Incidence, risk factors, and clinical outcomes associated with Epstein‐Barr virus‐DNAemia and Epstein‐Barr virus‐associated disease in patients after haploidentical allogeneic stem cell transplantation: A single‐center study

Abstract

Human leukocyte antigen (HLA)‐haploidentical hematopoietic stem cell transplantation (haplo‐HSCT) is an effective alternative to HLA‐matched transplantation. However, Epstein‐Barr virus (EBV) infection causes morbidity and mortality in patients undergoing haplo‐HSCT. Here, we retrospectively evaluated the incidence and risk factors of EBV‐DNAemia and EBV‐associated diseases in 131 patients who underwent haplo‐HSCT. Patients were classified into the no EBV infection groups, EBV‐DNAemia group and EBV‐associated disease group. Cumulative incidences of acute graft‐vs‐host disease, EBV infections, overall survival (OS), and relapse were analyzed. The cumulative incidences of EBV‐DNAemia and EBV‐associated disease were 26.9% and 33.3%, respectively. In multivariate analysis, cytomegalovirus (CMV)‐DNAemia was confirmed as an independent risk factor associated with EBV‐DNAemia and EBV‐associated disease. Patients with EBV‐associated disease had higher transplant‐related mortality (TRM) rates and lower OS rates, but similar relapse rates. Overall, these findings demonstrated the cumulative incidences of EBV‐DNAemia and EBV‐associated disease and identified correlations of EBV infection with TRM, relapse, and OS. Additionally, CMV‐DNAemia was a risk factor for EBV‐DNAemia and EBV‐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 two studies, aGvHD was dichotomized in grade ≥3 versus <3; one of them (Juvonen et al [ 66 ]) showed that patients with aGvHD grade ≥3 had a higher risk of active EBV infection (HR = 1.70 (95% CI: 1.11–2.62)). However, this result was not corroborated by other studies [ 51 , 91 , 101 ]. Among eight studies [ 4 , 39 , 41 , 57 , 59 , 74 , 86 , 89 ] that compared grade ≥2 versus <2, two [ 59 , 89 ] showed that an aGvHD grade ≥2 significantly increased the risk of active EBV infection, one reported a positive association without reporting the relative risk (Hiwarkar et al [ 58 ]), and the other (Sirvent-Von Bueltzingsloewen et al [ 89 ]) reported an OR = 3.4 (95% CI: 1.2–9.7).…”

“…Among the 62 articles included to analyze risk factors for post-transplant EBV infection, two relate exactly to the same patient cohort (Bogunia-Kubik et al [ 36 ] and Bogunia-Kubik et al [ 35 ]) and 11 relate to non-disjoint samples (include some of the same patients) (Cesaro et al [ 41 ] and Cesaro et al [ 42 ]; Liu et al [ 74 ] and Liu et al [ 27 ]; Xuan et al [ 99 ] and Liu et al [ 74 ]; Liu et al [ 75 ] and Liu et al [ 73 ]; Wang et al [ 97 ] and Ru et al [ 86 ]; Zhou et al [ 102 ] and Zhou et al [ 101 ]). However, none of these studies but one [ 101 ] were excluded from the qualitative synthesis for duplication because the risk factors explored were different. The study by Zhou et al [ 102 ] was excluded because all variables in this paper were explored using univariate analysis and were considered in the study by Zhou et al [ 101 ] using multivariate analysis.…”

“…However, none of these studies but one [ 101 ] were excluded from the qualitative synthesis for duplication because the risk factors explored were different. The study by Zhou et al [ 102 ] was excluded because all variables in this paper were explored using univariate analysis and were considered in the study by Zhou et al [ 101 ] using multivariate analysis. With respect to the analysis of PTLD risk factors, the studies by Sundin et al [ 103 ] and Omar et al [ 81 ] were discarded because Uhlin et al [ 94 ] explored the same factors and sample population as these two studies.…”

“…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.…”

“…Other possible risk factors were analyzed in the retained studies; these factors were not associated with EBV infection or PTLD, or their relationship was more ambiguous ( Table 2 and Table S4 ). The association between the primary diagnosis and post-transplant active EBV infection was explored in several reports [ 4 , 23 , 35 , 39 , 46 , 56 , 59 , 69 , 85 , 86 , 88 , 101 ]; three showed a strong positive and statistically significant association [ 23 , 39 , 88 ]. According to Carpenter et al [ 23 ], the risk of active EBV infection was greater in patients with Hodgkin’s lymphoma (HR = 3.53 (95% CI: 1.51–8.25)) or chronic lymphocytic leukemia (HR = 3.77 (95% CI: 1.38–10.32)) compared to patients with acute myeloid leukemia.…”