CLL

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