The effect of immunosuppression on posttransplant lymphoproliferative disease in pediatric transplant patients

Background. Posttransplant lymphoproliferative disease (PTLD) is a serious complication associated with the use of chronic immunosuppression for solid organ transplantation. This study represents a retrospective analysis of UCLA's experience with PTLD in all pediatric liver transplant recipients between 1984-1997. We assessed the clinical presentation, risk factors, incidence density, immunological characteristics, management, and outcome of patients who developed PTLD when receiving either primary cyclosporin A (CsA) or tacrolimus. Methods. A total of 251 children received primary CsA therapy of which 70 required OKT3 for steroid resistant rejection and 29 required tacrolimus rescue for OKT3 resistance and/or chronic rejection. One hundred forty one children received tacrolimus as primary therapy. Sixty patients who survived for less than 6 months after transplantation were excluded from the study. Results. The total incidence density (ID) rate of PTLD was 1.8±0.4 per 100 patient-years (30/392). The overall ID rate of PTLD in the CsA group was 0.93±0.2 per 100 patient-years (15/251). Within this group of primary CsA-treated patients, the ID rate of PTLD was 0.49±.01 without OKT3 or tacrolimus, 0.67±0.2 with OKT3, and 6.42±1.1 with tacrolimus rescue. The over-all PTLD ID rate in the primary tacrolimus-treated patients was 4.86±1.2 per 100 person-years (15/141). There was a 5-fold increase in the ID rate of PTLD in the primary tacrolimus group when compared to the comparable, primary CsA group (P<0.001). The mean time to PTLD was 5-fold longer (49.7±20.7 months) in the CsA group when compared to the CsA/tacrolimus rescue group (9.8±3 months, P<0.05) or the tacrolimus primary group (12.6±5.1 months, P<0.05). Five patients had monoclonal disease in the CsA group, but only one in the tacrolimus group (P<0.05). Clinical presentations with enlarged lymph nodes, fevers, malaise, anorexia, weight loss, hypoalbuminemia, and gastrointestinal blood loss were common, Mortality was 20%, three patients died in each group. Conclusion. The use of primary tacrolimus therapy was associated with a significant 5-fold higher rate of PTLD when compared to those treated with primary cyclosporine. Early diagnosis, decrease and/or discontinuation of potent immunosuppressive agents may contribute to decrease morbidity and mortality of this entity.