The Neutrophil/Lymphocyte Ratio (N/L) Is a Prognostic Marker in Patients with Diffuse Large B Cell Lymphoma: A Prospective Study from the Lazio Lymphoma Registry
Authors: Annibali Ombretta , Hohaus Stefan , Tomarchio Valeria , Anticoli Borza Paola , Cantonetti Maria , Battistini Roberta , Montanaro Marco , De Angelis Federico , Cimino Giuseppe , Palombi Francesca , Liberati Anna Marina , Abruzzese Elisabetta , Tesei Cristiano , Tisi Maria Chiara , Alma Eleonora , Rizzuto Giuliana , Pupo Livio , Zoli Valerio , Maiolo Elena , Ansuinelli Michela , Naso Virginia , Bianchi Maria Paola , Cox Maria Christina 
Published: October 2019

Abstract
The neutrophil/lymphocyte ratio (N/L) at diagnosis has been shown to be a prognostic factor for survival in solid tumors. An increase in the neutrophil count is a marker of inflammation which is an essential part of the neoplastic process. Conversely, a decrease of the peripheral lymphocyte count might reflect an impairment of the host defense mechanism associated with advanced and aggressive cancers. Since There are only few reports on the N/L ratio in non-Hodgkin lymphomas.
We studied the prognostic role of the N/L ratio at diagnosis in 286 patients with diffuse-large-B-cell lymphoma (DLBCL) enrolled in a multicenter prospective registry of the Lazio region in Italy The median age at diagnosis was 69 years (27-91) and the female/male ratio was:141/145.First, we analyzed for associations between N/L ratio and patient characteristics. The optimal cut-off value for the N/L was obtained using the Receiver Operating Curve (ROC) and according to the published data in solid tumor. N/L ≥ 4 was significantly associated with presence of B-symptoms (p=0.01) and elevated LDH levels (p=0.007) at diagnosis.
Most patients were treated with R-CHOP (rituximab, cyclophosphamide, Adriamycin, vincristine, and prednisone) or R-CHOP-like (90%). Complete Remission (CR) + Partial Remission (PR) were obtained in 210/286 (73%). The median follow up period was 15 months (range: 1-33 months): 27 patients died for lymphoma relapse/progression and 16 for other causes. Patients with N/L ≥ 4 experienced a higher rate of relapse, while N/L< 4 was associated to a significantly better Overall (OS, P < 0.05) and Event Free Survival (EFS, P< 0.01). (Figure 1, panel a and b).Furthermore, considering only patients with IPI score ≤ 3, those with N/L <4, (Figure 1, panel c), had a better OS compared to those with N/L≥ 4 (P < 0.01).
Conclusion: The N/L ratio may be a useful and unexpensive prognostic marker in patients with DLBCL. The inferior outcome observed in patients with N/L ≥ 4 might reflect an immune and inflammatory imbalance induced by a more aggressive tumor, releasing directly or indirectly inflammatory cytokines and/or inducing immune suppression or exhaustion. A link with inflammation is suggested by the correlation of N/L ratio ≥ 4 with high LDH levels and the presence of B symptoms.
Figure 1.
Panel A. Overall Survival (OS) and Panel B. Event Free Survival (EFS) by N/L ratio. Panel C. Overall Survival (OS) by N/L in patients with IPI score ≤ 3.
Table 1.Baseline patients characteristics (N = 268) and compared by N/L < 4 or ≥ 4 by using Chi-Square Test for categorical variables.
Abbreviations not included in the text: IPI = International Prognostic Index; LDH = lactate dehydrogenase, PD: Progression Disease, NA: Not Applicable.

Disclosures
Cimino: Celgene: Honoraria; Bristol-Mayer: Honoraria.