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Comparison of different rabbit ATG preparation effects on early lymphocyte subset recovery after allogeneic HSCT and its association with EBV-mediated PTLD

  • Original Article – Clinical Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Rabbit antithymocyte globulin (ATG) is commonly used before allogeneic hematopoietic stem cell transplantation (allo-HSCT) to prevent graft-versus-host disease. Studies comparing the effect of different ATG preparations and dosages on immune reconstitution and risk for Epstein–Barr virus (EBV)-mediated post-transplant lymphoproliferative disorder (PTLD) are rare.

Methods

In this retrospective study, we determined T and B cell subsets by flow cytometry after allo-HSCT in children, who received ATG-Genzyme (ATG-G, n = 15), ATG-Fresenius (ATG-F, n = 25) or no-ATG treatment (n = 19). Additionally, PCR-quantified EBV-genome copy counts were correlated with incidence of PTLD.

Results

We could confirm a dose-dependent impairment of CD8+ and CD4+ T cell regeneration by ATG-G, including naïve and memory CD4+ T cells. No differences were seen between the currently applied dosages of 5–10 mg/kg ATG-G and 20–60 mg/kg ATG-F. Significantly delayed T cell subset reconstitution was determined only at high dosages of 20–60 mg/kg ATG-G compared to ATG-F. B cell reconstitution was comparably impaired in ATG-G- and ATG-F-treated patients. Although the incidence of EBV reactivation was similar in both ATG groups, EBV copy counts of >104 copies/105 peripheral blood mononuclear cells and the occurrence of PTLD were only found in ATG-G-treated patients.

Conclusions

We conclude that high, but importantly not currently applied low dosages of ATG-G, impair thymic T cell regeneration and memory T cell immunity to a greater extent than ATG-F in pediatric patients. In addition, our results suggest an increased risk for EBV-PTLD when treated with ATG-G. Prospective studies are warranted to compare different ATG preparations with regard to the immune reconstitution and EBV-PTLD.

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Acknowledgments

The technical assistance of Doris Glaser and Sabine Becker is acknowledged. The nurses and physicians of the Stem Cell Transplant Unit are thanked for their care of patients and assistance in obtaining patient samples.

Conflict of interest

We declare that we have no conflict of interest.

Ethical standard

The study was approved by the institutional review board and patients and parents gave informed consent.

Author information

Authors and Affiliations

  1. Institute of Medical Immunology, Charité CVK, Berlin, Germany

    Angela Mensen

  2. Experimental and Clinical Research Centre (ECRC), Berlin, Germany

    Angela Mensen & Il-Kang Na

  3. Department of Hematology, Oncology and Tumor Immunology, Charité CVK, Berlin, Germany

    Il-Kang Na

  4. Department of Pediatrics, Jena University Hospital, Kochstr. 2, 07740, Jena, Germany

    Ralf Häfer & Bernd Gruhn

  5. Institute of Virology and Antiviral Therapy, Jena University Hospital, Jena, Germany

    Astrid Meerbach

  6. Department of Neonatology, University Medical Centre, Mainz, Germany

    Maria Schlecht

  7. Department of Pediatrics, Hospital St. Elisabeth and St. Barbara, Halle, Germany

    Marie-Luise Pietschmann

Authors
  1. Angela Mensen
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  2. Il-Kang Na
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  3. Ralf Häfer
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  4. Astrid Meerbach
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  5. Maria Schlecht
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  6. Marie-Luise Pietschmann
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  7. Bernd Gruhn
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Corresponding author

Correspondence to Bernd Gruhn.

Additional information

Angela Mensen, Il-Kang Na have contributed equally to this work.

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Mensen, A., Na, IK., Häfer, R. et al. Comparison of different rabbit ATG preparation effects on early lymphocyte subset recovery after allogeneic HSCT and its association with EBV-mediated PTLD. J Cancer Res Clin Oncol 140, 1971–1980 (2014). https://doi.org/10.1007/s00432-014-1742-z

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  • DOI: https://doi.org/10.1007/s00432-014-1742-z

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