Summary:
We assayed helper T-lymphocyte precursor frequencies (HTLPf), interferon (IFN)-γ-producing cell frequencies (IFN-γPf) and CTL precursor frequencies (CTLPf) to see if they could predict the severity of acute graft-versus-host disease (aGVHD) and disease relapse after transplantation. In all, 48 bone marrow transplantation (BMT) patients and their HLA-identical sibling (n=29) or matched unrelated donors (MUD) (n=19) were recruited. HTLPf, IFN-γPf and CTLPf were measured using a limiting dilution assay (LDA). Patients were followed prospectively to assess the severity of aGVHD and the status of the primary disease after BMT. High (>5 × 10−6) HTLPf, CTLPf and IFN-γPf were significantly associated with the occurrence and severity of aGVHD in patients who received transplants from HLA-identical sibling. Among patients receiving BMT from MUD, HTLPf and CTLPf, but not IFN-γPf, were associated with aGVHD. Five patients had disease relapse post-BMT and the risk was not significantly associated with HTLPf, CTLPf or IFN-γPf. Patients with high (>5 × 10−6) HTLPf , IFN-γPf or CTLPf before BMT are at higher risk of developing aGVHD after transplantation from both matched sibling donors and MUD. Whether these parameters can predict disease relapse would have to be investigated with a larger cohort of patients.
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References
Martin PJ, Hansen JA, Storb R, Thomas ED . Human marrow transplantation: an immunological perspective. Adv Immunol 1987; 40: 379–438.
Beatty PG, Clift RA, Mickelson EM et al. Marrow transplantation from related donors other than HLA-identical siblings. N Engl J Med 1985; 313: 765–771.
Storb R, Thomas ED . Allogeneic bone-marrow transplantation. Immunol Rev 1983; 71: 77–102.
Beatty PG, Dahlberg S, Mickelson EM et al. Probability of finding HLA-matched unrelated marrow donors. Transplantation 1988; 45: 714–718.
Anasetti C, Amos D, Beatty PG et al. Effect of HLA compatibility on engraftment of bone marrow transplants in patients with leukemia or lymphoma. N Engl J Med 1989; 320: 197–204.
Beatty PG, Hansen JA, Longton GM et al. Marrow transplantation from HLA-matched unrelated donors for treatment of hematologic malignancies. Transplantation 1991; 51: 443–447.
Hows J, Bradley BA, Gore S et al. Prospective evaluation of unrelated donor bone marrow transplantation. The International Marrow Unrelated Search and Transplant (IMUST) Study. Bone Marrow Transplant 1993; 12: 371–380.
Hows JM, Yin JL, Marsh J et al. Histocompatible unrelated volunteer donors compared with HLA nonidentical family donors in marrow transplantation for aplastic anemia and leukemia. Blood 1986; 68: 1322–1328.
Kernan NA, Bartsch G, Ash RC et al. Analysis of 462 transplantations from unrelated donors facilitated by the National Marrow Donor Program. N Engl J Med 1993; 328: 593–602.
Marks DI, Cullis JO, Ward KN et al. Allogeneic bone marrow transplantation for chronic myeloid leukemia using sibling and volunteer unrelated donors. A comparison of complications in the first 2 years. Ann Intern Med 1993; 119: 207–214.
Leung AY, Kwok J, Lie AK et al. Helper T-lymphocyte precursor frequency predicts the occurrence of graft-versus-host disease and disease relapse after allogeneic bone marrow transplantation from HLA-identical siblings. Haematologica 2001; 86: 652–656.
Glucksberg H, Storb R, Fefer A et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation 1974; 18: 295–304.
van der Meer A, Joosten I, Ruiter J, Allebes WA . A single [3H]thymidine-based limiting dilution analysis to determine HTLp and CTLp frequencies for bone marrow donor selection. Bone Marrow Transplant 1997; 20: 149–155.
Strijbosch LW, Does RJ, Buurman WA . Computer aided design and evaluation of limiting and serial dilution experiments. Int J Biomed Comput 1988; 23: 279–290.
Fazekas dSG . The evaluation of limiting dilution assays. J Immunol Methods 1982; 49: R11–R23.
Schwarer AP, Jiang YZ, Brookes PA et al. Frequency of anti-recipient alloreactive helper T-cell precursors in donor blood and graft-versus-host disease after HLA-identical sibling bone-marrow transplantation. Lancet 1993; 341: 203–205.
Glucksberg H, Storb R, Fefer A et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation 1974; 18: 295–304.
Kaplan EL, Meier P . Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–481.
Kaminski E, Sharrock C, Hows J et al. Frequency analysis of cytotoxic T lymphocyte precursors – possible relevance to HLA-matched unrelated donor bone marrow transplantation. Bone Marrow Transplant 1988; 3: 149–155.
Kaminski E, Hows J, Man S et al. Prediction of graft versus host disease by frequency analysis of cytotoxic T cells after unrelated donor bone marrow transplantation. Transplantation 1989; 48: 608–613.
Roelen DL, Stobbe I, Young NT et al. Permissible and immunogenic HLA-A mismatches: cytotoxic T-cell precursor frequencies reflect graft survival data. Hum Immunol 2001; 62: 661–667.
Roosnek E, Hogendijk S, Zawadynski S et al. The frequency of pretransplant donor cytotoxic T cell precursors with anti-host specificity predicts survival of patients transplanted with bone marrow from donors other than HLA-identical siblings. Transplantation 1993; 56: 691–696.
Schwarer AP, Jiang YZ, Brookes PA et al. Frequency of anti-recipient alloreactive helper T-cell precursors in donor blood and graft-versus-host disease after HLA-identical sibling bone-marrow transplantation. Lancet 1993; 341: 203–205.
Speiser DE, Loliger CC, Siren MK, Jeannet M . Pretransplant cytotoxic donor T-cell activity specific to patient HLA class I antigens correlating with mortality after unrelated BMT. Br J Haematol 1996; 93: 935–939.
Spencer A, Szydlo RM, Brookes PA et al. Bone marrow transplantation for chronic myeloid leukemia with volunteer unrelated donors using ex vivo or in vivo T-cell depletion: major prognostic impact of HLA class I identity between donor and recipient. Blood 1995; 86: 3590–3597.
Theobald M, Nierle T, Bunjes D et al. Host-specific interleukin-2-secreting donor T-cell precursors as predictors of acute graft-versus-host disease in bone marrow transplantation between HLA-identical siblings. N Engl J Med 1992; 327: 1613–1617.
Leung AY, Kwok J, Lie AK et al. Helper T-lymphocyte precursor frequency predicts the occurrence of graft-versus-host disease and disease relapse after allogeneic bone marrow transplantation from HLA-identical siblings. Haematologica 2001; 86: 652–656.
Panina-Bordignon P, Corradin G, Roosnek E et al. Recognition by class II alloreactive T cells of processed determinants from human serum proteins. Science 1991; 252: 1548–1550.
Adams PW, Opremcak EM, Orosz CG . Limiting dilution analysis of human, tetanus-reactive helper T lymphocytes. A rapid method for the enumeration of helper T lymphocytes with specificity for soluble antigens. J Immunol Methods 1991; 142: 231–241.
Deacock S, Schwarer A, Batchelor R et al. A rapid limiting dilution assay for measuring frequencies of alloreactive, interleukin-2-producing T cells in humans. J Immunol Methods 1992; 147: 83–92.
Clouse KA, Adams PW, Orosz CG . Enumeration of viral antigen-reactive helper T lymphocytes in human peripheral blood by limiting dilution for analysis of viral antigen-reactive T-cell pools in virus-seropositive and virus-seronegative individuals. J Clin Microbiol 1989; 27: 2316–2323.
van der Meer A, Wissink WM, Schattenberg AV, Joosten I . Interferon-gamma-based mixed lymphocyte culture as a selection tool for allogeneic bone marrow donors other than identical siblings. Br J Haematol 1999; 105: 340–348.
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This project was carried out under the sponsorship of the Ho Hung-Chiu Medical Education Foundation.
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Kwok, J., Leung, A., Lie, A. et al. Antirecipient helper and cytotoxic T-cell frequencies in bone marrow transplantation. Bone Marrow Transplant 34, 207–213 (2004). https://doi.org/10.1038/sj.bmt.1704566
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DOI: https://doi.org/10.1038/sj.bmt.1704566