Pretreatment Neutrophil/Lymphocyte Ratio Predicts Relapse in Stage I and II Hodgkin Lymphoma

Hodgkin lymphoma (HL) management has traditionally relied on multiple pre-treatment characteristics to risk stratify patients and guide treatment. Recent insights into the relationship between immunology and cancer have identified the neutrophil/lymphocyte ratio (NLR) as an important prognostic factor in multiple cancer types, including diffuse large B-cell lymphoma. The purpose of this study was to determine if pre-treatment NLR predicts for progression in early-stage HL. We identified 345 consecutive stage I and II HL patients treated at our institution from 2002-2015. Clinical, pathologic, and treatment characteristics were extracted from medical records. Pre-treatment absolute neutrophil (ANC) and lymphocyte counts (ALC) were obtained and used to generate an NLR (ANC/ALC). Actuarial overall survival (OS) and progression-free survival (PFS) curves were calculated using the Kaplan-Meier method calculated from the date of diagnosis to the date of last follow-up or relapse/refractory disease. Independent factors associated with these outcomes were identified using a multivariate Cox regression model. Median age at diagnosis was 32 years (range: 18-90), and 189 patients were female (54.8%). 292 patients (84.6%) had stage II disease. 249 patients (72.2%) received consolidation radiation (median dose of 30.6 Gy). Median follow-up for the entire cohort was 60.3 months (range, 4.8-147.8). 5-year OS and PFS was 94.7% and 90%, respectively. 32 patients (9.3%) experienced a relapse or had refractory disease. Median NLR at diagnosis was 4.1 (IQR, 2.5-7.1). Table 1 shows that increasing NLR, when subcategorized into quintiles, correlates with higher risk of relapse/refractory disease (P = 0.02, chi square). A receiver operator curve (ROC) analysis was then applied to determine the NLR cutoff value of 6.5, which optimally identified the risk of relapse. On univariate analysis, NLR > 6.5 was significantly associated with relapse/refractory disease (HR: 3.39, 95% CI: 1.69—6.94, P = 0.0007). 5 year PFS for patients with NLR > 6.5 was 81.2% as opposed to 93.6% in the remainder of patients (P = 0.0003). On multivariate analysis, even after adjusting for bulky disease, NLR > 6.5 remained a significant, independent predictor of progression (HR: 2.22, 95% CI: 1.08—4.68, P = 0.03). In this cohort of stage I and II HL patients, pre-treatment NLR above a threshold is significantly associated with increased risk of relapse or refractory disease and predicts for worse PFS. If validated, pre-treatment NLR could be an effective, low cost screening test that, in conjunction with other clinical parameters, could be used to identify patients at highest risk of progression.Tabled 1Abstract 48; Table 1. Increasing NLR correlates with risk of relapse/refractory diseaseNLR StratificationNo Relapse/Refractory (%)Relapse/Refractory (%)< 2.361 (93.9)4 (6.2)> 2.3 – < 3.470 (94.6)4 (5.4)> 3.4 – < 566 (95.7)3 (4.4)> 5 – < 7.859 (88.1)8 (11.9)> 7.857 (81.4)13 (18.6)*P = 0.02 Open table in a new tab