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Graft-versus-tumor Effects

Evidence for a GVL effect following reduced-intensity allo-SCT in ALL: a British Society of Blood and Marrow Transplantation study

A Corrigendum to this article was published on 09 October 2013

Abstract

Myeloablative allo-SCT decreases relapse incidence (RI) in ALL. Reduced intensity conditioning (RIC) may extend allo-SCT to older and less fit patients. Sixty-nine ALL patients reported to the BSBMT underwent fludarabine-based RIC allo-SCT, 38 from unrelated donors (UD). Forty-four patients received alemtuzumab. ALL was in CR in 64 patients (93%). This was a second or third SCT in 23 patients. Two-year OS and PFS were 36% and 32%, respectively. In multivariate analysis male recipients demonstrated better OS and PFS (hazard ratio (HR)=0.42, P=0.008 and HR=0.45, P=0.012, respectively). Two-year TRM was 29%: higher with younger age (HR=0.97/year, P=0.041), female recipient (HR=2.55, P=0.049) and increasing grade of acute GVHD (HR=1.87, P=0.001). Two-year RI was 38% and was lower in patients with acute and chronic GVHD (HR=0.62 per increasing grade, P=0.035 and HR=0.52, P=0.025, respectively). Long-term ALL-free survival is achievable following fludarabine-based RIC allo-SCT. The association between GVHD and decreased RI suggests the presence of a GVL effect.

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Acknowledgements

We wish to thank the following data managers and transplant physicians for providing data and responding to requests for further information: J Horn and D Culligan, Aberdeen Royal Infirmary; J Gribben and J Cavenagh, St Bartholomew’s Hospital London; W Clay, Birmingham Heartlands Hospital; P Breslin, University Hospitals Bristol NHS Trust; T Dalton and A Bloor, The Christie Hospital Manchester; S Kukkapalli and M Koh, St George’s Hospital London; S Greep and H Hunter, Derriford Hospital Plymouth; K Hussein and M Kamzi, Guy’s Hospital London; B Holt and J Snowden, The Hallamshire Hospital Sheffield; F O’Boyle and J Apperley, Hammersmith Hospital London; S Hardaker and M Gilleece, Leeds Teaching Hospitals NHS Trust; R Lewin and A Hunter, The Leicester Royal Infirmary; J Ward and A Stewart, Queen Elizabeth Hospital Birmingham; S Littlewood, The Royal Marsden Hospital Sutton; J Sudak and S Mackinnon, The Royal Free Hospital London; L McNally and G Jackson, The Royal Victoria Infirmary Newcastle; K Thompson, University College Hospital London and A Robertson and P Johnson, The Western General Hospital Edinburgh.

Author contributions: PM designed the study, collected data and wrote the manuscript, AP and TL designed the study, performed transplants and contributed data, JP and KK ran the data registry and collected data, RP performed statistical analysis, BS, MP, AF, DM, CC, DM and GC performed transplants and contributed data, all authors critically reviewed and approved the manuscript.

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Medd, P., Peniket, A., Littlewood, T. et al. Evidence for a GVL effect following reduced-intensity allo-SCT in ALL: a British Society of Blood and Marrow Transplantation study. Bone Marrow Transplant 48, 982–987 (2013). https://doi.org/10.1038/bmt.2012.261

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