ORIGINAL ARTICLE Features of EBV reactivation after reduced intensity conditioning unrelated umbilical cord blood transplantation Z Peric 1,2 , X Cahu 1,7 , P Chevallier 1 , E Brissot 1 , F Malard 1 , T Guillaume 1 , J Delaunay 1 , S Ayari 1 , V Dubruille 1 , S Le Gouill 1,2,3 , B Mahe´ 1 , T Gastinne 1 , N Blin 1 , B Saulquin 1,2 , J-L Harousseau 1,3,4 , P Moreau 1,2,3 , M Coste-Burel 5,6 , B-M Imbert-Marcille 5,6 and M Mohty 1,2,3 1 Service d’He´matologie Clinique, Centre Hospitalier et Universitaire (CHU) de Nantes, Nantes, France; 2 Centre d’Investigation Clinique en Cance´rologie (CI2C), CHU de Nantes, Nantes, France; 3 Universite´de Nantes and INSERM CRNCA UMR 892, Nantes, France; 4 Centre Re´gional de Lutte contre le Cancer (CRLCC) Rene´Gauducheau, Nantes, France; 5 Laboratoire de Virologie, CHU de Nantes, Nantes, France and 6 EA4271, Universite´de Nantes, IFR26, Nantes, France This single centre study assessed the incidence, kinetics and predictive factors of EBV reactivation and EBV- related lymphoproliferative diseases (LPD) in 33 consecu- tive 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 life- threatening LPD. Bone Marrow Transplantation (2012) 47, 251–257; doi:10.1038/bmt.2011.64; published online 28 March 2011 Keywords: EBV; EBV-LPD; cord blood transplantation Introduction Umbilical cord blood (UCB) is being increasingly used as an alternative source for patients who require allogeneic hematopoietic SCT (allo-HSCT) but who lack an HLA- matched donor. 1,2 Compared with grafts from unrelated adult donors, UCB has advantages of immediate avail- ability, easy procurement with no risk to the donor, low risk of infection transmission, greater tolerance of HLA disparity and lower than expected incidence of severe GVHD. 3,4 On the other hand, reduced intensity condition- ing (RIC) regimens are also increasingly used before allo- HSCT with the aim to decrease TRM in elderly patients, heavily pretreated patients or patients with medical comorbidities precluding the use of standard myeloablative preparative regimens. 5 The majority of these RIC protocols are designed to produce a state of profound immuno- suppression rather than myeloablation. 6 Following allo- HSCT, EBV reactivation and EBV-related proliferation are well recognized complications. 7 EBV reactivation may be associated with a spectrum of clinical presentations, going from fever to lymphoproliferative disease (LPD), which arise as a consequence of an outgrowth of B cells latently infected with EBV in the setting of loss or suppression of normal cytotoxic T-cell surveillance. Risk factors for EBV-related complications include the degree of mismatch between donor and recipient, manipulation of the graft to deplete T cells, and degree and duration of immunosuppression used to prevent and treat GVHD. 7 Despite concerns regarding immune reconstitution follow- ing UCB transplantation (UCBT), early reports documen- ted the rates of EBV-LPD to be comparable to those documented after HLA-matched unrelated BM or PBSC HSCT. 8 However, a marked increased risk of EBV-LPD has been observed with the use of RIC before UCBT. 9 With this background, the aim of this analysis was to investigate Received 31 December 2010; revised 14 February 2011; accepted 15 February 2011; published online 28 March 2011 Correspondence: Professor M Mohty, He´matologie Clinique, CHU de Nantes, Place A. Ricordeau, Nantes F-44093, France. E-mail: mohamad.mohty@univ-nantes.fr 7 Current address: CHU de Rennes, Rennes, France. 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