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Increase of interleukin-18 serum levels after engraftment correlates with acute graft-versus-host disease in allogeneic peripheral blood stem cell transplantation

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Abstract

Purpose

Acute graft-versus-host disease (GvHD) is a constant and severe complication after allogeneic stem cell transplantation regularly involving skin, liver, gut, and lungs. The cytokine interleukin-18 (IL-18) has been shown to increase in patients who develop acute GvHD after bone marrow tranplantation (BMT).

Materials and methods

Here, we measured IL-18 serum levels after peripheral blood stem cell transplantation (PBSCT) at several characteristic time points in 24 patients (median age 46 years). Patients received a median of 7.3×106/kg bodyweight CD34-positive blood stem cells from HLA-matched family donors (n=5), matched unrelated donors (n=18), and one mismatched unrelated donor. GvHD prophylaxis consisted of cyclosporin A alone or combined with methotrexate and/or mycophenolate mofetil.

Results

In 14 patients we observed no GvHD or only GvHD grade I whereas ten patients developed GvHD grade II–IV post transplant. Low, intermediate, and high levels of serum IL-18 were found in patients after allogeneic PBSCT independently of GvHD after transplantation. In contrast to GvHD arising after BMT, there was no clear correlation between absolute IL-18 serum levels and GvHD grade after PBSCT. However, the individual time course of IL-18 serum level after engraftment correlates with acute GvHD after PBSCT. In detail, an increase of serum IL-18 of at least 1.6-fold after engraftment is associated with acute GvHD II or higher with a sensitivity of three out of four. Using the 1.6 “cut-off” for IL-18 increase after engraftment, a specificity of up to 100% can be achieved.

Conclusion

The time course of IL-18 serum levels might be used for GvHD prediction after PBSCT comparable to absolute serum levels after BMT.

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Acknowledgments

We thank Anja Markusch for her contributions to patient characteristics and Ms. Herrmann and Ms. Franke who determined cellular subpopulations of grafts and CD34 content of transplants

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Authors and Affiliations

  1. “Mildred Scheel Station für Knochenmarktransplantation”, Department of Internal Medicine II, Friedrich Schiller University, Erlanger Allee 101, 07740, Jena, Germany

    Sebastian Scholl, Herbert G. Sayer, Lars-Olof Mügge, Christoph Kasper, Marko Pietraszczyk, Kay-Oliver Kliche, Joachim H. Clement & Klaus Höffken

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  1. Sebastian Scholl
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  2. Herbert G. Sayer
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  3. Lars-Olof Mügge
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  4. Christoph Kasper
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  6. Kay-Oliver Kliche
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  7. Joachim H. Clement
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  8. Klaus Höffken
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Correspondence to Sebastian Scholl.

Additional information

S. Scholl and H. G. Sayer contributed equally to this work.

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Scholl, S., Sayer, H.G., Mügge, LO. et al. Increase of interleukin-18 serum levels after engraftment correlates with acute graft-versus-host disease in allogeneic peripheral blood stem cell transplantation. J Cancer Res Clin Oncol 130, 704–710 (2004). https://doi.org/10.1007/s00432-004-0603-6

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  • DOI: https://doi.org/10.1007/s00432-004-0603-6

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