Published online 30 January 2009
Haematologica, Vol 94, Issue 3, 348-354 doi:10.3324/haematol.13829
Copyright © 2009 by Ferrata Storti Foundation
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Original Article

Treatment of severe aplastic anemia with a combination of horse antithymocyte globulin and cyclosporine, with or without sirolimus: a prospective randomized study

Phillip Scheinberg1, Colin O. Wu2, Olga Nunez1, Priscila Scheinberg1, Carol Boss1, Elaine M. Sloand1, Neal S. Young1

1 Hematology Branch and
2 Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA

Correspondence: Phillip Scheinberg, Hematology Branch, NHLBI, 10 Center Drive, Building 10 CRC, Room 3-5140, MSC 1202, Bethesda, MD 20892-1202, USA. E-mail:scheinbp{at}mail.nih.gov

Background: We hypothesized that the addition of sirolimus to standard horse antithymocyte globulin (h-ATG) and cyclosporine (CsA) would improve response rates in severe aplastic anemia, due to its complementary and synergistic properties to cyclosporine A.

Design and Methods: To test this hypothesis, we conducted a prospective randomized study comparing hATG/CsA/sirolimus to standard h-ATG/CsA. A total of 77 patients were treated from June 2003 to November 2005; 35 received h-ATG/CsA/sirolimus and 42 h-ATG/CsA. The two groups were well matched demographically and in blood counts prior to therapy. The primary end-point was hematologic response rate at 3 months, defined as no longer meeting the criteria for severe aplastic anemia. The study was powered to show a superior hematologic response rate of h-ATG/CsA/sirolimus compared to standard h-ATG/CsA.

Results: The overall response rate at 3 months was 37% for h-ATG/CsA/sirolimus and 50% for h-ATG/CsA and at 6 months 51% for h-ATG/CsA/sirolimus and 62% for h-ATG/CsA. After a planned interim analysis of 30 evaluable patients in each arm, accrual to the h-ATG/CsA/sirolimus arm was closed, as the conditional power for rejecting the null hypothesis was less than 1%. The rate of relapse, clonal evolution, and survival (secondary outcomes) did not differ significantly between patients treated with the two different regimens.

Conclusions: Despite a theoretical rationale for its use, sirolimus did not improve the response rate in patients with severe aplastic anemia when compared to standard h-ATG/CsA

Key words: aplastic anemia, antithymocyte globulin, cyclosporine, sirolimus, immunosuppression, pancytopenia.


Related Article

Immunosuppressive treatment for aplastic anemia: are we hitting the ceiling?
Jakob R. Passweg, André Tichelli
Haematologica 2009 94: 310-312. [Full Text] [PDF]



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J. R. Passweg and A. Tichelli
Immunosuppressive treatment for aplastic anemia: are we hitting the ceiling?
Haematologica, March 1, 2009; 94(3): 310 - 312.
[Full Text] [PDF]