Originally published as JCO Early Release 10.1200/JCO.2008.17.7279 on November 10 2008

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Armand, P. Articles by Antin, J. H. Search for Related Content PubMed PubMed Citation Articles by Armand, P. Articles by Antin, J. H. Social Bookmarking                            What's this?

Improved Survival in Lymphoma Patients Receiving Sirolimus for Graft-Versus-Host Disease Prophylaxis After Allogeneic Hematopoietic Stem-Cell Transplantation With Reduced-Intensity Conditioning

Philippe Armand, Supriya Gannamaneni, Haesook T. Kim, Corey S. Cutler, Vincent T. Ho, John Koreth, Edwin P. Alyea, Ann S. LaCasce, Eric D. Jacobsen, David C. Fisher, Jennifer R. Brown, George P. Canellos, Arnold S. Freedman, Robert J. Soiffer, Joseph H. Antin

From the Departments of Medical Oncology and Biostatistics, Dana-Farber Cancer Institute, Boston; and the Department of Medicine, Cambridge Hospital, Cambridge, MA

Corresponding author: Philippe Armand, MD, PhD, Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115; e-mail: parmand{at}partners.org

Purpose Inhibitors of the mammalian target of rapamycin (mTOR) kinase have shown clinical activity in several lymphoma subtypes. Sirolimus, an mTOR inhibitor, also has activity in the treatment and prophylaxis of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem-cell transplantation (HSCT). We hypothesized that the use of sirolimus for GVHD prophylaxis in patients with lymphoma might lead to improved survival after transplantation through a decreased incidence of disease progression.

Patients and Methods We retrospectively analyzed 190 patients who underwent transplantation for lymphoma. We compared the outcomes of patients who received sirolimus for GVHD prophylaxis with those of patients who received transplantation with a combination of a calcineurin inhibitor and methotrexate without sirolimus.

Results Overall survival (OS) after transplantation was significantly superior in the sirolimus group, which was confirmed in multivariable analysis. The benefit was restricted to patients undergoing reduced-intensity conditioning (RIC) HSCT (3-year OS, 66% for sirolimus group v 38% for no-sirolimus group; P = .007; hazard ratio [HR] for mortality in multivariable analysis = 0.5, P = .042). Patients who received sirolimus had a similar incidence of nonrelapse mortality but a decreased incidence of disease progression compared with patients who did not receive sirolimus (3-year cumulative incidence of progression, 42% v 74%, respectively; P < .001; HR for progression in multivariable analysis = 0.4, P = .01). The effect of sirolimus persisted after adjusting for the occurrence of GVHD. No such survival advantage was apparent in a similar comparison of patients who underwent transplantation for diseases other than lymphoma.

Conclusion This study suggests that sirolimus can independently decrease the risk of lymphoma progression after RIC HSCT, paving the way for prospective clinical trials.

published online ahead of print at www.jco.org on November 10, 2008.

Supported in part by Grant No. P01 HL070149 from the National Heart, Lung, and Blood Institute. P.A. is a recipient of a career development award from the Leukemia and Lymphoma Society.

Presented in part at the American Society of Blood and Marrow Transplantation/Center for International Blood and Marrow Transplant Research Tandem Meeting, February 13-17, 2008, San Diego, CA.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				B. N. Savani, P. R. Pohlmann, M. Jagasia, W. Chinratanalab, A. Kassim, B. Engelhardt, J. Greer, F. Schuening, and S. Goodman Does peritransplantation use of rituximab reduce the risk of EBV reactivation and PTLPD? Blood, June 11, 2009; 113(24): 6263 - 6264. [Full Text] [PDF]

				Survival Benefit from mTOR Inhibition in Lymphoma Journal Watch Oncology and Hematology, January 13, 2009; 2009(113): 2 - 2. [Full Text]