Does the emergence and persistence of donor-derived leukaemia-reactive cytotoxic T lymphocytes protect patients given an allogeneic BMT from recurrence? Results of a preliminary study

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Abstract

The frequency of CTL precursors (CTLp) directed towards recipient-derived pre-transplant leukaemic blasts (LB) was measured in the peripheral blood of nine children with acute leukaemia and given BMT from either an HLA-identical sibling or a matched unrelated donor (MUD). Patients were evaluated at various time points between 1 month and more than 2 years after transplantation. A high frequency of donor-derived LB-reactive CTLp was detectable 2-6 months after BMT in all children and persisted for at least up to 18 months in the eight patients in haematological remission, while it rapidly declined in the only patient who relapsed. Generation of LB-reactive T cell clones obtained from some of these patients demonstrates that various T lymphocyte subsets, either HLA class I-restricted/TCR-dependent or HLA-unrestricted, contribute to this phenomenon. The in vitro GVL effect here described seems to be at least partially separated from GVHR, since no correlation was observed between the emergence of LB-reactive CTLp and the development and/or severity of GVHD. Development of LB-reactive CTL in the patients was independent of the frequency of these cells in the donor. These data suggest that donor-derived CTL activity specifically directed towards leukaemic blasts may develop in patients given allogeneic BMT and contribute to the maintenance of a state of haematological remission.

Original languageEnglish
Pages (from-to)743-750
Number of pages8
JournalBone Marrow Transplantation
Volume22
Issue number8
Publication statusPublished - 1998

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Cytotoxic T-Lymphocytes
Leukemia
Tissue Donors
Recurrence
Unrelated Donors
T-Lymphocyte Subsets
Siblings
Clone Cells
Transplantation
Maintenance
T-Lymphocytes
Transplants

Keywords

  • Bone marrow transplantation
  • CTL
  • Graft-versus-host disease
  • Graft-versus-leukaemia
  • Leukaemia relapse

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

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title = "Does the emergence and persistence of donor-derived leukaemia-reactive cytotoxic T lymphocytes protect patients given an allogeneic BMT from recurrence? Results of a preliminary study",
abstract = "The frequency of CTL precursors (CTLp) directed towards recipient-derived pre-transplant leukaemic blasts (LB) was measured in the peripheral blood of nine children with acute leukaemia and given BMT from either an HLA-identical sibling or a matched unrelated donor (MUD). Patients were evaluated at various time points between 1 month and more than 2 years after transplantation. A high frequency of donor-derived LB-reactive CTLp was detectable 2-6 months after BMT in all children and persisted for at least up to 18 months in the eight patients in haematological remission, while it rapidly declined in the only patient who relapsed. Generation of LB-reactive T cell clones obtained from some of these patients demonstrates that various T lymphocyte subsets, either HLA class I-restricted/TCR-dependent or HLA-unrestricted, contribute to this phenomenon. The in vitro GVL effect here described seems to be at least partially separated from GVHR, since no correlation was observed between the emergence of LB-reactive CTLp and the development and/or severity of GVHD. Development of LB-reactive CTL in the patients was independent of the frequency of these cells in the donor. These data suggest that donor-derived CTL activity specifically directed towards leukaemic blasts may develop in patients given allogeneic BMT and contribute to the maintenance of a state of haematological remission.",
keywords = "Bone marrow transplantation, CTL, Graft-versus-host disease, Graft-versus-leukaemia, Leukaemia relapse",
author = "D. Montagna and F. Locatelli and V. Calcaterra and P. Comoli and A. Moretta and G. Giorgiani and M. Zecca and F. Bonetti and E. Giraldi and G. Rondini and R. Maccario",
year = "1998",
language = "English",
volume = "22",
pages = "743--750",
journal = "Bone Marrow Transplantation",
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TY - JOUR

T1 - Does the emergence and persistence of donor-derived leukaemia-reactive cytotoxic T lymphocytes protect patients given an allogeneic BMT from recurrence? Results of a preliminary study

AU - Montagna, D.

AU - Locatelli, F.

AU - Calcaterra, V.

AU - Comoli, P.

AU - Moretta, A.

AU - Giorgiani, G.

AU - Zecca, M.

AU - Bonetti, F.

AU - Giraldi, E.

AU - Rondini, G.

AU - Maccario, R.

PY - 1998

Y1 - 1998

N2 - The frequency of CTL precursors (CTLp) directed towards recipient-derived pre-transplant leukaemic blasts (LB) was measured in the peripheral blood of nine children with acute leukaemia and given BMT from either an HLA-identical sibling or a matched unrelated donor (MUD). Patients were evaluated at various time points between 1 month and more than 2 years after transplantation. A high frequency of donor-derived LB-reactive CTLp was detectable 2-6 months after BMT in all children and persisted for at least up to 18 months in the eight patients in haematological remission, while it rapidly declined in the only patient who relapsed. Generation of LB-reactive T cell clones obtained from some of these patients demonstrates that various T lymphocyte subsets, either HLA class I-restricted/TCR-dependent or HLA-unrestricted, contribute to this phenomenon. The in vitro GVL effect here described seems to be at least partially separated from GVHR, since no correlation was observed between the emergence of LB-reactive CTLp and the development and/or severity of GVHD. Development of LB-reactive CTL in the patients was independent of the frequency of these cells in the donor. These data suggest that donor-derived CTL activity specifically directed towards leukaemic blasts may develop in patients given allogeneic BMT and contribute to the maintenance of a state of haematological remission.

AB - The frequency of CTL precursors (CTLp) directed towards recipient-derived pre-transplant leukaemic blasts (LB) was measured in the peripheral blood of nine children with acute leukaemia and given BMT from either an HLA-identical sibling or a matched unrelated donor (MUD). Patients were evaluated at various time points between 1 month and more than 2 years after transplantation. A high frequency of donor-derived LB-reactive CTLp was detectable 2-6 months after BMT in all children and persisted for at least up to 18 months in the eight patients in haematological remission, while it rapidly declined in the only patient who relapsed. Generation of LB-reactive T cell clones obtained from some of these patients demonstrates that various T lymphocyte subsets, either HLA class I-restricted/TCR-dependent or HLA-unrestricted, contribute to this phenomenon. The in vitro GVL effect here described seems to be at least partially separated from GVHR, since no correlation was observed between the emergence of LB-reactive CTLp and the development and/or severity of GVHD. Development of LB-reactive CTL in the patients was independent of the frequency of these cells in the donor. These data suggest that donor-derived CTL activity specifically directed towards leukaemic blasts may develop in patients given allogeneic BMT and contribute to the maintenance of a state of haematological remission.

KW - Bone marrow transplantation

KW - CTL

KW - Graft-versus-host disease

KW - Graft-versus-leukaemia

KW - Leukaemia relapse

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