Tricholeukaemia or hairy cell leukaemia

Leukaemia is a type of cancer of the blood and bone marrow cells. See Leukaemia, bone marrow and blood cells.

Tricholeukaemia (TL) also known as hairy cell leukaemia, is a rare and indolent leukaemia (slowly progressive), which starts in a particular subtype of B-lymphocyte (post-germinal centre memory lymphocytes). The name hairy cell leukaemia comes from the projections on the surface of the cells that look like hairs when examined under a microscope.

B-lymphocytes are white blood cells that help the body fight infection and are an essential part of the body’s immune system.

A mutation or alteration in one or more genes in a B-lymphocyte can cause it to become a leukaemic cell. A healthy B-lymphocyte, after a certain time and once it has fullfield its function, stops dividing and eventually dies. In tricholeukaemia, the mutations acquired by the B lymphocyte cause it to continue growing and dividing. Since all the cells that arise from the initial leukaemic cell have the same alterations, they multiply uncontrollably. This proliferation causes them to infiltrate the bone marrow, spleen, and even the liver and lymph nodes.

Infiltration of the bone marrow (the soft, spongy tissue at the centre of most bones where blood cells are formed) affects the production of healthy blood cells. As the leukaemic cells accumulate in the bone marrow, they displace the progenitors of blood cells, including red blood cells, platelets and white blood cells. As a result, there are too few functional normal cells due to an excess of leukaemic cells in the bone marrow. This can lead to a deficiency of blood cells which in turn can cause anaemia, excessive bleeding and/or infections.

Hairy cell leukaemia is uncommon. Each year, between 2 and 4 cases are diagnosed per million inhabitants, with an estimated annual average of 28 cases for 2026.

There are two types of hairy cell leukaemia: the typical form described above and the so-called “variant” form. Initially, the variant was thought to be a subtype of hairy cell leukaemia. However, in 2008, the World Health Organization concluded that it is a disease distinct from hairy cell leukaemia and that there is no biological relationship between the two.

It is rarer, has a different clinical course, and is treated differently. It is usually seen in older patients (median age 71 years) and does not predominate in either sex. It frequently presents with MAP2K1 (MEK1) mutations, while the BRAF V600E mutation is not identified, which biologically distinguishes it from classic hairy cell leukaemia. TP53 mutations are also frequent and confer an unfavourable prognosis compared with classic hairy cell leukaemia.

The specific causes of most cases of leukaemia in adults are not known. There are also some risk factors that are associated with a higher chance of developing leukaemia. A risk factor is anything that increases the likelihood that a person will develop cancer.

Risk factors associated with tricholeukaemia are:

• Age: much more common in adults aged 50-60.
• Gender: more common in men than women (4:1 ratio).
• Exposure to certain herbicides.

Leukaemia, like other cancers, is not contagious and cannot be transmitted.

See section Leukaemia, bone marrow and blood cells.

The signs and symptoms of HCL are completely non-specific and, in up to 25% of cases, there are no symptoms at all. It is an incidental laboratory finding during a routine blood test, which detects circulating hairy cells in the blood. The most common symptoms are attributable to insufficient bone marrow production: fatigue due to a lack of red blood cells, bleeding due to a lack of platelets, and infections due to a lack of leukocytes. See section Leukaemia, bone marrow and blood cells.

Occasionally, fever, weight loss and pain below the ribs on the left side may be observed, due to enlargement of the spleen.

Physical examination shows enlargement of the spleen in 90% of cases, enlargement of the liver in 35% or, infrequently, enlargement of the lymph nodes, in up to 20% of cases in variant HCL.

Diagnosis of this disease requires some experience as it is rare and can be mistaken for other blood diseases. As the symptoms and physical examination are non-specific, the diagnosis will be based on information provided by a number of laboratory tests:

• The haemogram will show altered (decreased) blood counts.
• Blood smear (microscopic examination of circulating blood) may show small to medium-sized leukaemic cells with hair-like projections.
• The bone marrow aspiration-puncture is performed through a hollow needle puncturing the hip bone (or sternum) to aspirate a liquid sample of cells.

In these patients it is not uncommon for the bone marrow aspiration to be “dry” (the expected liquid sample is not obtained because the hairy cells often produce fibrous tissue that dries out the bone marrow). This problem is solved by bone marrow biopsy, which uses a special wider needle to extract a bone sample with its bone marrow.

Flow cytometry must always be performed on the aspirate, or immunohistochemistry on the biopsy, in both types of sample. This test makes it possible to identify the cells present in the sample. Since the proteins on the surface of hairy cells have a different characteristic arrangement than those of healthy B cells and other abnormal (malignant) B cells, their examination allows a diagnosis of certainty. Nowadays, all these studies must be complemented by molecular studies that study the presence of the characteristic genetic mutations of this disease.

In almost all cases of tricholeukaemia, the leukaemic cells have a mutation in the BRAF V600E gene. This mutation can serve as a molecular marker to differentiate this leukaemia from other leukaemias and lymphomas. Other mutations (such as the IGHV gene) may serve as factors in predicting the likely clinical outcome of the disease (prognosis). Thus, 90% of patients with this mutation will respond to classic treatments, so its presence implies a better prognosis.

Imaging tests such as computed tomography, or CT scan, are not diagnostic but are important, as they make it possible to determine the extent of the disease — affected organs — at diagnosis and, therefore, to assess the response to treatment.

Based on symptomatology, blood work, imaging tests and presence or absence of major prognostic factors, treatment planning should be carried out.

There are essentially two options: the standard treatment or a clinical trial. Since hairy cell leukaemia is usually slowly progressive, not all patients need to start treatment after initial diagnosis. About 10-20% of patients have mildly altered blood tests and are asymptomatic and therefore it is recommended to “wait and see”, i.e. postpone the start of treatment until the appearance of symptoms or noticeable blood test abnormalities. It is relatively common for patients with tricholeukaemia to live for many years without any symptoms and without receiving any treatment. This behaviour requires a relatively frequent analytical follow-up adapted to the patient’s evolution.

Initial treatment

In patients with significant abnormalities in blood tests or symptoms, initial treatment is usually given with chemotherapy agents known as purine analogues: cladribine (Leustatin®) and pentostatin (Nipent®). Both appear to be equally effective in achieving lasting remission. In 80–85% of patients, this means normalisation of blood counts, reduction in spleen size, disappearance of symptoms and absence of leukaemic cells in the bone marrow. It is therefore important, once treatment has finished, to perform a CT scan and a bone marrow biopsy to confirm and ensure a good response. The response may last for years and the patient only requires follow-up with periodic visits.

Since infections are the most common cause of problems in these patients, it should be known that after receiving purine analogues, which are immunosuppressive agents, the risk of infections increases. Patients should therefore be instructed on how to prevent infections and to inform the healthcare staff monitoring them if they develop a fever.

Treatment for relapses or resistant cases

Treatment with purine analogues has improved the survival of patients with hairy cell leukaemia, and some patients achieve remissions that last for years without the need for further treatment. Even so, some patients do not respond to them or have a very short response duration. In these patients, additional treatments are needed.

1. Disease relapses

If the relapse has occurred more than 2 years after the first treatment, the same medicine used initially may be used again, that is, the purine analogue, in this case combined with a medicine that is a form of immunotherapy called rituximab.

If the relapse occurs earlier, within 2 years of completing treatment, the previous regimen may be used, or alternatively a medicine called vemurafenib, which acts on the BRAF mutation present in this disease.

In patients who have multiple medical problems and cannot tolerate purine analogues, immunotherapy with rituximab alone, known as monotherapy, is an option.

2. Refractory or treatment-resistant disease

If patients do not respond to treatment with purine analogues, the options are medicines that act on the BRAF mutation, or on a receptor found on B lymphocytes called BCR, both combined with rituximab:

• Vemurafenib + rituximab
• Ibrutinib + rituximab
• Dabrafenib

Or:

• Venetoclax + rituximab

Finally, if there is a clinical trial with novel drugs for their disease at a referral hospital, they will be asked whether they wish to take part in the trial.

In any case, because all these medicines affect the immune or defence system, oral drugs to prevent infections — Septrim, aciclovir — will be administered until the immune system recovers, usually for 6 to 12 months.

Treatment of variant hairy cell leukaemia

This disease does not usually respond as well to treatment as classic hairy cell leukaemia.

As first-line treatment, a purine analogue combined with rituximab is used, or chemotherapy (bendamustine) combined with rituximab.

After completing treatment, the patient will continue to have regular check-ups with their haematologist and with other specialists whenever necessary. These check-ups are carried out to assess for a possible relapse and to monitor and treat any possible long-term complications.

Tricholeukaemia is classified as a “chronic” or indolent leukaemia, as its progression is usually slow and not very aggressive, although, unfortunately, at present, it cannot be cured. Even so, patient survival is close, or very similar, to that of the general population.

In many patients, chemotherapy treatment can produce a remission that may last for years. However, despite major advances in controlling the disease, many patients relapse after treatment and need to receive additional therapy.

• Hairy Cell Leukemia Treatment. National Cancer Institute

• Understanding Hairy Cell Leukemia. Hairy Cell Leukemia Foundation

• Hairy cell leukemia (HCL). Leukemia & Lymphoma Society

TESTIMONIAL MATERIALS

• Ebook “Here and now: Álvaro’s story”.
• Ebook “Here and now: Clàudia’s story”

You can order the booklets in paper format for free delivery in Spain by e-mail: imparables@fcarreras.es

BONE MARROW TRANSPLANT

• Bone Marrow Transplant Guide. Josep Carreras Foundation (content in Spanish)
• What is HLA and how does it work? Josep Carreras Foundation (content in Spanish)
• Graft-versus-Host Disease. Josep Carreras Foundation (content in Spanish)
• History of Bone Marrow Transplantation. Josep Carreras Foundation (content in Spanish)
• How is the search for an anonymous donor conducted? Josep Carreras Foundation (content in Spanish)

FOOD

• How to maintain a healthy diet during treatment? Josep Carreras Foundation (content in Spanish)
• Nutrition guide. Leukemia & Lymphoma Society

OTHER

• Ideas on what to take with me to the isolation chamber. Josep Carreras Leukaemia Foundation (content in Spanish)
• Travel tips for people with cancer. Josep Carreras Leukaemia Foundation (content in Spanish)
• Physiotherapy manual for haematological and transplant patients. Josep Carreras Leukaemia Foundation (content in Spanish)
• Prevention and treatment of oral mucositis. Josep Carreras Leukaemia Foundation (content in Spanish)
• Oral hygiene in oncohaematological patients. Josep Carreras Leukaemia Foundation (content in Spanish)
• Fertility manual: Suffering from blood cancer and becoming a parent. Josep Carreras Leukaemia Foundation (content in Spanish)
• Skin care in the oncohaematological patient. Josep Carreras Leukaemia Foundation (content in Spanish)
• Aesthetic Oncology Manual. Josep Carreras Leukaemia Foundation (content in Spanish)
• Leukaemia and sexuality. Josep Carreras Leukaemia Foundation (content in Spanish)
• 7 ways to wear a scarf. Josep Carreras Leukaemia Foundation (content in Spanish)

In Spain there is a large network of associations for haematological cancer patients that, in many cases, can inform you, advise you and even carry out certain procedures. These are the contacts for some of them by Autonomous Community:

All these organisations are external to the Josep Carreras Foundation.

STATE

• CEMMP (Comunidad Española de Pacientes de Mieloma Múltiple) 
• AEAL (ASOCIACIÓN ESPAÑOLA DE AFECTADOS POR LINFOMA, MIELOMA y LEUCEMIA)
• AECC (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER). Present in the different provinces and in many municipalities. Contact the nearest branch or call 900 100 036 (24h).
• AELCLES (Agrupación Española contra la Leucemia y Enfermedades de la Sangre)
• JOSEP CARRERAS LEUKAEMIA FOUNDATION
• FUNDACIÓN SANDRA IBARRA
• GEPAC (GRUPO ESPAÑOL DE PACIENTES CON CÁNCER)
• MPN España (Asociación de Afectados Por Neoplasias Mieloproliferativas Crónicas)

ANDALUCÍA

• AECC (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER). Present in the different provinces and in many municipalities. Contact the nearest branch.
• ALUSVI (ASOCIACIÓN LUCHA Y SONRÍE POR LA VIDA). Sevilla
• APOLEU (ASOCIACIÓN DE APOYO A PACIENTES Y FAMILIARES DE LEUCEMIA). Cádiz

ARAGÓN

• AECC (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER). Present in the different provinces and in many municipalities. Contact the nearest branch.
• ASPHER (ASOCIACIÓN DE PACIENTES DE ENFERMEDADES HEMATOLÓGICAS RARAS DE ARAGÓN)
• DONA MÉDULA ARAGÓN

ASTURIAS

• AECC (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER). Present in the different provinces and in many municipalities. Contact the nearest branch.
• ASTHEHA (ASOCIACIÓN DE TRASPLANTADOS HEMATOPOYÉTICOS Y ENFERMOS HEMATOLÓGICOS DE ASTURIAS)

CANTABRIA

• AECC (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER). Present in the different provinces and in many municipalities. Contact the nearest branch.

CASTILLA LA MANCHA

• AECC (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER). Present in the different provinces and in many municipalities. Contact the nearest branch.

CASTILLA LEÓN

• ABACES (ASOCIACIÓN BERCIANA DE AYUDA CONTRA LAS ENFERMEDADES DE LA SANGRE)
• AECC (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER). Present in the different provinces and in many municipalities. Contact the nearest branch.
• ALCLES (ASOCIACIÓN LEONESA CON LAS ENFERMEDADES DE LA SANGRE). León.
• ASCOL (ASOCIACIÓN CONTRA LA LEUCEMIA Y ENFERMEDADES DE LA SANGRE). Salamanca.

CATALUÑA

• ASSOCIACIÓ FÈNIX. Solsona
• FECEC (FEDERACIÓ CATALANA D’ENTITATS CONTRA EL CÁNCER
• FUNDACIÓ KÁLIDA. Barcelona
• FUNDACIÓ ROSES CONTRA EL CÀNCER. Roses
• LLIGA CONTRA EL CÀNCER COMARQUES DE TARRAGONA I TERRES DE L’EBRE. Tarragona
• MielomaCAT 
• ONCOLLIGA BARCELONA. Barcelona
• ONCOLLIGA GIRONA. Girona
• ONCOLLIGA COMARQUES DE LLEIDA. Lleida
• ONCOVALLÈS. Vallès Oriental
• OSONA CONTRA EL CÀNCER. Osona
• SUPORT I COMPANYIA. Barcelona
• VILASSAR DE DALT CONTRA EL CÀNCER. Vilassar de Dalt

VALENCIAN COMMUNITY

• AECC (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER). Present in the different provinces and in many municipalities. Contact the nearest branch.
• ASLEUVAL (ASOCIACIÓN DE PACIENTES DE LEUCEMIA, LINFOMA, MIELOMA Y OTRAS ENFERMEDADES DE LA SANGRE DE VALENCIA)

EXTREMADURA

• AECC (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER). Present in the different provinces and in many municipalities. Contact the nearest branch.
• AFAL (AYUDA A FAMILIAS AFECTADAS DE LEUCEMIAS, LINFOMAS; MIELOMAS Y APLASIAS)
• AOEX (ASOCIACIÓN ONCOLÓGICA EXTREMEÑA)

GALICIA

• AECC (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER). Present in the different provinces and in many municipalities. Contact the nearest branch.
• ASOTRAME (ASOCIACIÓN GALLEGA DE AFECTADOS POR TRASPLANTES MEDULARES)

BALEARIC ISLANDS

• ADAA (ASSOCIACIÓ D’AJUDA A L’ACOMPANYAMENT DEL MALALT DE LES ILLES BALEARS)
• AECC (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER). Present in the different provinces and in many municipalities. Contact the nearest branch.

CANARY ISLANDS

• AECC (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER). Present in the different provinces and in many municipalities. Contact the nearest branch.
• AFOL (ASOCIACIÓN DE FAMILIAS ONCOHEMATOLÓGICAS DE LANZAROTE)
• FUNDACIÓN ALEJANDRO DA SILVA

LA RIOJA

• AECC (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER). Present in the different provinces and in many municipalities. Contact the nearest branch.

MADRID

• AECC (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER). Present in the different provinces and in many municipalities. Contact the nearest branch.
• AEAL (ASOCIACIÓN ESPAÑOLA DE LEUCEMIA Y LINFOMA)
• CRIS CONTRA EL CÁNCER
• FUNDACIÓN LEUCEMIA Y LINFOMA

MURCIA

• AECC (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER). Present in the different provinces and in many municipalities. Contact the nearest branch.

NAVARRA

• AECC (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER). Present in the different provinces and in many municipalities. Contact the nearest branch.

BASQUE COUNTRY

• AECC (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER). Present in the different provinces and in many municipalities. Contact the nearest branch.
• PAUSOZ-PAUSO. Bilbao

AUTONOMOUS CITIES OF CEUTA AND MELILLA

• AECC CEUTA (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER)
• AECC MELILLA (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER)

We also invite you to follow us through our main social media (Facebook, Twitter and Instagram) where we often share testimonies of overcoming this disease.

If you live in Spain, you can also contact us by sending an e-mail to imparables@fcarreras.es so that we can help you get in touch with other people who have overcome this disease.