Graft-versus-host disease (GVHD) represents a serious complication of allogeneic BMT and remains one of the most difficult challenges for clinicians. Rapamune (sirolimus) is indicated for the prophylaxis of organ rejection in patients aged 13 years or older receiving renal transplants. It is off-label for grft versus host disease that may occurr after an allogeneic stem cell transplant.
A retrospective study of 190 patients suggested that Rapamune is beneficial in reduced intensity allogeneic transplantation. The publicatio of this study was followed by a dissenting voice that pointed out that it was a retrospective study that hinged on outcome of only 23 patients.
Reliable evidence shows that Sirolimus is in clinical trials, for example, Rapamycin for Prevention of Chronic Graft-Versus-Host Disease, NCT00623012. A prospective phase II study is ongoing: “A Phase II/III Randomized, Multicenter Trial Comparing Sirolimus Plus Prednisone, Sirolimus/Extracorporeal Photopheresis Plus Prednisone, and Sirolimus/Calcineurin Inhibitor Plus Prednisone for the Treatment of Chronic Graft-versus-Host Disease (BMT CTN #0801)”
A 2012 guideline (Dinghan et al) recommends it for second line treatment.
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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. Ant, Improved Survival in Lymphoma Patients Receiving Sirolimus for Graft-Versus-Host Disease Prophylaxis After Allogeneic Hematopoietic Stem-Cell Transplantation With Reduced-Intensity Conditioning in JCO December 10, 2008 vol. 26 no. 35 5767-5774
Jayesh Mehta Sirolimus-Containing Graft-Versus-Host Disease Prophylaxis in Patients With Lymphoma JCO October 1, 2009 vol. 27 no. 28 e138