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ACUTE LEUKAEMIA. LEUKAEMIA. A disorder characterised by the accumulation of malignant white cells in the bone marrow and peripheral blood. 2 main types: Acute leukaemia Chronic leukaemia. ACUTE LEUKAEMIA. A malignant disorder in which blasts constitute >30% of the bone marrow cells
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LEUKAEMIA • A disorder characterised by the accumulation of malignant white cells in the bone marrow and peripheral blood. 2 main types: • Acute leukaemia • Chronic leukaemia
ACUTE LEUKAEMIA A malignant disorder in which blasts constitute >30% of the bone marrow cells 2 main groups: • Acute Myeloid Leukaemia (AML) • Acute Lymphoblastic Leukaemia (ALL)
Epidemiology and Aetiology • ALL commoner in childhood with a peak age of 4 years • AML commoner in adults • No proven geographical or environmental agents
Aetiology • Genetic / Constitutional • Down’s syndrome • Fanconi’s anaemia • Acquired • Myelodysplasia • Chemotherapy/radiotherapy • Chronic myeloproliferative disorders
FAB CLASSIFICATION M1 myeloblastic undifferentiated M2 myeloblastic with differentiaion M3 promyelocytic M4 myelomonocytic M5 monoblastic M6 erythroleukaemia M7 megakaryoblastic WHO CLASSIFICATION AML with recurrent genetic abnormalities AML with multilineage dysplasia AML therapy related AML not otherwise categorised AML of ambiguous lineage ACUTE MYELOID LEUKAEMIA CLASSIFICATION
ACUTE LEUKAEMIAS Basis of disease: maturation defect of BM stem cells Cell proliferation might be s lo w e r than normal!!! abnormal blasts dominate the BM picture normal haemopoietic elements are blocked – this is due not only to space occupation lymphoid leukaemias belong to lymphoma/ leukaemia group
CLINICAL APPEARANCE OF ACUTE LEUKAEMIAS Weakness - anaemia Fever, infection - granulocytopenia Hemorrhage - thrombocytopenia - (anywhere in the body) Bone pain, tenderness - subperiosteal leukaemic infiltration Meningeal symptoms - CNS involvement / (headache, nausea, vomit, subarachnoidal bleeding cerebral palsy, intracerebral, meningeal infiltration)
Symptoms, specific to certain leukaemias AML M3 - (promyelocytic) DIC AML M1-2 - soft tissue,or subperiostal infiltration AML 4-5 - skin, gum infiltration
Clinical Features • Bone marrow failure • Anaemia, bruising/bleeding, DIC (M3), infection • Lymphadenopathy / hepatosplenomegaly • Commoner in ALL • Tissue infiltration • CNS, testes (ALL), gum hypertrophy (M4) • Increased cellular catabolism
Laboratory Features Blood Count • Anaemia, Thrombocytopenia, Neutropenia • High or low white cell count (WCC) • Circulating blasts Coagulation • Often abnormal • Disseminated Intravascular Coagulation(DIC)
Laboratory Features Bone Marrow (BM) Aspirate • Marrow is usually replaced by blasts with little or no remaining normal haemopoietic tissue Trephine Biopsy • Useful if the marrow is hypocellular or fibrotic
Laboratory Features Diagnosis • Morphology • Cytochemistry • Immunophenotyping • Cytogentics
Morphology • Bone marrow and peripheral blood • BM shows >30% blasts • Cells often contain granules or inclusions called Auer rods
Cytochemistry AML • Sudan black, Myeloperoxidase, Chloroacetate Esterase • Monoblastic – Non Specific Esterase ALL • B lineage – PAS • T lineage – Acid Phosphatase
Immunophenotyping • Use of antibodies to identify cell antigens (clusters of differentiation or CD) • The pattern of antigens expressed by the cells correlates with lineage and maturity • Eg AML - CD 13, CD33 positive, CD19, CD20 negative
Cytogenetics • Chromosomal abnormalities are found in the blasts in 70% of cases of AML and 90% of ALL • Important in the pathogenesis of the disease • Important for diagnosis • Prognostic implications • Eg t(15;17) and M3 AML
LABORATORY FINDINGS Anaemia variable severity WBC 50 % < 10000/mm3 20 % > 100000/mm3 Blasts both in peripheral and BM smears, HIATUS LEUKAEMICUS Thrombocyte < 100000 / mm3 Rarely : aleukaemic leukaemia Peripheral pancytopaenia : BM biopsy- RULE OUT - aplastic anaemia
LABORATORY FINDINGS CYTOCHEMISTRY ALL AML PAS + - Tdt + (95 % ) - (95 %) myeloperoxidase + (M1-3) NON spec. esterase - + (M4-5)
Clinical Management • Supportive care • Remission induction • Maintenance therapy • Bone marrow transplantation • Treatment of relapse
Clinical Management AML • Remission induction + consolidation usually with 4 courses of chemotherapy • M3 – chemotherapy + ATRA • Bone Marrow or stem cell transplantation for those with poor prognosis disease who have a suitable donor
Clinical Management • ALL • Remission induction + consolidation • CNS prophylaxis • Maintenance therapy for 2-3 years • Bone marrow or stem cell transplant for those with poor prognosis disease with a suitable donor
Prognosis Childhood ALL • 70% cure • Poor prognosis • High WCC • Male • Age <1yr or>15yr • Poor cytogenetics
Prognosis • AML and adult ALL • 30% cure • Poor prognosis • Age > 60 yr • Poor cytogenetics • Failure to achieve remission after 1st course of chemotherapy • Secondary AML
PROGNOSIS , THERAPY ALL - 2-10 5 year survival over 60 % CHEMOTHERAPY T cell, and adult form- grave AML - BM TRANSPLANTATION