Effects of treating marrow with a CD3-specific immunotoxin for prevention of acute graft-versus-host disease

P. J. Martin, J. A. Hansen, B. Torok-Storb, L. Moretti, O. Press, R. Storb, E. Donnal Thomas, P. L. Weiden, E. S. Vitetta

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30 Citations (Scopus)

Abstract

Data from human clinical trials and animal experiments have suggested that T lymphocytes in donor marrow help to facilitate engraftment after allogeneic bone marrow transplantation, possibly through a suppressive effect on the immunity of the recipient. In previous studies marrows from HLA-identical donors were treated ex vivo with a mixture of eight monoclonal antibodies together with rabbit complement to achieve a 3-log depletion of T cells and CD3-negative lymphoid cells. Transplantation of this marrrow was associated with a 27% actuarial risk of graft failure in leukemic recipients conditioned with cyclophosphamide (120 mg/kg) and 15.75 Gy fractionated total body irradiation. In the present study, we employed an anti-CD3 ricin A-chain-containing immunotoxin (64.1-A) together with 20 mM NH4Cl to achieve a selective 3-log depletion of CD3-positive cells. The patient entry criteria and pretransplant conditioning regimen were identical to those used in previous studies. Despite the differences in marrow treatment, the clinical outcome of the previous study was similar to that obtained previously. Graft-versus-host disease (GVHD) was largely prevented without the need for post-transplant immunosuppression, but two of the eight patients developed graft failure. These results indicate that CD3-negative cells have little or no ability to initiate GVHD. To the extent that graft failure in this study was not caused by stem cell damage or loss of CD3-negative cells during ex vivo processing of the marrow, it appears that the lymphoid cells required for facilitating allogeneic engraftment under these conditions are CD3-positive.

Original languageEnglish (US)
Pages (from-to)437-444
Number of pages8
JournalBone Marrow Transplantation
Volume3
Issue number5
StatePublished - 1988

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Immunotoxins
Graft vs Host Disease
Bone Marrow
Transplants
Tissue Donors
Lymphocytes
T-Lymphocytes
Ricin
Whole-Body Irradiation
Homologous Transplantation
Bone Marrow Transplantation
Cyclophosphamide
Immunosuppression
Immunity
Stem Cells
Transplantation
Monoclonal Antibodies
Outcome Assessment (Health Care)
Clinical Trials
Rabbits

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Martin, P. J., Hansen, J. A., Torok-Storb, B., Moretti, L., Press, O., Storb, R., ... Vitetta, E. S. (1988). Effects of treating marrow with a CD3-specific immunotoxin for prevention of acute graft-versus-host disease. Bone Marrow Transplantation, 3(5), 437-444.

Effects of treating marrow with a CD3-specific immunotoxin for prevention of acute graft-versus-host disease. / Martin, P. J.; Hansen, J. A.; Torok-Storb, B.; Moretti, L.; Press, O.; Storb, R.; Donnal Thomas, E.; Weiden, P. L.; Vitetta, E. S.

In: Bone Marrow Transplantation, Vol. 3, No. 5, 1988, p. 437-444.

Research output: Contribution to journalArticle

Martin, PJ, Hansen, JA, Torok-Storb, B, Moretti, L, Press, O, Storb, R, Donnal Thomas, E, Weiden, PL & Vitetta, ES 1988, 'Effects of treating marrow with a CD3-specific immunotoxin for prevention of acute graft-versus-host disease', Bone Marrow Transplantation, vol. 3, no. 5, pp. 437-444.
Martin PJ, Hansen JA, Torok-Storb B, Moretti L, Press O, Storb R et al. Effects of treating marrow with a CD3-specific immunotoxin for prevention of acute graft-versus-host disease. Bone Marrow Transplantation. 1988;3(5):437-444.
Martin, P. J. ; Hansen, J. A. ; Torok-Storb, B. ; Moretti, L. ; Press, O. ; Storb, R. ; Donnal Thomas, E. ; Weiden, P. L. ; Vitetta, E. S. / Effects of treating marrow with a CD3-specific immunotoxin for prevention of acute graft-versus-host disease. In: Bone Marrow Transplantation. 1988 ; Vol. 3, No. 5. pp. 437-444.
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