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 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+/-0.1 without OKT3 or tacrolimus, 0.67+/-0.2 with OKT3, and 6.42+/-1.1 with tacrolimus rescue. The overall 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.

The involvement of the gastrointestinal tract in posttransplant lymphoproliferative disease in pediatric liver transplantation.

BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) is a serious complication associated with the use of immunosuppression after transplantation. In a retrospective study the clinical features of PTLD located primarily in the gastrointestinal tract were analyzed. METHODS: Three hundred ninety-two consecutive pediatric patients who underwent orthotopic liver transplantation (OLT) during a 13-year period with a survival of more than 6 months were reviewed. Two immunosuppression protocols were used: cyclosporin A, or tacrolimus-based primary therapy. Twenty-nine randomly selected liver transplant recipients without PTLD were used for comparison of signs and symptoms of gastrointestinal PTLD. RESULTS: Among the 30 patients identified with PTLD, 9 had gastrointestinal PTLD. The overall incidence density of PTLD was 1.8 per 100 patient-years (30/392). Nine patients (30%) had involvement of the gastrointestinal tract, whereas 7 (23%) had the gastrointestinal tract as the only involved site. When compared with a cohort of liver transplant recipients without PTLD, only gastrointestinal bleeding, weight loss, hypoalbuminemia, and protein-losing enteropathy were signs most likely associated with gastrointestinal PTLD. Hypoalbuminemia was the most sensitive sign of gastrointestinal PTLD. The lower tract (ileum and colon) was the most common site of involvement. CONCLUSIONS: gastrointestinal involvement is common and occurs in 30% of all patients with PTLD. It may be the only affected organ in a subgroup of patients. Hypoalbuminemia, gastrointestinal bleeding, and weight loss are features that are characteristic of gastrointestinal PTLD. Patients with aggressive gastrointestinal signs and symptoms should undergo upper and lower gastrointestinal tract endoscopy with biopsy, to establish the diagnosis.