Transplantation 2000 Jul 15;70(1):94-9

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

Younes BS, McDiarmid SV, Martin MG, Vargas JH, Goss JA, Busuttil RW, Ament ME

Abstract
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