Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of mature looking lymphocytes in the blood, bone marrow, and lymph nodes. It is most common in older adults over age 50 and is more prevalent in males. The disease has both genetic and environmental etiologies. Diagnosis is based on sustained lymphocytosis in the peripheral blood and bone marrow infiltration of greater than 30% lymphocytes that are monoclonal B-cells. Prognosis depends on disease stage and characteristics like genetic abnormalities, with early stage disease associated with more favorable outcomes.

1. CHRONIC LYMPHOBLASTIC
LEUKEMIA
D R M U S T A F A A L I

2. CHRONIC LYMPHOBLASTIC LEUKEMIA
Definition
Epidemiology
Etiopathogenesis
Classification
Diagnosis

3. Definition
Accumulation of mature
looking lymphocytes in the
peripheral blood, bone marrow
and lymph nodes

4. Epidemiology
Commonest in USA and EUROPE
Very low in ASIA
Age- old age >50 year
Sex- preponderance in male
M:F ratio 2:1
1/3 cases are asymptomatic

5. Etiopathogenesis
Genetic
Cytokines
(1) TNF- α
(2) TGF- β
(3) IL- 2

6. Clinical features
 Fatigue
 Lymphoadenopathy
 Pallor
 Splenomegaly
 Hepatomegaly
 Sternal tenderness
 Patechial hemorrhage / bruising
 Skin rash

7. Diagnosis
 Criteria proposed by International CLL
workshop
 (1) PERIPHERAL BLOOD :- a sustained
lymphocyte count of >10x109 / L
 (2) BONE MARROW :- >30% lymphocytes
 (3) MONOCLONAL B-CELLS :- mature
lymphocytes in blood are monoclonal B-
cells.

8. Diagnosis
For diagnosis of CLL
(1) Criteria 1 and 2 or 3 should be
present
(2) If lymphocytes count is <10x109 /L,
then criteria 2 and 3 must be present

9. Peripheral blood smear
 Hb decreased <13 g/dl
 TLC increased 20,000-5,00,000 /L
 DLC lymphocytosis >15,000 /L
 >50% -98% of white cells
 Mature lymphocyte small with a very thin rim
of cytoplasm
 Notching of nuclei in few cells
 Basket cells or Smudge cells
 Neutropenia
 coomb’s test positive in 10-20% cases

12. Bone marrow
 Hyper cellular
 Myelopoisis :- normal
 Erythropoisis :- normal normoblastic
reaction
 Megakaryopoisis :- normal in initial stages
 Lymphocytic infiltrate :- >30% of the
nucleated cells of marrow are mature
lymphocytes and is diagnostic features of
CLL marrow

13. Immunophenotyping
 Helpful when lymphocytosis <5,000/cmm
or atypical lymphocytes
 Pan B cell marker CD19+, CD20(weakly+) ,
CD21+,CD23+
 CD2-, FMC7-
 Single light chain (either к or λ expressed on
surface of cells

14. Cytogenetic analysis
Common abnormalities
(FISH technique)
13q-
11q-
Trisomy 12
17p-

15. Immunological study
M band :- 5% cases
Hypogammaglobulinaemia :- ⅔rd cases

16. Staging system
 Binet stages
 A :- <3 Iymphoid areas
enlarged
 B :- ≥3 Iymphoid areas
enlarged
 C :- Anaemia
(Haemoglobin <10
gm/dI) and/or
thrombocytopaenia
(Platelet count
<1lac/cmm)
 Rai stages
 O :- Lymphocytosis
only
 I :- Lymphadenopathy
 II :- Hepatomegaly
and / or
splenomegaly ±
Iymphadenopathy
 III :- Haemoglobin
< 11gm / dl
 IV :- Platelet count
<1,00,000 /cmm.

17. Prognostic factors
 Low risk
 Early stage disease (Binet :-
A, Rai :- 0,I)
 Predominance of small
mature lymphocytes
 Interstitial or nodular
marrow infiltration
 Normal Karyotype or 13q-
 Antigen CD38-
 Normal β2 microglobulin
 Mutated IgVH gene
 LDT > 12 months
 High risk
 Advanced stage disease
(Binet :-B, C; Rai :- II, III,
IV)
 >10% prolymphocytes
 Diffuse marrow infiltration
 11q-, 12+, 17p-
 Antigen CD 38+
 Elevated β2 microglobulin
 Nonmutated Ig Vн gene
 LDT < 12 months

18. Complication
 Infections :- Bacterial, viral and fungal
 Autoimmune hemolytic anemia
 Thrombocytopenic purpura
 Second malignancy :- skin and solid tumor
 Aggressive transformation
(1) Richter’s syndrome
(2) Prolymphocytic leukemia
(3) Multiple myeloma
(4) Acute lymphoid leukemia