BackgroundRecent research has shown a correlation between immune microenvironment and lymphoma biology. This study aims to investigate the prognostic significance of the immunologically relevant lymphocyte-to-monocyte ratio (LMR), in diffuse large B-cell lymphoma (DLBCL) in the rituximab era.Methodology/Principal FindingsWe analyzed retrospective data from 438 newly diagnosed DLBCL patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. We randomly selected 200 patients (training set) to generate a cutoff value for LMR by receiver operating characteristic (ROC) curve analysis. LMR was then analyzed in a testing set (n = 238) and in all patients (n = 438) for validation. The LMR cutoff value for survival analysis determined by ROC curve in the training set was 2.6. Patients with low LMR tended to have more adverse clinical characteristics. Low LMR at diagnosis was associated with worse survival in DLBCL, and could also identify high-risk patients in the low-risk IPI category. Multivariate analysis identified LMR as an independent prognostic factor of survival in the testing set and in all patients.Conclusions/SignificanceBaseline LMR, a surrogate biomarker of the immune microenvironment, is an effective prognostic factor in DLBCL patients treated with R-CHOP therapy. Future prospective studies are required to confirm our findings.

No abstract

Objectives:  Rituximab has significantly improved the survival of patients with DLBCL, especially those with non‐germinal center B‐cell‐like (non‐GCB) subtype. The impact of Ki‐67 expression, an index of proliferation, on the clinical outcomes of patients with DLBCL has largely been unexplored. This study aimed to investigate whether Ki‐67 expression is an indicator of outcome in DLBCL patients (especially non‐GCB DLBCL patients) treated with standard chemotherapy combined with rituximab. Methods:  Expression of Ki‐67 protein was examined immunohistochemically in 118 tumor specimens from patients newly diagnosed with DLBCL and treated with R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Results:  Overall survival (OS) and progression‐free survival (PFS) were lower in patients with high Ki‐67 expression than in those with low Ki‐67 expression (3‐year OS: 65.2% vs. 81.7%, P = 0.030; 3‐year PFS: 56.4% vs. 73.3%, P = 0.020), similar in patients with GCB subtype and those with the non‐GCB subtype (OS: P = 0.330; PFS: P = 0.287). According to Ki‐67 expression status by immunophenotype subgroups, patients with high Ki‐67 expression in non‐GCB subgroup had the most unfavorable PFS and OS, comparing with the other three subgroups (P = 0.004 and P = 0.002, respectively). In multivariate analysis, non‐GCB with high Ki‐67 expression was an independent prognostic predictor of inferior survival in DLBCL patients treated with R‐CHOP. Conclusion:  For DLBCL patients with non‐GCB DLBCL and high Ki‐67 expression, the survival benefit from R‐CHOP therapy is limited.

BackgroundExtranodal natural killer/T-cell lymphoma (ENKL) has heterogeneous clinical manifestations and prognosis. This study aims to evaluate the prognostic impact of absolute monocyte count (AMC) in ENKL, and provide some immunologically relevant information for better risk stratification in patients with ENKL.MethodsRetrospective data from 163 patients newly diagnosed with ENKL were analyzed. The absolute monocyte count (AMC) at diagnosis was analyzed as continuous and dichotomized variables. Independent prognostic factors of survival were determined by Cox regression analysis.ResultsThe AMC at diagnosis were related to overall survival (OS) and progression-free survival (PFS) in patients with ENKL. Multivariate analysis identified AMC as independent prognostic factors of survival, independent of International Prognostic Index (IPI) and Korean prognostic index (KPI). The prognostic index incorporating AMC and absolute lymphocyte count (ALC), another surrogate factor of immune status, could be used to stratify all 163 patients with ENKL into different prognostic groups. For patients who received chemotherapy followed by radiotherapy (102 cases), the three AMC/ALC index categories identified patients with significantly different survivals. When superimposed on IPI or KPI categories, the AMC/ALC index was better able to identify high-risk patients in the low-risk IPI or KPI category.ConclusionThe baseline peripheral monocyte count is shown to be an effective prognostic indicator of survival in ENKL patients. The prognostic index related to tumor microenvironment might be helpful to identify high-risk patients with ENKL.

No abstract