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

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

Research output: Contribution to journalArticle

15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)307-316
Number of pages10
JournalJournal of Neuro-Oncology
Volume124
Issue number2
DOIs
StatePublished - Sep 29 2015

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Keywords

  • High grade glioma
  • IL-7
  • Lymphocyte reinfusion
  • Lymphopenia
  • Radiation

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

Cite this

Campian, J. L., Ye, X., Gladstone, D. E., Ambady, P., Nirschl, T. R., Borrello, I., Golightly, M., King, K. E., Holdhoff, M., Karp, J., Drake, C. G., & Grossman, S. A. (2015). Pre-radiation lymphocyte harvesting and post-radiation reinfusion in patients with newly diagnosed high grade gliomas. Journal of Neuro-Oncology, 124(2), 307-316. https://doi.org/10.1007/s11060-015-1841-y