Time course of interferon-γ production deficiency after autologous and allogeneic stem cell transplantation for malignancies

H. Hanenberg, D. Dilloo, H. J. Laws, N. Zessack, A. Heyll, S. Burdach

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

While success of autologous bone marrow transplantation (BMT) for malignancies largely depends on the cytotoxicity of the ablative regimen, achievement of relapse-free survival after allogeneic BMT is thought to be enhanced by immunologic effects. We therefore investigated in vivo and in vitro production of interferon-γ (IFN-γ), soluble interleukin-2 (IL-2) receptor α-chain (sCD25), tumor necrosis factor-α (TNF-α), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients before and during various time periods up to 2 years after autologous and allogeneic BMT. Cytokine levels were assessed in patient plasma and in supernatants of patient-derived peripheral blood mononuclear cells (PBMNC) cultured for 3 days in the presence of T cell-specific stimulation via CD3 plus IL-2. Our studies show that IFN-γ plasma levels are decreased in autologous graft recipients before and during the first 30 days posttransplant. In allogeneic graft recipients, IFN-γ plasma levels are also decreased during the first 30 days posttransplant, but otherwise are comparable to normal control (NC) values. In vitro stimulated PBMNC from autologous graft recipients also exhibit an IFN-γ production defect before and during the first 30 days posttransplant. In contrast, before and up to 30 days after allogeneic BMT, stimulated IFN-γ production is comparable to NC values but then gradually decreases, reaching its trough levels at between 61 and 180 days post-BMT. The IFN-γ production defects in both patient groups seem to be specific, as sCD25, TNF-α and GM-CSF production in stimulated PBMNC is normal or even enhanced at any time after autologous or allogeneic BMT. Deficient IFN-γ production in patient-derived PBMNC does not correlate with variation in monocyte, T cell, or natural killer (NK) cell numbers during the posttransplantation course.

Original languageEnglish (US)
Pages (from-to)1543-1552
Number of pages10
JournalExperimental Hematology
Volume23
Issue number14
StatePublished - Dec 1 1995

Keywords

  • Allogeneic transplantation
  • Autologous transplantation
  • Cytokines
  • Interferon-γ deficiency

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

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  • Cite this

    Hanenberg, H., Dilloo, D., Laws, H. J., Zessack, N., Heyll, A., & Burdach, S. (1995). Time course of interferon-γ production deficiency after autologous and allogeneic stem cell transplantation for malignancies. Experimental Hematology, 23(14), 1543-1552.