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A decade of development in chronic lymphocytic leukaemia has prolonged lives and shifted expectations

iStock / Getty Images Plus / KatarzynaBialasiewicz
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Dr. Amjad Hayat MBBS MRCP FRCPath PhD

Consultant Haematologist, University Hospital Galway

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Dr. Mark Gurney MB BCh BAO MRCPI

Haematology Specialist Registrar, Wellcome-HRB ICAT Fellow, NUI Galway

The treatment of chronic lymphocytic leukaemia (CLL) has changed dramatically over the past decade with a growing understanding of the disease biology guiding the use of established therapies and driving the introduction of new and effective chemo-free treatments.


Chronic lymphocytic leukaemia is the most common leukaemia in adults. In Ireland, 250-300 new cases are diagnosed annually.

CLL develops when a normal immune cell called a B-lymphocyte undergoes a series of genetic changes promoting growth and survival. These cells accumulate within the bone marrow and enter the blood where they may be detected on a routine blood test.

Many patients do not need immediate treatment and are managed by watchful waiting. Over time, the accumulation of cells can cause enlargement of the spleen and lymph glands and impair the function of the bone marrow with anaemia, bleeding and infection risks.

Many patients also experience tiredness, sweats and weight loss. Treatments aim to eliminate the leukaemic cells, resolve symptoms and restore bone marrow function.

Developments in CLL treatment

Chemotherapies have been the mainstay of CLL treatment for over 50 years. Clinical trials established the best combination therapies. Development of antibodies that target a common marker on the leukaemia cell surface improved treatment further.

Modified forms of chemotherapy are used for older patients for whom treatment is harder and riskier to endure. These approaches to treatment are effective in eliminating leukaemic cells but seldom lead to long-term cure.

The discovery that genetic and molecular changes can predict the effectiveness of chemotherapy laid a foundation for the modern personalised approach to chemotherapy use.

The past decade has seen radical new CLL treatments emerge. Targeted drugs that inhibit the signals  leukaemic cells rely upon for survival or signals that prevent cell death have become available. They have shown dramatic benefits in clinical trials.

These tablets are taken continuously and possess a very different but generally milder side effect profile. There are now many patients for whom CLL is controlled on long-term therapy.

This has required a coordinated approach across medical specialties and primary care in managing longer-term effects such as cardiovascular changes and infections.

Looking to the future

The dramatic achievements of the past decade have raised further questions and shifted the goals for patients and researchers alike. Quality of life for patients receiving long-term therapy has become a key consideration.

The range of treatments now available requires additional knowledge and understanding from patients and carers to enable informed decision making in conjunction with clinical teams.

The patient-led group, Chronic Lymphocytic Leukaemia Ireland (CLLI), has emerged as a key resource for patients and families navigating this new landscape of CLL care in Ireland.

Irish patients have benefited from and contributed to clinical trials establishing targeted therapies in CLL. This process continues through Cancer Trials Ireland’s involvement in the international CLL13 trial.

The new generation of trials assess chemotherapy-free combinations given for a fixed period of time aiming to suppress the disease to undetectable levels.

New therapies and combinations have inherent and considerable cost associated. It is vital that we advocate for prompt and equitable economic assessments to maximise the benefit of future developments to Irish CLL patients.

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