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Graft-Versus-Leukaemia

Generation of alloreactive anti-leukemic cytotoxic T lymphocytes with attenuated GVHD properties from haploidentical parents in childhood acute lymphoblastic leukemia

Bone Marrow Transplantation volume 30, pages 687–697 (2002)Cite this article

Abstract

We sought to generate alloreactive leukemia-reactive cytotoxic T lymphocytes from haploidentical parents by culture of peripheral blood mononuclear cells in vitro with irradiated leukemic blasts and IL-2 from children with ALL. After 21 days in culture the mean cytotoxicity of haploidentical lymphocytes against ALL blasts was 38% (n = 11). Cultured parental CTL were not leukemia specific but alloreactive as evidenced by equivalent cytotoxicity against stimulating ALL blasts and ConA-stimulated blasts from the other parent. The cultures yielded primarily CD8+ T cells (59%). Irradiation of CTL limited proliferation by 96% but had no short-term effects on leukemia reactive cytotoxicity, suggesting a means to limit GVHD potential in vivo. One patient was treated for relapse of ALL post-haploidentical transplant with CTL generated from the original donor. A total of nine infusions were given: the first three were irradiated, while the last six were not due to disease progression. The patient experienced clearance of peripheral blasts, and despite concomitant infusion of IL-2 with the last three CTL infusions, did not experience immediate GVHD reactions. We conclude that ALL blasts are sufficiently immunostimulatory to generate in vitro CTL with provision of exogenous IL-2, and that these CTL could exert an anti-leukemia effect in vivo.

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Acknowledgements

This work was supported by: Translational Research Grants from the Leukemia and Lymphoma Society of America (EKW, MWB); The Phil Niekro Beat Leukemia Celebrity Classic/Jill Andrews Leukemia Research Fund (IJ, AMY, MWB); and The Stott Research Fund (IJ, AMY, MWB).

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Authors and Affiliations

  1. Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA

    I Jurickova, AM Yeager & MW Boyer

  2. Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA

    EK Waller & AM Yeager

  3. Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA

    EK Waller, AM Yeager & MW Boyer

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  1. I Jurickova
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  2. EK Waller
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Jurickova, I., Waller, E., Yeager, A. et al. Generation of alloreactive anti-leukemic cytotoxic T lymphocytes with attenuated GVHD properties from haploidentical parents in childhood acute lymphoblastic leukemia. Bone Marrow Transplant 30, 687–697 (2002). https://doi.org/10.1038/sj.bmt.1703718

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