PTLD is a devastating complication of organ transplantation, occurring in 3.9% of transplant recipients in this cohort between 1992 and 2005, with a mortality rate of 48%, similar to previous reports (1
). Only 27% of patients responded to RISM, as we defined it. Specimens from 9 of 24 evaluated cases were positive for BCL6 expression. BCL6 expression was found significantly more frequently in monomorphic lesions as compared to polymorphic lesions. While not statistically significant, it is noteworthy that only one of the patients with BCL6 expression responded to RISM. However, BCL6 expression did not predict RFS or OS. The only variable that was significantly associated with poor OS was being the recipient of a heart transplant as compared to other organ transplants.
Management of PTLD requires close collaboration among surgeons, transplant physicians, pathologists and oncologists. The determination of when to intervene with more aggressive therapy than simple reduction of immune suppression can be difficult, particularly when the threat of organ loss due to rejection is high. The data from this study demonstrate that BCL6 expression is more likely to be found in monomorphic PTLD than polymorphic PTLD. This finding, coupled with data previously reported by Hayashi, et al.
on the association with monomorphic histology and poor response to RISM (6
), highlights that early biopsy specimens from children in whom PTLD is considered may aid in management decisions for these patients. While we did not find a significant association between histologic subtype and response to RISM, only 15% of our patients with monomorphic disease responded to RISM, a percentage even lower than previously reported (6
). Far fewer of the patients in the current cohort with polymorphic PTLD responded to RISM. The differences in our findings may reflect a difference in our definition of response to RISM.
The data from the recipients of heart transplants were particularly discouraging, as 4 of 8 died, and 3 of these were due to cardiac rejection or its treatment. Since only 1 of the heart transplant recipients responded to RISM long-term, this may be a population for whom RISM alone is used cautiously, particularly if they have BCL6 positive and monomorphic disease.
The major limitations of this study are the small size of the cohort and retrospective nature of the study. Thus, these findings will need to be confirmed in larger, prospective studies.
In conclusion, BCL6 expression is associated with monomorphic PTLD. These data suggest that the addition of BCL6 analysis to standard analysis of PTLD may help predict those patients that will require therapy beyond reduced immune suppression. Larger, prospective studies may provide useful information about the significance of BCL6 gene mutation and protein expression in children with PTLD.