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Donor Lymphocyte Infusions

Changes in T cell receptor repertoire associated with graft-versus-tumor effect and graft-versus-host disease in patients with relapsed multiple myeloma after donor lymphocyte infusion

Bone Marrow Transplantation volume 25, pages 623–632 (2000)Cite this article

Abstract

Recent reports of clinical responses following donor lymphocyte infusions (DLI) in patients with relapsed multiple myeloma (MM) after allogeneic BMT have demonstrated the ability of allogeneic cells to mediate a graft-versus-myeloma (GVM) effect, but the mechanisms involved have not been determined. To identify changes in the T cell compartment associated with DLI, we performed a molecular analysis of the T cell receptor (TCR) repertoire in four patients with relapsed MM who received infusions of CD4+ lymphocytes from HLA-identical sibling donors. Three of the four patients demonstrated a clinical anti-myeloma response following DLI but also developed graft-versus-host disease (GVHD). The TCR repertoire was examined after PCR amplification of 24 Vβ gene subfamilies. This method determines the relative utilization of each Vβ gene subfamily and also allows the identification of clonal and oligoclonal T cell populations through analysis of CDR3 regions for each TCR Vβ gene subfamily. Serial blood samples were obtained over at least a 1 year period before and after DLI and results compared to 10 normal donors. Serial analysis of CDR3 size profiles demonstrated the appearance of clonal T cell populations after DLI in each of the three responding patients. The appearance of some clones was noted within the first 3 months after DLI and coincided with decreasing levels of monoclonal paraprotein indicating an ongoing GVM response. Other T cell clones appeared at later time points and coincided with the development of GVHD. These findings demonstrate that T cell clones with different patterns of onset can be identified in the peripheral blood of MM patients following DLI. Further functional characterization of these distinct clonal expansions will be required to determine whether these T cell clones are mediators of either anti-myeloma or anti-host activity. Bone Marrow Transplantation (2000) 25, 623–632.

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Acknowledgements

This work was supported by NIH grants AI29530 and CA78378 and by a grant from Associazione ‘Cristina Bassi’. Dr Alyea is a Special Fellow of the Leukemia Society of America. Dr Soiffer is a Clinical Research Scholar of the Leukemia Society of America.

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Authors and Affiliations

  1. Department of Adult Oncology, Dana-Farber Cancer Institute and Department of Medicine, Center for Hematologic Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA

    E Orsini, EP Alyea, R Schlossman, C Canning, RJ Soiffer, A Chillemi, KC Anderson & J Ritz

  2. Department of Biostatistics, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA

    D Neuberg

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  1. E Orsini
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Orsini, E., Alyea, E., Schlossman, R. et al. Changes in T cell receptor repertoire associated with graft-versus-tumor effect and graft-versus-host disease in patients with relapsed multiple myeloma after donor lymphocyte infusion. Bone Marrow Transplant 25, 623–632 (2000). https://doi.org/10.1038/sj.bmt.1702187

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