Leukemia 101

Leukemia 101 9.16.25 Transcript

Participants:   

Dr. Michael Drazer, University of Chicago

Lindsey Whyte, Leukemia Research Foundation

-  Thank you so much for joining us for the first webinar of Leukemia Research Foundation's Leukemia Awareness Month series. Today we'll be covering things that you should know as a leukemia patient or caregiver and we're joined by Dr. Michael Drazer from the University of Chicago, who will talk a little bit about approaches to diagnosis and treatment, and respond to questions that have been sent by participants or are submitted throughout the program.

My name is Lindsay Whyte and I'm the Director of Programs & Partnerships here at Leukemia Research Foundation. I would like to take a moment to acknowledge the supporters of this series. We have AstraZeneca, Autolus, Rigel, Astellas, AbbVie, and Novartis. We're grateful to them for their support. The Leukemia Research Foundation's mission is to cure leukemia through innovative research funding and to support patients and families. The Foundation has raised over 90 million in support of its mission since our founding in 1946 and has funded research grants to over 750 researchers and investigators worldwide. Our support programs for leukemia patients and their loved ones include information and resources on our website, education programs like today's, financial assistance and a directory of other helpful organizations.

For today's program, participants will be muted, but we welcome your questions through the Q & A box at the bottom of your screen. This is a very important point. If you want your question to be anonymous, it's important that you click the button that requests that your question be anonymous before you submit it. Otherwise, your name may show. If you already submitted a question through the registration, please know that we have your questions. Dr. Drazer will be addressing many of the previously submitted questions in his prepared remarks. After today's program, you will be sent a brief evaluation through email. Please take a moment to complete the evaluation so that we can improve our future programs. Also, this program will be recorded and a link to it will be sent to participants afterward.

We are grateful to have Dr. Michael Drazer with us today. Dr. Drazer is an Assistant Professor at the University of Chicago, a hematologist oncologist and geneticist specializing in the care of people with blood disorders, blood cancers, including hereditary blood disorders and hereditary cancer syndromes. Dr. Drazer's clinical research is largely focused on optimizing the care of people with hereditary blood and cancer syndromes, including the development of clinical bioinformatics pipelines that improve the diagnosis of patients with these syndromes. He's a member of multiple clinical disease groups at the University of Chicago. That's just a very brief summary of the many things that he does at the U of C and we're really grateful to have him here. So I'm going to turn it over to him so he can get us started.

- Thanks Lindsey. I'm going to share my screen here. Is that showing up? Okay?

- Yes.

- So yeah, thanks Lindsey and to the LRF for supporting this webinar today and also for the work that you do and supporting the research of blood cancer researchers like me. So I was tasked with basically talking about the 101 of leukemia, and this can encompass a lot of different topics. So what I try to do with this talk is I'm going to generally just focus on the broad overview of how we diagnose various forms of leukemia and blood cancers in general. And then very briefly, I'll touch base about the treatments that we use. But really when I was looking through the questions that people submitted before the webinar, there were so many questions that I'm really going to just focus on the questions that people submitted. And I'm going to go through it in as much detail as I reasonably can. And as I go through this, feel free to, you know, put questions in the q & a box like Lindsey said. You know, if you want to be anonymous, please click the anonymous setting before you turn in your question just to protect your own privacy. And then hopefully during the course of this we'll be able to cover most of people's questions and go through the nuts and bolts of what it means to be diagnosed with one of these blood cancers. So people oftentimes will say you know everything about me. I don't know a whole lot about you as a physician. So as Lindsey said, I'm a leukemia physician at University of Chicago. So for people who don't know Chicago, we're on the south side of the city, which has been where I've been since 2008. So I opened my clinic in 2018, but I did my medical school, my residency, my fellowship, and my PhD here. And as Lindsey referenced, I really care for people with all forms of blood cancer, but my "super specialty" is really these hereditary blood cancer syndromes. And I'll talk about some of these hereditary blood cancer syndromes in response to the questions that people submitted that directly pertain to these types of blood cancers. And then we have a research laboratory here at U of C as well. And my lab, which we opened back in 2018, studies hereditary blood cancer syndromes and rare blood cancers. And we have a particular interest in what we call the orphan blood cancers. And the way that I describe these generally is, you know, the orphan blood cancers have been kind of neglected in terms of research and discovery and drug company investment in terms of trying to find new treatments. And particularly now I think there's a trend in the field where if people are going to study these orphan blood cancers, it's really going to come from labs like mine. So we've made a very concerted effort to take up that responsibility and move the field along. I do have two disclosures here that I wasn't required to say this, but I just want to make sure that people know that I'm giving you kind of unbiased advice. So I have advised two companies basically on the development of a FLT3 inhibitor that is Daiichi Sankyo. And I won't really be kind of pitching this inhibitor or anything like that specifically, but I just want to make note of that. And then Blueprint Medicines, they make a treatment for an orphan blood disease called systemic mastocytosis. So I've also advised them in the use of their treatment. And then outside the lab in the clinic, I'm a trail runner so that picture there is with my kids running towards the finish line of a 103 mile trail race I did two weekends ago. So there's some people from Minnesota that submitted questions. So if you're from Minnesota, this is from the North Shore by the boundary waters by Duluth. And I always wanted to have a picture of my kids running towards the finish line with me and now I have one. So I figured to throw that in here.

Thank you for everyone who has joined the webinar. You know, this is a stressful type of diagnosis to get and I think the questions reflect the uncertainty that people go through both in terms of the patients and people who care for them themselves. So without further ado, this is really the 30,000 foot overview of how a leukemia diagnosis is made. And I always tell my patients when they come to me in the clinic that the most frustrating part in my opinion of going through this process is at the very beginning where the diagnostic odyssey, as I call it, begins because no matter how you kind make your way to the clinic, it might be you had a blood test that looked a little bit scary that your primary care team ordered and they said you need to see a blood doctor or you have symptoms that prompted you to be evaluated. You know, the uncertainty from the time that you initially are told you need to see hematologist to the time that you get your diagnosis, that can often take days to weeks to really finalize that diagnosis. And many of my patients when I meet them, that's one of the most frustrating parts of this journey.

And when you come in to see a doctor like me, one of the things that this is really emphasized in this organization, this is the pathology group that really helps us behind the scenes making our diagnoses. One of the things that they like to say is make sure that your doctor has your complete medical history. And based on the research that I do and the type of clinic that I run, I would also emphasize that when you're meeting with your doctor, if you are a patient or the caregiver of a patient who comes from a family with multiple people with blood cancer diagnoses, or there are multiple people in your kind of first degree family who have other types of cancer diagnoses, I always tell my patients, please let me know about that. Because the next step of what we do, these blood tests, you know, that really the blood tests that we order depend on the type of diagnosis that we're suspicious of. But if we think that there might be a hereditary cause or hereditary contribution to the blood cancer diagnosis, it's better that we know as soon as possible because the tests that we order will actually reflect that kind of concern. And so there are some questions that people submitted about this, you know, particularly like could there be a hereditary basis to their disease? I tell people, yes, there can be. It's more common than people realize. And if you're worried about that, you should let your doctor know as soon as you can.

Most of the time, but not always, we ultimately end up doing a bone marrow biopsy. So many people ask questions about bone marrow biopsies. And a key point is, I don't think anybody who submitted questions for this webinar were kind of in this stage of the diagnostic kind of process where they were thinking about having bone marrow, and, maybe, we're going to get a second opinion at a bigger kind of blood cancer center like, you know, the one I work at University of Chicago. But oftentimes people will say to me, should I do a bone marrow biopsy the minute someone is concerned about this and I'm in a hospital, you know, maybe a little bit further away from a major academic center or a major center that takes care of a lot of people with a blood cancer diagnosis? And I oftentimes will tell people, you know, you will most likely have another bone marrow biopsy when you make it to one of these bigger centers that really specializes in what you have. And it's sometimes okay to hold off on that bone marrow biopsy until you make that kind of trip to the major academic center or the major clinical center.

Behind the scenes we order these molecular tests and you know, this is really where I call myself a clinician, but the pathology doctors behind the scenes, they look at your samples from the bone marrow and the blood under the microscope, and they often are the ones who are performing these very, very specialized tests to ultimately make a diagnosis of a blood cancer. And on this figure, they really emphasize acute leukemias, acute lymphoblastic leukemia, acute myeloid leukemia, and also this type of disease called a mixed phenotype leukemia. But the same principle really does apply to the chronic leukemias as well. So we had a lot of questions from people focused on chronic lymphoblastic leukemia and chronic myeloid leukemia, but this general process is very much the same. And then oftentimes this is the main indicator of what kind of treatment we should use. And we really do try a personalized treatment for people now in 2025. Even, you know, two decades ago we didn't have some of the options that we have available now and we have a lot of options coming down the pike as well. So, you know, this is a general framework for how we think about leukemia diagnoses. And this applies to both acute and chronic leukemias.

This is a textbook blood cancer formation, kind of a little schematic that I use, when I talk about this. So, you know, in theory, we're all born with healthy bone marrow baseline. And then what can happen as we all go through our lives is our bone marrow will kind of pick up these changes in our DNA called mutations. And oftentimes those are just completely harmless by themselves, but as time goes on, just by chance or by exposure to environmental risk factors, we will additionally pick up more of these mutations. And that's really where this diagnosis of leukemia broadly comes from. And patients will oftentimes ask me, well, you know, can I be born with a change in my DNA that increases the risk of this happening, you know, eventually get getting to the diagnosis of leukemia. And you know, in my clinic, it's not uncommon for me to start going through my kind of, I almost have my spiel about, this is the diagnosis, this is what we're going to do for treatment. And patients will say to me, oh, you know, I am very familiar with this because, you know, if I'm this patient, I actually had a brother here, this is a, this is what we call a pedigree or, or a family tree. I had a brother who had leukemia, I had another brother who had leukemia, and my mom had leukemia and her mom had leukemia. And by the way, I also have some cousins with leukemia. And this is what increasingly people are talking about as hereditary blood cancers.

This is a family that was cared for at the University of Chicago about a decade ago. And they were ultimately found to have a mutation that you know, most of these people were born with and increased the odds of this happening. And a mutation was in a gene called DDX41, and which we now know is one of the more common causes of a hereditary blood cancer syndrome. So I tell patients in these categories of blood cancer, you know, when you were born, if you looked at the bone marrow under a microscope, which, we don't really do that, but if we could go back in time and look at your bone marrow under the microscope, we could actually see subtle abnormalities in the bone marrow that would reflect the DNA changes that these people were born with. And we've done a lot of work trying to really optimize the care of people with these types of changes because oftentimes they can cause problems decades down the line. But we actually try to avoid overtreating these people because the bone marrow looks a little bit unhealthy. We now know that oftentimes these patients can be watched very safely for decades before they need treatment. And we've done a lot of work trying to really inform the care of those patients.

So we're about 16 minutes in or 14 minutes in, and these are, I'm just going to go all through the questions that people ask me because I think we have plenty of room to run here in terms of hopefully answering your questions and providing some helpful information for you and your family members. So thank you for submitting all the questions. We received over 180 questions. So I did my best to try to condense them into general categories and I typed out brief responses that you can read, but I'll try to say more detail as I'm speaking through these questions so that, you know, you both can take a look at the screen, maybe take a screenshot, but then you can also listen to what I'm saying and you know, follow up with additional questions in the q & a. I have to really be clear that for treatment questions, I can only speak generally. So many of the questions were really, really good and they're the type of questions that I would have in my own clinic, but it's, you know, really impossible for me to, you know, when I meet with my patients, I factor in all of these factors about, you know, who the patient is in front of me, right? So different patients based on who they are, their preferences, the details of the disease that we're, you know, fighting together. Oftentimes the treatments that I pick for my patients might not be like the textbook response that we would choose for a patient. And you know, that goes back to this idea that all these treatments have to be very individualized. So, you know, for people who are asking me what should I do for my next treatment, I try to generally address those questions and let you know what options might be out there. But you know, ultimately you really have to go to your main doctor and you know, please feel free to take, you know, the responses I give you and use that to inform the discussions with your main doctors and I'm hope hopeful that those will be helpful for you.

So we'll get right into the questions here. So these were some questions regarding symptoms that people had. So what I did was I tried to say what kind of disease the people who are asking the questions kind of told me that they had when they asked the question. So there was a patient who was diagnosed with CLL and they said, I'm newly diagnosed and I'm on watch and wait, but the fatigue is overwhelming despite their blood work is being reassuring. So this is a great question. And they said, can I get help for the fatigue? So what they're basically implying here is, you know, when they got this diagnosis of fatigue or of CLL and they have this fatigue, their doctor did all the blood work that we typically do, they did all the diagnostic maneuvers that we typically do. And what they're implying here is that everything looks pretty good, but despite that they have fatigue and they're wondering, they're kind of implying could this be coming from the CLL itself or is there something else that we should be thinking about? And in my clinic, what I tell a lot of my patients is often this is not an uncommon situation where I'll do all the right testing, it looks reassuring and we don't necessarily need treatment right now. And then I started saying to myself, okay, what might the fatigue be coming from that might not be related to the CLL? Could it be coming from the CLL? It could be, but oftentimes in my experience what I've seen is people say, oh, it's just the CLL, we'll watch it. And you know, the patient says, well, you know, this is something you have to deal with on a daily basis on a weekly basis. And oftentimes these patients will come to my clinic and I say to myself, there might be something else going on here. Right? And you know, one of the number one referrals I actually will make is, you know, I'll have patients and they come to me with fatigue and I'll say, well, you know, do you know if you snore at night? Are you, are you focused on like the basics of getting really good sleep? And in my experience, oftentimes people in this situation, it's to those kind of non-CLL related things that we end up addressing. So I make a lot of referrals from my sleep medicine colleagues, you know, these are doctors who focus on making sure that people get quality sleep and adequate amount of sleep. And what I've seen a lot is, you know, you have this life changing diagnosis of CLL and sometimes patients will say, you know, yeah it is a little bit hard for me to unwind at the end of the day and you know, I'm, maybe I'm on my computer or my phone right up until I go to bed, I go to bed and I get six hours of sleep and I'm waking up in the middle of the night pretty frequently and I feel really drained the next day. That's the classic situation where, you know, we can really address some of those issues around the quality of the sleep and the duration of the sleep and people feel better with those interventions and it ends up not being related to the CLL at all.

Another big thing is emotional health, right? So, you know, a life changing diagnosis, it's stressful for you is stressful for the people who care about you. And sometimes people will tell me, you know, yeah, we went through all this testing and everything was okay, but you know, maybe it is, I'm feeling a little bit blue and I'm having a harder time kind of dealing with the stress and the anxiety of this diagnosis. And I do send a lot of people to my colleagues in, you know, psychology and psychiatry. A lot of my patients end up kind of enrolling with therapists even remotely, things like that just to make sure that we have a check-in and a support system for patients behind the scenes. Because you know, in my mind I'm thinking if, if this patient who's on the watch and wait protocol, they might not need treatment ever or they might need not need treatment for another decade. I don't want to just chalk everything up to the CLL when it could be something else that we can address.

There's also very basic blood work that we can think about too, you know, thyroid levels and things like that. So I would just make sure to go back to your doctor and say, you know, is there anything not related to the CLL that we're missing here and are there any referrals to, you know, sleep specialists, endocrinologists, psychologists or psychiatrist that can be helpful for me.

There was a patient with AML who submitted question, they said canker sores and how best to deal with them. I also have horrible constipation from the treatment itself. So the constipation is a little bit tricky for me to address because I don't know the details of the treatment that were chosen for this patient. But you know, oftentimes my goal is to try have my patients have a bowel movement once a day and we have different approaches for doing that, but that should ultimately be the goal. I can't really give a specific medication suggestion because I don't know what the treatment was.

But in terms of the canker sores, there's something called magic mouthwash that I use a lot. Magic mouthwash, it's kind of a combination of different medications. It's usually something like an antihistamine like Benadryl. Lidocaine is oftentimes in there, so it's like a topical anesthetic and then an antacid. And particularly for our patients with AML, they oftentimes will develop, they have a higher risk for developing like little fungal infections in their mouth. So sometimes I'll actually put a little bit of an antifungal medication in there or like a steroid medication to try really heal things up. And that's something that if you ask your doctor or one of the people involved in your care, you know, can you consider magic mouthwash for my mouth sores? That can be very helpful for a lot of my patients.

And then, you know, at the end of the day I would definitely consider asking for a referral to palliative care. So you know, for people who have not interacted with palliative care in the past, these are experts in the treatment of symptoms related to either a cancer diagnosis, in our case, or the treatment stemming from it. So in this patient's case the treatment seems to be causing them a lot of difficulties but you know, most of the time we can't really change the treatment all that much. So that's when I lean on my expert colleagues in this field and I say, you know, hey I've, I've tried my magic mouthwash for the canker sores but my patient still has really awful canker sores. Can you please help me brainstorm ideas that could get these symptoms under better control? And particularly the constipation, this is something they see all the time so they can be very, very helpful. And oftentimes they can do telehealth too. They don't have to meet with you in person. So you have options there.

And then a patient with CLL asked can an enlarged spleen cause a full feeling most of the time. Definitely this is like a classic symptom of CLL. I tell people, you know, before gastric bypasses and ozempic, the only other people who felt full when they sat down at the dinner table halfway through the meal were people with CLL or some of these other blood cancers where their spleen is big enough to actually push on your stomach. So anatomically the spleen is sitting right next to the stomach in our bellies and when the spleen enlarges it actually pushes and compresses that stomach and you might only have half the capacity in your stomach and you, you know, the classic situation is you sit down at the dinner table and you have your full plate of food there and you say, oh you know, this looks great. And you get halfway through it and you say, yeah, I think I'm done. That's very, very classic for CLL. It's not always, you know, it is not something that you necessarily have to start treatment for oftentimes, but it's something to keep an eye on, particularly if you start losing weight or you're really concerned about weight loss.

So we had a bunch of questions about diagnosis. So I've tried to type out brief responses here but I'll talk in more detail. So a patient with AML said, I'm certain that this is an issue for all people who are diagnosed with AML who have children. I have been told that AML is very rarely hereditary, but with no good explanation how to distinguish. So this is a great question. Back when I was in medical school we were kind of told, yeah, very rare cases of AML can run through families. That was, you know, more than a decade ago now. And since that time there's been a lot of research done demonstrating that I tell the number I tell my patients is at least 14% of AML cases. So that data is from 2022. So three years ago and that was a group of patients who had AML who were older, they were in their sixties on average. And yeah, if you take a hundred people with AML, 14 of them on average will have some type of hereditary basis for the disease. And in this particular situation I would recommend meeting with a genetic counselor and, and this is really key, some patients will be cared for by teams that don't necessarily have someone who is really comfortable with hereditary blood cancer diagnoses, who's a leukemia doctor like me. But oftentimes they do have access to genetic counselor and sometimes these genetic counselors work more with people for like hereditary breast cancer or hereditary ovarian cancer. But they tend to be really, really good that if they meet a family with AML and they can't figure out what to do, the genetic counseling field is really good about reaching out and asking for help in terms of making these diagnoses. So that would be someone who in this situation I'd really recommend meeting with. And the key here is when they do the genetic testing, they can't just take a blood sample because the AML itself can throw off the results of the test. So we have to do special testing that doesn't have blood involved in it. So that tends to be skin biopsies, hair samples or nails depending on where you are in the institution that you get tested, they will have different approaches and you know, for the most part they all tend to be equivalent in my experience. And the genetic counselors can really help you get that testing process underway.

And particularly for people under the age of 50 who have MDS or AML, this is actually supported by the guidelines now from the National Comprehensive Cancer Network. So you should be able to get this covered by your insurance company and if they say no, you should be able to have your team cite the NCCN guidelines If you're under the age of 50 and you have one of these blood cancer diagnoses of MDS or AML, in particular, and you should be able to say this is covered by the guidelines, you should cover my testing. And they eventually should agree to do the testing.

Another patient asks how prevalent is a change in diagnosis due to new research specifically in the AML. And what I tell my patients is generally, now there are always exceptions, but generally we don't change the diagnosis. So usually when I have someone who comes to me with a diagnosis of AML, very rarely do I change that actual diagnosis. I have done it. But for the most part what I end up doing is I will oftentimes change based on the testing that we do, I might say, oh you know, you were told that you need a stem cell transplant and actually based on the testing that we did, it turns out you may not need a stem cell transplant or vice versa, right? So that's more often what I end up changing is the prognosis and the treatment choice. But very rarely do I change the more global diagnosis.

There was a patient with CLL who said, I'm concerned that I will get too sick to start treatment while I'm on watch and wait. What kind of tests should my doctor do? I live too far from CLL specialists. So I think the basic, you know, evaluation is still blood work, symptom checks and the physical exam in this patient's case. But I would really strongly consider telehealth options. Lindsey, am I allowed to say where this patient's from? Yeah. Okay. Yeah so, so this patient lives in New Jersey and you know, I know that there are some telehealth specialists in New Jersey who you can get into contact with and this is one of my favorite little factoids. I have a lot of patients in my clinic who have CLL who I started caring for during the pandemic and I've never actually met them in person. They have their local doctor who does their physical exam every year and I check in with them, you know, maybe every three to six months and I ask them, you know, how are you doing? Is there anything new that we should be worried about? We go through their blood work but you know, I can do most of the things I do for my in-person patients except for the physical exam via telehealth. So I have patients really, you know, all over the Midwest and really all over the country and even the world now who I kind of am a sounding board for them more than anything.

This is a really interesting question and a really tough situation. So, you know, I'm really thinking about this patient who asked this last question, they said, my doctors are not sure if I have CLL or MCL. So these are basically two kind of cousin blood cancer diagnoses. They said I am in watch and wait and they also put in some details of the actual pathology and bone marrow biopsy samples here. They didn't put into the chat but they basically said, you know, these are the factors of the disease that I've been told. And they said, how will the doctors know how to treat me when the time comes if they're not even sure which disease I have? I have seen three specialists now. So, you know, this is a tough situation where this patient is seeing, you know, experts in the field and it's not really clear what's going on and you know, I'm sorry about this situation. It's super difficult and you know, this is a great example of what I call the diagnostic odyssey where there's a lot of frustration, right? Like you're seeing all the right people, they're doing all the right tests and they just can't make the diagnosis. And what I tell my patients in this situation which is, you know, relatively uncommon but I have seen it quite a bit over the years, is I say, usually over time we will kind of crack that code and there will be some tests that you know, when you initially had it at the time that you have it again five years later or something that oftentimes will change over time and that oftentimes will be the clue that we needed to really make this diagnosis. But say, you know, let's go to the worst case scenario in terms of this frustration, right? Say we don't get the diagnosis completely sealed down and we all think that there's time to like this is the time to start treatment. Oftentimes under the microscope and in the laboratory where we do this testing, there are clues that's the right treatment even if the diagnosis isn't clear. And it, and what I mean by that is there are characteristics that are shared by these blood cancers that make them vulnerable to our treatments that we use. So sometimes people say I'm not really sure if it's CLL or MCL but the treatment's ultimately the same so you know, let's move ahead with the treatment. And then you know, the diagnosis in a way is not as important. It's really making sure that the treatment is correct. And your doctors, it sounds like you're really plugged in, which is great. If you're really plugged in the doctors are really, really good about this. They say, you know, we're not sure if what we're dealing with is X or Z but based on the things that we see in the laboratory, the right treatment is pretty clear in this situation and we'll move ahead with that and on the back end of this we might have some clues but, for the meantime, let's just get this patient on treatment and get them, you know, in a safer spot.

Alright and then some more questions regarding diagnosis. So there's a patient from California who said, I have ALL. Is it possible for ALL to be slow in progression? And you know, my very brief blurb was "very rarely." I mean I have seen patients where the ALL is kind of smoldering, so to speak, but because you're in California, if possible I'd really recommend meeting with an ALL specialist near you who really is at a high volume center because there's some really, really good ALL specialists in California and I would really bring the particular testing, if you have it, that you're worried about, to them. And you know, if this is more based on like a symptom, if you say, you know, I don't have testing I'm worried about, but I just feel symptomatically as if something is kind of smoldering by having had testing done recently, that would be a great situation where an ALL specialist could do specialized testing looking for very, very, very low amounts of disease that might be changing over time. And we do have those tests available to us.

There was a patient with CLL who said my brother and I both have had CLL since 2017. My brother's diagnosis was then changed to MDS and then to AML. So it's a really, you know, tough situation in terms of this diagnosis evolving. I also have a cousin who has von Willebrand's disease. It certainly seems like there's a potential hereditary link here and I completely agree with this patient. You know, your spidey sense is exactly right that, and this is a very common scenario where people come to me and they say, I have a feeling there's something going on here. I was told there isn't. This is a classic situation where ideally you can meet with a team kind of like mine where there's a leukemia doctor who also has an interest in caring for people with these hereditary blood cancer syndromes and a genetic counselor. If you can't get seen by a leukemia doctor who is really comfortable with these diagnoses, you should definitely meet with a genetic counselor. And, as I alluded to on the other slide, they tend to be really good about reaching out for help in situations where they might not be sure what to do.

The next slide is about treatments. So patient with CLL and you know, once again I just have to reiterate, I can only kind of speak broadly because I don't have all the details I would normally have in my own clinic, but I'll do my best to answer these, you know, broadly and give you some general guidance. So a patient with CLL said, I've been slowly reducing my ibrutinib dose. And ibrutinib is a classic treatment for CLL for people who are on watch and wait and think about options and they've been reducing the dose to address skin side effects, but my numbers recently got worse. Should I go back up on the dose or should I consider switching to something new? So you know, based on these details I would strongly consider switch because if this is the only treatment this patient's ever had, we have a lot of other options for this patient that both kind of look like cousins of ibrutinib but could be effective in this situation with less of the side effects. Or there are treatments that don't like look like ibrutinib that would have a different side effect profile, particularly in terms of the skin. So I would highly recommend talking to your doctor about, you know, considering a switch to a different treatment and it, you know, ibrutinib is still kind of working for this patient. It's just the side effects are tough. So it's not like you're taking it completely off the table. You can always go back to it down the road. This is not like a set in stone situation by any means, but I would definitely think about talking to your main doctor about switching to a different treatment in this situation because I think there are good ones out there for this patient.

A patient asks, just broadly have there been advances in CMML treatment? So CMML, for people who are not familiar with this disease, it's a relatively rare blood cancer syndrome and I would describe CMML treatments right now as we have steady progress and we have a lot of clinical trials available. So I would definitely recommend going to clinical trials.gov and typing in C-M-M-L and see if there's something available near you because you know, for example, we have things available at UofC for CMML, but I don't know if this patient lives near us, but there is progress in terms of people trying to find new treatments for this disease. There's also been a lot of, and I think this is important, the patient asks about treatments, but I oftentimes will tell my patients with CMML, do you need treatment? And one of the big advances in CMML in the past five years has been we have better and better what we call calculators to determine who with CMML is at the highest risk for needing treatment and having progression of their disease. And it's not uncommon for me to use these new calculators for my patients with CMML and I can oftentimes tell them we're going to talk about treatments, but based on this calculation that we've done, which I really trust, the most likely scenario is you may not need treatment for 10 years. And that's a very important distinguishing factor about CMML that's unique to this disease.

Another patient asked, are there any new drugs for FLT3 recurrence? So for the FLT3 question the patient said, are there any new drugs for FLT3 recurrence? So Lindsey sent me a very helpful note. She said there was actually a webinar from May from the Leukemia Research Foundation that you all can refer back to, and that's a very, very detailed description of all these different drugs that are available. So I would definitely look at that. I'd also say, you know, it's the same answer as the CMML question. It really depends on where you live and who you have access to. But I would go to clinicaltrials.gov as well and look there for basically acute myeloid leukemia. You can put that in the disease category. And then there's this “other terms” category and you can type in FLT3 there and you might be able to find trials that are available for you that have drugs that you haven't seen before. The other thing I tell my patients a lot is sometimes you might not need a trial, you just need a drug that's new to you. So we have multiple agents now that we can use for these FLT3 mutations and it's not uncommon for me to switch from one to the other. So, you know, one of my patients I've cared for many years now, she was initially on Sorafenib, which was a FLT3 inhibitor that was used more broadly many years ago and it was doing the job for her, but it was really having a lot of side effects for her. And we ended up switching her to a different FLT3 inhibitor. Had a lot of good luck with her with that, and we got her into a stem cell transplant and she's been in remission now for going on six years. So, you know, we oftentimes have flexibility in the actual FLT3 inhibitor that we use. So just because you had one before and it didn't do the job doesn't mean that you can't use other ones as well.

There's a patient with CLL who said, I was diagnosed with CLL after mammogram showed enlarged nodes. I've been watched for several years with a white blood cell count now of 19. My bone marrow is 50% involved and Trisomy 12, but my blood tests are stable. I'm 76, I'm worried about treatment. So this is a very classic tough situation where people are saying right now I don't need treatment, but I'm worried that as time goes on, if the time comes that I need treatment, will it be too intense for me? And I have patients who are in their eighties and some of them now approaching their nineties who have been on an active treatment for CLL and they do really well. And this has been really one of the big advances in CLL therapy over the past 20 years. As time has gone on, the treatments have actually tended to get more tolerable. They're not side effect free. But oftentimes patients will say to me, you know, I was really worried about treatment and whether or not I would need it, and then you told me I needed it and I went on it and it wasn't nearly as bad as I thought it would be. So, you know, I would say for the time being, focus on the step that you're in and if you don't need treatment, just embrace that, live your life to the fullest and then, if the time comes where you need treatment, most blood cancer doctors are really, really good about trying to match you with a treatment that fits who you are and the type of things that you want to do in your life and the side effects that you're trying to avoid. So I have a good feeling about this patient, even though I know it's very stressful to be in this situation.

A patient with AML said, is it possible to be cured of AML without a bone marrow transplant? My latest MRD blood test didn't show my FLT3 or NPM1 mutations, and I have been advised to continue my treatment and I will do so, but I wonder if I'm cured? So the question is, yes, it is possible to be cured of AML without bone marrow transplant. We have these patients walking around my clinic and our clinic at the University of Chicago, and it's always wonderful to see them in clinic, those patients in clinic. So yeah, the short answer is yes. The longer answer though is sometimes I tell people, you might be on a treatment where you might be effectively cured, but the standard of care, and I'm going to talk about this on a future question here, but the standard of care oftentimes is to continue these treatments indefinitely. And it's a very, I would say as of 2025, a very contemporary approach. There is a lot of interest just like CML, are there patients out there who are effectively cured with treatments that in theory they have to continue for their whole lives? The answer is undoubtedly yes. We just, we are not great at picking out those patients right now safely, but that is an area of interest. So, you know, stay tuned. I think my hope would be in the next five years or so, we'll have a test that we can use to more effectively pick patients who can safely stop treatment that they were previously told they have to do their whole lives.

Questions regarding treatment. So there's a patient with AML from Illinois, so I put that here. Do you know which hospital specializes in essential thrombocytosis that turns into AML? Really, you know, this patient lives very close to the city. We have multiple options in the city. You're talking to the guy from UofC, so I put our number there. We have multiple people who would love to help you out here and be involved in your care. So that number is the new patient line for U Chicago. But we have plenty of centers in the city, so there'd be a different number if there was somebody from Loyola talking to you. But you know, that would be another option, for example.

Can hearing loss be caused by CLL or the treatment Calquence? I haven't seen the side effect. Oh yeah, so I haven't seen the side effect previously. I would recommend seeing an audiologist. That being said, every patient says, you know, well, nobody thought could be a side effect and then it would turn out to be a side effect. So I haven't- I'm a physician, not a prophet. So is this possibly a side effect of the Calquence? Yes. I just haven't seen it. So I definitely recommend an expert in audiology first. And then it'll be a little bit of a process of elimination trying to figure out what might be going on. You know, if it is a Calquence, you do have other options most likely. So you know something to talk about with your local doctor after the audiology team evaluates you.

This is a patient with AML, they said, how likely is a cytarabine Idarubicin treatment to work for a 72-year-old patient with an NPM1 mutation? Can this be enough to obtain a last remission? So I said, it's definitely possible that you can obtain a last remission with this treatment. We've seen this happen plenty of times. Without the details of this particular case, you know, I can't give you an exact percentage estimate of that, which I try to do that for my own patients. Something that might be useful based on the treatment choice here I have a kind of a general idea about where you might be treated. And if I'm right, I think the hospital that's treating you should have what we call a measurable residual disease assay. So we call this an MRD assay. So MRD for people on the call who aren't familiar with this term, you know, the general idea of leukemia or blood cancer treatment is to get people into remission, which ultimately means we look under the microscope and we see very little evidence of leukemia in the bone marrow under the microscope. We know that some people who are in a remission, the disease can still come back. And we now have newer testing that says, okay, this person under the microscope, we don't see any leukemia. Can we look for DNA evidence that's left behind of the leukemia because we see evidence of that DNA, that person has a higher likelihood of this disease coming back, unfortunately than if we couldn't find any genetic or DNA evidence of the disease. So this is what we call MRD testing. So for this patient, if you were in my clinic and you said, I'm not really sure how good this remission is, I would order you an MRD test. And if that was negative, as we say, the odds of this coming back are, are relatively low, they're not zero, but they're relatively low. And that can be something that can kind of further inform this thought process.

A patient with CML wrote, I have been on nilotinib and I've been having difficulties with clogged arteries. Can I switch to an alternative treatment? And you know, I wrote very clearly, definitely. So the next treatment, I can't tell you exactly which one makes the most sense because what I would ask your doctor to do is, you can ask the doctor, can I switch to a different treatment? And they should respond hopefully, sure. But what would they want to do is they want to actually look at the DNA in the CML to see is there a clue there as to which treatment work would work better for you than others? And you should have options here based on what you wrote in the question box. But just make sure that the doctor is actually looking at the DNA and the CML, making sure that they're making an informed decision about the next treatment.

And then next patient with CML says, what can be done to get to a 0.00 BCR/ABL level? Best thing, get a pill box. Don't miss any of your doses. That's it - it sounds kind of cheesy, but that really is the most important thing. So I have a patient who, his wife, I will always remember this, he's one of my favorite patients with CML. His wife says, we're giving you a pill box, I'm going to take my birth control and you're going to take your life control. And he has not missed a single dose in five years and he is doing great with a BCR/ABL level approaching this. Also, it's important to let people know you might get close to zero and not get all the way there. We, in the CML guidelines, which I help write the guidelines for CML on national level, people who get close but not to zero, they tend to do really, really, really well. And oftentimes just as well, if it gets to zero, the only difference is you can't stop the treatment. And that's, you know, close is oftentimes really, really good too. So, if you don't get to zero, that's still okay. And I have patients in my clinic who are close to zero and they're going to be on treatment for a long time, but they're going to live normal healthy lives.

Patient with CLL said, I was treated with venetoclax and obinutuzumab, I was in a 16 month remission, but then came back, what should I do? So the first thing I'd say is consider restudying or reprofiling the CLL. You might find some clues there about what to do. So just ask your doctor, you can you re-profile everything, but you should have very good options for treatment and some of them you haven't seen yet. So I think you'll have a good option here. Just make sure that the doctor retests things. Okay.

And then a patient with AML, they said basically what are the side effects of azacitidine and venetoclax? I tell my patients number one, two, and three on the list is infections. So I tell, I go through in great detail, what kind of fever do you need to look out for when you're on the therapy? And I really reiterate in certain situations you can call me and say, Hey, I have a fever, but we can keep you at home. In other situations, if you're in the middle of therapy and your temperature is 101 or higher, I tell people, I want you to call me from the front seat of the car that your family member or your partner is driving on the way to the emergency room. But don't wait to call me, just get in the car and go. That's the number one thing I worry about for my patients. And as I mentioned on the previous slide, the current standard of care is to keep the treatment going. Even if we can't find the disease in your blood, unless your doctor's considering a stem cell transplant, but if they're not thinking about transplant, you keep on going with the treatment. My hope is eventually we find a way to figure out who we can safely stop the treatment for. But right now, as of 2025, we're not there.

Patient with LGL leukemia, it's an orphan leukemia. I take care of a lot of patients with this. It said I'm being monitored on an annual basis. Are there other options for treatment? So there are other options for treatment other than surveillance. I would be careful though. I always tell patients, you know, this depends on your individual situation, which I don't know all the details, but you know, a lot of my patients with LGL they say to me, if a doctor didn't tell me I had this diagnosis, I wouldn't know I have the diagnosis. And in those patients, if the numbers are safe enough, I tell them, well the only thing I can do is make you feel worse with starting treatment. So it's really okay to keep a close eye on this and not do treatment for many of my patients. So, you know, you would have options and there are plenty of options out there, but I would just be very careful thinking about the goals of your care, you know. If you feel otherwise okay it's okay to just keep an eye on things.

And then we have some questions in the chat, so I'm going to move through these a little bit more quickly. So patient with CLL, they want to know what testing other than blood work every few months and doctor's appointments would you recommend? MRD testing? So that's a measurable residual disease. Like these low levels of DNA? If it brings anxiety, is it worth getting done? It depends on you. It really does. You know, I have some patients who say I can handle this anxiety, I want to know. And other patients say, I don't want to know. I feel great, just let me live my life. So it really does depend on you. I have patients in this situation who do both options.

Patient with CML- I have been in remission, can I stay in remission after stopping the gleevec pill? Yes, it depends on the details of your case. But I tell people if you're in the ideal situation with Gleevec and you stop it, about half the time you have to go back on it and it gets things under control again. But half the time you don't need gleevec anymore. So congratulations.

How long do people tend to live after completing CLL treatment? Depends on the details of the CLL and the patient. Honestly. I mean, I can't really give you a great estimate sadly. And that's just honesty.

Patient with ALL- do I have to have a port for two years? It depends on your doctor. I don't want to speak for your doctor and have them send me hate mail. But I have seen patients get their ports removed before two years, but don't tell them I said said that.

Questions regarding prognosis. Is it possible to have an average lifespan with CLL? It is. So I have patients who, in my very first clinic that I had in 2018, I had some CLL patients in that clinic and they're still in my clinic and they're doing great and they have, some of them haven't even required treatment, so it is possible.

Alright, research and diet. So I grouped these together. So people said - a patient with CLL- Is there research as to the impacts of one's microbiome from either leukemia or the drugs used for treatment. Yeah, so there's a lot of [research] going on in the space. It's very, very preliminary though I wouldn't really recommend changing diet based on that research yet. I think we will have more details in the upcoming years. What I tell my patients is, you know, number one, avoid heavily processed foods and try to focus on eating food that your great-great great grandparents would recognize. Like that's my number one key. Like if, if my great-great-great grandma in Poland wouldn't recognize the food in front of me, I try not to eat it. Now it doesn't mean you have to be militant about it, right? Like sometimes I'm tired after clinic, I eat Taco Bell, that's okay. You know, so don't worry about too much, but eat non-processed food. And then, same as above for the second question and then same as above for the CML patient.

And then this family member of a patient with AML- so this is a very detailed question. I think actually I might know who this person is, but with reference to the GATA2 mutation, have you found in your research why this hereditary mutation can cause activation of MDS or AML in young adults but not in their parents? So I could talk about this for hours and I won't, but we do have hints now as to why this occurs. And my suspicion, so for people who don't know what this mutation is, GATA2 mutations - people tend to be born with them and they dramatically increase the risk for infections and for blood cancers. And historically, my suspicion is that we met people with these changes who had the most dramatic stories, you know, the most severe cases so to speak, where the family, it is very obvious what's going on. As time has gone on and our testing has gotten better, we are meeting more and more of these patients who have very subtle presentations. And I actually think that the disease itself is not as severe in these patients just by chance. So I think there's a bigger spectrum than we expected. So that might be why a parent might not be affected, but their child might be. The other part of this too is, patients will ask me, is there a way of monitoring me to see how at risk I am? And you know, part of the work I did for my PhD was looking at that question and trying to identify people with GATA2 mutations at the highest risk for developing leukemia. And we found that about a third of these patients have what we call clonal hematopoiesis, which is DNA changes that kind of look a little bit like blood cancer, but the people don't have blood cancer. And if I find evidence of that in my patients in my clinic, I keep a very, very close eye on them. I don't have data showing that that's more effective, but I just, for my own peace of mind and for their peace of mind, I want to keep a closer eye on them as compared to patients who don't have those changes. So my suspicion is that in this family, in particular, the parent probably has a mutation that is not uniformly problem causing, but unfortunately in the child it did cause some problems and I hope that the child got effective treatment and they're doing well now.

This is our genetics team at the University of Chicago. So we have our physician assistants on the top and genetic counselors on the top and we have the doctors on the bottom. So Adam and Lorraine. Nice. We cover the whole age spectrum. So Lorraine is a pediatrician. Adam takes care of both pediatric and adult patients. And then I'm an adult doctor so if you want an appointment with the genetics team at U of C, this is the number and this actually works for general leukemia appointments as well and blood cancer appointments. Alright, so I will stop sharing and we'll get to these questions if that's okay Lindsey?

- Yes, that sounds great and I love that you talked a little bit about NCCN. People who have been on our programs in the past may recall that I talk about NCCN sometimes as well. I have here on this slide that you should see now I have just the covers for the NCCN patient guidelines. So there's a patient guideline for many different types of leukemia and you can find them at this nccn.org/patient/guidelines. I highly recommend that patients go there and check it out. And I also really appreciated that you mentioned specifically that the genetic testing is covered. So I think that's a really important point that a lot of people don't realize and many times doctors just don't pursue that because they think that it's not covered. So it's important for patients to advocate for that.

- All right, so we have some questions here. I will, I'll try to go through them kind of together when it makes sense. So I'm going to, I'm going to do my best to go in order here. So one patient said, I just learned I have an ATM mutation. Please explain what that means for my chances of survival of CLL. So, you know, I would say this ATM mutation, there are other things about the CLL that are probably more important for your prognosis. You know, the ATM mutation is only one part of this. So I always tell my patients that things like how fit of a patient are you, what kind of treatments can I use for that patient, right? If I have all the tools in my toolbox or my tool belt that I can use for a patient with CLL, I feel pretty good about that situation. So if you're someone who, you know, your doctor is saying we have a lot of options available for you and I feel very comfortable using all those, I think that's actually more important than the ATM mutation itself. The same thing I often get the same question about like P53 mutations. And you know, there'll be people who say to me, I have a P53 mutation in my CLL, does this mean I need treatment like right away? And oftentimes those people in my clinic, they do go longer than expected before they need treatment and we have treatments that we have kind of tailored specifically for these people with P53 mutations as well. So that's a long-winded answer, but I would say the short answer is, I would not focus so much on the ATM mutation as kind these more holistic assessments for you as a whole person and not just the lab result.

There's another question. What has research shown about the pre-birth exposure of a fetus to tobacco smoke on the risk of developing cancer, including leukemia years later as an adult. If it hasn't been studied, why not? So this is a really good question that it has kind of been studied not as directly as I think you or I would want it to be. But what's interesting from a blood cancer standpoint is, we are all born with these, what we call pools of stem cells in our bone marrow. And this is going to get a little bit scientific, but you know, we can nerd out together. The pools of stem cells you have, we'll just say hypothetically speaking, you have 40 pools of stem cells that make all the blood in your body. As time goes on, some of those pools will actually dry up and by the time that we're in our eighties or nineties, it's just a symptom of being human. These stem cells will dry up and you might have two or three pools left that make all of your blood when you're 80. And what happens is the pools that get left behind and kind of keep on working as we're older, they tend to have these mutations in them that are associated with blood cancers and they're one or two steps away from developing a blood cancer. So this is partly why as time goes on, people develop blood cancers as we grow older. It's actually an artifact of these pools - the stem cell pool phenomenon. And smoking can introduce more mutations into these pools. So you know, every doctor's going to tell you, you know, don't smoke and don't expose yourself to smoke or carcinogens. And that's partly why. They didn't look in those studies specifically of smoking to the degree that I would want it them to. But that's partly what's going on here. If there's a family history, a certain early detection test one can take, not really, unfortunately we're working on that. But I do tell people if there's a family history, what I have seen is patients will see their primary care doctors and they say, oh, the blood test is a little bit abnormal, come back and see me in six months. If you have a really strong family history, I'd say, you know, based on my family history, can't I just see hematologist now and do the testing right away. And I have patients in my clinic like that where they came to me very early, they were okay, but now they're with me and I'm almost like their new primary care doctor. I kind of jokingly say that, but I do say that with some sincerity because we keep an eye on both the blood issues in addition to the primary care issues.

So is CLL always a mutation in the stem cell or can it be from a mature B cell that mutates in a transition to an active B cell. Oh my gosh, that's a high-level question and the answer is it's not always in a stem cell. It can be a little bit further upstream from a stem or downstream from a stem cell. So you're spot on that it doesn't have to be in the stem cell.

For a third round treatment after failure of chemotherapy and ibrutinib, do you recommend venetoclax and obinutuzumab or pirtobrutinib? I'm not really sure based on the details of this. I think they both might be very reasonable options. I just don't know for sure. I would have to have access to all your lab results and honestly would have to kind of sit down and have a long conversation about this and what your preferences are. But I think both of those at the 30,000 foot overview, I think they're both very reasonable.

How similar is multiple myeloma to acute lymphoblastic leukemia. I was initially diagnosed after transplant with myeloma, but then the next day it was ALL. So you know, first of all, sorry to hear about the situation. I was initially diagnosed after transplant with myeloma, so it seems like this patient went through a transplant, I'm guessing for myeloma. And then sometime after that there was this diagnosis made of a concern that the myeloma had maybe come back, but then the next day it was ALL. So these diseases are kind of cousins of each other. They're, they both involve what we call the lymphoid immune system, but they're treated very differently. So in your case I would say it's very, very important to, you know, get the diagnosis as correct as you can and then, you know, engage the treatment that's effective.

I was diagnosed in November, 2022 with stage one CLL. In 2024 June I was hospitalized and found I have autoimmune hemolytic anemia now, which was treated. How likely will autoimmune hemolytic anemia return? So the odds of returns are relatively high compared to people who have never had it. So it depends on how good the counts look now and things like that. But what I generally tell people is most of the time it doesn't come back but there's, depending on the situation, anywhere from like a 10 to 30% chance it comes back. The important thing is staying in contact with your hematologist and keep a very, very close eye on your test results so that if it starts kind of brewing again, you catch it earlier than the first time. So you can kind of tamp it down with less intensive therapy then you had to go through.

 

What are stem cells and or- when are stem cell transplants done and who qualifies? So that is, I'm guessing Lindsey, you guys might have a webinar about this. If you do, please put in the chat. But what I tell people is, depending on the diagnosis that you have, if you have an aggressive blood cancer diagnosis, we respond with an aggressive treatment and the most aggressive treatment that we have is a stem cell transplant. So if your doctors think that your blood cancer diagnosis is relatively aggressive, they might offer a stem cell transplant. To the second part of your question, who qualifies? I always think about it as three legs of a stool. So number one is, is the blood cancer under really good control? If it is, I think that's a person who we might want to think about a stem cell transplant for. Number two, can I safely give the stem cell transplant? There are patients where I might not be able to safely give a stem cell transplant. I can cause more harm than good by doing that. So I tend not to offer those patients the stem cell transplant. Instead I say, okay, you have an aggressive blood cancer, we can't safely do a stem cell transplant. So now our goal is going to be let's keep this this blood cancer under good control for as long as we possibly can. But, and there are ways that we have doing that, but we're not going to use the stem cell transplant. And then number three, you really have to live relatively close to a stem cell transplant specialist for your own safety because a lot can go wrong and you have to be able to get to us relatively quickly. So those are the kind of the three types of requirements for a stem cell transplant.

- I think we might want to, there's a couple of pretty long questions coming up and we're really running short on time, so maybe we can just kind of wrap up? And if we can kind of follow up with answers, if applicable, to some of these questions or some of the ones that you previously prepared.

- Of, yeah, let me see if I can find one. So we didn't really cover in the session, so a lot of questions about like diagnostic uncertainty and treatment uncertainty. And I would say generally I would lean more towards the direction of people who see this kind of 24/7, you know, there's City of Hope has been mentioned multiple times here and I feel very confident about City of Hope and their quality of care. So I would generally defer to them.

- And I think the person who was asking about the change diagnosis to ALL, it was not after a transplant, it was after a bone marrow biopsy.

- Oh, okay. Yeah, yeah,

- That makes more sense.

- Yeah, that does make more, thank you for clarifying that. So yeah, I agree. Yeah, so the bone marrow biopsy was key to that diagnosis. Yeah, so that's a very common situation where when we do a bone marrow biopsy for people who have gone through this, I tell people in that first two to three day window, we look under the microscope and we kind of make our best diagnosis at that point. But oftentimes the fancy testing comes back two to three weeks later and that can change the diagnosis slightly. So it sounds like you were kind of that window where they looked under the microscope and thought one thing, but some of the fancy tests sort of come in and it indicated it was a different thing. So yeah, that's what I think was going on here.

- Okay. Well I'm sorry that we have to end this because it's been a great conversation and really hope that we can- I've shared the link to our next webinar, which is coming later this month, and hope as many of you can join us as possible, but we will be sending the video out or a link to the video and with a transcript and hope that you all can take a look at that. And if you have follow up questions, please don't hesitate to reach out to me. And in the meantime, just want to say thank you so much Dr. Drazer for your hard work in preparing for this. You did so much great work on taking each question and preparing responses. And also I wanted to acknowledge our sponsors one last time. Did you want to say any last things before we finish up here?

- Yeah, thank you Lindsey again for hosting this and thank you everybody for participating. We have 20 unanswered questions, so I apologize, but maybe I'll come back for another round and we can go through more of them. But yeah, thank you to Lindsey and all the work that you guys do with LRF, you know, it's really appreciated. When you zoom out and do what I do, you see the advances being made left and right and, you know, patient focused research is at the heart of that. So LRF, that's what you guys are about. So thank you.

- Thank you. Yeah, thank you. And, and don't worry about those 20 questions. I think a lot of them came in in the last five minutes. So I think, you know, hopefully everyone will continue to send their questions along in advance and, and we'll keep having events like this. So thanks to everyone for your participation and we hope to see you in a program again soon.