Researchers from Ohio State University have reported that statins may have an impact on the incidence of acute graft-versus-host disease (GVHD) in recipients of allogeneic stem cell transplants. The details of this Phase II study were reported at the 2008 annual meeting of the American Society of Clinical Oncology in Chicago, May 30-June 2.¹

Prevention and treatment of acute and chronic GVHD without abrogating the graft-versus-tumor effect remains one of the elusive goals of allogeneic stem cell transplantation. Despite 40 years of intensive research, GVHD remains a major stumbling block to the success of allogeneic stem cell transplantation.

Atorvastin has been found to have immunomodulatory effects in central nervous autoimmune disease.² These observations led to a study by researchers from Stanford, which showed that atorvastin protected animals from acute GVHD without impacting a graft-versus-leukemia effect.³ A previous small study from Japan suggested that statins may be active for the treatment of chronic GVHD.⁴

The current study included 10 patients with leukemia who received statins for one month before allogeneic stem cell transplantation and for three months after. Only one patient developed grade II-IV acute GVHD. However, half the patients developed chronic GVHD. These authors suggested that there was a potential for statins to reduce acute GVHD compared with historical controls.

Comments: This was a very small study, and no conclusions can be reached based on these results. However, there is enough background data on the immunomodulatory effects of statins to further pursue this study with the aim of developing a rationale for a randomized trial.

Reference:

¹ Hamadani M, Awan FT, Elder P, et al. Statins reduce acute graft-versus-host disease in patients with acute leukemia undergoing allogeneic stem cell transplantation. Journal of Clinical Oncology. 2008;26: abstract number 7040.

² Youssef S, Stube O, Patarroyo JC, et al. The HMG-CoA reductase inhibitor, atovastin, promotes a Th2 and reverse paralysis in central nervous system autoimmune disease. Nature. 2002;420:78-84.

³ Zeiser R, Youssef S, Baker J, et al. Preemptive HMG-CoA reductase inhibition provides graft-versus host disease protection by Th-2 polarization while sparing graft-versus-leukemia activity. Blood. 2007;110:4588-4598.

⁴ Hori A, Kanda Y, Goyama S, et al A prospective trial to evaluate the safety of pravastin for the treatment of refractory chronic graft-versus-host disease. Transplantation. 2005;79:372-374.