POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDER IN PEDIATRIC BONE-MARROW TRANSPLANT RECIPIENTS - DISSEMINATED DISEASE OF DONOR ORIGIN DEMONSTRATED BY FLUORESCENCE IN-SITU HYBRIDIZATION

Background.-Posttransplant lymphoproliferative disorders in bone marro w transplantation are typically rapidly progressive and fatal B-cell l ymphoid proliferations associated with Epstein-Barr virus, and are mos tly of donor origin. We report three pediatric bone marrow transplant cases in which posttransplant lymphoproliferative disorder was diagnos ed at postmortem examination. Epstein-Barr virus in these cases was id entified by a combined in situ hybridization-immunoperoxidase techniqu e and donor origin was identified by fluorescence in situ hybridizatio n. Methods.-Tissues obtained from postmortem examination were evaluate d by light microscopy, immunohistochemistry, combined in situ hybridiz ation-immunoperoxidase technique with Epstein-Barr virus-encoded RNA p robe, and fluorescence in situ hybridization with X and Y centromeric probes. Results.-Three pediatric patients underwent sex-mismatched, T- cell-depleted bone marrow transplants complicated by graft versus host disease, rapidly progressive multiple organ failure, and postmortem d iagnosis of posttransplant lymphoproliferative disorder, Histologic ex amination and immunohistochemistry studies demonstrated immunoblastic lymphoma (one case) or polymorphic B-cell lymphoma (two cases). In all cases, Epstein-Barr virus-encoded RNA was detected by a combined in s itu hybridization-immunoperoxidase technique. Fluorescence in situ hyb ridization for X and Y chromosomes in paraffin sections demonstrated d onor origin in two cases (one case was indeterminate). Conclusion.-Flu orescence in situ hybridization was used to prove donor derivation of Epstein-Barr virus-associated posttransplant lymphoproliferative disor ders in pediatric bone marrow transplant recipients. Many features of posttransplant lymphoproliferative disorders in pediatric bone marrow transplant recipients are very similar to adult cases, although a high er proportion of children appear to be diagnosed postmortem and have a fatal outcome.