Blood Lymphocyte-to-Monocyte Ratio Identifies High-Risk Patients in Diffuse Large B-Cell Lymphoma Treated with R-CHOP

Li, Zhi Ming; Huang, Jia Jia; Xia, Yi; Sun, Jian; Huang, Ying; Wang, Yu; Zhu, Ying; Li, Ya Jun; Zhao, Wei; Wei, Wen; Lin, Tong; Huang, Hui Qiang; Jiang, Wen Qi

doi:10.1371/journal.pone.0041658

Cited by 133 publications

(129 citation statements)

References 33 publications

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“…17 These peripheral blood monocytes suppress host immunity by inhibiting the proliferative ability of interferon-γ, impairing the differentiation ability of dendritic cells. 1 In this study, however, the impact of AMC was still significant even after adjusting for systemic relapse as a timedependent covariate. In addition, among patients who developed systemic relapse, the incidence of subsequent CNS relapse was significantly higher in patients with high AMC at diagnosis.…”

Section: Discussioncontrasting

confidence: 60%

“…DLBCL accounts for 25-30% of non-Hodgkin lymphomas among adults in the west, and it is even more prevalent in developing countries. 1 In Japan, it was reported that DLBCL is the most frequent subtype and accounts for over 30% of cases of non-Hodgkin lymphomas among adults. 2 Central nervous system (CNS) involvement is not common in DLBCL, but several risk factors for CNS involvement have been identified, including high International Prognostic Index score, involvement of more than one extranodal site, elevated lactate dehydrogenase level, poor Eastern Cooperative Oncology Group performance status (PS), advanced stage, and involvement of bone marrow, breast, testis, retroperitoneal lymph nodes, orbit, or epidural space.…”

Section: Introductionmentioning

confidence: 99%

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Absolute peripheral monocyte count at diagnosis predicts central nervous system relapse in diffuse large B-cell lymphoma

et al. 2014

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ABSTRACTnation of blood smears in cases in which the automated counts were abnormal.CNS relapse-free survival was calculated by cause-specific function, censoring patients who died without CNS relapse, in accordance with previously published studies.11-14 The starting date of the time-to-event analysis was defined at diagnosis. Univariate and multivariate analyses of estimated risk factors for CNS relapse in DLBCL patients were performed using the log-rank test and Cox proportional hazard regression analysis. P values <0.05 were considered statistically significant. Background characteristics of the patients with and without CNS involvement were compared using the Fisher exact test and Student t-test. All statistical analyses were performed with EZR 15 (Saitama, Medical Center, Jichi Medical University, Japan).

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Section: Discussioncontrasting

confidence: 60%

Section: Introductionmentioning

confidence: 99%

Absolute peripheral monocyte count at diagnosis predicts central nervous system relapse in diffuse large B-cell lymphoma

et al. 2014

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“…These findings are in line with previously published studies from hematological cancer. 15,16,25 Furthermore, supplementing the Kattan nomogram by the L/M ratio improved the predictive ability …”

Section: Discussionmentioning

confidence: 99%

“…8 Another study showed a correlation between low L/M ratio and poor survival in diffuse large B-cell lymphoma patients. 25 In patients with metastatic melanoma, elevated monocyte counts in peripheral blood were associated with poor survival. 26 In our study, we found a statistically significant association between a low L/ M ratio and CCS and DFS in STS patients in univariate as well as multivariate analysis for both data sets.…”

Section: Discussionmentioning

confidence: 99%

The lymphocyte/monocyte ratio predicts poor clinical outcome and improves the predictive accuracy in patients with soft tissue sarcomas

et al. 2014

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Increasing evidence indicates the involvement of inflammation and coagulation in cancer progression and metastases. Inflammatory biomarkers hold great promise for improving the predictive ability of existing prognostic tools in cancer patients. In the present study, we investigated several inflammatory indices with regard to their prognostic relevance for predicting clinical outcome in soft tissue sarcoma (STS) patients. Three hundred and forty STS patients were divided into a training set (n 5 170) and a validation set (n 5 170). Besides well-established clinico-pathological prognostic factors, we evaluated the prognostic value of the neutrophil/lymphocyte (N/L) ratio, the lymphocyte/monocyte (L/M) ratio and the platelet/lymphocyte (P/L) ratio using Kaplan-Meier curves and univariate as well as multivariate Cox regression models. Additionally, we developed a nomogram by supplementing the L/M ratio to the well-established Kattan nomogram and evaluated the predictive accuracy of this novel nomogram by applying calibration and Harrell's concordance index (c-index). In multivariate analysis, a low L/M ratio was significantly associated with decreased CSS and DFS (HR 5 0.41, 95% CI 5 0.18-0.97, p 5 0.043; HR 5 0.39, 95% CI 5 0.16-0.91, p 5 0.031, respectively) in the training set. Using the validation set for confirmation, we found also in multivariate analysis an independent value for CSS (HR 5 0.33, 95% CI 5 0.12-0.90, p 5 0.03) and for DFS (HR 5 0.36, 95% CI 5 0.16-0.79, p 5 0.01). The estimated c-index was 0.74 using the original Kattan nomogram and 0.78 when the L/M ratio was added. Our study reports for the first time that the pre-operative L/M ratio represents a novel independent prognostic factor for prediction the clinical outcome in STS patients. This easily determinable biomarker might be helpful in improved individual risk assessment.Soft tissue sarcomas (STS) account for nearly 11,280 cases per year and are responsible for about 3,900 deaths in the United States annually, mainly due to local recurrence or metastatic disease. 1 Therefore, it is crucial to understand the biological mechanisms that contribute to tumor progression and to identify novel prognostic markers to generate individualized treatment and follow-up schedules. In a large retrospective study of 2,136 STS patients, Kattan et al. developed a postoperative prognostic model that predicts sarcomaspecific death, based on traditional prognostic factors such as age at diagnosis, tumor size, histologic grade, histologic subtype, tumor depth and site. 2 This nomogram is useful for general risk assessment and has potential value in determining surgical strategy and adjuvant management. Nevertheless, novel prognostic factors might be helpful in improving its predictive ability. Current approaches in cancer research have focused on the characterization of novel biomarkers, which ideally should be easily accessible, highly reproducible, cheap and most importantly, identify patients at high risk for disease-recurrence and death. Increasing evidence su...

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“…In the non-immunosuppressed, DLBCL biopsies display features of a host immune response, including genes and proteins associated with lymphocytes and monocytes [10][11][12][13]. In this respect, recent studies have demonstrated circulating immune cells measured by the complete blood counts (CBC), such as absolute lymphocyte counts (ALC) and absolute monocyte counts (AMC), either alone or in combination with each (e.g., lymphocyte/monocyte ratio: LMR), predict outcome independent of the R-IPI [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

CD4⁺ Tumor infiltrating lymphocytes are prognostic and independent of R‐IPI in patients with DLBCL receiving R‐CHOP chemo‐immunotherapy

Keane,

Gill,

Vari

et al. 2013

American J Hematol

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Despite the Revised International Prognostic Index's (R-IPI) undoubted utility in diffuse large B-cell lymphoma (DLBCL), significant clinical heterogeneity within R-IPI categories persists. Emerging evidence indicates that circulating host immunity is a robust and R-IPI independent prognosticator, most likely reflecting the immune status of the intratumoral microenvironment. We hypothesized that direct quantification of immunity within lymphomatous tissue would better permit stratification within R-IPI categories. We analyzed 122 newly diagnosed consecutive DLBCL patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemo-immunotherapy. Median follow-up was 4 years. As expected, the R-IPI was a significant predictor of outcome with 5-year overall survival (OS) 87% for very good, 87% for good, and 51% for poor-risk R-IPI scores (P < 0.001). Consistent with previous reports, systemic immunity also predicted outcome (86% OS for high lymphocyte to monocyte ratio [LMR], versus 63% with low LMR, P 5 0.01). Multivariate analysis confirmed LMR as independently prognostic. Flow cytometry on fresh diagnostic lymphoma tissue, identified CD41 T-cell infiltration as the most significant predictor of outcome with 23% infiltration dividing the cohort into high and low risk groups with regard to event-free survival (EFS, P 5 0.007) and OS (P 5 0.003). EFS and OS were independent of the R-IPI and LMR. Importantly, within very good/good R-IPI patients, CD41 T-cells still distinguished patients with different 5 year OS (high 96% versus low 63%, P 5 0.02). These results illustrate the importance of circulating and local intratumoral immunity in DLBCL treated with R-CHOP. Am. J.

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Blood Lymphocyte-to-Monocyte Ratio Identifies High-Risk Patients in Diffuse Large B-Cell Lymphoma Treated with R-CHOP

Cited by 133 publications

References 33 publications

Absolute peripheral monocyte count at diagnosis predicts central nervous system relapse in diffuse large B-cell lymphoma

Absolute peripheral monocyte count at diagnosis predicts central nervous system relapse in diffuse large B-cell lymphoma

The lymphocyte/monocyte ratio predicts poor clinical outcome and improves the predictive accuracy in patients with soft tissue sarcomas

CD4⁺ Tumor infiltrating lymphocytes are prognostic and independent of R‐IPI in patients with DLBCL receiving R‐CHOP chemo‐immunotherapy

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Blood Lymphocyte-to-Monocyte Ratio Identifies High-Risk Patients in Diffuse Large B-Cell Lymphoma Treated with R-CHOP

Cited by 133 publications

References 33 publications

Absolute peripheral monocyte count at diagnosis predicts central nervous system relapse in diffuse large B-cell lymphoma

Absolute peripheral monocyte count at diagnosis predicts central nervous system relapse in diffuse large B-cell lymphoma

The lymphocyte/monocyte ratio predicts poor clinical outcome and improves the predictive accuracy in patients with soft tissue sarcomas

CD4+ Tumor infiltrating lymphocytes are prognostic and independent of R‐IPI in patients with DLBCL receiving R‐CHOP chemo‐immunotherapy

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CD4⁺ Tumor infiltrating lymphocytes are prognostic and independent of R‐IPI in patients with DLBCL receiving R‐CHOP chemo‐immunotherapy