Prognostic Significance of the Ratio of Absolute Neutrophil Count to Absolute Lymphocyte Count in Classic Hodgkin Lymphoma
ABSTRACT The aim of this study was to determine the prognostic effect of the absolute neutrophil count/absolute lymphocyte count ratio (ANC/ALC ratio) in patients with classic Hodgkin lymphoma (cHL). We performed a retrospective analysis of 312 patients with cHL. Univariate analysis revealed that a high ANC/ALC ratio (≥4.3) correlated with poor overall survival (OS) (P < .001). Subgroup analysis of advanced-stage disease showed that the ANC/ALC ratio was significant for OS (P = .032). Multivariate analysis revealed the ANC/ALC ratio to be an independent prognostic factor for OS (P = .048). The ANC/ALC ratio allowed further risk stratification in patients who were considered to be at low risk on the basis of an International Prognostic Score less than 4 (P = .002). The ANC/ALC ratio is a simple, inexpensive, and independent prognostic factor for OS that may improve the ability to identify high-risk patients with cHL.
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ABSTRACT: High risk, unfavorable classical Hodgkin lymphoma (cHL) includes those patients with primary refractory or early relapse, and progressive disease. To improve the availability of biomarkers for this group of patients, we investigated both tumor biopsies and peripheral blood leukocytes (PBL) of untreated (chemo-naive, CN) Nodular Sclerosis Classic Hodgkin Lymphoma (NS-cHL) patients for consistent biomarkers that can predict the outcome prior to frontline treatment.Methods and materials: Bioinformatics data mining was used to generate 151 candidate biomarkers, which were screened against a library of 10 HL cell lines. Expression of FGF2 and SDC1 by CD30+ cells from HL patient samples representing good and poor outcomes were analyzed by qRT-PCR, immunohistochemical (IHC), and immunofluorescence analyses. To identify predictive HL-specific biomarkers, potential marker genes selected using bioinformatics approaches were screened against HL cell lines and HL patient samples. Fibroblast Growth Factor-2 (FGF2) and Syndecan-1 (SDC1) were overexpressed in all HL cell lines, and the overexpression was HL-specific when compared to 116 non-Hodgkin lymphoma tissues. In the analysis of stratified NS-cHL patient samples, expression of FGF2 and SDC1 were 245 fold and 91 fold higher, respectively, in the poor outcome (PO) group than in the good outcome (GO) group. The PO group exhibited higher expression of the HL marker CD30, the macrophage marker CD68, and metastatic markers TGFbeta1 and MMP9 compared to the GO group. This expression signature was confirmed by qualitative immunohistochemical and immunofluorescent data. A Kaplan-Meier analysis indicated that samples in which the CD30+ cells carried an FGF2+/SDC1+ immunophenotype showed shortened survival. Analysis of chemo-naive HL blood samples suggested that in the PO group a subset of CD30+ HL cells had entered the circulation. These cells significantly overexpressed FGF2 and SDC1 compared to the GO group. The PO group showed significant down-regulation of markers for monocytes, T-cells, and B-cells. These expression signatures were eliminated in heavily pretreated patients. The results suggest that small subsets of circulating CD30+/CD15+ cells expressing FGF2 and SDC1 represent biomarkers that identify NS-cHL patients who will experience a poor outcome (primary refractory and early relapsing).Journal of Hematology & Oncology 08/2013; 6(1):62. DOI:10.1186/1756-8722-6-62 · 4.93 Impact Factor
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ABSTRACT: Objectives: The aim of this study was to determine the prognostic relevance of colony-stimulating 1 receptor (CSF-1R) expression in both Hodgkin/Reed-Sternberg (HRS) cells and the surrounding cells (non-HRS cells) in patients with classical Hodgkin lymphoma (CHL) . Methods: Diagnostic tissues from 112 patients with CHL treated with doxorubicin, bleomycin, vinblastine, and dacarbazine were evaluated retrospectively by immunohistochemical analysis for CSF-1R and CD68 and CD163 for tissue-associated macrophages. Results: High numbers (≥30%) of non-HRS cells expressing CSF-1R conferred inferior event-free survival and overall survival in univariate and multivariate analysis. High numbers of non-HRS cells expressing CSF-1R were significantly associated with a high number of tumor-associated macrophages as detected by CD163 expression (P < .001). In particular, coexpression of CSF-1R and CD163 was associated with a worse survival outcome than either CSF-1R or CD163 expression alone or no expression. Conclusions: Our data demonstrate that a high number of non-HRS cells expressing CSF-1R are correlated with an increased tumor macrophage content and worse survival.American Journal of Clinical Pathology 04/2014; 141(4):573-83. DOI:10.1309/AJCPR92TDDFARISU · 3.01 Impact Factor
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ABSTRACT: ObjectivesA recent study suggested a prognostic role for the peripheral blood absolute lymphocyte/monocyte ratio (LMR) at diagnosis of diffuse large B-cell lymphoma (DLBCL).Here we investigated the significance of LMR in DLBCL patients in relation to advanced age.Methods We examined the prognostic impact of LMR in 603 DLBCL treated with rituximab plus CHOP, using the receiver operating characteristic curve analysis for optimal cut-off values, and performed a subgroup analysis according to age.ResultsIn elderly groups (age≥70), absolute monocyte count was significantly increased, whereas LMR was significantly decreased compared to younger groups. Patients under 70 years of age with LMR <3.04 had significantly lower overall survival (OS) and progression-free survival (PFS) compared to those with LMR ≥3.04 (P<0.001 for both). However, in elderly patients (age≥70), there was no significant difference in OS between patients’ LMR levels using the 3.04 cut-off value (P=0.059).Therefore, a new LMR cut-off value of 2.36 was selected in elderly patients, having observed that elderly patients with LMR <2.36 had significantly lower OS compared to those with LMR ≥2.36 (P=0.021). In multivariate analysis, LMR remained a significant prognostic factor for OS (P = 0.004) or PFS (P < 0.001).Conclusions We suggest the use of a different cut-off value of LMR in elderly patients to distinguish high-risk from low-risk groups.This article is protected by copyright. All rights reserved.European Journal Of Haematology 04/2014; 93(4). DOI:10.1111/ejh.12354 · 2.41 Impact Factor