Gene Expression Profiling of Epstein-Barr Virus-positive and -negative Monomorphic B-cell Posttransplant Lymphoproliferative Disorders

PURPOSE Organ recipients are at a high risk of posttransplant lymphoproliferative disorders (PTLD) as a result of immunosuppressive therapy. Most B-cell lymphomas are associated with Epstein-Barr virus (EBV) infection. We describe a morphologically and clinically distinct group of PTLD in 11 patients that occurred late after organ transplantation and were not associated with EBV. PATIENTS AND METHODS There were seven kidney, three heart, and one liver transplant recipients (group I). The clinical manifestations, pathologic findings, treatment, and outcome were compared with those in 21 patients with EBV-associated PTLD treated in our institution (group II). EBV was detected with at least two techniques: Epstein-Barr-encoded RNA (EBER) in situ hybridization with EBER 1 + 2 probes, Southern blotting, and detection of latent membrane protein 1 (LMP1) expression by immunohistochemistry. RESULTS The time between transplantation and the diagnosis of lymphoma ranged from 180 to 10,220 days in group I (mean, 2,234; median, 1,800) and from 60 to 2,100 days in group II (mean, 546; median, 180), and was significantly shorter in group II (P = .02). Among 19 tumors diagnosed within 2 years after the graft, 16 were associated with EBV; among 13 tumors diagnosed after more than 2 years, only five were associated with EBV. All of the B-cell PTLDs in group I were classified as monomorphic, meeting the criteria of B diffuse large-cell lymphoma (B-DLCL) with a component of immunoblasts, and genotyping confirmed their monoclonality. Three tumors were T-cell pleomorphic lymphomas. Tumor sites were mainly bone marrow and lymph nodes. Overall median survival was 1 month in group I and 37 months in group II, with two patients still alive in group I and nine in group II. The survival time was significantly longer in group II (P < .01). CONCLUSION EBV-negative PTLD may be a late serious complication of organ transplantation. Half the tumors observed after kidney transplantation in our center were not associated with EBV and emerged after more than 5 years, which suggests the number of EBV-negative PTLDs in organ recipients might increase with time.

Download Full-text

Concomitant Epstein-Barr Virus (EBV)-Positive B-Cell and EBV-Negative T-Cell Posttransplant Lymphoproliferative Disorders After Renal Allografting: Pathogenetic Implications

Transplantation Journal ◽

10.1097/tp.0b013e31823915f6 ◽

2011 ◽

Vol 92 (12) ◽

pp. e67-e68

Author(s):

Wing-Yan Au ◽

Man-Fei Lam ◽

Annie Pang ◽

Rock Y. Y. Leung ◽

Yok-Lam Kwong

Keyword(s):

T Cell ◽

B Cell ◽

Epstein Barr Virus ◽

Lymphoproliferative Disorders ◽

Barr Virus ◽

Epstein Barr ◽

Posttransplant Lymphoproliferative Disorders

Download Full-text

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

Blood ◽

10.1182/blood.v71.5.1234.1234 ◽

1988 ◽

Vol 71 (5) ◽

pp. 1234-1243 ◽

Cited By ~ 362

Author(s):

RS Shapiro ◽

K McClain ◽

G Frizzera ◽

KJ Gajl-Peczalska ◽

JH Kersey ◽

...

Keyword(s):

Bone Marrow ◽

Bone Marrow Transplantation ◽

B Cell ◽

Marrow Transplantation ◽

Cytogenetic Analysis ◽

Epstein Barr Virus ◽

Lymphoproliferative Disorders ◽

Solid Organ ◽

Barr Virus ◽

Epstein Barr

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.

Download Full-text