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Lookup NU author(s): Dr Su Han Lum, Dr Geoff Shenton, Professor Sophie HambletonORCiD, Professor Andrew GenneryORCiD, Professor Mary Slatter
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2023Data comparing hematopoietic stem cell transplantation (HSCT) using bone marrow (BM) or peripheral blood stem cell (PBSC) grafts in children after alemtuzumab-based conditioning are lacking. We investigated whether in vivo T cell depletion using alemtuzumab could reduce the risk of severe acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD) after HSCT with matched unrelated donor (MUD) BM or PBSCs. This retrospective multicenter study included 397 children (BM group, n = 202; PBSC group, n = 195) who underwent first MUD HSCT at 9 pediatric centers in the United Kingdom between 2015 and 2019. The median age at transplantation was 7.0 years (range, .1 to 19.3 years), and the median duration of follow-up was 3.1 years (range, .3 to 7.5 years). The 3-year overall survival was 81% for the entire cohort (BM group, 80%; PBSC group, 81%). The incidence of grade II-IV aGVHD was significantly higher in the PBSC group (31%) compared to the BM group (31% versus 19%; P = .003), with no difference in the incidence of grade III-IV aGVHD (BM, 7%; PBSC, 12%; P = .17). CD3+ T cell dose >5 × 108/kg and the use of PBSCs were independent predictors of grade II-IV aGVHD. When considering CD3+ T cell dose and GVHD prophylaxis, PBSC transplantation with a calcineurin inhibitor (CNI) and mycophenolate mofetil (MMF) and a CD3+ T cell dose ≤5 × 108/kg had a comparable grade II-IV aGVHD to BM transplantation plus a CNI (20% versus 18%; P = .52). PBSC transplantation was associated with a lower incidence of cGVHD compared to BM transplantation (6% versus 11%; P = .03). Within the limits of this study, we identified a potential strategy to reduce the risk of severe GVHD in pediatric PBSC recipients that includes a combination of in vivo T cell depletion using alemtuzumab and dual GVHD prophylaxis (with a CNI and MMF) and limiting the CD3+ T cell dose to ≤5 × 108/kg.
Author(s): Lum SH, James B, Ottaviano G, Ewins A-M, Patrick K, Ali S, Carpenter B, Silva J, Tewari S, Furness C, Thomas A, Shenton G, Bonney D, Moppett J, Hambleton S, Gennery AR, Amrolia P, Gibson B, Hough R, Rao K, Slatter M, Wynn R
Publication type: Article
Publication status: Published
Journal: Transplantation and Cellular Therapy
Year: 2024
Volume: 30
Issue: 3
Pages: 314.e1-314.e12
Print publication date: 01/03/2024
Online publication date: 14/12/2023
Acceptance date: 09/12/2023
Date deposited: 14/02/2024
ISSN (print): 2666-6375
ISSN (electronic): 2666-6367
Publisher: Elsevier B.V.
URL: https://doi.org/10.1016/j.jtct.2023.12.005
DOI: 10.1016/j.jtct.2023.12.005
PubMed id: 38103787
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