Chronic Lymphocytic Leukaemia: Symptoms, Causes, Treatment

Chronic Lymphocytic Leukaemia(CLL) is a cancer of the blood and bone marrow (the spongy, soft tissue inside a person’s bones where blood cells are produced). This type of leukaemia comprises two words, “chronic”, which means that it progresses slower than other types of cancer and “lymphocytic”, which signifies the cells affected by the disease, i.e., lymphocytes. 

It develops when healthy blood cells in the bone marrow change into cancerous cells. These cancerous cells multiply uncontrollably, crowding out healthy blood cells and platelets. CLL may not always present symptoms. Most people may get to know they have CLL after blood tests for routine physical examination. 

Now that chronic lymphocytic leukaemia definition is clear, it is important to understand that it can develop in a person’s B-cells or T-cells, which are both types of white blood cells. 

1. B lymphocytes or B-cells make antibodies to target bacteria, viruses, and other cancer cells. 

2. T lymphocytes or T-cells control the body’s immune system response. They help the immune system fight and destroy abnormal cells, including cancer cells. 

B-cell chronic lymphocytic leukaemia develops in almost every individual with CLL. A condition that affects T-cells is called T-cell prolymphocytic leukaemia (PLL).  

Stages of Chronic Lymphocytic Leukaemia

CLL is typically classified into different stages based on the extent of the disease and the number of abnormal lymphocytes present. The two commonly used CLL staging systems are the Rai and Binet systems.

1. Rai Staging System: According to this system, CLL is divided into five different stages, from 0 to IV. These stages are as follows:

1. Stage 0: In this stage, there is an increased number of abnormal lymphocytes in the blood (lymphocytosis), but there is no enlargement of the lymph nodes, spleen, or liver.

2. Stage I: Lymphocytosis and enlargement of lymph nodes are observed. However, there is no liver or spleen enlargement, and red blood cells and platelet are near normal. 

3. Stage II: Lymphocytosis and enlargement of the spleen (and maybe liver) are present. Swollen lymph nodes may or may not be present. 

4. Stage III: Lymphocytosis and anaemia (low blood cell count) are present. The patient may or may not have swelling in lymph nodes and an enlarged spleen or liver.

5. Stage IV: Lymphocytosis and thrombocytopenia (low platelet counts) are present. The patient may or may not or may not have swollen lymph nodes, an enlarged liver or spleen, or anaemia. 

Stage 0 is low risk, stages I and II are intermediate risk, and stages III and IV are high risk. 

2. Binet Staging System: The Binet classification stages of CLL are based on whether the lymph nodes are found under the arms, neck, or groin area and whether patients have low levels of platelets and red blood cells.

   1. Stage A: In this stage, enlarged lymph nodes are present in less than three areas of lymphoid tissue. Red blood cells and platelet counts are within normal limits.

   2. Stage B: Enlarged lymph nodes are present in three or more areas of lymphoid tissue. Patients do not have anaemia or thrombocytopenia. 

   3. Stage C: There are several enlarged lymphoid tissue areas. Patients have anaemia and/or thrombocytopenia. 

Chronic lymphocytic leukaemia symptoms can vary from person to person, and in some cases, individuals may not experience any symptoms, especially in the early stages of the disease. It may take months or even years for people to notice CLL symptoms. 

As the disease progresses, the following symptoms or clinical features of chronic lymphocytic leukaemia may occur:

1. Swollen Lymph Nodes in the Underarm, Neck, Stomach, or Groin: This is usually the first common CLL symptom. Enlarged lymph nodes are generally not painful. 

2. Fever: It is a sign of infection (CLL affects white blood cells, increasing the risk of infections)

3. Fatigue: It can result from anaemia caused by CLL’s effect on red blood cells. 

4. Fullness or Discomfort in the Upper Left Part of the Abdomen: This may be caused due to an enlarged spleen

5. Shortness of Breath: Individuals may experience shortness of breath when enlarged lymph nodes or spleen press on the airway. 

6. Frequent Infections: CLL impairs the immune system, making individuals more susceptible to infections.

7. Night Sweats: Excessive sweating during the night is a symptom that some individuals with CLL may experience.

8. Unexplained Weight Loss: CLL patients may experience unexplained weight loss, generally accompanied by loss of appetite. It is not a result of diet or exercise.

The exact chronic lymphocytic leukaemia causes are not known. However, it is known that these cancers develop from a change (mutation) in the DNA of the blood-forming cells. The DNA contains instructions that inform the cell what to do. Changes in the DNA inform the blood cells to produce abnormal lymphocytes.

The abnormal lymphocytes grow and multiply when healthy lymphocytes die. This accumulation of abnormal lymphocytes crowds healthy cells out of the bone marrow, interfering with blood cell production and causing complications. The cause for the change in the DNA is not understood. 

Chronic Lymphocytic Leukaemia Risk Factors

While it is not known what triggers changes in the cell’s DNA, there are certain identified risk factors. Factors that may increase the risk of developing chronic lymphocytic leukaemia include:

1. Family History: Having a close relative, such as a parent or sibling with CLL, increases the risk of developing the disease by two to four times, but is not the sole reason. 

2. Age: CLL is more commonly diagnosed in older adults. The average age at diagnosis is around 71 years. The risk of developing CLL increases with age.

3. Gender: Men are at a slightly greater risk of developing CLL than women. However, the reasons for this gender difference are not fully understood.

4. Exposure to Certain Chemicals: Prolonged exposure to certain chemicals, such as certain herbicides, insecticides, and pesticides, has been suggested as a possible risk factor for CLL. However, the evidence linking specific chemicals to CLL development is limited and further research is needed. 

5. Monoclonal B-cell Lymphocytosis: This condition causes an increased number of identical B-cells in the patient’s blood. A small number of people with this condition may develop CLL. 

6. Smoking and Alcohol Consumption: Several research evidence have found out smoking and alcohol consumption is one of the leading risk factors for major types of cancer. Smoking and alcohol consumption can also put an individual at a higher risk of CLL.

There are very few known risk factors for CLL, most of which cannot be avoided. Most people who develop CLL have no risk factors. Therefore, currently, there are no known strategies for preventing the disease. However, one can reduce the risk of cancer by following these general preventive measures:

1. Avoid Smoking: Tobacco use can lead to multiple cancers. Individuals should avoid using tobacco products to reduce their risk of cancer. 

2. Limit Alcohol Consumption: Alcohol intake can increase the risk of breast, colon, oropharyngeal, and oesophageal cancer. Therefore, it is best to avoid or limit its consumption.  

3. Avoid Radiation Exposure: People who work in an environment that requires radiation exposure should follow appropriate work safety measures.

4.  Stay Physically Active: Inactivity can cause excess weight gain that leads to multiple types of cancer. Thus, individuals should lead a healthy and active life.

The diagnosis of chronic lymphocytic leukaemia typically involves a combination of medical history assessment, physical examination, blood tests, and sometimes additional tests. Here are the main chronic lymphocytic leukaemia tests for diagnosis:

1. Medical History and Physical Evaluation: The healthcare provider will inquire the patient about their symptoms, medical history, and family history of cancer or blood disorders. Next, they will perform a physical examination, including checking for enlarged lymph nodes, spleen, or liver.

2. Complete Blood Count (CBC): A CBC is a blood test that measures the type and number of blood cells. In CLL, the CBC may reveal increased lymphocytes in the blood. Other blood cell counts, such as red blood cells and platelets, may also be evaluated.

3. Peripheral Blood Smear: It is a microscopic examination of a blood sample. The test allows the doctor to visually examine the size, shape, and characteristics of cancerous blood cells. 

4. Flow Cytometry: Flow cytometry is a laboratory technique that analyses the characteristics of cells in a blood sample. It can determine the proportion of different types of cells, including lymphocytes, and identify specific markers on the surface of these cells. In CLL, flow cytometry helps confirm if the lymphocytes in the blood sample contain CLL cells. 

5. Genetic Tests: Tests such as fluorescent in situ hybridisation (FISH) and immunoglobulin heavy chain (IGHV) examine the patient’s chromosomes and genes. Understanding the mutation in chromosomes and genes can help determine prognosis and choose treatment. 

6. Bone Marrow Biopsy and Aspiration: Usually, blood tests are enough to diagnose CLL. However, in some cases, a bone marrow biopsy may be performed to assess the involvement of CLL in the bone marrow. During this procedure, a small bone marrow sample (biopsy) and a small amount of bone marrow fluid (aspiration) are collected using a needle. The samples are then examined under a microscope. 

7. Imaging Tests: X-rays, ultrasounds, CT scans, and MRIs are not done to diagnose CLL. However, they may be performed for other reasons, such as finding cancerous areas, determining cancer spread, or seeing if the treatment works. 

How to Prepare for Doctor’s Consultation?

Preparing for a doctor’s consultation is important to make the most of an individual’s time and ensure that their concerns and questions about chronic lymphocytic leukaemia are addressed effectively. Here are some steps to help prepare for a doctor’s consultation:

1. Follow any pre-appointment restrictions: If the doctor has provided specific instructions or requested specific tests or reports before the consultation, the patient must comply with those requests.

2. Note the symptoms: The patient must write down any symptoms they have been experiencing, even if they may be unrelated to CLL. Be specific and note when the symptoms started, their duration, and any factors that worsen or alleviate them.

3. Prepare a list of questions: It is recommended to prepare a list of questions that the patient would like to ask their doctor, covering topics such as treatment options, potential side effects, prognosis, lifestyle modifications, and support resources.

4. Make a list of medications: The patients must list all their medications, including prescription, over-the-counter, supplements, and herbs. They should include their dosages. This helps the doctor understand if there are any drug interactions. 

5. Bring a trusted companion: Patients must consider bringing a family member or friend to the consultation for support and to help them remember the details discussed during the appointment. They can also help them ask questions or take notes.

What to Expect from the Doctor?

During a consultation appointment for chronic lymphocytic leukaemia, the doctor may ask the patient various questions to gather information about their condition and develop an appropriate treatment plan. Here are some questions the doctor may ask:

1. What are the symptoms you are experiencing?

2. When did you start experiencing these symptoms?

3. How severe are your symptoms?

4. Does anything seem to worsen or improve the symptoms?

5. Have you had a recent injury or infection?

6. Have you lost weight without trying?

7. Do you have a family history of CLL or other blood disorders?

8. What medications do you take?

9. Have you received any previous treatments for CLL or other conditions?

What Questions to Ask the Doctor?

During a consultation for chronic lymphocytic leukaemia, individuals must ask their doctor relevant questions to understand their condition and make informed treatment decisions. Here are some questions they may consider asking:

1. What type of CLL do I have?

2. What is the stage of my leukaemia, and what does it mean for me?

3. Do I need treatment right away?

4. If not, how will I know when I need treatment?

5. Should I get a second opinion?

6. Will I need other tests before deciding on the treatment?

7. What are my treatment choices? Which one do you recommend?

8. What are the side effects of each treatment option?

9. Will treatment put my cancer into remission?

10. How long will the treatment last?

11. How will CLL treatment affect my daily life?

12. What is the outlook for my survival?

13. What type of follow-up care will I need after CLL treatment?

14. What are my treatment options if leukaemia returns?

15. Are there any support services available for me and my family?

Chronic lymphocytic leukaemia treatment depends on several factors, including the stage of the disease, the presence of symptoms, the rate of disease progression, and individual patient characteristics. The following are common treatment approaches for CLL:

1. Watchful Waiting: If CLL does not show any symptoms or does not get worse, the patient may not need treatment right away. The healthcare provider may recommend a “watch and wait” approach in early-stage CLL with no or minimal symptoms. 

   Rather than putting the patients through the potential complications of treatments before they need them, doctors regularly monitor blood counts, perform physical exams, and evaluate symptoms. This helps determine when treatment should be initiated.

2. Chemotherapy: Administered through a vein or taken in a pill form, chemotherapy treatment is typically given in cycles to kill cancer cells. Chronic lymphocytic leukaemia medications for chemotherapy include fludarabine, cyclophosphamide, bendamustine, etc., which may be used alone or in combination.

3. Targeted Therapy: Targeted therapy drugs, such as ibrutinib or venetoclax, specifically target certain molecules or pathways involved in CLL cell growth and survival. They can be highly effective and often have fewer side effects than traditional chemotherapy.

4. Immunotherapy: The drugs used in this chronic lymphocytic leukaemia treatment strengthen the immune system to attack cancerous cells or slow down cancerous cell growth. Immunotherapy drugs like lenalidomide may be used to treat CLL that did not respond to chemotherapy, recurrent CLL, or CLL that gets worse. 

5. Stem Cell Transplant: For individuals with high-risk CLL or relapsed/refractory disease, a stem cell transplant or a bone marrow transplant may be considered. This procedure involves replacing diseased bone marrow with healthy donor stem cells. 

   However, stem cell transplants have become less common with the development of newer, more effective drug combinations. 

6. Clinical Trials: Clinical trials for CLL are research studies investigating new treatments to improve chronic lymphocytic leukaemia treatment protocols. Some individuals with CLL may participate in clinical trials to explore novel treatments, new drug combinations, or experimental therapies.

7. Supportive Care: It aims to relieve signs and symptoms of the condition. The doctor may regularly monitor any complications the patient may experience. Supportive care measures include vaccinations to prevent infections, cancer screening, and monitoring other health problems. 

   Please Note: The selection of treatment approach is based on the patient’s health condition and the treating doctor’s opinion. 

Cost of Chronic Lymphocytic Leukaemia Treatment

The cost of chronic lymphocytic leukaemia treatment in India is generally influenced by several factors, including the stage of the cancer, treatment method used, patient’s age, patient’s comorbidities, hospital type and location, doctor’s expertise, insurance coverage and much more.

To know the exact cost of the CLL treatment, one must consult a reputed medical oncologist or the below table provides the approximate cost for various treatment modalities for CLL.

Chronic Lymphocytic Leukaemia Survival Rates

Generally, chronic lymphocytic leukaemia treatment prognosis is good, and the condition has a high survival rate than other types of cancer. The five-year relative chronic lymphocytic leukaemia survival rate for people aged 20 and older is 87%. However, the individual prognosis may vary based on several factors, including:

1. The stage of the disease

2. Patient response to treatment

3. Certain cellular and genetic markers

Chronic lymphocytic leukaemia affects a person’s white blood cells, red blood cells, and platelets. Without healthy blood cells and platelets, an individual may develop the following complications:

1. Frequent Infections: CLL can weaken the immune system, making individuals more susceptible to infections. This includes bacterial, viral, and fungal infections, which can be potentially life-threatening.

2. Lymphoma: Approximately 2% to 10% of individuals with CLL develop lymphoma (cancer of the lymphatic system). 

3. Increased Risk of Other Cancers: Individuals with CLL may have a higher risk of developing other forms of cancer, like skin cancer, lung cancer, or colon cancer. This usually happens due to abnormalities in immune function caused by CLL. 

4. Anaemia: CLL may result in an inadequate supply of red blood cells carrying oxygen throughout the body, which can lead to anaemia. 

5. Thrombocytopenia: CLL can affect the platelet supply, causing thrombocytopenia.  

6. Autoimmune Diseases: CLL can disrupt the normal functioning of the immune system, leading to the development of autoimmune disorders. Examples include autoimmune haemolytic anaemia (the immune system mistakenly attacks red blood cells) and autoimmune thrombocytopenia (the immune system mistakenly attacks platelets).

7. An aggressive form of Cancer: In some cases, CLL can transform into an aggressive form of non-Hodgkin lymphoma, called diffuse large B-cell lymphoma or Richter syndrome.

Risks of Delaying Treatment

Indolent (slow-growing) CLL may remain stable without treatment for years. In its early stages, doctors may recommend watchful waiting without any risk of treatment delay. However, if the CLL is aggressive or fast-growing, it may require immediate treatment. Delaying treatment can lead to serious complications, such as:

1. Anaemia

2. Shortness of breath

3. Fatigue

4. Bleeding

5. Difficulty fighting off infections

When to Call A Doctor?

An individual should see their doctor if they notice a change that is not normal or experiences any possible chronic lymphocytic leukaemia symptoms, including:

1. Weight loss

2. Fatigue

3. Feeling full after just a few bites

4. Swollen lymph nodes

5. Night sweats

6. A rapid heartbeat

7. Unexplained bruising

Nutrition is important for everyone but becomes even more important for cancer patients. While no specific diet can cure CLL or replace medical treatment, maintaining a healthy diet may help boost energy and support recovery. Here are some general dietary recommendations that may be beneficial for individuals with CLL:

What to Include

1. Water: Staying well-hydrated by drinking plenty of water throughout the day is crucial for maintaining optimal bodily functions and overall health. It also helps prevent treatment side effects like dry mouth and constipation. 

2. Fruits and Vegetables: They include many antioxidants and phytochemicals, which may help individuals protect against cancer. People should eat vegetables like cauliflower, broccoli, cabbage, pumpkins, carrots, beets, etc., to receive the necessary minerals, vitamins, fibre, and other nutrients. 

3. Healthy Fats: Cancer patients must consume healthy fats, such as extra virgin olive oil, olives, avocado oil, avocados, seeds, nuts, and fish like salmon and tuna. Some studies show that olive oil can reduce the risk of cancer. Moreover, the omega-3 fatty acids found in flax seeds have also been shown to protect individuals against cancer. 

What to Avoid

1. Processed foods: Consumption of fast foods and processed meats can increase the risk of certain forms of cancer, such as colorectal, ovarian, and brain cancers.

2. Alcohol: Heavy alcohol consumption can increase the risk of certain cancers. However, if someone chooses to drink alcohol, they must limit their alcohol intake to two drinks daily for men and one for women.

Chronic lymphocytic leukaemia is a complex disease characterised by the rapid growth of abnormal lymphocytes. It varies in progression and treatment options, requiring personalised approaches for each patient.

Ongoing research and advancements in treatment have improved outcomes and increased the possibility of long-term remission. Individuals with CLL must work closely with their healthcare team, staying informed and proactive in managing the disease.

HexaHealth offers valuable support for individuals with CLL. Our network of specialists provides access to haematologists, oncologists, and other experts who can provide expert guidance and personalised treatment plans.

We offer resources and information about CLL, including the latest updates in chronic lymphocytic leukaemia pathology outlines, enabling you to stay informed and actively participate in your healthcare decisions. With HexaHealth, you can confidently navigate your treatment journey, knowing you have a reliable support system in your corner. Contact us TODAY!

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