Leukaemias
Leukaemias: Malignant Disease of WBC Forming tissue or other hemopoietic elements: Lymphoblastic (ALL) Acute Myeloid (AML) Lymphatic (CLL) Chronic Myeloid (CML)Acute leukaemias: ALL Childhood AML Adults
Aetiology: Unknown in individual case * Viral * Radiation * Chemicals and Drugs * Genetics factorsPathology:
BLAST CELLSTissue invasion (L.N., spleen, liver, skin, C.N.S)
BLOOD Pancytopenia + Blastaemia Normal Haemopoiesis (Depressed)
Bone Marrow
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.
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.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.Blood Picture: Hb Clinically (Normochronic - - - - Pallor, Tiredness Anaemia - - - - Dyspnea, etc. . . =4-9 g/dl) DIC (AProl) Platelet Count - - - Bleeding (Thrmbocytopenia Tendency = 10 – 80 x 109/L) Neutrophil - - - Infections count (Fever, septicoemia) ( 0.1 – 1.5 x 109/L)Organ infiltration: Lymphadenopathy (systemic) Hepatosplenomegaly - Gum Hypertrophy in Monocytic leukaemia (rarely, skin, bone, C.N.S) Viral Fungal Bacterial
Total WBC count Normal, low, or increased
Leukaemia: Neoplastic disease of WBC forming tissue.Classification (FAB)I. Acute lymphoblastic leuk. ALL Morphological L1 – Monomorphic type . . . . Good riskL2 – Heterogenous type L 3 – Burkitt’s type Immunological 1) Non T, Non B ALL (common) good risk ALL2) T- ALL3) B- ALL
II. Acute Myeloid Leukaemia (AML) [ FAB]M0 AML . . . Poorly differentiated M1 AML . . . Without Maturation M2 AML . . . With Maturation M3 AproL . . . Promyelocytic M4 AMML . . . MyeloMonocyticM5 AMOL .M5a (Monoblastic) .M5b . Monocytic M6 A. ErythroLeukaemia M7 A. Megakaryoblastic LAge groups : ALL – mostly in children AML – mostly in Adults