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Bone marrow failure and myelodysplasia

Bone marrow failure and myelodysplasia. David Lee, MD, FRCPC. Outline. Approach to pancytopenia Myelodysplasia Aplastic anemia Febrile neutropenia. Approach to pancytopenia. pancytopenia. increased destruction. sequestration. decreased production. MDS infiltration B12 def AA

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Bone marrow failure and myelodysplasia

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  1. Bone marrow failure and myelodysplasia David Lee, MD, FRCPC

  2. Outline • Approach to pancytopenia • Myelodysplasia • Aplastic anemia • Febrile neutropenia

  3. Approach to pancytopenia pancytopenia increased destruction sequestration decreased production • MDS • infiltration • B12 def • AA • drugs • viruses • radiation • immune • sepsis • hypersplenism

  4. A practical approach pancytopenia meds spleen sepsis retics, B12/folate, ANA, SPE, abdo U/S bone marrow hypocellular hypercellular

  5. hypercellular destruction hypersplenism MDS infiltration B12 def myelofibrosis other hypocellular aplastic anemia

  6. Myelodysplastic syndrome (myelodysplasia or MDS) • a heterogeneous group of clonal myeloid stem cell disorders characterized by cytopenias • dysplasia of one or more cell lines is the morphologic hallmark of MDS • increased apoptosis despite increased proliferation in the marrow • a common condition in the elderly

  7. Dysplastic erythroid maturation (dyserythropoiesis) Dyserythropoiesis Normal

  8. MDS • cause is unknown in most patients • chemotherapy and radiation can cause MDS (ie can be a late adverse effect) • immunological and microenvironmental factors may have a pathogenic role

  9. Clinical and laboratory manifestations • anemia • macro-, normocytic (occasionally microcytic) • oval macrocytes on blood film • neutropenia • thrombocytopenia • dysplastic features • cytogenetic abnormalities are common

  10. Ring sideroblasts

  11. Management • MDS is not known to be curable with conventional Rx such as chemotherapy • consider transplant in the young, or investigational Rx. • for most patients, treatment is supportive (RBC transfusions, treat infections) • growth factors, erythropoietin effective in some patients • lenalidomide effective in some

  12. Prognosis of MDS • median survival: 0.3 to 12 years • worse prognosis if • increased blasts in marrow • presence of poor prognosis karyotype • 2 or 3 cytopenias • many patients with increased blasts evolve to AML

  13. Aplastic anemia

  14. Aplastic anemia • pancytopenia with hypoplastic marrow • not due to marrow involvement with neoplastic cells • rare

  15. Causes of aplastic anemia • drugs/chemicals • radiation • viruses: hep C, CMV, EBV, HIV • congenital (Fanconi’s anemia) • no underlying condition or external cause in 50% • immune-mediated aplasia

  16. Relationship between radiation dosage and marrow aplasia from: Hoffman Hematology 4th ed. 2005.

  17. Clinical and laboratory features • symptoms due to pancytopenia • no lymphadenopathy or splenomegaly • anemia is usually normocytic • hypocellular marrow is the hallmark • need to rule out other disorders

  18. Course • survival is usually limited by the severity of neutropenia • death usually due to infection • neutrophil count < 0.2 x 109/L: median survival of less than 1 year with supportive care alone

  19. Treatment • allogeneic stem cell transplant • immunosuppression • cyclosporine • anti-thymocyte globulin • supportive care • transfusions

  20. The neutropenic patient • Compromise of host immunity • underlying disease • myeloma, lymphoma, acute or chronic leukemias, etc • therapy for underlying disease • chemotherapy • steroids • iatrogenic manipulations • indwelling catheters • exposure to nosocomial pathogens

  21. Neutropenia • Neutropenia = ANC < 0.5 - 1.0 x 109/L • common adverse effect of chemotherapy • increased risk of bacterial infections increases with severity & duration of neutropenia • ~ 14% when ANC < 0.5 - 1.0 x 109/L • 24-60% risk when ANC < 0.1 x 109/L • 100% when duration of neutropenia > 5 wk • (also increasing risk of fungal infections as duration of neutropenia increases)

  22. Febrile neutropenia • Fever > 38.3 and ANC < 0.5 - 1.0 x 109/L • At risk of sepsis! – inpatient mortality ~7% • Look for focus of infection • Must culture and start antibiotics • cover Pseudomonas aeruginosa and other gram negatives (eg. ceftazidime) • consider G-CSF (filgrastim) for current or future cycles of chemotherapy

  23. Outline • Approach to pancytopenia • Myelodysplasia • Aplastic anemia • Febrile neutropenia

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