Chronic Lymphocytic Leukmia (CLL)

What is Chronic Lymphocytic Leukemia?

Chronic Lymphocytic Leukemia (CLL) is a type of cancer of the blood in which the bone marrow makes too many lymphocytes (a type of white blood cell). Chronic Lymphocytic Leukemia is one of the few diseases occurring exclusively in adults. This arises from abnormality in mature lymphocytes, which are a normal component of white blood cells resulting in proliferation of mature lymphocytes.

The incidence of Chronic Lymphocytic Leukemia increases with age and is the commonest blood cancer in the developed countries.

Natural History of Chronic Lymphocytic Leukemia

Chronic Lymphocytic Leukaemia has several phases

• Most patients are asymptomatic. Some develop lymph glands and others can develop low haemoglobin and platelets.
• Richter’s Transformation: The disease transforms to a high grade Lymphoma.
• Blast Crises: rarely CLL can transform to ALL

What are the Causes / risk factors of Chronic Lymphocytic Leukaemia?

What causes CLL is unknown as in most cases of leukemia.

What are the Symptoms of Chronic Lymphocytic Leukemia?

Fifty percent patients have no symptoms and are diagnosed during routine blood tests. The other 50% may have the following symptoms:

• Repeated infections
• Tiredness
• Breathlessness
• Weakness
• Night sweats
• Swelling / fullness in the left side of abdomen due to enlargement of spleen.
• Swollen lymph nodes (glands)
• Abnormal bruising (if platelets are low)
• Excessive sweating, night sweats
• Fatigue
• Fever
• Loss of appetite or becoming full too quickly (early satiety)
• Weight loss

How do we Diagnose Chronic Lymphocytic Leukaemia?

• Complete Blood Count: The characteristic finding of CLL is high white blood cell count with excess of lymphocytes and no other abnormalities.
• Bone Marrow Examination: This is not absolutely necessary for confirmation of the diagnosis.
• Flow Cytometry: This is essential to confirm the diagnosis and differentiate CLL from other low grade lymphomas.
• Cytogenetics: This is testing for abnormalities in the chromosomes and is essential for finding out the real bad ones. The abnormality 17pdel for example has very poor outcome and responds poorly to routine treatment.

Staging of Chronic Lymphocytic Leukaemia

Staging for chronic lymphocytic leukemia is done as under :

• Stage 0 There are too many lymphocytes in the blood, but there are no other signs or symptoms of leukemia. Stage 0 Chronic Lymphocytic Leukemia is indolent (slow growing)
• Stage I - There are too many lymphocytes in the blood and the lymph nodes are enlarged.
• Stage II - There are too many lymphocytes in the blood, the liver or spleen is larger than normal, and the lymph nodes may be enlarged.
• Stage III - There are too many lymphocytes in the blood, and there are too few red blood cells. The lymph nodes, liver, or spleen may or may not be enlarged.
• Stage IV - There are too many lymphocytes in the blood and too few platelets. The lymph nodes, liver, or spleen may or may not be larger than normal and there may be too few red blood cells.

How do we treat Chronic Lymphocytic Leukemia?

Treatment options depend on:

• The stage of the disease.
• Red blood cell, white blood cell, and platelet blood counts.
• Whether there are signs or symptoms, such as fever, chills, or weight loss.
• Whether the liver, spleen, or lymph nodes are enlarged.
• The response to initial treatment.
• Whether the CLL has recurred (come back).

The prognosis (chance of recovery) depends on:

• Whether there is a change in the DNA and the type of change, if any.
• Whether lymphocytes are spread throughout the bone marrow.
• The stage of the disease.
• Whether the CLL gets better with treatment or has recurred (come back).
• Whether the CLL progresses to lymphoma or prolymphocytic leukemia.
• The patient's general health.

Chronic Lymphocytic Leukemia does not always require treatment. If the patient is asymptomatic and has only high lymphocyte count with or without small lymph glands, treatment is generally not recommended. If there are large lymph glands or ‘B symptoms’ or anemia and/or low platelet count, treatment is indicated.

Five types of standard treatment lines are used:

• Watchful waiting
• Chemotherapy
• Monoclonal antibodies such as Rituximab and Ofatumumab.
• Other treatment option is Bone Marrow Transplantation or BMT.

BMT for Chronic Lymphocytic Leukemia

BMT is the treatment of choice for Chronic Lymphocytic Leukaemia if the disease is advanced or has bad chromosomes.

When is BMT needed for Chronic Lymphocytic Leukemia?

• When patients relapse after first line therapy
• When CLL has bad chromosomes.

How is Conditioning for BMT done in Chronic Lymphocytic Leukemia?

Reduced Intensity Conditioning is the preferred choice.

Who can be a donor for BMT?

Although, a matched family donor is preferred, a Half matched (Haploidentical) family donor or an unrelated volunteer donor are suitable alternatives.

What are the results of BMT in Chronic Lymphocytic Leukemia?

BMT remains the only curative treatment for Chronic Lymphocytic Leukemia.

• Relapsed Disease in Complete Remission- 80-90% cure rate
• Chronic Lymphocytic Leukaemia with bad chromosomes – 30 - 60% cure rate

Points to remember:

• Patient with Chronic Lymphocytic Leukemia should undergo BMT, if he/she relapses early after treatment or never achieves remission with Standard Therapy.
• Patient should undergo BMT upfront, if he/she has bad chromosomes, after initial treatment to control the disease.
• Autologous BMT does not help in Chronic Lymphocytic Leukemia.