Establishment of Definitions and Review Process for Consistent Adjudication of Cause-specific Mortality after Allogeneic Unrelated-donor Hematopoietic Cell Transplantation

Abstract

Clinical trials commonly use adjudication committees to refine endpoints, but observational research or genome-wide association studies rarely do. Our goals were to establish definitions of cause-specific death after unrelated-donor allogeneic hematopoietic cell transplantation (URD-HCT), to estimate discordance between reported and adjudicated cause-specific death, and to identify factors contributing to inconsistency in cause-specific death determination. A consensus panel adjudicated cause-specific death in 1484 patients who died within 1 year after HCT, derived from 3532 acute leukemia or myelodysplasia patients after URD-HCT from 2000 to 2011 reported by 151 US transplant centers to the Center for International Blood and Marrow Transplant Research. Deaths were classified as disease-related or transplant-related. The panel agreed with >99% of deaths reported by centers as disease-related and 80% reported as transplant-related. Year of transplant (cohort effect) and disease status significantly influenced agreement between the panel and centers. Sensitivity analysis of deaths < 100 days post-transplant yielded the lowest agreement between the panel and centers for myelodysplastic syndrome patients. Standard predefined criteria for adjudicating cause-specific death led to consistent application to similar clinical scenarios and clearer delineation of cause-specific death categories. Other studies of competing events such as cancer-specific versus treatment-related mortality would benefit from our results. Our detailed algorithm should result in more consistent reporting of cause-specific death by centers.

Keywords: Acute leukemia; Adjudication; Allogeneic HCT; Cause-specific mortality.

Figure 1. Visual Summary of the Proportion of Causes of Death in Each Category as Reported by the Transplant Center that were Reclassified by the Consensus Panel, for Both Cohorts

Black boxes indicate >15% of deaths in that TRM category were reclassified Boxes with dots indicate ≥5 but <15% of deaths in that TRM category were reclassified White boxes indicate <5% of deaths in that TRM category were reclassified Grey boxes indicate the percent agreement of the Consensus Panel with the Transplant Center