The effect of immunosuppression on posttransplant lymphoproliferative disease in pediatric liver 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 U CLA's experience with PTLD in all pediatric liver transplant recipients bet ween 1984-1997, Ne assessed the clinical presentation, risk factors, incide nce density, immunological characteristics, management, and outcome of pati ents who developed PTLD when receiving either primary cyclosporin A (CsA) o r tacrolimus. Methods. A total of 251 children received primary CsA therapy of which 70 r equired OKT3 for steroid resistant rejection and 29 required tacrolimus res cue for OKT3 resistance and/or chronic rejection, One hundred forty one chi ldren received tacrolimus as primary therapy. Sixty patients who survived f or 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 10 0 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+/-0.1 without OKT3 or tacro limus, 0.67+/-0.2 with OKT3, and 6.42+/-1.1 with tacrolimus rescue. The ove rall 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, pr imary 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 gr oup (9.8+/-3 months, P<0.05) or the tacrolimus primary group (12.6+/-5.1 mo nths, P<0.05), Five patients had monoclonal disease in the CsA group, but o nly one in the tacrolimus group (P<0.05). Clinical presentations with enlar ged lymph nodes, fevers, malaise, anorexia, weight loss, hypoalbuminemia, a nd gastrointestinal blood loss were common. Mortality was 20%, three patien ts died in each group. Conclusion. The use of primary tacrolimus therapy was associated with a sig nificant 5-fold higher rate of PTLD when compared to those treated with pri mary cyclosporine. Early diagnosis, decrease and/or discontinuation of pote nt immunosuppressive agents may contribute to decrease morbidity and mortal ity of this entity.