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.

Non‐endocrine late complications of bone marrow transplantation in childhood: part II

“…They also found that higher risks of PTLD were linked to the method of T-cell depletion that selectively targeted T cells or T plus natural killer cells, rather than those that removed both T and B cells (Curtis et al, 1999). Similar risk factors have been identified by others (Shapiro et al, 1988;Witherspoon et al, 1989;Bhatia et al, 1996;Gerritsen et al, 1996;Socie et al, 2000) and additionally include a diagnosis of primary immunodeficiency (Bhatia et al, 1996). Fourteen per cent of children transplanted with non-HLA-identical grafts, mainly for primary immunodeficiency and other congenital diseases and leukaemia, developed LPD compared with none after HLA-identical transplants (Gerritsen et al, 1996).…”

Factors involved in the generation of memory CD8+ T cells in patients with X-linked lymphoproliferative disease (XLP)

“…In contrast to results reported for post-transplant patients [26], it has been shown that a high EBV viral load may not always be associated with the increased occurrence of EBVassociated malignancy [27]. For instance, the high EBV viral load that is observed frequently after HIV infection has no predictive value for the occurrence of AIDS-related non-Hodgkin's lymphoma [28].…”

Establishment of anti-Epstein–Barr virus (EBV) cellular immunity by adoptive transfer of virus-specific cytotoxic T lymphocytes from an HLA-matched sibling to a patient with severe chronic active EBV infection

“…Virus-induced transformation of infected cells is associated with various malignant diseases [3][4][5][6]. EBV-associated lymphoproliferative disease has been observed in patients with X-linked lymphoproliferative disease [7] and those receiving intensive immunosuppressive therapy, such as bone marrow transplantation [8][9][10].…”