Secondary Treatment of Acute Graft-versus-Host Disease: A Critical Review

Management of steroid-resistant or steroid-refractory acute graft-versus-host disease (aGVHD) poses one of the most vexing and difficult problems faced by transplantation physicians. In the current study, we used 10 criteria to evaluate 67 reports describing secondary treatment of patients with aGVHD. The goal of this exercise was not only to provide a critical summary of the literature but also to offer suggestions that could improve future studies. Areas especially in need of improvement include the use of a consistent treatment regimen, the assessment of response at a consistent prespecified time point, consideration of concomitant treatment in assessing response, documentation that selection bias was minimized, and the use of methods that test a formal statistical hypothesis based on a contemporaneous or historical benchmark. Our results suggest that previous published reports collectively offer little guidance in discerning the most effective treatments for patients with steroid-resistant or steroid-refractory aGVHD. Adherence to the proposed criteria in future reports would enable meaningful comparisons across studies and thereby accelerate progress in evaluating new treatments for patients with aGVHD.