logical Malignancies. Prstn

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3/19/12

HAEMATOLOGICAL

MALIGNANCIESOncology group presentation


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OUTLINE

Definition of haematologicalmalignancies

Definition of BM Classification of BM malignancies

ALL

CLL

AML

CML


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Introduction

The haematological malignancies areclonal diseases that derive from asingle cell in the marrow or

peripheral lymphoid tissue which hasundergone a genetic mutation

Represent approximately 7%of all

malignant disease

BM is the soft, spongy fatty vasculartissue which fill cavities of bones

responsible for production of


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Etiology

Exactly how genetic mutationsaccumulate in haematologicalmalignancies is largely unknown.

As in most diseases it is thecombination of genetic backgroundand environmental influence that

determines the risk of developing amalignancy.

However, in the majority of individual

cases neither a genetic susceptibility


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Etiology cont

Genetic factors :

incidence of leukaemia is greatly

increased in some genetic diseases,particularly Down's syndrome (whereacute leukaemia occurs with a 20 to30 fold increased frequency),

Bloom's syndrome, Fanconi'sanaemia, ataxia telangiectasia,Klinefelter's syndrome


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Etiology cont

Environmental influences

Chemicals eg. Benzene and otherindustrial solvents

Drugs eg. Alkyating agents(chlorambucil)

Radiation

Infections eg. HTLV-1, H.pylori


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Classification

Haematological malignancies arisefrom two major cell lineages i.e.myeloid and lymphoid

4 main types;

1. Acute lymphoblastic leukemia(ALL)

2. Chronic lymphoblasticleukemia(CLL)

3. Acute myeloid leukemia(AML)

4. Chronic myeloid leukemia(CML)


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Acute lymphoblasticleukemia

Is caused by anaccumulation/proliferation ofimmature lymphoid cells

(lymphoblasts) in the bone marrow It can arise from B or T lymphocytes

(85% arise from B cell)

Common malignancy of childhoodwith male predominance

Incidence highest at 3-7 yrs andthere is a secondar rise after a e of


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Clinical features

Bone marrow failure

Anemia(pallor,lethargy and

dyspnoea) Neutropenia(fever,malaise,mouth,ski

n,respiratory infections)

Thrombocytopenia(spontaneousbruises,purpura,bleedinggums,menorrhagia)


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Clinical features cont

Organ infiltration

Tender bones

Lymphadenopathy Moderate splenomegally

Hepatomegally

Meningeal syndrome(headache,nausea,vomiting,blurredvision)


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Diagnosis

FBP (anaemia, thrombocytopenia,leukopenia or leukocytosis)

Peripheral smear study-circulatingblasts can be seen

Biochemical tests(raised serum uric

acid, LDH) Confirmatory-bone marrow

aspiration/biopsy


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Diagnosis cont

Cytogenic analysis-may also beperformed on bone marrow specimento look for chromosomal

abnormalities associated withleukemia

Immunophenotyping -pathologist

look at specimen to see if leukemiaoriginates from B or T lymphocytes

Lumbar puncture


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Management

Supportive therapy (central venouscanula, blood products support;prevention of tumour lysis syndrome)

Specific therapy (chemotherapy,radiotherapy, chemotherapy withstem cell transplant)


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chemotherapy

Induction therapy: to bring aboutbone marrow remission. (vincristine,dexamethasone/prednisolone

,methotrexate, daunorubicin andasparaginase)

Consolidation/intensification therapy:

to eliminate any remaining leukemiacells and

Maintenance: (methotrexate and 6-

mecaptopurine)

Prognostic Factors Good Poor


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Prognostic Factors:

Prognostic Factors Good Poor

WBC Low High (>50x109/L)

Sex Girls Boys

Immunophenotype B-ALL T-ALL (in children)

Age Child ( 4 weeks

CNS disease atpresentation

Absent Present

Minimal residual disease Negative at 1-3 months Still positive at 3-6 months


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Chronic LymphocyticLeukemia (CLL)

most often affects adults over theage of 55

It sometimes occurs in youngeradults (15%), but it almost neveraffects children.

Two-thirds of affected people aremen. The male to female ratio of 2:1


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CLL

Is characterized by the accumulationof non-proliferating matureappearing lymphocytes

In most cases the cells aremonoclonal B lymphocytes

T cell CLL can occur rarely


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Etiology & Risk factors

High familial risk with two-fold toseven-fold higher risk.

No documented association withenvironmental factors.

No established viral etiology.


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Clinical findings

Most patients are asymptomatic

Most symptomatic patients haveenlarged lymph nodes (commonlycervical and inguinal). The lymphnodes are usually descret,movableand non tender

Splenomegally

Tonsillar enlargement

Hepatomegally (later stages)


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Lab findings

FBP-Lymphocytosis >4000cells/ L;anincrease in one type of white bloodcell, with mature appearing cells

Hypogammaglobulinemia seen>50%

Positive Combs test 30%

Immunophenotyping: B cells

Normocytic, normochromic Anaemia

in later stages


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Bone Marrow

Not required for diagnosis.

Recommended to estimate theextent for prognostic implications.

Diffuse infiltration has poorprognosis.


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3/19/12 J Mol Med 1999;

Cytogenetics

Deletions in chromosome 13 at q 14

Chromosome 11 at q22 or q23.

Trisomy-12. Less common are deletions in

chromosome 17 & 6.


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Treatment

The primary chemotherapeutic planis combination chemotherapy(CHOP-cyclophosphamide, doxorubicin,

vincristine and prednisolone) Radiotherapy

Bone marrow transplant


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The Rai Staging System

Stage 0 Lymphocytosis only (> 15,000/mm3)

Stage 1 Lymphocytosis and lymphadenopathy

Stage 2 Lymphocytosis and splenomegaly withor without lymphadenopathy

Stage 3 Lymphocytosis and anemia (Hgb


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Modified Rai Staging Low-risk: stage 0, MS > 13 years. Intermediate-risk: stage I & II with MS

about 8 years.

High-risk: stages III & IV with MSabout

3 years


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The Binet Staging System

Stage ANo anemia, nothrombocytopenia, =3 involvednodal areas

Stage CAnemia (Hgb < 10 g/dL)and/or thrombocytopenia (Plt

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