Selective depletion of CD8+ cells for prevention of graft-versus-host disease after bone marrow transplantation: A randomized controlled trial

Stephen D. Nimer, Janis Giorgi, James L. Gajewski, Nora Ku, Gary J. Schiller, Kyoung Lee, Mary Territo, Winston Ho, Stephen Feig, Michael Selch, Valentin Isacescu, Thomas A. Reichert, Richard E. Champlin

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Abstract

We performed a prospective randomized, doubleblind study to assess the efficacy of selective depletion of CD8+ bone marrow cells in preventing acute graftversus-host disease (GVHD) in 38 patients undergoing HLA-identical sibling donor bone marrow transplantation for leukemia. All patients received CsA for GVHD prophylaxis. Nineteen patients received marrow depleted of CD8+ cells by ex vivo treatment with anti-leu2, an anti-CD8 mAb and complement; four patients had moderate (grade 1 or 2 acute GVHD) and the only patient who experienced grade 3 manifestations was a technical failure. The control group consisted of 19 patients who received unmodified bone marrow; one patient had grade 1,4 patients had grade 2, and 10 had grade 3 or 4 acute GVHD. The actuarial incidence of grade ≥ 2 acute GVHD was 20±20% in the CD8depleted group compared with 80±18% in the controls (P=0.004). Death in 5 of the control patients and the single patient in whom CD8 depletion was a technical failure was related to acute GVHD. Graft failure occurred in 2 patients in the CD8-depleted group and in none of the controls. Leukemic relapse occurred in 2 patients receiving CD8-depleted bone marrow and 2 patients in the control group. Seven patients receiving marrow depleted of CD8+ cells are alive and free of leukemia and 9 patients in the control group are alive, 7 of whom remain leukemia-free (P=0.88). The 3-year actuarial leukemia-free survival is 37±22% of the CD8depleted group and 36 ±22% for the control group. These results indicate that selective depletion of CD8+ cells from the bone marrow significantly reduces the incidence and severity of acute GVHD.

Original languageEnglish (US)
Pages (from-to)82-87
Number of pages6
JournalTransplantation
Volume57
Issue number1
StatePublished - 1994
Externally publishedYes

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Graft vs Host Disease
Bone Marrow Transplantation
Randomized Controlled Trials
Leukemia
Bone Marrow
Control Groups
Bone Marrow Cells
Incidence
Siblings

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Nimer, S. D., Giorgi, J., Gajewski, J. L., Ku, N., Schiller, G. J., Lee, K., ... Champlin, R. E. (1994). Selective depletion of CD8+ cells for prevention of graft-versus-host disease after bone marrow transplantation: A randomized controlled trial. Transplantation, 57(1), 82-87.

Selective depletion of CD8+ cells for prevention of graft-versus-host disease after bone marrow transplantation : A randomized controlled trial. / Nimer, Stephen D.; Giorgi, Janis; Gajewski, James L.; Ku, Nora; Schiller, Gary J.; Lee, Kyoung; Territo, Mary; Ho, Winston; Feig, Stephen; Selch, Michael; Isacescu, Valentin; Reichert, Thomas A.; Champlin, Richard E.

In: Transplantation, Vol. 57, No. 1, 1994, p. 82-87.

Research output: Contribution to journalArticle

Nimer, SD, Giorgi, J, Gajewski, JL, Ku, N, Schiller, GJ, Lee, K, Territo, M, Ho, W, Feig, S, Selch, M, Isacescu, V, Reichert, TA & Champlin, RE 1994, 'Selective depletion of CD8+ cells for prevention of graft-versus-host disease after bone marrow transplantation: A randomized controlled trial', Transplantation, vol. 57, no. 1, pp. 82-87.
Nimer, Stephen D. ; Giorgi, Janis ; Gajewski, James L. ; Ku, Nora ; Schiller, Gary J. ; Lee, Kyoung ; Territo, Mary ; Ho, Winston ; Feig, Stephen ; Selch, Michael ; Isacescu, Valentin ; Reichert, Thomas A. ; Champlin, Richard E. / Selective depletion of CD8+ cells for prevention of graft-versus-host disease after bone marrow transplantation : A randomized controlled trial. In: Transplantation. 1994 ; Vol. 57, No. 1. pp. 82-87.
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abstract = "We performed a prospective randomized, doubleblind study to assess the efficacy of selective depletion of CD8+ bone marrow cells in preventing acute graftversus-host disease (GVHD) in 38 patients undergoing HLA-identical sibling donor bone marrow transplantation for leukemia. All patients received CsA for GVHD prophylaxis. Nineteen patients received marrow depleted of CD8+ cells by ex vivo treatment with anti-leu2, an anti-CD8 mAb and complement; four patients had moderate (grade 1 or 2 acute GVHD) and the only patient who experienced grade 3 manifestations was a technical failure. The control group consisted of 19 patients who received unmodified bone marrow; one patient had grade 1,4 patients had grade 2, and 10 had grade 3 or 4 acute GVHD. The actuarial incidence of grade ≥ 2 acute GVHD was 20±20{\%} in the CD8depleted group compared with 80±18{\%} in the controls (P=0.004). Death in 5 of the control patients and the single patient in whom CD8 depletion was a technical failure was related to acute GVHD. Graft failure occurred in 2 patients in the CD8-depleted group and in none of the controls. Leukemic relapse occurred in 2 patients receiving CD8-depleted bone marrow and 2 patients in the control group. Seven patients receiving marrow depleted of CD8+ cells are alive and free of leukemia and 9 patients in the control group are alive, 7 of whom remain leukemia-free (P=0.88). The 3-year actuarial leukemia-free survival is 37±22{\%} of the CD8depleted group and 36 ±22{\%} for the control group. These results indicate that selective depletion of CD8+ cells from the bone marrow significantly reduces the incidence and severity of acute GVHD.",
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