Chronic lymphocytic leukaemia

Start here

Chronic lymphocytic leukaemia at a glance

Chronic lymphocytic leukaemia, or CLL, is a cancer of mature B lymphocytes, a type of white blood cell. It often develops slowly and may be found on a routine blood test. Many people do not need treatment when first diagnosed, and some remain well without treatment for a long time. Active monitoring is an established approach when treatment criteria are not met.

Small lymphocytic lymphoma, or SLL, is the same underlying disease pattern when it is mainly found in lymph nodes or other tissues rather than as a high circulating blood-cell count. CLL and SLL share many treatment principles. This guide covers both, while explaining when a tissue biopsy or a different assessment is needed.

Current treatment commonly uses targeted medicines that interfere with cancer-cell growth or survival rather than traditional chemotherapy. The choice depends on disease genetics, other illnesses, previous treatment and whether a fixed-duration or continuous approach is more suitable. The aim is usually durable control and good quality of life; routine treatment is not generally described as a cure.

Symptoms and when to seek help

Some people have no symptoms. Others notice enlarged lymph nodes (small immune-system structures), tiredness, repeated infections, night sweats, weight loss or fullness under the left ribs from an enlarged spleen. Low red cells or platelets may develop from marrow involvement or from the immune system attacking the body's own cells.

Fever, shaking chills, new breathlessness or feeling very unwell needs prompt advice because infection can become serious. Rapid enlargement of one lymph node, persistent unexplained fever, drenching sweats, marked weight loss or a sudden decline in health should also be reported. These may reflect infection, active CLL or, less commonly, transformation into a more aggressive lymphoma.

Understanding active monitoring

Monitoring is not the same as doing nothing. It includes planned reviews, examination and blood counts, with earlier assessment for new symptoms. Starting treatment before it is needed does not necessarily improve outcomes and exposes a person to side effects. Ask what findings would mean it is time for you to start treatment and whom to contact between appointments.

Making this information useful to you

A cancer diagnosis can arrive before you have had time to understand the tests. You do not need to learn every treatment name at once. Begin with the exact diagnosis, where the cancer is, and what the team recommends next. A relative or friend can join the appointment if you would find that helpful. Ask for an interpreter when language makes a discussion harder; important decisions should not depend on guessing unfamiliar words.

This guide explains possibilities, not a prescription for your situation. Your blood and tissue test results, scan findings, general health, previous treatment and priorities determine which possibilities apply. Two people with the same cancer name may appropriately receive different treatment. If a recommendation differs from something you have read, ask the team to explain the reason and the evidence behind it.

Keep a list of medicines, allergies and other health conditions, including non-prescription products, vitamins and herbal remedies. Tell the team about previous cancer treatment, pregnancy or breastfeeding, and anything that could affect attending appointments. Do not stop an established medicine without advice. Bring your questions in the order that matters most to you, so that the most important concern is discussed first.

Understand

CLL, SLL and monoclonal B-cell lymphocytosis

CLL cells build up in blood, bone marrow (where blood cells are made), lymph nodes and the spleen, an immune-system organ under the left ribs. Flow cytometry, a test that identifies proteins on cells, helps recognise the CLL pattern.

Clonal B cells belong to the same abnormal cell family. When there are fewer of these cells in the blood and no other features establishing CLL or SLL, the condition may be called monoclonal B-cell lymphocytosis, or MBL. MBL is not automatically treated as CLL.

A diagnosis uses the absolute clonal B-cell count and the broader clinical picture, not just the percentage of lymphocytes on a routine report. SLL generally needs a tissue diagnosis when the disease is concentrated in lymph nodes. A haematopathologist, a doctor who examines blood and tissue samples for blood disorders, helps distinguish it from other lymphomas that can appear in the blood.

How CLL affects immunity

Although CLL involves increased numbers of B cells, they do not provide normal immune protection. Protective antibodies may be low, and other parts of immunity can be affected. Infection risk can therefore be increased even before treatment. Treatment may add further immune suppression.

CLL can also be associated with autoimmune haemolytic anaemia or immune thrombocytopenia, in which the immune system destroys red cells or platelets. These problems are assessed separately from marrow failure. Their initial treatment may involve steroids or other immune treatment rather than immediately changing the CLL drug plan.

Genetic tests that matter

Deletion 17p means a piece of chromosome 17 is missing; this region includes the TP53 gene, which helps control abnormal cell growth. A change within TP53 itself is called a TP53 mutation. Either can affect treatment choice and how long a response may last.

Immunoglobulin heavy-chain variable region (IGHV) mutation status is another important test of the CLL cells. The word mutated has a specific meaning in this test and should not be assumed to mean a worse result. These are usually features of the CLL cells, not inherited findings shared by all family members.

TP53 mutation and deletion 17p testing are reassessed before a new treatment line because the disease can evolve. IGHV status is usually stable and generally does not need repeated testing. Results should guide a whole treatment strategy, not be used to predict an individual lifespan from a single marker.

When treatment is needed

A high lymphocyte count alone is not usually a reason to start therapy. The pattern and speed of change, marrow function, symptoms and effects on organs matter. Similarly, a high-risk genetic result does not automatically mean treatment is needed immediately in an otherwise stable, symptom-free person.

Tests and diagnosis

Blood tests and examination

A full blood count and blood film identify the blood-cell pattern. Flow cytometry usually confirms CLL in blood. The examination checks lymph nodes, liver and spleen, and the team asks about infections, weight change, fever, sweats, bleeding and fatigue.

Kidney and liver function help plan treatment. Immunoglobulin levels, which measure protective antibodies, may be checked when infections keep returning. Tests for haemolysis (red cells being destroyed) can clarify why haemoglobin, their oxygen-carrying protein, has fallen. A low count may have more than one cause, so it should not automatically be attributed to progression of CLL.

When marrow tests, scans or biopsy are useful

A bone marrow biopsy is not required to diagnose every straightforward case of blood-based CLL. It can help explain low blood-cell counts or answer particular treatment questions. Computed tomography (CT) may be useful before some therapies, particularly when large nodes increase the risk of tumour lysis syndrome: rapid breakdown of cancer cells that can upset blood chemistry and damage the kidneys.

Positron emission tomography combined with CT (PET-CT) is not a routine surveillance test for stable CLL. It can help identify a suspicious site for biopsy when transformation is suspected. A rapidly growing node generally needs tissue assessment rather than an assumption that ordinary CLL has simply become more active. SLL and an uncertain diagnosis may also require a lymph-node biopsy.

Before starting treatment

Genetic assessment should include TP53 mutation testing and fluorescence in situ hybridisation (FISH), a test for chromosome changes, to check for deletion 17p, with IGHV status available if not already known. Kidney function, node size and blood-cell burden help assess tumour-lysis risk with venetoclax. Blood pressure, heart rhythm, cardiovascular history and bleeding medicines are particularly important when considering a Bruton tyrosine kinase (BTK) inhibitor, a medicine that blocks a growth signal in B cells.

Hepatitis B screening is essential before anti-CD20 antibodies, medicines that target the CD20 protein on B cells, because this virus can become active again during treatment. Other infection tests are selected according to the treatment and clinical history. Tell the team about previous hepatitis, recurrent shingles, unusual infections and all current medicines, including blood thinners and supplements.

Measuring response

Response is assessed through symptoms, examination and blood counts, with scans or marrow testing when needed for the chosen regimen. Measurable residual disease (MRD) testing looks for very small amounts of CLL that routine tests may miss. It can provide useful information in treatment programmes with a planned stopping point. It is not a reason to stop a continuous BTK inhibitor outside an appropriate specialist plan.

Some targeted medicines temporarily increase blood lymphocytes as cells move out of lymph nodes. This can occur while the disease is responding and is not automatically progression. Your team will interpret the pattern alongside shrinking nodes, symptoms and the drug being used.

Preparing for your appointment

If scans have been performed, bring a CD containing your scan images in Digital Imaging and Communications in Medicine (DICOM) format, the standard used for medical images, together with the software needed to view them, along with the written scan reports. Bring your biopsy report and ask whether the pathology slides or tissue blocks are needed for specialist review or additional tests. Keep originals safe and agree how borrowed material will be returned. Having the actual images allows the team to compare changes and plan treatment accurately.

A repeat test is sometimes needed because an earlier sample was too small, a scan did not cover the necessary area, or a new result will change treatment. Ask what question the test will answer, how it may affect the plan, and when you should expect the result. A result described as uncertain does not automatically mean the cancer is worse. Sometimes discussion between the scan specialist (radiologist), tissue specialist (pathologist) and treating team resolves the uncertainty without another procedure.

Before a scan or procedure, mention kidney problems, previous contrast reactions, implanted devices, diabetes medicines, blood-thinning medicines and the possibility of pregnancy. Follow the testing centre's instructions about food, drink and medicines. If you have not received those instructions, contact the centre rather than making changes yourself.

Planning your treatment

When treatment becomes appropriate

Reasons to start include progressive marrow failure, troublesome or enlarging lymph nodes or spleen, significant disease-related symptoms and certain rapidly progressive patterns. Autoimmune complications that do not respond adequately to their usual treatment may also influence the decision. Infection and other explanations for symptoms should be considered before labelling them as active CLL.

Ask what specific criterion you meet and what improvement treatment is expected to provide. If monitoring remains appropriate, agree the review interval and the symptoms that should bring the appointment forward. Being anxious about the count is understandable, but reassurance and a monitoring plan may be safer than unnecessary therapy.

Fixed-duration or continuous treatment

Some regimens have a planned stopping point, such as venetoclax-based combinations. Others, including many BTK-inhibitor approaches, continue until progression or unacceptable toxicity. A fixed-duration plan may offer time without treatment but can require more intensive early monitoring. A continuous tablet may be simpler to start but creates an ongoing commitment.

Discuss convenience, travel, interactions, heart and kidney health, infection history and your preferences. The genetics of CLL may influence which approach is favoured and the expected durability. No single strategy is best for every patient.

Planning for tumour lysis

Venetoclax can cause rapid breakdown of CLL cells. The starting process uses a gradual dose increase, hydration, preventive medicines and timed blood tests. People at higher risk may need hospital monitoring for part of the introduction. Kidney function and disease burden are central to this assessment.

Do not start a full dose, restart after a significant interruption or change the ramp-up schedule without the team. Certain interacting medicines are particularly dangerous during the introduction period. The pharmacist should review prescriptions from other clinicians before treatment begins.

Questions to ask your care team

• What is the exact blood cancer type and risk category, and are any important results still pending?
• Is the aim to cure the cancer, reduce the chance of recurrence, control it, or relieve a particular symptom?
• What benefit do you expect from this option, and what are the reasonable alternatives for me?
• How will treatment affect everyday activities, fertility, sexual health and the things I most value?
• How will we know whether it is working, and when will we review the plan?
• Who should I contact between visits, including at night or over a weekend?

Clinical trials and newer treatments

A clinical trial can be worth considering at diagnosis or when treatment needs to change. Trials ask a defined question; some compare established treatments and others study a newer approach. Eligibility depends on the cancer, previous treatment, test results and health. Taking part is voluntary, and choosing not to participate does not remove your right to standard care. Ask about extra visits, possible randomisation (allocation to a treatment group by chance), travel, side effects and what happens when the study ends.

Newer treatments are considered using the clinical evidence, recognised guidelines and the exact cancer type, biomarkers (features found by laboratory tests) and previous treatment. Some options have less mature evidence than established treatments. Ask what is known, what remains uncertain and whether a clinical trial would be appropriate.

Your priorities and supportive care

Tell the team what you are hoping treatment will make possible: returning to work, caring for family, keeping independence, reducing pain or attending an important event. These priorities can influence a choice between reasonable options. If the likely benefit is small and the burden is substantial, discussing a less intensive approach is appropriate. Decisions can be revisited when your health or circumstances change.

Supportive and palliative care help with symptoms, sleep, mood, family concerns and planning. They can be provided alongside treatment intended to cure or control cancer. A referral does not mean that active treatment is ending. If the cancer cannot be cured, ask what treatments may help you live longer or more comfortably and how their burdens compare with their likely benefits.

Treatment options

Initial targeted treatment

Acalabrutinib or zanubrutinib are commonly used BTK inhibitors. They attach firmly to the BTK protein, a way of binding called covalent. Depending on the regimen, a BTK inhibitor may be given alone or with an anti-CD20 antibody. Ibrutinib is also effective in CLL but its cardiovascular and other risks may make a newer BTK inhibitor preferable for some patients.

Venetoclax blocks B-cell lymphoma 2 (BCL-2), a protein that helps CLL cells survive. Venetoclax with obinutuzumab is an established initial treatment with a planned stopping point. It requires tumour-lysis precautions and attention to low counts and infection. Obinutuzumab is an anti-CD20 antibody given by infusion, with particular monitoring around early doses.

Acalabrutinib with venetoclax is a further fixed-duration option for adults with CLL or SLL. The suitability of this combination still depends on genetics, other illnesses and previous treatment. In particular, evidence for a particular trial population should not be assumed to apply equally to every TP53-disrupted case; the specialist should explain the choice.

Pirtobrutinib is also an initial option for selected adults with previously untreated CLL or SLL and no known 17p deletion. It binds differently from covalent BTK inhibitors and is called a non-covalent BTK inhibitor. This is usually ongoing treatment, with monitoring for infection, bleeding, low blood counts, liver problems and heart-rhythm changes. A newer option is not automatically the best choice for you.

TP53 disruption and other treatment considerations

CLL with deletion 17p or a TP53 mutation generally responds poorly to traditional chemoimmunotherapy. Targeted treatment is therefore central. A second-generation BTK inhibitor is often a strong option, while venetoclax-based treatment may be considered according to circumstances and patient preference.

For other patients too, targeted medicines have substantially reduced the role of chemotherapy. Chemoimmunotherapy is now reserved for selected circumstances after a careful discussion of alternatives and long-term risks. A previously common regimen should not be chosen simply because it appears in outdated treatment information.

If treatment is poorly tolerated

Side effects may be managed with supportive care, a supervised interruption or a switch to another appropriate medicine. Intolerance is different from disease resistance. For example, switching between certain BTK inhibitors may help with intolerance, whereas resistance during one covalent BTK inhibitor generally requires a different strategy rather than assuming another drug in the same class will overcome it.

Do not stop a BTK inhibitor abruptly without a plan, because disease flare can occur in some circumstances. If a procedure requires a pause because of bleeding risk, the haematology team will specify when to stop and restart.

If CLL returns or does not respond

Relapsed CLL has returned after a response; refractory CLL has not responded adequately to the treatment being used. Another treatment may still provide useful control.

Reassessment includes TP53 and deletion 17p testing, review of the earlier treatment and investigation for transformation when suspected. A long treatment-free interval after a fixed-duration regimen is different from progression while actively receiving the drug. This distinction helps determine whether retreatment is reasonable or a new class is needed.

Venetoclax with rituximab is a fixed-duration option in appropriate previously treated CLL. A BTK inhibitor may be selected if the CLL has not already become resistant to that treatment approach. If the disease progresses during a covalent BTK inhibitor, venetoclax-based therapy or a non-covalent BTK inhibitor may be considered, depending on previous exposure and fitness.

Pirtobrutinib is a non-covalent BTK inhibitor for appropriate relapsed or refractory CLL/SLL after a covalent BTK inhibitor. It is not simply another name for the earlier class. Infection, bleeding, low counts and heart-rhythm issues remain relevant and need monitoring.

Lisocabtagene maraleucel is a chimeric antigen receptor (CAR) T-cell therapy. It modifies your own immune T cells to recognise the CD19 protein on CLL cells. It is an option for selected adults after at least two previous treatment programmes, including both a BTK inhibitor and a BCL-2 inhibitor.

It requires specialist assessment, cell collection and monitoring for cytokine release syndrome (an excessive inflammatory reaction), effects on the brain and nerves, and prolonged weakening of immunity. A donor transplant has a role in a small, carefully selected group with difficult-to-control disease.

Richter transformation

Richter transformation most often means CLL has changed into an aggressive large B-cell lymphoma. A biopsy is needed to establish the diagnosis; symptoms or a PET scan alone are not enough. Management differs from routine CLL and may involve lymphoma-directed antibody treatment with chemotherapy, a specialist trial or transplantation in suitable patients.

The team assesses whether the lymphoma is related to the original CLL and what that means for treatment. Prompt specialist review is important. Do not assume that a rising lymphocyte count or every new node represents transformation; those findings need assessment in context.

Supportive and local treatments

Steroids, rituximab or other immune treatments may help autoimmune destruction of blood cells. Immunoglobulin replacement may be considered for selected people with recurrent serious infections and impaired antibody production, rather than for everyone with a low immunoglobulin level.

Radiotherapy can occasionally help a local problem, and surgery has a limited role in selected situations. These are not the usual main treatments for CLL. Symptom management, infection prevention and care for other medical conditions continue during monitoring as well as during active treatment.

Managing side effects

BTK inhibitors and cardiovascular health

Report palpitations, fainting, chest discomfort, new breathlessness or a marked rise in blood pressure. BTK inhibitors can increase bleeding risk, and some can cause atrial fibrillation (an irregular heart rhythm) or other heart problems. The team should review blood thinners, medicines such as aspirin that reduce platelet clotting, and supplements before treatment and before surgery or dental procedures.

Bruising may occur, but major bleeding or a head injury requires urgent assessment. Do not assume that a tablet is mild because it is taken at home. Regular blood counts and review of new symptoms are part of safe prescribing.

Venetoclax and antibody treatment

During venetoclax introduction, keep every scheduled blood test and follow the agreed fluid plan. Nausea, weakness, muscle cramps, reduced urine or palpitations can signal a problem and need prompt advice. Do not change the ramp-up because the tablets appear to be tolerated well.

Anti-CD20 infusions can cause reactions, particularly early in treatment. Staff provide preventive medicines and monitor breathing, blood pressure and symptoms. Hepatitis B prevention or monitoring is arranged when needed. Low neutrophils, the white cells that fight infection, may require a delay, adjustment or additional support.

Infection prevention

Discuss influenza, COVID-19, pneumococcal and other recommended non-live vaccines with the team. Responses may be weaker in CLL and after B-cell-directed treatment, so timing matters. Live vaccines may be unsuitable. Family members and close contacts can help reduce exposure by staying up to date with appropriate vaccination and avoiding visits when ill.

Early treatment of infection is important. Recurrent sinus or chest infections, shingles, persistent diarrhoea or unusual skin changes should be reported. Preventive antimicrobials are selected for the regimen and history; they are not automatically required for every person on monitoring.

Keeping treatment manageable

Keep the team's contact details available and know where to go outside clinic hours. Report side effects early rather than waiting until the next appointment. A short record of symptoms, temperature, fluid intake and medicines can help the team decide what is needed. Do not change cancer medicine doses, restart a stopped treatment, or use leftover antibiotics without instructions. A planned delay or dose adjustment can be an important part of safe treatment.

If you receive treatment that can lower white blood cells, a temperature of 38°C (100.4°F) or higher needs urgent advice. Follow any lower threshold or additional instructions your team gives you. Chills, sudden weakness, confusion or feeling very unwell also need urgent assessment, even without a fever. Do not wait for a blood test appointment or try to hide the fever with medicine before speaking to the team.

Severe breathlessness, chest pain, a new seizure, sudden weakness, heavy bleeding or collapse require emergency care. New severe back pain with leg weakness, numbness around the bottom, or loss of bladder or bowel control also needs immediate assessment. Contact the nearest emergency service when necessary; a website contact form or routine messaging service is not an emergency pathway.

Eating, drinking and energy

Treatment may change appetite, taste, bowel habits and energy. Small, frequent meals and foods containing protein can be easier than large meals. Ask for dietitian support if weight is falling, swallowing is difficult, or you are avoiding many foods. There is no single diet that treats cancer, and severe restriction or prolonged fasting can make it harder to tolerate treatment. Check supplements with your team because some interact with medicines.

Take anti-sickness medicine as prescribed and report vomiting that prevents you keeping down fluids or essential medicines. Seek advice for persistent diarrhoea, dizziness, very little urine or increasing weakness. Fluid recommendations may need adjustment if you have heart or kidney disease. Mouth ulcers, pain or infection that interferes with eating should be treated promptly rather than accepted as unavoidable.

Gentle movement, short walks and planned rest may help fatigue, but activity should match your condition and any surgical or bone-safety restrictions. Fatigue can also reflect anaemia, infection, hormone changes, pain, poor sleep or low mood. Let the team assess a marked or persistent change. Accepting help with shopping, transport or meals can conserve energy for the activities that matter to you.

Live well

Monitoring without active treatment

A monitoring visit usually includes symptoms, examination and blood counts. Routine repeated CT or PET scans are not necessary for every stable patient. Ask what will be checked at each visit and what changes would trigger additional testing.

It can be difficult to live with a cancer diagnosis while being advised not to start medicine. Ask for an explanation of the evidence and the specific features that make monitoring appropriate. A rising count may need interpretation, but it should not become the only measure of wellbeing.

Skin health and other conditions

People with CLL have an increased risk of some other cancers, including skin cancers. Use sensible sun protection, report changing skin lesions and continue age-appropriate screening. A new symptom should not automatically be attributed to CLL; other common health problems still need ordinary medical care.

Keep dental care, cardiovascular prevention and diabetes management up to date. Tell clinicians about CLL even when you are not receiving treatment, because immune function and medicine choices can still be affected. A medication list and treatment summary are useful if care is shared between services.

Life after a fixed-duration course

At the end of a planned course, monitoring continues. Stopping on schedule can be part of a successful treatment strategy rather than a sign that care is being withdrawn. The team will explain how response was assessed and what follow-up is needed.

If the disease later returns, another treatment may still provide useful control. The choice will take account of the earlier response and time off therapy. Support for anxiety, fatigue and relationships should remain available between treatment courses, when the practical impact of living with CLL can be less visible to others.

Emotional and practical support

Feeling frightened, angry, sad or uncertain is understandable. You do not have to appear positive all the time. Ask about counselling, psycho-oncology (support for the emotional effects of cancer), support groups or a social worker if worry is affecting sleep, relationships or daily life. Persistent depression, panic or thoughts of self-harm need prompt professional help. Caregivers may need their own support and breaks; one person should not have to manage every appointment and household task alone.

It can help to agree who will update relatives and how much information you want shared. Children usually benefit from honest, age-appropriate explanations and reassurance about who will care for them. Ask permission before discussing private medical information with others. If concentration or memory is difficult, use reminders, a calendar and a trusted companion at important consultations.

Relationships, fertility and sexual health

Cancer and treatment can affect desire, comfort, fertility, body image and confidence. These are valid medical concerns. Raise fertility questions before treatment when possible, because some protective options need to be arranged early. The right approach depends on age, the treatment and how urgently it must start. Do not assume that absent periods or reduced fertility means pregnancy is impossible. Ask about contraception and the safe timing of pregnancy for your specific medicines.

Explain any pain, dryness, erection difficulties or changes in intimacy to the team. Appropriate treatments, rehabilitation and counselling can help. You can choose how much to involve a partner. Advice about hormone-containing treatments needs to take the cancer type and treatment into account; do not start them without discussing suitability.

Planning ahead while living well

Ask for a clear follow-up plan and know which symptoms should be reported between visits. Continue care for other conditions and discuss vaccinations with your oncology team; the timing and suitability of live vaccines can change during treatment. Avoid tobacco and ask for practical cessation support if needed. Activity, food and sleep plans should be realistic for your health rather than another source of pressure.

If treatment is long term, arrange periodic discussions about what is helping, what is difficult and what you want next. Planning for future care can protect your preferences and reduce uncertainty for family. You can discuss who should help with decisions if you become too unwell to speak for yourself, while continuing treatment and everyday life now.

Related care

Explore treatments

Medical Oncology↗Ports, PICCs, and venous access↗Stem Cell Transplant & Cellular Therapy↗Radiation Oncology↗Cancer Diagnostics & Molecular Testing↗Supportive & Holistic Cancer Care↗

Meet our doctors

Dr (Prof) Vijay Agarwal

Professor and Lead Consultant – Medical Oncology

Dr Prathyush V

Senior Consultant – Medical Oncology & Haemato-Oncology

Dr Darshan R S

Consultant – Medical Oncology & Haemato-Oncology

Where to get care

Bannerghatta Road

Apollo Hospitals
Bengaluru

Seshadripuram

Apollo Hospitals
Bengaluru

Sarjapur

Apollo Hospitals
Bengaluru

Jayanagar

Apollo Speciality Hospital
Bengaluru