Journal of Neuro-Oncology

, Volume 124, Issue 2, pp 307–316 | Cite as

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
Clinical Study


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.


High grade glioma Lymphopenia Radiation Lymphocyte reinfusion IL-7 



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

Conflict of interest



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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Jian L. Campian
    • 1
    • 2
  • Xiaobu Ye
    • 2
  • Douglas E. Gladstone
    • 2
  • Prakash Ambady
    • 3
  • Thomas R. Nirschl
    • 2
  • Ivan Borrello
    • 2
  • Marc Golightly
    • 4
  • Karen E. King
    • 2
  • Matthias Holdhoff
    • 2
  • Judith Karp
    • 2
  • Charles G. Drake
    • 2
  • Stuart A. Grossman
    • 2
  1. 1.Departments of Medicine, Oncology DivisionWashington University in St. LouisSt. LouisUSA
  2. 2.Departments of OncologyThe Johns Hopkins University School of MedicineBaltimoreUSA
  3. 3.Departments of NeurologyOregon Health & Science UniversityPortlandUSA
  4. 4.Departments of PathologyStony Brook School of MedicineStony BrookUSA

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