentical transplant and they had really high remission rates. People tolerated it quite well. It was provocative. It hasn't yet been reproduced on a larger scale, but the strong hints that the strategy is going to work.  Now, CD33 is a little tricky to have a CAR T when CD33 is expressed on normal hematopoietic cells. CD123 likewise. That's been something where there's, I think, still promise, but we've struggled to find the trials that make that work. Right now, there's a lot of interest in leveraging NK cells and looking, for a couple of reasons, but NK cells are attractive and NK cell markers might be attractive targets. NK cells might have similar degrees of immune efficacy. It's speculative, but they are likely to have less cytokine release syndrome and less neurotoxicity than you see with CAR T. And so it's kind of attractive to leverage that. We have had some ongoing trials looking at it with bispecifics and there certainly are trials looking at it with CAR NK-based strategies. One of the antigens that people looked at is the NK group 2D. NK group 2D or NKG2D is overexpressed in AML and its ligands overexpressed. And so that's a particular potential target. So, John, it's happening and we're looking for the hints of efficacy that could then drive a pivotal trial to get something approved.  One of the other areas is not restricting yourself just to a single antigen. For instance, there is a compound that's looking at a multi-tumor-associated antigen-specific T-cell therapy, looking at multiple antigens in AML that could be overexpressed. And there were some hints of activity and efficacy and actually a new trial looking at a so-called multi-tumor associated antigen-specific T cell therapy. So without getting into specific conflicts of interest or trials, I do think that's an exciting area and an evolving area, but still an investigational area. I'll stop there and say that we're excited about it. A lot of work's going there, but I'm not quite sure which direction the field's going to pivot to there. I think that's going to take us some time to sort out. Dr. John Sweetenham: Yeah, absolutely. But as you say, exciting area and I guess continue to watch this space for now.  So you've mentioned allogeneic stem cell transplants two or three times during this discussion. Recognizing that we don't have an imatinib for AML, which has kind of pushed transplant a long way further back in the treatment algorithm, can you comment a little on, you know, whether you think the role of stem cell transplantation is changing in AML or whether it remains pretty much as it was maybe 10 years ago? Dr. James Foran: By the way, I love that you use imatinib as an introduction because that was 6 TKIs ago, and it tells you the evolution in CML and you know, now we're looking at myristoyl pocket as a target, and so on. That's a great way to sort of show you the evolution of the field.  Allogeneic transplant, it remains a core treatment for AML, and I think we're getting much smarter and much better about learning how to use it. And I'm just going to introduce the topic of measurable residual disease to tell you about that. So I am a little bit of a believer. Part of my job is I support our allogeneic transplant program, although my focus is acute myeloid leukemia, and I've trained in transplant and done it for years and did a transplant fellowship and all that. I'm much more interested in finding people who don't need a transplant than people who do. So I'm sort of looking for where can we move away from it. But it still has a core role. I'll sidestep and tell you there was an MDS trial that looked at intermediate or high-risk MDS and the role of allogeneic transplant that shows that you about double your survival. It was a BMT CTN trial published several years ago that showed you about double your three-year survival if you can find a donor within three months and get to a transplant within six months. And so it just tells you the value of allotransplant and myeloid malignancy in general. In AML we continue to use it for adverse risk disease – TP53 is its own category, I can talk about that separately – but adverse risk AML otherwise, or for patients who don't achieve a really good remission. And I still teach our fellows that an allotransplant decreases your risk of relapse by about 50%. That's still true, but you have to have a group of patients who are at high enough risk of relapse to merit the non-relapse mortality and the chronic graft versus host disease that comes with it. Now, our outcomes with transplant are better because we're better at preventing graft versus host disease with the newer strategies such as post-transplant cyclophosphamide. There are now new FDA-approved drugs for acute and chronic graft versus host disease, ruxolitinib, belumosudil, axatilimab now. So we have better ways of treating it, but we still want to be discriminating about who should get it.  And it's not just a single-minded one-size-fits-all. We learned from the MORPHO study that was published in the JCO last year that if you have FLIT3-positive AML, FLIT3/IDT-positive AML, where we would have said from retrospective studies that your post-transplant survival is 60% give or take, as opposed to 15% or 20% without it, that we can discriminate who should or shouldn't get a transplant. Now that trial was a little bit nuanced because it did not meet its primary endpoint, but it had an embedded randomization based upon MRD status and they used a very sensitive test of measurable residual disease. They used a commercial assay by Invivoscribe that could look at the presence of a FLT3/ITD in the level of 10 to the minus 5th or 10 to the minus 6th. And if you were MRD-negative and you went through a transplant, you didn't seem to get an advantage versus not. That was of maintenance with gilteritinib, I'll just sort of put that on there. But it's telling us more about who should get a transplant and who shouldn't and who should get maintenance after transplant and who shouldn't.  A really compelling study a year ago from I don't know what to call the British group now, we used to call them the MRC and then the NCRI. I'm not quite sure what to call their studies at the moment. But Dr. Jad Othman did a retrospective study a year ago that looked at patients who had NPM1 mutation, the most common mutation AML, and looked to see if you were MRD positive or MRD negative, what the impact of a transplant was. And if you're MRD negative there was not an advantage of a transplant, whereas if you're MRD positive there was. And when they stratified that by having a FLT3 mutation that cracked. If you had a FLT3 mutation at diagnosis but your NPM1 was negative in remission, it was hard to show an advantage of a transplant. So I think we're getting much more discriminating about who should or should not get a transplant by MRD testing for NPM1 and that includes the patients who have a concomitant FLT3 mutation. And we're really trying to learn more and more. Do we really need to be doing transplants in those who are MRD-negative? If you have adverse risk genetics and you're MRD-negative, I'll really need good data to tell me not to do a transplant, but I suspect bit by bit, we'll get that data. And we're looking to see if that's really the case there, too. So measurable residual disease testing is helping us discriminate, but there is still a core role of allogeneic transplant. And to reassure you, compared to, I think your allotransplant days were some time ago if I'm right. Dr. John Sweetenham: Yes. Dr. James Foran: Yeah. Well, compared to when you were doing transplants, they're better now and better for patients now. And we get people through graft versus host disease better, and we prevent it better. Dr. John Sweetenham: That's a great answer, James. Thanks for that. It really does help to put it in context, and I think it also leads us on very nicely into what's going to be my final question for you today and perhaps the trickiest, in a way. I think that everything you've told us today really emphasizes the fact that the complexity of AML treatment has increased, primarily because of an improved understanding of the molecular landscape of the disease. And it's a complicated area now. So do you have any thoughts on what type of clinical environment patients with AML should be evaluated and treated in in 2025? Dr. James Foran: Yeah, I want to give you a kind of a cautious answer to that because, you know, I'm a leukemia doctor. I work at a leukemia center and it's what we focus on. And we really pride ourselves on our outcomes and our diagnostics and our clinical trials and so on. I am very aware that the very best oncologists in America work in private practice and work in community practice or in networks, not necessarily at an academic site. And I also know they have a much harder job than I have. They have to know lung cancer, which is molecularly as complicated now as leukemia, and they have to know about breast cancer and things that I don't even know how to spell anymore. So it's not a question of competence or knowledge. It's a question of infrastructure. I'll also put a little caveat saying that I have been taught by Rich Stone at Dana-Farber, where I did a fellowship a long time ago, and believe Rich is right, that I see different patients than the community oncologists see with AML, they're seeing different people. But with that caveat, I think the first thing is you really want to make sure you've got access to excellence, specialized hematopathology, that you can get expedited cytogenetics and NGS testing results back. There was a new drug, approved just a few months ago, actually, for relapsed AML with a KMT2A rearrangement, revumenib. We didn't talk about the menin inhibitors. I'll mention them in just a second. That's a huge area of expansion and growth for us. But they're not found on NGS platforms. And normal cytogenetics might miss a KMT2A-rearrangement. And we're actually going back to FISH panels, believe it or not, on AML, to try to identify who has a KMT2A-rearrangement. And so you really want to make sure you can access the diagnostic platforms for that.  I think the National Referral Labs do an excellent job. Not always a really fast job, but an excellent job. At my institution, I get NGS results back within three days or four days. We just have an expedited platform. Not everybody has that. So that's the key, is you have to be able to make the diagnosis, trust the pathologist, get expedited results. And then it's the question of trying to access the targeted medications because a lot of them are not carried in hospital on formulary or take time to go through an insurance approval process. So that's its own little headache, getting venetoclax, getting gilteritinib, getting an IDH1 inhibitor in first line, if that's what you're going for. And so I think that requires some infrastructure. We have case managers and nurses who really expedite that and help us with it, but that's a lot of work. The other piece of the puzzle is that we're still with AML in the first month and maybe even the second month. We make everybody worse before we make them better. And you have to have really good blood bank support. I can give an outpatient platelet transfusion or red cell transfusion seven days a week. We're just built for that. That's harder to do if you're in a community hospital and you have to be collaborating with a local blood bank. And that's not always dead easy for somebody in practice. So with those caveats, I do find that my colleagues in community practice do a really good job making the diagnosis, starting people on therapy, asking for help. I think the real thing is to be able to have a regional leukemia center that you can collaborate with, connect with, text, call to make sure that you're finding the right patients who need the next level of diagnostics, clinical trial, transplant consults, to really get the best results.  There was some data at ASH a couple of years ago that looked at – the American Society of Hematology and ASCOs had similar reports – that looked at how do we do in academic centers versus community practice for keeping people on therapy. And on average, people were more likely to get six cycles of therapy instead of three cycles of therapy with azacitidine venetoclax at an academic center. Now, maybe it's different patients and maybe they had different cytogenetics and so on, but I think you have to be patient, I think you have to collaborate. But you can treat those patients in the community as long as you've got the infrastructure in place. And we've learned with virtual medicine, with Zoom and other platforms that we can deliver virtual care more effectively with the pandemic and beyond. So I think we're trying to offer virtual consults or virtual support for patients so they can stay in their home, stay in their community, stay with their oncologists, but still get access to excellent diagnostics and supportive care and transplant consults, and so on. I hope that's a reasonable answer to that question. It's a bit of a nuanced answer, which is, I think there's an important role of a leukemia center, and I think there's a really fundamental role of keeping somebody in the community they live in, and how we collaborate is the key to that. And we've spent a lot of time and effort working with the oncologists in our community to try to accomplish that.  John, I want to say two other things. I didn't mention in the molecular platforms that NPM1 mutations, we can now target those on clinical trials with menin inhibitors. We know that NPM1 signals through the Hoxa9/Meis1 pathway. We know that similar pathways are important in KMT2A rearrangements. We know that there are some other rare leukemias like those with NUP98 rearrangement. We can target those with menin inhibitors. The first menin inhibitor, revuminib, was approved by the FDA for KMT2A. We have others going to the FDA later this year for NPM1. There are now pivotal trials and advanced expanded phase 1/2 studies that are showing 30% response rates. And we're looking to see can we add those into the first-line therapy. So, we're finding more targets.  I'll say one last thing about molecular medicine. I know I'm a little off topic here, but I always told patients that getting AML was kind of like being struck by lightning. It's not something you did. Now, obviously, there are risk factors for AML, smoking or obesity or certain farm environments, or radioactive exposures and so on. But bit by bit, we're starting to learn about who's predisposed to AML genetically. We've identified really just in the last five or eight years that DDX41 mutations can be germline half the time. And you always think germline mutations are going to cause AML in a younger patient, but the median age is 60 to 70 just like other AMLs. They actually might do pretty well once they get AML. We've reported that in several papers. And so we're trying to understand who that has a RUNX1 mutation needs germline testing, who with a DDX41 needs germline testing. And we're trying to actually come up with a cleaner pathway for germline testing in patients to really understand predisposition, to help with donor selection, to help with family counseling. So I think those are other areas where a leukemia center can contribute for somebody in who's community practice to understand genomic or genetic complexity in these patients. And we're starting to develop the databases that support that. Dr. John Sweetenham: Yeah, great. Thanks, James. I loved your answer about the clinical environment too. And I know from a patient-centric perspective that I know that patients would certainly appreciate the fact that we're in a situation now where the folks taking care of them will make every effort to keep them close to home if they possibly can.  I want to thank you, James, for an incredible review of a very complex subject and I think you did a great job. I think we all will have learned a lot. And thanks again for being willing to share your insights with us today on the ASCO Daily News Podcast. Dr. James Foran: John, it's my pleasure. And as you know, I'll do anything for a latte, so no problem at all. Dr. John Sweetenham: Okay. I owe you one, so thank you for that.  And thank you to our listeners for your time today. You'll find links to the studies we've discussed today in the transcript of this episode. And finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review and subscribe wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement. Find out more about today's speakers:  Dr. John Sweetenham  Dr. James Foran Follow ASCO on social media: @ASCO on Twitter ASCO on Bluesky ASCO on Facebook  ASCO on LinkedIn  Disclosures:    Dr. John Sweetenham:    No relationships to disclose Dr. James Foran: Stock and Other Ownership Interests: Aurinia Pharmaceuticals Consulting or Advisory Role: Peerview, CTI BioPharma Corp, Remix Therapeutics, Cardinal Health, Medscape, Syndax, Autolus Therapeutics Research Funding (Inst.): Chordia Therapeutics, Abbvie, Actinium Pharmaceuticals, Kura Oncology, Sellas Life Sciences, Novartis, Roivant, Celgene/Bristol-Myers Squibb, Astellas Pharma, SERVIER Travel, Accommodations, Expenses: Peerview

This week, Jonathan is joined by Anna Sureda, Head of the Clinical Hematology Department at Institut Català d'Oncologia - Hospital Duran i Reynals, Barcelona, Spain, and President of the European Society for Blood and Marrow Transplantation (EBMT) Association, to discuss the latest in lymphoma therapies and stem cell transplantation. Timestamps:     (00:00)-Introduction  (01:48)-Memorable travels  (07:44)-Sureda's journey into hematology   (12:40)-Breakthroughs in lymphoma treatment   (17:54)-Advances in stem cell transplantation   (20:26)-EBMT initiatives  (29:17)-Allogeneic transplantation for T cell lymphomas  (34:32)-Challenges in treatment accessibility   (41:35)-How can we ensure health equity?  (46:00)-Advice to young hematologists   (47:40)-Sureda's three wishes for healthcare 

Send us a textThe MedStar Georgetown University Hospital Stem Cell Transplant and Cellular Immunotherapy Program is the only adult, FACT-accredited program in the Washington, D.C., area. We give patients with cancers affecting the blood or immune system and other disorders access to life-saving treatment options not otherwise available in our region. These include:·       Allogeneic stem cell transplant·       Autologous stem cell transplant·       CAR T-cell therapyAlaa Ali, MD, MSC, is a clinician, instructor, and investigator in clinical and translational research at MedStar Georgetown's Stem Cell Transplant and Cellular Immunotherapy program. Concurrrently, he holds the position of Assistant Professor at Georgetown University School of Medicine.For an interview with Dr. Ali, or for more information about this podcast, contact MedStar Georgetown University Hospital Manager Media Relations, Ryan.M.Miller2@Medstar.net. Learn more about Dr. Ali. For more episodes of MedStar Health DocTalk, go to medstarhealth.org/doctalk.

Editor's Summary by Linda Brubaker, MD, and Preeti Malani, MD, MSJ, Deputy Editors of JAMA, the Journal of the American Medical Association, for articles published from December 7-13, 2024.

Allogeneic stem cell transplantation is a potentially life-saving therapy for some patients with hematologic and bone marrow cancers and certain nonmalignant conditions such as sickle cell disease. Hermioni L. Amonoo, MD, MPP, MPH, of Harvard Medical School and Dana-Farber Cancer Institute, joins JAMA Deputy Editor Kristin Walter, MD, MS, to discuss the process of allogeneic stem cell donation. Related Content: Allogeneic Stem Cell Donation

In today's episode, we welcome back Dr. Amar Kelkar for part 2 of our two-part discussion on allogeneic transplant. In this episode, we build on our prior discussion regarding transplant, this time focusing on transplant for the treatment of AML. Episode contents: - What are the different conditioning regimens available? - How do we decide which regimen is optimal for our patients? - What is the role of MRD testing? - What is the role of maintenance therapy post-transplant? - What are treatment options for GVHD? - A discussion on racial disparities in transplant ****Get paid to participate in market research surveys: https://affiliatepanel.members-only.online/FOC_24?utm_campaign=FOC&utm_source=email&utm_medium=email** Want to review the show notes for this episode and others? Check out our website: https://www.thefellowoncall.com/our-episodesLove what you hear? Tell a friend and leave a review on our podcast streaming platforms!Twitter: @TheFellowOnCallInstagram: @TheFellowOnCallListen in on: Apple Podcast, Spotify, and Google Podcast

Welcome to the second installment of an exclusive 8-part ASTCT Talks series, supported by an educational grant from Sanofi US. In this series, ASTCT President Dr. Corey Cutler speaks with authors from each article in the latest Graft versus Host Disease and Late Effects Following Allogeneic Transplantation Journal collection. In this episode, Dr. Cutler is joined by Dr. Nathaniel S. Treister, a recognized expert in oral medicine, to discuss the intricacies of oral chronic GVHD and its impact on oral health following allogeneic hematopoietic cell transplantation. They explore the diagnostic criteria, effective management strategies, and long-term care considerations for patients, highlighting the importance of both supportive care and multidisciplinary collaboration. For further insights, read Dr. Treister's article, “Oral Chronic Graft-versus-Host Disease and Oral Health after Allogeneic Hematopoietic Cell Transplantation — What the Care Team Needs to Know”, and stay tuned as Dr. Cutler and authors continue to provide a comprehensive guide on cGVHD management through this supplement series.

In today's episode, we welcome back Dr. Amar Kelkar for part 1 of our two-part discussion on allogeneic transplant. In this episode, we discuss the fundamental approach to patient selection and stem cell source selection. As you all know from this series, allogeneic transplants play a pivotal role in the management of AML. Dr. Kelkar's pearls of wisdom help make this confusing topic so much more approachable!Episode contents: - What factors do we incorporate when considering a patient for allogeneic transplant? - How do we use HLA-matching?- What are the pros and cons of the different sources of stem cells? ****Get paid to participate in market research surveys: https://affiliatepanel.members-only.online/FOC_24?utm_campaign=FOC&utm_source=email&utm_medium=email** Want to review the show notes for this episode and others? Check out our website: https://www.thefellowoncall.com/our-episodesLove what you hear? Tell a friend and leave a review on our podcast streaming platforms!Twitter: @TheFellowOnCallInstagram: @TheFellowOnCallListen in on: Apple Podcast, Spotify, and Google Podcast

In this episode of LifeSciences 360, we dive into the fascinating world of cell and gene therapy manufacturing with Carlos Yuraszeck. With over 16 years of experience, Carlos shares his deep insights into the unique challenges, opportunities, and innovations in the field, offering a detailed look into what it takes to bring life-saving therapies to patients. We cover everything from the design of manufacturing facilities to the complexities of quality systems, patient-centric innovations, and the future of allogeneic therapies.If you're interested in the life sciences, cell and gene therapy, or just curious about cutting-edge advancements in medicine, this episode is for you!Chapters:00:00 - Intro  00:02 - Understanding Cell and Gene Therapy Facilities  00:09 - Challenges in Cell Therapy Facility Design  00:26 - Automation in Manufacturing  00:42 - Balancing Quality, Cost, and Time  00:53 - Patient-Centric Manufacturing  01:21 - Guest Introduction: Carlos Yuraszeck  02:06 - Carlos's Journey in Cell and Gene Therapy  03:21 - Unique Factors in Facility Design  04:14 - Making Facilities Operational  05:09 - Subscription Appeal  06:13 - Autologous vs. Allogeneic Cell Therapies Explained  08:13 - Adjusting Processes Based on Patient Variability  09:37 - Stem Cell Derived Therapies  10:39 - Biotech Companies: Autologous or Allogeneic?  12:07 - Strategic Decisions in Facility Design  14:50 - Phase-Appropriate Quality Systems  16:45 - Regulatory Flexibility and Urgency for Patients  18:08 - Change Control in Early vs. Late Phases  19:02 - Batch Records and Operator Judgment  20:27 - Training Focus for Different Phases  22:38 - Balancing Regulatory Requirements and Innovation  24:32 - Risk Assessment Based on Patient Needs  26:18 - The Potential of CAR T Therapies  28:05 - The Allogeneic Space and Future Prospects  31:00 - The Transformative Impact of Cell Therapy  32:22 - Carlos's Career Lessons and Fear of the Unknown  34:45 - Closing Remarks and Subscription Reminder  36:37 - Outro---

This week, we continue our discussion on consolidation and maintenance therapies for AML, this time highlighting the role of allogeneic stem cell transplants. This episode builds on our prior episode, so if you have not listened to this just yet, we highly recommend doing so! Episode contents: - A recap on approach to AML consolidation - The role of allogeneic transplants - The role of MRD testing in AML management****Have some time and want to make some extra money? Get paid to participate in market research surveys: https://affiliatepanel.members-only.online/FOC_24?utm_campaign=FOC&utm_source=email&utm_medium=email** Want to review the show notes for this episode and others? Check out our website: https://www.thefellowoncall.com/our-episodesLove what you hear? Tell a friend and leave a review on our podcast streaming platforms!Twitter: @TheFellowOnCallInstagram: @TheFellowOnCallListen in on: Apple Podcast, Spotify, and Google Podcast

We're online with Adrian Rawcliffe, the CEO of Adaptimmune, the TCR cell therapy company behind the first engineered cell therapy for solid tumors that was approved for a rare form of sarcoma. We talked about Tecelra's commercial rollout. We also talked about what's next in cell therapy, and Philly Cheesesteak vs Fish and Chips. — — — Thank you to today's sponsor, Merck, who can support your antibody drug discovery. Learn more and claim a cool antibody pin here: https://bit.ly/3AhZFUA — — — ⭐️ ABOUT THE SPEAKER Adrian Rawcliffe has been in the biopharma industry for over 20 years and has worked in high positions for companies such as GSK. Adrian has been with Adaptimmune for almost 10 years, serving as CFO before becoming the CEO in 2019. I didn't know him personally but have heard and seen great things about him.

BUFFALO, NY- October 11, 2024 – A new #editorial was #published in Oncotarget's Volume 15 on October 1, 2024, entitled, “Transplant or no transplant for TP53 mutated AML.” As highlighted in this editorial, TP53 mutations (mut) occur in 10–15% of acute myeloid leukemia (AML) cases, commonly associated with therapy-related AML (t-AML) and complex cytogenetics (CG). TP53-mut AML is inherently resistant to conventional chemotherapies and continues to show a poor prognosis, even with venetoclax-based therapies. Allogeneic hematopoietic stem cell transplant (allo-HCT) remains a potential curative option, though only 10–15% of patients receive it. In a recent study, allo-HCT was the only variable significantly improving survival, despite only 16% of patients successfully bridging to it. In their editorial, researchers Talha Badar, Moazzam Shahzad, Ehab Atallah, Mark R. Litzow, and Mohamed A. Kharfan-Dabaja from the Division of Hematology-Oncology and Blood and Marrow Transplantation and Cellular Therapy Program at Mayo Clinic (Jacksonville, Florida) evaluated the outcomes of TP53-mutated AML patients based on data from the Consortium of Myeloid Malignancies and Neoplastic Diseases (COMMAND). The study found a “dismal” survival rate of 8.5 months, with no significant difference among treatment types, and allo-HCT was the only variable associated with improved survival. The authors also report on the “better long-term outcomes” when allo-HCT was performed during Complete Remission 1 (CR1) in previous observations. They acknowledge the limitations of their retrospective analysis, including selection bias, data heterogeneity from participating institutions, and the lack of complete molecular data prior to allo-HCT that might have influenced the results. Nevertheless, the findings are encouraging and suggest that allo-HCT improves long-term outcomes in this poor prognostic disease, where effective therapies remain limited. “In summary, this study reported improved survival when allo-HTC was performed in CR1 versus after later lines of therapy.” DOI - https://doi.org/10.18632/oncotarget.28652 Correspondence to - Talha Badar - badar.talha@mayo.edu Video short - https://www.youtube.com/watch?v=OQue9gbqsxE Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28652 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, AML, TP53 mutation, allogeneic stem cell transplant About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science). To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

In this week's episode we'll discuss a novel tripartite fusion drives treatment resistance in acute promyelocytic leukemia. In some patients with atypical APL, these novel retinoic acid receptor gene fusions result in truncation of the ligand binding domain of the retinoic acid receptor protein, resulting in non-responsiveness to treatment with all-trans retinoic acid. After that: managing immune thrombotic thrombocytopenia or iTTP without therapeutic plasma exchange, or TPE. Finally, hope for motherhood after allogeneic HCT.Featured Articles: Critical role of tripartite fusion and LBD truncation in certain RARA- and all RARG-related atypical APLManagement of immune thrombotic thrombocytopenic purpura without therapeutic plasma exchangeHope for motherhood: pregnancy after allogeneic hematopoietic cell transplantation (a national multicenter study)

We love to hear from our listeners. Send us a message.Allogene Therapeutics' EVP of R&D and CMO, Dr. Zachary Roberts, penned an original article for Cell & Gene titled, The Path Forward for CLL is Allogeneic. In his article, Dr. Roberts explains that chronic lymphocytic leukemia (CLL) is the most common leukemia in the U.S. And that while CLL remains a disease that is managed, it is not one that is often cured. In this episode, Host Erin Harris follows up Roberts' article with in-depth questions around existing issues with current CAR T approaches, "auto versus allo," and why allogeneic is the path forward. They also discuss how and why allogeneic therapies are truly scalable.

We love to hear from our listeners. Send us a message. Kristin Yarema, Ph.D. thinks the progress of CAR T therapeutics is allogeneic. In fact, she says CAR T-cell therapies have to become a one-to-many proposition, if their early autologous success can possibly live up to the promise of offering widespread accessibility to life-saving treatments. Dr. Yarema is the newly-appointed CEO at Poseida Therapeutics, a company we first covered with founding CEO Eric Ostertag, Ph.D. On this episode of the Business of Biotech, we'll learn about Dr. Yarema, how she earned the company's reins, how Poseida is positioning itself to crack the allogeneic CAR T code, and how strategic collaborations with the likes of Astellas and Roche are fueling the effort. Complex protein-based therapies — think antibody-drug conjugates and fusion proteins — don't play by the same process-engineering rules as small molecules and more traditional biologics. They require developers to see the unforeseen and embrace new roles and responsibilities in sourcing both raw materials and outsourced expertise. Successful developers can't let this winding road slow their time to IND. Join Bioprocess Online Live on Thursday, August 8 at 11 AM ET for a free, virtual, and interactive discussion on early workflow considerations for developers of complex protein-based therapeutics. Register now, bring your questions for our expert panel, and join us on the 8th!

In this week's episode we'll discuss the safety and efficacy of acalabrutinib, venetoclax and obinutuzumab in relapsed/refractory CLL; learn more about alternative donor transplantation for severe aplastic anemia and discuss clonal relapse dynamics in acute myeloid leukemia following allogeneic hematopoietic cell transplantation.Featured Articles: Acalabrutinib, venetoclax and obinutuzumab in relapsed/refractory CLL: Final efficacy and ctDNA analysis of the CLL2-BAAG trial Alternative donor transplantation for severe aplastic anemia: a comparative study of the SAAWP EBMT Clonal relapse dynamics in acute myeloid leukemia following allogeneic hematopoietic cell transplantation 

This week on Data in Biotech, we're joined by Amy Gamber, VP of Manufacturing at Atara Biotherapeutics, an allogeneic T-cell immunotherapy company developing off-the-shelf treatments to help achieve faster patient outcomes. As a treatment that sits at the cutting edge of options available for cancer and autoimmune disease, host Ross Katz explores how Atara is able to deliver personalized medicine that can be with the patient inside a three-day window.   Amy is clear-eyed about what works well in this field and what doesn't. We gain insight into the complexity of developing this type of cell therapy and the subsequent production challenges of manufacturing at scale. We also cover the manufacturing process, corresponding data problems Amy encounters on a day-to-day basis in her role as VP of Manufacturing, and the strategies she employs to overcome them. Amy discusses the importance of continuous quality monitoring and the need to introduce it from an early stage to see how a program changes through the development phases. She highlights the importance of data as a tool for the ‘detective work' needed to understand where problems arise during manufacturing. Finally, she and Ross close the episode by discussing the future of cell therapy manufacturing, a world where modeling enables predictive QC, the possibilities of AI, and the need to standardize data.  Data in Biotech is a fortnightly podcast exploring how companies leverage data innovation in the life sciences. Chapter Markers [1:56] Introduction to Amy and the manufacturing process at Atara, including the importance of cryo storage to facilitate faster patient treatment.   [6:37] Amy and Ross discuss the challenge of donor variability in cell therapy manufacturing and how to manage it. [12:38] Ross asks about scaling cell therapy production and the different considerations for small batch versus commercial-scale manufacturing. [15:47] Amy discusses the importance of continuous quality monitoring, highlighting the value of tracking metrics to ensure quality control and identify improvement opportunities [18:46] Ross moves the focus to automating data collection, as he and Amy emphasize the need for more efficient data access and analysis for timely decision-making. [20:50] Ross and Amy explore the data challenges biotechnology companies face, including the problem with manual data processes, creating feedback loops, and regulatory compliance. [25:16] Amy explains how Atara addressed manufacturing efficiency challenges, the importance of ‘detective work' to understand problem causes, and the process of solving them.  [33:28] Ross and Amy examine how to use data to gather meaningful manufacturing insights, particularly identifying true signals when analyzing small datasets. [36:33] Ross talks about predictive QC measures as the solution to the point Amy makes about being able to guarantee product quality from the outset. [37:31] Amy gives her perspective on the future of biotech manufacturing, the role of AI, predictive modeling, and the need for standardization in the industry. Download our latest white paper on “Using Machine Learning to Implement Mid-Manufacture Quality Control in the Biotech Sector.” Visit this link: https://connect.corrdyn.com/biotech-ml

Professor Johannes Schetelig joins us to discuss the results of the ASAP phase 3 trial comparing remission induction with immediate allogeneic haematopoietic stem cell transplantation for patients with relapsed or poor responsive acute myeloid leukaemia.Read the full article:https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(24)00065-6/fulltext?dgcid=buzzsprout_icw_podcast_generic_lanhaeContinue this conversation on social!Follow us today at...https://twitter.com/thelancethttps://instagram.com/thelancetgrouphttps://facebook.com/thelancetmedicaljournalhttps://linkedIn.com/company/the-lancethttps://youtube.com/thelancettv

Dr. Guy Handley, Assistant Professor of Medicine with the Division of Infectious Diseases, USF Morsani College of Medicine, provides an overview of Human Herpesvirus 6 in Stem Cell Transplant Patients. Dr. Handley uses clinical cases to describe several scenarios related to HHV6 infection. Topics discussed include background, HHV6 latency, reactivation, clinical presentation, encephalitis, treatment strategies, and outcomes. Guidelines for HHV care are also discussed. Dr. Handley closes by discussing controversies and future directions in HHV6 management.

In this week's episode we'll discuss the utility of MRD in identifying patients with NPM1 AML who benefit from allogeneic transplant in first remission, learn more about the contribution of circulating hematopoietic stem/progenitor cell subsets to human hematopoietic hemostasis, and discuss the role of Let-7 miRNAs in regulation of BCL11A transcription and hemoglobin switching. Featured Articles:Postinduction molecular MRD identifies patients with NPM1 AML who benefit from allogeneic transplant in first remissionlet-7 miRNAs repress HIC2 to regulate BCL11A transcription and hemoglobin switching Circulating Hematopoietic Stem/Progenitor Cell subsets contribute to human hematopoietic homeostasis

Orca Bio's CMO, Dr. Scott McClellan, joins Erin Harris on this episode of Cell & Gene: The Podcast to discuss how and why toxicities continue to stymie allogeneic cell therapies. They cover Orca Bio's plan to potentially lowering the risk of GvHD as well as Orca-T, the investigational high-precision allogeneic cell therapy being evaluated in clinical trials for the treatment of multiple hematologic malignancies.

In this episode of Biohacking Superhuman Performance with guest Dr. Amy Killen, we explore the world of stem cells - what they are, how they perform in the body, and how they work to increase longevity. Stem cell therapy is still being researched and regulated, but there is an amazing amount of potential for healing and increasing longevity with these powerful cells.    We also dive into exosomes - the small molecules that can penetrate places that stem cells can't. Aesthetic procedures are popular with exosomes- they have the power to restore hair and rejuvenate skin, and are used in many skincare products. We even go over ovarian rejuvenation and Rapamycin, a potential prescription drug for delaying menopause.     Overall, this episode offers guidance on stimulating stem cells right in your own home. We talk through different tips such as supplements, fasting, and getting sun in a healthy way for those who aren't in a place to budget for stem cell therapy.    Dr. Amy Killen is an outspoken advocate for empowering people to look and feel their best by merging lifestyle modification, integrative medicine, body-identical hormones, energy modalities, and stem cell therapies. She is the founder and CEO of the Human Optimization Project (HOP), a longevity-based subscription supplement company that stays on top of the science and constantly updates its ingredients for customers who can't devote their lives to reading the latest research sourcing the best therapies. I absolutely love her Instagram. You guys need to go follow her @dr.amybkillen.    Get Rapid Rebound oral BPC157 with PEA and AOD9604. Visit https://lelabs.co/ and use code NAT20 Thank you to our sponsors for making this episode possible:   Sensate: Use code NAT at www.getsensate.com/Nat   BEAM Minerals: Go to https://www.beamminerals.com code Nathalie to get 20% off your order   Profound Health: Use code longevity15 to save 15% off your first order at https://profound-health.com/ Find more from Dr. Amy B. Killen:  Website: https://dramykillen.com/  Youtube: https://www.youtube.com/channel/UCBLk8xTa4qzE7J8bID7KIKg  Instagram: @dr.amybkillen Human Optimization Project (HOP box): https://hopbox.life/    Find more from Nathalie: YouTube: https://www.youtube.com/channel/UCmholC48MqRC50UffIZOMOQ Facebook Group: https://www.facebook.com/groups/biohackingsuperhumanperformance Instagram: https://www.instagram.com/nathalieniddam/ Website: https://www.NatNiddam.com Join Nat's Membership Community: https://www.natniddam.com/bsp-community   Work with Nat: Book Your 20 Minute Optimization Consult: https://calendly.com/nniddam/intro-call?month=2021-08   What We Discuss:  (1:30) Women's unfounded fear around Hormone Replacement Therapy  (5:38) When you start hormones early you reduce the risk of major women-killing diseases such as heart disease and obesity.  (7:20) The world of stem cells and exosomes- what they are, and why they are important.   (11:20) MSC cells are very safe, don't cause cancer, and they're not embryonic cells (no fetus is harmed!)  (13:50) The Pros of using birth product stem cells (from the placenta and umbilical cord) (18:08) The environment where the stem cells are placed matters.  (22:50) Helpful therapies to stack with stem cell therapy.  (30:50) What the research shows about stem cell therapy and diseases like MS. (34:15) Exosomes - one of the signaling molecules of stem cells. i (41:37) Fat transfers are a great natural filler, but adding stem cells creates better results.  (44:50) How to stimulate stem cells naturally if you don't have the budget for stem cell therapy.  (58:30) The overuse of supplements and HOP box.  (1:04:00) Rapamycin and ovarian rejuvenation using stem cells.  (1:10:38) Where to find more from Dr. Amy B Killen.   Key Takeaways:   1. Stem cells do two main things. They can replicate themselves and they can turn into other types of cells. Stem cells send out signals so that an injured area heals itself. When we age, we have fewer, less active stem cells. They aren't able to signal repair as well, so recovery takes much longer. Stem cell therapy gives you back signaling molecules so that you're able to heal yourself faster. Autologous stem cells are your own cells from fat tissue or bone marrow.  Allogeneic stem cells come from somewhere else - like birth tissue products (placenta/umbilical cord).  The environment affects the stem cells. The area where you put stem cells matters, and if your body is not healthy, is inflamed, or has uncontrolled blood sugar issues, the cells cannot work as well. For example: a smoker or poorly controlled diabetic won't have the best results. Take the time to get in the best shape that you can before a costly procedure like stem cell therapy.  Exosomes are powerful signaling molecules that can be transported into cells to change the behavior of that cell. These small molecules can pass through the skin- they can be applied topically - and they can cross the blood brain barrier to decrease inflammation. They're great for aesthetic purposes like hair restoration and skin rejuvenation. The FDA regulates the application - they can only be applied topically.  Bonus takeaway:  No drug can do what hormones do when used properly at the right time in the right way. If you want to be healthy for longer, especially after menopause, you need to be looking into HRT. 

Wael Hashad, Chief Executive Officer of Longeveron, is focused on developing cell therapy for aging-related conditions such as aging frailty, dementia, and Alzheimer's disease. Using mesenchymal stem cells, also known as medicinal signaling cells, obtained from healthy donors 18-45, Longeveron is seeing promising results in clinical trials with improvements in brain volume and cognitive function. This approach is also being explored in the pursuit of a treatment for hypoplastic left heart syndrome, a rare congenital heart disease. Wael explains, "We believe there is a huge unmet need for bringing safe and effective products to try to slow the progression of the disease, improve the quality of life, and reduce the burden on the caregivers of such a disease. As for the aging frailty in general, as you know, with aging, there are a lot of things that affect the vascular system, muscle wasting, and all of those things that affect the quality of life during the aging years of an individual. Anything we can impact to improve the quality of life and the ability to lead a normal life in the aging years is definitely one of our goals." "Lomecel-B was initially licensed from the University of Miami to Longeveron. It is mesenchymal stem cells. As I said, we get GMP-grade donations of bone marrow from healthy adults and volunteers aged 18 to 45. Then we take this donation, harvest them in our facility in Miami, grow the cells, and then do all the required testing and release criteria to ensure safety. It is allogeneic, meaning that it is off the shelf, that any patient can take these cells. It is not autologous cells. It is allogeneic cells, giving it a much broader application. We are able to produce enough quantities from each donation to support these patients with aging frailty, Alzheimer's, or dementia." #Longeveron #CellTherapy #Aging #MedicinalSignalingCells #MSC #AlzheimersDisease #Dementia #AgingFrailty #RareDisease longeveron.com  Download the transcript here

Wael Hashad, Chief Executive Officer of Longeveron, is focused on developing cell therapy for aging-related conditions such as aging frailty, dementia, and Alzheimer's disease. Using mesenchymal stem cells, also known as medicinal signaling cells, obtained from healthy donors 18-45, Longeveron is seeing promising results in clinical trials with improvements in brain volume and cognitive function. This approach is also being explored in the pursuit of a treatment for hypoplastic left heart syndrome, a rare congenital heart disease. Wael explains, "We believe there is a huge unmet need for bringing safe and effective products to try to slow the progression of the disease, improve the quality of life, and reduce the burden on the caregivers of such a disease. As for the aging frailty in general, as you know, with aging, there are a lot of things that affect the vascular system, muscle wasting, and all of those things that affect the quality of life during the aging years of an individual. Anything we can impact to improve the quality of life and the ability to lead a normal life in the aging years is definitely one of our goals." "Lomecel-B was initially licensed from the University of Miami to Longeveron. It is mesenchymal stem cells. As I said, we get GMP-grade donations of bone marrow from healthy adults and volunteers aged 18 to 45. Then we take this donation, harvest them in our facility in Miami, grow the cells, and then do all the required testing and release criteria to ensure safety. It is allogeneic, meaning that it is off the shelf, that any patient can take these cells. It is not autologous cells. It is allogeneic cells, giving it a much broader application. We are able to produce enough quantities from each donation to support these patients with aging frailty, Alzheimer's, or dementia." #Longeveron #CellTherapy #Aging #MedicinalSignalingCells #MSC #AlzheimersDisease #Dementia #AgingFrailty #RareDisease longeveron.com  Listen to the podcast here

The process of identifying which patients with acute myeloid leukemia (AML) can benefit from allogeneic stem cell transplantation in first complete remission (CR1) has taken a step forward thanks to analysis of the UK NCRI AML17 and AML19 studies, reported at the 65th ASH Annual Meeting and Exposition. Patients who achieved molecular residual disease (MRD) negativity in their peripheral blood were at low risk of relapse, and had no benefit from allogeneic transplant in CR1, including those with the FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication mutation of the NPM1 (nucleophosmin 1) gene, that is generally considered to be a marker of poor risk. Peter Goodwin spoke with Jad Othman, MBBS, from King's College London and the Guy's and St Thomas' Hospital in London, and now based at the Royal North Shore Hospital in Sydney, Australia. Othman explained how testing for the FLT3 mutation of the NPM1 gene can be used along with assessment of molecular MRD to help choose patients who can benefit from transplant and spare those for whom the risk/benefit ratio is adverse.

On today's episode we'll discuss the prognostic significance of the ETP phenotype in children with T-cell ALL, address knowledge gaps in the management of chronic granulomatous disease and learn about the effects of pathogenic and likely pathogenic variants for inherited hemostasis disorders.

Allogeneic hematopoietic cell transplantation (HCT) in patients with myelodysplastic syndrome (MDS) improves overall survival. The authors evaluated the impact of MDS genetics on the benefit of HCT in a biological assignment (donor v no donor) study. https://pubmed.ncbi.nlm.nih.gov/37607457/ ALSO AS VIDEO ON https://youtu.be/JbHS_-2sJQc CONNECT WITH US https://twitter.com/TheEBMT_Trainee https://www.ebmt.org/trainee-committee https://twitter.com/CarmeloGurnari

In this week's episode, we'll discuss if some patients with relapsed or refractory primary mediastinal B-cell lymphoma can be cured by checkpoint blockade alone. Next, autologous CAR T cells are highly effective, yet not always feasible in children with relapsed or refractory B-cell precursor acute lymphoblastic leukemia. Lastly, we'll discuss ironing out beta-thalassemia during pregnancy.

Jeff Liter is the CEO and Founder of Luminary Therapeutics, which is using gamma delta cells in their approach to CART-T cell therapy because of the ability of these cells to infiltrate solid tumors. With a multi-targeting system, Luminary has demonstrated promise treating multiple types of solid tumors, blood tumors, and autoimmune diseases. Their goal is to create a scalable model to manufacture allogeneic cells to drive down the cost and availability of effective cell therapies. Jeff explains, "We're focused primarily on three big challenges in the CAR-T industry. The first is the overall manufacturing approach and cost. The second is why do CAR-Ts, to date, not work in solid tumors. And then finally, the third is antigen escape and relapse of patients currently being treated by CAR-T therapies."  "We have moved into coming back to the manufacturing area. We have moved into an allogeneic platform, which for your listeners, if they're not familiar with that term, means that we can make multiple products from one healthy donor. And we do that in a very special way, using gamma delta cells and preserving both subsets of the gamma delta cells. Then we also add some immune cloaking with our non-viral gene engineering, and that makes us very unique on the allogeneic front." "If you look at those 800 companies, probably 80, 85% of them use what's called alpha beta normal white blood T cells. A fair number of companies, maybe 7% to 8%, use NK cells. And then there's a new group using a different kind of subset of cells called IPSC. But in the gamma delta, there are only 12 to maybe 15 companies. So we're very differentiated on that front from the 800. And then, as I noted, we are the only company to have both Vdelta1 and Vdelta2 subsets in our final product."   #LuminaryTherapeutics #CARTCellTherapy #CARTTherapies #Allogeneic #Autologous #CellTherapy #GammaDeltaCells #SolidTumors #Cancer #BloodCancers #AutoimmuneDiseases luminarytx.com Listen to the podcast here

Jeff Liter is the CEO and Founder of Luminary Therapeutics, which is using gamma delta cells in their approach to CART-T cell therapy because of the ability of these cells to infiltrate solid tumors. With a multi-targeting system, Luminary has demonstrated promise treating multiple types of solid tumors, blood tumors, and autoimmune diseases. Their goal is to create a scalable model to manufacture allogeneic cells to drive down the cost and availability of effective cell therapies. Jeff explains, "We're focused primarily on three big challenges in the CAR-T industry. The first is the overall manufacturing approach and cost. The second is why do CAR-Ts, to date, not work in solid tumors. And then finally, the third is antigen escape and relapse of patients currently being treated by CAR-T therapies."  "We have moved into coming back to the manufacturing area. We have moved into an allogeneic platform, which for your listeners, if they're not familiar with that term, means that we can make multiple products from one healthy donor. And we do that in a very special way, using gamma delta cells and preserving both subsets of the gamma delta cells. Then we also add some immune cloaking with our non-viral gene engineering, and that makes us very unique on the allogeneic front." "If you look at those 800 companies, probably 80, 85% of them use what's called alpha beta normal white blood T cells. A fair number of companies, maybe 7% to 8%, use NK cells. And then there's a new group using a different kind of subset of cells called IPSC. But in the gamma delta, there are only 12 to maybe 15 companies. So we're very differentiated on that front from the 800. And then, as I noted, we are the only company to have both Vdelta1 and Vdelta2 subsets in our final product."   #LuminaryTherapeutics #CARTCellTherapy #CARTTherapies #Allogeneic #Autologous #CellTherapy #GammaDeltaCells #SolidTumors #Cancer #BloodCancers #AutoimmuneDiseases luminarytx.com Download the transcript here

Allogeneic stem cell transplantation (alloSCT) remains a valuable treatment option for fit patients with acute myeloid leukemia (AML), and the... The post The important role of transplantation in AML: improving outcomes for patients & the value of pre-transplant MRD appeared first on VJHemOnc.

Allogeneic stem cell transplantation (alloSCT) remains a valuable treatment option for fit patients with acute myeloid leukemia (AML), and the... The post The important role of transplantation in AML: improving outcomes for patients & the value of pre-transplant MRD appeared first on VJHemOnc.

In December 2022, Atara Biotherapeutics' Ebvallo received European Commission approval as the first-ever therapy for adults and children with EBV+ PTLD. The ground-breaking approval represents the first approval of an allogeneic T-cell immunotherapy ever, globally. Atara Bio's CEO, Pascal Touchon, talks to Cell & Gene: The Podcast's Erin Harris about the biopharma's path to regulatory approval, commercialization plans for Ebvallo, an in-depth look at EBV+ PTLD, the connection between EBV and serious diseases like multiple sclerosis (MS), and much more.

Marty Giedlin, vice president and head of technology operations at Senti Bio, speaks with moderator Ben Locwin, vice president of project solutions at Black Diamond Networks, to share his experiences and provide advice on how allogeneic cell therapy companies can implement better manufacturing strategies. He discusses understanding and managing manufacturing expectations, letting biology drive strategic operations, and why data must drive chemistry, manufacturing, and controls. Giedlin also outlines how to best characterize starting materials, why a one-size-fits-all approach to process manufacturing is unrealistic, his predictions for the industry over the next five years, and his work developing NK-CAR treatments for various cancer cells. Links from this episode:  Evaluating Biopharma Senti Biosciences Black Diamond Networks Evaluating Biopharma boiler: Evaluating Biopharma taps into the insight and experience of biopharmaceutical leaders so today's decision makers can leverage their knowledge, learn from their successes, and avoid repeating similar mistakes. This series offers a new guest and moderator with each episode and aims to equip executives and science leaders with the necessary information to make better business and process decisions. The Evaluating Biopharma podcast is a reproduction of content originally presented at recent Evaluating Biopharma digital and educational networking events.

Brian Culley is the CEO of Lineage Cell Therapeutics, a clinical-stage biotech company whose mission is to pioneer a new branch of medicine based on transplanting specific cell types to patients with serious medical conditions. Lineage currently has several programs undergoing clinical and preclinical investigation for indications in ophthalmology, neurology, and oncology. Prior to joining Lineage in 2018, Brian held a number of senior leadership and executive roles at various biotech companies, including Artemis Therapeutics and Mast Therapeutics. Brian has more than 25 years of business and scientific experience in the life sciences industry and started at the bench, working in drug development research at Neurocrine Biosciences. He received a B.S. in biology from Boston College, a master's in biochemistry and molecular biology from the University of California, Santa Barbara, and an M.B.A. from The Johnson School of Business at Cornell University.In this episode, we discuss Brian's path to biotech senior leadership, Lineage's proprietary platform technology, and bringing partnered programs to the clinic.Hosted by Joe Varriale.This episode was recorded on September 27th, 2022.

In this bonus episode Associate Editor, Dr. Helen Heslop discusses Banked Allogeneic Immune Effector Cells with Blood Author Dr. Jeffrey Miller.  

In this week's episode we'll discuss the benefits of allogeneic hematopoietic stem cell transplantation in older and medically infirm patients with AML, learn more about the efficacy and safety of cilta-cel in patients with progressive multiple myeloma after exposure to other BCMA-targeting agents, and review the role of anti-CD20 therapy in relapsed immune-mediated thrombotic thrombocytopenic purpura.

In this episode, Associate Editor, Dr. Robert Zeiser and Dr. Yi-Bin Chen discuss the series on How I Manage High-Risk Patients Following Allogeneic Hematopoietic Cell Transplantation.

Is a pre-treatment with low dose cyclosporine immunosuppression necessary to limit allogeneic cardiosphere-derived cell therapy rejection? Listen as Associate Editor Dr. Amanda LeBlanc (University of Louisville) interviews senior author Dr. John Canty (University of Buffalo) and expert Dr. Fabio Recchia (Scuola Superiore Sant'Anna; Temple University) about the latest study by Techiryan et al. In this blinded randomized controlled trial using swine, the authors tested whether low dose cyclosporine could be initiated at the time of reperfusion. In contrast to previous studies, the authors were not able to reproduce the cardioprotective effects demonstrated by allogeneic CDCs without cyclosporine. Conducting large animal studies is like conducting an orchestra, with many members of the lab playing specific roles. What is it like to take a pig with a balloon occluder in their anterior descending artery 100 yards down the hall to the imaging center for a CT scan while the animal is having an acute infarction? Listen as we discuss the challenges of blinded preclinical studies and how large animal studies can offer unique preclinical insights that may translate more effectively to clinical treatment of cardiovascular disease.   George Techiryan, Brian R. Weil, Rebeccah F. Young, and John M. Canty Jr. Widespread intracoronary allogeneic cardiosphere-derived cell therapy with and without cyclosporine in reperfused myocardial infarction Am J Physiol Heart Circ Physiol, published October 17, 2022. DOI: 10.1152/ajpheart.00373.2022

This podcast explores hematopoietic stem cell transplant in diffuse cutaneous systemic sclerosis (dcSSc) and the potential role of FCR001, an investigational allogeneic cell therapy. We are pleased to be joined by leading sclerosis expert Dinesh Khanna MD, MSc.  Dr. Khanna is the Sclerosis Program Director at University of Michigan, USA, Dr. Khanna discusses the symptoms, severity, and progressiveness of sclerosis, focusing on dcSSc. Dr. Khanna further explores the current treatment options, the unmet medical need, and the future of FCR001 and allogeneic stem cell transplants. This podcast is funded and developed by Talaris Therapeutics, Inc. Talaris Therapeutics is a late-clinical stage cell therapy company that is developing an investigational allogeneic stem cell therapy.

Mayo Clinic performed its first bone marrow transplant in 1963 and today hundreds of people receive blood and marrow transplants every year at Mayo Clinic in Arizona, Florida and Minnesota. Recently, Mayo Clinic in Rochester, Minnesota celebrated its 10,000th blood and marrow transplant.Bone marrow transplant is used to treat blood cancers and related disorders by infusing healthy blood-forming stem cells into your body to replace unhealthy bone marrow. A bone marrow transplant is also called a stem cell transplant. Bone marrow transplants may use cells from your own body, called autologous transplant, or from a donor, known as allogeneic transplant. Autologous stem cell transplants are typically used in people who are producing enough bone marrow but need to undergo high doses of chemotherapy and radiation to cure their disease. These treatments are likely to damage the bone marrow. Prior to treatment, healthy bone marrow cells are collected, frozen and stored for later use. After treatment, the stem cells are infused back into the patient to repopulate the bone marrow.Allogeneic bone marrow transplant is used when there is underlying bone marrow failure syndrome or for certain types of bone cancers and blood cancers. In those cases, donor bone marrow is needed to replace the diseased bone marrow.One common complication of allogenic transplant is developing graft versus host disease. This condition occurs when the donor stem cells see the body's tissues and organs as something foreign and attack them. Researchers have now discovered metabolic markers that can predict a person's risk for developing severe graft versus host disease, allowing for a more personalized treatment approach."Graft versus host disease occurs in patients that have had an allogeneic transplant from a donor," explains Dr. William Hogan, director of the Mayo Clinic Blood and Bone Marrow Transplant Program in Minnesota. "And this is where the donor immune system doesn't just recognize the leukemia that we're trying to treat — which is what we want — but it also attacks the patient's normal tissues. This can be anything from a relatively mild to a very devastating problem that can occur after transplant. And one of the challenges was that, by the time that has been fully developed, then it's harder to treat. So one of the goals of research in the last few years has been to develop markers that will tell us which patients are at risk of having the most severe graft versus host disease, and allowing us to target more effective treatment toward those patients."Other recent advances in blood and bone marrow transplant include the use of mismatched donors and the ability to use bone marrow transplant in older, more frail patients thanks to improvements in antibiotics, antifungal drugs and other medications.Another cellular therapy that is helping treat blood disorders and cancers is chimeric antigen receptor-T cell (CAR-T) therapy. CAR-T involves taking the T cells from a person and reengineering them to recognize and destroy cancer cells."CAR-T therapy is a very interesting therapy," says Dr. Hogan. "It's really come to fruition in the last five to 10 years. This is similar to bone marrow transplant, but not quite the same. It's a cellular-based therapy, so not a drug, but using cells that are modified in order to try and treat leukemias and other cancers. And basically, what it does is it takes our native immune system — and then the T cells specifically — and modifies them so that they are much more effective at recognizing targets that are on leukemia cells or other malignant cells. And that really kind of allows us to use the native immune system in a much more effective way of trying to kill leukemias." Dr. Hogan says CAR-T therapy also is being developed for noncancerous conditions, like aplastic anemia, and research is looking at CAR-T as a treatment for a particular form of inflammatory multiple sclerosis. "Things have really been transformed over the last five to 10 years with the advent of CAR-T therapy which has been groundbreaking," says Dr. Hogan. "The field of blood and bone marrow transplant continues to move forward, creating more effective treatments with less toxicity for many patients." On the Mayo Clinic Q&A podcast, Dr. Hogan discusses advances in bone marrow transplant and cellular therapy, including CAR-T.

Key papers discussed in the show:1. Landmark paper on HLA-mismatch and survival: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4568127/2. HLA-DP and Risk of GVHD: https://www.nejm.org/doi/full/10.1056/NEJMoa15001403. Outcomes of Allogeneic Transplant with HLA-Mismatched Unrelated Donor: https://ascopubs.org/doi/10.1200/JCO.20.035024. Review/perspective on fundamentals of unrelated donors and cord blood units: https://ashpublications.org/blood/article/120/2/259/30405/A-perspective-on-the-selection-of-unrelated-donors5. HLA-DQ heterodimers and HCT: https://ashpublications.org/blood/article-abstract/139/20/3009/484363/HLA-DQ-heterodimers-in-hematopoietic-cell6. PT-Cy as GVHD prophylaxis after HCT: https://pubmed.ncbi.nlm.nih.gov/20124511/7. Comparative outcome of MUD vs Haplo-HCT from Registry data: https://ashpublications.org/blood/article/138/3/273/475738/HLA-haploidentical-vs-matched-unrelated-donor 

Surgical site infection risk with allogeneic blood administration by AORNJournal

Dr. Metin Kurtoglu, COO at Cartesian Therapeutics, explains the clinical-stage biotech's autologous RNA cell therapies, Descartes-08 for Myasthenia Gravis and Descartes-11 for multiple myeloma. He also explains Descartes-25, their allogeneic RNA cell therapy and the reasons for the move to "off-the-shelf," and why the future of RNA cell therapy is not confined to rare and fatal diseases. We also discuss post-care for patients having received infusions.

In this week's episode we'll discuss the effects of intestinal microbial diversity on patient outcomes following allogeneic hematopoietic cell transplant and review the results of three different phase 3 trials comparing CAR T-cells to autologous stem cell transplant in patients with refractory or early relapsing large B cell lymphoma, which have the potential to result in a paradigm shift in the standard of care for second-line therapy.

Celyad Oncology's CMO, Dr. Charlie Morris, shares the benefits and challenges of the allogeneic approach versus the autologous approach and why a non-gene edited shRNA approach may result in better efficacy and safety for CAR-T therapies.

Betty Hamilton, MD, Interim Director of the Blood and Marrow Transplant (BMT) Program at Cleveland Clinic joins the Cancer Advances podcast to discuss research and findings that were presented at the 2021 American Society of Hematology Annual Meeting (ASH). Listen as Dr. Hamilton discusses graft-versus-host disease and the study that evaluates a new regimen.