Significance of Epstein–Barr virus status and post‐transplant lymphoproliferative disease in pediatric thoracic transplantation

Abstract

Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disease (PTLD) is a serious complication of organ and bone marrow transplantation. The importance of EBV matching between recipient and donor remains unclear. Between October 1987 and December 1997, 64 pediatric cardio-pulmonary transplants were performed at this center (58 hearts, two heart/lungs, four sequential single lungs). The EBV viral capsid antigen (VCA) immunoglobulin G (IgG) status of both donor and recipient was determined at the time of transplant. Of 56 patients from whom paired sera was available for analysis, 27 (50%) were recipient and donor EBV IgG positive, four (7%) were recipient EBV IgG positive and donor EBV IgG negative, and 12 (20%) were recipient EBV IgG negative and donor EBV IgG negative. The remaining 13 (23%) patients were EBV IgG negative but received organs from EBV IgG-positive donors. The EBV immunoglobulin M (IgM) status was determined from 6 weeks post-transplant in the 11 mismatches who survived for longer than 28 d. Seven became EBV IgM positive, two remained EBV IgM negative; the status of the remaining two remains unknown. The EBV IgM status was also determined retrospectively in patients who were EBV IgG negative pretransplant and received organs from EBV IgG-negative donors. Nine became EBV IgM positive; the rest remained negative. PTLD was diagnosed in two of 56 patients from whom paired sera was available; one was donor and recipient EBV IgG negative; the other was donor and recipient EBV IgG positive. No cases of PTLD were diagnosed in the remaining eight patients from whom paired sera was not available. Our experience suggests that PTLD does not occur with any greater frequency in the 'mismatch' group, and does not justify EBV matching in pediatric thoracic transplantation where there is a higher proportion of EBV-negative recipients than in adults.

Case–control study of risk factors for the development of post‐transplant lymphoproliferative disease in a pediatric heart transplant cohort*

“…This phenomenon has also been noted by others (10,17,18), although isolated GI disease with a good prognosis has been reported (1,7). Others have reported intrathoracic PTLD to be a fairly common complication following heart transplantation (1-3, 7, 10, 14, 18, 24, 29, 34); we had no cases of intrathoracic disease as a first presentation of PTLD, as has been the case in other series as well (11,24,25,30).…”

“…There was no significant association between PTLD development and sex, race, donor age, recipient diagnosis, the number of rejection episodes (treated or untreated) occurring between the time of transplant and the time of development of PTLD, or the number of times that lympholytics were used prior to development of PTLD. Most [but not all (25)] studies show that patients undergoing primary or reactivated EBV infection following transplantation are at the highest risk for developing PTLD, perhaps because they harbor more virus (26). The higher incidence of primary EBV infection in children accounts for the higher incidence of PTLD in pediatric as compared with adult transplant recipients (3, 6–8, 17, 18).…”

The post-transplant lymphoproliferative disorder?a literature review

“…The acquisition of donor EBV is a risk factor for PTLD development in a previously seronegative transplant recipient [19]. In a large series of renal transplant recipients, 86% of paediatric patients who were EBV negative received a kidney from an EBV-positive donor, compared with only 50% of EBV-negative adults who received a seropositive graft [20]. Also, it has been shown that in the transplant recipient primary EBV disease develops later, is more likely to be clinically symptomatic, and is associated with a greater rise in serum creatinine and risk of graft loss than reactivation disease [16].…”

Screening for PTLD in lung and heart–lung transplant recipients by measuring EBV DNA load in bronchoalveolar lavage fluid using real time PCR

“…Seronegative patients who receive organs from a seropositive donor are at particular risk for infection from the graft at a time when immunosuppression is maximal (2). Recipients of L‐HLTx are among the highest risk groups (3). Prompt diagnosis is essential in preventing the serious complications associated with this disorder (4).…”