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Webinar: Understanding Hairy Cell Leukemia
June 2026
This webinar was hosted by the Hairy Cell Leukemia Foundation (HCLF) with guest speaker Dr. James Blachly from the Ohio State University. This presentation is part of the HCLF’s ‘Understanding Hairy Cell Leukemia’ webinar series. Each webinar features a presentation by an HCL expert and an overview of diagnosis, standard treatments, and new research.
Below, view a webinar recording and transcript of the presentation and Q&A.
You can view Dr. Blachly’s slides here >>
Transcript of Dr. Blachly’s Presentation
Welcome and Introduction
I'm really delighted to be here. One of my favorite things is sharing information and making sure that patients and families understand what's happening to them.
I understand that we have a mix of people joining us today. Some may be very new to a diagnosis of Hairy Cell Leukemia, while others may have been living with the disease for many years.
Today, we'll provide a high-level overview of Hairy Cell Leukemia, including its history, how it is diagnosed, and the treatments that are available today. If there is something I don't cover that you'd like to know more about, I'm really excited to answer your questions at the end.
I'd also like to thank the Hairy Cell Leukemia Foundation for hosting this webinar. I can't say enough good things about the Foundation and everything they have done to help advance care for this disease.
Before we begin, I need to show my disclosure slide. I have consulted in the field of leukemia, have patents and patents pending, and have equity ownership and serve as a Chief Medical Officer for a biotechnology company.
What Is Hairy Cell Leukemia?
I like to begin with this photograph of Dr. Bertha Bouroncle, who was truly a pioneer in describing and treating this disease more than seventy years ago.
Hairy Cell Leukemia is a rare, chronic leukemia. "Chronic" means that it develops slowly over many years. "Leukemia" means it is a cancer of the white blood cells.
More specifically, Hairy Cell Leukemia develops from B lymphocytes, which are a type of white blood cell that normally helps protect us from infection by producing antibodies.
In 1958, Dr. Bertha Bouroncle here at Ohio State, along with another research group, first described the disease. At that time, they called it leukemic reticuloendotheliosis. From a branding perspective, that wasn't a very memorable name. Eventually, the disease was renamed Hairy Cell Leukemia, for reasons you'll see in just a moment.
How Hairy Cell Leukemia Is Diagnosed
The diagnosis of Hairy Cell Leukemia begins by identifying the leukemia cells themselves.
Hairy Cell Leukemia is especially interesting because the cells are remarkably distinctive under the microscope. It's one of the favorite diagnoses for medical students, pathology trainees, hematologists, and oncologists because the cells are so unique in appearance.
If you look at a blood smear, you'll see many normal red blood cells and a few dark purple leukemia cells. Surrounding the dark purple nucleus is a light blue area called the cytoplasm.
Most leukemia cells have a smooth outer border. Hairy Cell Leukemia cells are different. Instead of a smooth outline, they have tiny hair-like projections extending from the surface of the cell—almost like Albert Einstein's wild hair. Because these projections are so distinctive, the disease eventually became known as Hairy Cell Leukemia.
To make the diagnosis, we need to identify these cells somewhere in the body. Most often, that requires a bone marrow biopsy.
Although leukemia literally means "white blood cell cancer," Hairy Cell Leukemia behaves a little differently than many other leukemias. The leukemia cells do not always circulate in the bloodstream. Some patients have many hairy cells in their blood, and that's how the disease is discovered. However, in most patients, the first clue is low blood counts. Their physician notices low red blood cells, low white blood cells, or low platelets and performs a bone marrow biopsy.
The bone marrow is where Hairy Cell Leukemia most commonly accumulates.The disease can also involve the spleen, lymph nodes, and other organs, but the bone marrow is usually where the highest concentration of leukemia cells is found at diagnosis.
What Makes Hairy Cell Leukemia Different?
We identify Hairy Cell Leukemia in several ways.
First, we look at the appearance of the cells under the microscope. They resemble mature B lymphocytes but have those characteristic hairy projections extending from the cytoplasm.
Second, we use a laboratory technique called flow cytometry, which identifies proteins found on the surface of the cells. The characteristic pattern for classic Hairy Cell Leukemia includes: CD19, CD20, CD11c, CD25, CD103, CD123
That specific combination of markers is highly characteristic of Hairy Cell Leukemia.
Another major advance came about twelve years ago with the discovery that nearly every case of classic Hairy Cell Leukemia carries the BRAF V600E mutation. This mutation had already been recognized in melanoma and several other cancers, but discovering that it is present in essentially every case of classic Hairy Cell Leukemia was remarkable.
It is extremely unusual for an entire type of cancer to be defined by a single genetic mutation. Many cancers have common mutations, but they may occur in only 40% to 60% of patients. To find one mutation in nearly every case is unique.
Some patients, however, have Hairy Cell Leukemia Variant (HCLv). Within the Hairy Cell Leukemia community, we still commonly refer to it as Hairy Cell Leukemia Variant because it helps distinguish it from classic disease. Recently, the World Health Organization reclassified it as Splenic B-cell Lymphoma/Leukemia with Prominent Nucleoli. That's quite a mouthful.
Personally, I think that name creates some of the same branding challenges as the original term, leukemic reticuloendotheliosis.
Although HCL Variant does not carry the BRAF mutation, it often has mutations in related signaling pathways downstream of BRAF. The biology is different, but there are important similarities, which is why many specialists still use the familiar name Hairy Cell Leukemia Variant.
Hairy Cell Leukemia Under the Microscope
Here are some additional images of Hairy Cell Leukemia cells that do an even better job of showing the characteristic hair-like projections. The arrows identify these projections clearly.
A normal B or T lymphocyte should have a perfectly smooth, round outline. In contrast, Hairy Cell Leukemia cells have these distinctive cytoplasmic projections that give the disease its name.If you see cells that look like this under the microscope, the diagnosis is usually quite straightforward because very few other diseases produce this appearance.
When we examine the bone marrow, we can often identify the hairy projections there as well. One of the most interesting findings, however, is something called reticulin fibrosis. Reticulin fibrosis is essentially scar tissue within the bone marrow.
One consequence of this scarring is that when a bone marrow aspiration and biopsy are performed, it can be difficult to obtain the liquid portion of the marrow because the fibrosis prevents it from flowing freely. Some of you or your family members may have experienced what physicians call a dry tap.
A dry tap simply means that very little or none of the liquid marrow could be aspirated. This occurs because of the scarring, which is believed to result from substances produced by the hairy cells themselves.
I also want to acknowledge that these pathology slides were kindly provided by Dr. Gerard Lozanski, a pathologist here at Ohio State who specializes in Hairy Cell Leukemia and has been an important contributor to the Hairy Cell Leukemia Foundation. We are very grateful to Dr. Lozanski for sharing these images.
How Common Is Hairy Cell Leukemia?
Hairy Cell Leukemia is a rare disease. Leukemia itself is considered a rare cancer, but Hairy Cell Leukemia accounts for only about 2% of all adult leukemias. In the United States, there are approximately 900 to 1,200 new cases each year, or roughly 0.3 new cases per 100,000 people annually.
The average age at diagnosis is approximately 55 years old. The disease is also much more common in men than in women, occurring at approximately a 4-to-1 ratio. Hairy Cell Leukemia is seen more frequently in people of European ancestry, although the reasons for this are not completely understood. Similar patterns are also seen in diseases such as chronic lymphocytic leukemia and some types of non-Hodgkin lymphoma, suggesting there may be inherited differences within the immune system that contribute to risk.
The encouraging news is that today the expected survival of patients with Hairy Cell Leukemia is measured not in months or years, but in decades. With modern treatment, most patients can expect a normal life expectancy, and for many people the disease does not shorten their natural lifespan. This represents an extraordinary improvement compared with earlier decades.
Common Signs and Symptoms
Interestingly, many people diagnosed with Hairy Cell Leukemia have no symptoms at all. We call this being asymptomatic.
Instead, the diagnosis often begins with routine blood work performed before surgery or during an annual physical examination. A physician notices low blood counts—what we call cytopenias—and begins further evaluation.
Other patients do experience symptoms. One common problem is anemia, which means a low red blood cell count. Anemia often causes fatigue. Someone who has always been active may suddenly notice that they become exhausted during activities that used to be easy. They may be a regular tennis player or walk every day but suddenly find they cannot keep up.
Blood work reveals anemia, prompting a bone marrow biopsy, which then shows that Hairy Cell Leukemia has replaced much of the normal bone marrow. The bone marrow normally produces all of our blood cells: Red blood cells, which carry oxygen; white blood cells, which fight infection; platelets, which help blood clot. When Hairy Cell Leukemia infiltrates the marrow, production of these normal blood cells decreases.
Another very distinctive feature of Hairy Cell Leukemia is monocytopenia, or a low number of monocytes. Monocytes are an important type of white blood cell, and patients with untreated Hairy Cell Leukemia frequently have unusually low monocyte counts. This likely contributes to the increased risk of unusual infections seen in untreated patients. In some cases, an uncommon infection is actually what leads physicians to discover the leukemia.
Patients may also develop an enlarged spleen. The spleen sits beneath the left rib cage and acts as a giant filter for the bloodstream. It plays an important role in the immune system by helping remove bacteria, viruses, and damaged cells from circulation. Hairy Cell Leukemia commonly accumulates within the spleen, causing it to enlarge—sometimes dramatically.In some patients, the spleen becomes so enlarged that it can actually be seen through the abdominal wall.
Less commonly, Hairy Cell Leukemia can involve the lymph nodes, including those in the neck, under the arms, and in the groin. Very rarely, patients may develop bone lesions, an area that has been the subject of recent research. Finally, many patients experience fatigue that interferes with their daily activities. Although this may be caused by anemia, some patients experience fatigue directly from the leukemia itself, even when their hemoglobin level is relatively preserved. As mentioned earlier, another way patients may first present is with an infection,often an infection that is uncommon or unexpected.
When Is Treatment Needed?
One of the most common questions patients ask after diagnosis is:
"Doctor, if I have leukemia, why aren't we treating it?"
The answer is that not everyone needs treatment immediately.
If someone feels well, has stable blood counts, no significant infections, no troublesome fatigue, and no enlarged spleen causing symptoms, beginning treatment early has not been shown to improve overall survival or keep the disease away longer. Every treatment has potential side effects. If treatment is unlikely to provide benefit at that point, it is often better to monitor the disease carefully until treatment is truly needed.
In fact, up to one in ten patients may not require treatment at the time of diagnosis. Instead, they are followed closely with regular examinations and blood tests. Physicians generally use several standard criteria to decide when treatment should begin.
An easy way to remember the blood count thresholds is: 1,000 – 100 – 10
These numbers represent:
● Absolute neutrophil count below 1,000
● Platelet count below 100,000
● Hemoglobin below 10 g/dL
When blood counts fall below these levels, patients become increasingly vulnerable to infection, bleeding, or significant fatigue, and treatment is generally recommended.
Treatment may also be indicated if a patient develops: A massively enlarged or symptomatic spleen; Enlarged lymph nodes causing problems; Bone lesions; Significant constitutional symptoms.
Constitutional symptoms include: Persistent fevers, Chills, Night sweats. These symptoms suggest that the disease is becoming more active and are important reasons to begin treatment.
How Doctors Decide Which Treatment Is Best
Once it has been determined that treatment is necessary, there are several important factors that physicians consider before selecting the best treatment approach.
A bone marrow biopsy is very helpful because it establishes a baseline. Even if Hairy Cell Leukemia cells are circulating in the blood, it is important to understand the extent of disease in the bone marrow before treatment begins.
To know where you've ended up after treatment, you first have to know where you started.Doctors also consider the patient's overall health, including liver function, kidney function, mobility, immune status, and any previous treatments for cancer or other serious illnesses.These factors may influence which medications are safest and most appropriate.
Another critical consideration is whether the patient has an active infection.As we discussed earlier, many patients are diagnosed while they are already fighting an infection. This is especially important because the historical standard treatments for Hairy Cell Leukemia suppress the immune system quite profoundly.
These treatments are extremely effective at eliminating leukemia cells, but they also temporarily reduce healthy white blood cells. If a patient has an uncontrolled infection, beginning treatment too soon could allow that infection to become much more serious.Whenever possible, infections should be treated before leukemia therapy begins.
If an infection cannot be completely controlled, physicians may choose a different treatment strategy that restores immune function more rapidly.
Doctors also consider how the disease is affecting the patient.For example, someone who already requires blood transfusions before treatment will likely need more frequent monitoring because blood counts often fall before they recover.On the other hand, a patient with relatively preserved blood counts may require less intensive follow-up.
Finally, patient preferences matter. Some patients appreciate frequent visits and close monitoring throughout treatment. Others prefer a "one-and-done" approach, wanting to receive treatment and then return only periodically for follow-up.
Different treatments also have different side effect profiles, and previous experiences—either personal or within a family—may influence which option a patient feels most comfortable receiving. Treatment decisions are always individualized.
Standard Treatments for Hairy Cell Leukemia
Today, we have several highly effective treatments for Hairy Cell Leukemia.
The historical standard of care remains the purine nucleoside analogs, specifically:
● Cladribine
● Pentostatin
Worldwide, these continue to be the most commonly used treatments.
One remarkable feature of Hairy Cell Leukemia is that these treatments can often be used more than once. For example, a patient may receive cladribine, enjoy a remission lasting ten years, experience a relapse, and then receive cladribine again with another excellent response.That is unusual among cancers.In many solid tumors, such as colon, lung, kidney, or breast cancer, repeating exactly the same treatment years later often does not produce another durable remission.
Hairy Cell Leukemia behaves differently. These chemotherapy drugs are frequently combined with anti-CD20 monoclonal antibodies, including: Rituximab or Obinutuzumab
Beyond chemotherapy, we now have several non-chemotherapy targeted therapies.
These include:
● BRAF inhibitors, developed originally for melanoma
● BTK inhibitors, developed for chronic lymphocytic leukemia
● Other investigational agents, including MEK inhibitors, RAF inhibitors, and venetoclax
● Emerging immune therapies such as CAR T-cell therapy and bispecific antibodies
In selected situations, specialists may also recommend interferon, particularly during pregnancy, or splenectomy if the spleen becomes extremely enlarged or develops complications.
Cladribine and Pentostatin
Because these medications remain the standard of care, I'd like to spend a little more time discussing them.
Cladribine and pentostatin are known as purine nucleoside analogs.
They work by interfering with the production of DNA, preventing leukemia cells from making new genetic material and ultimately causing them to die. Although the drugs work in similar ways and produce similar outcomes, they differ in how they are administered.
Cladribine is generally given as a continuous infusion over five to seven days, after which treatment is complete. Pentostatin, on the other hand, is usually administered every two weeks, typically for about twelve treatments, or approximately six months.
Both therapies are highly effective. Approximately 80% of patients achieve a complete remission. The average remission lasts roughly seven to ten years, although some patients experience considerably longer remissions. The median time before additional treatment is needed is approximately seven to eight years. Importantly, studies have shown no meaningful difference in long-term outcomes between cladribine and pentostatin.
The introduction of these drugs completely transformed Hairy Cell Leukemia. When Dr. Bertha Bouroncle first described the disease in 1958, average survival after diagnosis was only about four years. Today, thanks to these treatments, most patients can expect a normal life expectancy. That is truly remarkable.
Rituximab and Combination Therapy
What happens when we add rituximab?
Rituximab is a monoclonal antibody that targets CD20, one of the proteins found on the surface of Hairy Cell Leukemia cells.
Researchers in the United Kingdom studied patients who received rituximab together with cladribine after they had relapsed.Remarkably, many patients experienced longer remissions after their second treatment than after their first.
For example, someone who received cladribine alone initially and remained in remission for seven years might later receive cladribine plus rituximab and remain in remission for ten, fourteen, or even twenty years. Those findings were transformative.
Building on those observations, additional treatment approaches were developed, including CDAR, which combines cladribine and rituximab.In 2020, investigators at the National Institutes of Health published results from a randomized Phase II clinical trial comparing:
● Cladribine plus rituximab
● Cladribine alone
The combination produced significantly better outcomes.The complete response rate reached 100% with combination therapy compared with 88% for cladribine alone.Even more striking was the rate of minimal residual disease (MRD)-negative remission.Using highly sensitive testing methods, nearly all patients receiving the combination achieved undetectable disease, compared with only about one-quarter of patients treated with cladribine alone.
These results suggest that combining cladribine with rituximab can produce deeper remissions than chemotherapy alone.
Newer Targeted Treatments
As our understanding of Hairy Cell Leukemia has improved, several targeted therapies have been developed that attack specific biological pathways within the leukemia cells.
These treatments work differently from traditional chemotherapy and have expanded the options available for patients, particularly those whose disease has relapsed or who cannot safely receive standard chemotherapy.
Current targeted approaches include:
● BRAF inhibitors
● BTK inhibitors
● Other investigational targeted therapies
● Cellular immunotherapies
Many of these treatments were originally developed for other blood cancers or solid tumors and later found to be highly effective in Hairy Cell Leukemia.
BRAF Inhibitors: Vemurafenib
One of the most exciting developments has been the use of vemurafenib, a BRAF inhibitor originally developed to treat melanoma.
Because nearly every patient with classic Hairy Cell Leukemia has the BRAF V600E mutation, targeting this mutation makes biological sense.Vemurafenib is an oral medication taken as pills, usually for less than six months.One of its greatest strengths is that it can produce very rapid improvements in blood counts. Overall response rates approach 100%.
However, when vemurafenib is used by itself, the average remission lasts only about nine months, after which the disease often returns.For that reason, vemurafenib is particularly useful in certain situations.
For example, if a patient is diagnosed with Hairy Cell Leukemia while also fighting a serious infection, physicians may be reluctant to begin cladribine because it causes profound suppression of the immune system. Instead, vemurafenib can rapidly reduce the leukemia burden, restore blood counts, improve immune function, and allow the patient to recover from the infection before transitioning to another treatment.
Vemurafenib Combined with Rituximab
Researchers have also studied combining vemurafenib with rituximab.
A Phase II clinical trial evaluated this combination in patients with previously treated Hairy Cell Leukemia. The study included 31 patients, most of whom had already received a median of three prior treatments.
The results were very encouraging.Approximately 87% of patients responded, and progression-free survival remained close to 80% at about three years.Another important advantage was the speed of recovery.Patients experienced improvement in their blood counts within two to four weeks, which is considerably faster than the recovery typically seen after treatment with cladribine and rituximab.Rapid blood count recovery can be especially valuable for patients who have active infections or severe cytopenias.
BTK Inhibitors: Ibrutinib
Another class of targeted therapy is the BTK inhibitors, including ibrutinib.
These medications were originally developed for diseases such as:
● Chronic lymphocytic leukemia (CLL)
● Mantle cell lymphoma
● Marginal zone lymphoma
● Waldenström macroglobulinemia
Researchers later discovered that they can also be effective in Hairy Cell Leukemia.
Dr. Kerry Rogers and colleagues at Ohio State published results in Blood in 2021 describing the use of ibrutinib in patients with Hairy Cell Leukemia. Most of the patients in that study had already received multiple previous treatments. Despite that, outcomes were encouraging. At the time of analysis, the median progression-free survival and overall survival had not yet been reached, indicating that many patients continued to benefit from treatment for prolonged periods.
Looking Beyond Traditional Chemotherapy
One of the most exciting areas of current research involves using the patient's own immune system to fight Hairy Cell Leukemia.
One approach is CAR T-cell therapy.
In this treatment, T cells are collected from the patient and genetically engineered to recognize a protein such as CD19 found on the surface of leukemia cells. The modified T cells are then returned to the patient, where they can identify and destroy cancer cells. CAR T-cell therapy has already transformed the treatment of diseases such as acute lymphoblastic leukemia and diffuse large B-cell lymphoma. Researchers are now investigating whether similar approaches can benefit patients with Hairy Cell Leukemia.
Another promising strategy involves bispecific antibodies.
These medications act as a bridge between the patient's own T cells and the leukemia cells, bringing them together so the immune system can recognize and kill the cancer more effectively.
Clinical Trials and Future Treatment Options
Several important clinical trials are currently underway.
One multicenter Phase II study, led by Dr. Robert Kreitman at the National Institutes of Health, is evaluating venetoclax in patients with relapsed classic Hairy Cell Leukemia and Hairy Cell Leukemia Variant.
Venetoclax is an oral medication already widely used in chronic lymphocytic leukemia and acute myeloid leukemia.
Another important national study is being led by Dr. Jae Park at Memorial Sloan Kettering Cancer Center. This randomized Phase II trial compares:
● Vemurafenib plus obinutuzumab
● Cladribine plus rituximab
in patients who have never been treated before.
One of the major questions this study hopes to answer is whether chemotherapy can eventually be replaced with a combination of targeted therapy and immunotherapy.
Another exciting study is being led by Dr. Seema Bhat at Ohio State University. This trial is evaluating tovorafenib, another RAF inhibitor, combined with rituximab. The study will initially enroll patients with relapsed or refractory Hairy Cell Leukemia. If successful, it will expand into a randomized Phase II study comparing:
● Tovorafenib plus rituximab
● Cladribine plus rituximab
Beyond these studies, numerous additional clinical trials are underway across the United States. Some are designed specifically for Hairy Cell Leukemia, while others include several different B-cell malignancies.
These studies include therapies such as:
● Additional MEK inhibitors
● CD22-directed CAR T-cell therapy
● LP-168
● Novel BCL-2 inhibitors
● Other emerging targeted therapies
Clinical trials remain an important way to improve treatment and continue advancing care for future patients.
Monitoring After Treatment
Once treatment has been completed, careful follow-up is an important part of long-term care.
The first formal evaluation is often performed approximately six months after treatment.
Many physicians repeat a bone marrow biopsy, although this is not standardized and practices vary among treatment centers.
As I mentioned earlier, it's important to know both where you've started and where you've ended up after treatment. Some physicians also assess minimal residual disease (MRD) using highly sensitive techniques, such as testing for the BRAF mutation by PCR.
The frequency of follow-up depends on several factors, including:
● How recently treatment was completed
● Whether any complications occurred during treatment
● The patient's overall health
● The severity of disease before treatment
Some patients are monitored every three months, others every six months, and some only once a year.
At follow-up visits, doctors generally perform:
● A complete blood count (CBC)
● A physical examination
● Evaluation of the spleen
● Examination for enlarged lymph nodes
Some treatment centers also measure the soluble interleukin-2 receptor (sIL-2R).
This blood test can sometimes provide useful information, although it is not specific for Hairy Cell Leukemia and may also be elevated during infections.
It's also important to recognize that routine, repeated bone marrow biopsies or ongoing MRD testing are not necessary for every patient. These decisions are individualized based on each patient's clinical situation.
Staying Healthy During Remission
One of the encouraging realities of Hairy Cell Leukemia today is that most patients can expect to live for many decades after diagnosis. Because of that, maintaining overall health becomes extremely important.
Patients should continue to receive all age-appropriate cancer screenings.
Sometimes, after someone is diagnosed with leukemia, routine preventive care unintentionally receives less attention because everyone is focused on the cancer. However, regular screening for other cancers remains just as important.
One area that deserves special attention is skin cancer screening.
Patients with Hairy Cell Leukemia, or a history of treatment for Hairy Cell Leukemia, have an increased risk of developing skin cancers. For that reason, I recommend a complete skin examination once or twice each year, performed by a dermatologist, primary care physician, or oncologist familiar with these risks.
Patients who have had Hairy Cell Leukemia also have an increased susceptibility to infections. That does not mean you need to stay isolated or avoid living your life. Instead, it means being thoughtful and using common sense.
Vaccinations remain an important part of staying healthy.
Recommended vaccines include:
● Pneumococcal vaccines
● Shingles vaccine
● Tetanus
● Pertussis
● RSV vaccine, when age-appropriate
● Annual influenza vaccination
● COVID-19 vaccination for many patients, depending on individual circumstances
On the other hand, live vaccines should generally be avoided.
Finally, because patients are now living long, healthy lives after treatment, all of the usual recommendations for healthy living continue to matter.
Eat a balanced diet.
Exercise regularly.
Take care of your overall health, not just your leukemia.
Questions Researchers Are Still Trying to Answer
Although tremendous progress has been made, many important questions remain.
One of the biggest questions is:
What is the optimal treatment for Hairy Cell Leukemia?
The clinical trials I discussed earlier are designed to help answer that question. We also continue to study how best to use anti-CD20 antibodies such as rituximab.
Should rituximab be given at the same time as cladribine? Should it be delayed? Can it safely be omitted in some patients? If so, which patients?
Another important question is whether chemotherapy is even necessary.
Perhaps some patients can achieve equally good—or even better—outcomes with targeted therapies combined with immunotherapy. We're also trying to determine:
● Which newer treatments should be used
● When they should be used
● Which patients benefit most from each approach
Hairy Cell Leukemia Variant remains another major area of investigation. Although it is clearly related to classic Hairy Cell Leukemia, it is biologically distinct. Patients with Hairy Cell Leukemia Variant generally do not respond as well to cladribine.
We continue to study:
● The best treatment approaches
● The implications of the World Health Organization's new classification
● How treatment can be further improved
Finally, we're asking broader questions about patient health. How can we better support people living with Hairy Cell Leukemia? How can we improve quality of life? How can we better understand the patient experience?
These are exactly the kinds of questions the Hairy Cell Leukemia Foundation Patient Data Registry is helping us answer.
Closing Remarks
That concludes the presentation I planned for today. I hope this overview has helped you better understand Hairy Cell Leukemia, how it is diagnosed, how it is treated, and where the field is heading.
The progress we've made over the past several decades has been remarkable. Hairy Cell Leukemia has gone from a disease associated with a very limited life expectancy to one in which most patients can expect to live for decades, often with a normal lifespan.
At the same time, research continues to move the field forward. We're developing better therapies, asking better questions, and working toward treatments that are increasingly effective while minimizing side effects.
Thank you again to the Hairy Cell Leukemia Foundation for inviting me to speak today and for everything the Foundation does to support patients, families, education, and research.
I'd be delighted to answer your questions.
Questions & Answers with Dr. Blachly
Shingles and Infection Prevention - How serious is shingles for someone with Hairy Cell Leukemia? How should it be managed?
Dr. James Blachly:
That's a great question.
First, let's define shingles. Shingles is a reactivation of the chickenpox virus. Most people diagnosed with Hairy Cell Leukemia are old enough to have had chickenpox as children. Although the infection goes away, the virus never completely leaves the body. Instead, it remains dormant in nerve roots along the spinal cord.
When the immune system becomes weakened, either because of stress or because of chemotherapy, that virus can reactivate, causing shingles, which can be extremely painful and uncomfortable.
Hairy Cell Leukemia treatments, particularly cladribine and pentostatin, are very effective at reducing T cells, which play an important role in preventing shingles. T-cell recovery can take 18 months or longer after treatment.
For that reason, physicians commonly prescribe preventive antiviral medications such as acyclovir or valacyclovir (Valtrex) before beginning treatment.
If shingles develops despite preventive medication, it should be considered a medical emergency. Patients should contact their healthcare team immediately because hospitalization and intravenous antiviral treatment may be necessary.
Immune System Recovery After Treatment - How long does it take for the immune system to recover after treatment?
Dr. James Blachly:
Both the leukemia cells and the normal B cells are very effectively targeted by treatments such as cladribine, pentostatin, rituximab, and obinutuzumab.
Recovery of normal B cells can take a year or longer. The cells are usually not completely absent, but they may remain significantly reduced for an extended period.
Because B cells produce antibodies that protect us from infections like pneumonia, it's important to keep vaccinations up to date and, when appropriate, check antibody levels to determine whether additional vaccination is needed.
Unfortunately, it's impossible to predict exactly when an individual patient's B cells will recover. In some people, recovery may take one to two years.
The encouraging news is that, beyond temporary depletion of B and T cells, we generally do not expect permanent immune system damage.
One possible exception involves patients who receive multiple courses of cladribine, since repeated exposure may affect bone marrow stem cells that produce neutrophils, increasing susceptibility to certain bacterial and fungal infections.
Fortunately, today's treatment strategies rely less on repeated cycles of cladribine than they did in the past.
Bone Marrow Fibrosis and Bone Pain - Does bone marrow fibrosis improve after treatment?
Dr. James Blachly:
Yes.
The hairy cells themselves produce substances that lead to fibrosis. Once those cells are eliminated with treatment, the fibrosis improves significantly.
If you examine a bone marrow biopsy about six months after successful treatment with cladribine, you'll usually see far less fibrosis than when the disease was active.
Should persistent bone pain after treatment raise concern about bone lesions?
Dr. James Blachly:
Bone pain can have several causes.
Before treatment, bone pain may simply reflect a bone marrow filled with leukemia cells.
However, if someone has been successfully treated but continues to experience persistent bone pain, it is reasonable to discuss further evaluation with their physician.
A nuclear medicine bone scan may help determine whether bone lesions are present, particularly if symptoms continue despite otherwise successful treatment.
Diagnosis and Flow Cytometry - Should patients worry about every CD marker listed on their flow cytometry report?
Dr. James Blachly:
Generally, no.
Pathologists provide a great deal of information in flow cytometry reports, often much more than is needed to establish the diagnosis.
They are intentionally very thorough.
From a treatment standpoint, the most important markers are:
● CD19
● CD20
● CD22
Most of the additional markers listed on a report are primarily useful to the pathologist and are not something patients generally need to worry about.
My initial blood tests make me worry that I might have Hairy Cell Leukemia Variant. Should I be concerned before all of the diagnostic testing is complete?
Dr. James Blachly:
I would encourage patients not to jump to conclusions before all of the diagnostic testing has been completed.
We've made tremendous progress in understanding Hairy Cell Leukemia Variant and how it differs from classic Hairy Cell Leukemia.
Today, we have multiple treatment options, as well as clinical trials specifically designed for patients with HCL Variant.
Patients with HCLv can respond well to treatments such as cladribine plus rituximab. While those remissions may not last as long as they often do in classic Hairy Cell Leukemia, treatment options continue to improve.
I would encourage patients not to worry prematurely. Research is advancing rapidly, and improving outcomes for Hairy Cell Leukemia Variant remains an important focus of the Hairy Cell Leukemia Foundation and the research community.
Preparing for Treatment - What should patients do before starting cladribine and rituximab? Should they receive vaccinations or see other specialists?
Dr. James Blachly:
These are excellent questions.
First, it's important to recognize that cladribine and rituximab are among the least toxic chemotherapy regimens we use in hematology and oncology.
That doesn't mean they can't have serious side effects, but unlike many other chemotherapy drugs, they generally do not damage organs such as the heart.
Because of that, patients usually do not require specialized cardiac testing such as an echocardiogram before treatment.
An electrocardiogram (EKG) is routinely performed, but additional cardiac evaluation is generally only necessary if another medical condition warrants it.
The primary complications associated with cladribine and rituximab involve the immune system and, to a lesser degree, the blood counts.
Vaccinations are an important part of preparation because vaccines tend to work better before treatment, while normal B cells are still present and able to generate immune memory.
Patients should receive all age-appropriate vaccinations.
Even younger patients with Hairy Cell Leukemia may benefit from vaccination against pneumococcal pneumonia.
We also recommend the shingles vaccine.
In the United States, the currently available shingles vaccine is not a live vaccine, so the concerns we had with the older live vaccine no longer apply.
First-Line Treatment Recommendations - Do you consider cladribine plus rituximab to be the preferred first-line treatment?
Dr. James Blachly:
Yes.
In my opinion, cladribine combined with rituximab represents the current standard of care for the initial treatment of classic Hairy Cell Leukemia.
Adding rituximab produces only a modest increase in side effects while substantially improving the depth of remission.
Studies from the United Kingdom showed that adding rituximab in later lines of therapy resulted in even longer remissions.
The National Cancer Institute studies also suggest that patients receiving cladribine plus rituximab are likely to experience exceptionally durable remissions.
Because this combination has only become standard relatively recently, we don't yet know exactly how long these remissions will ultimately last.
I'm hopeful that many patients I treat today in the frontline setting may never experience another relapse.
Should rituximab be given at the same time as cladribine or after cladribine?
Dr. James Blachly:
Both approaches are effective.
Whether rituximab is given concurrently with cladribine or sequentially afterward, patients achieve very high rates of minimal residual disease (MRD)-negative remission.
However, the available data suggest that concurrent treatment produces the highest rates of MRD negativity.
We also know that any rituximab is better than no rituximab, as patients receiving cladribine plus rituximab consistently achieve deeper remissions than those receiving cladribine alone.
Because Hairy Cell Leukemia patients often live for decades, it will take many years before we know whether those deeper remissions ultimately translate into longer survival.
Recovery After Treatment - How long does it take blood counts to recover after treatment?
Dr. James Blachly:
Every patient's recovery is different.
Even after successful treatment, anyone who has received chemotherapy may have blood counts that remain slightly lower than they were before treatment.
This doesn't necessarily indicate relapse.
Healthy people naturally experience fluctuations in their blood counts, but those variations often go unnoticed because their counts remain comfortably within the normal range.
After chemotherapy, patients are closer to the lower end of normal, so even small changes may appear alarming on laboratory reports.
Recovery also depends on how healthy the bone marrow was before treatment began.
If the bone marrow was heavily infiltrated with Hairy Cell Leukemia, there may have been relatively few healthy stem cells remaining.
Although treatment effectively removes the leukemia cells, those remaining healthy stem cells still need time to rebuild normal blood production.
Patients who begin treatment with relatively preserved bone marrow typically recover much more quickly than those whose marrow was extensively involved.
Is it normal for blood counts to fluctuate after treatment?
Dr. James Blachly:
Yes.
Some fluctuation is completely normal.
One phenomenon we occasionally see is delayed-onset neutropenia, which can occur several months after treatment with rituximab or obinutuzumab.
Patients may suddenly develop a drop in neutrophil counts six months or even longer after completing therapy.
Although this can be concerning, it is generally an immune-mediated phenomenon that is not fully understood.
It is usually managed with careful observation and, in some cases, corticosteroids.
Overall, most patients recover their blood counts within approximately one month.
Some require three months, while a small number may need up to six months before their blood counts return to normal.
New Therapies and Clinical Trials - Are there promising new treatments for Hairy Cell Leukemia beyond cladribine and rituximab?
Dr. James Blachly:
Yes. This is one of the most exciting areas of Hairy Cell Leukemia research.
Several promising therapies are currently being studied in clinical trials, with the goal of developing treatments that are highly effective while reducing or even eliminating the need for chemotherapy.
One example is venetoclax, a targeted therapy that has already transformed the treatment of chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). Clinical trials are currently evaluating venetoclax for both classic Hairy Cell Leukemia and Hairy Cell Leukemia Variant.
Another exciting area involves combining targeted therapies with monoclonal antibodies, with the hope of producing deep, durable remissions without traditional chemotherapy.
These studies represent the future of Hairy Cell Leukemia treatment, and we're optimistic that they'll continue to improve outcomes for patients.
Can you tell us more about the upcoming tovorafenib clinical trial?
Dr. James Blachly:
Certainly.
The upcoming study led by Dr. Seema Bhat will evaluate tovorafenib, which is a RAF inhibitor taken as a once-weekly oral medication.
In the study, patients will receive:
● Tovorafenib once each week, combined with
● Rituximab, administered weekly at first and then every other week for a total of eight doses.
If this approach proves effective, it has the potential to become a highly tolerable treatment regimen.
Ultimately, one of our goals is to determine whether targeted therapies like this can replace chemotherapy for some patients.
That's the direction the field is moving.
This transcript has been edited for clarity.