Chronic%20lymphocytic%20leukemia Diagnosis

• Diagnosis is based on the following criteria:
  • Presence of monoclonal B-cell lymphocytes ≥5 x 10⁹/L in peripheral blood
  • Clonality of circulating B lymphocytes confirmed by flow cytometry
  • Chronic lymphocytic leukemia cells are small, mature-looking lymphocytes with a narrow border of cytoplasm, dense nucleus with no visible nucleoli, and with partially aggregated chromatin
  • Immunophenotype: CD5, CD19, and CD23; low CD20, CD79b and FMC7 (typically negative); CD10 and cyclin D1 negative
• Assess patient's performance status based on clinical presentation

• Two staging systems are being used to predict patient outcome
• Also used in assessing patients to be included in clinical trials

Rai System

• A staging system based on physical examination and complete blood count results used to assess the degree of tumor burden

Stage	Description	Risk Status1
0	Lymphocytosis >5 x 109/L and >40% lymphocytes in bone marrow	Low
I	Stage 0 with enlarged node(s)	Intermediate
II	Stage 0-I with splenomegaly, hepatomegaly, or both	Intermediate
III	Stage 0-II with hemoglobin (Hb) <11.0 g/dL or hematocrit (Hct) <33%	High
IV	Stage 0-III with platelets <100 x 109/L	High
1Used in the modified Rai classification

• Based on the number of areas with lymph nodes >1 cm in diameter or organomegaly, and the presence of anemia or thrombocytopenia
• Involved areas include head and neck, axilla, groins including superficial femorals, spleen, and liver

  Stage	Description
  A	Hb ≥10 g/dL, platelets ≥100,000/mm3, and <3 enlarged areas
  B	Hb ≥10 g/dL, platelets ≥100,000/mm3, and ≥3 enlarged areas
  C	Hb <10 g/dL, and/or platelets <100,000/mm3, and any number of enlarged areas

• Used to assess how a disease affects the daily activities of a patient
• Commonly used performance status scoring systems:
  • Karnofsky performance status scale
  • Eastern Cooperative Oncology Group (ECOG) performance scale

• Node-bearing areas (eg Waldeyer’s ring)
• Spleen, liver enlargement, palpable lymph nodes
• Skin examination: Presence of macules, papules, plaques, nodules, ulcers, blisters

• Complete blood count, with differential and platelet count
• Metabolic panel, including lactate dehydrogenase (LDH) levels and serum beta-2-microglobulin
• Bilirubin, haptoglobulin
• Direct Coomb’s test/direct antiglobulin test: May help predict autoimmune hemolytic anemia
• Hepatitis B screening: If considering CD20 monoclonal antibody therapy

• Effectively differentiates chronic lymphocytic leukemia (CLL) from other forms of leukemia by identifying the specific cell lineage using antibodies
• Immunophenotyping:
  • Fast and reliable method of identifying single cell populations of surface antigens
  • Uses antibodies/markers to identify the presence and proportion of surface antigens
    • B-cell associated antigens: CD19, CD20 (low), CD23
    • T-cell antigen: CD5
    • Surface immunoglobulins: IgM, IgD (low)
  • Used for confirmation of clonality of B cells
• Fluorescence in situ Hybridization (FISH): Detects del(17p), del(11q), del(13q), and trisomy 12

TP53 Sequencing and Immunoglobulin Heavy Chain (IGHV) Gene Mutation Analysis

• Used for determination of the patient’s prognosis and to help in selecting the best treatment option
• IGHV mutation status is useful when considering treatment with chemoimmunotherapy

• Serum uric acid levels
• Quantitative serum immunoglobulin test - to determine patient’s immunological status
• Testing for hepatitis C, cytomegalovirus (CMV) and human immunodeficiency virus (HIV) is also suggested

Lumbar Puncture

• May be used for patients with possible central nervous system (CNS) involvement with overt symptoms

• Imaging studies are not routinely used

Computed Tomography (CT)

• Used to assess tumor load and for the assessment of symptoms
• Also used for baseline assessment of patients enrolled in clinical trials

Positron Emission Tomography (PET)

• Recommended for localized diseases and to identify occult sites of the disease or histologic transformation

Ultrasonography

• May be considered for the detection of lymphadenopathies and organ enlargement

• Aids in predicting survival or disease progression beyond clinical staging
• Includes serum markers [CD23, thymidine kinase, serum β2-microglobulin (B2M)], genetic markers [immunoglobulin heavy chain variable (IGHV) gene analysis] and tests for genomic abnormalities (CD38 expression, CD49d and ZAP-70 expression or methylation)