Efficacy and safety of mini-extracorporeal photopheresis for the treatment of refractory graft-versus-host-disease in children and adolescents

Abstract

Allogeneic stem-cell transplantation (allo-SCT) is the definitive treatment option of several malignant and non-malignant diseases. In Europe, more than 4500 allo-SCT are performed yearly in children. Technical innovations, and better strategies focused on preventing infections and reducing toxicity, among others, have improved the outcome of allo-SCT in the last decades (50% reduction of non-relapse mortality (NRM) and better survival). However, graft versus host disease (GVHD) remains the major cause of treatment failure and SCT related death. GVHD can be defined as a donor T-cell immune reaction after allo-SCT against genetically defined proteins in different organs in the immunosupressed recipient. It complies disturbances in pathways of immunological recognition, reconstitution and failure to acquire immunological tolerance, thereby resulting in both alloimmune and autoimmune attacks on multiple host tissues. The need for increased and prolonged immunosuppression (IS) to treat GVHD, in addition to the immunosuppressive effects of the disease itself, increases the risk of infection, organ impairment, poor quality of life and ultimately, mortality. GVHD has been classically classified according to its chronological pattern after allo-SCT, using day+100 as cut-off: acute GVHD (aGVHD) <100 days; chronic GVHD (cGVHD) >100 days. However, GVHD is now considered as a continuum and clinical manifestations, rather than time after SCT, should guide the difference between acute- and chronic-GVHD (Table 1). Regarding this consideration, the following categories of GVHD are recognized: classical aGVHD occurring within 100 days after SCT or donor leukocyte infusion; persistent, recurrent or late-onset aGVHD (> day+100); classical cGVHD; overlap syndrome with concomitant acute- and chronic-GVHD signs.