This cancer begins in the bone marrow — soft, spongy tissue inside bones. Bone marrow produces a number of different types of blood cells. Hairy cell leukemia involves the B cells (also called B lymphocytes), a type of white blood cell that normally helps the body fight infection by making antibodies. With hairy cell leukemia, the bone marrow produces large amounts of defective B cells. These cells have short, thin, hair-like projections on their surface (thus giving the disease its name). These leukemia cells overrun the bone marrow and blood. This results in low levels of normal white blood cells, red blood cells, and platelets. Low levels of these cells can cause a range of physical complications and symptoms. Hairy cells leave the bone marrow and circulate through the bloodstream, almost always collecting in the spleen (an organ in the left upper part of the abdomen that filters blood, removing old or worn-out blood cells). The accumulation of hairy cells in the spleen can enlarge it (a condition called splenomegaly). If the spleen gets too big, it can trap too many red blood cells, white blood cells and platelets from the blood, lowering levels even further. Hairy cells may also collect in the lymph nodes and the liver, another organ that filters blood. Although this rare form of leukemia is highly treatable, with patients often staying in remission with low to undetectable numbers of hairy cells for many years after therapy, it is considered a chronic disease because it may never go away completely. (1) Because hairy cell leukemia is slow-growing, some patients live symptom-free even without treatment. Around 10 percent of people with hairy cell leukemia don’t require any type of therapy whatsoever, although they require regular monitoring by a physician to make sure the disease hasn’t progressed. (2) In a recent breakthrough, scientists discovered that the vast majority of people with hairy cell leukemia have a mutation in the BRAF gene — a gene also implicated in a number of other cancers, including melanoma. In a healthy person, the BRAF gene instructs cells to grow, divide, and eventually die. A mutation disrupts this cycle, leading to the out-of-control cell growth that defines cancer. Scientists are still working to understand what causes the BRAF mutation, and hairy cell leukemia in general. They have investigated possible risk factors, including exposure to industrial or agriculture chemicals or radiation (which may affect people in occupations that involve X-rays). But studies so far have proved inconclusive or have resulted in conflicting findings. (1) HCL is four times more common in males than females, and usually presents at age 50 or above. (3) Scientists believe that the genetic mutations behind the disease aren’t passed down by one’s parents but rather acquired during one’s lifetime. (3) Hairy cell leukemia can also impact organs that filter blood, notably the spleen. Hairy cells can accumulate inside the spleen, causing it to swell and become overactive. These changes can lead to all kinds of symptoms. Unfortunately, many overlap with signs of more common, less worrisome medical conditions, leading to a delay in diagnosis. Symptoms of hairy cell leukemia include:
Fever without an obvious cause or a persistent, low-grade feverChillsFrequent infectionsDiscomfort, pain, or a “dragging” feeling in the upper left side of your abdomen, below the ribs (caused by an enlarged spleen)Unexplained weight lossBlack-and-blue marks (bruises) that appear on the skin for no clear reasonPale skinTiredness or lack of energyShortness of breath during normal physical activity (4)
People with hairy cell leukemia are also at increased risk of developing a second form of cancer, including lymphomas. It’s not clear whether these cancers are related to drugs used to treat hairy cell leukemia, or whether the leukemia itself raises the risk. (1)
Physical Exam The doctor will press on your abdomen to see if your spleen feels enlarged, and may also check for swollen lymph nodes that may contain hairy cells.Blood Tests A test called a complete blood count (CBC) measures levels of red blood cells, normal white blood cells, and platelets. Lower-than-normal amounts may be a sign of hairy cell leukemia. A second test, called a peripheral blood smear, looks for hairy cells in a blood sample.Bone Marrow Tests These generally involve removing two sample of bone marrow — liquid marrow and a tiny piece of bone filled with marrow — from the hip area. The procedure is done in a doctor’s office or a hospital using a local anesthetic and a special needle. A pathologist studies the sample under a microscope to search for hairy cells and measure levels of healthy blood cells.Imaging Scans Your doctor can look inside the body using ultrasound (a method that creates 3D pictures using high-frequency sound waves), a computerized tomography (CT) scan (a technology that uses X-rays), or a positron emission tomography (PET) scan (a technology that uses radioactive tracers). These scans can reveal if the spleen, liver, or lymph nodes are enlarged. (5)
A firm diagnosis of hairy cell leukemia requires another type of evaluation called immunophenotyping. For this test, a pathologist studies the cancerous lymphocytes — from the blood or bone marrow — looking for particular markers (antigens) on the surface of the B cells. Certain patterns will reveal hairy cells. A technique called flow cytometry that uses laser beams may be used for this purpose. (6) Your doctor may also use a genetic test on the cancerous cells to see if they carry the BRAF mutation. This information can help them target your treatment. (3) But the good news is that it is highly treatable. People can go into long, sustained remissions, with levels of hairy cells in the blood and marrow that are so low, they are undetectable even using the most advanced technologies. With proper medical attention, many patients do well for years or even decades and have a near-normal life expectancy. Finding a doctor who has specialized knowledge of this leukemia can make a significant difference in outcome. For the highest quality of care, the Leukemia & Lymphoma Society recommends that patients seek out physicians with experience in hairy cell leukemia (usually a hematologist oncologist) or a doctor who works closely with a specialist. (8) Treatment for hairy cell leukemia can take a number of forms. These include: Watch and Wait About 10 percent of patients with this slow-growing form of leukemia don’t take any medication or receive any other form of therapy at all. Instead, doctors monitor the condition with regular physical exams and blood tests. This approach allows patients to avoid medication and the potential side effects for as long as possible. Chemotherapy This is one of the front-line treatment for hairy cell leukemia. Chemo drugs are toxic: They damage or kill hairy cells. But they may also harm healthy cells in the process, causing side effects. Patients typically receive a type of chemo drug called a purine analog — usually cladribine (Leustatin), administered intravenously every day for up to a week. Around 85 percent of patients treated with Leustatin go into complete remission (meaning there is no evidence of disease) while 10 percent or so have a partial response. Doctors may also use a purine analog called pentostatin (Nipent). It causes remission rates similar to cladribine but is administered according to a different schedule. Patients may receive this medication every other week for three to six months. (5)
What Happens if Treatment for Hairy Cell Leukemia Doesn’t Work?
Some patients will still have detectable levels of hairy cells in their body after treatment, a condition called refractory hairy cell leukemia. Or the hairy cell leukemia may relapse — that is, it may return after a period of remission. Doctors use a number of drugs to treat refractory or relapsed hairy cell leukemia. Among the newest are targeted therapies that attack cancer cells without harming normal cells.
Cladribine or Pentostatin Physicians may go back to these first-line chemotherapy drugs.Rituximab (Rituxan) This drug is a monoclonal antibody — a laboratory-made version of an immune-system protein that is genetically engineered to find and attach to specific targets on hairy cells. Rituximab targets and binds to CD20, a protein on the surface of hairy cells, triggering the body’s immune system to attack. Moxetumomab Pasudotox (Lumoxiti) This drug was approved by the U.S. Food and Drug Administration (FDA) in September 2018 for the treatment of hairy cell leukemia. It is a monoclonal antibody that targets the CD22 protein on the surface of hairy cells, then delivers a deadly bacterial toxin right to the cells.Roferon-A or Intron A (interferon-alfa) This type of drug is called an immunomodulator. Interferon is a hormone naturally produced by the body to mount an immune response to infection.
Occasionally, patients with enlarged spleens may need to have the organ removed surgically in a procedure called a splenectomy. This won’t cure hairy cell leukemia but it can rid the body of the accumulated hairy cells in the spleen, helping normalize blood-cell levels. (8) Scientists are working to develop new drugs, new combinations of medication, and changes in how current drugs are administered that would make them more effective. The following are some of the most promising new drugs.
BL22 Immunotoxin Like moxetumomab pasudotox This agent uses a monoclonal antibody designed to target the CD22 protein on hairy cells and deliver a potent bacterial toxin.Imbruvica (Ibrutinib) This fights hairy cell leukemia by blocking some of the enzymes the cells need to multiply and survive.LMB-2 Immunotoxin This medication uses a monoclonal antibody that can find hairy cells with the CD25 protein on their surface, then bind to them. LMB-2 then delivers a potent bacterial toxin directly into the cancer cells.Rituximab Scientists are evaluating the effectiveness of using this drug at the same time as chemotherapy or immediately afterward.Vemurafenib (Zelboraf) This medication, part of a category of drugs called protein kinase inhibitors, is currently FDA-approved to treat patients with melanoma. Researchers are investigating whether vemurafenib may also people with hairy cell leukemia — specifically, the vast majority of patients who have BRAF mutations.
Any patients interested in participating in a clinical trial can find out about opportunities by going to ClinicalTrials.gov, a U.S. government–run database that is searchable by disease condition and location.
