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Chronic Lymphocytic Leukemia (CLL)

This is the most common variety of leukaemia, occurs in elderly person. CLL constitutes 25% of all leukaemia. Transformation into ALL is not a feature

Clinical Features (Mostly asymptomatic)
Weight loss stage, infection, bleeding, enlarged rubbery nontender nodes, hepatosplenomegaly.
Stages of CLL








Increase TLC






Investigations diagnosis on routine blood test
  1. Mild anemia: Coombs’ positive hemolytic anemia it occurs due to warm antibody present in CLL.
  2. WBC count: 50,000 to 200,000/ml. The cells are small B cell lymphocytes (Absolute lymphocytosis). 
  3. Platelet count is, normal or reduced.
  4. Total proteins and immunoglobulin levels are low as B lymphocytes fail to produce antibodies.

Genetic abnormality


1. Deletion on long arm of chromosome 13 (13q - 14): = Good prognosis
2. Chromosome 11 deletion (11q, 22-23 deletion), = bulky Lymphadenopathy = Poor prognosis
3. Chromosome 17 deletion (17 P 21 deletion) = Poor prognosis
4. Chromosome 12 trisomy (trisomy 12) = Intermediate prognosis


Extra Edge:


The interphase cytogenetics by FISH can accurately detect chromosomal abnormalities in more than 80% of all cases.

CLL = CD5 + CD19 +, CD23 + (Co expression of CD5 + CD19).


CLL whose cell of origin has the mutated IgVH : Good prognosis


CLL whose cell of origin has the un-mutated IgVH : Poor prognosis

Prognostic factors

IgVH = mutation in variable reason of heavy chain.

Table - Staging of Typical B Cell Lymphoid Leukemia
Stage Clinical Features Median Survival, Years
RAI System
0: Low risk Lymphocytosis only in blood and marrow >10
I: Intermediate risk Lymphocytosis + lymphadenopathy + splenomegaly ± hepatomegaly 7
III: High risk Lymphocytosis + anemia 1.5
IV Lymphocytosis + thrombocytopenia  
Binet System
A Fewer than three areas of clinical lymphadenopathy; no anemia or thrombocytopenia >10
B Three or more involved node areas; no anemia or thrombocytopenia 7
C Hemoglobin ≤10 g/dL and/or platelets <100,000/μL ffs

Pathology:  M/E pseudofollicular pattern with proliferative centre.
Rx: Chlorambucil

Newer Drugs
  1. Fludarabine
  2. Rituximab (AIIMS May 2008)
  3. Alemtuzumab

Rituximab is also effective in the treatment of lymphoma and rheumatoid arthritis. It is a anti CD-20 drug. (AIIMS May 2008)


Recent Advances - New Drug


Alemtuzumab is a monoclonal antibody. It is used in treatment of B-cell CLL in patients who have been treated with alkylating agents and who have failed fludarabine therapy. It is also effective in CD-52 expressing lymphoid tumor.

  1. Trastuzumab – CA breast             
  2. Cetuximab – Ca colon, Squamous cell carcinoma of Head and Neck.
  3. Panitumumab – Ca colon             
  4. Bevacizumab – Cancer of Lung, colon breast.


Lymphoid Disorders that Can Present as "Chronic Leukemia" and can be Confused with Typical B Cell Chronic Lymphoid Leukemia (Ref. Hari. 18th ed., Pg-919, table 110.1)

  1. Follicular lymphoma
  2. Splenic marginal zone lymphoma
  3. Nodal marginal zone lymphoma
  4. Mantle cell lymphoma
  5. Hairy cell leukemia
  6. Prolymphocytic leukemia (B cell or T cell)
  7. Lymphoplasmacytic lymphoma
  8. Sézary syndrome
  9. Smoldering adult T cell leukemia/ lymphoma


  1. It is a human monoclonal antibody (for the CD20 protein).
  2. It inhibit early-stage B lymphocyte activation.
  3. Uses
    1. It is for treating chronic lymphocytic leukemia that is refractory to fludarabine and alemtuzumab
    2. In treating follicular non-Hodgkin’s lymphoma, diffuse large B cell lymphoma
    3. Rheumatoid Arthritis
    4. Relapsing remitting multiple sclerosis.
Important Points

Mantle cell lymphoma

  1. Age: Middle – Elderly
  2. Cells +ve for PAN B marker CD19, CD2, CD22, CD24, CD5,
  3. Cell –ve for CD23, CD10,
  4. Ig: Increased are IgM, IgD
  5. Translocated: t (11:14) it lead to increased expression of cyclidin D1, (Cyclidin D1 +ve)


Co expression of B cell lineage marker CD19 + T cell marker CD5 in CLL & mantle cell.
  CD5 CD19 CD23 CD79b Cyclin D FM7
Mantle cell ++ ++ - ++ ++ ++
CLL ++ ++ ++ - - -

Ki-67 is an indicator of how fast cells mature and is expressed in a range from about 10% to 90%. The lower the percentage, the lower the speed of maturity, and the more indolent the disease.

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