<< Return to the main 2021 Patient Seminar page to view materials from our sessions.
2021 Hairy Cell Leukemia Patient Seminar Session
Understanding Hairy Cell Leukemia - New to HCL
October 10, 2021
Hosted by the Hairy Cell Leukemia Foundation with expert guest speaker Dr. Leslie Andritsos from the University of New Mexico. Moderated by Anna Lambertson, HCLF Executive Director.
Presentation Materials
A synced recording of the webinar can be accessed using the link below. The link will open a new window. You do not need a Box account to view the recording. Click ‘download’ if the video doesn’t open.
Please note that the Q&A is available through the written transcript only.
Transcript of Presentation and Q&A
Transcript of Presentation from Dr. Andritsos
Dr. Leslie Andritsos:
Understanding HCL, New to Hairy Cell Leukemia.
I do participate in advisory boards, mostly around new treatments for hairy cell leukemia. I have received research funding from the Foundation, the SASS Foundation, and I will be discussing some off-label use of some of these newer drugs for hairy cell with the caveat that there are very few things that are actually FDA approved specifically for hairy cell. So this is just an overview of my discussion today. What is hairy cell? Who develops the disease? How this is diagnosed, a little bit about the biology of the disease.
I wanted to make everyone aware that there are consensus guidelines for treatment and response assessments. And we'll go over that in a little bit of detail. There's not a lot of time to cover all the treatments, but I will provide a treatment overview on how we decide what treatment to apply. And then just some brief discussion about complications, survivorship and COVID-19. And those are certainly areas that we can cover later in the Q&A.
So just a brief history of hairy cell leukemia. It wouldn't be right to not give credit to Dr. Bertha Bouroncle, who was really a giant in this disease. It was first identified in 1923 that there were these hairy-like cells that could be seen under the microscope. At that time, it was called leukemic reticuloendotheliosis. I don't think anybody really liked that name.
But then Dr. Bouroncle started working on this in 1958. She had a number of patients with this problem and started trying to figure it out. And she was responsible for the characterization of the disease and people really understanding what it was. I would like to make the point not to scare anybody, but before we had good treatment for this, this disease was uniformly fatal. And people only survived an average of about five years.
And then in 1984, there was this clinical trial using interferon alpha. And some of the people who were on that trial may be on this webinar today, which shows how successful that was. And it really was a game changer in hairy cell to have an effective treatment and a pathway to treatment. And then quickly after that, we had the development of cladribine and pentostatin, and these two drugs basically transformed hairy cell into a chronic disease with a near normal life expectancy. So in a very short time, from 1984 to about 1995, the disease completely changed.
And here's just a timeline. Dr. Grever and I put this together for a paper that we published a while back, but I really like it because I think it shows the enormous progress, really just in the last 10 years or so, where we went from having really nothing in terms of treatments and then in 1958, people can have their spleens removed or have corticosteroids. In 1966, somebody called it officially hairy cell leukemia and then it was classified as a lymphoproliferative disorder. And then shortly thereafter, all of a sudden, we had all these new treatments. And these treatments here are still being studied but I think going to be part of the routine armamentarium of treatments for hairy cell leukemia, and there are many more on the way.
Dr. Leslie Andritsos:
So it is very challenging to do epidemiological studies in a rare disease. So as you all probably know by now, hairy cell leukemia is a rare disease. It's only about 2% of all leukemias. There's about six to 800 new cases of classical hairy cell diagnosed in the US each year. The median age at diagnosis is about 50 to 55. Most of the papers that you would read would say there's a four to one male predominance. Worldwide, it's about three to five to one male to female with some areas having a higher population of female patients. In our patient data registry, it's about exactly four to one and that's US patients. We know that there's definitely a higher incidence among Caucasians and a lower incidence among Asian, African and Arab populations. However, there definitely are cases of hairy cell leukemia in those populations.
I think those areas are a little bit underserved just in terms of being able to find specialists. Sometimes we receive emails from patients, for example, in Africa saying they are having trouble finding a doctor who has expertise in hairy cell. We know that there is a higher incidence of the disease in first degree relatives of patients with hairy cell, which is a clue that there is some genetic predisposition most likely. Also, environmental associations, farming. The biggest studies that were done looked at large animal farming, but I suspect that that kind of goes along with the second thing on the list, which is exposure to pesticides and herbicides. For example, Agent Orange is considered a service-related disease when it comes to hairy cell leukemia. Diesel exposure has been implicated and also exposure to ionizing radiation.
Dr. Leslie Andritsos:
So let's talk just briefly about hairy cell biology. As I said before, it's a lymphoproliferative disorder, meaning in the family of lymphomas. But in some patients, it does circulate in the bloodstream and that's why it's given a designation of leukemia because sometimes we do find these cells in the blood, which just sort of automatically gives it the name a leukemia. This disease is basically characterized by the accumulation of clonal B cells. That means all the cells are the same. They have the same characteristics, same markers, same genetic changes, and they have these surface hairy projections. The cell of origin is felt to be a late activated memory B cell. However, Dr. Omar Abdel-Wahab found CD34 cells in the bone marrow of patients that did have the BRAF mutation.
So these stem cells here, I don't know if everyone can see my arrow, but hematopoietic stem cells are the precursor cells to the rest of the blood cells. And that group found that there were actually BRAF mutations in some patients' stem cells when they went and looked for them. But as the stem cells differentiate into other types of blood cells, they go down all these different pathways to this activated memory B cell. And that means it has already been through the lymph nodes and had some memory training in order to fight infections. But somewhere along the way, the cell becomes abnormal, is not doing its job and starts accumulating in places where it doesn't need to be such as the bone marrow, the spleen and potentially other parts of the body. And eventually when enough of these cells accumulate, they'll start having problems related to the cell infiltration of whichever organ it's residing in.
Dr. Leslie Andritsos:
So we know now by relatively recent studies that most cases of classic hairy cell have a BRAF mutation. This mutation is felt to be an acquired driver mutation. So you don't start out life with it, but somewhere along the way, these cells acquire the mutation and that starts the cell in a proliferation situation. The BRAF V600E mutations have been identified in the leukemia stem cells as we discussed just a minute ago and there's alternative mutations that may also be acting as driver mutations in both the classical and variant versions of hairy cell leukemia.
And I think this does highlight the importance of getting sequencing done if treatment is not working. So we expect for most people, treatment will be effective but if that is not the case for you, it's time to think about getting some additional testing and we'll discuss that in just a minute. This is a chart of some of the mutations that have been identified in both classical and variant hairy cell. They pretty much segregate along the lines of the diseases. Just kind of looking at this graph, you'll see that even if you have hairy cell leukemia and you have a BRAF mutation, there may be other mutations of clinical significance that are present, especially in the variant of hairy cell. Some of these are present in high percentages and can impact treatment options.
So what is this mutation doing? Any of these mutations are basically activating some part of the cell. In the case of the BRAF V600E mutation, it is constitutively activating BRAF which is part of a signaling pathway and you get oncogenic signaling through this MEK/ERK cascade, and I'll show you a picture of that in just a minute. But basically, that means that once that is mutated, this part of the cell does not turn off and it activates this cellular proliferation. And we know that if you have these cells in a Petri dish or in a human, and you give a BRAF inhibitor or a MEK inhibitor, you're going to see silencing of this, of the transcriptional output of this pathway. You're going to see loss of hairy cell gene expression, and ultimately, the cells will die.
And then just additional support for the theory that these BRAF mutations are pathogenic, is that they're present in the majority of classic hairy cell. They're present in the entire tumor found. So if you take any of these cells, they will have this mutation and there's a high stability of relapse, meaning if the disease comes back, the mutation will be present. So this is just a little cartoon of this pathway.
This is showing the cell wall. So this is outside the cell. This is inside the cell. All the cells have these receptors on the outside. And I have actually a better image of this that I'll show in just a minute. But typically, what happens is you get something that activates this receptor, and then it starts the signaling cascade. And in the presence of some of these mutations, this cascade just keeps going, whether anything is signaling or not and so the cell is always turned on.
Dr. Leslie Andritsos:
So one of the questions I had when I first started taking care of patients with hairy cell leukemia was why are these cells hairy? I don't know if anybody else has wondered this, but this is actually a real life sign of ongoing cellular activation. The outside part of the cell is in a state of constant reorganization because of this cellular activity and the cells start developing this membrane ruffling and microvilli formation. And actually, this group noticed this back in 2003 and postulated, years before we had any scientific data showing that these mutations are present, they said that these cells probably have constitutive activation of that Raf–MEK–ERK pathway that is causing this ruffling and hairy projections to occur.
Dr. Leslie Andritsos:
So let's move on to how we diagnose hairy cell leukemia. So as probably everybody on this webinar knows already, the indicators of possible hairy cell is low blood counts, low monocyte counts, which is very specific for hairy cell leukemia, enlargement of the spleen, and some people have an infection when they're diagnosed. If it's an unusual infection, that's even more of a clue that that's because something is affecting the immune system. Lots of patients have fatigue, weight loss, and night sweats. You may have fevers without an active infection. We can't rely on blood tests because they may or may not show circulating hairy cells. The hairy cells kind of like to stay in the bone marrow and the spleen and in other places where they survive. And so it can be actually hard to isolate them, especially from the bloodstream.
Dr. Leslie Andritsos:
So we really need a bone marrow biopsy for a definitive diagnosis. A lot of people don't want to have a bone marrow biopsy, but sometimes we can't avoid it. I just wanted to show this for people who have already had a bone marrow biopsy, weren't really sure what happened or are contemplating getting one. There's basically two parts to the procedure. So we do take out a little core sample. It looks like a little worm. It's usually about two centimeters or an inch long. This is a very good sample that they got. And this is where we do all the staining on the bone marrow cells. It's very important to get a good core because a lot of the times, we're not able to aspirate the bone marrow.
This part of the slide is showing how we aspirate the bone marrow. You put the needle into the marrow space and kind of pull up on the syringe and the marrow cells should kind of go through these holes up into the syringe. But unfortunately, people with hairy cell leukemia, a lot of times don't have an aspirable marrow, meaning we put the needle in, we know it's on the right place, but we're unable to get cells out. That's a very common scenario. So then we have to rely on getting what we need from the bone marrow core sample.
This is what the core looks like after it's been decalcified and stained with hematoxylin and eosin. Those are the two stains that give you the pink and purple. This is showing the bone part of the bone marrow, and then in the middle there, that's where the bone marrow is with the cell formation. The little white spots that you see are actually fat cells. You're supposed to have fat cells in your bone marrow; about 60% of your bone marrow should be fat cells. So when you see that percentage on your bone marrow report, what it's referring to is, are there too many blood forming cells in the bone marrow that can indicate the presence of abnormal cells?
Dr. Leslie Andritsos:
And then I put a picture of a stained bone marrow to show you that the stains are pretty specific. They should only stain the malignant cells. And I picked this one, because this is how a CD20 stain looks under the microscope. You see what we call chocolate donuts and you see a bunch of them here. So when you get some of those reports back and you're looking at them, when we talk about the immunohistochemistry, that's what that is, we're staining the bone marrow.
Dr. Leslie Andritsos:
So we talked a little bit about how hard it is to get aspirates on most people. The aspirates give us some very specific information. That's where we do all the genetic and molecular testing. This is just a picture of the chromosomes. Usually, in hairy cell leukemia, there are not a lot of chromosomal changes. Usually, the changes are in the genetic portion. This was actually a colon cancer report. I put up a result from FoundationOne. Every institution has its own next generation sequencing. And so they might send the sequencing in-house or they might send it out somewhere or they might send FoundationOne. But typically, we'll get the results. What mutations are present? What percentage of the cells have the mutations and what the clinical significance is?
Most of the time, these are very thorough reports. I think this is very important to obtain if things are not going well. That can maybe give you a clue into the biology of your own personal disease, that there is an additional mutation that needs to be addressed.
Dr. Leslie Andritsos:
Now onto these consensus guidelines. So this was one of the first tangible outputs of our Hairy Cell Leukemia Foundation collaboration, which was we really wanted everyone to agree on how we were going to define, how to diagnose hairy cell, how to do response assessments and make some indications for treatment. So this group was able to come to agreements on this. It was a project that took several years, but this was the first paper to establish standards for diagnosis, indications for treatment, the response assessments, recommendations for first line therapy and at relapse.
Dr. Leslie Andritsos:
When you're looking at your pathology reports, you probably are seeing a lot of numbers and letters put together. So I put this little cartoon here, which is a cross section of a lymphoma cell or a B cell. And basically, there are all these proteins that are present on the outside of the cell that kind of stick out into the matrix where the cell lives. Every cell has its own unique combination of these proteins. And so the first thing that we want to know is if you have a lymphoma or something looks like hairy cell leukemia, what are the markers on the outside? And so the definition of hairy cell or classical hairy cell was that all of these markers should be present. If they're not present or not negative, then we call that sort of classical hairy cell leukemia with an atypical phenotype, meaning an atypical type or amount of proteins on the outside of the cell.
When we do these stains, the stains should be positive for CD20, which is your chocolate donut stain, Annexin-1 and BE1, which is actually the immunohistochemical stain for BRAF. So even if you don't have enough bone marrow coming out to send to sequencing, they can actually stain the bone marrow for BRAF and that's pretty accurate. We also want to see that the BRAF mutation is positive either by PCR sequencing or the immunohistochemistry.
For variant hairy cell, I have put a few slides in here on variant because I imagine there may be some people here today with variant hairy cell. It's pretty much as above, but would be negative for CD25 and CD123 and the BRAF should be negative however that's being tested. This is sort of a notoriously difficult disease to diagnose. And I think the sequencing findings can be extremely helpful in that disease.
Dr. Leslie Andritsos:
In some circumstances, it is useful, especially at the time of diagnosis to get an ultrasound of the spleen to obtain accurate measurements of the spleen, or if there's some concern that perhaps there are enlarged lymph nodes, and you want to know how big those are before you start treatment so you can repeat those scans at the end of treatment, make sure everything resolved. CT scans might be important to do. And then some people are doing PET/CT scans, which is where you get this sugar molecule injected with a contrast, those tend to go to areas of cancer cells and they kind of light up on the images and it can direct you to see what areas are involved and how involved. Dr. (Tamar) Tadmor is currently doing a clinical study looking at this, looking to see hairy cell patients that had PET/CTs and what they typically showed in the various subtypes of the disease.
Dr. Leslie Andritsos:
So just a few words about variant hairy cell. We know that typically this has a more aggressive clinical course than the classical hairy cell. As I said before, by definition, BRAF negative, and was originally thought to always be CD25 negative. But now once in a while, we're finding cases that kind of have variable CD25 expression, and there are enumerable subtypes of variant where it may look for all the world like classic hairy cell, but the BRAF is negative or there's other gene usages that we don't expect to see in the classical, different mutations that are more commonly seen in variant. And then Dr. Christopher Oaks presented at our scientific session that there's some new epigenetic variants. And so I think we still have a lot to learn about variant hairy cell, how best to diagnose it, how best to treat it and that there's a lot of work to be done yet in variants.
Dr. Leslie Andritsos:
So back in 2008, the World Health Organization separated classical hairy cell and hairy cell variant. They're biologically distinct entities. Variant is no longer considered biologically related to hairy cell. But if you happen to be reading a review article or something along those lines, usually they'll cover both diseases, but they are not biologically related. Right now, they're in the WHO section with the splenic B cell lymphomas unclassifiable. I have a feeling that it will get its own section at some point just because it is such a complex disease.
Dr. Leslie Andritsos:
So let's talk a little bit about indications for treatment, because this can be kind of a moving target, but most people with hairy cell need treatment at the time that they're diagnosed because of different issues going on, but there is a small percentage of people who can actually be managed on watch and wait, and some of them for a long time. But, the majority of people need treatment because the reason they got diagnosed was because they presented for medical care having a problem.
Dr. Leslie Andritsos:
So the consensus guidelines for treatment say if the hemoglobin is less than 11, that's your red cell count, if the platelet count is less than 100,000, if the absolute neutrophil count is less than 1000 or if there are symptoms related to enlargement of the spleen or some of those other issues. One thing I will say is the blood counts do tend to go up and down. We don't always know why. And so it probably is good to have a couple of values before making a decision about treatment because sometimes even inflammation or infection can cause these numbers to be sort of in the treatment range and they make it better when you get better. And so it's all about the trajectory of the blood counts and what else is going on symptomatically.
We try not to treat hairy cell unless there's a good reason to. And the number one reason is that the treatment will not be curative. And so anything that we give you has potential side effects and some of them can be serious and so we don't want to do that unless there's a good reason. Treatment may increase the risk of infection. It can decrease vaccine responses and across the board in lymphoproliferative disorders, early treatment has not been shown to be of benefit. So if a person is asymptomatic, their blood counts are okay, maybe not completely normal, but not going down and not having crossed the threshold for treatment, probably should hold off on treatment because you do get the risk of side effects and there may not be a long term benefit.
Dr. Leslie Andritsos:
So after you're treated for hairy cell, we try to define how the treatment went. I wanted to just go through the remission criteria a little bit, because I think this is helpful information that you can discuss with your treating oncologist or hematologist about how treatment has gone. And so if we are saying that you're in a complete remission, that means that your blood counts have normalized. If your spleen was enlarged, it has gone back down to a normal size and a post-treatment bone marrow biopsy does not show any evidence of hairy cell by H&E staining. So that is the pink and purple staining that we saw earlier. This is kind of a low bar because the other stains are much more sensitive. However, most pathologists can look at your bone marrow and see if they see hairy cells.
You can have a complete remission even if there is some measurable residual disease. And I'm going to talk about that a little bit more in just a second. But, I know that it scares people when they get that pathology report after they've been treated and there's still some percentage of hairy cells, like it may say one to two percent. That is still a subject of investigation because we don't know the significance of that in all cases. I wanted to bring to your attention that the timing of the post-treatment bone marrow biopsy is very important. The timing should depend on what therapy was used, and you don't want to do it too early because these hairy cells take some time to disappear.
So, if you've had chemotherapy, the recommendation is four to six months post-treatment. If you're out to six months, that should give a pretty accurate count on whether there's hairy cells still in the bone marrow. For other treatments, I would just recommend following whatever procedures that were used in the clinical trial, because each treatment would have a different type of follow up and that wasn't really specified in our guidelines. So, I would just have your oncologist go by whatever they did, for example, in the Vemurafenib trial.
Dr. Leslie Andritsos:
So there was some discussion at the scientific meeting this week about measurable residual disease. There is no consensus on how best to identify this, how best to count it, whether we should be using the staining, whether we should be running the bone marrow or peripheral blood through flow cytometers to try to get a count. Some people use more sensitive testing, especially in the setting of clinical trials. They may do sequencing of specific parts of the genome to try to find what percentage of cells are still there. There is no formal definition or cutoff for measurable residual disease.
And furthermore, we really don't know the significance. So we know in some patients who have either advanced disease or refractory disease, this can be prognostically significant in that at the end of treatment, if there's still measurable residual disease, those patients may relapse sooner than those who had a hundred percent clearance of their disease. And I think that that kind of makes sense, but we really don't know in the patients completing their first treatment how to respond to that. Because each center uses different MRD definitions, and the significance is not always known especially in the upfront setting, we would recommend not making treatment decisions based on MRD alone.
Dr. Leslie Andritsos:
So there's a couple of other categories of responses - the partial response, stable disease and disease progression. So a partial remission, you should have normalized your blood counts and had at least 50% improvement in the bone marrow and spleen involvement. For stable disease, that one's a little bit harder, because it just means you don't need any objective criteria for either of the remissions, either partial or complete remission, but there's also no evidence of disease progression. So that can be kind of a frustrating situation for patients because they're not really knowing whether treatment worked or what the next best steps are. And then for progressive disease you would have, this is what the consensus guidelines recommend, so an increase in symptoms related to the disease in conjunction with an increase in the size of the spleen or liver and a decrease in the blood counts. It does not give a bone marrow percentage and that's something that might be addressed in the next version of the consensus guidelines.
Dr. Leslie Andritsos:
Just a bit about treatment because I know that this is something that a lot of people have questions about. The chemotherapies that we use the most for hairy cell leukemia are cladribine and pentostatin. These drugs are very similar. They're both purine nucleoside analogs. And the biggest difference is probably the schedule because cladribine, we give all the doses upfront over the course of one week, usually five days by intravenous administration or subcutaneous administration, or pentostatin, which is given as a dose about every two weeks. And the biggest difference between the two is that the cladribine, you give all of it regardless of what's going on with the blood counts. The pentostatin, you can either adjust how often you give the treatments or you can adjust the dose based on what's going on. There are specific situations, including COVID-19 pandemics where some people started using pentostatin because if your patient developed a COVID-19 infection, especially before there was treatments or a vaccine available, you could stop the treatment and hopefully stop any side effects of the treatment while the patient was recovering from their virus.
We know that both of these are highly effective in both the upfront and relapse setting. Both of these agents have equivalent responses and long-term outcomes so there's really not a better choice here. A lot of times, it comes down to what's going on physically and a person's schedule. We know that when you give these to people who are initially diagnosed, they have about a hundred percent overall response rates, meaning the blood counts get better, the bone marrow gets better, the spleen gets better and about 70 to 90% of those are going to be complete remissions, which is very significant. Across the studies, there's a five year progression free survival of about 70%, but there's certainly lots of people walking around that are 10 or 15 years out from treatment that have never experienced a progression.
The chemotherapies for hairy cell have resulted in near normalization of life expectancy, meaning if you have hairy cell and you got either cladribine or pentostatin, you could expect to live about the same amount of time as somebody your same age without hairy cell leukemia. So that's incredibly significant, a real success story in oncology, but because it's a chronic disease and we don't cure it with chemotherapy, about 40% of patients will experience a relapse. And I will say that some cladribine or pentostatin-based regimen was the standard of care in fit patients prior to COVID. And then after the pandemic started, we really kind of put the breaks on chemotherapy because of some of the side effects.
And so probably the biggest side effects are an initial decrease in the blood count so you may start out with low blood counts and when we give the chemo, the blood counts get worse. And so many of you who have been treated on this paradigm, you may have even needed blood transfusion support because of how low the blood counts got. The biggest worry is that the white blood cells are going to go down, even more the neutrophils, and that's going to increase the risk of infection. There's two ways that these chemotherapies increase the risk of infection. One is immunosuppression, meaning it interferes with your immune system cells, either decreases their numbers or function and then also myelosuppression, meaning this kind of across the board will suppress bone marrow function. Both of these are problematic, especially in people who have active or uncontrolled infections. This can be a tough management situation and the people who end up in the hospital or in the ICU, it's probably because of an infection that they developed as a result of this particular chemotherapy side effect. There's also a potential for neurological toxicities, like balance problems, things like that, if the kidney function is not normal. So, that is a huge consideration before starting these chemotherapies. If the kidney function is off, then maybe it would be better to try something else first or do a dose adjustment, for example, with Pentostatin. And actually you could decrease the dose of either of those agents.
Dr. Leslie Andritsos:
The initial time of treatment is probably the scariest time because you get the chemo, the blood counts go down and it's about four weeks before they start to get better. And during that time, there is this increased risk of infection, but that gets better and better over time. But does not really normalize until roughly around a year after the treatment, because you still have the ongoing immunosuppression, which is the effects on the T-cells and other lymphocytes.
Dr. Leslie Andritsos:
As I said above, we really don't want these used in people with uncontrolled infections, because that can lead to major problems with trouble controlling the infections at a time when we've got to wait about four more weeks before the blood counts improve. And in addition, these chemotherapies can prevent a good vaccine response. These are the reasons not to use these, although, as I said before, they have been incredibly important treatments in hairy cell and remain the most effective treatments, especially over the long term that we have.
Dr. Leslie Andritsos:
So, Dr. (Farhad) Ravandi, a long time ago back in 2013 published a paper, looking at Cladribine plus Rituximab. So we know in other lymphomas, that Rituximab, which is this antibody directed against CD20, which has one of those proteins on the outside of the cell. Rituximab is synergistic with almost any chemotherapy you give it with. This has been looked at for a long time and we know that the responses are fantastic.
Dr. Leslie Andritsos:
Dr. (Dai) Chihara at NIH with Dr. (Robert) Kreitman did a study of looking at giving Cladribine with Rituxan right upfront or delaying the Rituxan administration, if there were still measurable residual disease. And about 68 patients participated and were randomized between the arms. At six months after therapy, a 100% of the patients that got the Cladribine with Rituxan had a complete response versus 88% in the delayed Rituxan group. And then 96 months after treatment, 94% of them maintain their MRD-free status. That's the concurrently treated patients versus 12% of the delayed Rituxan patients.
One of the reasons why people have been hesitant to combine these two agents, is because of a concern that it would increase the risk of infection to put the Rituxan together with the Cladribine, because the Rituxan can also inhibit normal B-cell function. But they did not find any significant increase in toxicities and there was no increased risk of infection when these two were used together.
So many people find this to be practice changing, paradigm changing, because people are staying in great remissions for such a long time. And we know that there is not a signal that it increases the danger of treatment.
Dr. Leslie Andritsos:
This is just a slide showing a lot of the newer treatments that are now being used for hairy cell. Of course, we have our BRAF inhibitors, the main one that's been studied is Vemurafenib, but there's a couple others; dabrafenib has been studied in hairy cell and in other diseases, also encorafenib. All three of these were originally developed for treatment of melanoma because melanoma patients, about 50% of them, will also have a BRAF mutation. So these were on the shelf when this mutation was discovered in hairy cell.
We have these anti-CD20 agents, rituximab and obinutuzumab are probably your most commonly used. There is a new FDA approved treatment for hairy cell, which is anti-CD22 immunotoxic conjugate. I put a little cartoon of it because there was a nice one on the website of the company, which is now back to AstraZeneca, but basically this is an antibody that takes with it some poison. And so the antibody goes into the cell, the cell takes up the endotoxin and the cell dies.
We also have drugs that target the B-cell receptor. Ibrutinib has been studied, and I'm going to present some of that data. But there's a lot of other drugs, a lot like Ibrutinib with better toxicity profiles, and maybe even more powerful. And so I think we'll be seeing clinical trials of those in use for hairy cell leukemia. And then MEK inhibitions. So that's all right along that same pathway that you have your BRAF in. Those agents have been studied, especially in varying hairy cell patients with specific mutations in that same pathway.
Dr. Leslie Andritsos:
So just a word about the Vemurafenib. As I said before, it has been studied as a single agent. It's now being studied along with rituximab, and in some studies it’s been used with obinutuzumab. But basically if you give an anti-CD20 along with Vemurafenib there's a much better response. So, (vemurafenib is) an oral BRAF inhibitor. A lot of studies have used the melanoma dosing strategy. There's not an established dose when treating hairy cell leukemia. The Germans have looked at very low dose Vemurafenib and that has been effective. I think we're still finding our way on the dosing strategy, but you probably won't go wrong with just using the dosing that was used in the clinical trial.
Dr. Leslie Andritsos:
And so, Dr. Tiacci, who is just an absolute rockstar of hairy cell leukemia clinical trials performed a Phase II Study of 30 patients with relapsed hairy cell. I think they had an average of three prior types of treatment. And they got Vemurafenib 960 mg, which is the highest dose twice a day, plus Rituxan for eight doses. And the responses were incredible; 26 of the patients achieved a complete response and 17 of those were MRD- negative. So 65% of the complete responders were actually MRD- negative. It took about two weeks for their counts to start to recover; first the platelets and then the neutrophils. And 78% of those patients were still in remission at 37 months. I think this is going to be a very widely used treatment strategy for hairy cell because it is not chemotherapy based and the results are comparable to chemotherapy, at least in the short term. It'll be interesting to see what the long-term data shows.
Dr. Leslie Andritsos:
I did want to say a word about Ibrutinib because it's really important to have a backup plan. And I think Ibrutinib is a very viable treatment option in hairy cell leukemia. It's also an oral agent; it's a Bruton's tyrosine kinase inhibitor, which is basically an enzyme that keeps the cell going. It's been used extensively in other diseases, especially CLL with excellent results.
Dr. Leslie Andritsos:
And Dr. Kerry Rogers, who spoke at this meeting last year, performed a multicenter Phase II Study looking at it in relapse of refractory HCL and variant patients were also eligible. So 37 patients were treated, some got the lower dose, which is like our CLL dosing and 13 of them received a higher dose. The overall response rates, when you look at these, you'll say, oh, it's not really that exciting. The best overall response rate was 54% across the study. It tends to go up over time. And so on this trial, the responses were not even assessed until nine months after the treatment started.
The 36 month progression free survival was 73% with 85% of those same patients surviving out to that timeframe. The higher dose did not really improve response and so most people are probably using the lower CLL -type dosing. And even though their responses are not as exciting as some of the other agents, this drug can lead to significant clinical benefit. And if you have someone who's at a point in their life where maybe they just had something like open heart surgery, or they're not really a great candidate to get an intensive therapy, this is a reasonable option and should not be overlooked.
Dr. Leslie Andritsos:
This is the last treatment that I'm going to cover because it is very exciting to have a new FDA approved treatment in hairy cell leukemia, moxetumomab pasudotox. This is sort of the baby of Dr. Robert Kreitman, he's been working on this approach for many years. It's immunotoxin conjugate targeting CD22, which is very widely expressed on hairy cells. The antibody carries this pseudomonas exotoxin with it and destroys the cell that way. It's been looked at in both relapsed and classical and variant hairy cell. The treatment schedule, I think for some people might be difficult, just depending on where you're at with your work schedule or other things going on in life, because it's given intravenously on days one, three and five of every 28 days. And it can be given up to six cycles.
Dr. Leslie Andritsos:
There were 80 patients treated in the Multicenter Study. These were heavily pretreated patients and 41% of them achieved a complete response. 75% of them had some response, meaning their blood counts got better, the spleen shrank, things improved. Among the patients that were complete responders 27% of them were negative for minimal residual disease at that follow-up bone marrow. And so again this drug certainly has some serious side effects potentially. So hemolytic uremic syndrome where the red blood cells and platelets start to break down was seen in 7.5% of patients. And that does require stopping treatment if that develops, because that can lead to kidney failure and other problems. But if you do stop the drug, it's reversible, as is capillary leak syndrome. There is a very complex management strategy for both of these processes and so if somebody is going to receive moxetumomab pasudotox, there are people that will help come to your center, provide education and make sure it can be given safely. And that everybody knows what to do if there's any problems. I think one of the most important things about this strategy is it's a non-chemotherapy option that does not alter the T-cell number or function. And that can go a long way towards preventing short and long term side effects.
Dr. Leslie Andritsos:
Dr. Gerard Lozanski, who I stole that picture of the hairy cell at the beginning of my talk, was commenting on some of these therapies. He's a pathologist but he's very wise. And he said you know in hairy cell leukemia, there is no free ride. When it comes to therapies, everything has a potential toxicity, even if it's a pill, you may have a lot of GI side effects, skin rashes, joint pain, or swelling. They can affect the liver or kidney function. You know, they still require close management.
So the choice of treatment depends on many, many factors, including the person's health at the time of needing treatment; what the blood counts are doing, what the kidney and liver are doing. Sometimes it's a no brainer, just give the chemo, and sometimes it really requires a lot of thought and careful consideration.
Dr. Leslie Andritsos:
And those are the times when I do think it's very worthwhile to find a Center of Excellence in your area. Or even contact Anna through the email on the website to see if you can get a conversation going between your treating doctor and a hairy cell expert. That is something that we do pretty frequently and are very happy to do, because we want people to get the best treatment based on what's going on with them at the time.
Dr. Leslie Andritsos:
So just a couple of slides here at the end about complications of hairy cell. So this is one of the main reasons why the registry was developed because people were hearing that there were complications, but nobody really knew percentages, what types. And so this is going to be really wonderful to have access to some of this information so we can start getting it out to patients and providers. But infection is probably still the number one complication.
Hairy cell, in and of itself, even if it's never been treated, is going to suppress your immune system. It's not going to function normally. And so this is the big thing to watch out for. And that's why Marc was mentioning it at the beginning, get your COVID vaccine, because we know that COVID is very serious in people with blood cancers.
There's this other problem in hairy cell of the potential for getting other types of cancer. Most of them are non-melanoma skin cancer. So squamous cell, basal cells, especially here in the Southwest, people get tons of sun exposure and this is a very common problem that we see. So you'll want to see your dermatologist once a year, for a skin survey, especially if you're fair haired with blue eyes and have that kind of easily sunburned skin. Other carcinomas are possible. So don't skip your mammogram or colonoscopy. It's really important to stay on top of the other health concerns. And there's also some suggestion in the literature of a possible increased risk of developing other types of lymphoma. And that's a big question on everybody's mind. When we look at the registry data.
There are multiple studies showing an increased risk potentially for auto-immune disorders. The most common is just this annoying arthritis, which is usually red and inflamed, and it kind of migrates around the body. It's called palindromic arthritis, we usually treat it with steroids, but that can go on to become a more stable and constant arthritis. And so if inflammatory arthritis does develop, you should probably make an appointment to see a rheumatologist, and the same thing goes for vasculitis. So this is an inflammation of the blood vessels that has been reported in hairy cell leukemia. There's a number of things that can happen long-term that you'll need your hematologist or oncologist helping with consultants to manage.
Dr. Leslie Andritsos:
I wanted to talk a little bit about survivorship because that goes along with the previous slide. We have done a study of quality of life and I want to thank anyone on this webinar who has participated in this because it's showing us some very, very interesting results. What we found is that quality of life is lowest at the time people are initially diagnosed and having to get their first treatment, and then it goes down again during relapse when you need treatment again. But the rest of the time, people with hairy cell leukemia have a better quality of life than normal people without hairy cell and cancer controls.
I think it is an upsy, downsy rollercoaster having hairy cell leukemia, but the majority of the time people report a good quality of life. I did want to make the comment because we had asked this question at one of our in-person patient seminars a long time ago, whether people had gotten these positive messages about how great it is that you have hairy cell and that's such a good leukemia.
And I think if you're in the ICU, because you have a terrible pneumonia, it's not a good leukemia to have. There's tons of side effects and complications that go along with having hairy cell. And in CLL patients, which is kind of a similar thing, they found that these positive messages lower the quality of life. And there's now a name for this: it's called toxic positivity, where people are telling you positive things when you're trying to tell them something that's bothering you. I think it's really important to know that this is very, very common. We don't really know why this happens, but, you can expect to hear this along the way, over the course of your disease.
So the survivorship is extremely important in a chronic disease. As we talked before, you need health screening for other types of cancer, you've also got to manage those non-cancer medical problems. So we need your kidneys to be working. You know, we need everything working if we can, so we can give you the best treatment if you need it.
Also consider getting treatment for PTSD or other psychological issues that can arise from what I think of as healthcare trauma, meaning you're diagnosed. Maybe you get whisked to the ICU because you're very sick or septic or something like that. These have long-term consequences and should not be ignored because there are lots of people that can help with coping strategies around this. There's also the worries that go along with having a chronic disease. There should be some monitoring for associated auto-immune conditions. This can be as simple as a physical exam and just someone taking your medical history. And then of course the judicious timing and choice of treatment.
Dr. Leslie Andritsos:
So just a word about COVID-19. I have a feeling there will be some questions about this today, but we know from very, very early on when the data was first coming out, before we had vaccines or any treatment patients with hematological malignancies were more likely to develop severe COVID-19. And that was pretty much across the board, any blood cancer. We know that if you have hairy cell, you're sort of intrinsically immunocompromised, and then when we treat you, we make that worse, at least for some period of time. However, they did see in some patients with CLL who get similar treatments, once they have completed treatment and in remission had great responses to vaccines. I don't know if that will also be the case in hairy cell, but there's some early signals that hairy cell patients are responding to the COVID-19 vaccine.
The Leukemia & Lymphoma Society recently published a paper that did include some hairy cell patients. They all responded to the vaccine. And so this is where we've had sort of a paradigm shift in treatment. Choice and timing of treatment are the key. So if you have not been immunized, you're probably going to want to avoid these anti-CD20 monoclonal antibodies because they suppress normal B-cell function. And you need those normal B-cells to make antibodies to a vaccine. It's a complex response, but B-cells are definitely part of it.
And the same thing goes with chemotherapy. If you can delay this until after you've been immunized, that would be best because it may be a year or so before you will mount a good vaccine response and there can be a lot of danger during that time. I think as a group we're leaning towards targeted therapies, especially Vemurafenib. If there has been a poor vaccine response or for some reason we don't expect you to be able to get a COVID vaccine. Vemurafenib is not a chemotherapy, it will not inhibit vaccine response. And it helps the blood counts to normalize very quickly.
I think a lot of people are leaning towards Vemurafenib with or without Rituximab, depending on whether the vaccine has been administered. And then of course, moxetumomab pasudotox. If there's a real reason to not give chemotherapy and the targeted therapies are not going to work, that is a chemo-free option for fit patients that's highly effective.
Dr. Leslie Andritsos:
I wanted to give a special thank you to our patients. We've had over 500 hairy cell patients who have consented to participate in the data registry. About 400 of those we've been able to get their records for upload into the registry. And a lot of those people have also consented to the quality of life study.
I just wanted to give a quick overview of the types of studies that are being planned by our colleagues, both in the U.S. and around the world, because we have a scientific review committee meeting to approve studies. And these are of course all anonymized data.
Dr. Eric Kraut is looking at blood counts and patients with hairy cell leukemia; with a hypothesis that these may not be as common as in other types of cancer, but we'll see. Dr. Tadmor, as I said previously, is looking at use of PET/CT scans in patients with hairy cell. Dr. Tadmor in Israel and Dr. Matthew Cross in the U.K. are looking at bone involvement by hairy cell.
And so we're here to do this research for you so that you have more information, but we absolutely could not do it without you. So I want to thank you all so much for being a part of this process. It's been a really wonderful thing to be involved in, and it's been definitely the best part of my career so far.
Dr. Leslie Andritsos:
So here's our team at UNM. The bear stands for strength and healing. That's our cancer center logo. And then we have a lot of collaborators, but I want to especially thank Anna Lambertson and Ken Jensen who have been at every single data registry meeting and been so helpful to work on this project and get it off the ground at other sites. We have a lot of collaborators, both at OSU and around the world. This research has been made possible by The Hairy Cell Leukemia Foundation, which is made up by you, and with additional support from the SASS Foundation.
Transcript of Question & Answer with Webinar Participants
Anna Lambertson:
So there have been a number of questions that have come in about the patient data registry. I just want to quickly say that if you would like to find out whether or not you have registered or been added to the patient data registry, you're welcome to reach out to us. If you go to our website, there is a form you can fill out and work with the team at the Ohio State University to join the patient data registry.
You can also email us and we can converse with the Ohio State directly to see if you are in it or not. If you want to email us at info@hairycellleukemia.org, and we can be in touch with them to see if you've joined. I just wanted to address that really quickly, because we've had quite a few questions about the patient data registry. Thank you Dr. Andritsos for bringing that up.
So Dr. Andritsos you did talk about COVID and as you had assumed, there would be a number of questions about that. It sounds like you are advising patients, if possible, to be vaccinated for COVID prior to treatment. What about the booster? There are a number of patients who have asked about getting a booster, getting that third shot, what is the right timing for them, given that if they have Hairy Cell Leukemia or have recently completed treatment, they're most likely immunocompromised? Can you advise those listening about how to, whether or not you're recommending the booster for your patients and what the right timing might be for them to consider with regard to that booster shot?
Dr. Leslie Andritsos:
This is a very tough recommendation in people who are actively undergoing treatment. Most of our treatments are done on a cycle basis. For example, Rituximab is given sometimes every four weeks, depending on the treatment, I'll recommend trying to get the booster just at the very end of that cycle. So as far away from the Rituxin as they can get it and then have a few days up to a week, if possible, to respond for maximal benefit before they get their next treatment.
I'm recommending that all my patients get the booster shot, they're eligible. The CDC guideline is within, if it's within 28 days of their second dose of their original vaccine. So if you're about a month out from your original vaccination, you can go ahead and get your booster.
One of the questions that comes up a lot is whether there has been a vaccine response. I do not get any kickbacks from these labs, but I will say that there are two labs in the US that will let you get COVID Titers drawn. One is LabCorp. The other is Quest. Some of them require a doctor's order. Some of them don't. They're not letting us send the test here because I think they're worried that it would overwhelm our testing system because everybody wants a test, but you can either ask at the center where you're being treated, or you can ask at one of these private labs.
But I think oftentimes it's really important to know if you've had a vaccine response that may really alter your behavior if you're thinking about going on a cruise or seeing your unvaccinated grandkids, certainly it's helpful to have a good vaccine response. And if you know that you have not, you might be in a situation where you might not travel or do some of those other things that would potentially increase your exposure.
Anna Lambertson:
And are you still recommending the vaccine for an HCL survivor who previously had COVID and may have developed some natural immunity?
Dr. Leslie Andritsos:
So that is the big controversy in COVID 19 right now. But I would say yes, because I saw a proof, it's not peer reviewed yet though, but there was a study in Israel looking at vaccine responses and people who had COVID had some natural immunity and then got vaccinated, had an outstanding vaccine response. And we know even if you've had COVID and you have some antibodies, you can get it again. And each time you get it, there's significant risk from this virus that causes blood clots. It causes pneumonia. Sometimes it can cause lung damage, even if you didn't know that you had pneumonia. So it's just better really not to get it. And certainly if you're in the middle of treatment, especially chemotherapy based treatment, I would recommend just continuing to wear a mask. Even if your community is not mandating it, you don't want to be exposed to this virus and the masks do work.
Anna Lambertson:
We've also received a few questions; sort of a two part question. The one is if someone has contracted COVID, they've tested positive for COVID, but they also have Hairy Cell Leukemia that might need treatment, how you might manage that difficult situation? And the second question is, you spoke about Vemurafenib, which we know some doctors are using as a bridge or as a treatment for patients given the ongoing risk of COVID, for patients who are immunocompromised like those with HCL. So how are you adjusting your treatment decisions for your patients given the risk of this ongoing pandemic?
Dr. Leslie Andritsos:
Right. So definitely if somebody has COVID, I would avoid chemotherapy. So if somebody has COVID and they're urgently in need of therapy, which we have seen for various reasons, sometimes people are neutropenic. That means the neutrophil count, which fights your bacterial infections, can be low just from the Hairy Cell. And so when we've had a few patients in the ICU, we actually published this a few years ago in Blood Advances, where we were able to rescue the situation using Vemurafenib to get those blood counts up because they come up pretty quickly with starting Vemurafenib.
And so I think for somebody with COVID, if they were in urgent need of therapy, I would probably give Vemurafenib at least initially by itself to get those blood counts up. And then depending on how things go you can add on an anti-CD 20 at some point, if you need to. It is important to know that the responses to Vemurafenib when you give it by itself are not that long. It's like an average of nine months, and so you will lose your treatment response eventually with just using it by itself. But if it's an emergency situation, it's the treatment of choice. I would say if you're also treating an infection.
Anna Lambertson:
And there have also been some questions about the right dosage of Vemurafenib. What are you recommending for patients with regards to Vemurafenib?
Dr. Leslie Andritsos:
I think the OSU group kind of split the difference. So the clinical trials have used 960, which is the melanoma dosing, but there can be some significant toxicities with that, especially rash and joint pain, other problems. The Germans looked at using a lower dose in people who really couldn't tolerate that high of a dose 240 milligrams and found very good outcomes. And so here in the US, we're just kind of splitting the difference at 480 twice a day. That's a dose where you have room to go up or down if you need to. And so that can always be dose decreased if there's a lot of side effects or you can increase the dose if it's not working as well as you hope.
Anna Lambertson:
I see a question about a vaccine with live virus versus non-live virus. And I just want to reiterate to everybody that it’s really important that you only use vaccines that do not have a live virus. I think it's our understanding that these vaccines that are being used for COVID are not using a live virus.
Dr. Leslie Andritsos:
So the COVID virus is not live. There are some other viruses that are commonly used, the Shingles virus vaccine, the original one, was a live attenuated vaccine. And we recommend that people do not get that. There is a killed vaccine that actually interestingly seems to work better, which is the Shingrix. And so we recommend that killed vaccine. It's also important to realize that it's possible to lose some immunity over the course of your life, and especially if you've developed Hairy Cell or had treatment for Hairy Cell, and so if you have young children in the family that have gotten their Measles, Mumps, Rubella, that is also a live vaccine, and so they usually recommend waiting three weeks to have close contact with MMR recipients if you're immunocompromised.
Anna Lambertson:
I want to circle back to some of the information you presented about Cladribine plus Rituximab, which we know has been given a lot of attention because of the research by Dr. Ravandi and Dr. Kreitman. With your patients, are you recommending the concurrent or the delayed addition of Rituximab to Cladribine. And what are you basing that decision on?
Dr. Leslie Andritsos:
So right now the biggest decision is whether people have been vaccinated and whether they're physically fit to receive that combination; for example if the kidneys are working well and things like that. But I think it is, in fit patients, it is the standard of care nowadays, and so that would be the recommendation, unless there was a really good reason to not give chemotherapy.
Anna Lambertson:
We've been in touch with an individual who was given Rituximab on day one of Cladribine then completed the Cladribine treatment, and now the doctor and the patient are trying to decide whether they should continue with Rituximab, so do the Rituximab for another five days or so. Do you feel that at that stage offering the delayed Rituximab would provide an additional benefit or what would you advise in this situation?
Dr. Leslie Andritsos:
Yeah, that's a really good question. And so I would say wait four to six months after the Cladribine and then do a bone marrow biopsy, because if you're in a complete remission there may not be any added benefit to giving the Rituxan. If you are not it may be beneficial, but the response will not be as long as the people who completely cleared out their bone marrow upfront. And so I think the strategy of giving them together is kind of hedging your bets that you want to treat the Hairy Cell Leukemia just as completely as possible upfront, because if you don't get it all there may be some leftover cells at the end that could make the time to needing treatment again shorter in that scenario.
I do think that most people that were in the scientific meetings and practicing all over the US and elsewhere are giving it upfront together. If you're in a complete remission, it's not clear what the benefit of that would be at the end.
Anna Lambertson:
There have been a number of questions that have come in about the BRAF mutation. Some of the questions that we've had about the BRAF mutation are: one individual said that their BRAF mutation results indicated a low level. What does that mean, if anything? When a patient is in remission, there is no further indication of the BRAF mutation. Is that true? And does the mutation return if a patient experiences a relapse of the disease?
Dr. Leslie Andritsos:
This is a really good question. I wonder if it's a scientist posing this question. So there is this new concept in blood cancers of circulating tumor DNA, where you can detect some of these mutations in the bloodstream. And usually they correlate pretty well to what's going on in the bone marrow or elsewhere in the body. And so if you see the BRAF mutation DNA in the bloodstream, that tells you that somewhere in the body, usually the bone marrow, there is hairy cell either still present or trying to come back.
The testing that we do by staining is pretty accurate in the bone marrow. And so if you've had a bone marrow biopsy and they stained it for BRAF that basically gives you the percentage of cells in the bone marrow that are hairy cells. And so for BRAF mutated, classical, Hairy Cell Leukemia, the BRAF mutation itself pretty much correlates with the amount of disease that you have at the time. I will say for circulating tumor DNA type of testing, that's still a research objective. Some places are doing it as part of clinical trials, and so you could ask your local center of excellence if that's a test that they're doing for surveillance after treatment.
Anna Lambertson:
We do hear from time to time from patients who hear about the BRAF mutation on one of these webinars for the first time. And then they say, "Wait, I haven't been told if I have this or not." You know, if they've successfully completed Cladribine treatment and are in remission they most likely did have it, but would you recommend to your patients that they confirm with their doctor, whether or not that is present?
Dr. Leslie Andritsos:
Yeah, I think the most important thing is to confirm that the test was done. So this data has been out for long enough now that I think pretty much all pathology departments at any hospital would perform a BRAF test if Hairy Cell Leukemia was suspected. But I did have a patient recently that had a bone marrow and it was not sent for BRAF. And so making sure, confirming that the test was sent and knowing whether it was positive or negative, because that dramatically alters your treatment options.
So if the mutation is positive, then you can get Vemurafenib or maybe one of the other BRAF inhibitors. And, if it's negative, that's an indicator of possible Variant Hairy Cell Leukemia, or you have an unusual BRAF mutation that the test does not pick up. And sometimes that can require additional sequencing. I know that Dr. Kreitman at his facility at the NIH is doing some alternative BRAF sequencing to try to pick up on these other mutations that are BRAF, but they're not the same sequence as the normal BRAF mutation. And so that might be worthwhile if you look for all the world like a classical Hairy Cell Leukemia, but your BRAF is negative.
Anna Lambertson:
So the most important piece of this is whether it's positive or negative. The patient who asked if their results come back a low level, that's not particularly significant.
Dr. Leslie Andritsos:
No, it's still positive.
Anna Lambertson:
Thank you for clarifying that.
We have an interesting question from someone about Hepatitis B and I have received questions from patients related to Hepatitis B before. So I think it'd be worthwhile to relay this to you. So for a newly diagnosed HCL patient who has also tested positive for Hepatitis B, it seems like the individual developed some antibodies when they got infected and the Hepatitis B is currently inactive. What would be the best treatment plan for this, the best treatment for the HCL for this newly diagnosed patient, given the Hepatitis B infection, which they have been told is currently inactive? Is that something that you need to take into account when you're deciding treatment for your patient?
Dr. Leslie Andritsos:
Yes, definitely. So we know that Rituxan administration can cause reactivation of Hepatitis B and in many places that's actually part of the laboratory testing panel prior to starting Rituxan, because it doesn't mean that you can't get Rituxan, It just means that you might have to take an additional antiviral treatment to prevent hepatitis reactivation during treatment.
Anna Lambertson:
Thank you. That's really good information. I do appreciate you taking a little bit more time with us given the number of questions that we've received. In terms of, you spoke about stem cells, you talked a bit about kind of the genetics of Hairy Cell Leukemia, and I think that when individuals with HCL hear that they start asking themselves questions like, "Well, is this a mutation that I can pass on to my children?" You know is there a defect in the patient's DNA or is it just the mutation? Do you mind clarifying that point just a little bit for those who are listening?
Dr. Leslie Andritsos:
Yeah, that is a really important point because as I presented there is an increased risk of Hairy Cell in first degree relatives of people with Hairy Cell. And so that tells us that there must be some familial susceptibility to developing the disease. And that may just come down to your white blood cell, we call haplotype, meaning what proteins are expressed and utilized by the white blood cells in the course of normal immune system activity. I don't know if I would say that the risk for Hairy Cell per se could be passed along to children. But I would say that there is a potential risk of a familial susceptibility to lympho proliferative disorders.
At the current time, I don't know of any tests, like genetic testing, that would tell us that. For example, with breast cancer there are very specific BRCA1 and BRCA2 gene mutations that we can sort of give somebody their lifetime risk of developing breast or ovarian cancer. We don't have that in Hairy Cell Leukemia, but it certainly is known that if you have Hairy Cell, there's a chance that a sibling or a parent or a child could be diagnosed with it as well. It's about an eightfold increased risk.
Anna Lambertson:
Dr. Andritsos, we're really grateful to you for not only such a substantive presentation, but also taking the time to answer questions. And I want to thank everyone who joined the webinar today. Thank you for sharing your stories and your experiences with other patients. Enjoy the rest of your day everyone.
Dr. Leslie Andritsos:
Thank you, everyone. It was very nice to be here.
This transcript has been edited for clarity.