ANTITHYMOCYTE IMMUNOGLOBULIN IN SEVERE APLASTIC-ANEMIA AND BONE-MARROW TRANSPLANTATION

OBJECTIVE: To review antithymocyte immunoglobulin (ATG) and its curren t role in the treatment of severe aplastic anemia (SAA), focusing on A TG in immunosuppressive therapy compared with bone marrow transplantat ion (BMT). DATA SOURCES: A MEDLINE search (1966 to 1996) of English-la nguage literature and human subjects pertaining to ATG and BMT therapy in SAA was performed. Additional literature was obtained from referen ce lists of pertinent articles identified through the search. STUDY SE LECTION AND DATA EXTRACTION: All articles were considered for possible inclusion in the review. Pertinent information, as judged by the auth ors, was selected for discussion. DATA SYNTHESIS: The hallmark of SAA is pancytopenia and bone marrow hypoplasia. Although the etiology in a majority of cases remains unknown, current data implicate an immune-m ediated destruction of stem cells. ATG is a potent immunosuppressive a gent and has emerged as an important therapy for patients with SAA. Th e exact mechanism of immunosuppressive action is not fully understood, although ATG appears to disrupt cell-mediated immune responses result ing in inhibition or altered T-cell function. Numerous trials have eva luated the use of ATG both as monotherapy and in combination with othe r immunosuppressive agents. Treatment with ATG in SAA has demonstrated a 40-70% response rate. Data suggest that intensive immunosuppressive therapy with ATG in combination with cyclosporine may provide the opt imal immunosuppressive treatment. Questions still remain concerning co mplications and long-term survival of the patients. Although more than a 2-year follow-up shows a decline in mortality, a plateau in the sur vival curve was not achieved. BMT is a potential treatment for SAA. Al though there is a high initial mortality due to treatment-related toxi cities, successful marrow engraftment provides a cure for SAA. Many pa tients (75-90%) experience long-term survival after allogenic BMT. Age , donor availability, and severity of disease limit the number of elig ible patients. CONCLUSIONS: Due to excellent results with BMT, it has become the therapy of choice for selected patients with SAA. For patie nts who are not eligible for BMT, intensive immunosuppressive therapy with ATG and cyclosporine is recommended. Further study to better unde rstand the pathogenesis of SAA and prevent treatment-related complicat ions is essential to provide the best care to all patients.