Dynamics of Epstein–Barr virus on post‐transplant lymphoproliferative disorders after antithymocyte globulin‐conditioned allogeneic hematopoietic cell transplant

Abstract

Background: The use of antithymocyte globulin (ATG) in allogeneic hematopoietic cell transplant (HCT) is associated with an increased risk of Epstein-Barr virus (EBV) reactivation and post-transplant lymphoproliferative disorders (PTLD). The dynamics and outcomes of EBV-DNAemia are not well described in this population. Methods:We retrospectively assessed the kinetics of EBV-DNAemia after ATG conditioning of HCT recipients. Receiver operating characteristic (ROC) curves were used to assess EBV-DNAemia to predict EBV-PTLD in this group.Results: A total of 174/405 (43%) consecutive HCT recipients from two centers met inclusion criteria of ATG conditioned, non-B-cell lymphoma patients. Of these with EBV-DNA measured using standardized IU/ml, 78.6% (92/117) developed EBV-DNAemia: 62% spontaneously resolved; 19% cleared after preemptive rituximab, and 13% developed EBV-PTLD. ROC curve analysis using maximum pre-EBV-PTLD

Epstein–Barr Virus Monitoring after an Allogeneic Hematopoietic Stem Cell Transplant: Review of the Recent Data and Current Practices in Canada

“…Of note, PTLD subtypes are inconsistently reported and mostly not within the frame of the most recent WHO classification. Across studies, there is again a wide variability in the reported incidence, ranging from as low as 0% to 3.5% in children [4,[8][9][10][11] and 0% to 14% in adults [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31], falling within the range of previously reported incidences. Again, this variability most likely results from the heterogeneity of the transplant populations studied, GvHD prophylaxis, including the use of ATG or not, conditioning regimen administered, as well as donor EBV status.…”

“…The results of EBV reactivation after HSCT in both adults and children are shown in Table 1. Incidence remains highly variable, ranging from 30% to 68% in children [4,[8][9][10][11] and 19% to 86% in adults [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] (excluding Marinho-Diaz et al, 2018, with an unrepresentative six adults studied). This variability reflects a high level of heterogeneity in the reported patient populations, including conditioning regimens, GvHD prophylaxis, donor type, or sensitivity of diagnostic tests.…”

“…Male donors [19], matched unrelated donors [8,18,24,27,32], mismatched unrelated donors [21,24,27,32], and sibling donors [25,29] have been identified as risk factors. Only three studies have found that myeloablative and reduced intensity conditionings are associated with increased incidence [8,21,28]. On the other hand, the administration of anti-thymocyte globulin (ATG) [4,11,14,[18][19][20][21]24,28,30,32,33], specifically horse ATG [9], is now a well-described risk factor.…”

“…Only three studies have found that myeloablative and reduced intensity conditionings are associated with increased incidence [8,21,28]. On the other hand, the administration of anti-thymocyte globulin (ATG) [4,11,14,[18][19][20][21]24,28,30,32,33], specifically horse ATG [9], is now a well-described risk factor. Interestingly, the administration of alemtuzumab seems to be associated with a lower incidence of reactivation, most likely due to its anti-B-cell properties [29,34].…”

“…Of note, all were monocentric retrospective cohort studies. The overall efficacity for EBV clearance varied between 85% [28] and 100% [12] for patients with EBV reactivation and between 65% and 100% for EBV-related PTLD. In the single largest cohort of adult patients reported to date (n = 107 treated patients), EBV clearance was achieved in 95% [56].…”