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CHILDHOOD LEUKAEMIA

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LEUKAEMIA

Heterogenous group of malignant disorders

Characterised by uncontrolled clonal proliferation

Accumulation of blasts cells in the bone marrow and body tissues

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CLASSIFICATION

Acute Acute lymphoblastic leukemia (T-ALL &

B-ALL) Acute myeloid leukemia

Chronic Chronic myeloid leukemia Chronic lymphocytic leukemia

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ACUTE LYMPHOBLASTIC LEUKAEMIA

A malignant (clonal) disease of the bone marrow in which early lymphoid precursors (blast cells) proliferate and replace the normal hematopoietic cells of the marrow.

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ALL

Cancer of the blood affecting the LYMPHOCYTES.

85% of childhood leukaemia Commonest in the age 2-10 years Peak at 3-4 years. Commoner among males than females

(1.2:1) Commoner among whites than blacks

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EPIDEMIOLOGY

In the US, ALL forms about 25% of all childhood cancers.

In Enugu, ALL formed 7.6% of all childhood cancers

Incidence is reported to be on the increase world wide for no known reason

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AETIOLOGY

Exact aetiology is unknown Genetic predisposition include: Down syndrome Neurofibromatosis Ataxia-telangiectasia

Environmental predisposition include: Exposure to tobacco smoke Exposure to pesticide Exposure to ionizing irradiation

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PATHOPHYSIOLOGY

The malignant cells of ALL are lymphoid precursor cells (ie, lymphoblasts) that are arrested in an early stage of development.

This arrest is caused by an abnormal expression of genes, often as a result of chromosomal translocations.

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PATHOPHYSIOLOGY

The lymphoblasts replace the normal marrow elements, resulting in a marked decrease in the production of normal blood cells.

Consequently, anemia, thrombocytopenia, and neutropenia occur to varying degrees.

The lymphoblasts also proliferate in organs other than the marrow, particularly the liver, spleen, and lymph nodes.

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CLINICAL FEATURES

Bone pains (Commonest) Arthritis and arthralgia Generalized Lymphadenopathy Hepatomegaly & Splenomegaly Enlarged thymus anterior mediastinal mass Easy bruising Severe anaemia Increased susceptibility to infections Testicular swelling

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MANAGEMENT

1.   Full blood count Reduced haemoglobin &

normochromic, normocytic anaemia, WBC

<1.0x109/l to >200x109/l, neutropenia and blast cells

Thrombocytopenia (<100x109/l).

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INVESTIGATIONS

2. Bone marrow aspiration and trephine biopsy

· confirm acute leukaemia

(blast > 30%) usually hypercellular

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INVESTIGATIONS

3. Cytochemical staining

)A Peroxidase :- * negative ALL * positive AML

B) Periodic acid schiff

*Positive ALL

* Negative AML

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INVESTIGATIONS

4.Immunophenotyping

· identify antigens present on the blast cells

· determine whether the leukaemia is lymphoid or myeloid

· differentiate T-ALL and B-ALL

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INVESTIGATIONS

5. Chest radiography ·   mediastinal mass - present in up to 70% of

patients with T -ALLIn childhood ALL bone lesions may also seen.

6.Lumbar puncture initial staging inv. to detect leukaemic cells

in the cerebrospinal fluid, indicating involvement of the CNS

Done in acute lymphoblastic leukemia

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MANAGEMENT

SUPPORTIVE CARE Blood support :- Platelet con. for bleeding episodes or if the platelet

count is <10x109/l with fever Fresh frozen plasma if the coagulation screen

results are abnormal Packed red cell for severe anaemia (caution : if

white cell count is extremely high) Antibiotic therapy if infections are suspected

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MANAGEMENT

Cytotoxic therapy involves 4 stages: Remission induction Intensification & consolidation Maintenance therapy CNS prophylaxis Combined therapy to forestall the

prevention of resistant leukaemic cells Therapy takes 2 to 3 years

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MANAGEMENT

REMISSION Defined as absence of lymphadenopathy,

presence of normal peripheral blood counts, blast cells <5% in the bone marrow.

Drugs used: Vincristine, Prednisolone, L-asparaginase and IT Methotrexate, hydrocortisone & cytosine arabinoside

98% of cases achieve remission within 4 weeks of therapy

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MANAGEMENT

CONSOLIDATION THERAPY Aimed to consolidate the gains of induced

remission to further eliminate remaining leukaemic cells

This has been shown to improve outcome Higher doses of drugs previously used for

induction of remission are used Several cycles of high dose Methotrexate,

doxorubicin or pulses of L-asparaginase.

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MANAGEMENT

MAINTENANCE THERAPY Weekly Methotrexate Daily 6-Metacarptopurine Pulses of Vincristine & Prednisolone

Duration: 2 to 3 years

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MANAGEMENT

CNS THERAPY The CNS is a sanctuary site for leukaemic

cells, hence specific treatment need to be directed at the CNS

Radiation is effective but flawed by many morbidities (so limited to children with high risk)

Intra-thecal high dose cytotoxic drugs (Methotrexate, Cytosine arabinoside/ Hydrocortisone) are equally effective

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PROGNOSIS

70% of cases are curable with chemotherapy and bone marrow transplantation

Poor prognostic factors: Age <1 year or >10 years High WBC count (>50,000/mm3) T-Cell ALL High Haematocrit (PCV >30%)