title: Molecular monitoring and stepwise preemptive therapy for Epstein-Barr virus viremia after allogeneic stem cell transplantation.
abstract: The optimal preemptive therapy for Epstein-Barr virus (EBV)-associated diseases remains under discussion. We developed a stepwise preemptive therapy (antiviral agents and reduction of immunosuppressants [RI] followed by rituximab) for EBV viremia, based on duration of EBV viremia and changes of viral loads. The blood EBV-DNA loads were regularly monitored by quantitative real-time polymerase chain reaction in 251 recipients undergoing allogeneic stem cell transplantation. The 3-year cumulative incidence of EBV viremia and EBV-associated diseases were 31.1% ± 3.1% and 15.6% ± 2.5%, which rose steeply with greater numbers of major risk factors. Of the 64 patients undergoing first-step preemption, 24 achieved complete response (CR) and 40 showed no response, including 25 progressing to EBV-associated diseases. The effective rates of antiviral agents and RI plus antiviral agents were 2/16 and 22/48 (P = 0.017). Fourteen achieved CR and one progressed to lymphoproliferative disease in the 15 patients undergoing rituximab preemption. Of the 26 patients progressing to EBV-associated diseases during preemptive therapy, 20 obtained CR in the 23 cases with rituximab-based treatments. The preemptive efficacy of RI plus antiviral agents was correlated with the numbers of major risk factors (rs  = -0.298; P = 0.04). B-cell reconstitution was significantly delayed for at least 6 months in patients with rituximab preemption. The risk of herpesvirus infection was similar in patients who showed effective progress to first-step and rituximab preemption (P = 0.094). RI plus antiviral agents could be given priority to low-risk patients, whereas more frequent monitoring of blood EBV-DNA and earlier preemptive rituximab should be advocated in high-risk patients.
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Qifa
authors.initials: Q
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Xuan
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Fen
authors.initials: F
authors.lastname: Huang
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Zhou
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Fan
authors.forename: Ke
authors.initials: K
authors.lastname: Zhao
authors.forename: Meiqing
authors.initials: M
authors.lastname: Wu
authors.forename: Lanping
authors.initials: L
authors.lastname: Xu
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhai
authors.forename: Fuhua
authors.initials: F
authors.lastname: Zhang
authors.forename: Can
authors.initials: C
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Huang
mesh_terms: D000293:Adolescent; D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000187:drug effects / Q000473:pathology / Q000821:virology; D002648:Child; D004279:DNA, Viral / Q000097:blood; D016903:Drug Monitoring; D020031:Epstein-Barr Virus Infections / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D004854:Herpesvirus 4, Human / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D000069283:Rituximab; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects; D014766:Viremia / Q000473:pathology / Q000517:prevention & control* / Q000821:virology
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000998:Antiviral Agents; D004279:DNA, Viral; D007166:Immunosuppressive Agents; D000069283:Rituximab