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Infusion of bcr/abl peptide-reactive donor T cells to achieve molecular remission of chronic myeloid leukemia after CD34+ selected allogeneic hematopoietic cell transplantation

Leukemia volume 20, pages 2055–2057 (2006)Cite this article

Allogeneic hematopoietic cell transplantation represents an effective and potentially curative therapy for patients with chronic myeloid leukemia (CML).1 The efforts to decrease the risk of graft-versus-host disease (GVHD) as a major cause of transplant-related mortality by depleting T cells from the graft resulted in an increased incidence of CML relapse.2 These observations revealed that donor T cells representing the mediators of GVHD are also capable of inducing therapeutic graft-versus-leukemia (GVL) effects. Patients with disease recurrence after transplantation have been treated with donor lymphocyte infusion (DLI), which induced complete remissions in the majority of patients with CML in chronic phase.3 However, DLI is often associated with significant acute or chronic GVHD. The main challenge is therefore to augment the donor T-cell-mediated antileukemia effects without causing relevant GVHD.

To dissociate the GVL effect from GVHD, much attention has been paid to the identification of well-defined peptides derived from CML-associated antigens that may serve as target structures for T cells. Thus, a human leukocyte antigen (HLA)-A2-restricted proteinase 3-derived peptide which is capable of inducing CML-reactive cytotoxic T cells (CTLs) has been identified and a strong correlation between the presence of proteinase 3 peptide-reactive CTLs and clinical responses of CML patients after therapy with interferon-alpha or allogeneic hematopoietic cell transplantation has been reported.4 Further studies demonstrated the identification of peptides derived from the b3a2 breakpoint region of bcr/abl which bind to different HLA molecules and efficiently elicit CTL responses.5 Recently, the existence of circulating CD8+ T cells directed against bcr/abl peptides in CML patients and healthy donors has been documented.6, 7

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Acknowledgements

We would like to thank Bärbel Löbel, Diana Döhler, Verona Schwarze, Anja Maiwald and Anja Zenkel for the excellent technical assistance as well as Michelle Meredyth-Stewart for proof-reading of the manuscript. This work was supported in part by the Deutsche Krebshilfe Grant 70-2755 (MB and CT) and 70-2980 (MB and MS).

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Authors and Affiliations

  1. Medizinische Klinik und Poliklinik I, University Hospital, Dresden, Germany

    M Bornhauser, C Thiede, J Babatz, J Schetelig, T Illmer, A Kiani, U Platzbecker & G Ehninger

  2. Medizinische Klinik und Poliklinik III, University Hospital, Mainz, Germany

    W Herr

  3. Institute for Immunology, University Hospital, Dresden, Germany

    E-P Rieber & M Schmitz

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Bornhauser, M., Thiede, C., Babatz, J. et al. Infusion of bcr/abl peptide-reactive donor T cells to achieve molecular remission of chronic myeloid leukemia after CD34+ selected allogeneic hematopoietic cell transplantation. Leukemia 20, 2055–2057 (2006). https://doi.org/10.1038/sj.leu.2404383

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