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.

Targeted monitoring of patients at high risk of post‐transplant lymphoproliferative disease by quantitative Epstein–Barr virus polymerase chain reaction

“…Juvonen et al (37) reported an increased risk of PTLD in patients receiving ATG for treatment of steroid‐resistant acute GVHD. The use of ATG has been associated with a risk of PTLD in several other studies (5, 8, 13, 38–40). We use ATG in the conditioning regimen for patients with mismatched and unrelated donors and in spite of the fact that all patients in the study cohort who developed PTLD had received ATG, there was no significant impact of ATG or other forms of T‐cell medication on the risk of PTLD, presumably because ATG was also used in a high proportion of the patients who did not develop the disease.…”

Epstein-Barr virus-associated pneumonia in patients with post-transplant lymphoproliferative disease after hematopoietic stem cell transplantation

“…On the basis of data from 234 centers reported to the International Bone Marrow Transplant Registry and the Fred Hutchinson Cancer Research Center between 1964 and 1992, the cumulative incidence of PTLD is 1.0±0.3% at 10 years after allo‐HSCT, and 58% of PTLD occurred within 1–5 months, and 82% occurred before 1 year (1). The incidence of PTLD is up to 24% after T‐cell‐depleted allo‐HSCT (21). The common risk factors of PTLD include HLA disparity, donor type (unrelated), T‐cell depletion of the graft, use of ATG in the preparative regimen, or GVHD prophylaxis and treatment in allo‐HSCT (1, 5).…”

“…The common risk factors of PTLD include HLA disparity, donor type (unrelated), T‐cell depletion of the graft, use of ATG in the preparative regimen, or GVHD prophylaxis and treatment in allo‐HSCT (1, 5). PTLD has rarely been reported after auto‐HSCT (21–24). PTLD usually occurs after transplantation of positively selected autologous CD34 + stem cells and in autologous transplant patients with autoimmune disease who use ATG (21, 23).…”

“…PTLD has rarely been reported after auto‐HSCT (21–24). PTLD usually occurs after transplantation of positively selected autologous CD34 + stem cells and in autologous transplant patients with autoimmune disease who use ATG (21, 23). In this report, 6 out of 7 PTLD cases were recipients of allo‐HSCT (from HLA‐matched‐related [ n =3], HLA‐mismatched‐related [ n =2], and ‐unrelated [ n =1] donors) and 1 was a recipient of auto‐HSCT.…”

EBV PCR in the Diagnosis and Monitoring of Posttransplant Lymphoproliferative Disorder: Results of a Two-Arm Prospective Trial

“…Posttransplant lymphoproliferative disorder (PTLD) is a serious complication of pharmacologic immunosuppression used routinely in solid organ and stem‐cell transplant patients. Up to 15% of transplant patients develop PTLD with a mortality rate of 40–70% (1–6). PTLD is often detected at a late stage when patients have a poor performance status and are suffering from side effects of their lymphoma.…”