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Myelodysplastic syndromes

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  1. 2. Myelodysplasia : from marrow failure to malignant transformation Ahmed Elshebiny, MD University of Menoufyia
  2. 3. Blood is continuously renewed
  3. 4. The Bone Marrow is the blood Factory May be exposed to damage or failure
  4. 7. Bone Marrow Failure Syndromes Bone Marrow Failure Syndromes AA PNH MDS Acquired Constitutional Autoimmune Fanconi DC Diamond-Blackfan others Toxic, Irradiation, Infection Pure Red Cell Aplasia Agranulocytosis
  5. 8. Bone Marrow Failure <ul><li>May involve one or more cell lines </li></ul><ul><li>Lymphocytes are usually spared </li></ul>
  7. 10. Bone Marrow Failure Syndromes
  8. 11. Hematology lectures Myelodysplasia
  9. 12. Myelodysplastic syndrome (MDS) <ul><li>It is a term for a heterogeneous collection of haemopoietic stem cell disorders usually affecting older adults. </li></ul><ul><li>There is underlying ineffectiveness of haemopoiesis that results in dysplasia of bone marrow precursors and peripheral cytopenias. </li></ul>
  10. 13. Dysplastic erythroid maturation (dyserythropoiesis) Normal Dyserythropoiesis
  11. 14. Pathology <ul><ul><li>The cardinal features of MDS are </li></ul></ul><ul><ul><ul><li>Increased marrow proliferation </li></ul></ul></ul><ul><ul><ul><li>Failure of stem cells to differentiate </li></ul></ul></ul><ul><ul><ul><li>And increased marrow apoptosis. </li></ul></ul></ul><ul><ul><li>The disease is of clonal origin </li></ul></ul><ul><ul><li>Chromosomal abnormalities are detectable in 30-70% of patients. The no. of chromosomal abn. may correlate with the risk of progression to AML. </li></ul></ul>
  12. 15. Epidemiology <ul><li>MDS is primarily a disease of the elderly, with a median age at diagnosis of between 60-80 years. </li></ul><ul><li>The incidence is approximately double that of AML. </li></ul><ul><li>The recent increase in MDS incidence may be related to growing awareness, better diagnosis, and an aging population. </li></ul>
  13. 16. Etiology <ul><li>Primary </li></ul><ul><li>Secondary </li></ul>
  14. 17. MDS (clinical) <ul><li>Moderate anaemia is the most common clinical problem in MDS patients, but complete myeloid bone marrow failure also occurs leading to death from bleeding or infection. </li></ul><ul><li>Approximately half of the patients transform to AML. </li></ul>
  15. 18. MDS (clinical) <ul><li>May be preceded by a few years by an unexplained macrocytic anemia with no evidence of megaloblastic anemia and a mild thrombocytopenia or neutropenia. </li></ul><ul><li>Thrombocytopenia as the presenting symptom may be mistaken for immune thrombocytopenia. </li></ul>
  16. 19. Cytogenetic abnormalities in MDS
  17. 22. FAB classification of MDS <ul><li>In 1982 The FAB group classified MDS according to Morphology and the % of myeloblasts in the BM and PB. </li></ul><ul><li>These included </li></ul><ul><ul><li>Refractory anaemia (RA) </li></ul></ul><ul><ul><li>Refractory anaemia with ringed sideroblasts (RARS) </li></ul></ul><ul><ul><li>Refractory anaemia with excess blast in marrow (RAEB) </li></ul></ul><ul><ul><li>CMML </li></ul></ul><ul><ul><li>Refractory anaemia with excess blast in transformation </li></ul></ul><ul><ul><li>(RAEB-t) </li></ul></ul>
  18. 23. FAB classification of MDS
  19. 24. Newer classifications <ul><li>WHO </li></ul><ul><li>IPSS </li></ul>
  20. 25. Treatment <ul><li>Stem cell transplant </li></ul><ul><li>DNA methyl transferase inhibitors </li></ul><ul><ul><li>Azacytidine </li></ul></ul><ul><li>Immunomodulation </li></ul><ul><ul><li>Thalidomide and lenalidomide </li></ul></ul><ul><li>Immunosupression </li></ul><ul><li>Histone deacetylase inhibitors </li></ul><ul><li>Chemotherapy </li></ul>
  21. 26. Fate of MDS <ul><li>Transformation to acute leukaemia occurs in up to 40% of patients. </li></ul><ul><li>Although progression to frank AML is a primary concern, 20-40 % or more of patients die of infections and/or haemorrhagic complications. </li></ul>
  22. 27. Sideroblastic anemias <ul><li>Inherited (X-linked) </li></ul><ul><li>Acquired </li></ul><ul><ul><li>Myelodysplasis </li></ul></ul><ul><ul><li>Myeloproliferative disorders </li></ul></ul><ul><ul><li>Myeloid leukemia </li></ul></ul><ul><ul><li>Lead toxcicity </li></ul></ul><ul><ul><li>Drugs e.g INH </li></ul></ul><ul><ul><li>Alcohol </li></ul></ul><ul><ul><li>others </li></ul></ul>
  23. 28. Ring sideroblasts
  24. 29. Aplastic Anemias Aplastic Anemias Acquired Conistituitional Single line Agranulocytosis Pure Red Cell Aplasia Multilineage
  25. 30. Aplastic Anemia <ul><li>Named so in 1904 </li></ul><ul><li>The theoretical basis for marrow failure includes primary defects in or damage to the stem cell or the marrow microenvironment </li></ul><ul><li>Distinction between congenital or acquired may be difficult </li></ul><ul><li>80 % of patients have acquired cause which is an autoimmune disease </li></ul>
  26. 31. Aplastic Anemia
  27. 32. Drugs associated with AA <ul><li>NSAIDs(Butazones, Indomethacin,Piroxicam, Diclofenac) </li></ul><ul><li>Antibiotics( e.g sulfonamides) </li></ul><ul><li>Furosemide </li></ul><ul><li>Phenothiazines </li></ul><ul><li>Corticosteroids </li></ul><ul><li>Penicillamine </li></ul><ul><li>Gold </li></ul><ul><li>Allopurinol </li></ul>
  28. 33. Pancytopenia <ul><li>Pancytopenia has many causes of which AA is not the most common </li></ul>
  29. 34. 1-Pancytopenia with hypocellular bone marrow <ul><li>Acquired Aplastic Anemia </li></ul><ul><li>Inherited Aplastic Anemia </li></ul><ul><li>Some MDS </li></ul><ul><li>Rare aleukemic leukemia </li></ul><ul><li>Some acute lymphoblastic leukemia </li></ul><ul><li>Some lymphomas of bone marrow </li></ul>
  30. 35. 2-Pancytopenia with cellular bone marrow <ul><li>Primary bone marrow disease </li></ul><ul><li>MDS </li></ul><ul><li>PNH </li></ul><ul><li>Myelofibrosis </li></ul><ul><li>Mylophthisis </li></ul><ul><li>Hairy cell leukemia </li></ul><ul><li>Aleukemic leukemia </li></ul><ul><li>Secondary to systemic disease </li></ul><ul><li>SLE </li></ul><ul><li>alcoholism </li></ul><ul><li>B12 or folate difficiency </li></ul><ul><li>Hypersplenism </li></ul><ul><li>Overwhelming infection </li></ul><ul><li>Brucellosis </li></ul><ul><li>Sarcoidosis </li></ul><ul><li>T.B. </li></ul>
  31. 36. 3- Hypocellular marrow with or without cytopenia <ul><li>Q fever </li></ul><ul><li>Ligionaires </li></ul><ul><li>Toxoplasmosis </li></ul><ul><li>Anorexia Nervosa </li></ul><ul><li>T.B. </li></ul><ul><li>Hypothyroidism </li></ul>
  32. 37. Investigations of MDS <ul><li>CBC, film, retics….. </li></ul><ul><li>Bone marrow examination </li></ul><ul><li>Cytogenitics </li></ul>
  33. 38. Iron Studies <ul><li>SI </li></ul><ul><li>TIBC </li></ul><ul><li>Transferrin Saturation </li></ul><ul><li>Ferritin </li></ul>
  34. 39. Bone marrow aspiration and biopsy
  35. 40. PNH <ul><li>Hemolysis </li></ul><ul><li>Venous thrombosis </li></ul><ul><li>Aplastic anemia </li></ul>
  36. 41. P.N.H
  37. 42. PNH and Aplastic Anemia <ul><li>PNH is caused by an acquired genetic defect limited to the stem-cell compartment affecting the PIGA gene. </li></ul><ul><li>Mutations in the PIGA gene render cells of hematopoietic origin sensitive to increased complement lysis. </li></ul><ul><li>Approximately 20% of patients with aplastic anemia have evidence of PNH at presentation, as detected by means of flow cytometry. </li></ul><ul><li>Furthermore, patients whose disease responds after immunosuppressive therapy frequently recover with clonal hematopiesis and PNH. </li></ul>
  38. 44. Approaches to treatment of Bone Marrow Failure Syndromes <ul><li>Transfusions </li></ul><ul><li>Growth Factors </li></ul><ul><li>Immunosuppression </li></ul><ul><li>SCT </li></ul><ul><li>Others drugs </li></ul>
  39. 45. References <ul><li>Bethesda Handbook of Clinical hematology 2010 </li></ul><ul><li>Hamilton et al : Hematology in Clinical practice 2005 </li></ul><ul><li>E-medicine online textbook, Hematology </li></ul><ul><li>Other web resources </li></ul>
  40. 46. THANK YOU