Survival in Patients With Severe Lymphopenia Following Treatment With Radiation and Chemotherapy for Newly Diagnosed Solid Tumors

Abstract

Background The immune system plays an important role in cancer surveillance and therapy. Chemoradiation can cause severe treatment-related lymphopenia (TRL) (<500 cells/mm3) that is associated with reduced survival. Materials and Methods Data from 4 independent solid tumor studies on serial lymphocyte counts, prognostic factors, treatment, and survival were collected and analyzed. The data set included 297 patients with newly diagnosed malignant glioma (N=96), resected pancreatic cancer (N=53), unresectable pancreatic cancer (N=101), and non–small cell lung cancer (N=47). Results Pretreatment lymphocyte counts were normal in 83% of the patient population, and no patient had severe baseline lymphopenia. Two months after initiating chemoradiation, 43% developed severe and persistent lymphopenia (P=.001). An increased risk for death was attributable to TRL in each cancer cohort (gliomas: hazard rate [HR], 1.8; 95% CI, 1.13–2.87; resected pancreas: HR, 2.2; 95% CI, 1.17–4.12; unresected pancreas: HR, 2.9; 95% CI, 1.53–5.42; and lung: HR, 1.7; 95% CI, 0.8–3.61) and in the entire study population regardless of pathologic findings (HR, 2.1; 95% CI, 1.54–2.78; P<.0001). Severe TRL was observed in more than 40% of patients 2 months after initiating chemoradiation, regardless of histology or chemotherapy regimen, and was independently associated with shorter survival from tumor progression. Conclusions Increased attention and research should be focused on the cause, prevention, and reversal of this unintended consequence of cancer treatment that seems to be related to survival in patients with solid tumors.

Association between treatment-related lymphopenia and overall survival in elderly patients with newly diagnosed glioblastoma

“…Dichotomization between grade 0-II and III-V was performed as grade III (TLC <500 cells/mm 3 ) and above adverse events are defined as severe or medically significant (CTCAE—Version 4.03). Furthermore, the literature on TRL in high grade gliomas and other solid tumors have found an association with TLC <500 cells/mm 3 at 2 months and OS [11–17]. Overall survival time was measured from the date of diagnosis to the date of death due to any cause, and those subjects alive at the time of last follow-up were censored.…”

“…Multivariate analysis revealed these significant reductions in CD4 counts at 2 months was independently associated with inferior OS due primarily to tumor progression [11]. The association of treatment related lymphopenia (TRL) and decreased OS has also been observed in non-small cell lung cancer, head and neck cancer, and pancreatic cancer [12–17]. …”

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

“…[56][57][58] Lymphopenia in GB, relative or absolute, negatively affects prognosis and success of both current standard treatment of GB with temozolomide plus radiation. 59,60 In mice subjected to controlled cortical impact, Kelso et al 15 showed that treatment with GM-CSF increased CD4 + CD25 + regulatory T-cell (Treg) numbers in cervical lymph nodes coincident with decreased CNS lesion volumes and increased cortical tissue sparing. Transcriptomic analysis showed that GM-CSF induces robust immune inhibitory and neuroprotective responses 7 days following controlled cortical impact.…”

Invasive pulmonary aspergillosis in a HIV-infected patient with metastatic, non-small cell lung cancer

“…The results show that two months after initiating chemoradiation, 43% of patients developed severe and persistent lymphopenia (< 500 cells/μl), regardless of histopathology and the type of chemotherapy. Further lymphopenia was connected with shorter survival independently of cancer progression [10].…”