title: Impact of Alemtuzumab Scheduling on Graft-versus-Host Disease after Unrelated Donor Fludarabine and Melphalan Allografts.
abstract: Alemtuzumab conditioning is highly effective at reducing the incidence of acute and chronic graft-versus-host disease (GVHD) in reduced-intensity fludarabine and melphalan transplantation with cyclosporine monotherapy. Less frequent and lower dose scheduling may be used with sibling donors, but an optimal regimen for matched unrelated donors has not been defined. In this retrospective observational study of 313 patients, the incidence and severity of GVHD was compared in patients receiving 3 different dose schedules: the standard 100-mg regimen (20 mg on days -7 to -3), 60 mg (30 mg on days -4 and -2), or 50 mg (10 mg on days -7 to -3). Patients treated with 100 mg, 60 mg, or 50 mg developed acute GVHD grades I to IV with an incidence of 74%, 65%, and 64%, respectively, whereas 36%, 32%, and 41% developed chronic GHVD. An excess of severe acute grades III/IV GVHD was observed in the 50-mg cohort (15% versus 2% to 6%; P = .016). The relative risk of severe acute grade GVHD remained more than 3-fold higher in the 50-mg cohort compared with the 100-mg cohort after adjustment for differences in HLA match, age, gender mismatch, cytomegalovirus risk, and diagnosis (P = .030). The findings indicate that the 60-mg alemtuzumab schedule was comparable with the 100-mg schedule, but more attenuated schedules may increase the risk of severe grade GVHD.
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Kile
authors.initials: K
authors.lastname: Green
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Kim
authors.initials: K
authors.lastname: Pearce
authors.affiliation: Cancer Institute, University College London, London, United Kingdom; Department of Haematology, University College London Hospitals NHS Foundation Trust, London, United Kingdom.
authors.forename: Rob S
authors.initials: RS
authors.lastname: Sellar
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; Northern Centre for Bone Marrow Transplantation, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.
authors.forename: Laura
authors.initials: L
authors.lastname: Jardine
authors.affiliation: School of Cancer Sciences, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Phillip L R
authors.initials: PLR
authors.lastname: Nicolson
authors.affiliation: Centre for Clinical Haematology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Nagra
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; Northern Centre for Bone Marrow Transplantation, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.
authors.forename: Venetia
authors.initials: V
authors.lastname: Bigley
authors.affiliation: Northern Centre for Bone Marrow Transplantation, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom; Northern Institute for Cancer Research, Newcastle University, Newcastle Upon Tyne, United Kingdom.
authors.forename: Graham
authors.initials: G
authors.lastname: Jackson
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Dickinson
authors.affiliation: Cancer Institute, University College London, London, United Kingdom; Department of Haematology, University College London Hospitals NHS Foundation Trust, London, United Kingdom.
authors.forename: Kirsty
authors.initials: K
authors.lastname: Thomson
authors.affiliation: Cancer Institute, University College London, London, United Kingdom; Department of Haematology, University College London Hospitals NHS Foundation Trust, London, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Mackinnon
authors.affiliation: School of Cancer Sciences, University of Birmingham, Birmingham, United Kingdom; Centre for Clinical Haematology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom.
authors.forename: Charles
authors.initials: C
authors.lastname: Craddock
authors.affiliation: Cancer Institute, University College London, London, United Kingdom; Department of Haematology, University College London Hospitals NHS Foundation Trust, London, United Kingdom.
authors.forename: Karl S
authors.initials: KS
authors.lastname: Peggs
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; Northern Centre for Bone Marrow Transplantation, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom. Electronic address: matthew.collin@newcastle.ac.uk.
authors.forename: Matthew
authors.initials: M
authors.lastname: Collin
mesh_terms: D000328:Adult; D000368:Aged; D000074323:Alemtuzumab / Q000008:administration & dosage*; D064591:Allografts / Q000737:chemistry / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000150:complications / Q000628:therapy; D006801:Humans; D008297:Male; D008558:Melphalan / Q000627:therapeutic use; D008875:Middle Aged; D012189:Retrospective Studies; D019172:Transplantation Conditioning / Q000379:methods; D061349:Unrelated Donors; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000074323:Alemtuzumab; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan
keywords: Alemtuzumab; Conditioning regimens; Graft-versus-host disease; T cell depletion