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

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

doi:10.1007/s11060-015-1841-y

Cited by 39 publications

(31 citation statements)

References 29 publications

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“…Campian et al 21 reported similar results in human GB/anaplastic astrocytoma where pre-radiation lymphocyte harvesting followed by reinfusing these nonirradiated lymphocytes after radiation session did not significantly ameliorate lymphopenia. G-CSF actively suppresses BM lymphocytopoiesis in mice.…”

Section: Elevated G(m)-csf Is Immunosuppressive In Gbmentioning

confidence: 72%

Glioblastoma-synthesized G-CSF and GM-CSF contribute to growth and immunosuppression: Potential therapeutic benefit from dapsone, fenofibrate, and ribavirin

Kast¹,

Hill

Wion

et al. 2017

Tumour Biol.

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Increased ratio of circulating neutrophils to lymphocytes is a common finding in glioblastoma and other cancers. Data reviewed establish that any damage to brain tissue tends to cause an increase in G-CSF and/or GM-CSF (G(M)-CSF) synthesized by the brain. Glioblastoma cells themselves also synthesize G(M)-CSF. G(M)-CSF synthesized by brain due to damage by a growing tumor and by the tumor itself stimulates bone marrow to shift hematopoiesis toward granulocytic lineages away from lymphocytic lineages. This shift is immunosuppressive and generates the relative lymphopenia characteristic of glioblastoma. Any trauma to brain-be it blunt, sharp, ischemic, infectious, cytotoxic, tumor encroachment, or radiation-increases brain synthesis of G(M)-CSF. G(M)-CSF are growth and motility enhancing factors for glioblastomas. High levels of G(M)-CSF contribute to the characteristic neutrophilia and lymphopenia of glioblastoma. Hematopoietic bone marrow becomes entrained with, directed by, and contributes to glioblastoma pathology. The antibiotic dapsone, the lipid-lowering agent fenofibrate, and the antiviral drug ribavirin are Food and Drug Administration-and European Medicines Agency-approved medicines that have potential to lower synthesis or effects of G(M)-CSF and thus deprive a glioblastoma of some of the growth promoting contributions of bone marrow and G(M)-CSF.

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Section: Elevated G(m)-csf Is Immunosuppressive In Gbmentioning

confidence: 72%

Glioblastoma-synthesized G-CSF and GM-CSF contribute to growth and immunosuppression: Potential therapeutic benefit from dapsone, fenofibrate, and ribavirin

Kast¹,

Hill

Wion

et al. 2017

Tumour Biol.

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“…A recent study at Johns Hopkins University investigated the utility of reinfusing harvested pre-treatment circulating lymphocytes after radiation [36]. The use of exogenous Interleukin-7 is being studied in high grade gliomas by the Adult Brain Tumor Consortium and the Cancer Therapy Evaluation Program because a recent study showed that patients with high-grade gliomas did not have the expected IL-7 physiologic elevation in response to radiation-induced lymphopenia [37].…”

Section: Discussionmentioning

confidence: 99%

Lymphopenia and its association with survival in patients with locally advanced cervical cancer

Oduyebo

Cobb

et al. 2016

Gynecologic Oncology

125

106

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Objective To evaluate the association between lymphopenia and survival in women with cervical cancer treated with primary chemoradiation. Methods A single institution, retrospective analysis of patients with stage IB2-IVA cervical cancer who received upfront chemoradiation from 1998 to 2013 was performed. Complete blood counts from pre-treatment to 36 months post-treatment were analyzed. Lymphopenia and known prognostic factors were evaluated for an association with progression-free (PFS) and overall survival (OS). Results Seventy-one patients met study criteria for whom 47 (66%) had a documented total lymphocyte count (TLC) two months after initiating chemoradiation. FIGO stage distribution was 6% Stage I, 46% Stage II, 45% Stage III and 3% Stage IV. Pre-treatment TLC was abnormal (<1000 cells/mm3) in 15% of patients. The mean reduction in TLC was 70% two months after initiating chemoradiation. Severe post-treatment lymphopenia (TLC <500 cells/mm3) was observed in 53% of patients; they experienced inferior median OS (21.2 vs 45.0 months, P = 0.03) and similar 25th percentile PFS (6.3 vs 7.7 months, P = 0.06) compared to patients without severe lymphopenia. Multivariate analysis demonstrated pre-treatment TLC ≥1000 cells/mm3 and post-treatment TLC >500 cells/mm3 had a 77% (HR: 0.23; 95% CI 0.05–1.03; P = 0.053) and 58% decrease in hazards of death (HR: 0.42; 95% CI 0.12–1.46; P = 0.17) respectively. Conclusion More than half of cervical cancer patients treated with chemoradiation experienced severe and prolonged lymphopenia. Although statistical significance was not reached, the findings suggest that pre- and post-treatment lymphopenia may be associated with decreased survival. Further research is warranted, given that lymphopenia could be a reversible prognostic factor.

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“…This iatrogenic lymphopenia was not taken seriously until subsequent evidences indicated that patients with lowered peripheral lymphocyte counts (PLCs) suffered early death from tumor progression . Recent studies have brought attention to the treatment‐related lymphopenia observed in glioma patients . As the standard of care for gliomas, radiotherapy (RT), steroids, and temozolomide (TMZ) are well‐documented lymphotoxins.…”

Section: Introductionmentioning

confidence: 99%

“…This comprehensive therapy modality causes 40% of high‐grade glioma (HGG) patients to develop severe lymphopenia (grade III‐IV toxicity) within 2 months after course initiation . The state of immunosuppression is persistent and detrimentally affects patients with increased susceptibility to opportunistic infections, additional risk of secondary central nervous system (CNS) tumors, and deteriorated survival time …”

Section: Introductionmentioning

confidence: 99%

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Dosimetry of the brain and hypothalamus predicting acute lymphopenia and the survival of glioma patients with postoperative radiotherapy

Fan

et al. 2019

Cancer Medicine

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Background The aim of this study was to investigate dosimetric factors for predicting acute lymphopenia and the survival of glioma patients with postoperative intensity‐modulated radiotherapy (IMRT). Methods A total of 148 glioma patients were reviewed. Acute lymphopenia was defined as a peripheral lymphocyte count (PLC) lower than 1.0 × 109/L during radiotherapy with a normal level at pretreatment. PLCs with the corresponding dates and dose volume histogram parameters were collected. Univariate and multivariate Cox regression analyses were constructed to assess the significance of risk factors associated with lymphopenia and overall survival (OS). Results Sixty‐nine (46.6%) patients developed lymphopenia during radiotherapy. Multivariate analyses revealed that the risk increased with the maximal dose of the hypothalamus (HT Dmax) ≥56 Gy (58.9% vs 28.5%, P = 0.002), minimal dose of the whole brain (WB Dmin) ≥2 Gy (54.3% vs 33.9%, P = 0.006), or mean dose of the WB (WB Dmean) ≥34 Gy (56.0% vs 37.0%, P = 0.022). Patients with older age, high‐grade glioma, development of lymphopenia, high HT Dmax, WB Dmin, and WB Dmean had significantly inferior OS in the multivariate analyses. Conclusions HT Dmax, WB Dmin, and WB Dmean are promising indicators of lymphopenia and the survival of glioma patients undergoing postoperative IMRT. The necessity and feasibility of dosimetric constraints for HT and WB is warranted with further investigation.

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

Cited by 39 publications

References 29 publications

Glioblastoma-synthesized G-CSF and GM-CSF contribute to growth and immunosuppression: Potential therapeutic benefit from dapsone, fenofibrate, and ribavirin

Glioblastoma-synthesized G-CSF and GM-CSF contribute to growth and immunosuppression: Potential therapeutic benefit from dapsone, fenofibrate, and ribavirin

Lymphopenia and its association with survival in patients with locally advanced cervical cancer

Dosimetry of the brain and hypothalamus predicting acute lymphopenia and the survival of glioma patients with postoperative radiotherapy

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