Stephen D Marks1. 1. Department of Paediatric Nephrology, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street, London, UK. stephen.marks@gosh.nhs.uk
Abstract
PURPOSE OF REVIEW: This review examines new developments in the prophylaxis and treatment of rejection episodes as there has been a marked improvement in patient and allograft survival in pediatric solid organ transplant recipients over the last 20 years. Improved surgical techniques to allow transplantation of smaller recipients and a wider range of immunosuppressants available to transplant physicians have improved access and reduced the incidence and severity of acute rejection episodes and chronic allograft damage. RECENT FINDINGS: There is increasing knowledge of chronic allograft damage and the role of humorally-mediated rejection, leading to better understanding of the mechanisms involved and potential treatments. There is evidence in the literature of potential targets of B-cell survival factors by inhibiting novel pathways involved in B-cell and plasma cell activation. SUMMARY: There are currently trials underway investigating the use of eculizumab and bortezomib for treatment of antibody-mediated rejection as well as utilising these agents as part of desensitisation protocols. Minimal (or even monotherapy) maintenance immunosuppression regimens include monoclonal antibodies and fusion receptor proteins targeting different pathways (CD40-CD154, CD28-CD80/86, and LFA3-CD2 pathway). Phase III randomised controlled trials in adults are required before embarking on treatment of children.
PURPOSE OF REVIEW: This review examines new developments in the prophylaxis and treatment of rejection episodes as there has been a marked improvement in patient and allograft survival in pediatric solid organ transplant recipients over the last 20 years. Improved surgical techniques to allow transplantation of smaller recipients and a wider range of immunosuppressants available to transplant physicians have improved access and reduced the incidence and severity of acute rejection episodes and chronic allograft damage. RECENT FINDINGS: There is increasing knowledge of chronic allograft damage and the role of humorally-mediated rejection, leading to better understanding of the mechanisms involved and potential treatments. There is evidence in the literature of potential targets of B-cell survival factors by inhibiting novel pathways involved in B-cell and plasma cell activation. SUMMARY: There are currently trials underway investigating the use of eculizumab and bortezomib for treatment of antibody-mediated rejection as well as utilising these agents as part of desensitisation protocols. Minimal (or even monotherapy) maintenance immunosuppression regimens include monoclonal antibodies and fusion receptor proteins targeting different pathways (CD40-CD154, CD28-CD80/86, and LFA3-CD2 pathway). Phase III randomised controlled trials in adults are required before embarking on treatment of children.