title: Increased incidence of EBV-related disease following paediatric stem cell transplantation with reduced-intensity conditioning.
abstract: The incidence of Epstein-Barr virus (EBV) viraemia and lymphoproliferative disease (LPD) was studied in a consecutive cohort of 128 paediatric patients undergoing stem cell transplantation (SCT) with reduced-intensity conditioning (RIC; n = 65) or conventional-intensity conditioning (CIC; n = 68). Following CIC, six of 68 (8%) developed viraemia; all remained asymptomatic. EBV viraemia (23 of 65 patients = 35%, P < 0.001) and LPD (10 of 65 = 15%, P < 0.001) were significantly more frequent following RIC. Of the 23 RIC patients who developed viraemia, eight remained asymptomatic, five had symptomatic viraemia (fever +/- rash), and 10 patients developed LPD, two of whom died. An absolute lymphocyte count of <0.3 x 10(9)/l at the time of onset of viraemia was strongly predictive of development of LPD (P < 0.05) in this group. The incidence of viraemia was significantly higher in patients receiving serotherapy with antithymocyte globulin (ATG; 15 of 43, 35%) than Campath (12 of 73, 16.4%, P < 0.05). Primary immunodeficiency and acute graft-versus-host disease were associated with EBV viraemia in univariate analysis, but were not independent risk factors. In conclusion, EBV viraemia and LPD appear to be significantly more common in children following RIC SCT, particularly with selective depletion of recipient T cells relative to B cells following the use of ATG. This probably reflects the profound immunosuppression following RIC SCT, together with the incomplete ablation of recipient-derived B cells.
authors.affiliation: Department of Bone Marrow Transplantation, Great Ormond Street Hospital NHS Trust, London, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cohen
authors.forename: Minal
authors.initials: M
authors.lastname: Gandhi
authors.forename: Paru
authors.initials: P
authors.lastname: Naik
authors.forename: David
authors.initials: D
authors.lastname: Cubitt
authors.forename: Kanchan
authors.initials: K
authors.lastname: Rao
authors.forename: Urvashi
authors.initials: U
authors.lastname: Thaker
authors.forename: E Graham
authors.initials: EG
authors.lastname: Davies
authors.forename: H Bobby
authors.initials: HB
authors.lastname: Gaspar
authors.forename: Persis J
authors.initials: PJ
authors.lastname: Amrolia
authors.forename: Paul
authors.initials: P
authors.lastname: Veys
mesh_terms: D000293:Adolescent; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000276:immunology; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000821:virology; D004854:Herpesvirus 4, Human; D006801:Humans; D007116:Immunization, Passive; D015994:Incidence; D007223:Infant; D018655:Lymphocyte Count; D008232:Lymphoproliferative Disorders / Q000276:immunology / Q000601:surgery* / Q000821:virology; D008297:Male; D015999:Multivariate Analysis; D012307:Risk Factors; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes / Q000276:immunology; D019172:Transplantation Conditioning / Q000379:methods*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000961:Antilymphocyte Serum; D000074323:Alemtuzumab