title: EBV-associated post-transplant lymphoproliferative disorder following in vivo T-cell-depleted allogeneic transplantation: clinical features, viral load correlates and prognostic factors in the rituximab era.
abstract: EBV-associated post-transplant lymphoproliferative disease (PTLD) following Alemtuzumab-based allo-SCT is a relatively uncommon and challenging clinical problem but has not received detailed study in a large cohort. Quantitative-PCR (qPCR) monitoring for EBV reactivation post allo-SCT is now commonplace but its diagnostic and predictive value remains unclear. Sixty-nine patients with PTLD following Alemtuzumab-based allo-SCT were studied. Marked clinicopathological heterogeneity was evident; lymphadenopathy was frequently absent, whereas advanced extranodal disease was common. The median viral load at clinical presentation was 49 300 copies/mL (50-65 200 000 copies/mL) and, notably, 23% and 45% of cases, respectively, had 10 000 and 40 000 copies/mL. The overall response rate to rituximab as first-line therapy was 70%. For rituximab failures, chemotherapy was ineffectual but DLIs were successful. A four-parameter prognostic index predicted response to therapy (OR 0.30 (0.12-0.74); P=0.009] and PTLD mortality (hazard ratio (HR) 1.81 (1.12-2.93) P=0.02) on multivariate analysis. This is the largest detailed series of EBV-associated PTLD after allo-SCT. At clinical presentation, EBV-qPCR values are frequently below customary thresholds for pre-emptive therapy, challenging current paradigms for monitoring and intervention. A four-point score identifies a proportion of patients at risk of rituximab-refractory disease for whom alternative therapy is needed.
authors.affiliation: 1] Department of Clinical Haematology, Nottingham University Hospitals NHS Trust, Nottingham, UK [2] School of Cancer Sciences, University of Birmingham, Birmingham, UK.
authors.forename: C P
authors.initials: CP
authors.lastname: Fox
authors.affiliation: 1] School of Cancer Sciences, University of Birmingham, Birmingham, UK [2] University Hospitals Birmingham NHS Trust, Birmingham, UK.
authors.forename: D
authors.initials: D
authors.lastname: Burns
authors.affiliation: The Beatson, West of Scotland Cancer Centre, Glasgow, UK.
authors.forename: A N
authors.initials: AN
authors.lastname: Parker
authors.affiliation: University College London, Cancer Institute, London, UK.
authors.forename: K S
authors.initials: KS
authors.lastname: Peggs
authors.affiliation: Department of Clinical Haematology, Nottingham University Hospitals NHS Trust, Nottingham, UK.
authors.forename: C M
authors.initials: CM
authors.lastname: Harvey
authors.affiliation: Manchester Royal Infirmary, Manchester, UK.
authors.forename: S
authors.initials: S
authors.lastname: Natarajan
authors.affiliation: University Hospitals Bristol NHS Trust, Bristol, UK.
authors.forename: D I
authors.initials: DI
authors.lastname: Marks
authors.affiliation: The Royal Marsden, London, UK.
authors.forename: B
authors.initials: B
authors.lastname: Jackson
authors.affiliation: University Hospitals Birmingham NHS Trust, Birmingham, UK.
authors.forename: G
authors.initials: G
authors.lastname: Chakupurakal
authors.affiliation: The Christie NHS Foundation Trust, Manchester, UK.
authors.forename: M
authors.initials: M
authors.lastname: Dennis
authors.affiliation: King's College Hospital NHS Trust, London, UK.
authors.forename: Z
authors.initials: Z
authors.lastname: Lim
authors.affiliation: St James's Institute of Oncology, Leeds, UK.
authors.forename: G
authors.initials: G
authors.lastname: Cook
authors.affiliation: Royal Free London NHS Trust, London, UK.
authors.forename: B
authors.initials: B
authors.lastname: Carpenter
authors.affiliation: University of Liverpool, Liverpool, UK.
authors.forename: A R
authors.initials: AR
authors.lastname: Pettitt
authors.affiliation: The Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, UK.
authors.forename: S
authors.initials: S
authors.lastname: Mathew
authors.affiliation: University Hospitals of Leicester NHS Trust, Leicester, UK.
authors.forename: L
authors.initials: L
authors.lastname: Connelly-Smith
authors.affiliation: University College London, Cancer Institute, London, UK.
authors.forename: J A L
authors.initials: JA
authors.lastname: Yin
authors.affiliation: Cancer Research UK Clinical Trials Unit, University of Birmingham, UK.
authors.forename: M
authors.initials: M
authors.lastname: Viskaduraki
authors.affiliation: Royal Free London NHS Trust, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Chakraverty
authors.affiliation: University Hospital Southampton NHS Trust, Southampton, UK.
authors.forename: K
authors.initials: K
authors.lastname: Orchard
authors.affiliation: The Royal Marsden, London, UK.
authors.forename: B E
authors.initials: BE
authors.lastname: Shaw
authors.affiliation: Department of Clinical Haematology, Nottingham University Hospitals NHS Trust, Nottingham, UK.
authors.forename: J L
authors.initials: JL
authors.lastname: Byrne
authors.affiliation: Cancer Research UK Clinical Trials Unit, University of Birmingham, UK.
authors.forename: C
authors.initials: C
authors.lastname: Brookes
authors.affiliation: 1] School of Cancer Sciences, University of Birmingham, Birmingham, UK [2] University Hospitals Birmingham NHS Trust, Birmingham, UK.
authors.forename: C F
authors.initials: CF
authors.lastname: Craddock
authors.affiliation: 1] School of Cancer Sciences, University of Birmingham, Birmingham, UK [2] University Hospitals Birmingham NHS Trust, Birmingham, UK.
authors.forename: S
authors.initials: S
authors.lastname: Chaganti
mesh_terms: D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015331:Cohort Studies; D020031:Epstein-Barr Virus Infections / Q000188:drug therapy / Q000209:etiology*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D007167:Immunotherapy; D008232:Lymphoproliferative Disorders / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D000069283:Rituximab; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000009:adverse effects* / Q000379:methods; D019562:Viral Load
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D000069283:Rituximab