Absolut Lymphocyte Count At Diagnosis Is Predictive Of Survival In Patients With Classical Hodgkin Lymphoma: A Retrospective Multicenter Brazilian Study
Authors: Perini Guilherme Fleury , Cavalcante Egyla M , Rezende Joao Garibaldi , Borducchi Davimar Miranda , Vieira Fernanda Cunha , Cordeiro Faria Danielle Leão , Tavares Renato S , Amaral Camila Almeida , Santos Fabio S P , Hamerschlak Nelson , Cecyn Karin Zattar , Souza Eni Maria , Damasco Penna Adriana M. , Baiocchi Otavio C.G. 
Published: October 2019

Abstract

Introduction
Classical Hodgkin lymphoma (cHL) is one of the most curable cancers, with cure rates ranging from 65-90%, depending on different risk factors. These factors include both clinical (international prognostic score, IPS) and biological markers (tumor associated macrophages, for example). However, most biological biomarkers are not available in a routine basis and IPS does not offer risk stratification for patients diagnosed with early stage cHL. Recently, Porrata et al described the peripheral lymphocyte/monocyte ratio (LMR) as a strong prognostic factor in patients with cHL. In his study, an LMR of less than 1.1 was related with poor outcome.

Objectives
To assess the role of lymphocyte/monocyte ratio at diagnosis in predicting outcome and survival in cHL patients in Brazil.

Patient and Methods
This is a retrospective multicenter study conducted by the Universidade Federal de São Paulo, São Paulo, Brazil. Only confirmed cases of cHL, diagnosed between April 1986 to January 2013, with clinical, epidemiological and laboratorial parameters available after a thorough chart review were included in this study. Response was defined as complete (CR) or less than CR (partial response or refractory disease). Event was defined as treatment related mortality, progression (defined as time for initiation of salvage therapy) or relapse. Advanced stage disease was defined as stage I or II with B symptoms and/or bulky disease and stage III or IV. Patients with conflicted data or loss of follow up were excluded from the analysis.

Results
A total of 570 patients were diagnosed with cHL in this period. However, 303 patients were selected for this study. Nodular sclerosis subtype was diagnosed in 207 (68%) of all patients. Median age at diagnosis was 30 years old (raging from 12-78), with a 0,9:1 Female:Male ratio. The majority (210, 69%) presented with advanced disease. ABVD chemotherapy protocol was the initial therapy in 91% of patients, MOPP/ABV in 8% and 1% of patients received only radiotherapy. For early-stage disease, a median of 6 cycles was delivered and 8 cycles were given for patients with advanced disease. Consolidation radiotherapy was done in 175 (58%) of all patients after chemotherapy. Overall responses were: CR in 90,7% (n=274), Partial response/Refractory disease in 8,9% (n=27); one patient died due to treatment-related toxicity. CR rates were 97,8% in early stage disease and 89,4% in advanced stage (p=0.07). Overall Survival (OS) for the entire group was 95% in 5 years (CI95% 73-83%), with a progression free survival (PFS) of 78% (CI95% 91-97%). A Lymphocyte/Monocyte ratio (LMR) less than 1.1 was not predictive of survival in our patients, neither PFS (84% vs 78%, p=0.30) nor OS (95% vs 96%, p=0.48). However, absolute lymphocyte count (ALC) greater than 1000 cells/mL at diagnosis was related to a better OS (97% vs 88%, p=0.003).

Conclusions
Although cHL is highly curable, it is an unmet medical need to better stratify these patients at diagnosis, especially with simple and straightforward prognostic factors, such as absolute lymphocyte count at diagnosis. In our study, LMR less than 1.1 was not associated with survival, as recently pointed by Porrata et al., but an ALC greater than 1000 cells/mL was related to better overall survival. It is well known that the incidence of EBV-related cHL, disease presentation and severity are different in developing countries than in developed ones; therefore, prognostic factors may differ from different studied populations, highlighting the importance of our results.

Disclosures:
No relevant conflicts of interest to declare.