Induction of HA-1-specific cytotoxic T-cell clones parallels the therapeutic effect of donor lymphocyte infusion

Authors

  • Brigitte Kircher,

    1. Laboratory for Tumour- and Immunobiology, Bone Marrow Transplant Unit, Division of Haematology and Oncology, Department of Internal Medicine, Innsbruck University Hospital, Innsbruck, Austria,
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  • Stefan Stevanovic,

    1. Institute for Cellular Biology, Department of Immunology, University of Tuebingen, Germany,
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  • Martina Urbanek,

    1. Laboratory for Molecular Genetics and Diagnostics, Division of Haematology and Oncology, Department of Internal Medicine, Innsbruck University Hospital, Innsbruck, and
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  • Andrea Mitterschiffthaler,

    1. Austrian Bone Marrow Donor Registry, Vienna, Austria
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  • Hans-Georg Rammensee,

    1. Institute for Cellular Biology, Department of Immunology, University of Tuebingen, Germany,
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  • Kurt Grünewald,

    1. Laboratory for Molecular Genetics and Diagnostics, Division of Haematology and Oncology, Department of Internal Medicine, Innsbruck University Hospital, Innsbruck, and
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  • Günther Gastl,

    1. Laboratory for Tumour- and Immunobiology, Bone Marrow Transplant Unit, Division of Haematology and Oncology, Department of Internal Medicine, Innsbruck University Hospital, Innsbruck, Austria,
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  • David Nachbaur

    1. Laboratory for Tumour- and Immunobiology, Bone Marrow Transplant Unit, Division of Haematology and Oncology, Department of Internal Medicine, Innsbruck University Hospital, Innsbruck, Austria,
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Brigitte Kircher, PhD, Laboratory for Tumour- and Immunobiology, Division of Haematology and Oncology, Department of Internal Medicine, Innsbruck University Hospital, Anichstrasse 35, 6020 Innsbruck, Austria. E-mail: brigitte.eibl@uklibk.ac.at

Abstract

Summary.  Donor lymphocyte infusions (DLI) can induce a graft-versus-leukaemia (GvL) reaction in patients with relapsed disease. However, the mechanisms involved in remission induction are not completely known. A patient with chemotherapy-refractory relapse 1 year after human leucocyte antigen (HLA)-identical, unrelated stem cell transplantation (SCT) for bcr/abl-positive common acute lymphoblastic leukaemia (ALL) received a DLI from the original donor, and achieved complete cytogenetic and molecular remission concomitantly with extensive graft-versus-host disease (GvHD). Seven CD8+, donor-derived, alloreactive T-cell clones were generated by stimulating post-DLI remission cells with the patient's pretransplant mature dendritic cells. The minor histocompatibility antigen (mHag) recognized by these T-cell clones was identified as HA-1, a mHag associated with acute GvHD after SCT. Our finding provides evidence of HA-1-associated GvL effects after DLI that paralleled the eradication of full-blown, chemotherapy-refractory ALL relapse after allogeneic SCT.

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