A multivariate approach for assessing severity of acute graft-versus-host disease in bone marrow transplantation

Patients undergoing bone marrow transplantation are at high risk of developing acute graft-versus-host disease (GVHD) which is a primary limiting factor for this procedure inasmuch as it is responsible for high morbidity rates and is associated with poor survival outcome. To provide improved treatment assessment and better interpretation of clinical outcomes, we need a precise and objective assessment of GVHD. Severity of GVHD is commonly assessed using an imprecise categorical grading system that incorporates skin, gut and liver grades, as well as subjective assessment of clinical performance. These organ grades are based on arbitrary cutpoints of skin rash, diarrhoea volume and bilirubin level. The International Bone Marrow Transplant Registry proposed an alternative grading system based on different combinations of organ involvement and provided estimates of relative risk of treatment failure. On the basis of that work, we developed an empirical mathematical model that quantifies GVHD severity, and that uses continuous, rather than categorical, daily measurements for each organ system. We use model-predicted values as an index of severity for any combination of values. The proposed index allows a more precise comparison of GVHD profiles across different treatment protocols and also permits more refined analyses to address relationships between GVHD and clinical outcomes.