Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2009 Mar;94(3):348-54.
doi: 10.3324/haematol.13829. Epub 2009 Jan 30.

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

Phillip Scheinberg  1 , Colin O Wu, Olga Nunez, Priscila Scheinberg, Carol Boss, Elaine M Sloand, Neal S Young
Affiliations
Randomized Controlled Trial

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

Phillip Scheinberg et al. Haematologica. 2009 Mar.

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00061360.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Cumulative incidence of relapse in the groups treated with different immunosuppressive regimens. The h-ATG/CsA/sirolimus group (solid line) had a relapse rate of 28% by 3 years and the h-ATG/CsA taper group 25% (dotted line).
Figure 2.
Figure 2.
Cumulative incidence of disease evolution among the patients treated with each of the two immunosuppressive regimens. The evolution rate for the h-ATG/CsA/sirolimus arm (dotted line) was not different from that in the h-ATG/CsA taper arm (solid line).
Figure 3.
Figure 3.
Overall survival for patients in the h-ATG/CsA/sirolimus (solid line) and h-ATG/CsA taper arm (dotted line). Patients who underwent hematopoietic stem cell transplantation were censored at the time of transplantation.
See this image and copyright information in PMC

Comment in

References

    1. Locasciulli A, Oneto R, Bacigalupo A, Socie G, Korthof ET, Bekassy A, et al. Outcomes of patients with acquired aplastic anemia given first line bone marrow transplantation or immunosuppressive treatment in the last decade: a report from the European Group for Blood and Marrow Transplantation. Haematologica. 2007;92:11–8. - PubMed
    1. Rosenfeld S, Follman D, Nu¤ez O, Young NS. Antithymocyte globulin and cyclosporine for severe aplastic anemia. Association between hematologic response and long-term outcome. JAMA. 2003;289:1130–5. - PubMed
    1. Bacigalupo A, Bruno B, Saracco P, Di Bona E, Locasciulli A, Locatelli F, et al. Antilymphocyte globulin, cyclosporine, prednisolone, and granulocyte colony-stimulating factor for severe aplastic anemia: an update of the GITMO/EBMT study on 100 patients. European Group for Blood and Marrow Transplantation (EBMT) Working Party on Severe Aplastic Anemia and the Gruppo Italiano Trapianti di Midollo Osseo (GITMO) Blood. 2000;95:1931–4. - PubMed
    1. Kojima S, Hibi S, Kosaka Y, Yamamoto M, Tsuchida M, Mugishima H, et al. Immunosuppressive therapy using antithymocyte globulin, cyclosporine, and danazol with or without human granulocyte colony-stimulating factor in children with acquired aplastic anemia. Blood. 2000;96:2049–54. - PubMed
    1. Fuhrer M, Rampf U, Baumann I, Faldum A, Niemeyer C, Janka-Schaub G, et al. Immunosuppressive therapy for aplastic anemia in children: a more severe disease predicts better survival. Blood. 2005;106:2102–4. - PubMed

Publication types

MeSH terms

Associated data