Chronic Lymphocytic Leukemia:
Median age at presentation is 55y and there is 5:1 male predominace. Essentials of diagnosis include B-Cell Lymphocytosis > 5000/mcL and Co-Expression of CD19 and CD5
Immunophenotyping in CLL:
Usually Venous Blood Sample (for WBCs) is taken; Bone Marrow & Lymphnode specimen can also be used.
Co-Expression of CD19 (B- Lymphocyte Lineage Marker) with CD5 (T-Lymphocyte Marker). This finding is only observed in CLL and Mantle cell lymphoma. CLL is distinguished from Mantle cell lymphoma by expression of CD23
Most cases of early indolent CLL require no specific therapy, and the standard of care for early stage disease has been observation. Indications for treatment include:
· Progressive fatigue
· Symptomatic lymphadenopathy
The initial treatment of choice for patients younger than 70 years old without significant comorbidities is the combination of Fludarabine plus rituximab, with or without the addition of cyclophosphamide
Combination of bendamustine with rituximab is another reasonable choice of therapy
For older or frail patients, chlorambucil, 0.6–1 mg/kg, a well-tolerated agent given orally every 3 weeks for approximately 6 months, has been the standard therapy.
The novel monoclonal antibody, obinutuzumab, in combination with
chlorambucil produces a significant number of responses (75%) including elimination of disease at the molecular level (in 17%)
Rai Staging System
Absolute lymphocytosis (>15,000/mm3)
(without adenopathy, hepatosplenomegaly, anemia, or thrombocytopenia.)
Hepatomegaly or Splenomegaly
Anemia (hemoglobin <11 g/dL)
Clinical stage A*
Less than three areas of lymphoid involvement
no anemia or thrombocytopenia (Rai stages 0, I, and II).
Clinical stage B*
Three or more areas of lymphoid involvement
no anemia or thrombocytopenia (Rai stages I and II).
Clinical stage C
Anemia and/or thrombocytopenia regardless of the number of areas of lymphoid enlargement (Rai stages III and IV).
*[Note: Lymphoid areas include cervical, axillary, inguinal, and spleen.]
The Binet classification integrates the number of nodal groups involved with the disease with bone marrow failure. Its major benefit derives from the recognition of a predominantly splenic form of the disease, which may have a better prognosis than in the Rai staging, and from recognition that the presence of anemia or thrombocytopenia has a similar prognosis and does not merit a separate stage. Neither system separates immune from nonimmune causes of cytopenia. Patients with thrombocytopenia or anemia or both, which is caused by extensive marrow infiltration and impaired production (Rai III/IV, Binet C) have a poorer prognosis than patients with immune cytopenias.
High Risk Molecular Markers:
Elevated beta 2 microglobulin, LDH, sCD23
High Risk Cytogenetics:
Good Risk Cytogenetics:
We can divide patients in to two groups , Low risk or High risk having following parameters
Overall Survival 7-10 years
Doubling Time > 12 months
Overall Survival 2-5 years
High risk molecular/cytogenetic changes
Doubling Time < 12 months
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