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Immunosuppressive therapies in the management of acquired immune-mediated marrow failures.

AbstractPURPOSE OF REVIEW:
Immunosuppression is a key treatment strategy for patients suffering from aplastic anemia or related immune-mediated bone marrow failure syndromes. Several attempts have been performed to improve the standard immunosuppression regimen of horse antithymocyte globulin (h-ATG) and cyclosporine A (CyA).
RECENT FINDINGS:
The addition of a third immunosuppression agent to h-ATG + CyA did not result in any improvement. Antilymphocyte agents other than h-ATG have been investigated. A rabbit-ATG preparation, which was known to be more immunosuppressive than h-ATG, resulted in markedly inferior outcome in a large randomized study from the National Institutes of Health. These data seem to be confirmed in additional experiences with rabbit-ATG from other groups. Cyclophosphamide and alemtuzumab have been proven to be biologically active in small studies, but available data suggest inferior outcomes when compared with h-ATG. All these alternative agents result in a more pronounced lymphocyte depletion, suggesting that the actual mechanisms of action of immunosuppressive therapy in aplastic anemia are not fully understood.
SUMMARY:
Immunosuppression by h-ATG and CyA remains the standard of care for aplastic anemia patients lacking a low-risk transplant procedure, resulting in a 60-70% response rate. Rabbit-ATG, cyclophosphamide and alemtuzumab demonstrated a biological activity, but resulted in inferior outcome as compared with h-ATG; thus, they are not recommended as front-line therapy of aplastic anemia.
AuthorsAntonio M Risitano
JournalCurrent opinion in hematology (Curr Opin Hematol) Vol. 19 Issue 1 Pg. 3-13 (Jan 2012) ISSN: 1531-7048 [Electronic] United States
PMID22143074 (Publication Type: Journal Article, Review)
Chemical References
  • Antilymphocyte Serum
  • Immunosuppressive Agents
  • Cyclosporine
Topics
  • Anemia, Aplastic (drug therapy)
  • Animals
  • Antilymphocyte Serum (therapeutic use)
  • Bone Marrow Diseases
  • Bone Marrow Failure Disorders
  • Cyclosporine (therapeutic use)
  • Hemoglobinuria, Paroxysmal (drug therapy)
  • Horses
  • Humans
  • Immunosuppression Therapy (methods)
  • Immunosuppressive Agents (therapeutic use)
  • Rabbits

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