W4-LP-Chronic lymphocytic leukemia

Question 1

Differentiate between Chronic Lymphoid Leukemia (CLL) and Small lymphocytic lymphoma

Answer 1

CLL: Characterized primarily by an increase of the abnormal B-lymphocytes in the blood and bone marrow. It is typically diagnosed based on high levels of these cells in the blood.

SLL: Characterized by the accumulation of the same type of abnormal B-lymphocytes, but primarily in the lymph nodes and other lymphoid tissues rather than in the blood. Diagnosis is usually made by biopsy of an affected lymph node showing these abnormal cells.

Question 2

Has a peak incidence between 60-80 years with a mean age of diagnosis of 65. Incidence increases with age

Answer 2

CLL

Question 2

Most common leukaemia of adults in Western countries but very rare in the Far East.

Answer 2

Chronic Lymphoid Leukemia (CLL)

Question 2

What’s the criteria for diagnosing Chronic Lymphoid Leukemia?

Answer 2

• Criteria for diagnosis of CLL require ≥5x109/l monoclonal lymphocytes in the peripheral
  blood,
  -With a CLL phenotype (characteristic phenotypic markers identified through flow cytometry) for a period of at least 3 months

*Monoclonal: meaning they are derived from a single malignant B-cell clone.

Question 3

Features or characteristics of Chronic Lymphoid Leukemia

Answer 3

• Lack of Increased Incidence After Chemotherapy or Radiotherapy
• CLL has the highest genetic predisposition among hematological neoplasias: There is a notable familial risk, with first-degree relatives of patients having a seven-fold increased risk of developing CLL themselves.
• CLL B-cells typically express surface immunoglobulin (Ig) weakly. The weak expression might contribute to the dysfunctional immune response observed in CLL.
• The accumulation of CLL cells is primarily due to their prolonged lifespan rather than increased proliferation. This longevity is a result of impaired apoptosis, meaning the cells do not die off as they normally would.

Question 4

Lab diagnostics of CLL

Answer 4

• An absolute peripheral blood lymphocytosis of ≥5x109/l.
• Usually between 70 and
  99% of white cells are small lymphocytes. Smudge cells are also present. These
  are damaged lymphocytes because the CLL cells are particularly fragile.
• Immunophenotyping of the lymphocytes shows them to be B-cells weakly expressing surface immunoglobulin. They express only one form of light chain (κ or λ). PCR of the
  immunoglobulin heavy chain variable region would also give a single band on gel
  electrophoresis.
• Normochromic normocytic anaemia is present in later stages as a result of
  marrow infiltration or hypersplenism. At any stage autoimmune haemolysis may
  occur with the production of spherocytes – hyperchromic, microcytic anaemia.
• Bone marrow aspiration shows lymphocytic replacement of normal marrow elements.
• Immunologic abnormalities:
  -Immunosuppression:
  An increased susceptibility to viral and bacterial infections is often present.
  Altered cellular immunity, hypogammaglobulinaemia and an imbalance between TCD4 (helper) and T CD8 (suppressor) cells are frequent.

-Autoimmunity:
When autoantibodies are present, they are preferentially targeted against cells of the haemopoietic system. Autoimmune haemolytic anaemia is most common but immune thrombocytopenia, neutropenia and pure red
cell aplasia are also seen

Question 5

Discuss CLL tumour staging

Answer 5

The Rai and Binet clinical staging systems are used to define disease extent and prognosis. They are based on factors such as:
-the presence or absence of anaemia and thrombocytopenia,
-as well as the degree of involvement of lymphoid tissue

Question 6

Discuss the prognostic markers of CLL

Answer 6

• Cytogenetics abnormalities are discovered in at least 80% of cases by conventional
  cytogenetics or FISH analysis.
• Currently a microarray panel is used for evaluation of
  patients.
• The four most common chromosomal abnormalities are: deletion 13q24, trisomy
  12, deletions at 11q23 and structural abnormalities of 17p involving the p53 gene.
  *The chromosomal anomalies are of prognostic significance.

Question 7

Treatment techniques or procedures for CLL

Answer 7

Patients with advanced CLL need to be treated whereas those with asymptomatic, earlier
stage disease may be observed for disease progression (“watchful waiting”).

Treatment options include:
1. Chemotherapy
2. Monoclonal antibody therapy (anti-CD52 and anti-CD20).
3. Stem cell transplantation-allogeneic transplantation is a consideration for young
patients.