Epstein-Barr Virus-Associated Post-Transplantation Lymphoproliferative Disease in Patients Who Received Anti-CD20 after Hematopoietic Stem Cell Transplantation

Abstract

transplantation lymphoproliferative disease (PTLD) is a serious complication associated with Epstein-Barr virus (EBV) infection after hematopoietic stem cell transplantation (HSCT). Although anti-CD-20 therapy is now used as a preemptive strategy for EBV reactivation, PTLD still occurs in some patients. Here we analyzed outcomes and risk factors associated with PTLD transformation in 208 HSCT recipients who were diagnosed with EBV-DNAemia and received at least 1 course of rituximab. The median patient age was 42.52 years (range, 8.35 to 74.77 years), and the median duration of follow-up was 47.33 months (range, 3.18 to 126.20 months). The 2-year overall survival of the entire cohort was 62.8 (95% confidence interval [CI], 56.4 to 69.9), and the 2-year cumulative incidence function of PTLD was 6.3% (95% CI, 3.5% to 10.1%), for a median follow-up of patients diagnosed with PTLD of 37.85 months. Multivariable analysis identified 4 risk factors associated with PTLD: HSCT from an unrelated donor, recipient HLA-DRB1*11:01, fever at diagnosis of EBV infection, and donor-recipient sexmismatched HSCT. The presence of more than 2 of these risk factors was associated with an increased risk of developing PTLD. This retrospective study identifies risk factors associated with PTLD in EBV-infected patients after HSCT and defines patient subgroups that may benefit from intensified preemptive strategies.

Risk factors for post‐transplant Epstein‐Barr virus events in pediatric recipients of hematopoietic stem cell transplants

“…Several studies have examined the association between EBV DNAemia or EBV-VL and the type of graft, considering as variable either HLA compatibility, [26][27][28][33][34][35][36]40,41,49,69 related/unrelated donor 6,14,25,26,33,42,69,85 or the combination of these characteristics 18,20,22,32,36,37,39,63,64 with very few significant associations found (only two studies reporting significant associations in adult/pediatric population 39,40 and one in pediatric patients 85 ). Some studies have considered the association between PTLD and HLA compatibility, 1,10,26,38,47,49,50 (one found a significant association 1 ) or between PTLD and related/unrelated donor 10,26,38,86 (none showing a significant association), or by combining HLA mismatched/matched and unrelated/related donor [46][47][48]…”

Epstein-Barr virus induced post-transplant lymphoproliferative disorder presenting with unilateral retinal involvement

“…PTLD represents a spectrum of lymphoproliferative disorders associated with EBV infection in the setting of pharmacologic immunosuppression 1 , 2 that usually occurs within 1 year of hematopoietic stem cell or solid organ transplantation. 2 Although PTLD is a common condition after hematopoietic stem cell transplantation with a reported incidence ranging from 1 to 17%, 2 , 3 ocular involvement remains a rare finding in this context. 4 …”

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

“…Moreover, no statistically significant association was found between the donor/recipient sex combination and post-transplant EBV infection [35,41,53,57,65]. Among all studies that examined the sex of the dyad donor/recipient and PTLD [57,82,94,98], only one [82] found a statistically significant association suggesting a higher risk of PTLD in patients who received a transplant from a different sex donor.…”

“…Other factors associated with PTLD include: (1) CD8 + count (≥median vs. <median) 30 days after HSCT (HR = 0.34 (0.13-0.92)), (2) prior HSCT ((HR = 2.6 (1.1-6.4)) [57], (RR = 3.5 [1.7-6.3)) [70]), (3) splenectomy (SHR = 4.81 (1.51-15.4)) [94], (4) infusion of mesenchymal stromal cells (SHR = 3.05 (1.25-7.48)) [94], (5) a stepwise increase of EBV-DNA by 1 log (HR = 2.9 (1.7-4.8)) [96], (6) HLA DRB1*11:01 (SHR = 4.85 (1.57-14.97)) [82], and (7) HLA mismatch (SHR = 5.89 (2.43-14.3)) [94]. Fujimoto et al [55] found that, compared to matched related donor grafts, the risk of PTLD is higher when using mismatched related donor grafts (HR…”