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Acute leukaemia

Acute leukaemia. Dr. MO Kehinde Department of Medicine CMUL/ LUTH. Acute Leukaemia. These are a heterogeneous group of diseases characterized by infiltration of the blood, bone marrow and other tissues by neoplastic cells of the haematopoietic system. There are two main types

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Acute leukaemia

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  1. Acute leukaemia Dr. MO Kehinde Department of Medicine CMUL/ LUTH

  2. Acute Leukaemia • These are a heterogeneous group of diseases characterized by infiltration of the blood, bone marrow and other tissues by neoplastic cells of the haematopoietic system. • There are two main types • myeloid leukaemia and • lymphoid leukaemia .

  3. TABLE 1The FAB classification of acute leukemia • Lymphoblastic(ALL)* • L1 Small, monomorphic, high N: C ratio (SCORES 0 , 1 or 2 ) + • L2 Large, heterogenous, nucleolated, low N: C ratio (Scores - 1, -2 or - 3) • L3 Burkitt – cell type, basophilic, vacuolated

  4. Myeloid (AML) • M0 Undiferentiatedmyeloblastic(requires cell markers ) • M1 Myeloblastic without maturation (requires cytochemistry: peroxidase or SSB) • M2 Myeloblastic with maturation • M3 Hypergranularpromyelocytic • M3 – variant Micro – or hyper granular bilobed promyelocytes

  5. M4 Myelomonocytic with both granulocytic and monocytic differentiation • M5 Monoblastic (M5a requires cytochemistry : ANAE or ANBE ) and promonocytic- monocytic(M5b) • M6 Erythroleukaemia ,with > 50% erythroblasts and < 30% blasts • M7 Megakaryoblastic (requires cell markers )

  6. Diagnosis • SBB=Sudan black B; • ANAE= alpha naphthyl acetate esterase: • ANBE=alpha naphthyl butyrate esterase • A diagnosis of ALL now requires cell markers to demonstrate B. or T lineage commitment.

  7. Conditions predisposing to acute leukaemia • Down’s syndrome { Transient { Persistent (ALL or AML) • Genetic or constitutional • Bloom’s syndrome • Fanconi’s anaemia (AML) • Ataxia telangiectasia (ALL, lymphoma

  8. Conditions predisposing to acute leukaemia • Acquired • Myelodysplasia (AML) • Chemotherapy +radiotherapy ( MDS  AML) • Chronic myeloproliferative disorders (CML, PRV,myelofibrosis) (AML) • Aplastic anaemia (ALL) • Paroxysmal nocturmal haemoglobinuria (AML, rarely ALL)

  9. Abbreviation • MDS= myelodysplastic syndrome; • PRV= polycythaemia rubra vera; CML=chronic myeloid leukaemia

  10. Acute Leukaemias • are defined pathologically as blast cell leukaemias or malignancies of immature haemopoietic cells. • The bone cell marrow shows > 30% blast cells and they are divided into two main groups: Acute myeloid leukaemia (AML) and acute Lymphoblastic Leukaemia (ALL).

  11. Acute Leukaemia • There are two main age groups: Childhood (< 15 years ) and adult (> 15 years). • A third group is that of adults aged > 60 years because of their response to current treatment protocols both for ALL and AML, is inferior and because the Patients are not usually included for the more radical approaches using autologous or allogeneic bone marrow transplantation (BMT). • AML comprises about 80% of adult cases

  12. Epidemiology • (ALL and AML • Incidence : (1) Age differences (as above) • (2) Urban industrialized and rural areas (commoner in industrialized than rural) • (3) Socio – cultural factors Common CD 10 + form of ALL ( c ALL) less frequent compared with T – All in African countries and in poorer sections of the community in the USA (e.g Black or Spanish)

  13. Acute LeuKaemia • (4) Environmental agents implicated in the induction of certain types of Leukaemia. • a. Ionising radiation • b. Chemical carcinogens especially alkylating agents used for treatment of other • malignancies. • (5) Host susceptibility e.g. genetic disorders • (6) Blast transformation in pre existing myeloproliferative disorders • (7) In Down’s syndrome.

  14. Acute Leukaemia • (8) Oncogenic viruses in causation of human acute Leukaemia • HTLV -1 ( human T – cell lymphoma virus -1 ] directly implicated in adult – Tcell leukaemia /Lymphoma.

  15. Acute Leukaemia • Ionizing radiation : • X-rays and other ionizing rays can induce leukaemia (as observed in survivors of the atomic bomb explosions in Hiroshima and Nagasaki) • Chemicals • Two types of chemicals strongly suspected of being leukaemogenic are • benzene and other petroleum derivatives • alkylating agents

  16. Acute Leukaemia • Chromosomes and oncogene abnormalities: • Cytogenetic abnormalities are found in AML and ALL.

  17. Clinical Features • may include • A General Symptoms of anaemia (Tiredness, weakness lassitude, lethargy, shortness of breath). • Bleeding • Infections • Anorexia, weight loss • Lymphadenopathy(very uncommon in AML except in monocytic variant of AML )

  18. Specific organ /system involvement • Skin with nonspecific Lesions like macules or papules, vesicles , pyoderma gangrenosum, • Neutrophilic dermatitis • Leukaemic cutis • Granulocytic sarcoma of the skin.

  19. Acute leukaemia • Differential diagnosis • Septicaemia • Miliary tuberculosis • malignant histiocytosis • Complications • Worsening Continuous ill health • Death

  20. Relevant investigations • Complete blood count, and ESR, reticulocyte count, comb’s test • Bone marrow examination • Biochemical tests such as serum electrolytes, urea, creatinine, uric acid • Liver function tests. • Prothrombin time, partial thromboplastic time • Human Leucocyte antigen typing • HIV I and II.

  21. Relevant investigations • 1 Cytochemical tests such as • (i) Peroxidase , Sudan black B • (ii) Non – specific esterase reaction such as alpha napthyl acetate esterace • 2 Bone marrow cultures • 3 Cytogenetic Findings • 4 Electron microscopy

  22. Relevant investigations • Cell Markers e.g. using a panel of antibodies combined with flow cytometric analysis or the alkaline phosphase – antialkaline phosphate (APAAP) technique for the identification of specification antigens and / or enzymes on the membrane and / or in the cytoplasm or the nucleus which identify the blast cells to be of lymphoid or myeloid lineage • 6 Abdominal scan or CT scan

  23. Relevant investigations • 7 Immunological Classification • Terminal deoxy nucleotidyl transferase demonstration in nucleus of B- and T – lineage by means of a • αN antibody using.

  24. Management • (a)Treatment objectives • . Induce remission to achieve complete remission • . Maintenance of disease free patients • (b) Non –drug treatment • - Appropriate Nutrition. • - Adequate hydration (at least 3 liters/24 hours) • - Provision of • (1) Erythrocytes transfusion as required • (2) Platelets concentrate transfusion as required • - Maintenance of electrolyte balance.

  25. Drug –treatment • For Acute lymphoblastic leukaemia • Allopurinol 300mg daily p.o. • To use DVP or COAP • DVP i.e. • Daunorubicin 30mg/ m2 iv d8,15,22,29 • Vincristine 1.4mg/ m2 to a maximum of 2mg iv d8,15,22, 29 • Prednisolone 60mg p.o.d 1-28 • L-asparaginase 1000IU/ m2 i.v. 12,15,18,21,24,27,30,33.

  26. Drug –treatment COAP Cyclophosphamide 650mg/m2 1V day 1 and day8 day14 day 22 • Vincristine I.V 1.4mg/m2 to max . of 2mg.day 1 and day 8 day 14 and day 22 • Cytosine arabinoside S .C 50 mg/ m2 12 hourly x 12 days or • I/V bolus 100 mg/ m2 daily x 7 days • Prednisolone 40mg/ m2 p.o. x 14/7 • Drugs are given every 28 days

  27. Drug –treatment • Number of courses= 3 • Criteria for complete remission assess patient clinically and haematologically (including bone marrow and blood examination) • Nervous system prophylaxis • Methotrexate intrathecal 12.5mg /m2 to a max 15mg. x 5 doses over 3 weeks • i.e. twice weekly

  28. Drug –treatment • Consolidation; This is to be given on day 29 COAP once provided WBC ≥ 1x109/ L and Platelet count ≥ 100 x109/ L • Maintenance;to have bone marrow every 12 weeks • 6 Mercaptopurine 75mg/ m2 daily p.o. • Methotrexate 20mg/ m2 weekly p.o.

  29. Drug –treatment • Pulse therapy - (Intensification) To be given every 3 months with • Vincristine 1.4 mg/ m2 to a maximum of 2mg weekly day1 and day8 • Maintenance therapy to continue for 3 years if remission is maintained • otherwise re assessment.

  30. Acute Myeloblastic leukaemia • a clonal disease that result from a acquired genetic change in a pluri potential haemopoietic stem cell . This altered stem cell proliferatial and generates a population of differented cells that gradually replaces normal haemopoiesis and leads to a greatly expanded total myeloid mass.

  31. Use either TAD or COAP as shown below: • TAD • Cytarabine 100mg/ m2 (cont inf) d1+2 and • 100mg/ m2 b.i.d. i.v. (30 min inf) d3-8 • Thioguanine 100mg/ m2 b.i.d. p.o. every 12h 3-9 • Daunorubicin 60mg/ m2 i.v.(1 h inf) d3-5

  32. AML • Or COAP as shown below; • Cyclophosphamide 650mg/m2 1V day 1 and day8 • Vincristine I.V 1.4mg/m2 to max . of 2mg.day 1 and day 8 • Cytosine arabinoside S .C 50 mg/ m2 12 hourly x 7 days • Prednisolone 40mg/ m2 p.o. x 14/7 • 14 day cycle

  33. AML • Nervous system prophylaxis is not required. • Assess for remission after 3 courses. • Maintenance • Patient to have COAP every 6 weeks for 2 years. • If there is CNS disease and it is monocytic give intrathecal treatment as for ALL.

  34. Thank you • For • Your • Attention

  35. ACUTE MYELOID LEUKAEMIA • Def.Introduction • . Clonal malignant disease of the haemopoietic tissue • characterized by • . Proliferation of abnormal blast cells • . Impaired production of normal blood cell • :. Leukaemia blast cells • accumulate in the marrow. ↓ • Suppress the proliferation & differentiation of normal haemopoietic cells.

  36. Classification of AML ( FAB classification) • M0 Undifferentiated myeloblastic • MI Myeloblastci without maturation • M2 Myeloblastic with maturations • M2 BASO M2 with basophil blasts • M3 Hypergranular pronyelocytic • M3 Variant micro.or hypogranular bilobed progranular

  37. AML • M4 .Myelomonocytic with both granulocytic and hypogranulocytic with both granulocytic and monocytic differentation • M4 Eo M4 with bone marrow eosinoplilia • M5 Monocytic monoblastic (m5a) and promonocytic –monocytic (M5b) • M6 Erythroleukaemia with > 50% erythroblasts • M7 Megakaryoblastic

  38. EPIDEMIOLOGY • Age incidence: • predominant form of leukaemia • From middle age onward, the incidence increases progressively • Sex incidence • It is slightly more common in male M > F

  39. PATHOPHYSIOLOGY • arises following malignant transformation of a single haemopoietic progenitor followed by cellular replication and expansion of the transformed done. • Defect in maturation beyond the myeloblast or promyelocyte level in AML. • Proliferating leukaemia cell accumulate in BM ↓

  40. PATHOPHYSIOLOGY • Suppress normal haemopoiesis • ↓ • result in replacement of normal elements. • ↓ • anaemia, infections & bleeding complications. • - Primarily proliferate in BM

  41. PATHOPHYSIOLOGY • circulate in the blood and infiltrate into other • tissues such as • Lymph nodes, skin, gum, • . Liver viscera, CNS. • . Spleen

  42. PATHOPHYSIOLOGY • Growth. Advantages of Leukaemia cells • Mechanisms ? unknown • Postulates : - GF production • GF Receptors. • . Factor Receptor coupling on normal versus Leukaemia cells may play a role • . Transforming genes or cellular oncogene expressed in leukaemia cells code for GF receptors

  43. PATHOPHYSIOLOGY • BM Failures due to • Def. of normal stem cell differentiation proliferation & maturation • As a result of failure of production humoral or microenviromental stimulators • Mechanism of Neoplastic Transformation • - Poorly understood .

  44. May involve a fundamental alteration of DNA conferring hereditable malignant xteristics to the transformed cell, • In animal , Leukaemia can be induced by retroviruses which either carry a transforming gene (viral mcogene ) or integrate into specific sites in DNA causing activation of cellular proto- oncogenes (insertional mutagenesis)

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