Addition of Absolute Lymphocytes/Monocytes Ratio Improves the Revised-International Prognostic Index (R-IPI) in Patients with Diffuse Large B Cell Lymphoma (DLBCL) Treated with R-CHOP
Authors: Bento Leyre , Bautista-Gili Antonia María , García Francesc , Martínez-Serra Jordi , García-Mañó Lucía , García-Recio Marta , Ballester Carmen , Ginés Jordi , López Paloma , Daumal Jaime , Ramos Rafael , Salar Antonio , Sampol Antonia , Besalduch Juan , Gutiérrez Antonio 
Published: October 2019

Abstract
Introduction:
DLBCL is the most common non-Hodgkin lymphoma. There is increasing evidence that tumor microenvironment and host immunity play an important role in lymphoma progression. The absolute lymphocyte count (ALC), calculated from the complete blood count, is considered a surrogate for host immunity and has been proposed as a part of a score in combination with IPI. In contrast to a high ALC being associated with a good prognosis, high levels of blood monocytes (AMC) have just the opposite effect. The absolute lymphocytes/monocytes ratio (LMR) is under investigation and could be a useful prognostic marker in DLBCL. The aim of this study is to analyze the prognostic role or LMR in patients with DLBCL and definite a new score with the combination of RLM and R-IPI that could improve its risk definition.
Patients and methods:
All patients diagnosed of DLBCL from January-1999 to June-2013 at University Hospital Son Espases were retrospectively identified from Pathology and Pharmacy Departments registries to avoid selection bias. Only patients treated with R-CHOP +/- radiotherapy were included (N=79). Other regimes, consolidations or maintenance were excluded. The ALC and AMC were derived from pre-treatment CBC counts. LMR at diagnosis was calculated using ROC curves. Also, other standard prognostic factors including R-IPI and NCCN-IPI were obtained.
Results:
The cutoff for LMR was determined as 2.55. Main characteristics of patients are summarized in Table 1. Patients with LMR≤2.55 were associated with ECOG PS>1 (p=0.019), high LDH (p=0.025), a-IPI>1 (p=0.043) and NCCN-IPI intermediate-high (p=0.007). The complete response rate was similar in both groups: 82% for the LMR≤2.55cohort and 95% for LMR>2.55cohort(p=0.15). With a median follow up of 73 months (8-137) the progression free survival (PFS) was influenced by LMR, R-IPI, stage and B-symptoms. However, the multivariate analysis confirmed only LMR as independent significant predictor for PFS [HR 4,7; CI95% 1.5-14.1 (p=0.006)]. In the univariate analysis, only age, B-symptoms and NCCN-IPI were predictors for overall survival (OS). A prognostic score with the combination of LMR and R-IPI was stablished (LMR-R-IPI): patients with very good/good R-IPI and LMR>2.55 in one group and patients with poor R-IPI and/or LMR≤2.55 in other group with 6y-PFS of 96% and 59% (p=0.001), as well as 6y-OS of 87% and 64% (p=0.031), respectively. The multivariate analysis confirmed this new prognosis score as the only independent significant predictor for PFS and OS in our series.
Conclusions:
The addition of LMR improves the R-IPI in patients with DLBCL treated with R-CHOP. In our series, LMR-R-IPI was the only independent significant predictor for PFS and OS. This score identifies a high risk population that could benefit from different therapeutic approaches.
Table 1. Overall group LMR ≤ 2.55(n=40) LMR > 2.55(n=39) P Median age (range) 62 (20-87) 64 (20-87) 60 (29-79) 0.19 Sex M/F (%) 44 (56%) / 35 (44%) 20 (50%) / 20 (50%) 24 (61%) / 15 (38%) 0.37 ECOG PS > 1 20 (25%) 15 (37%) 5 (13%) 0.019 Stage III-IV 49 (62%) 26 (65%) 23 (59%) 0.65 B symptoms 32 (40%) 19 (47%) 13 (33%) 0.25 High LDH 41 (52%) 19 (53%) 15 (38%) 0.025 > 1 extranodal site 12 (15%) 8 (20%) 4 (10%) 0.35 Bulky mass 25 (32%) 16 (40%) 9 (23%) 0.15 a-IPI > 1 38 (48%) 24 (60%) 14 (36%) 0.043 Poor R-IPI 29 (37%) 19 (47%) 10 (26%) 0.062 NCCN-IPI:- Low- Low-intermediate- High-intermediate- High 9 (11%)34 (44%)30 (38%)5 (6%) 3 (8%)11 (28%)22 (56%)3 (8%) 6 (15%)23 (59%)8 (20%)2 (5%) 0.007 High Beta-2-microglobulin 36 (49%) 19 (53%) 17 (46%) 0.64

Disclosures
No relevant conflicts of interest to declare.