This is a ppt containing basic overview of Chronic leukaemia. It was made for the education purpose of MBBS 2nd year students.

1. Chronic Leukemia
Dr Payal Desai

2. What is Leukemia ???
 Abnormal rapid monoclonal proliferation of
white blood cells in the blood and bone
marrow.
 Can be acute or chronic
 Can be Myeloid or Lymphoid

4. Topics that will be covered
 Chronic myeloid leukemia
 Chronic lymphocytic leukemia
- Definition
- Pathogenesis
- Clinical features
- Hematological changes
- Microscopic findings
- Immunophenotyping and genetics

5. Chronic Myeloid Leukemia (CML)
 It is clonal myeloproliferative neoplasm.
 Affected Age group: 25 – 60 years
 Peak in 4th and 5th decades

6. Common Pathogenesis
 Presence of mutated, constitutively activated
tyrosine kinases
leads to
growth factor–independent proliferation and
survival of marrow progenitors

8. 4 Major myeloproliferative
neoplasms
 Chronic myeloid leukemia
 Polycythemia vera
 Primary myelofibrosis
 Essential thrombocythemia

9. Pathogenesis of CML
 CML is distinguished from other
myeloproliferative disorders by the presence
of a chimeric
BCR-ABL gene
t(9,22)
BCR gene on chromosome 22
ABL gene on chromosome 9

10. Philadelphia Chromosome
t(9;22) (q34;q11)- BCR-ABL fusion protein
The Philadelphia ( Ph’ ) chromosome: reciprocal translocation
Also found
- B ALL
- AML

11. Formation of Philadelphia
chromosome and BCR/ABL fusion gene
product

12. Clinical Features
 Insidious onset
 Initially – easy fatigability, weakness and weight loss
 Splenomegaly – dragging sensation on abdomen
 Accelerated phase – Increased anemia
- thrombocytopenia
 Blast crisis – Severe anemia
- multiple lymphadenopathis
- hepatosplenomegaly

14. Investigations
 Complete Blood Count
 Peripheral smear and bone marrow examination
 Flow cytometry
 Karyotyping
 FISH
 RT-PCR

15. Haematological changes
 Peripheral blood
 Marked leucocytosis Usually > 100,000/mm3
 Elevated myelocyte count
 Blasts usually <3%
 Basophilia
 Eosinophilia
 Monocytosis
 Thrombocytosis (300-1000 x 10^9/L)

16. Peripheral blood smear
 RBC – Normocytic normochromic cells with few
macrocytes
 WBC – Total count is markedly raised
Differential count shows increased neutrophils,
basophils and eosinophils
Myelocytes 20-40%
Blast cell <10%
 Platelets – Increased count

17. Peripheral blood smear
Eosinophil
Neutrophil
Basophil

19. Haematological changes
Bone marrow
100% cellularity
Myeloid precursors with
maturation
↑ megakaryocytes
Variable fibrosis

22. Immunophenotyping
 Tumor cells are positive for CD13, CD33,
CD41, CD14, CD117, CD34 and HLA-DR
 Detected by flow cytometry and IHC

23. Diagnosis of CML
 Complete Blood Count
 Peripheral smear and bone marrow
examination
 Karyotyping
 FISH
 RT-PCR

24. Targeted therapy
 BCR-ABL inhibitor, imatinib, results in
sustained hematologic remissions in greater
than 90% of patients
 Nilotinib
 Dasatinib

26. Chronic Lymphoid neoplasms

27. LYMPHOID NEOPLASMS
(WHO Classification)
 Precursor B-cell and T cell lymphoblastic
leukemia (ALL)
 Peripheral B-cell neoplasms (neoplasms of
mature B cells)
 Precursor T-cell neoplasms (neoplasms of
immature T cells)
 Peripheral T-cell and NK-cell neoplasms
(neoplasms of mature T cells and NK cells)
 Hodgkin lymphoma (neoplasms of Reed-Sternberg
cells and variants)

29. Chronic lymphocytic leukemia
 Chronic lymphocytic leukaemia (CLL) is a neoplastic disorder
characterised by monoclonal proliferation of mature B-
lymphocytes.
 Most common leukemia in adults of Western world
 Age affected > 50 years (median 60 years)

30. Pathogenesis
Increase activity of
B cell receptor
(BCR)
Survival and
proliferation of B
cells

31. Clinical features
 Mostly nonspecific
 Easy fatigability
 Weight loss
 Generalized lymphadenopathy and
hepatosplenomegaly (50-60%)
 Increased susceptibility to infections
(hypogammaglobulinemia)

32. Investigations
 Complete Blood Count
 Peripheral smear and bone marrow examination
 Flow cytometry
 Karyotyping
 FISH
 RT-PCR

33. Haematological findings
B cell lymphocytosis (> 5 x 10^9/L)
>90% cells are lymphocytes in smear
Bone marrow: - increased cellularity
- >30% lymphocytes
- decreased normal
hemopoietic precursors

34. Peripheral blood smear
 RBC – Normocytic normochromic
(May show presence of spherocytes)
 WBC – Total count is markedly raised
Differential count shows lymphocytosis
Smudge cells are seen
 Platelets – Adequate
(may decrease in advanced cases)

37. Immunophenotyping
 Tumor cells are positive for
 CD19
 CD23
 CD5
 CD 27

38. Quick revision
 What is Leukemia ?
 What are myeloproliferative neoplasms ? Name 4
 What is the pathogenesis of CML ?
 What are the phases of CML ?
 What investigations can be done in CML/CLL ?
 Peripheral smear findngs of CML
 WHO classification of lymphoid neoplasms
 What are the peripheral smear findings of CLL ?

39. Write the PBF for this smear

40. Write the PBF for this smear