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Sickle Cell Disease in the 21 st Century

Sickle Cell Disease in the 21 st Century . James R. Eckman, MD Professor of Hematology, Oncology, and Medicine Emory University School of Medicine. Disclosures. Dr. James Eckman, Personal/Professional Financial Relationships with Industry.

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Sickle Cell Disease in the 21 st Century

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  1. Sickle Cell Disease in the 21st Century James R. Eckman, MD Professor of Hematology, Oncology, and Medicine Emory University School of Medicine

  2. Disclosures Dr. James Eckman, Personal/Professional Financial Relationships with Industry *Consulting, scientific advisory board, industry-sponsored CME, expert witness for company, FDA representative for company, publishing contract, etc. **Does not include stock in publicly-traded companies in retirement funds and other pooled investment accounts managed by others.

  3. AMERICAN DISCOVERYHerrick JB Arch Intern Med 6:517-521, 1910

  4. OBJECTIVES • Understand the change in prognosis in sickle cell disease • Define the role of hydroxyurea in patients with sickle cell disease • Understand the unique considerations for transfusion in sickle cell disease.

  5. SICKLE SURVIVALQuinn et al Blood 2010;103:4023

  6. Improving Survival • Sergeant et al. Int J Lab Hem 2009;31:585-596. • Cohort of 106 individuals with Hb SS over the age of 60. • Female age and increased fetal hemoglobin associated with survival • 40 were still alive ages 60 to 87 • Aging associated with decreased frequency of pain episodes, more anemia and renal insufficiency

  7. HYDROXYUREA

  8. MULTICENTER HYDROXYUREA TRIAL * Group Hydroxyurea Placebo p value Pain Episodes 2.5 / year 4.5 / year p < 0.001 Pain Admits 1.0 / year 2.4 / year p < 0.001 Acute Chest 25 episodes 51 episodes p < 0.001 Transfused 48 73 p < 0.001 Total Units 336 586 p = 0.004 * Van der Waerden’s test. Charache et al. N Engl J Med 322:1317, 1995.

  9. Hydroxyurea Improves Survival

  10. Hydroxyurea Improves Survival 10 Year Predicted Survival Adults: 131 treated with Hydroxyurea and 199 usual care for up to 17 years (median 8 verses 5 years) Voskaridou E et al. Blood 2010; 115: 2354-2363

  11. Hydroxyurea is Effective • 312 North Carolina Medicaid enrollees 6/2000 – 8/2008, 12 month follow-up • 35 % adherent MPR ≥ 80%, mean 60% • Adherence associated with: • Reduced SCD hospitalizations (HR = 0.65, p=.03510) • SCD related ER visits (HR = 0.58, p = .0079) • All cause ER visits (HR = 0.72, p = .0388) • Pain crisis ER visits (0.66, p = .0130) Candrilli et al. Am. J. Hematol. 2011;86:273-277.

  12. Hydroxyurea may be Cost Effective Candrilli et al. Am. J. Hematol. 2011;86:273-277.

  13. Hydroxyurea Dosing • Starting dose 10 mg/kg/day • Dose is increased by 5 mg/kg/day every 12 weeks to toxicity or a maximum of 35 mg/kg/day • After toxicity, the dose is reduced 2.5 mg/kg/day after counts recover • If no further toxicity, this is the maximum tolerated dose ( MTD ) • Monitoring q 2 weeks to MTD then q 8 weeks

  14. Hydroxyurea Toxicity • Predictable effects on bone marrow • Increased pigmentation and hair breakage • Azospermia in males • Concerns about pregnancy while taking the drug • No data or scientific basis for use in Hb SC disease

  15. Reasons For TransfusionSickle Cell Anemia • Physiologic correction of symptomatic anemia • Reduce the whole blood viscosity • Suppress production of sickle cells • Reduction in hemolysis • Prevention of complications

  16. COMPLICATIONS OF TRANSFUSION • Cardiovascular Complications • Alloimmunization • Delayed Transfusion Reactions • Autoimmune Hemolytic Anemia • Transmission of Infection • Hepatitis • Human Immunodeficiency Virus • Other Agents - CMV, EB • Bacterial Infections • Iron Overload

  17. WHOLE BLOOD VISCOSITY Erslev in Williams, Beutler, Erslev. Hematology 1990.

  18. WHOLE BLOOD VISCOSITY Schmalzer et al. Transfusion 1987;27:228 - 233

  19. SICKLE CELL DISEASEALLOANTIBODY RESPONSE Reisner et al. Tissue Antigens 30:161, 1987

  20. ALLOIMMUNIZATION 107 SICKLE CELL PATIENTS Vichinsky et al. New Engl J Med 322:1617, 1990

  21. ALLOIMMUNIZATION IN SICKLE CELL Vichinsky et al. New Engl J Med 322:1617, 1990

  22. TRANSFUSION IN SICKLE CELL • Transfuse C, D, E, Kelly similar units • Transfuse exclusively with phenotypically similar blood after the first alloantibody • Some advocate phenotypically similar blood for all transfusions • Recruit for blood donation from the African American population *Eckman and Reid, Charache, Lubin NIH Pub No. 95-2117, 1995.

  23. Transfusion Number Inati et al. Blood 2010;115(14):2980

  24. Ferritin in Assessing Iron BurdenAdamiewicz et al. Blood 2009;114(21):4632

  25. MRI Assessment of LICWood et al. Blood 2005 106: 1460-1465

  26. MAINTENANCE OF LOWER FERRITIN LEVEL PREDICTS SURVIVAL AT UCLH 1.00 Ferritin <2500 μ/L on more than two thirds of occasions 0.75 Ferritin >2500 μ/L on more than one thirdof occasions Survival probability 0.50 0.25 0 0 5 10 15 Years of follow-up UCLH = University College London Hospital. Porter. Unpublished data.

  27. EXJADE® (DEFERASIROX)A Novel Once-daily Oral Iron Chelator

  28. Thank You for Your Attention ! WWW . SCINFO . ORG

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