Rabbit antithymocyte globulin induction and risk of post-transplant lymphoproliferative disease in adult and pediatric solid organ transplantation: An update

The most modifiable risk factor for post-transplant lymphoproliferative disease (PTLD) is the type and dose of induction and maintenance immunosuppressive therapy. It is challenging to identify the contribution of a single agent such as rabbit antithymocyte globulin (rATG) in the setting of multidrug therapy. Registry analyses can be helpful but are limited by methodological restrictions and inclusion of historical patient cohorts. These are typically from eras when rATG dosing was markedly higher than current dosing (e.g. total dose 14 mg/kg versus 6 mg/kg now), accompanied by higher exposure to maintenance therapies, and often an absence of antiviral prophylaxis. The largest registry analysis to assess rATG specifically found no risk of PTLD after kidney transplantation, but conflicting results have been reported, highlighting the difficulty of interpreting this type of analysis. The relative rarity of PTLD means that individually controlled trials are underpowered to assess its occurrence, but the available data do not suggest an effect of rATG. A pooled analysis of data from studies of rATG induction in kidney and heart transplantation found the incidence of PTLD to be comparable to published reports in the overall transplant population. Data on the effect of rATG dose are inconclusive, but in patients receiving antiviral prophylaxis it does not appear to be influential. Nevertheless, it would seem reasonable to employ the lowest dose of rATG compatible with effective induction, particularly in EBV-seronegative recipients and other high-risk groups such as heart-lung transplant recipients. Overall, the risk of PTLD following rATG induction therapy with modern dosing regimens and under current management conditions appears unlikely to make an important contribution to the risk:benefit balance.