Advances in medical decision support systems for diagnosis of acute graft-versus-host disease: molecular and computational intelligence joint approaches

Acute graft-versus-host disease (aGVHD) is a serious systemic complication of allogeneic hematopoietic stem cell transplantation (HSCT) causing considerable morbidity and mortality. Acute GVHD occurs when alloreactive donor-derived T cells recognize host-recipient antigens as foreign. These trigger a complex multiphase process that ultimately results in apoptotic injury in target organs. The early events leading to GVHD seem to occur very soon, presumably within hours from the graft infusion. Therefore, when the first signs of aGVHD clinically manifest, the disease has been ongoing for several days at the cellular level, and the inflammatory cytokine cascade is fully activated. So, it comes as no surprise that progress in treatment based on clinical diagnosis of aGVHD has been limited in the past 30 years. It is likely that a pre-emptive strategy using systemic high-dose corticosteroids as early as possible could improve the outcome of aGVHD. Due to the deleterious effects of such treatment particularly in terms of infection risk posed by systemic steroid administration in a population that is already immune-suppressed, it is critical to identify biomarker signatures for approaching this very complex task. Some research groups have begun addressing this issue through molecular and proteomic analyses, combining these approaches with computational intelligence techniques, with the specific aim of facilitating the identification of diagnostic biomarkers in aGVHD. In this review, we focus on the aGVHD scenario and on the more recent state-of-the-art. We also attempt to give an overview of the classical and novel techniques proposed as medical decision support system for the diagnosis of GVHD.