title: Response to rituximab-based therapy and risk factor analysis in Epstein Barr Virus-related lymphoproliferative disorder after hematopoietic stem cell transplant in children and adults: a study from the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation.
abstract: BACKGROUND
  The objective of this analysis was to investigate prognostic factors that influence the outcome of Epstein-Barr virus (EBV)-related posttransplant lymphoproliferative disorder (PTLD) after a rituximab-based treatment in the allogeneic hematopoietic stem cell transplant (HSCT) setting.
  
  
  METHODS
  A total of 4466 allogeneic HSCTs performed between 1999 and 2011 in 19 European Group for Blood and Marrow Transplantation centers were retrospectively analyzed for PTLD, either biopsy-proven or probable disease.
  
  
  RESULTS
  One hundred forty-four cases of PTLD were identified, indicating an overall EBV-related PTLD frequency of 3.22%, ranging from 1.16% for matched-family donor, 2.86% for mismatched family donor, 3.97% in matched unrelated donors, and 11.24% in mismatched unrelated donor recipients. In total, 69.4% patients survived PTLD. Multivariable analysis showed that a poor response of PTLD to rituximab was associated with an age ≥30 years, involvement of extralymphoid tissue, acute GVHD, and a lack of reduction of immunosuppression upon PTLD diagnosis. In the prognostic model, the PTLD mortality increased with the increasing number of factors: 0-1, 2, or 3 factors being associated with mortality of 7%, 37%, and 72%, respectively (P < .0001). Immunosuppression tapering was associated with a lower PTLD mortality (16% vs 39%), and a decrease of EBV DNAemia in peripheral blood during therapy was predictive of better survival.
  
  
  CONCLUSIONS
  More than two-thirds of patients with EBV-related PTLD survived after rituximab-based treatment. Reduction of immunosuppression was associated with improved outcome, whereas older age, extranodal disease, and acute graft-vs-host disease predicted poor outcome.
authors.affiliation: Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland. jstyczynski@cm.umk.pl
authors.forename: Jan
authors.initials: J
authors.lastname: Styczynski
authors.forename: Lidia
authors.initials: L
authors.lastname: Gil
authors.forename: Gloria
authors.initials: G
authors.lastname: Tridello
authors.forename: Per
authors.initials: P
authors.lastname: Ljungman
authors.forename: J Peter
authors.initials: JP
authors.lastname: Donnelly
authors.forename: Walter
authors.initials: W
authors.lastname: van der Velden
authors.forename: Hamdy
authors.initials: H
authors.lastname: Omar
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Martino
authors.forename: Constantijn
authors.initials: C
authors.lastname: Halkes
authors.forename: Maura
authors.initials: M
authors.lastname: Faraci
authors.forename: Koen
authors.initials: K
authors.lastname: Theunissen
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kalwak
authors.forename: Petr
authors.initials: P
authors.lastname: Hubacek
authors.forename: Simona
authors.initials: S
authors.lastname: Sica
authors.forename: Chiara
authors.initials: C
authors.lastname: Nozzoli
authors.forename: Franca
authors.initials: F
authors.lastname: Fagioli
authors.forename: Susanne
authors.initials: S
authors.lastname: Matthes
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Diaz
authors.forename: Maddalena
authors.initials: M
authors.lastname: Migliavacca
authors.forename: Adriana
authors.initials: A
authors.lastname: Balduzzi
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Tomaszewska
authors.forename: Rafael de la
authors.initials: Rde L
authors.lastname: Camara
authors.forename: Anja
authors.initials: A
authors.lastname: van Biezen
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hoek
authors.forename: Simona
authors.initials: S
authors.lastname: Iacobelli
authors.forename: Hermann
authors.initials: H
authors.lastname: Einsele
authors.forename: Simone
authors.initials: S
authors.lastname: Cesaro
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000097:blood; D020031:Epstein-Barr Virus Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000601:surgery / Q000821:virology; D005060:Europe / Q000453:epidemiology; D018380:Hematopoietic Stem Cell Transplantation; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007223:Infant; D053208:Kaplan-Meier Estimate; D008232:Lymphoproliferative Disorders / Q000188:drug therapy* / Q000453:epidemiology / Q000601:surgery / Q000821:virology; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D000069283:Rituximab; D019562:Viral Load
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D004279:DNA, Viral; D007155:Immunologic Factors; D000069283:Rituximab
keywords: Epstein-Barr virus; hematopoietic stem cell transplantation; post-transplant lymphoproliferative disorder; prognostic model; risk factors