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Pre-radiation lymphocyte harvesting and post-radiation reinfusion in patients with newly diagnosed high grade gliomas

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Abstract

Radiation (RT), temozolomide (TMZ), and dexamethasone in newly diagnosed high grade gliomas (HGG) produces severe treatment-related lymphopenia (TRL) that is associated with early cancer-related deaths. This TRL may result from inadvertent radiation to circulating lymphocytes. This study reinfused lymphocytes, harvested before chemo-radiation, and assessed safety, feasibility, and trends in lymphocyte counts. Patients with newly diagnosed HGG and total lymphocyte counts (TLC) ≥ 1000 cells/mm3 underwent apheresis. Cryopreserved autologous lymphocytes were reinfused once radiation was completed. Safety, feasibility, and trends in TLC, T cell subsets and cytokines were studied. Serial TLC were also compared with an unreinfused matched control group. Ten patients were harvested (median values: age 56 years, dexamethasone 3 mg/day, TLC/CD4 1980/772 cells/mm3). After 6 weeks of RT/TMZ, TLC fell 69 % (p < 0.0001) with similar reductions in CD4, CD8 and NK cells but not Tregs. Eight patients received lymphocyte reinfusions (median = 7.0 × 107 lymphocytes/kg) without adverse events. A post-reinfusion TLC rise of ≥300 cells/mm3 was noted in 3/8 patients at 4 weeks and 7/8 at 14 weeks which was similar to 23 matched controls. The reduced CD4/CD8 ratio was not restored by lymphocyte reinfusion. Severe lymphopenia was not accompanied by elevated serum interleukin-7 (IL-7) levels. This study confirms that severe TRL is common in HGG and is not associated with high plasma IL-7 levels. Although lymphocyte harvesting/reinfusion is feasible and safe, serial lymphocyte counts are similar to unreinfused matched controls. Studies administering higher lymphocyte doses and/or IL-7 should be considered to restore severe treatment-related lymphopenia in HGG.

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Acknowledgments

This study was supported by philanthropic contributions under the auspices of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.

Conflict of interest

None.

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Authors and Affiliations

  1. Departments of Medicine, Oncology Division, Washington University in St. Louis, 660 South Euclid Avenue, Campus Box 8056, St. Louis, MO, 63110, USA

    Jian L. Campian

  2. Departments of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA

    Jian L. Campian, Xiaobu Ye, Douglas E. Gladstone, Thomas R. Nirschl, Ivan Borrello, Karen E. King, Matthias Holdhoff, Judith Karp, Charles G. Drake & Stuart A. Grossman

  3. Departments of Neurology, Oregon Health & Science University, Portland, OR, 97239, USA

    Prakash Ambady

  4. Departments of Pathology, Stony Brook School of Medicine, Stony Brook, NY, 11794, USA

    Marc Golightly

Authors
  1. Jian L. Campian
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  2. Xiaobu Ye
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  3. Douglas E. Gladstone
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  4. Prakash Ambady
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  5. Thomas R. Nirschl
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  6. Ivan Borrello
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  7. Marc Golightly
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  8. Karen E. King
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  9. Matthias Holdhoff
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  10. Judith Karp
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  11. Charles G. Drake
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  12. Stuart A. Grossman
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Corresponding author

Correspondence to Jian L. Campian.

Additional information

Jian L. Campian conducted this study at the Johns Hopkins University and changed affiliation to Washington University in St Louis after this study was completed in 2014.

Xiaobu Ye—co-first author.

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Campian, J.L., Ye, X., Gladstone, D.E. et al. Pre-radiation lymphocyte harvesting and post-radiation reinfusion in patients with newly diagnosed high grade gliomas. J Neurooncol 124, 307–316 (2015). https://doi.org/10.1007/s11060-015-1841-y

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  • DOI: https://doi.org/10.1007/s11060-015-1841-y

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