The graft-versus-leukaemia effect after allogeneic bone-marrow transplantation: assessment through competing risks approaches.

In failure time studies involving a chronic disease such as cancer, data often focus on one or more non-fatal events, in addition to survival, to describe the course of the disease. In the example of allogeneic bone marrow transplantation in leukaemic patients, acute graft-versus host disease (aGvHD), relapse and death were taken as the reported events, and we focused on testing the existence of graft-versus-leukaemia (GvL) effect, i.e. that the occurrence of aGvHD modifies the probability of relapse. One of the weaknesses of the standard competing risks models is their inability to model secondary relapses. We thus derived, from two competing risks models, two estimators of cumulative incidence functions of primary and secondary relapses, as well as statistics to test the GvL effect. The approach is illustrated by application to a data set from a cohort of 442 children with acute leukaemia who received an unrelated transplant.