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2025 HCL Patient Seminar Session: Understanding HCL
The Hairy Cell Leukemia Foundation hosted this session with guest speaker Dr. Kerry Rogers from the Ohio State University.
View a recording of Dr. Rogers’ presentation below.
Transcript of Dr. Rogers’ presentation
What Is Hairy Cell Leukemia?
Hairy cell leukemia is a rare, chronic B-cell leukemia, which is a type of blood cancer. Some people call them bone cancers or lymph node cancers, but that's all kind of the same type of tissue. So usually, I just call these blood cancers. And the reason we call it a B-cell leukemia is that the cell that went on to become a cancer cell in the body is called a B lymphocyte.
And so that is an immune system cell. So, this is also a cancer of immune system cells. And just so you know, there are a lot of B-cell cancers and hairy cell leukemia is just a small portion of all the B-cell cancers there are. It was originally described in the late fifties by two different groups, and I have a picture up there of Dr. Bouroncle, because she was at Ohio State University, so I thought it'd be good to share her. And really, just my institution has put a lot of effort into hairy cell leukemia, and it's been so nice for me to get involved in that too.
How HCL Is Diagnosed
Hairy cell leukemia is diagnosed based on the presence of the leukemia cells. This usually requires a bone marrow biopsy at diagnosis, although sometimes there's enough of this in the blood or there are some of the hairy cells in something like a lymph node. And so, then that tissue is sampled to get the diagnosis. It is leukemia, which usually means that the cancer cells are in the blood, and so you can actually see them in the blood.
I'm showing you a picture there on the screen of hairy cell leukemia cells. So those kinds of pink cells in the background are actually red blood cells. And then the two purple ones are hairy cell leukemia cells from the blood of someone with hairy cell leukemia. And you can see the edge of them looks a little bit fuzzy. So, the fuzziness to the edge is actually the “hairy” projections. It just looks a little bit blurry. These are actually the hairy cells. And so having these in the body is what leads to the diagnosis of hairy cell leukemia. And then there are actually ways that physicians identify these that go beyond just what they look like, because there are a few other cancers that can have these hairy projections. So usually, the diagnosis is made by them looking like hairy cell just visually under the microscope, and then there are some other features other than just the hairs. But the hairs are an easier one to spot.
Then there's something called immunophenotype, which is like the markers on the surface of the cell that we can test for. So, I've just put up some of the names of some of the markers that you see in hairy cell leukemia. And then most cases of classic hairy cell leukemia have a mutation in a gene called BRAF, and the mutation is the V600E mutation.
So that can really help with the diagnosis, too, if it's a little unclear. There is a hairy cell variant. So that has slightly different markers, definitely different mutations. And this has become a little controversial recently because the group of physicians and researchers that classify cancers for the WHO reclassified variant hairy cell leukemia, along with some other similar cancers.
And so, the field is still trying to sort that one out. But really, you can still identify hairy cell leukemia variant so that you can use that information to treat patients based on all the research and information we have on that diagnosis. So don't worry that the information we have about variant is lost just because some of our classification groups have decided to go in a different direction.
But we use all this information together to determine if someone has hairy cell leukemia. I just wanted to put a few more pictures in here. These are from Dr. Lozanski in Ohio State. And so here it's different, this is also blood from someone with hairy cell leukemia. The kind of darker red on there is red blood cells.
The reason they look like that is just because it's a different type of, or part of, the blood film. So, it's a little thicker, so the cells balled up. It's not something wrong with the red blood cells. But you can see really these purple splotches all have this fuzz on the outside,
and that's the hairs for hairy cell leukemia. I have a couple of arrows on them. The other thing that can really help with the diagnosis of hairy cell leukemia is that, for some reason, the hairy cells cause the bone marrow cells—and not the blood-producing bone marrow cells, but the connective tissue bone marrow cells that hold everything in your bone marrow—to make these extra types of connective tissue called reticulin fiber, or reticulin fibrosis.
I'm showing you two pictures of bone marrow. So, there you can see all the cells are together because this is a core biopsy from someone's bone marrow, and it looks pink on the one. And then on the other side, where you can see these little black things that have the arrow on, there is a special stain to look at reticulin fibrosis.
And that black is stuff that you really shouldn't see—or shouldn't see that much of. The good news is when hairy cells are in remission, you can actually see that go away. So, it's something where hairy cells actually likely cause the bone marrow to make these extra fibers, but that can crowd out some of the bone marrow blood-producing cells and lead to lower blood counts, too.
And it's a feature of hairy cell leukemia and a couple of other types of blood cancers. So just a few more facts about it in case anyone is new to learning about this, and it's always just good to have a refresher.
How Common Is HCL?
So, this is a rare leukemia. It's about 2% of adult leukemias. So, this is not a pediatric leukemia.
So, when you think about the types of leukemias kids get, hairy cell leukemia is a cancer of adults. There are about 1,100 new cases per year in the US, so that's 0.3 per 100,000 people per year. So, this is pretty rare. And then there are the demographics of those experiencing hairy cell leukemia.
So, the median age at diagnosis is 55 years. If you don't know what a median is, you can think of it as an average, although it's not exactly the same as average. You probably might be thinking, “Oh, but I've seen people who are younger who have hairy cell leukemia.” That's absolutely true. So, this is definitely a type of leukemia where we see people in their thirties and forties being diagnosed with hairy cell leukemia quite commonly, sometimes as young as their twenties.
And then you do see people in their sixties, seventies, and even eighties diagnosed with it. So, the middle is kind of 55. But we do see a lot of younger people diagnosed. It is more common in men and more common in white people. And that's actually true of B-cell cancers. So, it doesn't mean it only occurs in men or only occurs in white people; it's just more common in that particular demographic, probably because of the biology.
I also want to point out that the expected survival is decades. So, this is something that, while we can't cure it, people live with it for a very long time. So, you always have to think about how to remain healthy with a diagnosis of hairy cell leukemia for decades. And in many cases, it doesn't shorten someone's natural lifespan.
So, this is something where people get to finish their whole life living with it and then die of something else in the future. And I think that's really an important thing to realize.
Common Clinical Features: Symptoms
There are some clinical features of hairy cell leukemia that some of you might be aware of. One thing that I see quite a bit is that some people are diagnosed with no symptoms whatsoever.
I think this occurs more commonly in modern times because blood counts get done for a variety of reasons. They're inexpensive and very easy to get blood counts. So many people are diagnosed with no symptoms at all. I've also seen a few people who were diagnosed because they had just slightly low blood counts and someone thought, “Okay, watch this.”
Then, eventually, the pathologist—when they got blood drawn—found circulating hairy cells. These people felt well and just had low blood counts. That's how they came to find out about this. I will say, though, that a lot of people are diagnosed with very low blood counts. And so, this is because the hairy cell leukemia either fills up the marrow or creates those fibers in the marrow that kind of crowd out the healthy blood-producing cells.
All of your blood cells are made in your bone marrow, and they go into the blood and have a lifespan. So, your bone marrow's constantly making cells, and then they have a lifespan and are reabsorbed back into the body. That makes sense, right? People donate blood, so you have to make new blood cells, and if your bone marrow's not functioning well,
it's kind of like having too many weeds in the garden and then the flowers can't do their thing because there's too many weeds in there—with, in this case, the hairy cells being weeds. So, you can see people with low platelets, low red blood cells—when your red blood cells are low, that's what we call anemia, and then actually low white blood cells, specifically low neutrophils, which can lead to bacterial infections. Neutrophils are the white blood cells that fight bacterial infections. And then interestingly, hairy cell causes low monocyte counts. Monocyte is a type of white blood cell. And for reasons that I think we don't fully understand, people have low monocyte counts even when their other blood counts aren't that bad.
It's just a very specific and interesting feature of classic hairy cell leukemia. We do get people who find out they have this when they have symptoms of anemia, like exercise intolerance, shortness of breath, or just feeling really fatigued, and then you find out their blood counts are very low.
This happens a lot, especially in people in their thirties and forties, because they have otherwise good exercise tolerance and cardiovascular fitness. So, they get much lower levels of hemoglobin before they have symptoms, and they're less likely to have blood counts done for other reasons.
Hairy cell leukemia can cause an enlarged spleen. In fact, it usually does. I've had a couple of patients who were diagnosed because they're like, “Hey, my abdomen's sticking out,” including one woman who's like, “I feel like I'm pregnant and I'm definitely not.” So, you can actually get the spleen that's so big that you can feel it, or it'll actually fill up the abdomen to the point where it's uncomfortable.
You can get enlarged lymph nodes, although that's not super common. And then some people with hairy cell leukemia actually have bone lesions. So, not like the bone marrow, which is the inside of the bone where blood cells are made, but the cortex, or the hard outer part of the bone, can actually have leukemia cells in it.
And then fatigue can happen, as I was saying, from anemia. But you can also get fatigue from the release of hormones from the hairy cells. These are called cytokines, or immune system hormones. And since this is a cancer of immune system cells, they can release some of the same hormones that get released during infection and lead to things like night sweats, weight loss, or fatigue from that.
And then many people actually have an infection at the time of diagnosis. So, it's not completely uncommon for someone to end up in the hospital with pneumonia or another infection, and then their blood counts are low, and they find out they have hairy cell leukemia. So, these aren't the only ways people find out they have hairy cell, but these are some of the more common ones.
When and why to treat hairy cell leukemia?
Treatment is really only needed when there's something to improve. In some other kind of slow-growing B-cell cancers, they actually have randomized studies where they assigned people to treatment when they're diagnosed or treatment when they needed it, and found that treatment at diagnosis did not improve survival. In other words, people didn't live any longer, getting treated sooner or right away. That has not really been done in hairy cell because it's rare and there are not enough people with it to do that kind of study. Nor is it really, I think, of the kind of value that would make us want to do that, because early treatment's really not a benefit in any similar cancers. So early treatment, meaning when you're feeling well, having no symptoms and nothing symptomatic, doesn't actually help people live any longer or better. And it doesn't really have a known benefit. It just exposes people to side effects sooner.
So, some people actually find out that they have hairy cell leukemia and then are just observed by their physician for a while, and it can be really unnerving for people to know they have leukemia and not be actively treating it. But that is the recommendation. Some people, of course, are very ill from it at the time they're diagnosed, and that's probably more people than not with hairy cell.
And in those cases, obviously, treatment is planned right away. So, some things that might make someone need treatment: clearly, people who need blood transfusions, who are very sick when they're diagnosed, need treatment very urgently. But sometimes if people are monitored, they'll see some things develop with their blood counts, like their neutrophil count less than a thousand— that usually shows up as “1.0” on most blood count reports in the US—a hemoglobin less than 10 or 11, or platelets less than 100. It's 100,000, but it'll say “100” on the lab report. And it's not that when the blood counts get below just one of those lines, you have to do treatment the next day.
But if you see those marks being hit and the blood counts are going down, it is time to think about doing a bone marrow biopsy to confirm this is from the hairy cell leukemia and starting hairy cell treatment. Spleen enlargement is a reason for treatment. If the spleen is just a little enlarged, there's plenty of space in the abdomen, it's really not a problem, you just have a spleen that's slightly big—but if you do have one that's really filling up the abdomen, is uncomfortable, or certainly if you can feel it or it's denting out your abdominal wall, that's really a reason to do treatment. Enlarged lymph nodes or bone lesions should be treated.
And then every once in a while, you get someone who gets night sweats, weight loss, or other what we call constitutional symptoms that are interfering with their life. Most adults in the US, and especially those with these types of cancers, experience some degree of fatigue. Mild fatigue is something that is hard to improve with treatment, but fatigue that's interfering with your enjoyment of your life is something that usually improves with treatment.
I do say I want to acknowledge it's a little tough, though, because sometimes you find people have sleep apnea and fatigue’s not really from the hairy cells. So, you have to be really careful there, understanding why people are having fatigue. So, considerations when starting treatment. One is that a bone marrow biopsy is helpful.
That's to show us what the bone marrow looks like before treatment. I also think it can be vital to confirm that the low blood counts are actually from hairy cell and not something else, because you want to be really sure that it is what you think it is if you're going to do treatment. Definitely, you want to make sure someone has another good organ function because it can matter for the treatment type.
Look for any infections or signs of infection. Definitely figure out—if they're needing a lot of blood transfusions, it's going to be more difficult if you do a treatment that really suppresses blood cell production, like cladribine. And then also preferences about treatment. And I think preferences have been able to be incorporated more because we now have more really effective treatments.
When faced with a situation where there's only one effective treatment, you have to try to make people fit that into their lifestyle. But I think when you have multiple effective treatments, you end up in the position that what patients want, and what matters most for them in their life in terms of schedule, side effects, things like that, really can be given the kind of consideration that we want to give it when you have multiple options.
Treatment Options
So, there's what I like to think of as three categories of treatment options. There are purine nucleoside analogs, so that's cladribine or pentostatin. These are the drugs that have really changed the natural history of hairy cell leukemia. This is the most commonly used treatment. It can be repeated, sometimes used with other drugs in combination, like drugs such as anti-CD20 antibodies, like rituximab.
Recently, we've had a bunch of non-chemotherapy treatments, and I think this has represented a huge advancement. Some of these are now being studied as an initial treatment. These drugs can work very well for people where purine analogs like cladribine or pentostatin were not really controlling the hairy cell for very long.
And there are a couple of different types of agents there, including ones that are being investigated. Some of these have really been boosted, too, thanks to the Hairy Cell Leukemia Foundation, that's funded quite a bit of research on these, which has been amazing. And then there are older treatments that can be of value, but that's usually in very specific cases.
So that's things like interferon, which is an immune system hormone, or splenectomy, which is removing the spleen. So that’s something like interferon, which is an immune system hormone, or splenectomy, which is removing the spleen. So that’s something like interferon, which is an immune system hormone, or splenectomy, which is removing the spleen. Those are not highly effective treatments, but there can be times when that is the best thing to do for a particular situation. So, I just want to say a few words about the two most common treatments.
I will say cladribine is much more commonly used than pentostatin. These are drugs that interfere with DNA synthesis. They are traditional-type chemotherapy agents. You can get fatigue and nausea from them. Neither of these causes hair loss—the technical word for that is alopecia—which most people are really relieved to hear.
You can get some hair thinning, but it doesn't usually cause baldness. These are both, in the scheme of chemotherapies that exist, pretty tolerable. So, they're not super, super easy to take, but they have fewer side effects than some chemotherapies you might see people get for aggressive lymphomas or an acute leukemia.
The key difference is that cladribine is usually given for one week only. So, you get all the treatment in one week, and then it can take weeks or months to recover. And pentostatin is given every two weeks until remission is achieved. So, some people really see the benefit of getting all of the treatment done in one week.
I don't want people to think that they're in remission and everything's normal after one week, though, because it does take weeks or months to really recover from getting that. And if blood counts are really low, it can be really hard to get all your chemotherapy in one week because it'll also suppress your healthy blood cell production even more. Pentostatin is kind of drawn out. So sometimes that's hard for people because they have to keep getting treatments for a longer period of time. Outcomes are really good. So these are the drugs that have changed the survival for people with hairy cell leukemia from a lifespan expectation of something like three to five years to a lifespan expectation of a normal or near-normal life expectancy.
So, this class of drugs is what changed the survival in hairy cell leukemia from years to decades. And I don't want to minimize that here. Remission rates are high; complete remission rates are high. The average amount of time people stay in remission is seven to eight years. And you can see people with a complete response, which means there's no visible hairy cell in the bone marrow. Some other markers of response are good—usually get more time after treatment.
The average amount of time people are in remission is about 16 years, and it's shorter, at only four years, if only a partial remission is achieved. So that's improvement, but still some hairy cells there. I don't want people to worry, though, about folks getting a partial remission, because you can repeat purine analog treatment with cladribine or pentostatin. And unlike most cancers, you can sometimes see an even longer second remission with the same drug than the first remission. Usually, you give it with a drug like rituximab if you're giving it as a subsequent treatment.
I think the biggest news for using purine analogs as a first treatment for hairy cell is this regimen, which we've called CDAR. That is a combination of cladribine, which again is the chemotherapy you get for one week, but with eight weekly doses of rituximab starting with the beginning of cladribine. This is a regimen studied at the NIH in a randomized study that compared getting CDAR, which is this rituximab with cladribine, to cladribine alone.
I will say the results are a little complicated to understand because people who got cladribine alone were allowed to get rituximab later, and how long people are in remission, actually, at the almost eight years of follow-up we have, was the same, but more people with the CDAR had no detectable leukemia.
So, these graphs I'm showing are swimmer’s plots. The numbers one through 34 are patients who were treated in the trial, and then the “time since cladribine” is in months. So that top line is how many months patient one in that arm of the trial is still followed in the trial. And then anything that's red—or red or teal, actually—is when there's detectable hairy cell, and the blue means no detectable hairy cell.
So, giving the rituximab with cladribine really leads to lower amounts of leukemia being detectable. And I think that will result in better outcomes in the future. However, with more drugs, there are always more side effects, so you have to think about that carefully. Especially when cladribine is really good. If someone's in their eighties or nineties, you probably don't want to give them two drugs. If someone is very healthy and younger, you definitely do want to think about this. So, I think this is a really exciting thing.
The other exciting thing that has really made a huge difference in the last few years is vemurafenib. Vemurafenib is a drug that's not approved for hairy cell; it's approved for melanoma, although we do consider it standard in hairy cell because it's in the guidelines and because of the amount of research and evidence we have that it works. And vemurafenib is a pill that actually targets the mutant BRAF protein in the hairy cell.
So BRAF can be mutated in a variety of cancers, which is why this drug was developed for melanoma. But in hairy cell leukemia that has this BRAF mutation, it actually works really well. So, I'm showing you some bone marrow biopsies. This is in a publication from Dr. Tiacci, and that pink on the before-treatment is CD20-positive cells. So that's the hairy cells. And you can see they're gone on the after-treatment one. So, the overall response rate is really high. You think, “Okay, it's like a hundred percent effective, that's great,” and it is. But if you give it for six months and then stop, people don't stay in remission that long. In fact, if there's still detectable hairy cell, that can be less than a year.
It can be a couple of years. But I think the problem here with this is that it works great, but it doesn't maintain the remissions for as long. It is also extremely useful in cases where people have an infection because it doesn't suppress the immune system. So, if people are really sick from an infection when they need hairy cell treatment, using this to improve how they're doing and then allowing them to get a purine analog or something later is a great strategy.
It does have side effects, including some rashes, joint pain, and a really unusual situation where people are extremely photosensitive. So, you can't go in direct sunlight without a lot of sunblock. So, in order to improve the effectiveness of vemurafenib, it's been combined with an antibody called rituximab.
There's a little scheme there, so you can see there are two different four-week blocks of taking vemurafenib, and then the little arrows are weeks where someone would get rituximab, which is an antibody—that's an IV treatment. This phase 2 study, also by Dr. Tiacci, was in people who had prior treatments for hairy cell leukemia. And this actually works better than giving the vemurafenib alone and is being studied as a—here's the durability—this is being studied with obinutuzumab or rituximab as a first treatment, comparing it actually to cladribine and rituximab or cladribine-based chemotherapy.
There's more than one study; I don't want to get too specific on it. But it will be very interesting to see how this does as a first treatment. This plot, I'm showing you something called the Kaplan–Meier curve. That's the percentage of patients and then time. So, if you look at any time on there, like if you look at 30 months, it's just under 80% of patients that are alive and in remission.
So, when you see these really flat lines, that means most people are doing well, meaning most are alive and in remission. So that's really good. So, these remissions are lasting longer for people than with vemurafenib alone, I think, is my point. BRAF inhibitors, to stay on the theme: dabrafenib is a drug similar to vemurafenib.
It's another BRAF inhibitor, and it was combined with a drug called trametinib, which is a MEK inhibitor. MEK and BRAF are very close in the cells. So, combining them works in a variety of cancers. And this actually worked very well. This was in something we call a “basket trial,” meaning that they treated a variety of people with BRAF-mutated cancers.
But this works very well. This is at the NIH. There's more information coming, I believe at ASH, on a combination of a BRAF inhibitor and a MEK inhibitor. ASH is our hematology meeting that's next month. So, this is really exciting. I think this is going to be increasingly utilized now that we're getting some results with this.
So, it's two targeted drugs, and I look forward to learning more about how we're going to use this for people. And then ibrutinib, which I always love talking about. So BTK inhibitors are another oral targeted agent and inhibit something called B-cell receptor signaling, which is in these B cells.
So, it actually works in several B-cell cancers. I've listed a few of them on there. And the reason I'm excited about this one is there's a multi-site study that a lot of institutions that are really involved in the hairy cell leukemia academic community participated in. But Ohio State got to lead this trial, which was a National Cancer Institute–sponsored clinical trial for people to take ibrutinib with hairy cell leukemia.
We also had a lot of people participating who had variant hairy cell, which was cool. This is just showing you that, because blood counts were still maybe a little low, even though that wasn't hurting people, the response rates weren't that high. But if you look at those Kaplan–Meier curves, you see they're really flat even out to 60, 70, 80 months.
That means that most people are doing well. And the people who participated in this study had mostly had hairy cell for more than 10 years and had four treatments on average during that time. So, these are people who had a lot of treatments that didn't work too well, and then this worked really well for them.
I will say there are other BTK inhibitors, like zanubrutinib, that have fewer side effects. Ibrutinib causes a lot of high blood pressure and abnormal heart rhythms. So zanubrutinib is probably more useful these days. And then I'm not going to spend a lot of time on this, but one really exciting thing that was discussed actually, at the Leukemia Foundation scientific meeting last month—yes, that was last month—is that using the immune system to target cells has been really big in cancer overall, very big in B-cell cancers. And so, there are therapies called chimeric antigen receptor T-cell therapy, CAR T-cell therapy—very sci-fi. You actually take T cells out of someone's body through a process called apheresis.
That's where they take your blood out, spin it, and put most of it back in. And then they actually engineer them to have a receptor on them that goes after the cancer cells. Sometimes it gets some healthy cells in there too, but not to the degree of other types of cell therapies. So that's really exciting. And then bispecific antibodies have been investigated in B-cell cancers, and I think hopefully at some point we'll get some data in hairy cell. And that actually brings us back to were talking about antibodies before—antibodies are immune system proteins.
So, things like rituximab just target the cell, and then the immune system comes in and destroys it. These [bispecific] actually have one end of the antibody that targets the cell, and one end that actually pulls in the immune system T cells to do the job better. So, these are things that—I think we've seen a few people treated in things like clinical trials—but this might be something in the future that'll be of benefit.
Health Maintenance for Patients With HCL
And then just one of the last few things I want to touch on is reminding everybody about health maintenance for people with hairy cell leukemia. So again, this is something where I was talking about a bunch of treatments, but most people spend years of their life not needing treatment, either before they need treatment the first time or in observation after treatment.
And a good portion of people's lives are spent living with hairy cell leukemia, but not taking an active treatment. And this is really important. So, people with hairy cell leukemia have a higher risk of other cancers. That's because it modifies the immune system, and your immune system is what protects you from cancer. And by other cancers, I mean skin cancer, things like lung cancer, things like colon cancer. So, we recommend everybody get their cancer screenings. So, if you're someone with hairy cell leukemia, your doctor's recommending a screening colonoscopy or colon cancer screening, and you're thinking, “Maybe I don't wanna do that,” you probably do wanna do that.
And then annual dermatology exams are really important. That's where a dermatologist looks at all your skin surfaces to make sure that you don't have any skin cancers that need to be removed. It doesn't hurt. It is a little weird because you have to have someone staring at your skin for a few minutes. And then there's a higher risk of infection.
So, this does not mean living in a bubble or avoiding people or activities for most of your life. Sure, sometimes, surrounding a treatment, you have to do that. But it does mean that people with hairy cell should really get all their vaccines that they're owed, including seasonal influenza, COVID-19 vaccination, and really avoiding live vaccines, which would be things like the MMR vaccine or the older shingles vaccine Zostavax.
The Shingrix shingles vaccine is fine. And I think that because people are going to live decades with hairy cell leukemia, you really want to make sure that you do everything else you can to protect your health.
And I wanted to end there before the Q&A, showing you again the picture of hairy cell leukemia and also where I work, which is the James Cancer Hospital.
Transcript of Q&A
Bone Lesions and Bone Pain
Question: You mentioned bone lesions. Could you clarify how they are observed? What tools are used to detect them? And how common is bone discomfort in your patients?
Dr. Rogers:
Great questions. First, it helps to distinguish bone marrow from bone lesions. Hairy cell leukemia typically lives in the bone marrow, which is the inner cavity of the bone where blood cells are produced. When we talk about bone lesions, we mean abnormalities in the cortex, the hard outer layer of the bone—more in the territory of orthopedic surgeons.
Bone lesions can sometimes be seen on an X-ray, but they’re more often detected using:
● MRI, which uses magnetic fields to obtain highly detailed images, or
● PET scans, which use a radiolabeled sugar to show metabolically active cells.
On PET scans, active areas in the cortex appear as bright spots.
We don’t routinely scan every patient for bone lesions because whole-body MRIs aren’t practical, and most patients don’t have symptomatic lesions.
Regarding bone pain, there are two general categories:
Localized pain: If the lesion affects the cortex, pain tends to occur in a single area—such as a rib, shoulder, or hip. Imaging like MRI or PET helps clarify the cause. Sometimes a biopsy of the outer bone is needed.
Diffuse pain: This is more common across blood cancers—not limited to one area, affecting places like the thighs, sternum, or both shoulders. It’s usually related to changes in the marrow.
Diffuse bone pain is not extremely common in hairy cell leukemia, but it can occur, especially when treatment is needed.
Some treatments can also cause bone pain, such as:
● G-CSF (Neupogen/Neulasta), used to help raise neutrophil counts.
● Chemotherapy-induced inflammation as leukemia cells die.
Management depends on the cause:
● Leukemia-related pain usually improves after treatment.
● Treatment-related pain often resolves as the body recovers.
● Localized cortical bone pain may require systemic therapy or radiation.
Oddly, Claritin (loratadine) sometimes helps with G-CSF bone pain. Acetaminophen is also useful.
Treatment Response and Lingering Low Lymphocytes
Question: How should patients understand treatment response after cladribine or pentostatin? And what about lymphocytes that remain low for many months?
Dr. Rogers:
Purine analogs like cladribine and pentostatin have very high response rates in hairy cell leukemia.
After cladribine, the best response may not occur until 4–6 months after treatment.
We do not assess response one month after treatment; it takes time for both the drug’s effect and bone marrow recovery.
Formal response criteria include:
● Blood counts returning toward normal (not necessarily fully normal)
● Bone marrow biopsy showing minimal or no detectable hairy cells
● Spleen size decreasing
Bone marrow evaluation tells us how deep the response is.
Now, regarding lymphocytes:
Hairy cell leukemia is a cancer of B lymphocytes, but treatments like cladribine, pentostatin, and rituximab also deplete healthy lymphocytes.
So, it is common—and not a sign of active disease—for lymphocyte counts to stay low for months to years.
Some people never return to their exact pre-treatment lymphocyte levels.
When Treatment Doesn’t Work Well
Question: A participant shared they had cladribine twice without rituximab, then tried vemurafenib with rituximab, but it did not work optimally. How do you decide what to pursue next?
Dr. Rogers:
I’ve seen many patients with this experience. Some people respond beautifully to purine analogs for decades—but others don’t.
If someone needs treatment every 1–2 years, instead of the average 7–8 years, that suggests purine analogs are not working effectively.
This is when other mechanisms of action become very important:
● BRAF inhibitors (vemurafenib)
● MEK inhibitors in selected mutation patterns
● BTK inhibitors (ibrutinib), which we have seen help long-term even in heavily pre-treated patients
● Venetoclax, a BCL-2 inhibitor now in clinical trials
● Clinical trials at NIH and major centers
● CAR-T cell therapy, which has shown very promising emerging results for difficult cases
In these situations, it is especially valuable to be evaluated at a Center of Excellence, ideally with molecular testing to identify mutations (e.g., BRAF V600E vs. other BRAF or MAP2K1 mutations), which can guide therapy.
There is real hope for patients whose first-line treatments don’t work.
Cladribine + Rituximab (CDAR) – Concurrent vs. Delayed
Question: Is cladribine plus rituximab becoming standard? And how do patients choose between concurrent vs. delayed rituximab?
Dr. Rogers:
The CDAR study compared:
● Concurrent cladribine + rituximab (CDAR)
vs.
● Cladribine alone, adding rituximab only if hairy cells were still detectable at or after 6 months
It was not a direct comparison of concurrent vs. universally delayed rituximab.
We don’t yet know if planned delayed rituximab is better or worse than concurrent rituximab for everyone.
However, in practice:
● CDAR is an excellent option for younger, healthy patients needing a first treatment
● Two drugs mean more side effects, so CDAR is not ideal for:
o older patients
o patients with active infections
o patients with significant frailty
o people with chronic lung disease or high infection risk
CDAR increases rates of undetectable minimal residual disease, which is likely beneficial long-term, though we don’t have definitive remission-duration data yet.
Rituximab Alone
Question: When is rituximab alone appropriate? And is it an option for older patients or those with HCL variant?
Dr. Rogers:
Rituximab alone can work in classic hairy cell leukemia. Responses vary across studies, but it can be a good option for:
● Older or frail patients
● Patients with multiple health issues
● Those unable to tolerate purine analogs or BRAF inhibitors
In hairy cell leukemia variant (HCL-v), purine analogs are not as effective.
Depending on the subtype—HCL-v is biologically heterogeneous—rituximab can be helpful, sometimes for years, especially in slower-growing forms.
For younger patients with aggressive HCL-v, rituximab alone is usually not sufficient.
Bone Marrow Biopsies After Treatment
Question: Do you recommend bone marrow biopsies after treatment? If so, when?
Dr. Rogers:
Bone marrow biopsies are useful when they help answer a clinical question.
● Before treatment: usually helpful to confirm diagnosis
● After purine analog treatment: typically at 6 months, to assess response
● During pentostatin treatment: biopsies help determine when to stop
● During BTK inhibitor therapy: biopsies are not useful for routine monitoring because responses develop slowly and therapy is continuous
If biopsies were very difficult or the patient had complications, we individualize.
Always ask your physician: “What decision will this biopsy help make?”
Pregnancy and Hairy Cell Leukemia
Question: What options exist if someone is diagnosed with hairy cell leukemia while pregnant?
Dr. Rogers:
This is highly individualized. Key considerations include maternal health, the trimester, and the patient’s wishes.
What we know:
● Purine analogs do not appear to severely reduce future fertility for men or women.
● Pregnancies should be avoided during treatment and for ~6 months after, though this is precautionary.
● Chemotherapy can be given safely in the 2nd and 3rd trimesters.
● Rituximab can be used during pregnancy, though it may deplete fetal B-cells.
● Interferon-alpha is considered safe during pregnancy and is often used.
● Sometimes monitoring without treatment is appropriate.
● Splenectomy is occasionally considered, but not ideal during pregnancy.
● Pregnancy termination is not always required, but is an option depending on severity of disease, trimester, and patient preference.
This transcript has been edited for clarity.