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AML-CLINICAL FEATURES,CLASSIFICATION,TREATMENT

. Acute myeloid leukemiaAcute myelogenous leukemiaAcute nonlymphocytic leukemiaWell defined hematopoetic neoplasm involving precusor cells committed to myeloid line of cellular development. . EpidemiologyMost common acute leukemia in adultsIncidence 3-5/100000AML accounts for 10% of acute leu

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AML-CLINICAL FEATURES,CLASSIFICATION,TREATMENT

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    1. AML-CLINICAL FEATURES,CLASSIFICATION,TREATMENT

    2. Acute myeloid leukemia Acute myelogenous leukemia Acute nonlymphocytic leukemia Well defined hematopoetic neoplasm involving precusor cells committed to myeloid line of cellular development

    3. Epidemiology Most common acute leukemia in adults Incidence 3-5/100000 AML accounts for 10% of acute leukemia in children Median age of diagnosis is 65yrs Male female ratio is 5/3

    4. Clonal proliferation of myeloid precursors with reduced capacity to differentiate into more mature cellular elemens There is accumulation of leukemic blasts or immature forms in the bone marrow,peripheral smear and other tissues with reduction of n/l redcells,platelets,and mature granulocytes

    5. Heriditary Trisomy 21,fanconis anaemia,blooms syndrome,ataxia telengectasia Congenital neutropenia,myeloproliferative syndromes

    6. Exposure to radiation,benzene Paints,embalming fluids,ethylene oxide, Herbicides and pesticides Anti cancer drugs -alkylating agents Topoisomerase 2 inhibitor Cloramphenicol,phenylbutazone,chloroquine, methoxypsoralen

    8. Clinical features Related to anaemia,neutropenia,thrombocytopenia Weakness Easy fatiguebility Infections of varying severity Haemarrhagic findings Gingival bleeding Ecchymosis Epistaxis/menorrhagia

    9. Pallor Bone pain Fever-due to associated infections Skin-pallor,petechia and ecchymosis Infiltrative lesions suggestive of leukemic invovlement-leukemia cutis/myeloid sarcoma

    10. Eyes-haemarrage/plaques Cns-cranial nerve palsies,visual changes Headache,vomiting Pappiloedema,convulsions Oropharynx-gingival hypertrophy,oral candidiasis,herpetic lesions organomegaly

    11. Joint involvement Myeloid sarcoma

    12. Diagnosis Peripheral blood Normocytic normochromic anaemia of varying intensity Reticulocyte count-n/l or decreased 75% have platelet count-<100000/microl 25% <25000/microl Both morphological and functional platelet abnormality may be seen

    13. Median leucocyte count-15000/microl 20%will have above 100000cells//microl 25-45%-leucocyte count<5000/microl 95%will have circulating myeloblasts in peripheral smear

    14. Myeloblasts Immature cells with large nuclei,prominent nucleoli,and a variable amt of dark blue cytoplasm staining with wright giemsa Nuclear cytoplasmic ratio and the morphology vary depending on the maturity of the cell

    16. Auer rods-vary in no depending on the aml subtype Pink/red rod like granular structure in cytoplasm Myeloperoxidase test can be done to detect the blasts are myeloid

    17. Bone marrow biopsy and aspirate Usualy hypercellular Blasts in aml include myeloblasts ,monoblasts,promonocytes ,abnormal promyelocytes,and megakaryoblasts In the current WHO classification blasts forms must account atleast 20% of the total cellularity

    18. FAB classification cut off is 30% 20-30%-refractory anaemia with excess blast transformation

    19. Exceptions AML with t(8:9)(q22:22) t(15:17) AML with inv16 Presence of myeloid sarcoma is diagnostic independent of blast count

    20. Flow cytometry Can detect myeloblasts by charecteristic pattern of surface antigen expression Majority have CD 34 CD 117,CD13,CD33 HLA DR

    21. Cytogenetic features Patients with suspected AML should undergo cytogenetic study Abt 50% demonstrate cytogenetic abnormality Conventional karyotyping analysis RT-PCR FISH

    22. Certain aml subtypes are defined by recurrent genetic abnormality For determinig prognosis For choosing appropriate post remission therapy Molecular studies

    23. Blasts in aml differentiated from blasts of lymphoid lineage by Presence of auer rods Positivity to sudan black,myeloperoxidase Flow cytometry identifying the expression of myeloid antigens Specific cytogenetic abnormalities

    24. WHO CLASSIFICATION There are four main groups of AML recognized in this classification system: AML with recurrent genetic abnormalities AML with myelodysplasia-related features Therapy-related AML and MDS AML, not otherwise specified

    25. WHO CLASSIFICATION AML WITH RECURRENT GENETIC ABNORMALITIES 1)Aml with t(8;21)(q22:q22) May not have 20% blasts Identified by cytogenetic abnormality Typical morphological features will be there Myeloid markers+,also CD19,CD56 more favourable prognosis Presence of c-kit mutation is an adverse prognostic feature

    26. 2)AML with abnormal bone marrow eosinophils Inv16 Previously acute myelomonocytic leukemia FAB M4 Occurs in young individuals Can present as extra medullary myeloid sarcoma

    27. 3)ACUTE PROMYLOCTIC LEUKEMIA AML with t (15:17) Malignant cells in APL are atypical promyelocytes 4)AML with 11q23 abnormalities

    28. ACUTE PRONYELOCYTIC LEUKEMIA Morphology — APL is characterized by the presence of atypical promyelocytes in the bone marrow and prominent nucleoli.

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