CHILDHOOD LEUKAEMIA

1. CHILDHOOD LEUKAEMIA TA OGUNLESI (FWACP)

2. LEUKAEMIA • Heterogenous group of malignant disorders • Characterised by uncontrolled clonal proliferation • Accumulation of blasts cells in the bone marrow and body tissues TA OGUNLESI (FWACP)

3. CLASSIFICATION • Acute • Acute lymphoblastic leukemia (T-ALL & B-ALL) • Acute myeloid leukemia • Chronic • Chronic myeloid leukemia • Chronic lymphocytic leukemia TA OGUNLESI (FWACP)

4. 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. TA OGUNLESI (FWACP)

5. 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 TA OGUNLESI (FWACP)

6. 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 TA OGUNLESI (FWACP)

7. 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 TA OGUNLESI (FWACP)

8. 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. TA OGUNLESI (FWACP)

9. 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. TA OGUNLESI (FWACP)

10. 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 TA OGUNLESI (FWACP)

11. MANAGEMENT 1.Full blood count • Reduced haemoglobin& normochromic, normocytic anaemia, • WBC <1.0x109/l to >200x109/l, neutropenia and blast cells • Thrombocytopenia (<100x109/l). TA OGUNLESI (FWACP)

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14. INVESTIGATIONS 2. Bone marrow aspiration and trephine biopsy • confirm acute leukaemia (blast > 30%) • usually hypercellular TA OGUNLESI (FWACP)

15. INVESTIGATIONS 3. Cytochemical staining A) Peroxidase :- • * negative ALL • * positive AML B) Periodic acid schiff *Positive ALL * Negative AML TA OGUNLESI (FWACP)

16. INVESTIGATIONS 4.Immunophenotyping · identify antigens present on the blast cells • determinewhether the leukaemia is lymphoid or myeloid • differentiate T-ALL and B-ALL TA OGUNLESI (FWACP)

17. INVESTIGATIONS 5. Chest radiography ·   mediastinal mass - present in up to 70% of patientswith T -ALL In childhood ALL bone lesions may also seen. 6.Lumbar puncture • initial staging inv. to detect leukaemic cells in thecerebrospinal fluid, indicating involvement of the CNS • Done in acute lymphoblastic leukemia TA OGUNLESI (FWACP)

18. 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 resultsare abnormal • Packed red cell for severe anaemia (caution : if white cell count isextremely high) • Antibiotic therapy if infections are suspected TA OGUNLESI (FWACP)

19. 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 TA OGUNLESI (FWACP)

20. 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 TA OGUNLESI (FWACP)

21. 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. TA OGUNLESI (FWACP)

22. MANAGEMENT • MAINTENANCE THERAPY • Weekly Methotrexate • Daily 6-Metacarptopurine • Pulses of Vincristine & Prednisolone Duration: 2 to 3 years TA OGUNLESI (FWACP)

23. 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 TA OGUNLESI (FWACP)

24. 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%) TA OGUNLESI (FWACP)