1. Myelodysplastic disorders
Clonal disorder
Stable cytopenias for 2-6 weeks
Morphologic evidence of dysplastic changes in at least 2 hematopoietic cell lines
Hypercellular or normocellular bone marrow
Propensity to transform into AML in 20% of cases

2. Myelodysplastic disorders
Ineffective erythropoiesis due to increased apoptosis (programmed cell death)
Impaired cellular maturation due to intrinsic defects in cells of neoplastic clone
Altered responses to regulatory hormones

3. Myelodysplastic disorders
Most over age 60
Slight male predominance
History of acquired or congenital risk factors
radiation, chemotherapy (alkylating agents, topoisomerase inhibitors)
Hodgkin’s disease, non-Hodgkin’s lymphoma, multiple myeloma
ovarian CA, breast CA
NH3, diesel, benzene
aplastic anemia, paroxysmal nocturnal hemoglobinuria
Fanconi’s anemia, Down’s syndrome, Turner’s syndrome, Bloom’s syndrome

4. Myelodysplastic disorders
Red Cells
Macrocytosis
Low reticulocyte count
Ringed sideroblasts
Nuclear-cytoplasmic asynchrony
Bizarre nuclear configurations
Abnormal Fe metabolism

5. Macrocytosis, biphenotypic population Ringed sideroblast
Dysmorphic nucleated rbc’s
Increased iron stores

6. Myelodysplastic disorders
White Cells
Hypogranulation
Nuclear-cytoplasmic asynchrony
Pseudo-Pelger-Huet anomaly
Defective adhesion, phagocytosis, and bacterial killing

7. Hypogranulation, nuclear-cytoplasmic asynchrony
Pseudo-Pelger-Huet anomaly
Stodtmeister cell
Aberrant granulation

8. Myelodysplastic disorders
Platelets
Giant, agranular platelets
Micromegakaryocytes and mononuclear megakaryocytes
Abnormal platelet function

9. Hypogranular platelets Circulating micromegakaryocyte
Abnormal megakaryocyte
Mononuclear megakaryocyte

10. Other manifestations:
Myelodysplastic disorders
Other manifestations:
Rheumatologic - vasculitis, arthritis, lupus-like syndromes
Neurologic - peripheral neuropathy
Metabolic - abnormal LFT’s
Dermatologic - urticaria pigmentosa, chloroma, Sweet’s syndrome

11. Chloroma Sweet’s Syndrome
Granulocytic Sarcoma
Extramedullary aggregates of blast cells
Acute neutrophilic dermatosis
Tender red plaques and nodules Benign infiltration of PMN’s in lower dermis

12. Myelodysplastic disorders
C.M.L.
M.D.S. - five types:
Refractory Anaemia
Refractory Anaemia with ring sideroblasts
Refractory Anaemia with excess blasts
Refractory Anaemia with excess blasts in transformation
Chronic myelomonocytic leukaemia

13. FAB Classification of MDS

14. Supportive care of MDS Supportive care
Hormonal and immunosuppressive therapy
Hematopoietic growth factors
Differentiating agents
Chemotherapy
Bone marrow transplantation

15. Supportive care of MDS RBC and platelet transfusions
Deferoxamine (Desferal)
Antibiotics
Avoidance of myelotoxic medications
Pyridoxine 200 mg QD

16. Immunotherapy in MDS Antithymocyte globulin +/- cyclosporine
Complete remissions in hypoplastic MDS
Eliminated transfusion requirement in 44% with normocellular and hypercellular MDS
Monoclonal antibody against CD33
Disproportionately expressed on blast cells
Effective in those with <10% blasts

17. Chemotherapy in MDS Single agents Low-dose cytarabine (LoDAC)
High-dose cytarabine (HiDAC)
Homoharringtonine
Topotecan
Combination therapy
Standard AML induction therapy
Fludarabine, cytarabine, idarubicin
Cyclophosphamide, cytarabine, topotecan

18. Bone Marrow Transplantation in Myelodysplastic Syndrome
Allogeneic BMT
Best results with
young patients (DFS 75%)
marrow blasts counts < 5%
absence of marrow fibrosis
interval to BMT < 5 years
matched sibling donor
Treatment-related mortality 34-55%
Disease-free survival 26-45%
Relapse 19-34%

19. Bone Marrow Transplantation in Myelodysplastic Syndrome
Autologous BMT
Higher relapse rate