Epstein-Barr virus associated B cell lymphoproliferative disorders following bone marrow transplantation

Abstract

B cell lymphoproliferative disorders (BLPD) developed in eight patients following bone marrow transplantation (BMT) for leukemia (five patients) or immunodeficiency (three patients). Recipients of T depleted marrow from a mismatched donor were at particularly high risk of this complication. Six of 25 (24%) recipients of mismatched T depleted bone marrow developed BLPD. In contrast, none of 47 matched T depleted transplants, one of ten (10%) who received non-depleted marrow from an unrelated donor, and only one of 424 matched non-depleted transplants were associated with BLPD. Epstein-Barr virus (EBV) specific serology and DNA hybridization studies demonstrating five to 50 copies of EBV genome/cell in involved tissues implicate this virus as an associated etiologic agent. Restriction fragment length polymorphism (RFLP) and cytogenetic analysis of involved tissue demonstrated donor origin (five of seven) or host origin (two of seven). Histologic appearance was similar to EBV-induced polymorphic B cell proliferations described following solid organ transplantation, or which occur de novo in primary immunodeficiency. Six of seven patients with adequate tissue available for study were found to have monoclonal proliferations by: in situ immunofluorescence (six of seven), and/or immunoglobulin gene rearrangement, (four of six). Cytogenetic analysis of involved tissues from four patients showed a normal karyotype, whereas two had multiple clonal chromosomal abnormalities. Seven patients died despite aggressive attempts at therapy with combinations of antiviral, immunologic, and chemotherapeutic agents.