REDUCTION OF THE INCIDENCE OF REJECTION BY ADJUNCT IMMUNOSUPPRESSION WITH PHOTOCHEMOTHERAPY AFTER HEART TRANSPLANTATION

Abstract

In this study, photochemotherapy (PCT) was used for adjunct immunosuppression in the first six months after heart transplantation (HTx). Fifteen patients after orthotopic HTx were included in the study; all received standard triple-drug immunosuppression including cyclosporine, azathioprine and glucocorticoids, but no adjunct therapy with mono- or polyclonal antibodies. The patients were divided into three groups: group I served as control with no additional treatment; group II received adjunct treatment with 10 courses of PCT (single-day treatments); and group III received 20 PCT courses since it was given each time on two consecutive days. PCT was started in both groups on day one after HTx; it was applied with a higher frequency in the early postoperative period and thereafter continued at four-week intervals for a total of 6 months. The photopheresis method for PCT included extracorporeal UVA irradiation of mononuclear cells that were treated with the photosensitive drug 8-methoxypsoralen (8-MOP) and subsequently retransfused to the patient. A new liquid form of 8-MOP was added directly to the buffy coat, resulting in reliable and sufficient drug levels in the cell suspension during the irradiation period; problems caused by oral application due to unpredictable variations in gastrointestinal absorption were thus prevented. Analysis of the total numbers of acute rejection episodes (AREs) within the first four weeks after HTx revealed a more impressive decrease by double PCT (group III, 3 AREs) than by single PCT (group II, 5 AREs) in comparison with the control (group I, 6 AREs). Over the total observation time (mean: 9.6 months), however, both PCT schedules reduced the total number of AREs observed in the control group (20 AREs) equally by more than 50% (9 AREs each in groups II and III) (P = 0.007). Furthermore, PCT treated patients had significantly fewer infections (6 infections in each group) than control group patients (15 infections) (P = 0.026); this, however, may be accounted for by the higher number of acute rejections in the control group and consequent increase in unspecific immunosuppression treatment. Our results suggest that PCT is a safe and effective method of adjunct immunosuppression that can be applied early in the postoperative period; it reduces the number of rejection episodes and does not increase the risk of infections.