1. Leukaemias

2. Leukaemias: Malignant Disease of WBC Forming tissue or other hemopoietic elements: Lymphoblastic (ALL) Lymphoblastic (ALL)Acute Myeloid (AML) Myeloid (AML) Lymphatic (CLL) Lymphatic (CLL)Chronic Myeloid (CML) Myeloid (CML)

3. Acute leukaemias: ALL Childhood AML Adults Aetiology: Unknown in individual case * Viral * Viral * Radiation * Radiation * Chemicals and Drugs * Chemicals and Drugs * Genetics factors * Genetics factors

4. Pathology: BLAST CELLS Tissue invasion (L.N., spleen, liver, skin, C.N.S) BLOOD Pancytopenia + Blastaemia Normal Haemopoiesis (Depressed) Bone Marrow

5. In tumors manifesting as leukemias,blast accumulating in the marrow suppress the growth of normal hemopoietic cells by physical displacement and by other poorly understood mechanisms.Eventully this suppresion manifested as bone marrow failure. Which account for the major clinical presentation.

6. Pathogenesis The principle pathogenic defect in acute leukemia is a block in differentiation. This defect result from acquired mutations in specific transcription factors that regulate the differentiation of immature lymphoid or myeloid progenitors. Normal B cell, T cell,and myeloid differentiation are regulated by different lineage -specific transcription factors, accordingly, the mutated transcription factor genes found in acute leukemias.

7. Clinical features - Abrupt, onsent -Clinical signs and symptoms related to suppressed marrow function, including fatigue due to anemia -Bone pain and tenderness resulting from marrow expansion and infiltration of subperiosteum. _Generalized lymphadenopathy, splenomegaly and Hepatomegaly,thymic mass in ALL. -CNS manifestation from meningeal spread. More common in chidren than adult and ALL than AML.

8. Blood Picture: Hb Clinically (Normochronic - - - - Pallor, Tiredness (Normochronic - - - - Pallor, Tiredness Anaemia - - - - Dyspnea, etc... Anaemia - - - - Dyspnea, etc... =4-9 g/dl) =4-9 g/dl) DIC (AProl) Platelet Count - - - Bleeding DIC (AProl) Platelet Count - - - Bleeding (Thrmbocytopenia Tendency (Thrmbocytopenia Tendency = 10 – 80 x 10 9 /L) = 10 – 80 x 10 9 /L) Neutrophil - - - Infections Neutrophil - - - Infections count (Fever, septicoemia) count (Fever, septicoemia) ( 0.1 – 1.5 x 10 9 /L) ( 0.1 – 1.5 x 10 9 /L) Organ infiltration: Lymphadenopathy (systemic) Hepatosplenomegaly Hepatosplenomegaly - Gum Hypertrophy in Monocytic leukaemia - Gum Hypertrophy in Monocytic leukaemia (rarely, skin, bone, C.N.S) (rarely, skin, bone, C.N.S) Viral Fungal Bacterial Total WBC count Normal, low, or increased

10. Leukaemia: Neoplastic disease of WBC forming tissue. Classification (FAB) I. Acute lymphoblastic leuk. ALL Morphological Morphological L1 – Monomorphic type.... Good risk L2 – Heterogenous type L 3 – Burkitt ’ s type Immunological Immunological 1) Non T, Non B ALL (common) good risk ALL good risk ALL 2) T- ALL 3) B- ALL

11. II. Acute Myeloid Leukaemia (AML) [ FAB] [ FAB] M 0 AML... Poorly differentiated M 1 AML... Without Maturation M 2 AML... With Maturation M 3 AproL... Promyelocytic M 4 AMML... MyeloMonocytic M 5 AMOL.M5a (Monoblastic).M5b. Monocytic M 6 A. ErythroLeukaemia M 7 A. Megakaryoblastic L Age groups : ALL – mostly in children AML – mostly in Adults AML – mostly in Adults