INTRODUCTION TO CHRONIC LEUKEMIA WHITE BLOOD CELLS MALIGNANCY

Lecture on the characteristics of chronic leukaemia on haematological perspective

1. NORASIDI RAFFIE
UNIVERSITI SELANGOR

2. CHRONIC LEUKAEMIA
Definition:
•Accumulation of malignant mature cells (immature cells) due to
clonal disorder of pluripotential stem cells .
•Classified as one of myeloproliferative disorders (myelodysplasia).
•Slower progression and difficult to cure.
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3. CHRONIC LEUKAEMIA
•It is characterized by the excessive build- up of relatively mature,
but still abnormal, white blood cells.
•Typically taking months or years to progress, the cells are
produced at a much higher rate than normal, resulting in many
abnormal white blood cells.
•Mostly occurs in older people but can occur in any age group.
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4. •Malignancy of the haemopoietic system
•Transformation of the pluripotent stem cell
•9;22 translocation giving rise to the Philadelphia (Ph’) chromosome
•Creation of a leukaemia specific mRNA (BCR-ABL)
•Resistance to apoptosis, abnormal signalling and adhesion
•Molecular diagnostics
•Molecular and cellular therapeutics
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CHRONIC MYELOCYTIC LEUKAEMIA

5. CHRONIC
MYELOCYTIC
LEUKAEMIA
6 subtypes:
1.Chronic Myeloid Leukemia, Philadelphia
(Ph) positive / Chronic granulocytic
leukaemia)
2.Chronic Myeloid Leukemia, Philadelphia
(Ph) negative
3.Juvenile Chronic Myeloid Leukemia
4.Chronic Neutrophilic Leukemia
5.Chronic Eosinophilic Leukemia
6.Chronic Myelomonocytic leukemia (CMML)
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6. CHRONIC MYELOID LEUKAEMIA
(CML)
•Chronic Myeloid Leukaemia, Philadelphia
(Ph) positive a.k.a Chronic granulocytic
leukaemia).
•Translocation of part of long arm
chromosome 22 (BCR gene) to the long arm
of chromosome 9 and reciprocal
translocation of part of long arm
chromosome 9 (ABL gene) to chromosome
22.
•This abnormality is called Philadelphia
chromosome.
•The five-year survival rate is 90%.

7. Cytogenetic Abnormality of CML:
The Ph Chromosome
1 2 3 4 5
6 7 8 10 119 12
13 14 15 16 17 18
19 20 21 22 x Y

8. LAB DIAGNOSIS
OF CML
1.Anaemia-
normochromic,
normocytic & mild
anisopoikilocytosis
2.Leukocytosis is usually >
50x10
9
/L & sometimes
up to 500 x10
9
/L
3.Increased circulating
basophils
4.Neutrophil Alkaline
Phosphatase (NAP)/
LAP/GAPA is invariably
low to negative
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9. •The GAPA/LAP activity in CML is very low, the cells here are completely
negative (left). GAPA activity is normal in normal peripheral blood (right)
– the brown segment denote positivity
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10. LAB DIAGNOSIS OF CML
5.Bone marrow appears hypercellular with granulopoietic
predominance including promyelocytes, myelocytes,
metamyelocytes, band and segmented neutrophil.
6.Cytogenetics analysis - karyotyping of chromosome shows
translocation between chromosomes 9 and 22 resulting
t(9;22)(q34;q11)
7.Serum vitamin B12 binding capacity are increased
8.Serum uric acid - increased
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11. Molecular Methods the Ph Chromosome
Fluorescence in situ hybridisation (FISH)
Interphase Metaphase
Courtesy of Charles Sawyers, UCLA.

12. •PBF in a patient with
CML. Often, the
numbers of basophils
and eosinophils, as well
as bands and more
immature myeloid cells
(metamyelocytes and
myelocytes) are
increased.
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13. CHRONIC MYELOID LEUKAEMIA (CML)

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14. Treatment
1.Chemotherapy - is a treatment which uses anti-cancer drugs to kill
cancer cells, or to stop them from multiplying. e.g., hydroxyurea,
alkylating agent busulphan, allopurinol, interferon-α
2.Interferon alpha - given by a small injection under the skin several
times a week. It normally helps to combat viral infections. It has
also been shown to help the immune system to combat cancer and
leukaemia cells.
3.Stem cell transplantation / BM transplant
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15. CHRONIC LYMPHOCYTIC LEUKAEMIA
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B- cell
(the most common ~95%)
T- cell
1. B-cell CLL 1.Large granular lymphocytic
leukemia - involve either T-cells or
NK cells
2. B-cell prolymphocytic
leukemia (B-PLL)
2.T-cell prolymphocytic leukemia (T-
PLL) - very rare and aggressive
3. Hairy cell leukemia
4. Plasma cell leukemia

16. Chronic Lymphocytic leukemia
Commonest
leukemia in the
western world
Clonal proliferation
of the B-
Lymphocytes
Disease of the
elderly
Younger patients
now seen
M:F ratio, 2:1CLL is highly variable
disorder
75% cases, diagnosis
by chance on a
routine blood test

17. Aetiology
Cause unknown
Not associated with radiation or exposure to
occupational hazards
Among the leukemias, CLL has the strongest tendency for familial incidence

18. CLINICAL
FEATURES
Most common in adults between 60-80 yrs, rare
before 40 yrs of age (the five-year survival rate is
75%).
Symmetrically enlargement of superficial lymph nodes
is the most frequent sign
Hepatosplenomegaly
Bacterial or fungal infections are common in later
stages because of immune deficiency & neutropenia
Thrombocytopenia may show bruising & bleeding
Loss of weight (L.O.W) and appetite (L.O.A)

19. Prognosis
Late-stage patients have usually progressive disease
Highly Variable for early-stage patients
•Refractory to treatment
•Infectious Complications
•Autoimmune complications
Significant subset of early stage eventually progress

20. Laboratory investigations
1.Lymphocytosis: the absolute lymphocyte count is 5x10
9
/L &
may be up to 300x10
9
/L or more.
2.PBF: Between 70- 90% of WBC shows small lymphocytes.
3.Thrombocytopenia
4.Anaemia
5.Bone marrow aspiration shows lymphocytic replacement of
normal marrow elements
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21. These mature leukemic lymphocytes are increased markedly in
number. They are indicative of chronic lymphocytic leukemia, a
disease most often seen in older adults.
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22. Laboratory investigations
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Immunological markers
•CD3- LGLL
•CD7-T-PLL
T-chronic lymphocytic leukemia
•CD5- BCLL
•CD 22- B-PLL
•CD79- HCL
B-chronic lymphocytic leukemia

23. Treatment
1.Chemotherapy (e.g., chlorambucil,
corticosteroids, purine analogues)
2.Radiotherapy
3.Immunoglobulin (Ig) replacement
4.Splenectomy
5.Stem cell transplantation

24. B-Hairy cell
leukemia
•These abnormal
lymphocytes are
intermediate cells
with abundant
cytoplasm and
villous cytoplasmic
projections. The
nuclei are round,
oval, or slightly
lobulated.
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25. Plasma Cell Leukemia (PCL)
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26. T-PLL
•PBF from patient with T-
PLL (May Grunwald
Giemsa stain).
•The lymphoid cells are
medium in size have an
irregular nucleus,
prominent nucleolus,
and basophilic
cytoplasm with
protrusions.
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27. L-GLL
•Examples of lymphocytes
with abundant cytoplasm
and eosinophilic
cytoplasmic granules.
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28. Lymphoma
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29. INTRODUCTION
•Lymphoma is a group of blood cell tumours that develop from lymphocytes (a type of
white blood cell).
•Lymphoma most often spreads to the lungs, liver, and brain.
•Lymphoma’s symptoms are like enlarged lymph nodes, fever, sweat, itching etc.
•The enlarged lymph nodes are usually painless.
•There are two types of lymphomas:
•Hodgkin’s lymphomas (Reed-Stenberg cells present)
•Non- Hodgkin lymphoma
•About 90% of lymphomas are non-Hodgkin lymphomas.
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30. SYMPTOMS
•Enlarged lymph nodes Or lymphadenopathy.
•B symptoms (systemic symptoms) - can be associated with both Hodgkin
lymphoma and non- Hodgkin lymphoma. They consist of :
•Fever
•Night Sweats
•Unintended weight loss
•Itching
•Feeling tired/fatigue.
•Anorexia or loss of appetite.
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31. RISK FACTORS
•Risk factors for Hodgkin lymphoma include:
•Infection with Epstein-Barr virus.
•History of the disease in the family.
•Risk factors for common types of non-Hodgkin lymphomas
include:
•Autoimmune disease.
•HIV/AIDS.
•Infection with human T- lymphotropic virus.
•Immunosuppressant medications.
•Pesticides.
•Tobacco smoking.
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32. TREATMENT
•Treatment may involve chemotherapy, medication, radiation therapy
and rarely stem-cell transplant.
•Medications
•Chemotherapy,
•Bone marrow stimulant,
•Steroid, and Blood transfusion
•Surgery
•Auto-transplantation
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33. References
1.Hoffbrand, A.V. and Petit, J.E., & Moss P.A.H. Essential
Haematology, 5
th
Edition, Blackwell Science Publications,
2003
2.Dacie and Lewis Practical Haematology. Lewis SM, Bain BJ,
Bates I. Ninth Edition. Churchill Livingstone, 2002.
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