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Mds

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Myelodysplastic syndromes

Myelodysplastic syndromes

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  • 1.  
  • 2. Myelodysplasia : from marrow failure to malignant transformation Ahmed Elshebiny, MD University of Menoufyia
  • 3. Blood is continuously renewed
  • 4. The Bone Marrow is the blood Factory May be exposed to damage or failure
  • 5.  
  • 6.  
  • 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
  • 8. Bone Marrow Failure
    • May involve one or more cell lines
    • Lymphocytes are usually spared
  • 9. Venn Diagram AML APLASTIC ANEMIA MDS PNH
  • 10. Bone Marrow Failure Syndromes
  • 11. Hematology lectures Myelodysplasia
  • 12. Myelodysplastic syndrome (MDS)
    • It is a term for a heterogeneous collection of haemopoietic stem cell disorders usually affecting older adults.
    • There is underlying ineffectiveness of haemopoiesis that results in dysplasia of bone marrow precursors and peripheral cytopenias.
  • 13. Dysplastic erythroid maturation (dyserythropoiesis) Normal Dyserythropoiesis
  • 14. Pathology
      • The cardinal features of MDS are
        • Increased marrow proliferation
        • Failure of stem cells to differentiate
        • And increased marrow apoptosis.
      • The disease is of clonal origin
      • Chromosomal abnormalities are detectable in 30-70% of patients. The no. of chromosomal abn. may correlate with the risk of progression to AML.
  • 15. Epidemiology
    • MDS is primarily a disease of the elderly, with a median age at diagnosis of between 60-80 years.
    • The incidence is approximately double that of AML.
    • The recent increase in MDS incidence may be related to growing awareness, better diagnosis, and an aging population.
  • 16. Etiology
    • Primary
    • Secondary
  • 17. MDS (clinical)
    • 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.
    • Approximately half of the patients transform to AML.
  • 18. MDS (clinical)
    • May be preceded by a few years by an unexplained macrocytic anemia with no evidence of megaloblastic anemia and a mild thrombocytopenia or neutropenia.
    • Thrombocytopenia as the presenting symptom may be mistaken for immune thrombocytopenia.
  • 19. Cytogenetic abnormalities in MDS
  • 20.  
  • 21.  
  • 22. FAB classification of MDS
    • In 1982 The FAB group classified MDS according to Morphology and the % of myeloblasts in the BM and PB.
    • These included
      • Refractory anaemia (RA)
      • Refractory anaemia with ringed sideroblasts (RARS)
      • Refractory anaemia with excess blast in marrow (RAEB)
      • CMML
      • Refractory anaemia with excess blast in transformation
      • (RAEB-t)
  • 23. FAB classification of MDS
  • 24. Newer classifications
    • WHO
    • IPSS
  • 25. Treatment
    • Stem cell transplant
    • DNA methyl transferase inhibitors
      • Azacytidine
    • Immunomodulation
      • Thalidomide and lenalidomide
    • Immunosupression
    • Histone deacetylase inhibitors
    • Chemotherapy
  • 26. Fate of MDS
    • Transformation to acute leukaemia occurs in up to 40% of patients.
    • Although progression to frank AML is a primary concern, 20-40 % or more of patients die of infections and/or haemorrhagic complications.
  • 27. Sideroblastic anemias
    • Inherited (X-linked)
    • Acquired
      • Myelodysplasis
      • Myeloproliferative disorders
      • Myeloid leukemia
      • Lead toxcicity
      • Drugs e.g INH
      • Alcohol
      • others
  • 28. Ring sideroblasts
  • 29. Aplastic Anemias Aplastic Anemias Acquired Conistituitional Single line Agranulocytosis Pure Red Cell Aplasia Multilineage
  • 30. Aplastic Anemia
    • Named so in 1904
    • The theoretical basis for marrow failure includes primary defects in or damage to the stem cell or the marrow microenvironment
    • Distinction between congenital or acquired may be difficult
    • 80 % of patients have acquired cause which is an autoimmune disease
  • 31. Aplastic Anemia
  • 32. Drugs associated with AA
    • NSAIDs(Butazones, Indomethacin,Piroxicam, Diclofenac)
    • Antibiotics( e.g sulfonamides)
    • Furosemide
    • Phenothiazines
    • Corticosteroids
    • Penicillamine
    • Gold
    • Allopurinol
  • 33. Pancytopenia
    • Pancytopenia has many causes of which AA is not the most common
  • 34. 1-Pancytopenia with hypocellular bone marrow
    • Acquired Aplastic Anemia
    • Inherited Aplastic Anemia
    • Some MDS
    • Rare aleukemic leukemia
    • Some acute lymphoblastic leukemia
    • Some lymphomas of bone marrow
  • 35. 2-Pancytopenia with cellular bone marrow
    • Primary bone marrow disease
    • MDS
    • PNH
    • Myelofibrosis
    • Mylophthisis
    • Hairy cell leukemia
    • Aleukemic leukemia
    • Secondary to systemic disease
    • SLE
    • alcoholism
    • B12 or folate difficiency
    • Hypersplenism
    • Overwhelming infection
    • Brucellosis
    • Sarcoidosis
    • T.B.
  • 36. 3- Hypocellular marrow with or without cytopenia
    • Q fever
    • Ligionaires
    • Toxoplasmosis
    • Anorexia Nervosa
    • T.B.
    • Hypothyroidism
  • 37. Investigations of MDS
    • CBC, film, retics…..
    • Bone marrow examination
    • Cytogenitics
  • 38. Iron Studies
    • SI
    • TIBC
    • Transferrin Saturation
    • Ferritin
  • 39. Bone marrow aspiration and biopsy
  • 40. PNH
    • Hemolysis
    • Venous thrombosis
    • Aplastic anemia
  • 41. P.N.H
  • 42. PNH and Aplastic Anemia
    • PNH is caused by an acquired genetic defect limited to the stem-cell compartment affecting the PIGA gene.
    • Mutations in the PIGA gene render cells of hematopoietic origin sensitive to increased complement lysis.
    • Approximately 20% of patients with aplastic anemia have evidence of PNH at presentation, as detected by means of flow cytometry.
    • Furthermore, patients whose disease responds after immunosuppressive therapy frequently recover with clonal hematopiesis and PNH.
  • 43.  
  • 44. Approaches to treatment of Bone Marrow Failure Syndromes
    • Transfusions
    • Growth Factors
    • Immunosuppression
    • SCT
    • Others drugs
  • 45. References
    • Bethesda Handbook of Clinical hematology 2010
    • Hamilton et al : Hematology in Clinical practice 2005
    • E-medicine online textbook, Hematology
    • Other web resources
  • 46. THANK YOU