title: Prevention of Epstein-Barr virus-lymphoproliferative disease by molecular monitoring and preemptive rituximab in high-risk patients after allogeneic stem cell transplantation.
abstract: Recipients of a partially T-cell-depleted (TCD) allogeneic stem cell transplantation (allo-SCT) developing reactivation of Epstein-Barr virus (EBV) with quantified viral DNA levels exceeding 1000 genome equivalents/milliliter (geq/mL) are at high risk for EBV-lymphoproliferative disease (EBV-LPD). We studied whether preemptive therapy with rituximab prevents EBV-LPD, LPD-mortality, and abrogates viral reactivation in high-risk patients. We monitored 49 recipients of a TCD allo-SCT weekly for EBV reactivation by quantitative real-time polymerase chain reaction (PCR). Preemptive therapy by a single infusion of rituximab was given to patients with viral reactivation more than or equal to 1000 geq/mL. Results were compared with an historical control group of patients retrospectively monitored for EBV reactivation at similar intervals. There were 17 prospectively monitored patients who showed EBV reactivation more than or equal to 1000 geq/mL and 15 received preemptive therapy. Median time to preemptive therapy was 113 days (range, 41-202 days) after SCT. There were 14 patients who showed complete response (CR) as characterized by prevention of EBV-LPD and complete clearance of EBV-DNA from plasma, which was achieved after a median number of 8 days (range, 1-46 days). One patient progressed to EBV-LPD despite preemptive therapy, but obtained CR after 2 infusions of rituximab and donor lymphocyte infusion. There were 2 patients who had already developed EBV-LPD prior to preemptive rituximab, but obtained CR following 2 rituximab infusions. Comparison of this prospectively followed series to our historical cohort with the same high-risk profile showed a reduction of EBV-LPD incidence (18% +/- 9% versus 49% +/- 11%, respectively) and a complete abrogation of LPD-mortality (0% versus 26% +/- 10%, respectively) (P =.04) at 6 months from EBV-DNA more than or equal to 1000 geq/mL. Frequent quantitative monitoring of EBV reactivation and preemptive therapy by rituximab improves outcome in patients at high risk of EBV-LPD. (Blood. 2002;99:4364-4369)
authors.affiliation: Department of Hematology, Erasmus Medical Center/Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
authors.forename: Joost W J
authors.initials: JW
authors.lastname: van Esser
authors.forename: Hubert G M
authors.initials: HG
authors.lastname: Niesters
authors.forename: Bronno
authors.initials: B
authors.lastname: van der Holt
authors.forename: Ellen
authors.initials: E
authors.lastname: Meijer
authors.forename: Albert D M E
authors.initials: AD
authors.lastname: Osterhaus
authors.forename: Jan Willem
authors.initials: JW
authors.lastname: Gratama
authors.forename: Leo F
authors.initials: LF
authors.lastname: Verdonck
authors.forename: Bob
authors.initials: B
authors.lastname: Löwenberg
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Cornelissen
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000494:pharmacology; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D004279:DNA, Viral / Q000097:blood; D020031:Epstein-Barr Virus Infections / Q000175:diagnosis* / Q000188:drug therapy / Q000209:etiology; D005260:Female; D019337:Hematologic Neoplasms / Q000150:complications / Q000628:therapy / Q000821:virology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000254:growth & development; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000188:drug therapy / Q000517:prevention & control* / Q000821:virology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018570:Risk Assessment; D000069283:Rituximab; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000379:methods; D019562:Viral Load; D014775:Virus Activation
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D004279:DNA, Viral; D000069283:Rituximab