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

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/mm(3) 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/mm(3)). 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 × 10(7) lymphocytes/kg) without adverse events. A post-reinfusion TLC rise of ≥300 cells/mm(3) 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.

• Authors: 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
• Journal: Journal of neuro-oncology (J Neurooncol) Vol. 124 Issue 2 Pg. 307-16 (Sep 2015) ISSN: 1573-7373 [Electronic] United States
• PMID: 26070554 (Publication Type: Clinical Study, Journal Article)

Chemical References

• IL7 protein, human
• Interleukin-7
• Transforming Growth Factor beta

Topics

• Adult
• Astrocytoma (blood, therapy)
• Blood Transfusion, Autologous (adverse effects, methods)
• Chemoradiotherapy (adverse effects, methods)
• Feasibility Studies
• Female
• Glioblastoma (blood, therapy)
• Humans
• Interleukin-7 (blood)
• Lymphocyte Count
• Lymphocyte Transfusion (adverse effects, methods)
• Male
• Middle Aged
• Prospective Studies
• Transforming Growth Factor beta (blood)
• Treatment Outcome