The lower peripheral blood lymphocyte/monocyte ratio assessed during routine follow-up after standard first-line chemotherapy is a risk factor for predicting relapse in patients with diffuse large B-cell lymphoma

Abstract

A specific predictor during routine follow-up to ascertain risk for relapse after standard first-line chemotherapy in non-Hodgkin's lymphoma (NHL) has not been identified, although blood counts, lactate dehydrogenase (LDH) and imaging studies, such as computed tomography (CT) scans or positron emission tomography, have been recommended. Therefore, we studied the absolute lymphocyte count/absolute monocyte count ratio (ALC/AMC ratio) as a marker of poststandard first-line chemotherapy for predicting relapse in patients with diffuse large B-cell lymphoma (DLBCL). 220 consecutive DLBCL patients, originally diagnosed, treated with CHOP or R-CHOP and followed up at two institutions. ALC/AMC ratio was obtained at the time of confirmed relapse or last follow-up. Patients at the time of confirmed relapse (n = 163) had a lower ALC/AMC ratio compared with those at last follow-up (n = 57) (P < 0.001). ALC/AMC ratio at the time of confirmed relapse was a strong predictor for relapse with an area under the curve = 0.813 (P < 0.001). The sensitivity and specificity for ALC/AMC ratio at the time of confirmed relapse or at last follow-up were 68.1% and 87.7%, respectively, and the relative risk of relapse with an ALC/AMC ratio < 2.8 at the time of confirmed relapse or at last follow-up was 1.845 with an odds ratio of 15.247 (95% cumulative incidence: 6.473–35.916) after CHOP or R-CHOP in DLBCL. Patients with an ALC/AMC ratio (<2.8) had a higher cumulative hazard rate of relapse compared with an ALC/AMC ratio (≥2.8) (P < 0.001). This study suggests that the lower ALC/AMC ratio can be used as a marker to assess risk of DLBCL relapse during routine follow-up after standard first-line chemotherapy.

Introduction

Despite recent major advances in treating diffuse large B-cell lymphoma (DLBCL) with dose-intense regimens and the addition of the anti-CD20 monoclonal antibody rituximab, a significant proportion of patients will experience disease relapse, mainly during the first two years after completing therapy [1]. A primary aim of follow-up is to detect early relapse, with the hope of improving outcome following salvage chemotherapy. The current recommendation for long-term follow-up in patients with DLBCL, who are not participating in clinical trials, by the National Comprehensive Cancer Network is a follow-up every 3–6 months or as clinically indicated [2]. The European Society of Medical Oncology's recommendations for follow-up in NHL include follow-up every 3 months for 1 years, every 6 months for 2 years and then once a year [3].

Risk factors used to assess clinical outcomes in DLBCL patients treated with standard therapy are identified before treatment implementation, such as the international prognostic index (IPI) [4], gene expression profiling [5] or immunohistochemistry-based detection of prognostic biomarkers [6], [7]. Even though these risk factors are useful to guide physicians in the identification of patients who would benefit from standard therapy, a limitation of these is that they are tested at one point in time [8]. An inexpensive factor that could be monitored during follow-up after standard therapy and predicts relapse would be needed to help to identify patients who might require further evaluation for relapse. In DLBCL, LDH has been reported to have a sensitivity of 42% and a specificity of 85% to predict relapse during follow-up [9]. Recently, absolute lymphocyte count/absolute monocyte count ratio (ALC/AMC ratio) at diagnosis, as a simple biomarker combining an estimate of host immune homeostasis and tumor microenvironment, was recently shown to be an independent prognostic indicator in DLBCL [10] and HL [11], [12], [13]. However, to our best knowledge, there is no data available on whether ALC/AMC ratio can help in detecting relapse. Thus, we set out to evaluate the prognostic value of peripheral ALC/AMC ratio at follow-up as a marker to assess relapse during follow-up.