Blood cells are formed in the bone marrow, which is the spongy tissue found inside the bones. Blood-forming stem cells divide to produce either more stem cells or immature cells that become mature blood cells over time. A blood stem cell may become a myeloid stem cell or a lymphoid stem cell. Hairy cell leukaemia (HCL) is a specific type of leukaemia in which the lymphocytic (antibody producing) white blood cells that are produced by the bone marrow are affected.
A lymphoid stem cell becomes a lymphoblast cell and then one of three types of lymphocytes (white blood cells):
- B lymphocytes that make antibodies to help fight infection.
- T lymphocytes that help B lymphocytes make the antibodies that help fight infection.
- Natural killer cells that attack cancer cells and viruses.
In HCL there is an excess number of lymphocytes in the circulating blood. These lymphocytes are abnormal and cannot help the body to defend against infections. They are called hairy cells because the cells have fine projections on the surface – which look like hairs under the microscope. When you have HCL, the marrow is not able to make enough normal blood cells.
HCL is very similar to a type of leukaemia called chronic lymphocytic leukaemia (CLL).
What causes HCL?
The cause of HCL is not known. The only factors which are definitely known to increase the chance of developing the condition are older age and being male. You cannot catch HCL from someone who has it and you cannot pass HCL on to your children.
What are hairy cells?
The normal equivalent of the hairy cell is a type of white blood cell called a B lymphocyte. The function of a B lymphocyte is to produce antibodies which help the body to defend itself against infection. A very important recent discovery has been the fact that a very high proportion, possibly all, hairy cells have a specific mutation of a gene called BRAF. This is not an abnormality which has been passed on by parents; the gene is only abnormal in your hairy cells and not in your normal cells. This may help in confirming diagnosis of HCL and in developing new treatments.
Signs and symptoms of HCL
About a quarter of all patients have no symptoms at the time of diagnosis. Typically these patients are identified because of abnormal results from a routine full blood count.
Symptoms can include:
- Weight loss
- Weakness and breathlessness
- Frequent infections
- Pale complexion
- Enlarged spleen
If you are experiencing any of the symptoms above, you should visit your doctor. A blood test will be arranged and if the results show HCL, you will be referred to a haematologist. They will take your full medical history, carry out a physical examination and initiate further blood tests.
The blood tests will show the number of abnormal white blood cells, and the typical appearance of ‘hairy’ cells may also be seen in the blood sample. People with HCL may also have low numbers of platelets and red blood cells. Other blood tests are usually done to check your general health.
The spleen becomes enlarged in most people with HCL. Your specialist will usually be able to feel this when examining you.
A bone marrow biopsy may also be taken from the hip to confirm diagnosis.
Treatment of HCL
For patients who do not have any symptoms, the watch and wait approach is a good option because evidence has shown that early treatment does not offer any benefit in terms of survival for these patients. This option is also called active monitoring.
For patients with symptoms, antimetabolite cancer drugs have markedly improved the treatment of HCL. They work by interfering with DNA synthesis to prevent the growth or reproduction of cancer cells. The drugs cladribine and pentostatin (less commonly given) have achieved complete response rates in up to 90% of patients with HCL. Complete response is defined by blood counts returning to normal, disappearance of hairy cells from the blood and bone marrow, and a reduction of at least 50% of an enlarged spleen.
Patients have also had treatment-free periods of 10 years or more.
Watch and wait
If you do not have any symptoms when you are first diagnosed with HCL and your blood counts are not very low, your haematologist may suggest a watch and wait approach. This is generally the case for around 10% of people with HCL. This usually involves regular check-ups and blood counts, as well as your haematologist advising you on ways to live a healthy lifestyle.
If symptoms develop and the disease progresses, you may then be started on a suitable treatment.
Chemotherapy is the use of anticancer drugs to destroy the cancer cells. It has a very high success rate in the treatment of HCL. It does not cure the disease but it gives very good control and most patients can expect a normal or near-normal lifespan.
The main drugs used to treat HCL are cladribine and pentostatin, which are antimetabolite purine analogues. Antimetabolites are drugs which interfere with the production of DNA, and therefore prevent the growth or reproduction of cancer cells. Antimetabolite cancer drugs can be divided according to their structure and function as:
- Purine analogues
- Folic acid analogues
- Pyrimidine analogues
- Cytidine analogues
The structure of these analogues are similar to the proteins used to make DNA but they differ enough to interfere with the process when they are incorporated into the DNA.
HCL responds well to both these drugs, although cladribine is the preferred choice because it can be given as a single five- to seven-day course, whereas pentostatin is given every other week for three to twelve months. Both drugs can be given into a vein (intravenously). Cladribine can also be given as injections just under the skin (subcutaneously).
Cladribine and pentostatin can affect the body’s immune system making you more vulnerable to infections. If you need a blood transfusion, you will be given irradiated blood to reduce your chance of infections and complications. Irradiated blood is not radioactive and is just as safe and effective as any other blood transfusion. You may also be given antiviral drugs to prevent some viral infections.
For patients with HCL who do not respond to cladribine or pentostatin, other drugs are available:
- Another antimetabolite purine analogue that can be used for the treatment of HCL is fludarabine which is also used to treat some lymphomas, often in combination with rituximab.
- Biological treatments such as interferon, which was widely used to treat HCL before cladribine and pentostatin were available.
- The monoclonal antibody rituximab can be added to cladribine or pentostatin to improve their efficacy.
The side effects of cladribine and pentostatin are similar. They include:
- Low levels of neutrophil white blood cells (potentially causing a fever)
- Nausea and vomiting
- Nerve damage (rare)
The aim of active treatments is to reduce the number of abnormal hairy cells to as low as possible. It is generally accepted that standard treatment will not cure HCL; but it does offer a very high chance of a normal, good quality of life.
Recommended first-line treatment for patients with HCL is cladribine or pentostatin and many people remain in remission for a long time without further treatment. However, approximately half of patients will relapse and require more treatment.
If the relapse is more than two years after the first treatment, re-treatment usually involves the same chemotherapy drug. If the relapse is less than two years after the first treatment, another chemotherapy drug is likely to be used. Additionally, rituximab (Mabthera) can be added to the chemotherapy with very good results. Other treatment options for a relapse are newer drugs or a bone marrow stem cell transplant.
Biological treatments seek to make the cancer cells more recognisable to your immune system. Once your immune system identifies the cancer cells as intruders, it can set about destroying them.
Rituximab is a monoclonal antibody which is widely used to treat chronic lymphocytic leukaemia (CLL) and lymphomas. Monoclonal antibodies are drugs that recognise, target and stick to particular proteins on the surface of cancer cells. They then stimulate the body’s immune system to destroy these cells.
As a monoclonal antibody, rituximab binds to the CD20 protein on the surface of B-cells and destroys the HCL B-cells by targeting them specifically. Rituximab has limited action when given on its own, but is very effective when combined with cladribine and pentostatin.
In patients with HCL, cladribine followed by rituximab has achieved complete remission rates of up to 100%, showing a high efficacy of the combination of chemotherapy and immunotherapy. Five-year overall survival of 96.8% has been reported. The regimen is well-tolerated, with no severe or unexpected toxicity.
The most common side effects with rituximab are similar to those for cladribine and pentostatin. Patients often have rashes or other mild reactions following administration of their first dose of rituximab but this is usually easily controlled and is less common with subsequent doses.
Interferon alpha is a substance which occurs naturally in the body and reduces the production of bone marrow cells. It can be made into a medicine to be given subcutaneously which reduces the rate at which blood cells are made, especially the abnormal hairy B-cells. Interferon is less used nowadays because newer chemotherapy drugs are more effective.
Interferon alpha is particularly useful for patients with HCL and fever due to an infection. Normally patients with an infection should be treated before using purine analogues, but if the infection cannot be controlled, then interferon alpha can be used in the short term. Interferon alpha can be helpful for pregnant women who cannot take purine analogues.
Side effects with interferon alpha include:
- Flu-like symptoms
- Vision disturbances
- Liver and thyroid disease
However, it does not increase the risk of leukaemia and can be used in pregnancy.
Splenectomy (surgical removal of the spleen)
Removal of the spleen was a standard treatment for HCL before purine analogues became available. It may be an option if your enlarged spleen is painful and your blood count results are not too low. Splenectomy can also be used for truly refractory HCL, although this is usually a last resort if all medications have failed. Refractory HCL is a type of HCL which does not respond to standard treatment. A splenectomy is also an option for pregnant women in order to postpone the administration of chemotherapy.
Despite the fact that removal of the spleen does not achieve remission, the blood counts return to normal in 40% to 70% of patients and five-year overall survival rates are 60% to 70%.
If you have had a splenectomy, it may take some time for it to improve your condition, so you will have a period of at least six months where you do not have any treatment to allow your haematologist to tell whether the splenectomy is controlling your HCL. After this time, you will have regular blood tests and will start drug treatment if these show that your HCL is progressing.
Questions to ask your medical team about HCL
We understand going through a blood cancer journey can be difficult. It may help to talk to a close friend or relative about how you are feeling. Here are some questions that may be useful to ask your doctor.
- How would I know if I had HCL?
- What tests will I need to have?
- What will the tests show?
- How long will the results take?
- How rare is HCL?
- What sort of treatment will I need?
- How long will my treatment last?
- What will the side effects be?
- Is there anything I should or shouldn’t eat?
- Will I be able to go back to work?
- Where can I get help with claiming benefits and grants?
- Where can I get help dealing with my feelings?
We have free patient information available for HCL patients.
You can download the booklets on our information pages here.
Alternatively, you can have the information delivered free of charge by requesting it through our resources page.
Published: July 2020
Review date: July 2023