Skip to main content

Health condition · Clinically reviewed

Hairy cell leukaemia, BRAF V600E, cladribine and modern targeted options.

A rare chronic B-cell leukaemia with a defining molecular signature and highly effective first-line therapy. Diagnosis, treatment and follow-up in one guide.

Jump to treatment
A radiographer guides a patient onto the bed of an advanced 3 Tesla MRI scanner in a London imaging suite

Why trust this guide

  • 01

    Clinically reviewed

    Written by our editorial team and reviewed by a registered UK clinician before publication.

  • 02

    Sourced from guidance

    Checked against BSH, ESMO, NICE and peer-reviewed haemato-oncology sources you can see at the end.

  • 03

    Current for 2026

    Reflects modern UK practice including BRAF V600E testing, cladribine-rituximab regimens and BRAF inhibitor pathways.

Key facts

Hairy cell leukaemia at a glance.

The essentials, in plain English - what it is, how it presents, and how it is treated in the UK today.

  • What it is

    A rare chronic B-cell leukaemia named for the fine cytoplasmic projections seen on the malignant lymphocytes.

  • How common

    Around 2% of adult leukaemias. Men are affected four to five times more often than women, with a peak in the 50s and 60s.

  • Molecular hallmark

    The BRAF V600E mutation is present in essentially all classic HCL and is now a defining feature.

  • Variant HCL

    A distinct BRAF wild-type disease, often IGHV4-34 positive, that is more aggressive and less responsive to standard therapy.

  • Classic presentation

    Pancytopenia with splenomegaly and opportunistic infections. Lymphadenopathy is uncommon, unlike other lymphomas.

  • Modern outlook

    A single cycle of cladribine gives durable remission in around 90% of patients, with several effective options at relapse.

Why this guide matters

A rare cancer, a well-defined pathway.

HCL is uncommon but highly treatable in the right hands. The three principles below shape everything else on this page.

  • The molecular signature matters

    BRAF V600E defines classic HCL and unlocks targeted therapy. Testing at diagnosis separates classic from variant disease.

  • Cladribine is transformative

    A single seven-day course produces high response rates and long remissions. Most patients need only one cycle at first line.

  • Options exist at relapse

    Rituximab combinations, BRAF inhibitors and immunotoxins mean relapse is usually manageable at a specialist centre.

How the diagnosis is made

From first blood count to a clear plan.

The steps a UK haematology team will normally follow, in order, so you know what to expect and why.

  1. 01

    Assessing

    History and examination

    A structured review of fatigue, infections, bruising and abdominal fullness, plus examination for splenomegaly and hepatomegaly.

  2. 02

    Assessing

    Full blood count and film

    Pancytopenia with monocytopenia is characteristic. A specialist blood film looks for hairy cells with fine cytoplasmic projections.

  3. 03

    Assessing

    Flow cytometry

    A specialist immunophenotype - CD19, CD20, CD22, CD11c, CD25, CD103 and CD123 positive - distinguishes classic HCL from mimics.

  4. 04

    Confirming

    Bone marrow biopsy

    Trephine biopsy typically shows the fried-egg appearance with reticulin fibrosis. A dry tap on aspirate is common and expected.

  5. 05

    Confirming

    BRAF V600E testing

    Immunohistochemistry or PCR confirms the defining mutation in classic HCL and helps separate it from variant HCL. Specialist commissioned.

  6. 06

    Confirming

    CT abdomen and pelvis

    Cross-sectional imaging maps splenomegaly and any abdominal disease. Specialist commissioned as part of staging.

  7. 07

    Preparing

    Specialist MDT review

    Discussed at a haemato-oncology MDT at a commissioned centre to agree on observation, first-line therapy or clinical trial entry.

Typical timeline: from first abnormal counts to an MDT-agreed plan in a few weeks at a specialist centre.

Symptoms

What HCL actually looks like.

The classic mix of pancytopenia, splenomegaly and infections. Lymphadenopathy is unusual, which is often a helpful clue.

  • Fatigue and pallor

    Anaemia from marrow infiltration causes tiredness, breathlessness on exertion and pale skin.

  • Recurrent infections

    Neutropenia and monocytopenia predispose to bacterial, atypical mycobacterial, fungal and Pneumocystis infections.

  • Bruising and bleeding

    Thrombocytopenia leads to easy bruising, gum bleeding, nosebleeds and petechiae.

  • Splenomegaly

    Often marked, causing left upper quadrant fullness, early satiety and discomfort. See our guide to an enlarged spleen.

  • Mild hepatomegaly

    The liver is less commonly enlarged than the spleen and rarely causes symptoms on its own.

  • Absent lymphadenopathy

    Palpable lymph node enlargement is uncommon in HCL, which helps separate it from other B-cell lymphomas.

  • Opportunistic infections

    Atypical mycobacteria, invasive fungi and Pneumocystis pneumonia can present at diagnosis or during treatment.

  • Red flag - rare complications

    Vasculitis, inflammatory arthritis and skin involvement are uncommon but recognised paraneoplastic features.

Treatment

How HCL is treated in the UK.

Purine analogues first, rituximab-containing regimens next, and BRAF-directed or immunotoxin options for relapsed disease.

  • Watchful observation

    Selected asymptomatic patients with preserved counts and no splenic symptoms can be safely monitored under specialist review.

  • Cladribine (2-CdA)

    A single seven-day cycle of this purine analogue produces response in around 90% of patients and long durable remissions - the UK first-line standard.

  • Pentostatin

    An alternative purine analogue given over several months. Effective and used when cladribine is not suitable.

  • Rituximab combinations

    Anti-CD20 rituximab added to or following cladribine deepens responses and is used at relapse or in high-risk disease. Specialist commissioned.

  • BRAF inhibitors

    Vemurafenib or dabrafenib target the BRAF V600E mutation and are used in relapsed or refractory classic HCL. Specialist commissioned.

  • Moxetumomab pasudotox

    An anti-CD22 immunotoxin (Lumoxiti) for heavily pre-treated disease. FDA-approved and available in the UK through specialist commissioned pathways.

  • Ibrutinib and BTK route

    Emerging role for BTK inhibitors in selected relapsed or variant disease, typically within clinical trials or specialist protocols.

  • Variant HCL regimens

    BRAF wild-type variant HCL is less responsive to cladribine alone and is usually treated with rituximab plus cladribine at a specialist centre.

Supportive care

Infection prevention is part of every plan.

PJP prophylaxis, antifungal cover and, in selected cases, immunoglobulin replacement (IVIG) sit alongside anti-leukaemic therapy. Splenectomy is now rarely used and is reserved for very selected historical or refractory scenarios. Every case is discussed at a specialist haemato-oncology MDT, with charities such as Blood Cancer UK, Leukaemia Care and Macmillan providing wraparound support.

What this guide is based on

The sources behind every claim on this page.

UK and international specialist society standards and patient information, current at the time of last review.

Key references

Guidelines and standards we relied on.

A quiet reminder

This guide is for information, not medical advice.

Your haematology team knows your history, blood counts and molecular profile and can tell you which parts apply to you. If in doubt, get seen.

  • British Society for Haematology (BSH). Guidelines for the diagnosis and management of hairy cell leukaemia and variant.

  • ESMO Clinical Practice Guidelines. Hairy cell leukaemia: diagnosis, treatment and follow-up.

  • NICE. Guidance relevant to leukaemia diagnostics and targeted therapy pathways.

  • Blood Cancer UK, Leukaemia Care and Macmillan patient information on hairy cell leukaemia.

Red flags

When HCL needs urgent attention.

Most HCL is managed in outpatient haematology. These are the situations that are not, and where same-day specialist review is needed.

  • Neutropenic sepsis

    Fever with a low neutrophil count is a medical emergency - go straight to an emergency department and quote your haematology diagnosis.

  • Uncontrolled bleeding

    Heavy nosebleeds, spontaneous bruising or bleeding gums with a very low platelet count need same-day haematology assessment.

  • Opportunistic infection

    Persistent dry cough, breathlessness or unexplained fever may signal Pneumocystis, atypical mycobacterial or fungal infection.

  • Rapid splenic enlargement

    A sudden increase in abdominal fullness, pain or early satiety warrants urgent imaging and haematology review.

  • Left shoulder tip pain

    Sharp referred pain suggests possible splenic capsular stretching or, rarely, splenic rupture - seek urgent care.

  • Suspected variant HCL

    BRAF wild-type disease or an aggressive course despite first-line therapy needs review at a specialist commissioned centre.

  • Relapse after remission

    Falling counts, returning splenomegaly or new symptoms after a treatment-free interval need prompt haematology reassessment.

  • Systemic B symptoms

    Drenching night sweats, unexplained fevers and significant weight loss warrant urgent workup for transformation or infection.

  • Second cancers on follow-up

    People with HCL have a slightly increased risk of second malignancies - keep up with UK screening programmes and flag new lumps early.

Living with it

A treatable cancer, with a clear pathway.

Four practical things that make the biggest difference day to day - infection awareness, vaccination, structured follow-up and using specialist charities well.

A quiet reminder

Rare does not mean untreatable.

HCL is uncommon, but decades of research have made it one of the most treatable adult leukaemias. Get seen at a centre that looks after it regularly.

  1. 01 Infections

    Take fever seriously

    Any fever above 38C or feeling unwell with low counts is a haematology emergency, not a wait-and-see moment.

  2. 02 Vaccines

    Stay up to date

    Annual flu, COVID boosters and pneumococcal vaccines are recommended. Live vaccines are avoided during and shortly after treatment.

  3. 03 Follow-up

    Plan for the long run

    Even after deep remission, lifelong haematology follow-up with periodic bloods and clinical review is standard practice.

  4. 04 Support

    Use the charities

    Blood Cancer UK, Leukaemia Care and Macmillan offer specialist nurses, financial guidance and peer support for people with HCL.

Frequently asked

Everything we get asked about HCL.

Quick answers on diagnosis, BRAF V600E, first-line therapy, relapse options and infection prophylaxis.

  • What is hairy cell leukaemia?

    Hairy cell leukaemia (HCL) is a rare chronic B-cell leukaemia in which abnormal lymphocytes with fine cytoplasmic projections accumulate in the bone marrow, spleen and blood. It typically causes pancytopenia, marked splenomegaly and opportunistic infections, and it accounts for around 2% of adult leukaemias.

  • How is HCL diagnosed?

    Diagnosis combines a blood film showing hairy cells with specialist flow cytometry (CD19, CD20, CD22, CD11c, CD25, CD103 and CD123 positive), a bone marrow trephine with the classic fried-egg appearance and reticulin fibrosis, and BRAF V600E testing. CT of the abdomen and pelvis assesses splenomegaly, and every case is discussed at a specialist haemato-oncology MDT.

  • What is the difference between classic and variant HCL?

    Classic HCL is defined by the BRAF V600E mutation and responds very well to purine analogues such as cladribine. Variant HCL is BRAF wild-type, often IGHV4-34 positive, more aggressive and less responsive to cladribine alone. It is usually treated with rituximab combined with cladribine at a specialist commissioned centre.

  • What is the first-line treatment?

    For most patients who need treatment, a single seven-day cycle of cladribine (2-CdA) is the UK first-line standard, giving response rates of around 90% and often long durable remissions. Pentostatin is an alternative purine analogue. Selected asymptomatic patients with preserved counts may be safely observed.

  • What happens if HCL comes back?

    Relapsed disease is common in the long term but usually treatable. Options include a second course of a purine analogue, rituximab combined with cladribine, BRAF inhibitors such as vemurafenib or dabrafenib, the anti-CD22 immunotoxin moxetumomab pasudotox and clinical trials. Treatment choice depends on prior therapy, fitness and molecular profile.

  • Do I need infection prophylaxis?

    Yes, in many cases. Purine analogues cause prolonged T-cell suppression, so Pneumocystis (PJP) prophylaxis and antifungal cover are often used during and after treatment. Immunoglobulin replacement (IVIG) is considered for recurrent bacterial infections with low IgG. Any fever above 38C needs urgent haematology assessment.

Related content

Keep reading.

Pulse Healthcare concierge

Send us your enquiry

A concierge service for UK private healthcare. We match you with the best vetted clinics and consultants in our network - they then contact you directly.

So we can match you to the right clinician close to you.

We reply to every enquiry within 24 hours (Mon–Fri). Confidential - your details are never shared outside our vetted consultant network.