title: 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.affiliation: Departments of Medicine, Oncology Division, Washington University in St. Louis, 660 South Euclid Avenue, Campus Box 8056, St. Louis, MO, 63110, USA. jcampian@dom.wustl.edu.|Departments of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. jcampian@dom.wustl.edu.
authors.forename: Jian L
authors.initials: JL
authors.lastname: Campian
authors.affiliation: Departments of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
authors.forename: Xiaobu
authors.initials: X
authors.lastname: Ye
authors.affiliation: Departments of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Gladstone
authors.affiliation: Departments of Neurology, Oregon Health & Science University, Portland, OR, 97239, USA.
authors.forename: Prakash
authors.initials: P
authors.lastname: Ambady
authors.affiliation: Departments of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Nirschl
authors.affiliation: Departments of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
authors.forename: Ivan
authors.initials: I
authors.lastname: Borrello
authors.affiliation: Departments of Pathology, Stony Brook School of Medicine, Stony Brook, NY, 11794, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Golightly
authors.affiliation: Departments of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
authors.forename: Karen E
authors.initials: KE
authors.lastname: King
authors.affiliation: Departments of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
authors.forename: Matthias
authors.initials: M
authors.lastname: Holdhoff
authors.affiliation: Departments of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
authors.forename: Judith
authors.initials: J
authors.lastname: Karp
authors.affiliation: Departments of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
authors.forename: Charles G
authors.initials: CG
authors.lastname: Drake
authors.affiliation: Departments of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Grossman
mesh_terms: D000328:Adult; D001254:Astrocytoma / Q000097:blood / Q000628:therapy*; D001804:Blood Transfusion, Autologous / Q000009:adverse effects / Q000379:methods; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods; D005240:Feasibility Studies; D005260:Female; D005909:Glioblastoma / Q000097:blood / Q000628:therapy*; D006801:Humans; D015851:Interleukin-7 / Q000097:blood; D018655:Lymphocyte Count; D017710:Lymphocyte Transfusion / Q000009:adverse effects / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016212:Transforming Growth Factor beta / Q000097:blood; D016896:Treatment Outcome
chemical_list: C508605:IL7 protein, human; D015851:Interleukin-7; D016212:Transforming Growth Factor beta
keywords: High grade glioma; IL-7; Lymphocyte reinfusion; Lymphopenia; Radiation