Background: This retrospective review was conducted to determine: 1) the frequency and severity of treatment related lymphopenia (TRL) in solid tumors, 2) its association with survival accounting for prognostic variables, and 3) its relationship to radiation or chemotherapy.

Methods: Serial lymphocyte counts (pre-treatment and monthly for one year), prognostic factors, treatment details, and survival were retrospectively reviewed in 338 newly diagnosed patients with 1) high grade glioma, 2) resected pancreatic cancer, 3) unresectable pancreatic cancer, 4) stage III lung cancer, and 5) HPV- head and neck cancer in this IRB approved study. Severe TRL was defined as grade III-IV lymphopenia (<500 cells/mm3).

Results: The findings in each patient cohort are similar: 1) About 40% of patients develop severe TRL two months after initiating radiation and this persists for many months, 2) There is an association between TRL at two months and shorter survival from tumor progression, and 3) The hazard ratio for reduced survival is high after adjusting for known prognostic factors. Lung cancer patients treated with neoadjuvant chemotherapy did not experience TRL until after radiation was initiated.

Conclusions: Severe TRL is common, severe, long-lasting and associated with earlier death from tumor progression in patients with solid tumors receiving radiation and chemotherapy. These studies suggest that radiation likely plays a major role in the development of TRL and that novel approaches to protect and/or restore immunologic function in patients with solid tumors are critical.

NeoplasmTotal number patientsPatients developing grade III-IV TRLMedian Survival <500 vs >500 lymphocytes (months)Multivariate association with reduced survival:HR, (CI), pvalue
High grade glioma 96 40% 13 vs 19.7 (p = 0.002) OS: 1.66, (1.05–2.64), 0.03 
Pancreatic resected 53 45% 14 vs 20 (p = 0.048) OS: 2.2, (1.17–4.12), 0.01 
Pancreatic unresectable 120 74% 9.2 vs 14.6 (p = 0.013) OS: 1.34, (0.09–2.0), 0.15 
     
NSCLC Stage III 47 50% 21.8 vs 28.3 (p = 0.38) OS: 1.7, (0.8–3.6), 0.17 
HEENT (HPV) 22 36% PFS only PFS: 6.2, (1.1–35.2), 0.04 
NeoplasmTotal number patientsPatients developing grade III-IV TRLMedian Survival <500 vs >500 lymphocytes (months)Multivariate association with reduced survival:HR, (CI), pvalue
High grade glioma 96 40% 13 vs 19.7 (p = 0.002) OS: 1.66, (1.05–2.64), 0.03 
Pancreatic resected 53 45% 14 vs 20 (p = 0.048) OS: 2.2, (1.17–4.12), 0.01 
Pancreatic unresectable 120 74% 9.2 vs 14.6 (p = 0.013) OS: 1.34, (0.09–2.0), 0.15 
     
NSCLC Stage III 47 50% 21.8 vs 28.3 (p = 0.38) OS: 1.7, (0.8–3.6), 0.17 
HEENT (HPV) 22 36% PFS only PFS: 6.2, (1.1–35.2), 0.04 

Citation Format: Stuart A. Grossman, Susannah Yovino, Jian Campian, Aaron Wild, Joseph Herman, Daniel Laheru, Malcolm Brock, Shanthi Marur, Ani Balmanoukian, Xiaobu Ye. The association between treatment-related lymphopenia and survival in patients with solid tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1242. doi:10.1158/1538-7445.AM2013-1242