Characteristics of Epstein–Barr virus reactivation after allogeneic haematopoietic stem cell transplantation in patients with chronic active Epstein–Barr virus disease: favorable responses to rituximab

Abstract

Epstein–Barr virus (EBV) belongs to the herpesvirus family. The infection rate exceeds 90% worldwide. Primary EBV infection is occult and lacks typical symptoms. The virus quickly enters the latent infection phase and is characterized by a lifelong presence in B cells [1]. In some cases, patients develop persistent fever, lymphadenopathy, hepatosplenomegaly, and significantly elevated EBV-DNA load and/or abnormal EBV antibodies in blood or EBVencoded RNA and viral proteins in affected tissues [2, 3]. When these situations persist for more than 3 months, it is determined as chronic active Epstein–Barr virus infection (CAEBV). In Chinese patients, the most infected lymphocyte cell types during CAEBV infection are T and NK cells. Without treatment, CAEBV patients develop progressive cellular and humoural immune deficiencies complicated by opportunistic infections, haemophagocytic lymphohistiocytosis (HLH), multiple organ failure, and lymphoma [4], often leading to death. The main purpose of CAEBV treatment is to clear EBV-infected cells and to avoid the occurrence of fatal complications. Unfortunately, the present treatment protocols, including traditional antiviral drugs, antitumor chemotherapy and immunotherapy, temporarily relieve symptoms without clearing EBV. Allogeneic haematopoietic stem cell transplantation (alloHSCT) is the only effective method for curing CAEBV, but relapse and transplant-related mortality are still high and affect overall survival (OS) [4, 5]. EBV reactivation is a common complication post alloHSCT. With the development of haploid, unrelated donor transplantation, and the application of antithymocyte globulin (ATG) in pretreatment, the incidence of EBV reactivation increases significantly. Some cases rapidly progress to posttransplant lymphoproliferative disease (PTLD), with a high mortality rate. CAEBV patients also have a risk of EBV reactivation post HSCT. However, unlike other blood disease patients, EBV DNAaemia post HSCT in CAEBV patients can be traditional B-cell EBV-PTLD; it can also be a result of CAEBV recurrence. This is the first study to analyse EBVDNA changes in CAEBV post HSCT. Thirty-two CAEBV patients who received allo-HSCT at the Hematology Department, Beijing Friendship Hospital, Capital Medical University from January 2018 to June 2019 were enrolled in the study. This retrospective analysis was approved by ethics committee of Beijing Friendship hospital. All patients met CAEBV diagnostic criteria [6]. The median age was 27 years (7–51 years). Males and females accounted for 62.5% and 37.5%, respectively. The median time from diagnosis to transplantation was 7 months (3–27 months). In addition, 71.9% of the patients had a history of HLH [7]. The EBV-infected lymphocyte types were T or NK cells or multiple lines. All patients received at least one cycle of etoposide-/dexamethasone-based chemotherapy pretransplant. Disease status pretransplant was defined as described previously [8]: there were five with no response, twenty-one in partial remission, and six in complete remission. Donors were matched (15.6%) or haplo-identically (84.4%) related. Total body irradiationand busulfanbased conditioning accounted for 59.4% and 40.6% of the patients, respectively. All patients used ATG during conditioning. Graft-vs.-host disease (GVHD) prevention was performed using cyclosporine in combination with * Zhao Wang [email protected]