TA OGUNLESI (FWACP)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 200x10 9 /l, neutropenia and blast cells Thrombocytopenia (<100x10 9 /l).

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

TA OGUNLESI (FWACP)15 INVESTIGATIONS 3.Cytochemical staining  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  determine whether 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 patients with T -ALL In 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

TA OGUNLESI (FWACP)18 MANAGEMENT SUPPORTIVE CARE Blood support :-  Platelet con. for bleeding episodes or if the platelet count is <10x10 9 /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

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 10 years  High WBC count (>50,000/mm 3 )  T-Cell ALL  High Haematocrit (PCV >30%)