title: EBV-related lymphoproliferative disease complicating therapy with the anti-CD2 monoclonal antibody, siplizumab, in patients with T-cell malignancies.
abstract: OBJECTIVE
  We report an increased incidence of EBV-induced B-cell lymphoproliferative disease (LPD) in patients treated with siplizumab, an anti-CD2 antibody. The development of EBV-LPD has been associated with the use of immunosuppressive agents used in solid organ, bone marrow, and stem cell transplantation and in certain congenital immunodeficiencies.
  
  
  METHODS
  We conducted a single-institution phase I dose-escalation trial of siplizumab, a humanized monoclonal antibody to CD2, in 29 patients with T-cell malignancies.
  
  
  RESULTS
  Although initial responses were encouraging, 4 (13.7%) patients developed EBV-LPD and the trial was stopped. Reductions in CD4(+) and CD8(+) cell count numbers in response to therapy were seen in all patients, but in those patients developing EBV-LPD a significantly greater reduction in natural killer (NK) cell number and CD2 expression on T cells was seen. These findings highlight the importance of NK-cell depletion and CD2 expression in addition to T-cell depletion in the etiology of EBV-LPD.
  
  
  CONCLUSIONS
  The emergence of EBV-LPD may be associated with the ability of siplizumab to deplete both T and NK cells without affecting B cells. Agents that deplete T- and NK-cell populations without affecting B cell number should be screened for this potentially serious adverse event.
authors.affiliation: Metabolism Branch, Center for Cancer Research, Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland and MedImmune, Inc, Gaithersburg, Maryland, USA.
authors.forename: Deirdre
authors.initials: D
authors.lastname: O'Mahony
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
authors.forename: Maryalice
authors.initials: M
authors.lastname: Stetler-Stevenson
authors.forename: Helen
authors.initials: H
authors.lastname: Matthews
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Brown
authors.forename: Thomas
authors.initials: T
authors.lastname: Fleisher
authors.forename: Stefania
authors.initials: S
authors.lastname: Pittaluga
authors.forename: Mark
authors.initials: M
authors.lastname: Raffeld
authors.forename: Paul S
authors.initials: PS
authors.lastname: Albert
authors.forename: Dirk
authors.initials: D
authors.lastname: Reitsma
authors.forename: Karen
authors.initials: K
authors.lastname: Kaucic
authors.forename: Luz
authors.initials: L
authors.lastname: Hammershaimb
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Waldmann
authors.forename: John E
authors.initials: JE
authors.lastname: Janik
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D020031:Epstein-Barr Virus Infections / Q000276:immunology*; D005260:Female; D006801:Humans; D054066:Leukemia, Large Granular Lymphocytic / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D008212:Lymphocyte Depletion; D008232:Lymphoproliferative Disorders / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000276:immunology* / Q000378:metabolism; D014057:Tomography, X-Ray Computed
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D051918:Sialic Acid Binding Ig-like Lectin 2; C544394:siplizumab