Abstract
Despite their critical roles in angiogenesis and host immunosuppression within the tumor microenvironment, the prognostic significance of myeloid-lineage cells expressing CD11b and CX3CR1 in diffuse large B-cell lymphoma (DLBCL) has not been well studied. We prospectively enrolled newly-diagnosed DLBCL patients at two Korean institutions between May 2011 and Aug 2015. CD11b+CX3CR1+ cells were analyzed by flow cytometry using peripheral blood (PB) and bone marrow (BM) aspirate samples before treatments. Eighty-nine patients (52 males) were enrolled. The median age was 65 years (range, 19–88 years). Thirty-seven patients (42%) were classified as high-intermediate or high risk according to the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI). Patients were categorized into either high or low PB-/BM-CD11b+CX3CR1+ monocyte group according to the cutoffs identified by the receiver-operating-characteristics analysis (PB, 3.68%; BM, 3.45%). The high PB-CD11b+CX3CR1+ monocyte group was significantly associated with high-intermediate and high risk NCCN-IPI group (P = 0.004). With a median follow-up of 27.7 months (range, 1.7-60.4 months), the low PB-CD11b+CX3CR1+ monocyte group showed significantly better overall survival (OS) than the high PB-CD11b+CX3CR1+ monocyte group (3-year, 92.3% vs. 51.2%, respectively; P < 0.001). In contrast, no significant difference was observed between the high and low BM-CD11b+CX3CR1+ monocyte groups. Among patients with high-intermediate to high risk NCCN-IPI, the high PB-CD11b+CX3CR1+ monocyte group showed significantly worse OS than the low PB-CD11b+CX3CR1+ monocyte group (3-year, 29.3% vs. 80.2%, respectively; P = 0.008). Taken together, PB-CD11b+CX3CR1+ monocyte percentage correlates with the NCCN-IPI risk stratification, which enables identification of subgroups with extremely poor clinical outcomes.
Highlights
Diffuse large B-cell lymphoma (DLBCL) is the most common histological subtype of aggressive non-Hodgkin’s lymphomas in Korea [1]
In the lower risk NCCN-IPI subgroup, the peripheral blood (PB)-CD11b+CX3CR1+ monocyte percentages failed to predict progressionfree survival (PFS) and overall survival (OS) (Figure 4C, 4D). In this prospective cohort study involving 89 diffuse large B-cell lymphoma (DLBCL) patients, we investigated the impact of PB
Our study demonstrated that the patients with high percentage of PBCD11b+CX3CR1+ monocytes were significantly associated with disease progression and death, compared to those with low percentage of PB-CD11b+CX3CR1+ monocytes
Summary
Diffuse large B-cell lymphoma (DLBCL) is the most common histological subtype of aggressive non-Hodgkin’s lymphomas in Korea [1]. Several investigators have reported that high circulating monocyte counts in combination with low lymphocyte counts have prognostic relevance in patients with DLBCL treated with R-CHOP, high-risk DLBCL patients [10,11,12]. These findings suggest that specific subsets of monocytes may be responsible for cancer prognosis in DLBCL. There has been no data on the prognostic relevance of CD11b+CX3CR1+ monocytes in DLBCL as well as its relationship with clinical variables This prospective study investigated the prognostic significance of CD11b+CX3CR1+ monocytes in peripheral blood (PB) and bone marrow (BM) on survival outcomes in newly-diagnosed DLBCL patients treated with R-CHOP immunochemotherapy
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