chronic myeloid leukemia & chronic lymphocytic leukemia

1. CML

2. DEFINITION
■ Myeloproliferative disorder
characterized by increased
proliferation of the granulocytic
cell line.
■ It is a clonal neoplastic
hematopoietic stem cell disorder as
evidenced by involvement of all
hematopoietic cell lines.

3. INCIDENCE
■ 40% of all leukaemias in Indian population.
■ Men >Women.
■ Mean age at diagnosis – fifth & sixth decades of life.

4. PATHOGENESIS
■ PHILADELPHIACHROMOSOME (Ph’) – t(9;22)(q34;q11) – BCR/ABL fusion gene.

5. STAGES
• Cells retain the capacity for differentiation and
maturation.
• 3-5 years.
• Responsive to chemotherapy.
CHRONIC
• Cells show increasing loss of differentiation and
maturation & increased proliferation.
• Few months.
• Resistant to chemotherapy
ACCELERATED
• Transformation to acute leukemia
• 2 to 6 months.
• Extremely resistant to chemotherapy.BLAST CRISIS

6. CHRONIC PHASE
■ Generalised weakness
■ Weight loss
■ Night sweats
■ Abdominal fullness
■ Easy bruisibilty
■ Spontaneous bleeding
■ Splenomegaly
■ Hepatomegaly
■ 40% - asymptomatic
CLINICAL FEATURES:

7.  LABORATORY FEATURES :
1. Peripheral Blood Examination:
• Mild to moderate anemia – normocytic
normochromic
• TLC - >100,000/cumm
• All stages if maturation are present – from
myeloblast to segmented neutrophils.
• Peaks of myelocytes and segmented neutrophils
seen.
• Blast cells < 10%.
• Basophils & eosinophils – mildly increased.
• Mild to moderate thrombocytosis.

8. 2. Bone Marrow Examination :
 Hypercellular
 Markedly increased granulopoiesis.
 Myeloid:Erythroid ratio – 10:1 to 50:1.
 Myeloblasts < 10%.
 Basophils, Eosinophils, Monocytes – increased.
 Megakaryocytes – increased in number, smaller in size, hypolobated nuclei.
 Pseudo-Gaucher cells & Blue Histiocytes may be seen.
3. Neutrophil Alkaline Phosphatase- NAP Score – decreased or absent (Normal- 40 to 100).
4. Cytogenetic Analysis – Ph’ chr, +8, +9, -Y.
■ Southern blot analysis, FISH, PCR.

9. ACCELERATED PHASE
■ IncreasedTLC despite treatment.
■ Blast cells – increased (10-19%) in PS and/or BM.
■ Basophilia >/= 20%.
■ Thrombocytopenia <1lac/cumm orThrombocytosis >10 lac/cumm.
■ Progressive splenomegaly.
■ Cytogenetic e/o Ph’ chr, +8 etc.

10. BLAST CRISIS
■ Blasts in peripheral blood or BM >/= 20%.
■ Blast proliferation at a site other than bone marrow.
■ Focal clustering of blasts in bone marrow.

11. PARAMETER CHRONIC ACCELERATED BLAST
1. Blast % < 10 % 10-19 % >/= 20%
2. Basophils < 20 % >/= 20 % Variable
3. Leucocytosis,
Thrombocytosis,
Splenomegaly
Responsive to therapy Not responsive to
therapy
-
4. LAP Score Low Increased Increased
5. Extramedullary
blast proliferation.
Absent Absent May be present
6. Clonal Evaluation - yes -

12. CLL

13. DEFINITION
■ A neoplastic disorder
characterised by monoclonal
proliferation of
immunologically incompetent,
slowly dividing, mature B-
lymphocytes.

14. INCIDENCE
■ CLL is the most common form of leukaemia in western countries, while it is the least
common type in India.
■ over 50 years of age (median age at presentation: 65–70 years).
■ It is twice as common in males as compared to females.
■ First-degree relatives of the patient have significantly increased risk of developingCLL
and other lymphoid malignancies.

15. CLINICAL FEATURES
■ Weakness
■ Fatigue
■ Weight loss
■ Repeated infections (due to hypogammaglobulinaemia)
■ Symptoms related to anaemia or thrombocytopaenia.
■ Generalised lymphadenopathy is the most common presenting feature
■ Mild to moderate splenomegaly is present in two-thirds of cases.
■ About 25% of patients are asymptomatic and are discovered incidentally on clinical or
laboratory examination.

16. LABORATORY FEATURES
1. PERIPHERAL BLOOD EXAMINATION:
■ Anaemia - normocytic and normochromic.
– Causes – progressive marrow replacement by tumor cells, hypersplenism and autoimmune
haemolysis.
■ Total leucocyte count - increased >50,000/cmm with >80% of cells being lymphocytes.
■ >90% of neoplastic cells are small, mature looking lymphocyteswith high N/C ratio, scanty
cytoplasm and dense, clumped chromatin. Nucleoli are not seen or are inconspicuous.
■ ‘Smudge’ or basket cells are a characteristic feature of CLL and are produced during spreading
of blood film because of fragility of lymphocytes.
■ Platelet count may be normal or decreased.
– Thrombocytopaenia becomes severe with progressive replacement of bone marrow by
leukaemic cells.
– Other causes are immune destruction of platelets and hypersplenism.

17. small, mature looking lymphocyteswith high N/C ratio, scanty cytoplasm and
dense, clumped chromatin. Nucleoli are not seen or are inconspicuous.

18. 2. BONE MARROW EXAMINATION:
■ lymphocyte > 30% - criteria for diagnosis.
3. IMMUNOPHENOTYPING:
■ CD19, CD20 (weak), CD5, CD23, weak surface membrane immunoglobulin, and
■ absent reactivity with FMC7 and with CD2.
4. CYTOGENETIC ANALYSIS:
■ FISH : 13q-, 11q-, trisomy 12, 17p-.
5. IMMUNOLOGICAL STUDIES:
■ Hypogammaglobulinaemia- in 2/3rd of patients.
■ M Band – 5% of patients.

19. THANKYOU