title: Greatly reduced risk of EBV reactivation in rituximab-experienced recipients of alemtuzumab-conditioned allogeneic HSCT.
abstract: EBV-associated post-transplant lymphoproliferative disease (PTLD) remains an important complication of allogeneic haematopoietic stem cell transplantation (allo-HSCT). We retrospectively analysed the incidence and risk factors for EBV reactivation in 186 adult patients undergoing consecutive allo-HSCT with alemtuzumab T-cell depletion at a single centre. The cumulative incidence of EBV reactivation was 48% (confidence interval (CI) 41-55%) by 1 year, with an incidence of high-level EBV reactivation of 18% (CI 13-24%); 8 patients were concurrently diagnosed with PTLD. Amongst patients with high-level reactivation 31/38 (82%) developed this within only 2 weeks of first EBV qPCR positivity. In univariate analysis age⩾50 years was associated with significantly increased risk of EBV reactivation (hazard ratio (HR) 1.54, CI 1.02-2.31; P=0.039). Furthermore, a diagnosis of non-Hodgkin lymphoma (NHL) was associated with greatly reduced risk of reactivation (HR 0.10, CI 0.03-0.33; P=0.0001) and this was confirmed in multivariate testing. Importantly, rituximab therapy within 6 months prior to allo-HSCT was also highly predictive for lack of EBV reactivation (HR 0.18, CI 0.07-0.48; P=0.001) although confounding with NHL was apparent. Our data emphasise the risk of PTLD associated with alemtuzumab. Furthermore, we report the clinically important observation that rituximab, administered in the peri-transplant period, may provide effective prophylaxis for PTLD.
authors.affiliation: Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.|Centre for Clinical Haematology, University Hospitals Birmingham NHS Trust, Birmingham, UK.
authors.forename: D M
authors.initials: DM
authors.lastname: Burns
authors.affiliation: Centre for Clinical Haematology, University Hospitals Birmingham NHS Trust, Birmingham, UK.
authors.forename: S
authors.initials: S
authors.lastname: Rana
authors.affiliation: Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK.
authors.forename: E
authors.initials: E
authors.lastname: Martin
authors.affiliation: Centre for Clinical Haematology, University Hospitals Birmingham NHS Trust, Birmingham, UK.
authors.forename: S
authors.initials: S
authors.lastname: Nagra
authors.affiliation: Centre for Clinical Haematology, University Hospitals Birmingham NHS Trust, Birmingham, UK.
authors.forename: J
authors.initials: J
authors.lastname: Ward
authors.affiliation: Health Protection Agency Laboratory, Birmingham Heartlands Hospital, Birmingham, UK.
authors.forename: H
authors.initials: H
authors.lastname: Osman
authors.affiliation: Centre for Clinical Haematology, University Hospitals Birmingham NHS Trust, Birmingham, UK.
authors.forename: A I
authors.initials: AI
authors.lastname: Bell
authors.affiliation: Centre for Clinical Haematology, University Hospitals Birmingham NHS Trust, Birmingham, UK.|Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
authors.forename: P
authors.initials: P
authors.lastname: Moss
authors.affiliation: Centre for Clinical Haematology, Nottingham University Hospitals NHS Trust, Nottingham, UK.
authors.forename: N H
authors.initials: NH
authors.lastname: Russell
authors.affiliation: Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.|Centre for Clinical Haematology, University Hospitals Birmingham NHS Trust, Birmingham, UK.
authors.forename: C F
authors.initials: CF
authors.lastname: Craddock
authors.affiliation: Centre for Clinical Haematology, Nottingham University Hospitals NHS Trust, Nottingham, UK.
authors.forename: C P
authors.initials: CP
authors.lastname: Fox
authors.affiliation: Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.|Centre for Clinical Haematology, University Hospitals Birmingham NHS Trust, Birmingham, UK.
authors.forename: S
authors.initials: S
authors.lastname: Chaganti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000074323:Alemtuzumab / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000517:prevention & control / Q000821:virology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D018570:Risk Assessment; D000069283:Rituximab / Q000008:administration & dosage*; D014775:Virus Activation / Q000187:drug effects*; D055815:Young Adult
chemical_list: D000074323:Alemtuzumab; D000069283:Rituximab