Webinar: Hairy Cell Leukemia and the Immune System
April 29, 2020
Hosted by the Hairy Cell Leukemia Foundation with Dr. Tim Call from the Mayo Clinic.
Presentation Materials
View a recording of Dr. Call’s presentation (audience Q&A is in the transcript only). >>
Transcript
The following is a transcript of the 1.) Presentation given by Dr. Call and 2.)Question & Answer session with participants.
Presentation from Dr. Tim Call
Tim Call:
Hello to everyone. I wish you all safety and peace in this time of the COVID-19 outbreak. This afternoon or morning depending on where you are, I'm going to take a tact of discussing really two topics. The first is an overview of hairy cell leukemia. And some of you who've been on these webinars in the past will recognize that I have abbreviated much of that. And the second half is to just give a little description of our immune system. That's a huge issue right now.
So I want to address, to call your attention to the picture on the slide. When we look at chronic leukemias, hairy cell, in particular we have to kind of realize bone marrow is an organ just like your heart, lungs, kidneys are organs. The bone marrow is an organ, but it's not in one area. It is diffusely located throughout our bones.
If you think of a round steak bone, you have the hard supporting bone and you have the liquid marrow. Marrow is a liquid. It's composed of cells and fat. I won't go through everything on this slide. On the far left side you will see there are earlier stem cells and precursor cells that are generated. And then from the bone marrow, they are matured into various what we call lineages. So one of those is the red blood cells or the erythrocytes. At the bottom of there with the platelets.
Tim Call:
The white blood cells, I tell people and those who have been my patients, they heard this analogy, white blood cells are kind of like a different vehicle. They are a different subtype, maybe convertibles or SUVs or pickups. There are different types of white blood cells that are important in immune functioning, fighting infections. And so when you look, you'll see at the top, lymphocytes, monocytes, neutrophils.
And then there are other things like eosinophils, which will be elevated with an asthma or a parasitic infection. So when we look at this then, the hairy cell leukemia is really a disorder of lymphocytes. Lymphocytes can be subdivided into multiple different subcategories. There are T cells, there are B cells and there are natural killer or NK cells. Among each of those subgroups there are multiple other subgroups.
So for instance, in the T cells, there are multiple subtypes, CD8, CD4, Tregs. And the B cells some provide immunity, some have memory from prior immunization or infection. There’s a lot of complexity in what we call hematopoiesis or the generation of blood cells. These are all under the control of various what we call cytokines or growth factors. And so depending on the challenge to the body, they may increase or decrease.
Tim Call:
With that as the background, I want to present a case. This is a 48 year old I saw a number of years ago who presented with a cough and fever. His chest x-ray that day in the emergency room showed pneumonia. He was advised admission, but refused admission. So the emergency room doctor gave him one IV injection and put him on oral antibiotics.
Unfortunately, he made poor choice and he was returned to the emergency room within 18 to 24 hours in respiratory failure. And that did require a mechanical ventilator, but he did survive. His initial blood count, remember we talked about the various lines, the reds, the platelets, the whites showed a decrease in all three of those lines. He was anemic with his hemoglobin less than 8. The normals are in parentheses, the platelets were low normal or low, and the white count was low. Lymphocytes, you see there.
Neutrophils are what are most important in fighting bacterial infections. So you have pneumonia, normally you have increased neutrophils. You have appendicitis, you have neutrophils. And then monocytes are also involved in engulfing and destroying organisms and those were low. He was pre antibiotics due to the severe lung disease, steroids and oxygen. And in fact, the cause of his pneumonia was Legionnaires or Legionella.
Tim Call:
Over the next week, his pneumonia improved, however, his blood counts remained low. Initially, the doctors taking care of him were thinking that these prop and blood counts could be due to overwhelming infection, which it can be, but the fact that they persisted, they submitted a consult to our hematology team. As you see his hemoglobin counts are better, but still very low three weeks later. Reviewing his case, a CT scan of the chest had been done to look at the pneumonia and it showed an enlarged spleen. His blood count, when we look at the blood under the microscope, what we call a Leukoerythroblastic smear, it showed immature red blood cells and white blood cells. That's what a myelocyte is. And it showed a low monocyte count.
In other words, the nuclear red blood cell site says that the marrow is under stress and the monocytes are just known to be low. So a bone marrow biopsy was recommended.
In the far right upper slide is a normal bone marrow. And what you see there is cells, the blue dots. This is under a lower power and you see those holes, where fat was. When we do a biopsy, the specimen has to be decalcified (overnight) and that leaches away the fat. And so you're left with what looks like holes. The amount of fat is proportional to your age. So if this patient was about 50 years old, this would be pretty normal.
Now going over to the bone marrow on the left side of the screen, I wrote the word aspirate or dry tap. If you look at that marrow, that is hairy cell leukemia, and you see there's very little fat. And in fact, these cells are closely packed together. Not on this stain, but on special stains we can see that there's an increased amount of fibrous strands. So obviously you can't make as many normal blood cells. It's less liquid. So sometimes with hairy cell when we pull back to get the liquid marrow, we just don't get much. The aspirates are where we pull back the liquid, the biopsy is when we take a core. And so that would be typical.
Tim Call:
On the bottom slide, on the left side. The bone marrow can have kind of a starry sky appearance, and that shows that. On the right lower part of the slide, this is what a hairy cell looks like. This was one that was found in the blood. You don't always find them in the blood, but there's a picture of the cell with the kind of shaggy border.
Looking at hairy cell leukemia, it's rare. It's around one to 2% of adult leukemia. There's a male to female predominance. And the most common presentation is just what we just described. We call it pancytopenia. So pan meaning all, cyto cells, penia low. So it's a suppression of the hemoglobin, white count and platelets. Only in about 15% is there an increased white blood cell count. We also see a decrease in what are called the monocytes.
Enlarged spleen is common, but not always present. One of the things that is not well understood, but clearly recognized is a deep aching bone pain. Often this will resolve with therapy.
Because of the low white blood cell counts, what's called the monocytopenia … monocytes, which again, help to engulf infected cells, we may often see presentations like this patient with the diagnosis being made when someone presents with pneumonia or also with what’s called atypical TB. So not tuberculosis, but there are tuberculosis like organisms which are present in the environment and normally don't cause disease unless you're immune suppressed. However, with more and more routine hematology screenings, it's also not uncommon now to find the diagnosis through low blood counts found at the time of screening.
Tim Call:
So when you have a diagnosis of hairy cell disease, what needs to be done? Well, obviously the blood counts, the review of the bone marrow. Either from the blood and the marrow or both, we can do what's called flow cytometry.
On the surface of cells there are various what are called antigens. Like a barcode, they really are the code for the cell. They identify the cell. These are given the word CD, it stands for cluster designation. So these various antigens are present on cells and different cells have different codes. And so whether it's leukemia, chronic lymphocytic leukemia, marginal zone lymphoma, it may look somewhat similar under the microscope, but will have different codes.
So what is done is antibodies to these antigens are used, they're linked to a fluorescent substance. They are incubated and then these are analyzed by using images and counting of these … how many cells or what's the density of these markers on the cells. So think of it as a barcode and a barcode scanner to be simple.
The bone marrow biopsy, we look at that both looking for the changes I showed on the previous slide, but we can also do special tests looking either with what's called immunohistochemistry, where we use molecules that will stain, or we can use molecular sequence analysis to look for things such as the BRAF gene.
Obviously examining the patient, getting the history. Certainly I would almost always want a chest X-Ray just to make sure that it's not an early infection and it's up to physicians based on symptoms, whether we need any additional scanning. I put down screening for hepatitis, that would be if one was going to be using rituximab. Because sometimes it can cause a recurrence of hepatitis.
Tim Call:
I'm not today going to discuss a lot about hairy cell variant. I will certainly take questions if they're there. But I think the most important thing, being in a center where we do a lot of second opinions, is that it is very important that we have expert pathology review of the samples. There are other conditions which can look similar; that includes the variant, which tends to be BRAF negative and have the other features. Splenic marginal zone lymphoma can sometimes have what are called villus lymphocytes, so irregular borders. There's a rare condition called red pulp lymphoma, et cetera. So one of the things that when a person comes here, I will always ask that their pathology be reviewed by our hematopathologists. And we've had patients who the most common thing would be some form of marginal zone lymphoma. And that's probably more common, more or equal to the presence of any kind of variant.
The indications for treatment really are certain numbers and certain symptoms. So looking at the blood counts, if you're becoming anemic with hemoglobins less than 10 to 11, platelets less than 90 to 100,000. Or neutrophils, remember, those are important in infection fighting, especially bacterial infections, they are normally at about 1700 or 1.7 thousand or greater. The lower they go, the more likelihood of infection. So although it is very reasonable to observe hairy cell leukemia, if there are no symptoms and the blood counts are normal, I rarely would observe if the neutrophil count fell less than 1,000. I'm just more concerned about infections. And then other features, is the spleen causing problems or are there other things, obviously bone pain.
Tim Call:
I'm going to try to use this slide to just give you an overview of hairy cell leukemia treatment. We will just make this brief because, I think this is well described. Historically, many years ago, splenectomy, then interferon. Cladribine is now, due to its response rate and durability, the most common treatment we use. It can be given either as a two hour infusion daily for five days or as a seven day continuous infusion. It can also, in some European countries be given subcutaneously.
It has a high greater than 90% response rate and about 80 to 90% CR, (which) means complete response. There is data more and more emerging that if we give rituximab with Cladribine, the complete response rate is higher. The treatment of hairy cell with Cladribine is associated with the very durable response with 60 to 65% still in remission.
We would recommend delaying a repeat bone marrow to assess response for six to nine months due to the fact that we can see a delayed response. Pentostatin is a cousin drug to Cladribine, high response rate and well tolerated. Either of these can be combined with Rituxan. But Rituxan only has not as high a complete response rate. Rituxan is not officially approved for hairy cell, but it doesn't seem to be hard to get it used in what we call off label. That means the FDA hasn't labeled it for the disease but we can use it.
Tim Call:
Vemurafenib is a drug that's been available for malignant melanoma, because the hairy cells are BRAF positive, and most malignant melanomas are BRAF positive. We know that this has a very high and rapid response rate in hairy cell disease. However, it does not appear to have anywhere near the durability of Cladribine. In other words, often within one and a half to three years you need to be retreated.
Ibrutinib, which is available for CLL is, there has been some data with this, but it tends to have few complete responses, but some stable disease. It can be used in patients who have failed other things off label. And then, one of the champions of hairy cell in this country is Dr. Kreitman. His agent, Moxetumomab or Lumoxiti, was approved about a year and a half ago. It's an immunotoxin that binds to the CD22. It has been approved only in relapsed disease. A final note on this page is if it's variant, we need to add Rituxan to Cladribine or Pentostatin.
Tim Call:
Post-therapy, we recommend monitoring every one or two weeks until counts are recovered and then periodically thereafter continue to watch for signs of infections.
In our meetings for the Hairy Leukemia Foundation, there have been multiple debates on bone marrow biopsies. If there's been a very quick response, the blood counts are normalizing, it is not absolutely mandatory. The question is, will it lead to change in management? Generally, I'm more in the do the biopsy. But certainly there are multiple hairy cell disease experts who have said, if it isn't going to change the management, why do it? One of the problems that can occur is, we can see continued improvement and deepening of response up to 12 to 18 months. And with the sensitivity of flow cytometry, now we can detect cells down to one in 10,000. But one of the questions we get is, we've had the marrow, we're in remission, clinically counts are normal, marrow doesn't show any hairy cells, but the flow shows four and 10,000 cells. Do I need more chemo? The answer generally is no.
Tim Call:
I just mentioned that there are these various cells. On the left hand, one of the cells at the top is called the plasma cell. And then what are called macrophages. Plasma cells generate antibodies. They are where our antibodies are generated and macrophages helping engulf bacteria or viruses.
Tim Call:
So there are many facets, many components of our immune system. First there are things we don't normally think about, our skin. It's a barrier. Mucus membranes are our barriers and also there is lymph tissue in those areas, for instance, in the intestine. There’s also what's called pyres patches, which are aggregated lymphoid nodules in the lungs can help move the mucus out. Stomach acid will inactivate many bacteria. Urine flowing appropriately will help cut down risk of infection. That's why, a large prostate or something causing one to retain urine is associated with infection. The second line of defense are these various cells that we have here. The DC stands for dendritic cell … DC, macrophage, monocyte. These are all cells that are involved in being stimulated or attaching to antigens, which would be infective agents, and then presenting them further for the immune system to react to.
Tim Call:
We've mentioned the neutrophil for bacterial infections, eosinophil for parasitic infection, natural killer cells, T cells. And then, a common cell that we talk about is what's called a CD4 or T helper cell. That's what is low in HIV AIDS and is associated with many of the infections. CD8 T cells are suppressor T cells. They can be stimulated by inflammation. And then B cells, this would be an example of a plasma cell that has antibodies that is producing.
All of these things are associated with the various lymph organs, which are the lymph nodes throughout the body, the spleen, the thymus, which is larger as a child and then gets smaller.
Tim Call:
So when we look at our immune system, it's important to divide it in our thought pattern between the innate system and the adapt system.
The innate system is really, if we're normal in terms of our blood forming ability, there are some conditions where we don't make normal neutrophils or we have lower numbers or they're abnormal. The innate system is everything I've just been talking about, that you have a certain number of neutrophils, certain number of monocytes and dendritic cells and these come from stem cells.
Tim Call:
The adaptive is really the, what can the body do on the fly? So the adaptive is saying we've been exposed to something, can we generate either a T cell response and then remember that so that in the future, if I'm re-exposed I can send T cells specifically to that antigen? And also the B cell part, which is stimulating B cells, memory B cells and making antibody that will increase after infection. So in the COVID, when we talk now about giving the antibody tests, this is a plasma cell, B cell generated antibody that can be checked for. And there are different subtypes which I won't get into right now. So, it's adaptive.
Tim Call:
So when one gets a vaccination, you go through the protective layer of the skin, you inject an antigen, which has been changed so it won't cause the disease. The dendritic cells find these, accumulates around. So you're getting inflammation from dendritic cells and T cells and they start to mature. They then move when you see the arrow down to the lower box, those dendritic cells present the antigen to the naive T and B cells. They start generating an immune response, which can result in T-cell immunity with memory. These are guided by various interleukins and interferons that help simulate or humoral where antibodies are generated.
Now, one of the things that can happen with an immune response to anything, these T cells sometimes can overreact. And that's part of the reason you've heard of the COVID-19 causing significant lung problems.
Tim Call:
What are the immune effects of hairy cell leukemia? Well, you can have low neutrophils, low monocytes. In some patients there may be elevated levels of IL-2. But you can have also abnormal T cells, abnormal NK cells. The dendritic cells may not present cells exactly.
You can actually have hypergammaglobulinemia, as opposed to hypo. That doesn't really cause any infection issues. And there can be auto-immune. Now treatments also can further complicate the immune system by suppressing. Cladribine and Pentostatin can decrease CD4 counts that can last for sometimes up to 18, 24 months. Interferon can help the immune system, but it can also suppress it.
All of these treatments basically can treat the hairy cell. Once the hairy cell is in remission, the risk of infections decreases. But sometimes they will each have risks of immune suppression of one of these multiple different areas. For instant, Rituximab doesn’t do much to the neutrophils and T-cells, but it can lower your immune globulin. Vemurafenib has less immune system but does have an increased risk of skin cancer and Moxetumomab has less immune system, but it does have a risk of what's called hemolytic uremic syndrome and capillary leak syndrome. The TD CD4 count may be low for six to 24 months. So often we will use Bacturum to cut down the risk of various pneumonias or shingles. If the person presents like the gentleman I mentioned at the beginning and they had a significant infection, we may consider starting with Vemurafenib and then maybe switching to Cladribine or Pentostatin.
Tim Call:
In the current COVID outbreak, there is information on the website you can share with your physician. In general, we're trying to stay away from the Cladribine and Pentostatin initially and if a person can delay treatment if possible, but otherwise consider Vemurafenib as an initial therapy. Finally, and this is brief is can we boost our immune system? I think that we know that deficiencies of certain things will weaken the immune system. So for instance, low vitamin D is associated with poor bone health. We have seen in chronic lymphocytic leukemia that having a normal vitamin D is important and patients have better outcomes.
Vitamin C probably has some benefits. I think, but I can't tell you how much. I think that there are many things we're all learning and I'm not opposed to anything. But my final point is looking at the far right, part of the things that we can do to boost our immune system. So we know that deficiency of certain vitamins suppress immunity, getting to normal levels improve immunity. But do supraphysiologic levels do that much, we don't know. But we do know that sleep, exercise, good diet, washing your hands and very, very important stress reduction. It has been shown over and over, high levels of stress will alter cortisol levels and decrease the body's lymphocytes. So that is something that we can all do.
2. Question & Answer session
Anna Lambertson (relaying questions from webinar participants):
There are a lot of concerns among patients, with regards to what risk COVID-19 poses for them as patients either newly diagnosed or even long time in remission. A patient who's been in remission for a long time with, counts at roughly normal levels. Does COVID-19 still pose a risk for them? If so, why? And what can they do to minimize that risk?
Tim Call:
As you see we are created with an incredibly complex immune system. And so nobody has no immunity. We have the physical things like skin and things. But I think it's pretty clear, but we don't have long-term immune function studies that I have available right now that if your neutrophils (and monocytes, etc.) have returned to normal, you're in remission. I think your risk of infection is clearly improved.
We can imply that because long term hairy cell survivors, we don't see multiple current infections. We tend to see the recurrent infections when the disease is active. So I think for individuals in that group, I think that I would look at it that, I've had leukemia, I don't have an entirely normal immune system, but I have many functioning elements. So I'm going to do everything that I can possibly do with, sheltering as much as you can, masking, gloving if needed, hand sanitizer.
I think that we in fact may be seeing less infections in patients with leukemia because we have harped on this for so many years and there more people taking it more seriously. So I would not live in fear. I would do what you need to do. This question has come up for me for a healthcare worker and I've been working on one of our COVID floors, I think it's okay.
Anna Lambertson (relaying questions from webinar participants):
If a patient is considering treatment, how do you go about making a decision for a patient as to whether or not they should pursue treatment right now in light of COVID-19?
Tim Call:
I think this is outlined in our statement on the Hairy Cell Leukemia Foundation website, but let me summarize. If treatment is not needed imminently, in other words, you're anemic, your platelets are 110,000, neutrophils are 1400 or 1300. You're feeling well. Most individuals right now, and this is going to change month to month, maybe even week to week, would try to delay initiation of therapy because especially if you're using Cladribine or Pentostatin, you're going to decrease the CD4 counts, which will impede your ability to fight infection.
And if you needed therapy because your neutrophils are really low, your platelets are low, you're anemic, we don't want you to just be getting blood transfusions, then most individuals would start right now with Vemurafenib. Generally it's not FDA approved, but, generally we have been able to get it or with one appeal to ensure we can get it. That's kind of how we would look at doing it.
The T cell suppression in COVID is two phase. One, having recent Cladribine, your CD4 count is lower. So you're higher risk of infection. However, what causes the lung injury is an overactive immune cells. So there's been some emerging data that, for instance, transplant patients who are on some medicines to decrease rejection may not get as sick as others.
Webinar participant:
I'm a physician. I'm a psychiatrist. My son is 33. He had hairy cell diagnosed a year ago and just finished his Cladribine round in mid March last year. He worked as a karate instructor and they kept him away from doing that until October of last year. So he went back to work, worked until the virus broke out and then the karate studio closed. He's recently been hired to work in a call center where he's going to be in an area where people are in cubicles, probably 20 to 25 people in a large room. Is that safe for him? And if it is, what kind of precautions should he take?
Tim Call:
So not knowing exactly the physical layout, I can't answer you specifically if it's safe or not. However, I think there are things that I would look at. Universally wearing a mask, hand sanitizer. You're in a room which multiple cubicles, so that makes it harder. But, I think it's possible for him to work there. But much like we do here, where we are instructed to have masks on throughout the day. We can't get in the a mask.
And bringing his own lunch. I think one of the big thing, and we've had this question with a number of people in the Midwest is the break rooms. Don't go to the break room. Use the bathroom and on your lunch if you need to go out to your car to eat. I think those are the common places that are probably more risky than the room itself. But he's far enough out from the Cladribine that he should, depending on his blood counts, he should be pretty close to normal. If there was a concern, his physician requests a CD4 count, and generally if the CD4 count is greater than 200, then the risk of infection is lower.
Webinar participant:
First of all, thank you for this great webinar. I would like to ask about maintenance treatment with Rituximab for a patient. My father was treated in August 2016 with Cladribine only and later in June 2019 with Cladribine followed by Rituximab after one month, eight doses of Rituximab. He feels good and right now everything is okay with his blood counts. I read that for some patients, especially when the Cladribine wasn't given concurrently with Rituximab (the Rituximab was given perhaps a month after), in some cancer centers they start maintenance treatment with Rituximab over two years. Another eight doses of rituximab for two years, like one every three months. Especially for patients that relapse and were treated for the second time with rituximab. And I know that there is kind of a debate around such a maintenance treatment with rituximab after completion of the regular treatment.
Tim Call:
Thank you for that question. I think a couple of things. When one has had a fairly early relapse, 2016 to 2019, then I am in favor of using combined Cladribine and Rituximab as my next step, as long as the Cladribine was tolerated the first time otherwise then Pentostatin and Rituximab. I have pretty much always used concurrent rituximab. And you alluded to some recent data that was published last June at American Society of Clinical Oncology was showing that that giving it concurrently versus subsequently has a higher response rate.
Many times when we’ve retreated with Cladribine and Rituxan, we’ve seen much, much longer second remissions than first remission. So, in your father's case, he didn't have concurrent, he had subsequent. But yet he did have good therapy.
There is no definite role for maintenance that I'm aware of. And when we are using maintenance like as described, we are extrapolating from the literature from non-Hodgkin's low grade lymphoma. Personally I would not use it, because I think it's an extrapolation. And Rituximab lowers the immunoglobulin level. So there can be side effects. So it would not be something I would do personally.
Anna Lambertson (relaying questions from webinar participants):
We’ve received a number of questions regarding, blood counts, platelet counts and whatnot that are falling. So, in your experience treating patients, naturally patients become very anxious if blood counts are decreasing. What else could be the because of some decrease in these blood counts other than of course, a dreaded relapse? Are there other things that could be causing that?
Tim Call:
Absolutely. And this in fact is one of the reasons I personally like to get a bone marrow biopsy afterwards to see how, six, nine months later after treatment and see how deep the remission is. Because then you know that if down the road, say you can't tell it was a virus, you can do a repeat marrow. And if the marrow was 3%, four years ago after treatment and now it's still 2%, then it's probably not the disease.
So it's number one would be the pattern of the blood counts. So if you're seeing all three blood counts go low, if you're seeing a drop in monocytes, I would be more concerned. But Cladribine does affect our stem cell. It’s not a drug that can be used indefinitely, a dozen times. And so it is not uncommon over two or three years after initial therapy to have a slightly low white blood count, a slightly low platelet count.
And yes, viruses, other medications, things like sulfa drugs, some various heart arrhythmias can cause a low blood count. So there's multiple viruses, inflammation, medications that can also do it. So, if you can't tell, then a marrow may be needed.
Webinar participant:
I had Cladribine in 2018, late 2018 and my blood counts didn't come back to normal. I had a bone marrow mid last year and yes, the hairy cells were still there. And I was due to have treatment, but because of COVID, everything's being put off. I'm generally quite healthy, but I've had low blood counts and things.
What's the long-term effect of, for example, living with low levels of hemoglobin, not particularly low, but low, like 130? What's the long-term effects it could have on maybe the brain cells or anything else?
Tim Call:
I think the first thing is we're built with a great reserve. So, we do not recommend transfusions unless the hemoglobin is less than seven to eight. Generally the recommendation is seven.
So at 103 or 10.3 with the hemoglobin, there's very, really should be no long-term side effects. Remember red cells carry oxygen. So what you may notice is that you certainly will get more short of breath if you're trying to do some work, take some stairs. So you'll have what's called exertional shortness of breath. But it should not because a lot of long term. Now when you get very low. So it's all a matter of degree. So if we have a person coming in with a hemoglobin of six, they've had a chronic bleeding ulcer or a five, what can happen is your cardiac output has to keep increasing to give blood supply and give oxygen to the tissues. So there is what's called an anemia associated heart failure, but that is when you're really down in those critical levels. Now if a person has heart disease, emphysema, they're going to be more sensitive. Again, if we were going down the eight range, seven range, then we start to reconsider that.
Webinar participant:
Thank you very much for an excellent presentation. I'm a doctor as well. I had Cladribine as an experimental protocol 28 years ago, and my flow cytometry studies have been excellent for the past couple of years. My bone marrow, the last bone marrow I had was two years ago, which was fine. My question is though my platelet count has been chronically low, anywhere from the range of 85,000 to 100,000. And also I've had significantly chronic bruising, namely on my forearms.
I've underwent some significant blood tests through actually two hematologists recently. Nothing significant has shown up so far. Do you have any explanation what may be causing my problems? The only anticoagulant I'm on is 81 milligrams of aspirin.
Tim Call:
With Cladribine long term, usually the platelets and that will return to normal in the first several years. But I've had patients who've had Cladribine 20 years ago, 15 years ago, whose platelets are a little higher than yours, but more in the 100 to 115 range, and they don't tend to be worsening. Very rarely, you can see secondary bone marrow problems causing low platelets, but, you’ve had bone marrows and there's no evidence of that.
So I suspect it's a combination of probably having a lower count, possibly from your past therapy and the aspirin.
For those out there who aren't medical, think of clotting as three basic legs to that stool. One is the platelet count and the platelets. So platelet is a number and also the quality of the platelets. Aspirin interferes with the quality, they don't clot as well.
The second is going to be your plasma clotting factors that are generated by the liver and then the intake, your own blood vessels and your skin and that. So I suspect that it's probably the aspirin plus that. And especially if the bruises are more on exposed surfaces like the thighs, on the outside of the arms, we'd be less concerned. Obviously if you started having nosebleeds or anything, I'd be more concerned. I don't know that I would do a lot more workup.
Anna Lambertson (relaying questions from participants):
There have been a number of patients and individuals joining today's webinar who are seeking greater clarity regarding what immunosuppression really means and what considerations they need to continue to think through, given the current pandemic. There are a number of therapies that are being discussed. Ibrutinib is one of those that you mentioned on your slide, Vemurafenib. So if a patient is needing to be retreated, what would you be considering for treatment for patients right now, given the immunosuppression issues that you talked about and COVID-19?
Tim Call:
Until we see clear, cross country drops in the cases of COVID-19, I would continue to be hesitant to use Cladribine or Pentostatin. I know there are certain different opinions out there. Some have said, well, Rituximab doesn't affect the T cells as much, which T cells are very important in fighting viruses. So the two things I would consider would be Rituxan and Vemurafenib.
The Rituxan is injections weekly for either four or eight weeks. But again we don't have a lot of durability. It doesn't tend to last real long.
I think that if I were to pick anything right now, it would be to apply for Vemurafenib. It's an oral agent that you take twice daily. We normally in hairy cell use a lower dose than what they use in melanoma. You can have some nausea and vomiting and some just some general malaise, but it's fairly well tolerated.
We can see very rapid responses. But again, it's not going to probably be a drug that will last 20 years. I think we had one gentleman said 28 years ago. I don't think we can expect that from Vemurafenib, but it can certainly get us to a point where it's a more safer time to give a more definitive therapy.
So that would be where I would be leaning. Well again, there is a slightly increased risk of skin cancer. So if you're on Vemurafenib, I would recommend that you see a dermatologist within a few months and maybe on a six month basis.
This transcript has been edited for clarity.