“Neoplastic proliferation of naïve B-cells, that express surface marker i.e. CD5, CD19, CD20”.
- Most common leukemia of adult.
- Chronic lymphocytic leukaemia (CLL) is the most common of the chronic lymphoid leukaemias and has a peak incidence between 60 and 80 years.
- If peripheral blood lymphocyte count exceeds 4000 cells/uL, the patient is diagnosed with CLL.
- If the peripheral lymphocyte count doesn’t exceeds 4000 cells/uL, the patient is diagnosed with SLL.
- The difference is that in SLL the tumour cells accumulate almost exclusively in the lymph node and there are fewer than 5×109 /L circulating monoclonal B cells
Incidence:
- The mean age at diagnosis is 72 years, with only 15% of cases before 50 years of age.
- The male:female ratio is approximately 2:1.
Pathogenesis:
CLL/SLL is an indolent (lazy), slowly growing tumor; there is increased tumor cell survival.
1. Tumor cells contain high levels of BCL2 (a protein that inhibits apoptosis).
2. Immune dysregulation:
- Accumulation of CLL/SLL cells suppresses normal B cell function, often results in hypogammaglobulinemia.
- Autoantibodies (in 15% pt) are against their own red cells and platelets, which results in autoimmune hemolytic anemia and autoimmune thrombocytopenia.
- Tumor cells tends to displace the normal marrow elements, leading to anemia, neutropenia, thrombocytopenia.
- CLL cells typically exhibit impaired apoptosis and a prolonged lifespan, and this is reflected in their accumulation in the blood, bone marrow, liver, spleen and lymph nodes.
Clinical Features:
Over 80% of cases are diagnosed from the results of a routine blood test, usually
taken for another reason.
- Enlargement of cervical, axillary or inguinal lymph nodes is the most frequent clinical sign.
- The nodes are usually non‐tender.
- Features of anaemia may be present and patients with thrombocytopenia may show bruising or purpura.
- Splenomegaly and, less commonly, hepatomegaly are common in later stages.
- Immunosuppression is often a significant problem resulting from hypogammaglobulinaemia and cellular immune dysfunction.
- Early in the disease course bacterial infections, such as sinus and chest infections, predominate but with advanced disease viral infections, especially herpes zoster and fungal infections are also seen.
- Patients should be vaccinated with a conjugated pneumococcal vaccine.
Lab Diagnosis:
Hematological investigation:
- Normochromic normocytic anaemia is present in later stages as a result of marrow infiltration or hypersplenism.
- Autoimmune haemolysis may also occur.
- Autoimmune haemolytic anaemia is most frequent but immune thrombocytopenia, neutropenia and red cell aplasia are also seen.
- Thrombocytopenia occurs in many patients and may also have an autoimmune basis.
Lymphocytosis:
- The absolute clonal B cell lymphocyte count is >5 × 109 /L and may be up to 300×109 /L or more.
- Between 70 and 99% of white cells in the blood film appear as small lymphocytes. ‘Smudge’ or ‘smear’ cells are also present.
- Smudge cells: “Circulating tumor cells are fragile and during the preparation of smears frequently are disrupted, producing characteristic smudge cells”.
Immunophenotyping:
- Immunophenotyping of the lymphocytes shows them to be B cells (surface CD19+).
- Characteristically, the cells are also surface CD5+ and CD23+ but are CD79b− and FMC7
Bone marrow:
- Aspiration shows up to 95% lymphocytic replacement of normal marrow elements.
- Trephine biopsy reveals nodular, diffuse or interstitial involvement by lymphocytes.
- Two surface proteins that can be detected by flow cytometry and have prognostic significance are CD38, a marker of differentiation, and ZAP70, a protein kinase involved in signalling process.
- Reduced concentrations of serum immunoglobulins are found and this becomes more marked with advanced disease. Rarely, a paraprotein is present.
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