Monocyte count at diagnosis is a prognostic parameter in diffuse large B-cell lymphoma: results from a large multicenter study involving 1191 patients in the pre- and post-rituximab era

Abstract

ABSTRACTand prednisone (CHOP), CHOP-like, or third-generation anthracycline-containing regimens, with or without rituximab; 521 patients (51%) received the above therapies with rituximab as part of the regimen. Statistical analysisSurvival was assessed by Kaplan-Meier estimates 14 and compared by risk groups using the log-rank test and Cox proportional hazard analysis. 15 The proportional hazard assumption was verified graphically by means of scaled Schoenfeld residuals. 16 The effect size was reported as a hazard ratio (HR) with the associated 95% confidence interval (95% CI).We 20 Thereafter we chose cut-off values with the best power in discriminating patients with either good or poor outcome, after adjusting for the IPI. The performance of the different cut-offs was checked by means of the hazard ratios and respective z-score (from Wald's test) and by comparing the discriminating power, expressed as Harrell's C index.21 The Harrell's C standard error and 95% confidence interval were estimated by means of a jackknife procedure. 22 We arbitrarily chose the cut-off on the basis of the compromise between the discriminative power of the factor and the size of the group at greatest risk. Whereas we analyzed different cut-off points for AMC and LMR, given the broad agreement regarding the definition of lymphopenia as an ALC<1000/mm 3 , we used this cut-off for ALC. 23,24The effect of rituximab on the prognostic power of AMC, ALC and LMR was evaluated by interacting prognostic factors with rituximab, after adjustment by IPI score. Results Patients' characteristicsWe analyzed data from 1191 patients with DLBCL diagnosed between 1993 and 2010. Patients with missing data on monocyte or lymphocyte counts or one of the IPI parameters before treatment were excluded, and the final cohort consisted of 1017 patients.The median age at diagnosis was 60 years (range, 25-81 years) and 47% of the patients were more than 60 years old; 53% were male and 54% of the patients had advanced, stage III-IV disease (Table 1); the clinical characteristics at diagnosis were comparable in the Israeli and Italian cohorts.A total of 496 patients (49%) were treated with chemotherapy alone, while 521 (51%) received immunochemotherapy including rituximab. The median follow-up of the entire cohort was 48 months (range, 0.2-180 months), and 64 months for patients still alive. Overall, 317 events were recorded with a death rate of 7.4x100 person-years (95% CI: 6.6-8.3x100 person-years) and a 5-year overall survival of 68% (95% CI: 65-71%). The overall survival at 5 years in patients treated with or without rituximab was 68% in both groups (HR 0.98, P=0.864). It is noteworthy that in our series there was an association between the use of rituximab and the IPI score; in the group of patients with IPI 0-2, only 43% of patients had been treated with rituximab compared to 70% of the patients with IPI 3-5. In a multivariate analysis, adjusted for IPI score, the risk of death in patients treated with rituximab was reduced by 30% (P=0.002). Absolute monocyt...

Prognostic Significance of Monocytes and Monocytic Myeloid-Derived Suppressor Cells in Diffuse Large B-Cell Lymphoma Treated with R-CHOP

“…Single-factor analysis or multi-factor analysis showed that AMC and ALC both were the independent poor prognostic factor and both of them adjusted to R-IPI may identify the high-risk patients in DLBCL and FL [15,17]. A multi-center study enrolled 1017 patients showed that AMC > 630 mm³ at diagnosis was a predictor to identify the high-risk patients in rituximab era [16]. During the period of R-CHOP treatment for patients with DLBCL, peripheral ALC/AMC ratio recovery may predict prognosis and ALC/AMC < 1.1 was an independent parameter of OS and PFS [29].…”

The prognostic utility and the association of serum light chains (free and total) and absolute lymphocyte count in patients with newly diagnosed diffuse large B-cell lymphoma

“…The International Prognostic Index (IPI), which includes parameters such as age, stage, number of extranodal sites, performance status and serum lactate dehydrogenase (LDH) levels, is wellknown scoring system for risk stratification of DLBCL patients at diagnosis. However, the prognostic discriminating power of IPI alone diminished in the rituximab or immunochemotherapy era [5,6]. Gene-expression profiling, immunohistochemistry-based detection of prognostic biomarkers and early interim analysis with positron emission tomography (PET) had been explored as predictors that may identify high-risk patients [7][8][9][10][11].…”

Absolute peripheral monocyte count at diagnosis predicts central nervous system relapse in diffuse large B-cell lymphoma

“…Recently, elevated peripheral blood monocyte counts have been shown to be an independent predictor of poor prognosis in patients with both non-Hodgkin and Hodgkin lymphoma. [5][6][7][8][9][10] Here, we investigated the relationship between peripheral blood monocytes at diagnosis and prognosis, focusing on CNS relapse in DLBCL.…”