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A. Types of Pure RBC Aplasia navigator

  1. Pure Red Cell Aplasia in Adults
    1. Most cases are idiopathic - associated with autoantibodies and/or cytotoxic T cells
    2. Associated with chronic lymphocytic leukemia or lymphoma - autoantibody mediated
    3. Some cases associated with parvovirus infection
    4. Thymoma associated
    5. Anti-erythropoietin (EPO) antibodies associated with certain EPO preparations
  2. Associated with Thymomas [1]
    1. 15% of pure RBC aplasia associated with thymomas
    2. Thymomas present as anterior mediastinal mass
    3. Dysglobulinemic processes with autoantibodies
  3. Red cell aplasia with anti-erythropoietin (Anti-EPO) antibodies [2]
  4. Anti-EPO Antibodies in Dialysis Patients Treated with EPO [3,4]
    1. Anti-EPO antibodies can develop in some patients treated with EPO
    2. Most of the patients received Eprex® (epoetin alpha)
    3. Mean time from EPO initiation to to ~11 months
    4. This can lead to pure red cell aplasia which was highest in 2001
    5. Drug monitoring program on Eprex® has lead to 80% reduction in pure red cell aplasia [5]
    6. Anti-EPO antibody titers decrease after cessation of treatment with EPO
    7. Blood transfusions generally required in setting of pure red cell aplasia
    8. Immunosuppressive therapy with cyclophosphamide associated with improved outcome [4]
  5. Blackfan-Diamond Syndrome [6]
    1. Chronic constitutional pure red cell aplasia in <2 year olds
    2. Selective decrease in bone marrow erythroid precursors
    3. Erythrocytes which are present are EPO responsive
    4. Appears in infants from birth to 2 years old
    5. 25-35% have congenital abnormalities
    6. About 15% of cases are inherited
    7. Patients present with pallor, fatigue, shortness of breath
    8. May be related to autoimmune attack on RBC precursors
    9. Role of IL3, IL6, and IGFs (possibly GM-CSF) under study
    10. Gene on chromosome 19q13 implicated in ~25% of inherited cases
    11. Chr 19q13 gene codes for a small ribosomal protein RPS19
    12. Another gene found on chr 8p associated with ~40% of cases

B. Laboratorynavigator

  1. Erythrocyte and reticulocyte numbers are specifically reduced
  2. Erythrocyte size (mean corpuscular volume) is low
  3. EPO levels are very high in most forms of pure RBC aplasia
  4. Other bone marrow lineages are normal
  5. Absence of chromosomal abnormalities, myelodysplasia, or marrow neoplastic involvement

C. Treatment navigator

  1. Blackfan Diamond Anemia
    1. Prednisone, initially 2mg/kg/day
    2. Followed by tapering to prednisone 2-4mg/3 times weekly if possible
  2. Chronic Glucocorticoids
    1. May be required for life usually at lower doses
    2. Immunosuppressive / glucocorticoid sparing agents may be used
    3. Prophylaxis for osteoporosis and other side effects may be required
  3. Plasmapheresis may be effective in some cases
  4. Parvovirus associated pure RBC aplasia responds to intravenous immunoglobulin (IVIg)
  5. Rituxumab (Rituxan®)
    1. Anti-CD20 monoclonal antibody specific for B lymphocytes
    2. Has been effective in chronic lymphocytic leukemia and lymphoma associated RBC aplasia
  6. Anti-IL2 Receptor Antibody (Daclizumab, Zenapax®) [7,8]
    1. Humanized (IgG1 Fc) anti-IL2R alpha chain (CD25) Ab
    2. Half life of the drug is ~20 days
    3. Dose for pure RBC aplasia is 1mg/kg over 15 minutes, biweekly for 5 infusions
    4. Approved by FDA for prevention of acute renal allograft rejection
    5. Good side effect profile with no increase in infections versus control in most studies
  7. Thymoma Treatment
    1. Surgical Resection
    2. Radioactive Octreotide - somatostatin analog in combination with prednisone [9]
  8. Cessation of treatment with EPO leads to reduction in Anti-EPO titers

References navigator

  1. Dhaliwal G, Schmidt KE, Gilden DJ, Saint S. 2004. NEJM. 350(1):60 (Case Discussion) abstract
  2. Casadevall N, Dupuy E, Molho-Sabatier P, et al. 1996. NEJM. 334(10):630 abstract
  3. 6. Casadevall N, Nataf J, Viron B, et al. 2002. NEJM. 346(7):469
  4. Verheist D, Rossert J, Casadevall N, et al. 2004. Lancet. 363(9423):1768
  5. Bennett CL, Luminari S, Nissenson AR, et al. 2004. NEJM. 351(14):1403 abstract
  6. Attar EC and Hasserjian RP. 2006. NEJM. 354(19):2047 (Case Record) abstract
  7. Basiliximab and Daclizumab. 1998. Med Let. 40(1036):93 abstract
  8. Sloand EM, Scheinberg P, Maciejewski J, Young NS. 2006. Ann Intern Med. 144(3):181 abstract
  9. Palmieri G, Lastoria S, Colao A, et al. 1997. NEJM. 336(4):263 abstract