There is evidence suggesting that Sirolimus, in combination with Tacrolimus, is active in the prevention of graft-versus-host disease ( GVHD ). Sirolimus-based immune suppression may suppress alloreactive T cells, while sparing the survival and function of regulatory T cells.

Researchers have conducted a randomized trial to compare the impact of Sirolimus / Tacrolimus against that of Methotrexate / Tacrolimus on the prevention of graft-versus-host disease and regulatory T-cell reconstitution.

Seventy-four patients were randomized 1:1 to Sirolimus / Tacrolimus or Methotrexate / Tacrolimus, stratified for type of donor ( sibling or unrelated ) and the patients' age.

The rate of grade II-IV acute graft-versus-host disease at 100 days was 43% ( 95% CI: 27-59% ) in the Sirolimus / Tacrolimus group and 89% ( 95% CI: 72-96% ) in the Methotrexate / Tacrolimus group ( P less than 0.001 ).

The rate of moderate / severe chronic graft-versus-host disease was 24% ( 95% CI: 7-47% ) in the Sirolimus / Tacrolimus group and 64% ( 95% CI: 41-79% ) in the Methotrexate / Tacrolimus group ( P=0.008 ).

Overall survival and patient-reported quality of life did not differ between the two groups.

On days 30 and 90 post-transplant, sirolimus-treated patients had a significantly greater proportion of regulatory T cells among the CD4+ cells in the peripheral blood, and isolated regulatory T cells were functional.

In conclusion, these data have demonstrated that Sirolimus / Tacrolimus prevents grade II-IV acute graft-versus-host disease and moderate-severe chronic graft-versus-host disease more effectively than does Methotrexate / Tacrolimus, and supports regulatory T-cell reconstitution following allogeneic hematopoietic cell transplantation. ( Xagena )

Pidala J et al, Haematologica 2012; 97:1882-1889

XagenaMedicine2012