TY - JOUR
T1 - Pre-radiation lymphocyte harvesting and post-radiation reinfusion in patients with newly diagnosed high grade gliomas
AU - Campian, Jian L.
AU - Ye, Xiaobu
AU - Gladstone, Douglas E.
AU - Ambady, Prakash
AU - Nirschl, Thomas R.
AU - Borrello, Ivan
AU - Golightly, Marc
AU - King, Karen E.
AU - Holdhoff, Matthias
AU - Karp, Judith
AU - Drake, Charles G.
AU - Grossman, Stuart A.
N1 - Funding Information:
This study was supported by philanthropic contributions under the auspices of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.
Publisher Copyright:
© 2015, Springer Science+Business Media New York.
PY - 2015/9/29
Y1 - 2015/9/29
N2 - 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.
AB - 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.
KW - High grade glioma
KW - IL-7
KW - Lymphocyte reinfusion
KW - Lymphopenia
KW - Radiation
UR - http://www.scopus.com/inward/record.url?scp=84942501867&partnerID=8YFLogxK
U2 - 10.1007/s11060-015-1841-y
DO - 10.1007/s11060-015-1841-y
M3 - Article
C2 - 26070554
AN - SCOPUS:84942501867
SN - 0167-594X
VL - 124
SP - 307
EP - 316
JO - Journal of Neuro-Oncology
JF - Journal of Neuro-Oncology
IS - 2
ER -