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.


CONCLUSIONS
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.
Younes
B S
BS
Division of Pediatric Gastroenterology and Nutrition UCLA Medical Center, Los Angeles, CA 90024-1752, USA.
McDiarmid
S V
SV
Martin
M G
MG
Vargas
J H
JH
Goss
J A
JA
Busuttil
R W
RW
Ament
M E
ME
D000293:Adolescent; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000009:adverse effects; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D015994:Incidence; D007223:Infant; D016031:Liver Transplantation / Q000009:adverse effects*; D008232:Lymphoproliferative Disorders / Q000453:epidemiology / Q000209:etiology* / Q000628:therapy; D016853:Muromonab-CD3 / Q000009:adverse effects; D012189:Retrospective Studies; D012307:Risk Factors; D016559:Tacrolimus / Q000009:adverse effects
D007166:Immunosuppressive Agents; D016853:Muromonab-CD3; D016572:Cyclosporine; D016559:Tacrolimus