Diagnosis of Chronic Lymphocytic Leukemia

Signs and Symptoms of Chronic Lymphocytic Leukemia

Signs and symptoms of chronic lymphocytic leukemia (CLL) develop in approximately 50% of patients and may include:

• Enlarged lymph nodes (lymphadenopathy) - represents the most common presenting symptom of CLL
• Enlarged liver (hepatomegaly) and/or an enlarged spleen (splenomegaly)
• Fatigue, generalized weakness
• Excessive sweating (especially at night)
• Loss of appetite
• Unintentional weight loss
• Fever
• Frequent infections
• Hemolytic anemia - low numbers of red blood cells in the bloodstream due to the premature destruction of red blood cells
• Thrombocytopenia - low platelet levels in the bloodstream
• Bleeding or bruising easily - usually occurs in the late stages of CLL

Laboratory Evaluation of Chronic Lymphocytic Leukemia

A variety of laboratory tests may be used to help establish the diagnosis of chronic lymphocytic leukemia (CLL). These tests include:

• Blood test to check for lymphocytosis
• Bone marrow biopsy
• Cytogenetic analysis
• Immunophenotyping

Lymphocytosis

The major blood abnormality in patients with CLL is an absolute increase in the numbers of lymphocytes in the bloodstream , a condition known as lymphocytosis. Lymphocytosis can usually be detected by a routine blood test. Once lymphocytosis is detected, repeat blood counts are usually performed for several weeks or months to differentiate CLL from other conditions that can cause lymphocytosis. If the lymphocytosis is due to CLL, the absolute lymphocyte counts will remain elevated in repeat blood counts over several months. If the lymphocytosis is caused by a condition other than CLL, the absolute lymphocyte counts will usually return to normal after several weeks upon repeat testing.

Bone Marrow Biopsy

If the results of the blood cells are abnormal, a bone marrow biopsy will usually be performed to determine if leukemia is present. During this procedure, a bone marrow sample is removed from the hip bone or breastbone with a special needle called a bone biopsy needle and the marrow is examined under a microscope to look for leukemic cells. Leukemic cells in the bone marrow or blood may be identified by special laboratory tests (e.g., cytochemistry; flow cytometry).

Cytogenetic Analysis

Cytogenetic analysis is a special test that detects genetic abnormalities of the chromosomes and identifies the specific genes that are affected by CLL. Cytogenetic testing can help doctors make better treatment decisions and can also be useful in monitoring the effectiveness of treatment.

Common chromosomal abnormalities identified by cytogenetic analysis in patients with CLL include:

• deletion [17p]
• deletion [11q22-23]
• deletion [13q14]
• trisomy 12

Immunophenotyping

This is a special immunological test that uses antibodies to not only identify leukemic lymphocytes but can also determine the types of lymphocytes that are involved (e.g., B-lymphocytes, T-lymphocytes, or NK cells). Most patients with CLL have a B-cell type of chronic lymphocytic leukemia. T-cell chronic lymphocytic leukemia, on the other hand, is very rare.

Immunophenotyping studies of patients with B-cell chronic lymphocytic leukemia has demonstrated that the leukemic B cells express certain biological markers, some of which have been found to be important prognostic indicators of disease progression. The biological markers with prognostic value include expression of an antigen called CD38 and expression of a protein called Zeta-associated protein 70 (ZAP-70).

Imaging Studies

There are no specific radiological (imaging) studies used to diagnose chronic lymphocytic leukemia. A chest x-ray or computed tomography (CT) scan may be performed to evaluate involvement of the lymph nodes or other body areas.