Chronic leukemias

1

Chronic Leukemia

2

What Are the Types of Chronic Leukemia?

3

Classification of CL.

There are two types:

1-chronic myeloid leukemia. 2-chronic lymphoid leukemia.

4

Chronic Myeloid Leukemia.

5

Definition of CML:

Is a clonal disorder of a pluripotent stem cell and is classified as one of the myeloproliferative disorder.

Constitute six different types of leukemia.

• See table.

6

Types of Chronic CML:

Type Name

1 (CML,Ph+)(chronic granulocytic leukemia)

2 (CML,Ph-)

3 Juvenile CML

4 Chronic neutrophilic leukemia.

5 Esinophilic leukemia

6 Chronic myelomonocytic leukemia

7

Cont:

The disease accounts for around 15% of leukemia.

May occur at any age.

8

What Is Philadelphia Chromosome?

9

Philadelphia :

Is the chromosome which result from the t(9;22)(q34;q11)part of the Abelson proto-oncogene ABL is moved to the BCR gene on chromosome 22 & part of chromosome 22 moves to chromosome 9.

The abnormal chromosome 22is the Ph.

See fig.

10

Fig

11

How Would the Patient With CML Present?

12

Clinical Presentation:

It can occur in any age .But the most age presentation is between 40-60.

Symptoms related to hyper metabolism:(weight loss,lassitude,anorexia or night

sweats).(Gout or renal impairment caused by

hyperuriceamia ).Bone marrow failure:Anemia.

13

Cont:

Bruising ,epistaxis,menorrhagia or hemorrhage from any site because of platelet dysfunction.

Organ infiltration:Splenomegally almost always present and is

frequently massive.Rare symptoms include visual disturbance.

14

How Would You Investigate the Patient With Suspected CML?….

15

Investigation:

CBC:Wbc is usually >50X10/l & some times

>500X10/l.Normocytic normochromic anemia.Platelets .

peripheral blood film:Ý circulating basophil.

16fig

17

Cont:

Neutrophil alkaline phosphatase score is invariably low.

BM: is hyper cellular with granulopoietic predominance.

Cytogenetics: ph chromosome.Serum vitamin B12 & vitamin b12-binding

capacity are.Serum uric acid is usually.

18

What Are the Phases of CML?…

19

Phases of CML:

Chronic phase :Accelerated phase:Blast phase:

20

How Would You Treat CML?…

21

Treatment:

Chemotherapy:Tyrosine kinase inhibitor:Interferon-.Stem cell transplant.

22

What Is the Course and Prognosis of CML?..

23

Course & prognosis:

Usually shows excellent response to chemtherapy in the chonic phase.

Death usually occur from terminal acute trasformation ,hemorrhage or infection.

24

Chronic lymphocytic Leukemia:

25

Introduction:

CLL is the most common of the chronic lymphoid leukemias.

Peak incidence between 60-80yrs.It is characterize by chronic persistent

lymphocytosis which later infiltrate different organs.

26

What Is the Clinical Presentation?

27

Clinical presentation:

The disease occurs in older subject,rare before 40yrs.

M:F is 2:1.Many cases discover routinely.Symmetrical enlargement of superficial

lymph node is the most frequent clinical sign.Feature of anemia.

28

Fig(1)

29

Cont:

Splenomegaly & hepatomegaly usual in later stage.

Repeated bacterial or fungal infection.

Thrombocytopenia.

30

Fig(2)

31

How would you investigate patient with CLL?..

32

Investigation:

CBC: Wbc:. Diff:lymphocytosis ,the absolute lymphocyte count

is>5x109/l and may be up to 300x109/l or.More.

Anemia:normocytic normochromic anemia is present in later stages,autoimmune haemolysis.

Platelets : thrombocytopenia may occur.

33

Cont:

Blood film:70-99% of white cells mature lymphocyte.

Smudge or smear cells also present.Immunophenotyping:Shows that the lymphocyte are B cells(CD19)expressing

one form of light chain( or only)cells are also CD5&CD23+ve.

34

Fig(3)

35

Cont:

Bone marrow aspiration:Lymphocytic replacement of normal marrow.

Immunoglobulinelectrophoresis:¯ of Ig more marker with advance disease.• Cytogenetic :The 4 most common abnormalities are;

deletion of13q14,trisomy 12,deletion of11q23&structural abnormality of 17p involving the p53 gene.

36

What Is the Staging of CLL?…

37

Staging :

Staging is very important for prognosis and treatment.

There are two staging system(Rai and Binet).

See table.

38

A-Rai Classification:

Stage definition

0 Absolute lymphocytosis >15x109/l.

1 Stage 0+enlarged lymph nodes.

11 Stage 0+liver or/and spleen adenopathy.

111 Stage 0+anemia organomegally or adenopathy.

1V Stage 0+thrombocytopenia organomegally or adenopathy.

39

B-Binet Classification:

Stage . Organomegally.

Hb Platelet.

A(50-60%) 0,1,or2areas

B(30%) 3,4,or 5areas 10 100

C(<20%) Not considered <10 and /or <100

40

How Would You Treat Patient With CLL?…

41

Treatment :

Since cure is rare,the treatment aim is only symptoms control.

Indication for treatment: Troublesome organomegaly. Hemolytic episodes. Bone marrow suppression.

42

Modality of Treatment:

1-chemotherapy:Chlorambucil: 6mg/m2 daily for 10 days monthly for

2-4 month after which remission will be obtain.

Fludarabine:more effective as single agent.

Corticosteroid :indicated in bone marrow failure,also indicated in autoimmune hemolytic anemia and thrombocytopenia.

43

Cont:

2-Radiotherapy:Is useful in reducing the size of lymphnode not

responsive to chemo.3-Monoclonal antibody:Both campath IH(anti CD52)and

Rituximab(anti CD20)produce response in proportion of patient.

44

Cont:

4-Splenectomy :For immune-mediated cytopenia or painful

bulky splenomegally.

5-immunoglobulin replacement:250mg/kg /month by IV for patient with

hypogammaglobulinemia and recurrent infection.

45

Cont:

5- Stem cell transplant:Under clinical trial.

46

Good Luck!……..