Higher Total Lymphocyte Counts Research Articles

Adequacy Assessment in Lymph Node Aspirates: An Exploratory Cytomorphologic Analysis of Negative Cervical Node Aspirates of Head and Neck Carcinomas

Introduction: Fine-needle aspiration cytology (FNAC) of lymph node is sensitive for detection of metastatic carcinoma but not without a significant false-negative rate. This study reviews clinicocytological features of negative node aspirates to identify predictive factors for establishing adequacy criteria. Methods: Negative FNAC specimens matched with neck dissection from a primary diagnosis of head and neck squamous cell, or undifferentiated (nasopharyngeal) carcinoma were reviewed for clinical and cytological parameters including lymphoid, inflammatory, and background components. Results: Slides from 86 lymph node aspirates including 50 positive for metastasis on follow-up were retrieved. Higher total lymphocyte count, lymphoid fragment count, germinal center fragment count, undifferentiated histology, presence of histiocytes and absence of blood were associated with a true negative cytologic diagnosis (p < 0.05), but not node size or location (p > 0.05). Undifferentiated histology, small lymphoid and germinal center fragments were independent factors indicative of a true negative diagnosis (p < 0.05). Large lymphoid fragments (p = 0.052) demonstrated a trend. Assessment of lymphoid components over five hotspots high-power fields (HPFs) was more robust in predictive value than only one hotspot. Receiver operating characteristic curve identified >10 small lymphoid, >20 large lymphoid and >2 germinal center fragment per five HPFs as optimal adequacy thresholds. Stricter total lymphocyte count cutoff accompanies increase of diagnostic accuracy, up to 0.67 for ≥5 HPFs with >500 lymphocytes. Conclusion: Total counts of lymphoid and germinal center fragments from multiple HPFs are useful in adequacy assessment of lymph node aspirates and improve diagnostic performance of FNAC in exclusion of metastatic carcinoma.

Prognostic significance of lymphocytic foci composition in minor salivary gland biopsies for severe disease flare and severity in Sjögren's syndrome: a 3-year follow-up cohort study.

This was an ambispective cohort study evaluating the prognostic significance of lymphocytic foci and its lymphoid composition in minor salivary gland biopsy (MSGB) for short-term disease flare and severity in Sjögren's syndrome (SS). The inclusion criteria comprised individuals meeting the ACR/EULAR 2016 criteria who underwent MSGB with an infiltration of more than 50 lymphocytes and received clinical diagnosis between September 2017 and December 2018. Patients with inadequate biopsy samples were excluded. The number of lymphocytic foci and their lymphoid composition in MSGB were assessed using immunofluorescence staining. Major organ damage and improvements in the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) were measured. Statistical analyses, including Cox and linear regressions, were conducted. A total of 78 patients with at least one lymphocytic focus were included in the study. The presence of higher T-cell counts in lymphocytic foci in MSGB was associated with severe disease flare, and a logarithmic transformation of T-cell count indicated increased risk (HR 1.96, 95% CI 0.91-4.21). Improvements in the ESSDAI were associated with higher total lymphocyte count and T- and B-cell numbers in the lymphoid composition of the lymphocytic foci. Seropositive patients exhibited higher T CD4+ cell numbers. Correlation analysis showed negative associations between age and lymphocytic foci and the T-cell count. Positive correlations were observed between antinuclear antibody (ANA) titers and total lymphocyte numbers. Patients with a higher number of T cells in the lymphocytic infiltrates of lymphocytic foci may have a two-fold risk of severe disease flare. The number of B cells and T CD4+ cells in the lymphocytic infiltrates of lymphocytic foci showed a weak but positive relation with the ESSDAI improvement during follow-up. Age and seropositivity appeared to influence the lymphoid composition of the lymphocytic foci.

Compassionate use of recombinant human IL-7-hyFc as a salvage treatment for restoring lymphopenia in patients with recurrent glioblastoma.

Addressing lymphopenia in cancer patients has been suggested as a novel immunotherapeutic strategy. As interleukin-7 (IL-7) is necessary for proliferation of lymphocytes and to increase total lymphocyte count (TLC), IL-7 therapy has been attempted in various cancers. Here, we describe the clinical results of treatment of recurrent glioblastoma (GBM) with a long-acting engineered version of recombinant human IL-7 (rhIL-7-hyFc). This prospective case series based on compassionate use was approved by the Ministry of Food and Drug Safety in South Korea. Primary outcomes were safety profile and TLC. Secondary outcomes were overall survival (OS) and progression-free survival (PFS). Among the 18 patients enrolled, 10 received rhIL-7-hyFc with temozolomide, 5 received rhIL-7-hyFc with bevacizumab, 1 received rhIL-7-hyFc with PCV chemotherapy, and 2 received rhIL-7-hyFc alone. Mean TLC of the enrolled patients after the first rhIL-7-hyFc treatment increased significantly from 1131 cells/mm3 (330-2989) at baseline to 4356 cells/mm3 (661-22,661). Higher TLCs were maintained while rhIL-7-hyFc was repeatedly administered. Median OS and PFS were 378 days (107-864 days) and 231 days (55-726 days), respectively. Our study reports that IL-7 immunotherapy can restore and maintain TLC during treatment with various salvage chemotherapies in recurrent GBM patients without serious toxicity.

Subclinical Inflammation and Adipose Tissue Lymphocytes in Pregnant Females With Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is accompanied by subclinical inflammation; however, little is known about local inflammation in adipose tissue and placenta. To analyze systemic and local subclinical inflammation and adipose tissue lymphocyte content and phenotype in pregnant women with and without GDM. Observational study. Academic hospital. Twenty-one pregnant women with GDM (GDM group), 16 pregnant women without GDM (non-GDM group) and 15 nonpregnant control women (N group). Serum samples taken at 28 to 32 (visit 1 [V1]) and 36 to 38 (V2) gestational weeks and 6 to 12 months after delivery (V3) in the GDM and non-GDM group and before elective gynecological surgery in the N group. Subcutaneous (SAT) and visceral adipose tissue (VAT) obtained during cesarean delivery or surgery. Serum levels and adipose tissue expression of proinflammatory cytokines, adipose tissue lymphocyte content and phenotype (for a subset of GDM and non-GDM subjects). Accented proinflammatory state in GDM was documented by increased circulating tumor necrosis factor-α (TNF-α) levels. In both groups of pregnant females total lymphocytes were higher in VAT compared to SAT. In GDM subjects B cells and NKT cells were higher in SAT compared to VAT and T helper cells were increased relative to SAT of non-GDM group, while no intercompartmental adipose tissue differences were seen in non-GDM women. Pregnant females had higher total lymphocyte count in VAT relative to SAT regardless of GDM. In addition to increased systemic subclinical inflammation, GDM was associated with significant differences in lymphocyte composition between subcutaneous and visceral adipose tissue depots.

Impact of Awake Breast Cancer Surgery on Postoperative Lymphocyte Responses.

Surgical stress and anesthesia affect the patient's immune system. Analysis of the lymphocyte response after breast-conserving surgery was conducted to investigate the differences between effects after general and local anesthesia. Fifty-six patients with breast cancer were enrolled for BCS through local or general anesthesia. Total leukocytes, total lymphocytes, lymphocyte-subsets including CD3+, CD19+, CD4+, CD8+, CD16+CD56+ and CD4+/CD8+ ratio was examined at baseline and on postoperative days 1, 2 and 3. Baseline data showed no statistical difference between the two groups. Within-group ANOVA test showed significant differences for total leukocyte count (p<0.001), total lymphocyte count (p=0.009) and proportion of natural-killer cells (p=0.01) in the control group. Between-group analysis showed lower median values of total lymphocytes in the awake surgery group on postoperative days 1, 2 and 3 (p=0.001, p=0.02 and p=0.01, respectively) when compared to the control group. Patients who underwent surgery under general anesthesia had higher total lymphocyte counts on postoperative day 2 (p=0.04). In this randomized study, breast-conserving surgery plus local anesthesia had a lower impact on postoperative lymphocyte response when compared to the same procedure performed under general anesthesia.

Total lymphocyte count, neutrophil-lymphocyte ratio, and platelet-lymphocyte ratio as prognostic factors in advanced non-small cell lung cancer with chemoradiotherapy.

ObjectiveThe objective of this study was to investigate the prognostic significance and the efficacy evaluation of total lymphocyte count (TLC), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in advanced non–small cell lung cancer (NSCLC) patients treated with chemoradiotherapy.Patients and methodsA total of 389 advanced NSCLC patients who received chemoradiotherapy from 2011 to 2016 were enrolled in this retrospective study. TLC, NLR, and PLR were analyzed with overall survival (OS). Survival data were identified with the Kaplan–Meier method and optimal cutoff values with receiver operating characteristic curves.ResultsThe median OS for all patients was 18.37 months. Pretreatment and median baseline TLC was 2.47×103/μL (±0.78); NLR, 3.15 (±3.96); and PLR, 143.82 (±91.77); corresponding cutoffs were 2.4, 3.4, and 136.1. Higher TLC was associated with superior median OS (21.78 vs 15.66 months, P<0.001), and higher NLR and PLR with worse median OS (NLR: 14.13 vs 23.8 months, P<0.001; PLR: 15.49 vs 22.04 months, P<0.001).ConclusionThe lymphopenia indicators (TLC, NLR, and PLR) were significant prognostic indicators of survival in advanced NSCLC patients treated with chemoradiotherapy.

Prognostic Significance of Total Lymphocyte Count, Neutrophil-to-lymphocyte Ratio, and Platelet-to-lymphocyte Ratio in Limited-stage Small-cell Lung Cancer

BackgroundWe sought reliable markers of survival and disease control among patients treated for limited-stage small-cell lung cancer (LS-SCLC). Patients and MethodsSubjects were 122 patients given (chemo)radiotherapy for LS-SCLC at MD Anderson in 2002 through 2015. Pretreatment total lymphocyte count (TLC), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were analyzed for associations with overall (OS) and progression-free survival. Optimal cutoff values were identified with receiver operating characteristic curves and survival probabilities with the Kaplan-Meier method. ResultsPretreatment TLC was 1.86 × 103/μL (±0.88); NLR, 3.44 (±3.69); and PLR, 170.53 (±101.56); corresponding cutoffs were 1.9, 2.9, and 140.1. Higher TLC was associated with superior median and 2-year OS (17.4 vs. 15.7 months and 33% vs. 29%; P = .029), and higher NLR and PLR with worse median and 2-year OS (NLR: 14.9 vs. 17.8 months, 29% vs. 31%; P = .026; PLR: 14.8 vs. 18.9 months, 24% vs. 37%; P = .009). Multivariate Cox regression adjusted for age, disease stage, number of chemotherapy cycles, and use of prophylactic cranial irradiation confirmed the links between high TLC and superior OS (hazard ratio [HR] 0.55; 95% confidence interval [CI], 0.32-0.94; P = .028) and between high NLR and PLR and inferior OS (NLR: HR, 1.86; 95% CI, 1.15-3.01; P = .011; PLR: HR, 1.72; 95% CI, 1.06-2.82; P = .030). ConclusionsBaseline lymphopenia was an indicator of poor prognosis in patients with LS-SCLC.

Associations Between Nutritional Parameters and Clinicopathologic Factors in Patients with Gastric Cancer: A Comprehensive Study

ABSTRACTThe aim of this study was to assess and analyze the nutritional status of gastric cancer (GC) patients. The analysis included 207 patients with GC treated in a large center of oncology. Patients were divided into two groups according to the cutoff value of the mean prognostic nutritional index (PNI): those with a PNI < 52.78 and those with a PNI ≥ 52.78. The higher PNI was associated with lower age and higher total protein and hemoglobin levels (P < 0.01). The total lymphocyte count (P = 0.02), albumin, total protein and PNI (P < 0.01) were significantly higher in stable-weight patients and lower in the group with weight loss > 10% (P = 0.000031). Body mass index (BMI) after disease recognition, albumin and total protein (0.003) levels, total lymphocyte count, and PNI were significantly lower in patients with nutritional risk. Significantly lower BMI before disease and BMI after disease recognition were noted in smoking patients. Significantly higher total lymphocyte count was observed in smoking patients (P < 0.01). Significantly lower PNI was noted in tumors with lymph node metastasis (N+). G3 tumors were associated with the lowest total lymphocyte count (P = 0.01). Assessment of nutritional status using PNI calculation should be the standard management of patients with GC before treatment.

Association between treatment-related lymphopenia and overall survival in elderly patients with newly diagnosed glioblastoma.

Management of patients with glioblastoma (GBM) often includes radiation (RT) and temozolomide (TMZ). The association between severe treatment-related lymphopenia (TRL) after the standard chemoradiation and reduced survival has been reported in GBM patients with the median age of 57. Similar findings were described in patients with head and neck, non-small cell lung, and pancreatic cancers. This retrospective study is designed to evaluate whether elderly GBM patients (age ≥65) develop similar TRL after RT/TMZ and whether such TRL is associated with decreased survival. Serial total lymphocyte counts (TLC) were retrospectively reviewed in patients (age ≥65) with newly diagnosed GBM undergoing RT/TMZ and associated with treatment outcomes. Seventy-two patients were eligible: median KPS 70, median age 71 years (range 65-86) with 56 % of patients >70 years, 53% female, 31% received RT ≤45 Gy. Baseline median TLC was 1100 cells/mm(3) which fell by 41% to 650 cells/mm(3) 2 months after initiating RT/TMZ (p < 0.0001). Patients with TLC <500 cells/mm(3) at 2 months had a shorter survival than those with higher TLCs with a median overall survival of 4.6 versus 11.6 months, respectively. Multivariate analysis revealed a significant association between TRL and survival (HR 2.76, 95% CI 1.30-5.86, p = 0.008). Treatment-related lymphopenia is frequent, severe, and an independent predictor for survival in elderly patients with GBM. These findings add to the body of evidence that immunosuppression induced by chemoradiation is associated with inferior clinical outcomes. Prospective studies are needed to confirm these findings suggesting that immune preservation is important in this cancer.

Association between severe treatment‐related lymphopenia and progression‐free survival in patients with newly diagnosed squamous cell head and neck cancer

Severe treatment-related lymphopenia occurs commonly in many cancers and is associated with early tumor progression. Data are lacking as to whether this occurs in squamous cell head and neck cancer. Serial total lymphocyte counts were retrospectively reviewed in patients with newly diagnosed squamous head and neck cancer undergoing chemoradiation and associated with treatment outcomes. The median baseline total lymphocyte count in 56 patients was 1660 cells/mm(3) , which fell by 73% to 445 cells/mm(3) 2 months after initiating chemoradiation (p < .0001). Human papillomavirus negative (HPV-) patients with a total lymphocyte count <500 cells/mm(3) at 2 months had significantly earlier disease progression than those with higher total lymphocyte counts (hazard ratio [HR], 5.75; p = .045). Baseline total lymphocyte counts were normal, but at 2 months approximately 60% of patients had severe treatment-related lymphopenia regardless of HPV status. Severe treatment-related lymphopenia in HPV- patients is independently associated with earlier disease progression. Prospective studies are needed to confirm these findings, which suggest that immune preservation is important in this cancer.

Abstract 4167: Prognostic Importance of Nutritional Status in Patients with Chronic Heart Failure

Background: Nutritional abnormalities are common among patients with chronic heart failure (CHF). However, little is known regarding clinical implication to evaluate the nutritional status in CHF patients. In this study, we examined the prognostic impact of nutrition-related factors, including serum albumin level (ALB), total lymphocyte count (TLC), and body mass index (BMI) in patients with CHF. Methods: We prospectively enrolled 280 stable patients with stage-C/D CHF since February 2000. Kaplan-Meier analyses and multivariate Cox regression analyses were performed to evaluate the association between the mortality and the nutrition-related factors mentioned above. Covariables used in the multivariate models were ALB, TLC, BMI, hemoglobin concentration, left ventricular ejection fraction, etiology of CHF, serum creatinine level, and age at the entry. Results: The mean age of the study population was 61.2±14.9 years and the mean follow-up period was 2.4±1.5 years. Kaplan-Meier analyses showed that the incidences of all-cause mortality were significantly higher in patients with lower ALB, lower TLC, or lower BMI as compared those without the nutritional abnormalities (Figure ). Multivariate analyses revealed that higher TLC was an independent significant predictor of freedom from cardiac-cause death (HR 0.9993, p=0.016) and higher ALB was significantly associated with increased survival (HR 0.563, p=0.03). Conclusions: The evaluation of nutritional status may be a powerful and cost-effective tool in predicting the mortality of patients with CHF. Further research is necessary to evaluate the importance of nutritional improvement in such patients.

Total Lymphocyte Count: A Promising Prognostic Index of Mortality in Patients on CAPD

In view of the limitations of albumin in peritoneal dialysis (PD), we set out to evaluate whether total lymphocyte counts (TLC) could serve as a better prognostic indicator. We were also interested in how these parameters might differ between PD and hemodialysis (HD) patients. In a retrospective study, we reviewed 113 charts from our dialysis unit. All laboratory analyses were performed by the Department of Clinical Pathology of the Nassau County Medical Center, using standard procedures. Intact parathyroid hormone (PTH) was sent out to Nichols Laboratories. All patients originated from the renal clinic at Nassau County Medical Center, a 612 bed public hospital. The 38 PD and 75 HD patients selected had been receiving dialysis for at least 12 months and up to 3 years. The PD patients received either continuous ambulatory and/or cycler PD. For the survivors, the averages of their routine chemical analyses were considered their representative values. For the nonsurvivors, the most recent laboratory values prior to their end point were considered. Mortality or apparent malnutrition leading to transfer to HD represented the end points for PD patients. Mortality alone was used as the end point for HD patients. Within the PD population, serum albumin was not significantly lower in nonsurvivors compared to survivors, while the TLC was significantly lower in nonsurvivors (1277 +/- 146/mm3 vs 2249 +/- 236/mm3, p = 0.0036). The HD population demonstrated a significant difference in both TLC and serum albumin levels between its two prognostic groups; albumin was the better discriminator. Nonsurvivors had a 20% lower serum albumin than did the survivors (27.0 +/- 1.6 g/L vs 34.0 +/- 0.5 g/L, p = 0.0001). Patients on PD had a higher TLC than those on HD (p = 0.0001). In the HD population, but not in the PD population, both serum albumin and TLC were significantly higher in the group that survived. Serum albumin is a more powerful discriminator of mortality in the HD population, while TLC is a better discriminator of mortality in the PD population. For uncertain reasons, PD patients have a higher TLC than those on HD.