Chronic Lymphocytic Leukaemia

Chronic lymphocytic leukaemia (CLL), also known as B-cell chronic lymphocytic leukaemia (B-CLL), is a type of cancer where the bone marrow produces excessive lymphocytes, a type of white blood cell. It usually affects individuals older than 50 and progresses gradually over years. Risk factors include family history, exposure to Agent Orange, certain insecticides, sun exposure, hepatitis C virus, and common infections.

Signs and Symptoms

Early-stage CLL is typically asymptomatic, often detected incidentally through routine blood tests showing high white blood cell counts. As the disease progresses, symptoms may include non-painful swelling of lymph nodes, fatigue, fever, night sweats, weight loss, spleen enlargement, and anaemia. CLL can also present with complications such as hypogammaglobulinaemia, autoimmune hemolytic anaemia, and bone marrow failure. Rarely, it may transform into a more aggressive form like diffuse large B cell lymphoma, known as Richter's transformation.

Diagnosis

Diagnosis of CLL is primarily based on blood tests revealing high numbers of mature lymphocytes and smudge cells. Confirmation involves molecular examination and flow cytometry to assess clonality and marker molecule expression. CLL cells typically express CD19, CD20, CD5, and CD23 surface markers.

Staging

Staging is very important in determining treatment and is done using the Rai staging system (common in the US) or the Binet classification (common in Europe). These systems are based on factors such as lymphocytosis, lymphadenopathy, hepatosplenomegaly, anaemia, and thrombocytopenia.

Treatment

Treatment for CLL is aimed at controlling symptoms rather than achieving a cure. In asymptomatic cases, a watchful waiting approach is often adopted. Symptomatic cases may be treated with chemotherapy, immunotherapy, or a combination of both.

Chemotherapy and Targeted Therapy

Chemotherapy combinations like fludarabine with cyclophosphamide and rituximab (FCR) are commonly used. Targeted therapies, such as BTK inhibitors (ibrutinib, acalabrutinib) and Bcl-2 inhibitors (venetoclax), are evolving as effective treatments. Monoclonal antibodies like rituximab and alemtuzumab are also used to target specific cell surface markers.

Stem Cell Transplantation

Allogeneic stem cell transplantation may be considered for high-risk, younger individuals. This procedure involves using donor cells and can be potentially curative, though it comes with significant risks.

Refractory CLL

For CLL that no longer responds to treatment, more aggressive targeted therapies may be employed. These include BCR or BCL2 pathway inhibitors, which have shown to increase survival rates.

During Pregnancy

CLL is rare during pregnancy. If treatment is necessary, it is usually delayed until the second or third trimester to minimise risk to the foetus.

Prognosis

Prognosis varies significantly based on genetic mutations. For instance, mutations in the IGHV region are associated with a longer median overall survival compared to unmutated cases. Chromosomal deletions and trisomies also affect prognosis. The overall five-year relative survival rate is approximately 86.1%.

Epidemiology

CLL is the most common type of leukaemia in the Western world, predominantly affecting older adults. The incidence is higher in men than in women and is notably less common in Asian populations. Industrial pollution exposure has been linked to an increased risk of developing CLL.

Research Directions

Research is focusing on new therapies such as gene therapy and targeted agents, reducing the need for bone marrow transplants. Early trials involving genetically modified T cells have shown promising results in treating CLL.

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Self-assessment MCQs (single best answer)

Sure! Here is the formatted HTML and pseudocode for the given questions:

Which age group is most commonly affected by Chronic Lymphocytic Leukaemia (CLL)?

Which of the following is NOT a typical symptom of progressing CLL?

Which surface markers are typically expressed by CLL cells?

What is the primary method used to confirm the diagnosis of CLL?

What is the name of the aggressive transformation that CLL can rarely undergo?

Which of the following is NOT commonly used in the treatment of CLL?

What type of transplantation might be considered for high-risk, younger individuals with CLL?

Which genetic mutation is associated with a longer median overall survival in CLL?

Which classification system is commonly used in Europe for staging CLL?

What is the approximate five-year relative survival rate for CLL?