Peripheral Blood Absolute Lymphocyte/Monocyte Ratio Recovery During RCHOP Treatment Cycles Predicts Clinical Outcomes In Diffuse Large B-Cell Lymphoma
Authors: Porrata Luis F. , Ristow Kay M. , Habermann Thomas M , Witzig Thomas E , Colgan Joseph P. , Inwards David J. , Ansell Stephen M , Micallef Ivana N. , Johnston Patrick B. , Nowakowski Grzegorz S. , Thompson Carrie A , Markovic Svetomir N. 
Published: October 2019

Abstract
The peripheral blood absolute lymphocyte/monocyte ratio at diagnosis (ALC/AMC-DX) predicts survival in diffuse large B-cell lymphoma (DLBCL). However, a limitation of the ALC/AMC-DX is its inability to sequentially assess the host/tumor interaction during treatment. Therefore, we studied the ALC/AMC ratio, as a surrogate marker of host immunity (i.e., ALC) and tumor microenvironment (i.e., AMC), at each RCHOP treatment cycle as a predictor for clinical outcomes. From 2002 until 20011, 107 DLBCL patients originally diagnosed, treated with six cycles of RCHOP, and followed at Mayo Clinic qualified for the study. Using the receiver operating characteristic and internally validated using the k-fold cross validation; an ALC/AMC ratio ≥ 1.1 was identified as the cut-off value at each RCHOP treatment cycle to discriminate for the binary clinical outcome of death/survival. Univariate analysis revealed the ALC/AMC ratio ≥ 1.1 at each RCHOP treatment cycle was a predictor for overall survival (OS) and progression-free survival (PFS). To explore whether the patterns of ALC/AMC ratio recovery during the RCHOP treatment cycles had a prognostic value, we performed an unsupervised hierarchical clustering on the studied ALC/AMC ratio and identified four patient clusters, A-D. Eighty percent of patients in cluster C had an ALC/AMC ratio ≥ 1.1 during all the cycles, the other 20% had an ALC/AMC ratio ≥1.1 in one cycle; in cluster D patients, the ALC/AMC ratio was ≥ 1.1 between cycles 2 and 5 and none had an ALC/AMC ratio < 1.1; in cluster A patients, 73% of patients only had an ALC/AMC ratio ≥ 1.1 in one cycle and 27% in two cycles; and cluster B patients had 85% of patients with an ALC/AMC ratio < 1.1 during all the cycles. Inferior OS and PFS were progressively observed in clusters of patients with fewer cycles achieving an ALC/AMC ratio ≥ 1.1. Patients in clusters C had superior outcomes compared with patients in clusters B. Thus, we dichotomized patients into patients with an ALC/AMC ratio ≥ 1.1 during any cycle versus patients with an ALC/AMC ratio < 1.1 during all cycles. By multivariate analysis, the stratification of patients into ALC/AMC ≥ 1.1 during any cycle versus ALC/AMC < 1.1 during all cycles was an independent predictor for OS [Hazard ratio (HR) = 0.02, 95% CI (0.006-0.08), p< 0.0001], and PFS [HR = 0.06, 95% CI (0.02-0.15, p< 0.0001] when compared with the International Prognostic index The median OS for patients with an ALC/AMC ratio ≥ 1.1 during any cycle versus patients with an ALC/ACM ratio < 1.1 during all cycles was not reached versus 1.7 years with 5 years OS rates of 97% (95% CI, 90%-99%) versus 0%, p< 0.0001, respectively. The median PFS for patients with an ALC/AMC ratio ≥ 1.1 during any cycle versus patients with an ALC/AMC ratio < 1.1during all cycles was not reached versus 0.9 years with 5 years PFS rates of 83% (95% CI, 72%-90%) versus 0%, p< 0.0001, respectively. The ALC/AMC ratio during RCHOP treatment cycles is a predictor for survival and provides a platform to develop therapeutic modalities to manipulate the ALC/AMC ratio during chemotherapy to improve clinical outcomes in DLBCL.

Disclosures:
No relevant conflicts of interest to declare.