What is Hairy Cell Leukemia?
Hairy cell leukemia (HCL) is a type of blood cancer that’s not very common. It impacts the white blood cells, specifically B-cells, and can affect the bone marrow, spleen, and the blood itself. The standard blood test might show reduced levels of all types of blood cells, including a drop in a specific type of white blood cells called monocytes. Most people get diagnosed around the age of 55.
Certain factors that might indicate a worsened outlook include things like being older, having a hemoglobin count (the molecule that carries oxygen in red blood cells) less than 10 g/dL, less than 100 platelets (cells that help stop bleeding), less than 1000 ANC (a measure of a specific type of white blood cell), presence of lymph nodes which are larger than normal, and an overly enlarged spleen. Other similar conditions like splenic marginal zone lymphoma (another type of blood cancer) need to be ruled out because they can look very similar.
There’s also a unique version of this disease known as hairy cell leukemia variant (HCL-V), which is biologically different from HCL, and doesn’t respond well to the usual HCL treatments. HCL-V is identified by different cell appearances, not having a certain genetic change called the BRAF mutation, and not having a drop in monocytes.
HCL accounts for around 2% of all leukemia cases, with roughly 1000 new instances reported in the US each year.
What Causes Hairy Cell Leukemia?
The exact cause of a type of cancer called hairy cell leukemia is not clear. However, it is believed that exposure to certain chemicals may contribute to its development. Most cases are thought to be caused by a specific change, or mutation, in a gene called V600E BRAF. This change typically occurs in specific cells of the immune system, known as late activated memory B cells.
Risk Factors and Frequency for Hairy Cell Leukemia
Hairy cell leukemia is an uncommon form of cancer, making up just 2% of lymphoid leukemias, a type of blood cancer. Most people are diagnosed around the age of 55, and while it can sometimes occur in younger people, it almost never affects children. Men are four times more likely to be affected than women.
Signs and Symptoms of Hairy Cell Leukemia
People affected with this condition often experience general symptoms like feeling tired and weak. These symptoms are connected to cytopenias (a reduction in the number of blood cells) and splenomegaly (enlarged spleen). On diagnosis, 80% of patients show significant cytopenias, with less than 10% suffering from severe pancytopenia (where the patient has low counts for all three types of blood cells). Although an enlarged spleen is a common sign, very large and symptomatic spleens are less common. This could be due to early detection during standard blood tests. Some patients could experience autoimmune thrombocytopenia (low blood platelet count) and hemolytic anemia (a condition leading to premature destruction of red blood cells), but these occurrences are rare. It is also common for patients to have infectious complications due to the reduced number of blood cells and suppressive therapies that reduce the capacity of the body’s immune system.
Testing for Hairy Cell Leukemia
To diagnose your condition, your doctor can conduct some blood tests. One of these is the flow cytometry, which sorts your blood cells into different types, while another is the peripheral smear test, where a droplet of your blood gets examined under a microscope.
In addition, your doctor may do a bone marrow biopsy. This is a procedure to remove a small amount of bone marrow, the spongy tissue inside your bones, for testing. However, there are times when the doctor might not be able to draw out the bone marrow fluid. This is often the case with a type of blood cancer called “hairy cell leukemia,” though not with its variant known as HCL-V.
The ‘hairy cell’ from this leukemia are irregular-looking blood cells. They are typically large with thin, hair-like extensions around them and have a distinct, round nucleus in the center.
Using flow cytometry, these cells often test positive for markers known as CD11c, CD25, CD103, and CD123, along with other markers of B-cell ( a type of white blood cell), like CD19, CD20, or CD22. They usually express a protein called cyclin-D1, but this is usually weak or only focal (unlike mantle cell lymphoma, another type of blood cancer). The variant HCL-V does not show CD25 and CD123.
Nearly all classic hairy cell leukemia cases present a specific mutation called BRAF-mutation V600E, although it’s not present in HCL-V.
Lastly, to check for swollen lymph nodes, your doctor might recommend a Computed Tomography (CT) scan, which is a type of X-ray that can show detailed images of the body’s interior.
Treatment Options for Hairy Cell Leukemia
Hairy cell leukemia is a type of cancer that can’t be cured, and treatment is typically given to patients who have symptoms. These symptoms may include extreme tiredness, a swollen spleen causing discomfort, and a significant drop in blood cell counts. Blood cell counts include hemoglobin (a protein in red blood cells that carries oxygen), platelets (cells that help blood clot), and ANC (a measure of the immune system’s strength). Individuals without symptoms should have regular check-ups every 3 to 6 months to monitor for any progression of the disease.
The go-to treatment for hairy cell leukemia involves two drugs called cladribine and pentostatin. Both work in similar ways and are equally effective at inducing and maintaining remission, meaning the disappearance of signs and symptoms of cancer. However, cladribine is generally favored due to its lower risk of side effects. A single round of cladribine can lead to a complete response in approximately 90% of patients, meaning that all signs of cancer are gone. It’s important to remember that patients will have a weakened immune system for several months following this treatment, which increases their risk of infections.
A recent study suggested that for those receiving treatment for the first time or experiencing their first relapse, the combination of cladribine and an additional drug called rituximab was most effective. Vemurafenib, yet another drug, has shown similar effectiveness but is usually saved for stubborn or advancing cases.
If a patient is pregnant and requires treatment, the recommended choice is interferon-alpha. This may also be the initial treatment for patients with low blood cell counts and/or active infection to help improve their counts before starting therapy with cladribine or pentostatin. However, some patients with HCL who have a certain marker on their cells known as the CD5 antigen, may not respond well to interferon-alpha.
If the spleen is extremely swollen leading to discomfort or low blood cell counts, it could be removed through a procedure called a splenectomy. This could also be a temporary solution in pregnant women who are experiencing symptoms.
After treatment, a repeat bone marrow biopsy should be performed to confirm that all signs of cancer are gone, which is known as complete remission. This is determined by the absence of hairy cells in the blood and bone marrow, a normal spleen size, and recovery of peripheral blood counts. If peripheral blood counts are normal, the spleen has shrunk by half, and less than 5% of circulating hairy cells remain, this is known as partial response. It is currently not clearly understood what the implications of having a small number of remaining cancer cells are, but many patients with these cells can still have long periods of complete remission.
If the leukemia comes back, it can be treated with another round of cladribine or pentostatin if it’s been more than a year since the initial treatment. However, the success rate is usually lower and the periods of remission shorter after relapse. There are several other options for treatment if the disease comes back or doesn’t respond to the initial treatment, such as combining cladribine or pentostatin with rituximab, using a drug called fludarabine alone or with rituximab, using a drug called bendamustine, or using interferon-alpha. Vemurafenib can be used to specifically target a mutation that is often found in hairy cell leukemia cells, and has been shown to be effective in both the relapsed and stubborn cases.
Supportive care is also an important part of treatment. This can include taking preventive measures against infections and providing blood products when needed. Special precautions should be taken with transfused blood products to prevent a severe complication known as graft-versus-host disease.
What else can Hairy Cell Leukemia be?
When diagnosing certain medical conditions, doctors would consider a number of other conditions that could show similar symptoms. These alternative conditions are:
- HCL variant: This condition is usually marked by noticeable nucleoli and and less infiltration of the bone marrow. It often includes extremely high white blood cell counts, and doesn’t usually result in low levels of neutrophils, monocytes, red blood cells and platelets like in HCL.
- Splenic diffuse red pulp small B cell lymphoma: This condition usually does not show annexin A1, CD25, CD103, CD123, and CD11c proteins.
- Splenic marginal zone lymphoma: This typically doesn’t express CD103, CD11c, and CD25 proteins.
- Other unclassifiable splenic lymphomas
- Mantle cell lymphoma: This condition shows CD5 protein and strong expression of cyclin D1 protein. It doesn’t usually show CD25, CD103, or annexin A1 proteins. Further, it doesn’t show any hairy cytoplasm in lymphocytes.
- Chronic lymphocytic leukemia: This condition shows CD5 protein and doesn’t show CD103 protein. It affects both red pulp and white pulp of the spleen, whereas HCV mostly affects red pulp.
- Prolymphocytic leukemia: This condition is marked by a significant increase in white blood cell count, the distinct morphology of prolymphocytes and absence of hairy cytoplasmic projections.
These potential diagnoses could all present similar symptoms, so it’s important for doctors to consider all possibilities when making their final diagnosis.
What to expect with Hairy Cell Leukemia
Without treatment, people typically survive around 4 years. If the factors known as VH4-34 are positive in HCL (hairy cell leukemia) cases, it points to a worse prognosis, meaning the disease may worsen over time or become harder to treat.
Possible Complications When Diagnosed with Hairy Cell Leukemia
Research has indicated that people with a type of cancer called hairy cell leukemia can sometimes develop other types of cancer as well. This could happen because the leukemia weakens the immune system, or because of the effects of chemotherapy drugs used to treat it.
Potential Risks and Complications:
- Development of other types of cancers
- Weakening of the immune system due to leukemia
- Potential side-effects of chemotherapy drugs
