Association of Epstein‑Barr virus infection with allogeneic hematopoietic stem cell transplantation in patients in Portugal

Abstract

The identification of patients at higher risk of developing Epstein-Barr virus (EBV) infection in hematopoietic stem cell transplants (HSCT) is useful for the prevention of EBV-associated diseases A prospective observational study was developed that included 40 patients (27 male and 13 females, with mean age of 32.2±1.5 years old) undergoing allogeneic-HSCT between January and December 2015. EBV was examined in whole blood samples collected during routine procedures at day (D)+30, D +60, +90, D+120, D+150 and D+180 post-transplant. EBV was detected, at least once during the follow-up period in 70.0% of our patients. Results indicated that patients with unrelated donors had increased risk of developing EBV infection at D+60 and D+150 (OR=3.9, P=0.058; OR=8.0, P=0.043; respectively). Moreover, myeloablative conditioning (OR=4.3, P=0.052), anti-thymocyte globulin use (OR=12.0, P=0.030) and graft-vs.-host disease (OR=6.7, P=0.032) were associated with EBV infection at D+60, D+150 and D+90, respectively. In our series, none of these patients developed post-transplant lymphoproliferative disease. To the best of our knowledge, the present study is the first study to report EBV infection in patients undergoing aHSCT from Portugal. The study revealed that EBV infection is associated with different factors. These findings provide evidence towards the identification of high-risk patients for EBV-infection and associated disease.

Factors Associated with Post-Transplant Active Epstein-Barr Virus Infection and Lymphoproliferative Disease in Hematopoietic Stem Cell Transplant Recipients: A Systematic Review and Meta-Analysis

“…In total, 3362 titles were identified in the research bases, 1883 in EMBASE and 1479 in Medline. Once duplicates and papers with exclusion criteria were removed, 77 articles [ 4 , 16 , 23 , 24 , 27 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 ,…”

“…The association between acute (a)GvHD and post-transplant EBV infection was examined in 21 studies [ 4 , 39 , 41 , 46 , 51 , 52 , 56 , 57 , 59 , 65 , 66 , 68 , 74 , 76 , 81 , 85 , 86 , 88 , 89 , 91 , 101 ]. Six statistically significant associations were highlighted using different grade categorization of the outcome.…”

“…Recipient age did not seem to be an important risk factor for active EBV infection post-transplant. Of the 20 studies [ 4 , 23 , 35 , 39 , 50 , 51 , 52 , 56 , 65 , 68 , 69 , 74 , 76 , 85 , 86 , 88 , 89 , 93 , 96 , 101 ] to consider this factor, only Bogunia-Kubik et al [ 35 ] highlighted a statistically significant association, showing that the propensity for active post-transplant EBV infection was higher in people over 25 years compared to others (OR = 1.54 (95% CI: 1.14–2.70)). Concerning the association between age and PTLD, only two [ 56 , 70 ] of the 10 studies [ 16 , 27 , 40 , 56 , 67 , 70 , 88 , 94 , 95 , 98 ] that explored this factor indicated a statistically significant association.…”

“…Several studies used multivariate analysis to examine the relationship between recipient sex and post-transplant active EBV infection [ 4 , 35 , 39 , 50 , 52 , 56 , 65 , 68 , 69 , 72 , 74 , 76 , 85 , 86 , 88 , 89 , 96 , 101 ] or PTLD [ 16 , 27 , 40 , 56 , 88 , 94 , 95 , 98 ]; none found a significant association. Three out of six studies [ 35 , 53 , 56 , 65 , 79 , 101 ] that analyzed the association between donor sex and post-HSCT active EBV infection showed a statistically significant association but in the opposite direction.…”

High-intensity interval training in allogeneic adoptive T-cell immunotherapy – a big HIT?

“…Latent herpes viruses such as Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) as well as lytic viruses such as Adenovirus (AdV) remain an important cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT) and solid organ transplantation (SOT) in immunocompromised patients [1][2][3]. With a median of 3 month after HSCT, 11% of all deaths are induced by viral infections with about one-third are caused mainly by CMV (up to 20%), EBV (up to 50%) and AdV (up to 75%) [4][5][6][7][8][9][10]. With an incidence of 6 to 28%, AdV infections are the most common infectious complications after HSCT, especially in children [2,5] Viral complications also influence the outcome of SOT [11] and in general, the incidence varies depending on the transplanted organ, the resulting immunosuppressive treatment, the serostatus of the donor and recipient, and the type of antiviral prophylaxis [12].…”