Prognostic role of pretreatment blood lymphocyte count in patients with solid tumors: a systematic review and meta-analysis

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Abstract

Background

To evaluate the prognostic value of pretreatment lymphocyte counts with respect to clinical outcomes in patients with solid tumors.

Methods

Systematic literature search of electronic databases (Pubmed, Embase and Web of Science) up to May 1, 2018 was carried out by two independent reviewers. We included Eligible studies assessed the prognostic impact of pretreatment lymphocytes and had reported hazard ratios (HR) with 95% confidence intervals (CIs) for endpoints including overall survival (OS) and progression-free survival (PFS). Only English publications were included.

Results

A total of 42 studies comprising 13,272 patients were included in this systematic review and meta-analysis. Low pretreatment lymphocyte count was associated with poor OS (HR = 1.27, 95% CI 1.16–1.39, P < 0.001, I ² = 58.5%) and PFS (HR = 1.27, 95% CI 1.15–1.40, P < 0.001, I ² = 25.7%). Subgroup analysis disaggregated by cancer type indicated that low pretreatment lymphocytes were most closely associated with poor OS in colorectal cancer followed by breast cancer and renal cancer.

Conclusions

Low pretreatment lymphocyte count may represent an unfavorable prognostic factor for clinical outcomes in patients with solid tumors.

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Most cited references 45

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Lymphopenia as a prognostic factor for overall survival in advanced carcinomas, sarcomas, and lymphomas.

Isabelle Ray-Coquard, Claire Cropet, Martine Van Glabbeke … (2009)

Lymphopenia is frequent in advanced cancers and predicts the toxicity of chemotherapy. Its effect on relapse and survival is uncertain. Its prognostic value for survival was analyzed in three databases of previously reported prospective multicenter studies: (a) FEC chemotherapy in metastatic breast carcinoma; (b) CYVADIC in advanced soft tissue sarcoma (European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group 62791); and (c) prospective, consecutive phase III studies of aggressive diffuse large-cell non-Hodgkin's lymphomas conducted at Centre Léon Bérard between 1987 and 1993. Univariate and multivariate analyses of prognostic factors for survival were performed. The incidence of lymphopenia of 1, non-Hodgkin's lymphoma patients with international prognostic index (IPI) of > 0, and advanced soft tissue sarcoma and metastatic breast cancer patients with bone metastases. Inunivariate analysis, lymphopenia of <1,000/microL significantly correlated to overall survival in patients with metastatic breast cancer (median, 10 versus 14 mo; P < 0.0001), advanced soft tissue sarcoma (median, 5 versus 10 months; P < 0.01), and non-Hodgkin lymphoma (median, 11 versus 94 months; P < 0.0001). In multivariate analysis (Cox model), lymphopenia was an independent prognostic factor for overall survival in metastatic breast cancer [RR (relative risk), 1.8; 95% CI (confidence interval), 1.3-2.4] along with liver metastases and PS; in advanced soft tissue sarcoma (RR, 1.46; 95% CI, 1.0-2.1) along with liver metastases, lung metastases, and PS; and in non-Hodgkin's lymphoma (RR, 1.48; 95% CI, 1.03-2.1) along with IPI. Our findings show that lymphopenia is an independent prognostic factor for overall and progression-free survival in several cancers.

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Transforming growth factor-beta in T-cell biology.

Leonid Gorelik, Wendy Flavell (2001)

Strict control of T-cell homeostasis is required to permit normal immune responses and prevent undesirable self-targeted responses. Transforming growth factor-beta (TGF-beta) has been shown to have an essential role in that regulation. Owing to its broad expression, and inhibitory effects on multiple cell types of the immune system, TGF-beta regulation is complex. Through advances in cell-specific targeting of TGF-beta signalling in vivo, the role of TGF-beta in T-cell regulation has become clearer. Recent in vitro studies provide a better understanding of how TGF-beta regulates T-cell homeostasis, through multiple mechanisms involving numerous cell types.

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Preoperative neutrophil-to-lymphocyte ratio is a predictor of survival after hepatectomy for hepatocellular carcinoma: a retrospective analysis.

Kazuki Takeishi, Ken Shirabe, SHIN-ICHI YAMASHITA … (2013)

To clarify the prognostic value of the preoperative blood neutrophil-to-lymphocyte ratio (NLR) in patients undergoing hepatectomy for hepatocellular carcinoma (HCC). Although a high NLR has been reported to be a predictor of poor survival in patients with various cancers, it has not been extensively examined in patients with HCC. This retrospective study enrolled 958 patients who underwent hepatectomy without preoperative therapy for HCC from 1996 to 2009. Clinicopathological parameters, including NLR, were evaluated to identify predictors of overall and recurrence-free survival after hepatectomy. Univariate and multivariate analyses were performed, using the Cox proportional hazards model. The best cutoff was determined with time-dependent receiver operating characteristic curve. To determine the mechanism of NLR elevation, immunohistological examination using CD163 staining was performed in 150 patients. Univariate and multivariate analyses showed that NLR was an independent prognostic factor in overall and recurrence-free survival. The best cutoff of NLR was 2.81, and 238 of 958 patients (24.8%) had NLR of more than 2.81. The 5-year survival rate after hepatectomy was 72.9% in patients with NLR less than 2.81 and 51.5% in those with NLR 2.81 or more (P < 0.0001). CD163-positive cell counts were significantly higher in tumors in the group with NLR 2.81 or more than in the group with NLR less than 2.81 (P = 0.0004). Our results show that NLR is an independent predictor of survival after hepatectomy in patients with HCC. Accumulation of tumor-associated macrophages in the tumor is associated with a high NLR.

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Author and article information

Contributors

Chengyang Li: 15277006345@163.com

Journal

Journal ID (nlm-ta): Cancer Cell Int

Journal ID (iso-abbrev): Cancer Cell Int

Title: Cancer Cell International

Publisher: BioMed Central (London )

ISSN (Electronic): 1475-2867

Publication date (Electronic): 10 January 2020

Publication date PMC-release: 10 January 2020

Publication date Collection: 2020

Volume: 20

Electronic Location Identifier: 15

Affiliations

[1 ]GRID grid.412594.f, Department of Urology, , The First Affiliated Hospital of Guangxi Medical University, ; 6 Shuangyong Road, Nanning, 530021 Guangxi Zhuang Autonomous Region China

[2 ]GRID grid.412594.f, Department of Gastrointestinal Surgery, , The First Affiliated Hospital of Guangxi Medical University, ; 6 Shuangyong Road, Nanning, 530021 Guangxi Zhuang Autonomous Region China

Article

Publisher ID: 1094

DOI: 10.1186/s12935-020-1094-5

PMC ID: 6954501

PubMed ID: 31938023

SO-VID: 662ef232-8cfb-40dc-99de-8bbac7c13909

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 23 May 2019

Date accepted : 2 January 2020

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;

Award ID: No. 81660125

Award Recipient : Chengyang Li

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: lymphocyte,pretreatment,prognosis,solid tumor

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: lymphocyte, pretreatment, prognosis, solid tumor

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Prognostic role of pretreatment blood lymphocyte count in patients with solid tumors: a systematic review and meta-analysis

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Most cited references 45

Lymphopenia as a prognostic factor for overall survival in advanced carcinomas, sarcomas, and lymphomas.

Transforming growth factor-beta in T-cell biology.

Preoperative neutrophil-to-lymphocyte ratio is a predictor of survival after hepatectomy for hepatocellular carcinoma: a retrospective analysis.

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