Chronic Leukaemias PDF

Chronic Leukaemias Can be broadly subdivided into Chronic myeloid leukaemia Chronic lymphoied leukaemia Chronic myeloid leukaemia Constitute six different types of leukaemias, the most common type is C.M.L associated with Philadelphia chromosome. Definition...

Chronic Leukaemias Can be broadly subdivided into Chronic myeloid leukaemia Chronic lymphoied leukaemia Chronic myeloid leukaemia Constitute six different types of leukaemias, the most common type is C.M.L associated with Philadelphia chromosome. Definition C.M.L is an acquired clonal disorder of pluripotent stem cell. 2 Types of Chronic CML: Type name 1 (CML,Ph+)(chronic granulocytic leukemia) 2 (CML,Ph-) 3 Juvenile CML 4 Chronic neutrophilic leukemia. 5 Esinophilic leukemia 6 Chronic myelomonocytic leukemia 3 4 Pathogenesis Reciprocal translocation between chromosomes 9 and 22 ,in which part of Abelson protooncogen (ABL) is moved to the (BCR) gene on chromosome 22 and part of chromosome 22 moves to chromosome 9. The abnormal chromosome 22 is the Philadelphia chromosome (Ph). 5 The resulting chimeric BCR-ABL gene codes for a fusion protein of size 210KDa ,normal ABL is145 KDa It has tyrosine kinase activity in excess of normal. In an other cases the break point in BCR is upstream and this chimiric BCR-ABL gene is 190 KDa. May be seen in a minority of cases of ALL. 6 Rarely you get breakpoint μ-BCR producing P230kda prominent in neutrophilic leukaemia. In a minority of patients the Ph abnormality can not be seen by microscopic karyotyping analysis. 7  Structure of the BCR-ABL fusion protein and mechanisms of leukemogenesis 8 Occur in male and female male: female 1.4:1 Can occur at any age even in children and neonates. In most cases no predisposing factors. 9 Clinical Presentation: The most age of presentation is between 40-60. Symptoms related to hyper metabolism: (weight loss, lassitude, anorexia or night sweats). (Gout or renal impairment caused by hyperuriceamia ). Bone marrow failure: 10 Cont: Bruising ,epistaxis,menorrhagia or hemorrhage from any site because of platelet dysfunction. Organ infiltration: Splenomegaly almost always present and is frequently massive. Rare symptoms include visual disturbance. 11 Laboratory findings C.B.C: anaemia normochromic normocytic Leucocytosis >50 109/L->500 109/L Platelet count increased, normal or decreased. Peripheral blood film: All myeloid series seen. Increased circulating basophil 12 13 B.M is hypercellular with myeloid hyperplasia. Neutrophil alkaline phosphatase is reduced. Serum uric acid is raised. 14 Cytogenetic Ph chromosome is detected. 15 16 17 Pathology : B.M haemopoietic marrow is replaced by soft pale pink tissue extending into long bones. Spleen enlarged and firm, the cut surface has mottled appearance. The red pulp is packed with leukaemic cells splenic enlargement is mainly due to extramedullary haemopoiesis. Liver may show extensive sinosoidal infiltration by leukaemic cells Diffuse infiltration of other organ including C.N.S. 18 Other features include fatty change of organs secondary to anaemia. Wide spread petechial haemorrhages due to thrombocytopenia or defective platelet function,occasionaly extensive haemorrhage occurs. Haemorrhagic infarct as a result of diffuse microvascular occlusion by leukaemic cells. 19 C.M.L has 3 phases Chronic phase ↑ WBC median 170x109/l with neutrophil & myelocyte peaks. Absolute basophilia and many patients have eosinophilia. Monocytes