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Intensive immunosuppression with antithymocyte globulin and cyclosporine as
treatment for severe acquired aplastic anemia
SJ Rosenfeld, J Kimball, D Vining and NS Young
Hematology Branch, National Heart, Lung, and Blood Institute, National
Institutes of Health, Bethesda, MD 20892, USA.
Immunosuppressive therapy can produce hematologic improvement in a large
proportion of patients with severe aplastic anemia. Antithymocyte globulin
(ATG) is the current treatment of choice for patients who do not have
histocompatible sibling donors or who are otherwise inegligible for
allogeneic bone marrow transplantation. About 50% of patients respond to an
initial course of ATG, and many nonresponders can be salvaged by subsequent
treatment with cyclosporine (CsA). To determine whether simultaneous
administration of these agents could further improve response rates, we
enrolled 55 patients in a therapeutic trial of 4 days of ATG and 6 months
of CsA. Among the 51 patients who had not received previous courses of ATG
or CsA, 67% had responded by 3 months, and 78% had responded by 1 year
(response was defined as an increase in peripheral blood counts sufficient
that a patient no longer met the criteria for severe disease). There was a
high incidence of relapse (36% actuarial risk at 2 years), but most
relapsed patients responded to additional courses of immunosuppression, and
relapse was not associated with a significant survival disadvantage.
Evolution to myelodysplastic syndromes and acute leukemia was rare (1 of 51
patients), but the later appearance of paroxysmal nocturnal hemoglobinuria
was more common (5 of 51 patients). Actuarial survival was 86% at 1 year
and 72% at 2 years. These data support the use of a combination
immunosuppressive regimen containing both ATG and CsA as first-line therapy
for severe aplastic anemia.
Volume 85,
Issue 11,
pp. 3058-3065,
06/01/1995
Copyright © 1995 by The American Society of Hematology
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