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Impact of Alemtuzumab Scheduling on Graft-versus-Host Disease after Unrelated Donor Fludarabine and Melphalan Allografts

Green, K; Pearce, K; Sellar, RS; Jardine, L; Nicolson, PLR; Nagra, S; Bigley, V; ... Collin, M; + view all (2017) Impact of Alemtuzumab Scheduling on Graft-versus-Host Disease after Unrelated Donor Fludarabine and Melphalan Allografts. Biology of Blood and Marrow Transplantation , 23 (5) pp. 805-812. 10.1016/j.bbmt.2017.02.007. Green open access

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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.

Type: Article
Title: Impact of Alemtuzumab Scheduling on Graft-versus-Host Disease after Unrelated Donor Fludarabine and Melphalan Allografts
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.bbmt.2017.02.007
Publisher version: https://doi.org/10.1016/j.bbmt.2017.02.007
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Life Sciences & Biomedicine, Hematology, Immunology, Transplantation, Alemtuzumab, T cell depletion, Graft-versus-host disease, Conditioning regimens, STEM-CELL TRANSPLANTATION, LONG-TERM OUTCOMES, INTENSITY ALLOGENEIC TRANSPLANTATION, BONE-MARROW TRANSPLANTS, ACUTE MYELOID-LEUKEMIA, IN-VIVO ALEMTUZUMAB, PERIPHERAL-BLOOD, CONDITIONING REGIMEN, FOLLICULAR LYMPHOMA, STATISTICAL-METHODS
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: https://discovery.ucl.ac.uk/id/eprint/1542855
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