2a MYELODYSPLASIA Year 4 Internal Medicine Notes OmpathStudy

2a MYELODYSPLASIA Year 4 · Internal Medicine Collection: 4TH YEAR ALL NOTES / IMED / IMED 4.2 / Mogere -- Slide 1 MYELODYSPLASIA Dr Alex Mogere Consultant Physician Slide 2 WHO Defn. A group of clonal hematopoietic stem cell diseases x-terized by; Cytopenia Dysplasia in one or more major myeloid cell lines Ineffective haematopoiesis Increased risk of devt of AML The threshold for cytopenia as recommended by the IPSS (INTERNATIONAL PROGNOSTIC SCORING SYSTEM)for risk stratification: Hb < 10g/dl Absolute neutrophil count < 1.8x10 9/L Plts < 100x10 9/L Slide 4 Ct. MDS may involve one, two, or all three myeloid hematopoiesis cell lineages—erythrocytic, granulocytic, megakaryocytic—depending on the subtype and stage of the disease. Slide 5 Pathophysiology MDS develops when a clonal mutation predominates in the bone marrow, suppressing healthy stem cells. The clonal mutation may result from genetic predisposition or from hematopoietic stem cell injury caused by exposure to any of the following: Cytotoxic chemotherapy\nRadiation\nViral infection\nGenotoxic chemicals (eg, benzene) Slide 6 Predisposing factors Hereditary Constitutional genetic disorders: downs, trisomy 8,monosomy 7 Neurofibromatosis Congenital neutropenia syndrome DNA repair defects: Fanconi anemia, ataxia telangiectasia, bloom syndrome Mutagen detoxification Slide 7 cont. Predisposing factors Acquired Mutagen exposure Environmental /occupational exposures eg benzene, solvents, insecticides etc Tobacco Senescence Aplastic anaemia Slide 8 Epidemiology actual incidence is unknown At all ages, MDS is more common in males than in females incidence increasing- elderly population increasing/ improved recognition primarily affects elderly people, with the median onset in the 7th decade of life Slide 9 Aetiology Primary/denovo Benzene exposure\ Cigarette smoking Agricultural chemicals Fhx of haematological neoplasms Fanconi anemia, schwanmann diamond, diamond-Blackfan Slide 10 Cont. Aetiology Secondary Prior exposure to cytotoxics Alkylating agents; cyclophosphamide Topoisomerase II inhibitors; etoposide, anthracyclines Risk increases with age Autologous transplantation for lymphoma-MDS seen in 12%,most cases develop within 5 years-poor outcome Slide 11 Classification on MDS FAB / WHO CLASSIFICATION Slide 15 MODALITY OF CLASSIFICATION RA- dysplasia in RBC only RCMD- dysplasia in 2 or more myeloid lineage RAEB- blasts increase in blood/BM (poor prognosis) 5q syndrome– good prognosis Unclassified- unilineage dysplasia of myeloid or megakaryocytic lineage Slide 16 Pathogenesis Inherited DNA damage myeloid stem\ncell Acquired\nIncreased apoptosis\nmyelodysplastic \nclone \nAbn marrow microenvt MDS Immune damage Increased angiogenesis sec epigenetic/genetic AML\nabnormalities Slide 17 Clinical presentation 50% of all pts 70yrs < 25% < 50yrs Symptoms of anemia, infection, easy bruising, bleeding Splenomegaly uncommon unless in CMML MDS Slide 18 Ct clinical presentation +/- unexplained macrocytic anemia with no evidence of megaloblastic anemia and a mild thrombocytopenia or neutropenia. Slide 19 DX/Lab Observe symptoms of BMF Splenomegaly in 10% CMML PBF-cytopenias Cbc- macrocytic anemia, rbcs- macro-ovalocytes,+/- neutropenia, low plts BMA- hypercellularity with trilineage dysplastic changes,some hypocellular(AA), increased marrow fibrosis(?myeloproliferative disorders) Trephine biopsy X-mosome analysis Slide 20 Dx/Lab-others Serum erythropoietin (prior to red blood cell [RBC] transfusion)\nRBC folate and serum vitamin B-12\nSerum ferritin, iron, and total iron-binding capacity (TIBC)\nThyroid-stimulating hormone (TSH)\nLactate dehydrogenase (LDH)\nHIV testing if clinically indicated Slide 21 Erythroid lineage Blood Hypochromic cells, occasionally normoblasts Macroovalocytes Basophilic stippling reticulocytopenia Bone marrow Increased marrow cellularity Multinucleate normoblasts Ringed sideroblasts Hypocellular cells eg in aplastic anemia Fibrosis Abn chromatin pattern Slide 22 myeloid Granulocytopenia Hypogranular neutrophils Pelger abnormality(bilobed nuclei) Hypolobated neutrophil nuclei myeloblasts Slide 23 megakaryocitic Blood Agranular platelets megakaryocytes Bone Marrow Macromegakaryocytes Micronuclear Mononuclear Slide 24 cytogenetics Slide 25 MX Before mx consider\nAge General fitness levels Prognosis Observation Supportive care: rbc/plt transfusions,abx,hemopoietic factors Immunosuppressive tx Low dose chemotx Intensive chemotx Transplantation(has a ltd role) Slide 26 Ct mx Iron chelation -in those pts who have received 20-25 units of packed RBCs or who have a serum ferritin level of 1000 μg/L. /deferoxamine Avoid repeated and frequent platelet transfusions on the basis of low platelet counts (< 20,000/µL) in pts who are not experiencing clinical bleeding. BM stimulation: Hematopoietic growth factors can stimulate bone marrow cell production and decrease excess bone marrow cell apoptosis eg EPO, ESAs Slide 27 Cytotoxics include:(use in high myeloblasts