CML.PPT,CHRONIC MYELOID LEUKEMIA:HEMATOLOGY

HEMATOLOGY:CML
CML HAS MADE EASY IN SLIDES

1. CHRONIC MYELOID
LEUKEMIA
BY : IVANA MARIYAM DEVASIA
M2162P

2. WHAT IS CML ?
CML is a clonal myeloproliferative disorder characterized by
Specific genetic abnormality i.e BCR-abl fusion gene
Leukocytosis with complete left shift
Basophillia
Hepatosplenomegaly
Thrombocytosis

3. EPIDEMIOLOGY
• CML-15% of all cases of Leukemia
• US Incidence ~ 2 per lakh persons for
men and 1.1 per lakh persons for women
• Sparse Indian data - 0.8-2.2/lakh in men
and 0.6- 1.6/lakh in women
• 50-70% of leukemias in India
• Male predominance (1.4:1)
• Average age at presentation - 50 yrs
• Incidence is least in Swedes

4. PATHOPHYSIOLOGY
• Genetic hallmark of CML is the presence of BCR-
ABL fusion gene product.
.The fusion protein is a result of reciprocal
translocation between the abelson oncogene on
chromosome 9 and break point cluster region on
chromosome 22.
• Fusion genes are generated that encode 190,210,
or 230 kda forms of the BCR-ABL tyrosine kinase.
Other genetic abnormalities LIKE :)
Trisomy 8,p53 loss.
• Interleukin 1 b involved in the progression of CML
to the blastic phase.

5. CLASSIFICATION
• Based on the presence or absence of
Philadelphia chromosome and the cell
precursors involved:
• 1.Classical CML with Philadelphia positive
• 2.CML without Philadelphia chromosome
• 3.CML of neutrophilic cell
• 4.CML of eosinophilic cell
• 5.CML of myelomonocyte
• 6. Juvenile CML

7. PHASES
The phases are based mainly on the number of immature WBC (blasts) blood or bone marrow.
1. Chronic phase
• less than 10% blasts in their blood or bone marrow.
• fairly mild symptoms (if any) and usually respond to standard treatments.
• Most patients are diagnosed in the chronic phase.
2. Blast phase (aka acute phase or blast crisis)
• 20% or more blasts
Large clusters of blasts are seen in the bone marrow.
• The blast cells have spread to tissues and organs beyond the bone marrow
These patients often have fever, poor appetite, and weight loss. In this phase the CML acts a lot like an acute
leukemia.

8. PHASES
3. Accelerated phase
Patients are considered to be in accelerated phase if any of the following are true:
•15% or more, but less than 30% blasts
•Basophils make up 20% or more of the blood
*Blasts and promyelocytes combined make up 30% or more of the blood
•Very low platelet counts (100 x 1,000/mm³or less) that are not caused by treatment
•New chromosome changes in the leukemia cells with the Philadelphia chromosome
*symptoms such as fever, poor appetite, and weight loss. CML in the accelerated phase doesn't
respond as well to treatment as CML in the chronic phase.

10. CLINICAL FEATURES
• At diagnosis - 70% symptomatic
• Easy fatigability
• Loss of sense of well-being
• Decreased tolerance to exertion
• Anorexia
• Abdominal discomfort
• Early satiety
• Weight loss
• Excessive sweating

11. CLINICAL FEATURES
• Uncommon symptoms
• Night sweats } thyrotoxicosis
Heat intolerance
• Gouty arthitis
• Left upper-quadrant and left shoulder pain*
• Urticaria
• Hyperleukocytic Syndrome -dyspnea,
tachypnea, hypoxia, lethargy, slurred speech
. Acute febrile neutrophilic dermatosis (sweat
syndrome)

12. SIGNS
• Pallor
• Splenomegaly
• Sternal tenderness
• Rarely hepatomegaly, lymphadenopathy -
Poor prognostic indicators

13. CLINICAL PRESENTATION
* CML is a malignant blood disorder
* Involves early hematopoietic cells Become clonally expanded.
* Disease originates from a single abnormal hematopoietic stem cell which proliferates over
months and years so that at diagnosis blood granulocytosis and marrow granulocytopoiesis
are apparent.
* The bone marrow becomes hypercellular.
* CML may be clinically categorized as follows

14. LAB DIAGNOSIS
1. CBC
2. Biochemical tests
3. Bone marrow
4. Immunological markers
5. Cytogenetic
6. Molecular assays

15. DIFFERENTIAL DIAGNOSIS
• Polycythemia vera
Essential thrombocythemia
Primary myelofibrosis
Leukemoid reactions

16. LAB INVESTIGATION
: 1. CBC : Blood cell count
WBC count ranges between 50 to 500 x109/1
Platelet count Thrombocytopenia Thrombocytosis
Laboratory finding:
Leukocytosis is usuallly > 50 ×109/L and some times
> 500×109/L
Hemoglobin: It is usually less than 11 gm/dL.
Increased circulating basophil count
Normocytic normochromic anaemia is usual
Platelet count may be increased normal or
decreased.

17. PERIPHERAL BLOOD FILM EXAMINATION
Normocytic, normochromic
anemia
Neutrophils show left shift
Eosinophils normal or some
time increased
• NRBCs are seen
• Absolute Basophilia

18. 2.BONE MARROW
Hypercellular
Increased M:E ratio i.e: 10:1
With mature neoplastic myeloid
Cells
Erythroid precursors decreased
Megakaryoblasts normal or
increased

19. • Immature myeloid precursor can be found away from bony
trabeculae
• Blasts not more than 10% in chronic phase
. Eosinophilic and basophilic granules are abnormal
• Nuclear to cytoplasmic asynchrony

20. BIOCHEMICAL FINDINGS
Serum Uric acid
Increased due to increased purine destruction
Serum iron
Increased
Serum B12 and B12 binding capacity
Increased
NAP score
Decreased
Serum LDH
Elevated
Ca++
Increase

21. IMMUNOLOGICAL MARKERS
• CD13 +
CD14 +
CD15 +
CD33 +

22. PROGNOSTIC FACTORS
Sokal index
Percentage of circulating blast, spleen size, platelet count, age and cytogenetic clonal
evolution.
Was developed based on chemotherapy treated patients.
Hassford system
Developed on interferon alpha treated patients.
Includes% of circulating blast, spleen size,platelet count,age,% of eosinophils and
basophils.

23. TREATMENT
1. Initial Cytoreduction Therapy
2. Tyrosine Kinase Inhibitor Therapy
3. Interferon therapy
4. Chemotherapy
5. Allogeneic Stem Cell Transplantation
6. Treatment of accelerated/blast phases
7. Treatment of CML in pregnancy
8. Treatment cessation

25. RISK FACTORS
• CML is more common in males than in females (male to
female ratio of 1.4:1) and appears more commonly in the
elderly with a median age at diagnosis of 65 years.
Exposure to ionising radiation appears to be a risk factor,
based on a 50 fold higher incidence of CML in Hiroshima
and Nagasaki nuclear bombing survivors. The rate of CML
in these individuals seems to peak about 10 years after the
exposure.

26. CONCLUSION
• Imatinib has revolutionized the
management of CML
• Long term survival is a reality
now
• TKI therapy is still not curative
• 3rd generation TKI and newer
drugs in the pipeline show some
promise at achieving a possible
cure

27. THANK
YOU