Abstract

Background

In the rituximab era, there are several studies that have reported the risk factors for central nervous system (CNS) involvement in non-Hodgkin lymphoma, but the same factors emerge, such as high international prognostic index (IPI) score, >1 extranodal site, elevated lactate dehydrogenase (LDH) level, poor performance status (PS), advanced stage, bone marrow involvement. Macrophages are an important component of the tumor microenvironment and the immune response to malignancy. Recently, elevated peripheral blood monocyte counts have been shown to be an independent marker associated with poor prognosis in patients with both non-Hodgkin and Hodgkin lymphoma.

Patients and methods

We reviewed data from a total of 1238 lymphoma patients(1185 non-Hodgkin lymphoma, 53 Hodgkin lymphoma) at our institution between February 2005 and May 2013. Of these, 42 patients (3.4%) developed CNS complications during the clinical course. Thirty patients out of these 42 (71.4%) were diagnosed with diffuse large B-cell lymphoma (DLBCL). Therefore, we focused on DLBCL. In this study, we retrospectively analyzed data from a total of 557 DLBCL patients, 30 patients (5.4%) who developed CNS involvement and 527 patients with DLBCL but without CNS involvement. This study was approved by the Institutional Review Board of the Cancer Institute Hospital of the Japanese Foundation for Cancer Research. The clinical features of all 557 DLBCL patients, including 30 patients with CNS involvement, are summarized in Table 1. CNS involvement was defined by the presence of at least one histologically confirmed CNS involvement; neuroimaging findings compatible with CNS involvement with lymphoma, in conjunction with consistent clinical presentation; and the absence of other clinically feasible diagnosis or positive cerebrospinal fluid (CSF) (lymphoma cells detected by cytology). The absolute monocyte counts (AMC) and monocyte ratio were derived from pre-treatment complete blood counts.

Table 1

Characteristics of DLBCL patients with or without CNS involvement

Characteristics DLBCL with CNS involvement n=30, n (%) DLBCL without CNS involvement n=527, n (%) P 
Gender; male 21 (70) 295 (56.0) 0.1840 
Age ≤60 years 16 (53.3) 172 (32.6) 0.0277 
Stage III-IV 23 (76.7) 208 (39.5) <0.0001 
IPI score 3-5 19 (63.3) 175 (33.2) 0.0013 
PS 2-4 12(40.0) 47 (8.9) <0.0001 
Elevated LDH level 18 (60) 231 (43.8) 0.0916 
Elevated soluble IL-2R level 28 (93.3) 380 (72.1) 0.0096 
Monocyte count ≥0.6 (×109/L) 12 (40) 117 (22.2) 0.0420 
Monocyte ratio ≥8 (%) 17 (56.7) 192 (36.4) 0.0325 
Characteristics DLBCL with CNS involvement n=30, n (%) DLBCL without CNS involvement n=527, n (%) P 
Gender; male 21 (70) 295 (56.0) 0.1840 
Age ≤60 years 16 (53.3) 172 (32.6) 0.0277 
Stage III-IV 23 (76.7) 208 (39.5) <0.0001 
IPI score 3-5 19 (63.3) 175 (33.2) 0.0013 
PS 2-4 12(40.0) 47 (8.9) <0.0001 
Elevated LDH level 18 (60) 231 (43.8) 0.0916 
Elevated soluble IL-2R level 28 (93.3) 380 (72.1) 0.0096 
Monocyte count ≥0.6 (×109/L) 12 (40) 117 (22.2) 0.0420 
Monocyte ratio ≥8 (%) 17 (56.7) 192 (36.4) 0.0325 
Pathological studies

Immunohistochemical analysis was carried out using mAbs against CD68 at our institution.

Results

The incidence of CNS involvement was 5.4%, 1.3% having CNS involvement at diagnosis with DLBCL. Intriguingly, absolute monocyte counts (AMC) ≥0.6 (×109/L) at diagnosis were significantly frequent in 30 DLBCL patients (p=0.0420) with CNS involvement, compared with in 527 DLBCL patients without CNS involvement. Furthermore, the monocyte ratio ≥8% in peripheral blood at diagnosis was significantly frequent in 30 DLBCL patients (p=0.0325) with CNS involvement, compared with in 527 DLBCL patients without CNS involvement. DLBCL patients with CNS involvement showed age ≤60 years, stage III-IV, IPI score ≥3, and PS ≥2, elevated soluble IL-2 receptor levels was significantly frequent, compared with in DLBCL patients without CNS involvement. Neither gender, elevated LDH level, white blood cell counts (WBC) differed significantly in the two groups. With regard to pathological immunohistochemistry, the numbers of CD68 positive cells in or around lymphoma samples did not differ in the 14 DLBCL patients with CNS involvement that we were able to analyze, compared with DLBCL patients without CNS involvement. CNS involvement free survival rate in DLBCL patients was significantly lower in AMC ≥0.6 (×109/L) and/or the monocyte ratio ≥8% (Log-rank test, P=0.0102) in peripheral blood at diagnosis, compared with in AMC less than 0.6 (×109/L) and the monocyte ratio less than 8%.

Conclusions

These results suggest that in DLBCL patients, AMC and monocyte ratios in peripheral blood at diagnosis are closely correlated with the risk of eventual CNS involvement. AMC and monocyte ratios in peripheral blood at diagnosis in DLBCL patients could be a useful prognostic marker for the risk of CNS involvement during the clinical course.

Disclosures:

Yokoyama:Chugai Pharmaceutical CO., LTD.: Consultancy. Nishimura:Chugai Pharmaceutical CO., LTD.: Consultancy.

Author notes

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Asterisk with author names denotes non-ASH members.