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Graft-Versus-Host Disease

Partial CD8+ T-cell depletion of allogeneic peripheral blood stem cell transplantation is insufficient to prevent graft-versus-host disease

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Summary:

Prior studies suggest that depletion of CD8+ T cells from donor bone marrow or donor lymphocyte infusions can reduce graft-versus-host disease (GVHD) without compromising graft-versus-leukemia. We explored CD8 depletion in patients undergoing matched related donor (MRD, n=25) and unrelated donor (URD, n=16) peripheral blood stem cell transplantation following myeloablative conditioning with cyclophosphamide (60 mg/kg/day i.v. × 2) and total body irradiation (200 cGy × 7 fractions). Ex vivo incubation of mobilized donor peripheral blood cells with anti-CD8 antibody coated high-density microparticles removed 99% of CD8+ cells. The median number of CD8+ cells infused was 3.9 × 105 cells/kg (2.2 × 105 in MRD, and 8.1 × 105 in URD patients). Post transplant immune suppression included tacrolimus in the MRD cohort, and tacrolimus plus mini-methotrexate (5 mg/m2 days +1, 3, 6, 11) in the URD cohort. All 41 patients engrafted. Grade 2–4 acute GVHD incidence was 61% (44% MRD, 88% URD). Chronic GVHD incidence was 50% (48% MRD, 55% URD). Relapse incidence was 4.9%. Estimated event-free and overall survival rates were 65 and 63%, respectively, at 1 year and 56 and 57%, respectively, at 2 years. There was no correlation between CD8+ number and GVHD or survival. A 2-log depletion of CD8+ cells from PBSC is insufficient to prevent GVHD.

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Acknowledgements

This work was supported by The Ted and Eileen Pasquarello Leukemia Research Fund and NIH Grants AI29530 and HL70149-01A1. VTH is a recipient of the ASH Clinical Fellow Scholar Award. RJS is a recipient of the LLSA Scholar for Clinical Research Career Development Award-# 2020-00.

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Authors and Affiliations

  1. Department of Medical Oncology, Biostatistics, Dana Farber Cancer Institute, Boston, MA, USA

    V T Ho, E P Hochberg, C Cutler, S J Lee, D C Fisher, G Kao, H Daley, J Levin, E P Alyea, J H Antin & R J Soiffer

  2. Department of Biostatistics, Dana Farber Cancer Institute, Boston, MA, USA

    H T Kim & S Li

  3. Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA

    V T Ho, E P Hochberg, C Cutler, S J Lee, D C Fisher, E Milford, E P Alyea, J H Antin & R J Soiffer

  4. Department of Radiation Therapy, Brigham and Women's Hospital, Boston, MA, USA

    A Ng & P Mauch

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  1. V T Ho
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Correspondence to V T Ho.

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Ho, V., Kim, H., Li, S. et al. Partial CD8+ T-cell depletion of allogeneic peripheral blood stem cell transplantation is insufficient to prevent graft-versus-host disease. Bone Marrow Transplant 34, 987–994 (2004). https://doi.org/10.1038/sj.bmt.1704690

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  • DOI: https://doi.org/10.1038/sj.bmt.1704690

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