Abstract
Background:In allogeneic hematopoietic stem cell transplantation recipients reactivation of Epstein‐Barr virus (EBV) can cause post‐transplantation lymphoproliferative disorder (PTLD), which may rapidly progress to multi‐organ failure and even death. Development of EBV PTLD correlates very closely with use of anti‐thymocyte globulin (ATG) and type of transplant.Aims:To assess the incidences and clinical features of EBV DNAemia and PTLD in the setting of stem cell transplantation using unmanipulated G‐CSF‐primed allogeneic peripheral blood stem cells as graft (PBSCT), we performed a retrospective analysis of stem cell transplantation from HLA‐matched (MSD) or haploidentical (HID‐SCT) sibling donors in patients with high‐risk hematological malignancies.Methods:The clinical characteristics of patients and donors were described in Table 1. EBV DNA were monitored by real‐time quantitative PCR on plasma samples weekly. The EBV DNAemia was defined as DNA loads more than 1,000 copies/mL of plasma. The diagnosis of EBV‐associated PTLD was defined as proven or probable according to the published definition. Probable PTLD was defined as significant lymphadenopathy, hepatosplenomegaly or other end‐organ manifestations accompanied by significant EBV DNAemia and the absence of other documented cause. Proven PTLD was defined as the detection of EBV in tissue specimen accompanied by symptoms and/or signs from the affected organ. Morphological classification of PTLD was based on histological WHO 2016 classification.Results:One‐year cumulative incidence of EBV DNAemia was 44.1%, ranging from 4.8% in MSD‐SCT recipients not using ATG to 20.0% in MSD‐SCT recipients using ATG, and 73.7% in HID‐SCT recipients. Risk factors for EBV reactivation included use of ATG (p = 0.008), male donor (p = 0.034), and reactivation of cytomegalovirus DNAemia (p < 0.001). One‐year incidence of EBV PTLD was 11.9%, ranging from 1.8% in recipients of MSD‐SCT not using ATG to 4.4% in recipients of MSD‐SCT using ATG, and 23.5% in recipients of HID‐SCT. Risk factors for PTLD included in fludarabine‐based conditioning regimen (p = 0.010), cytomegalovirus DNAemia (p = 0.036) and patient's age <40‐yr (p = 0.032). The 1‐yr relapse‐free survival and overall survival among the 19 patients with PTLD were 40.2% and 44.9%, respectively, as opposed to 63.4% and 68.4% among patients without PTLD (p < 0.05). In multivariate analyses, EBV DNAemia was associated with a lower risk of relapse (p = 0.025), while PTLD was marginally associated with a higher risk of relapse (p = 0.092). Neither EBV DNAemia nor PTLD independently predict inferior relapse‐free survival, overall survival and non‐relapse mortality (p>0.05).Summary/Conclusion:This study confirmed higher incidences of EBV DNAemia and PTLD after HID‐SCT than MSD‐SCT in the setting of unmanipulated with PBSCs as graft. Risk factors associated with reactivation of EBV were included in use of ATG, male donor, and CMV DNAemia. EBV PTLD developed mainly in HID‐SCT recipients with EBV DNAemia. The risk factor associated with EBV PTLD after HID‐SCT was fludarabine‐containing conditioning regimens. Although patients with EBV DNAemia did not have an inferior survival, they did have an increased risk of developing EBV PTLD, which was associated with worse RFS and OS after HID‐SCT.image
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