Features of EBV reactivation after reduced intensity conditioning unrelated umbilical cord blood transplantation

Abstract

This single centre study assessed the incidence, kinetics and predictive factors of EBV reactivation and EBVrelated lymphoproliferative diseases (LPD) in 33 consecutive patients who received a reduced intensity conditioning (RIC) before umbilical cord blood transplantation (UCBT). During the first 6 months after UCBT, weekly all patients were DNA-PCR screened in the peripheral blood for EBV reactivation and were clinically monitored for clinical features attributable to EBV. The cumulative incidences of EBV reactivation (defined as an EBV load 41000 EBV copies per 10 5 cells measured at least once during follow-up) at 6 months and 2 years after UCBT were 9 (95% confidence interval (CI), 2-22%) and 17% (95% CI, 6-33%), respectively. In 28 patients (85%), the EBV load remained negative at all times, and none of these patients experienced any sign of LPD. Five patients (15%) experienced at least one EBV reactivation episode. EBV reactivation was observed at a median of 132 days (range, 85-438) after UCBT. Two patients developed EBV-related LPD (cumulative incidence, 6% at 3 years). With a median follow-up of 468 days (range, 92-1277) post UCBT, the OS was 62% at 3 years. Five patients died of disease progression and seven patients died of transplant-related complications, including one case of EBV-related LPD. Univariate analysis did not identify any significant risk factor associated with EBV reactivation. We conclude that patients undergoing RIC UCBT are at risk for EBV reactivation, with the need for close EBV monitoring and the use of preemptive rituximab treatment as some cases may progress to lifethreatening LPD.

Incidence and risk factors of EBV reactivation after unrelated cord blood transplantation: a Eurocord and Société Française de Greffe de Moelle-Therapie Cellulaire collaborative study

“…A recent French single-center study, including 33 UCBT only with RIC regimen, found an overall incidence of EBV reactivation about 5/33 (15%) and 2 EBV-PTLD. 8 Given our results, we could speculate that patients who underwent UCBT have a risk of EBV reactivation probably correlated to the circumstances of the graft in terms of conditioning and immunosuppression. Immaturity of UCB lymphocytes could have been responsible for higher susceptibility to EBV reactivation, as previously described for HHV6, 14 adenovirus 15 and VZV.…”

“…5 The ability of cord blood-naive T cells to regulate EBV reactivation is uncertain, and the incidence of EBV viremia and EBV-PTLD have to be assessed in UCBT recipients. Three studies have been published on the subject, [6][7][8] and none of them performed systematic EBV RQ-PCR monitoring. The aim of this retrospective multicenter study was to investigate the incidence and risk factors of EBV events after UCBT.…”

Effect of Graft Source on Unrelated Donor Hemopoietic Stem Cell Transplantation in Adults with Acute Myeloid Leukemia after Reduced-Intensity or Nonmyeloablative Conditioning: A Study from the Société Francaise de Greffe de Moelle et de Thérapie Cellulaire

“…Indeed, patients eligible to RIC/NMA allo-SCT are frequently elderly, heavily pretreated, or impaired by comorbidities, and most physicians hesitate to use UCB to perform RIC/NMA allo-SCT in them when there is no matched related or unrelated donor available. The main cause of NRM after UCB transplantation is infectious complications [23][24][25], but in our retrospective study, we were unable to analyze the impact of infection-related NRM. The cumulative incidence of grade III and IV aGVHD and cGVHD was lower in the UCB group compared with the MisMUD.…”

Management of Epstein-Barr Virus infections and post-transplant lymphoproliferative disorders in patients after allogeneic hematopoietic stem cell transplantation: Sixth European Conference on Infections in Leukemia (ECIL-6) guidelines

“…The reported incidence of EBV DNA-emia ranging between 0.1-63% is largely dependent on the type of transplant, assay sensitivity, defined level of DNA-emia, use of systematic screening and its timing. [18][19][20][21][22][23][24][25][26][27] In a recent EBMT study, the overall incidence of PTLD after allogeneic HSCT was 3.2%, varying from 1.2% in matched family donor (MFD) to 2.8% in mismatched family donor (haploidentical/MMFD), 4.0% in matched unrelated donor (MUD), and 11.2% in mismatched unrelated donor (MMUD) recipients. 3 In recipients of unrelated cord blood (CBT), the incidence of EBV-PTLD was 2.6-3.3% for myeloablative transplants, and 7-12.9% in nonmyeloablative transplants.…”