Abstract
Allogeneic hematopoietic cell transplant (allo-HCT) is a potentially curative therapeutic strategy that showed encouraging long-term outcomes in hematological diseases. A number of factors can influence post-transplant clinical outcomes. While Epstein-Barr virus (EBV) constitutes a trigger for development of various adverse conditions, no clinical study yet has been powered to assess the effect of EBV serostatus on the clinical outcomes in allo-HCT population. To systematically summarize and analyze the impact of donor and recipient EBV serostatus on transplant outcomes in allo-HCT recipients, meta-analyses were conducted. Selected endpoints were overall survival (OS), relapse-free survival (RFS), relapse incidence (RI), non-relapse mortality (NRM), acute graft-versus-host disease (aGVHD), chronic graft-versus-host disease (cGVHD), and de novo cGVHD. Three studies with 26,650 patients, transplanted for acute leukemias, lymphomas, chronic hematological malignancies, or non-malignant hematological diseases were included in the meta-analysis. In the whole population, with a total of 53,300 donors and recipients, the rate of EBV seropositivity was 85.1%, including 86.6% and 83.6% among transplant recipients and healthy donors, respectively. Donor EBV seropositivity increased the risk of cGVHD by 17%, de novo cGVHD by 14%, and aGHVD by 5%. Recipient EBV seropositivity increased the risk of cGVHD by 12%, de novo cGVHD by 17%; increased NRM by 11%, increased RI by 11%, decreased OS by 14%, and decreased RFS by 11%. In performed meta-analyses, donor and recipient EBV seropositivity was found to have a significant impact on transplant outcomes in patients after allo-HCT.
Highlights
Epstein-Barr virus (EBV) is a widespread human herpesvirus (HHV4), infecting the majority of children, that establishes lifelong latent infection in the host memory B cells [1,2,3]
AGVHD, acute graft-versus-host disease; cGVHD, chronic graft-versus-host disease; D, donor; NRM, non-relapse mortality; OS, overall survival; R, recipient; RFS, relapse-free survival; RI, relapse incidence; Risk ratios (RRs), risk ratio heterogeneity p = 0.75; I2 = 0%), which resulted in a statistically significant decrease of RFS of seropositive recipients when compared with seronegative recipients, regardless of donor serostatus (R+/D− 55.13% (1386 of 2514) vs. R−/D− 60.38% (1120 of 1855); RR, 1.11; 95% confidence intervals (CIs), 1.03–1.19; p = 0.004; heterogeneity p = 0.04; I2 = 68% and R+/D+ 54.70% (11,245 of 20,557) vs. R−/D− 60.38% (1120 of 1855); RR, 1.07; 95% CI, 1.01–1.13; p = 0.02; heterogeneity p = 0.11; I2 = 54%)
Our main findings are that in patients undergoing allo-HCT, positive compared with negative EBV serology is associated
Summary
Epstein-Barr virus (EBV) is a widespread human herpesvirus (HHV4), infecting the majority of children, that establishes lifelong latent infection in the host memory B cells [1,2,3]. This virus accounts for a number of clinical syndromes and conditions, including post-transplantation lymphoproliferative disorder (PTLD), one of the most serious allogeneic hematopoietic cell transplantation (allo-HCT) complications [3, 4]. We aimed to systematically summarize and analyze the current evidence base regarding impact of donor and recipient EBV serostatus on transplant outcomes in allo-HCT recipients based on metaanalysis
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