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Chronic Leukemia

Dr.Huad alkarim.Dr.Huad alkarim.

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What Are the Types of Chronic Leukemia?

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Classification of CL.

There are two types:There are two types:

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

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Chronic Myeloid Leukemia.

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Definition of CML:

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

Constitute six different types of leukemia.Constitute six different types of leukemia.

• See table. See table.

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Types of Chronic CML:

Type Type namename

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

22 (CML,Ph-)(CML,Ph-)

33 Juvenile CMLJuvenile CML

44 Chronic neutrophilic leukemia.Chronic neutrophilic leukemia.

55 Esinophilic leukemia Esinophilic leukemia

66 Chronic myelomonocytic leukemiaChronic myelomonocytic leukemia

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Cont:

The disease accounts for around 15% of leukemia. The disease accounts for around 15% of leukemia.

May occur at any age.May occur at any age.

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What Is Philadelphia Chromosome?

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Philadelphia :

Is the chromosome which result from the t(9;22)Is the chromosome which result from the t(9;22)(q34;q11)(q34;q11)part of the Abelson proto-oncogene part of the Abelson proto-oncogene ABL is moved to the BCR gene on chromosome 22 ABL is moved to the BCR gene on chromosome 22 & part of chromosome 22 moves to chromosome & part of chromosome 22 moves to chromosome 9.9.

The abnormal chromosome 22is the Ph.The abnormal chromosome 22is the Ph.

See fig.See fig.

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Fig

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How Would the Patient With CML Present?

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Clinical Presentation:

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

Symptoms related to hyper metabolism:Symptoms related to hyper metabolism:

(weight loss,lassitude,anorexia or night sweats).(weight loss,lassitude,anorexia or night sweats).

(Gout or renal impairment caused by (Gout or renal impairment caused by hyperuriceamia ).hyperuriceamia ).

Bone marrow failure:Bone marrow failure:

Anemia.Anemia.

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Cont:

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

Organ infiltration:Organ infiltration:

Splenomegally almost always present and is Splenomegally almost always present and is frequently massive.frequently massive.

Rare symptoms include visual disturbance.Rare symptoms include visual disturbance.

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

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Investigation:

CBC:CBC:

Wbc is usually >50X10/l & some times >500X10/l.Wbc is usually >50X10/l & some times >500X10/l.

Normocytic normochromic anemia.Normocytic normochromic anemia.

Platelets Platelets ..

peripheral blood filmperipheral blood film:: circulating basophil.circulating basophil.

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fig

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Cont:

Neutrophil alkaline phosphatase scoreNeutrophil alkaline phosphatase score is is invariably low.invariably low.

BM:BM: is hyper cellular with granulopoietic is hyper cellular with granulopoietic predominance.predominance.

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

capacity arecapacity are.. Serum uric acid is usuallySerum uric acid is usually..

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What Are the Phases of CML?…

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Phases of CML:

Chronic phase :Chronic phase : Accelerated phase:Accelerated phase: Blast phase:Blast phase:

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How Would You Treat CML?…

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Treatment:

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

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What Is the Course and Prognosis of CML?..

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Course & prognosis:

Usually shows excellent response to chemtherapy Usually shows excellent response to chemtherapy in the chonic phase.in the chonic phase.

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

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Take a Break !…

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Chronic lymphocytic Leukemia:

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Introduction:

CLL is the most common of the chronic lymphoid CLL is the most common of the chronic lymphoid leukemias.leukemias.

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

lymphocytosis which later infiltrate different lymphocytosis which later infiltrate different organs.organs.

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What Is the Clinical Presentation?

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Clinical presentation:

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

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

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

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Fig(1)

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Cont:

Splenomegaly & hepatomegaly usual in later Splenomegaly & hepatomegaly usual in later stage.stage.

Repeated bacterial or fungal infection.Repeated bacterial or fungal infection.

Thrombocytopenia.Thrombocytopenia.

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Fig(2)

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How would you investigate patient with CLL?..

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Investigation:

CBC:CBC:– WbcWbc::..– DiffDiff:lymphocytosis ,the absolute lymphocyte :lymphocytosis ,the absolute lymphocyte

count is>5x10count is>5x1099/l and may be up to 300x10/l and may be up to 300x1099/l or./l or.

More.More.

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

PlateletsPlatelets : thrombocytepenia may occur. : thrombocytepenia may occur.

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Cont:

Blood film:Blood film:

70-99% of white cells mature lymphocyte.70-99% of white cells mature lymphocyte.

Smudge or smear cells also present.Smudge or smear cells also present.

ImmunophenotypingImmunophenotyping::

Shows that the lymphocyte are B Shows that the lymphocyte are B cells(CD19)expressing one form of light cells(CD19)expressing one form of light chain(chain( or or only)cells are also only)cells are also CD5&CD23+ve.CD5&CD23+ve.

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Fig(3)

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Cont:

Bone marrow aspiration:Bone marrow aspiration:

Lymphocytic replacement of normal marrow.Lymphocytic replacement of normal marrow. Immunoglobulinelectrophoresis:Immunoglobulinelectrophoresis: of Ig more marker with advance disease.of Ig more marker with advance disease.• Cytogenetic :Cytogenetic :

The 4 most common abnormalities are; deletion The 4 most common abnormalities are; deletion of13q14,trisomy 12,deletion of11q23&structural of13q14,trisomy 12,deletion of11q23&structural abnormality of 17p involving the p53 gene.abnormality of 17p involving the p53 gene.

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What Is the Staging of CLL?…

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Staging :

Staging is very important for prognosis and Staging is very important for prognosis and treatment.treatment.

There are two staging system(Rai and Binet).There are two staging system(Rai and Binet).

See table.See table.

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A-Rai Classification:

Stage Stage definitiondefinition

00 Absolute lymphocytosis >15x10Absolute lymphocytosis >15x1099/l./l.

11 Stage 0+enlarged lymph nodes.Stage 0+enlarged lymph nodes.

1111 Stage 0+liver or/and spleen Stage 0+liver or/and spleen adenopathy. adenopathy.

111111 Stage 0+anemia Stage 0+anemia organomegally or adenopathy.organomegally or adenopathy.

1V1V Stage 0+thrombocytopenia Stage 0+thrombocytopenia organomegally or adenopathy.organomegally or adenopathy.

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B-Binet Classification:

Stage .Stage . OrganomegallyOrganomegally..

HbHb Platelet.Platelet.

A(50-60%)A(50-60%) 0,1,or2areas0,1,or2areas

B(30%)B(30%) 3,4,or 5areas3,4,or 5areas 1010 100100

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

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How Would You Treat Patient With CLL?…

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Treatment :

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

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

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Modality of Treatment:

1-chemotherapy:1-chemotherapy:Chlorambucil: 6mg/mChlorambucil: 6mg/m22 daily for 10 days monthly for 2-4 daily for 10 days monthly for 2-4

month after which remission will be obtain.month after which remission will be obtain.

Fludarabine:more effective as single agent.Fludarabine:more effective as single agent.

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

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Cont:

2-Radiotherapy:2-Radiotherapy:

Is useful in reducing the size of lymphnode not Is useful in reducing the size of lymphnode not responsive to chemo.responsive to chemo.

3-Monoclonal antibody:3-Monoclonal antibody:

Both campath IH(anti CD52)and Rituximab(anti Both campath IH(anti CD52)and Rituximab(anti CD20)produce response in proportion of patient.CD20)produce response in proportion of patient.

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Cont:

4-Splenectomy :4-Splenectomy :

For immune-mediated cytopenia or painful bulky For immune-mediated cytopenia or painful bulky splenomegally.splenomegally.

5-immunoglobulin replacement:5-immunoglobulin replacement:

250mg/kg /month by IV for patient with 250mg/kg /month by IV for patient with hypogammaglobulinemia and recurrent infection.hypogammaglobulinemia and recurrent infection.

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Cont:

5- Stem cell transplant:5- Stem cell transplant:

Under clinical trial.Under clinical trial.

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Good Luck!……..