Lower Monocyte Counts Research Articles

Clinical and radiologic correlates of neurotoxicity after axicabtagene ciloleucel in large B-cell lymphoma

AbstractNeurotoxicity or immune effector cell-associated neurotoxicity syndrome (ICANS) is the second most common acute toxicity after chimeric antigen receptor (CAR) T-cell therapy. However, there are limited data on the clinical and radiologic correlates of ICANS. We conducted a cohort analysis of 100 consecutive patients with relapsed or refractory large B-cell lymphoma (LBCL) treated with standard of care axicabtagene ciloleucel (axi-cel). ICANS was graded according to an objective grading system. Neuroimaging studies and electroencephalograms (EEGs) were reviewed by an expert neuroradiologist and neurologist. Of 100 patients included in the study, 68 (68%) developed ICANS of any grade and 41 (41%) had grade ≥3. Median time to ICANS onset was 5 days, and median duration was 6 days. ICANS grade ≥3 was associated with high peak ferritin (P= .03) and C-reactive protein (P= .001) levels and a low peak monocyte count (P= .001) within the 30 days after axi-cel infusion. Magnetic resonance imaging was performed in 38 patients with ICANS and revealed 4 imaging patterns with features of encephalitis (n = 7), stroke (n = 3), leptomeningeal disease (n = 2), and posterior reversible encephalopathy syndrome (n = 2). Abnormalities noted on EEG included diffuse slowing (n = 49), epileptiform discharges (n = 6), and nonconvulsive status epilepticus (n = 8). Although reversible, grade ≥3 ICANS was associated with significantly shorter progression-free (P= .02) and overall survival (progression being the most common cause of death;P= .001). Our results suggest that imaging and EEG abnormalities are common in patients with ICANS, and high-grade ICANS is associated with worse outcome after CAR T-cell therapy in LBCL patients.

Lymphocyte to monocyte ratio-based nomogram for predicting outcomes of hepatocellular carcinoma treated with sorafenib

The ability of the pretreatment lymphocyte to monocyte ratio (LMR) to predict outcomes of patients with hepatocellular carcinoma (HCC) receiving sorafenib is not conclusively determined. We retrospectively studied patients treated with sorafenib for HCC in two tertiary referral centres in Asia and North America. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Predictive factors for the outcomes were determined by Cox proportional hazards models. A risk assessment tool was developed. Compared to the North America cohort, the Asia cohort was more heavily pretreated (72.1% vs. 35.2%; p < 0.001), had higher hepatitis B virus infection (87.6% vs. 5.6%; p < 0.001), and more distant metastases (83.2% vs. 25.4%; p < 0.001). Lower monocyte count in the Asia cohort (median 462.7 vs. 600.0/μL; p = 0.023) resulted in a higher LMR (median 2.6 vs. 1.8; p < 0.001). High LMR was associated with a significantly higher OS [hazard ratio (HR) 0.88; 95% confidence interval (CI) 0.81‒0.97; p = 0.007]. This was confirmed in a sensitivity analysis including patients treated in Asia only (HR 0.89; 95% CI 0.81‒0.97; p = 0.010). An OS nomogram was constructed with the following variables selected in the multivariate Cox model: LMR, treatment location, previous treatment, performance status, alpha-fetoprotein, lymph node metastasis, and Child‒Pugh score. The concordance score was 0.71 (95% CI, 0.67‒0.75). LMR did not predict PFS. LMR measured before sorafenib administration predicts OS in advanced HCC patients. Our OS nomogram, incorporating LMR, can be offered to clinicians to improve their ability to assess prognosis, strengthen the prognosis-based decision-making, and inform patients in the clinic.

IL-6–based mortality risk model for hospitalized patients with COVID-19

BackgroundCoronavirus disease 2019 (COVID-19) has rapidly become a global pandemic. Because the severity of the disease is highly variable, predictive models to stratify patients according to their mortality risk are needed.ObjectiveOur aim was to develop a model able to predict the risk of fatal outcome in patients with COVID-19 that could be used easily at the time of patients' arrival at the hospital.MethodsWe constructed a prospective cohort with 611 adult patients in whom COVID-19 was diagnosed between March 10 and April 12, 2020, in a tertiary hospital in Madrid, Spain. The analysis included 501 patients who had been discharged or had died by April 20, 2020. The capacity of several biomarkers, measured at the beginning of hospitalization, to predict mortality was assessed individually. Those biomarkers that independently contributed to improve mortality prediction were included in a multivariable risk model.ResultsHigh IL-6 level, C-reactive protein level, lactate dehydrogenase (LDH) level, ferritin level, d-dimer level, neutrophil count, and neutrophil-to-lymphocyte ratio were all predictive of mortality (area under the curve >0.70), as were low albumin level, lymphocyte count, monocyte count, and ratio of peripheral blood oxygen saturation to fraction of inspired oxygen (SpO2/FiO2). A multivariable mortality risk model including the SpO2/FiO2 ratio, neutrophil-to-lymphocyte ratio, LDH level, IL-6 level, and age was developed and showed high accuracy for the prediction of fatal outcome (area under the curve 0.94). The optimal cutoff reliably classified patients (including patients with no initial respiratory distress) as survivors and nonsurvivors with 0.88 sensitivity and 0.89 specificity.ConclusionThis mortality risk model allows early risk stratification of hospitalized patients with COVID-19 before the appearance of obvious signs of clinical deterioration, and it can be used as a tool to guide clinical decision making.

Low Absolute Lymphocyte Counts in the Peripheral Blood Predict Inferior Survival and Improve the International Prognostic Index in Testicular Diffuse Large B-Cell Lymphoma.

Low absolute lymphocyte counts (ALC) and high absolute monocyte counts (AMC) are associated with poor survival in patients with diffuse large B-cell lymphoma (DLBCL). We studied the prognostic impact of the ALC and AMC in patients with testicular DLBCL (T-DLBCL). T-DLBCL patients were searched using Southern Finland University Hospital databases and the Danish lymphoma registry. The progression free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier and Cox proportional hazards methods. We identified 178 T-DLBCL patients, of whom 78 (44%) had a low ALC at diagnosis. The ALC did not correlate with survival in the whole cohort. However, among the patients treated with rituximab (R) containing regimen, a pre-therapeutic low ALC was associated with an increased risk of progression (HR 1.976, 95% CI 1.267–3.086, p = 0.003). Conversely, intravenous (iv) CNS directed chemotherapy translated to favorable outcome. In multivariate analyses, the advantage of an iv CNS directed chemotherapy was sustained (PFS, HR 0.364, 95% CI 0.175–0.757, p = 0.007). The benefit of R and intravenous CNS directed chemotherapy was observed only in non-lymphopenic patients. The AMC did not correlate with survival. A low ALC is an adverse prognostic factor in patients with T-DLBCL. Alternative treatment options for lymphopenic patients are needed.

Nomogram for predicting pathological complete response to neoadjuvant chemotherapy in patients with advanced gastric cancer.

BACKGROUNDSurvival benefit of neoadjuvant chemotherapy (NAC) for advanced gastric cancer (AGC) is a debatable issue. Studies have shown that the survival benefit of NAC is dependent on the pathological response to chemotherapy drugs. For those who achieve pathological complete response (pCR), NAC significantly prolonged prolapsed-free survival and overall survival. For those with poor response, NAC yielded no survival benefit, only toxicity and increased risk for tumor progression during chemotherapy, which may hinder surgical resection. Thus, predicting pCR to NAC is of great clinical significance and can help achieve individualized treatment in AGC patients.AIMTo establish a nomogram for predicting pCR to NAC for AGC patients.METHODSTwo-hundred and eight patients diagnosed with AGC who received NAC followed by resection surgery from March 2012 to July 2019 were enrolled in this study. Their clinical data were retrospectively analyzed by logistic regression analysis to determine the possible predictors for pCR. Based on these predictors, a nomogram model was developed and internally validated using the bootstrap method.RESULTSpCR was confirmed in 27 patients (27/208, 13.0%). Multivariate logistic regression analysis showed that higher carcinoembryonic antigen level, lymphocyte ratio, lower monocyte count and tumor differentiation grade were associated with higher pCR. Concordance statistic of the established nomogram was 0.767.CONCLUSIONA nomogram predicting pCR to NAC was established. Since this nomogram exhibited satisfactory predictive power despite utilizing easily available pretreatment parameters, it can be inferred that this nomogram is practical for the development of personalized treatment strategy for AGC patients.

Outcome of patients with chlorpyrifos intoxication.

There is a paucity of literature analyzing outcome of chlorpyrifos intoxication. A total of 40 patients with chlorpyrifos intoxication were seen at Chang Gung Memorial Hospital between 2008 and 2017. Patients were stratified into two subgroups according to their prognosis, as good (n = 12) or poor (n = 28). Good prognosis group were defined as patients who survived without serious complications, and poor prognosis group included patients who died and survived after development of severe complications. Demographic, clinical, laboratory, and mortality data were obtained for analysis. Patients aged 53.8 ± 16.3 years and most were male (80.0%). All patients (100.0%) developed acute cholinergic crisis such as emesis (45.0%), respiratory failure (42.5%), tachycardia (30.0%), kidney injury (22.5%), and seizure (7.5%). Intermediate syndrome developed in 12.5% of patients, but none had delayed neuropathy (0%). The poor prognosis group suffered higher incidences of respiratory failure (p = 0.011), kidney injury (p = 0.026), and prolonged corrected QT interval (p = 0.000), and they had higher blood urea nitrogen level (p = 0.041), lower Glasgow coma scale score (p = 0.011), and lower monocyte count (p = 0.023) than good prognosis group. All patients were treated with atropine and pralidoxime therapy, but six patients (15.0%) still died of intoxication. In a multivariate logistic regression model, blood urea nitrogen was a significant risk factor for poor prognosis (odds ratio: 1.375, 95% confidence interval: 1.001-1.889, p = 0.049). Nevertheless, no mortality risk factor could be identified. The mortality rate of patients with chlorpyrifos intoxication was 15.0%. Furthermore, acute cholinergic crisis, intermediate syndrome, and delayed neuropathy developed in 100.0%, 12.5%, and 0% of patients, respectively.

Modeling Viral Suppression, Viral Rebound and State-Specific Duration of HIV Patients with CD4 Count Adjustment: Parametric Multistate Frailty Model Approach.

IntroductionCombination antiretroviral therapy has become the standard care of human immunodeficiency virus (HIV)-infected patients and has further led to a dramatically decreased progression probability to acquired immune deficiency syndrome (AIDS) for patients under such a therapy. However, responses of the patients to this therapy have recorded heterogeneous complexity and high dynamism. In this paper, we simultaneously model long-term viral suppression, viral rebound, and state-specific duration of HIV-infected patients.MethodsFull-parametric and semi-parametric Markov multistate models were applied to assess the effects of covariates namely TB co-infection, educational status, marital status, age, quality of life (QoL) scores, white and red blood cell parameters, and liver enzyme abnormality on long-term viral suppression, viral rebound and state-specific duration for HIV-infected individuals before and after treatment. Furthermore, two models, one including and another excluding the effect of the frailty, were presented and compared in this study.ResultsResults from the diagnostic plots, Akaike information criterion (AIC) and likelihood ratio test showed that the Weibull multistate frailty model fitted significantly better than the exponential and semi-parametric multistate models. Viral rebound was found to be significantly associated with many sex partners, higher eosinophils count, younger age, lower educational level, higher monocyte counts, having abnormal neutrophils count, and higher liver enzyme abnormality. Furthermore, viral suppression was also found to be significantly associated with higher QoL scores, and having a stable sex partner. The analysis result also showed that patients with a stable sex partner, higher educational levels, higher QoL scores, lower eosinophils count, lower monocyte counts, and higher RBC indices were more likely to spend more time in undetectable viral load state.ConclusionsTo achieve and maintain the UNAIDS 90% suppression targets, additional interventions are required to optimize antiretroviral therapy outcomes, specifically targeting those with poor clinical characteristics, lower education, younger age, and those with many sex partners. From a methodological perspective, the parametric multistate approach with frailty is a flexible approach for modeling time-varying variables, allowing for dealing with heterogeneity between the sequence of transitions, as well as allowing for a reasonable degree of flexibility with a few additional parameters, which then aids in gaining a better insight into how factors change over time.

Clinical Characteristics of COVID-19 Patients With Digestive Symptoms in Hubei, China: A Descriptive, Cross-Sectional, Multicenter Study.

OBJECTIVE:Since the outbreak of Coronavirus Disease 2019 (COVID-19) in December 2019, various digestive symptoms have been frequently reported in patients infected with the virus. In this study, we aimed to further investigate the prevalence and outcomes of COVID-19 patients with digestive symptoms.METHODS:In this descriptive, cross-sectional, multicenter study, we enrolled confirmed patients with COVID-19 who presented to 3 hospitals from January 18, 2020, to February 28, 2020. All patients were confirmed by real-time polymerase chain reaction and were analyzed for clinical characteristics, laboratory data, and treatment. Data were followed up until March 18, 2020.RESULTS:In the present study, 204 patients with COVID-19 and full laboratory, imaging, and historical data were analyzed. The average age was 52.9 years (SD ± 16), including 107 men and 97 women. Although most patients presented to the hospital with fever or respiratory symptoms, we found that 103 patients (50.5%) reported a digestive symptom, including lack of appetite (81 [78.6%] cases), diarrhea (35 [34%] cases), vomiting (4 [3.9%] cases), and abdominal pain (2 [1.9%] cases). If lack of appetite is excluded from the analysis (because it is less specific for the gastrointestinal tract), there were 38 total cases (18.6%) where patients presented with a gastrointestinal-specific symptom, including diarrhea, vomiting, or abdominal pain. Patients with digestive symptoms had a significantly longer time from onset to admission than patients without digestive symptoms (9.0 days vs 7.3 days). In 6 cases, there were digestive symptoms, but no respiratory symptoms. As the severity of the disease increased, digestive symptoms became more pronounced. Patients with digestive symptoms had higher mean liver enzyme levels, lower monocyte count, longer prothrombin time, and received more antimicrobial treatment than those without digestive symptoms.DISCUSSION:We found that digestive symptoms are common in patients with COVID-19. Moreover, these patients have a longer time from onset to admission, evidence of longer coagulation, and higher liver enzyme levels. Clinicians should recognize that digestive symptoms, such as diarrhea, are commonly among the presenting features of COVID-19 and that the index of suspicion may need to be raised earlier in at-risk patients presenting with digestive symptoms. However, further large sample studies are needed to confirm these findings.

Treatment with etanercept and low monocyte concentration contribute to the risk of invasive aspergillosis in patients post allogeneic stem cell transplantation

Invasive aspergillosis (IA) is a life-threatening complication among allogeneic hematopoietic stem cell transplant (alloSCT) recipients. Despite well known risk factors and different available assays, diagnosis of invasive aspergillosis remains challenging. 103 clinical variables from patients with hematological malignancies and subsequent alloSCT were collected. Associations between collected variables and patients with (n = 36) and without IA (n = 36) were investigated by applying univariate and multivariable logistic regression. The predictive power of the final model was tested in an independent patient cohort (23 IA cases and 25 control patients). Findings were investigated further by in vitro studies, which analysed the effect of etanercept on A. fumigatus-stimulated macrophages at the gene expression and cytokine secretion. Additionally, the release of C-X-C motif chemokine ligand 10 (CXCL10) in patient sera was studied. Low monocyte concentration (p = 4.8 × 10−06), severe GvHD of the gut (grade 2–4) (p = 1.08 × 10−02) and etanercept treatment of GvHD (p = 3.5 × 10−03) were significantly associated with IA. Our studies showed that etanercept lowers CXCL10 concentrations in vitro and ex vivo and down-regulates genes involved in immune responses and TNF-alpha signaling. Our study offers clinicians new information regarding risk factors for IA including low monocyte counts and administration of etanercept. After necessary validation, such information may be used for decision making regarding antifungal prophylaxis or closely monitoring patients at risk.

P1647Prognostic significance of circulating leukocyte subtype counts in patients with chronic heart failure

Abstract Background Inflammation, characterized by early leukocyte recruitment, is known to be associated with vascular endothelial dysfunction and atherosclerosis. Previous studies have reported that an increased leukocyte count is a risk factor for the progression of atherosclerosis in cardiovascular diseases, and we previously reported that a high monocyte count was an independent and incremental of cardiovascular events in patients with coronary artery disease. Furthermore, previous study also reported that inflammation play a role in the pathophysiology of heart failure (HF), but few studies have evaluated the prognostic role of monocyte in patients with HF. Purpose To elucidate the prognostic value of monocyte in HF, we investigated the association of monocyte counts in patients with HF with their future cardiovascular events, and compared them among new categories of HF in this study. Methods Consecutive HF patients referred for hospitalization at Kumamoto University Hospital between 2006 and 2015 were registered. Finally, a total of 678 HF patients were enrolled in the study, and were followed prospectively until 2016 or until the occurrence of cardiovascular events. We defined high monocyte group as monocyte counts ≥360/mm3 according to previous clinical reports. We further divided HF patients into three types according to left ventricular ejection fraction (LVEF) (HF with reduced LVEF (HFrEF), HF with mid-range LVEF (HFmrEF), and HF with preserved LVEF (HFpEF)). Results In this study, HFrEF was 82 patients, HFmrEF was 118 patients and HFpEF was 478 patients, respectively. The average of total monocyte counts were 397±136 in HFrEF and 375±172 in HFmrEF, and 341±138 in HFpEF patients. Kaplan-Meier analysis revealed that both HFrEF and HFmrEF patients with high monocyte group (≥360 /mm3) had a significant higher risk of HF-related events (P=0.03 and P=0.02, respectively) but not of total cardiovascular events compared with those with low monocyte groups (&lt;360/mm3) (P=0.001). By contrast, high and low monocyte groups in HFpEF patients had no significant difference in both total cardiovascular and HF-related events. Multivariate Cox hazard analysis identified a high monocyte count as an independent and significant predictor of future HF-related events in HFrEF and HFmrEF patients (hazard ratio: 3.02, 95% confidence interval: 1.20–7.59, p=0.018). Next, by whether they had ischemic heart disease (IHD), we divided HFrEF and HFmrEF patients into two groups. Non-ischemic HF group with high monocyte counts had a significant higher risk of HF-related events compared to those with low monocyte counts (P=0.014). By contrast, there was no statistically significant difference of the occurrences of future HF-related events between in ischemic HF group with high and low monocyte counts. Conclusion A high monocyte count was an independent and incremental predictor of HF-related events in HFrEF and HFmrEF especially with IHD, but not in HFpEF patients.

Peripheral Monocyte Count Predicts Outcomes in Patients with Acute Ischemic Stroke Treated with rtPA Thrombolysis.

The aim of this study was to investigate the predictive value of the monocyte count as a prognostic biomarker on 90days in patients with acute ischemic stroke (AIS) treated with recombinant tissue plasminogen activator (rtPA) thrombolysis. In total, 206 patients with AIS treated in our institute between 2013 and 2018 were retrospectively enrolled. All patients received rtPA thrombolytic therapy within 4.5h of AIS onset. Using receiver operating characteristic (ROC) curve analysis, patients were divided into two groups according to monocyte count: a low monocyte count (LMC) group (monocytes < 0.53 × 109/L) and a high monocyte count (HMC) group (monocytes ≥ 0.53 × 109/L). Patients' functional outcomes 90days after AIS were assessed using the modified Rankin Scale. More patients had a poor outcome in the HMC group than in the LMC group (49.32% vs.31.58%, p = 0.012). Multivariate logistic regression analysis revealed that infarct volume (odds ratio = 1.03, 95% confidence interval 1.01-1.04, p < 0.001), systolic pressure at admission (odds ratio = 1.02, 95% confidence interval 1.00-1.04, p = 0.016), fasting blood glucose at admission (odds ratio = 1.41, 95% confidence interval 1.18-1.67, p < 0.001), and monocyte count ≥ 0.53 × 109/L (odds ratio = 2.25, 95% confidence interval 1.09-4.62, p = 0.028) were independently associated with a poor outcome in AIS patients treated with rtPA thrombolysis. A peripheral monocyte count ≥ 0.53 × 109/L is an independent prognostic marker on 90-days in patients with AIS treated with rtPA thrombolysis.

Monocytes may be favorable biomarker and predictor of long-term outcome in patients with chronic heart failure: A cohort study.

Although some studies found that an increased monocyte count is a predictive, short-term marker of unfavorable outcomes for patients with acute heart failure (HF), others have reported that monocytosis predicts prolonged survival.The current follow-up study aimed to identify different monocyte count patterns and their prognostic association with HF outcomes.Baseline blood samples for complete blood counts, differential counts, renal function tests, and lipid profiles of 303 chronic HF patients (average NYHA classification 2.8) were prospectively obtained to evaluate whether there is an association between monocyte count and clinical outcomes.Mean follow-up was 11.3 years (range 1 month to 16 years) and 111 (36.6%) patients died during follow-up. Mean monocyte count was 10.6 ± 5.5 and mean left ventricular ejection fraction (LVEF) was 36%. Patients with low monocyte counts (≤6%) had significantly lower survival rates than did those with monocyte counts 6.1% to 14%, or >14% (14.3% vs 70.2% vs. 88%, P < .001). Poorest survival was predicted for patients with NYHA class 3 to 4 and monocyte counts ≤6. Regression analysis showed that monocyte levels, NYHA class, and LVEF values were predictors of mortality, in decreasing importance.The total monocyte count was found to be an important prognostic factor that was inversely associated with predicted long-term mortality among patients with chronic HF. A low total monocyte count was strongly correlated with NYHA class and B-type natriuretic peptide levels, but no correlation was found with LVEF and oxidized low-density lipoproteins. It emerged as an independent risk factor for mortality in patients with chronic HF.

The role of linoleic acid in asthma and inflammatory markers: a Mendelian randomization study

Asthma is a common respiratory disease, possibly caused by autoimmunity. Linoleic acid (LA), the main n-6 (ω-6) PUFA from widely used vegetable oils, is thought to suppress immune responses that might have benefits for asthma. However, this question has not been examined in randomized controlled trials. To obtain unconfounded estimates, we assessed how genetically predicted LA affected asthma using 2-sample Mendelian randomization. We also examined its role in white blood cell traits (eosinophil, neutrophil, and low monocyte counts) identified as potential causal factors in asthma. We used 18 uncorrelated, genome-wide significant genetic variants to predict LA, which we applied to a large genetic case (n=19,954)-control (n=107,715) study of asthma, to the UK Biobank (408,961 people of European ancestry with 26,332 asthma cases), and for white blood cell traits to the UK Biobank. We also repeated the analysis on asthma using 29 replicated, functionally relevant genetic variants. In addition, we examined the role of asthma in LA to assess reverse causality. Genetically predicted LA was associated with lower risk of asthma (OR: 0.89 per SD increase in LA; 95% CI: 0.85, 0.93), with no association of asthma with LA. Genetically predicted LA was associated with lower eosinophil count (-0.03; 95% CI: -0.061, -0.004) and lower neutrophil count (-0.04; 95% CI: -0.057, -0.023). These estimates were robust to different selections of genetic variants and sensitivity analyses. LA might protect against asthma possibly via white blood cell traits, with relevance to the identification of effective new interventions for asthma.

The association of plasma lipids with white blood cell counts: Results from the Multi-Ethnic Study of Atherosclerosis

Previous studies have demonstrated that elevated cholesterol results in increased white blood cell counts in mouse models. However, there is insufficient evidence to support this in humans. The objective of the study was to investigate the relationship of plasma lipids with white blood cell counts (basophils, eosinophils, monocytes, neutrophils and lymphocytes) in the Multi-Ethnic Study of Atherosclerosis. The analysis included 2873 Multi-Ethnic Study of Atherosclerosis participants witha complete white blood count and differential analysis. The cross-sectional association of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels with different white blood cell counts was analyzed by multivariable linear regression. After adjusting for sociodemographic and confounding factors including red blood cell counts, platelet counts, use of lipid-lowering medication, cardiovascular disease risk factors and other lipid measures, and multiple testing correction, a one-standard deviation increment in total cholesterol and low-density lipoprotein cholesterol was associated with 2.8% and 2.3% lower total white blood cell counts, 3.7% and 3.0% lower monocyte counts, and 3.4% and 2.7% lower neutrophil counts (all P<.01). The same increment in logarithm-transformed triglyceride levels was associated with 2.3% higher total white blood cell counts and 4.5% higher lymphocyte counts (both P<.001). Similar results were obtained after excluding participants taking lipid-lowering medication. A one-standard deviation increase in high-density lipoprotein cholesterol was associated with a 1.5% lower white blood cell count (P=.018) but was not significantly associated with changes in any individual cell type. While significant associations were observed between plasma lipid levels and white blood cell populations, the heterogeneous and modest nature of these relationships makes it hard to support the hypothesis that lipids are in the causal pathway for leukogenesis in humans.

Prognostic impact of the combination of neutrophil-to-lymphocyte ratio and Glasgow prognostic score in colorectal cancer: a retrospective cohort study.

Although neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte count, and Glasgow prognostic score (GPS) are well-known prognostic markers in cancer, their prognostic importance is still controversial. We evaluated the prognostic value of NLR, PLR, monocyte count, and GPS in colorectal cancer (CRC). We retrospectively evaluated 448 CRC patients undergoing curative resection. We compared overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) between dichotomized groups by the optimal cutoff point. Univariate and multivariate analyses were applied to identify prognostic factors. High NLR, high monocyte count, and high GPS exhibited significantly worse prognosis in OS, CSS, and DFS compared with low NLR, low monocyte count, and low GPS, respectively. In contrast, PLR was not significantly associated with OS, CSS, and DFS. The univariate and multivariate analyses indicated that poor OS was significantly associated with age ≥ 69 and high NLR; that poor CSS was significantly associated with age ≥ 69, M factor, high CA19-9, adjuvant chemotherapy, and high GPS; and that poor DFS was significantly associated with venous invasion, high NLR, and high GPS. When 448 patients were classified into three groups based on NLR and GPS, there was a significant difference in OS, CSS, and DFS between all the three groups. Patients with NLR ≥ 2.05 and GPS = 1/2 exhibited remarkably poorer prognosis, whereas those with both NLR < 2.05 and GPS = 0 exhibited remarkably better prognosis. Combination of NLR and GPS can be a novel scoring system to effectively stratify outcome in CRC.

Prognostic Value of IPSS-R Score, Cytogenetic Aberrations, and Cytopenias on Outcome of Allogeneic Hematopoietic Stem Cell Transplant in Myelodysplastic Syndrome in GATA2 Deficiency

Sporadic or familial germline mutations in GATA2 frequently result in a bone marrow failure syndrome characterized by recurrent life-threatening infections, cytopenias, and progression to myelodysplastic syndrome (MDS), acute myelogenous leukemia (AML), or chronic myelomonocytic leukemia (CMML). Hematopoietic stem cell transplantation (HSCT) represents the only definitive therapy for GATA2 deficiency. However, the highly variable disease penetrance in different families, and in mutation positive individuals within a single family, make the timing of HSCT challenging. We assessed the utility of scoring patient characteristics according to the Revised International Prognostic Scoring System (IPSS-R) to predict survival after HSCT in a cohort of 51 patients with GATA2 deficiency who had progressed to MDS. Higher IPSS-R scores significantly correlated with reduced overall survival after transplant. In evaluating the components of the IPSS-R score for patients with GATA2 deficiency, cytopenias, including anemia, neutropenia, and thrombocytopenia, were important variables in placing these patients in higher risk IPSS-R categories. Since GATA2 deficiency patients have very low peripheral blood monocyte, B cell, and NK cell counts, we evaluated these cytopenias in conjunction with IPSS-R scoring. These cytopenias also had prognostic value for outcome after HSCT in patients with GATA2 deficiency. Cytogenetics, another component of the IPSS-R score, also placed patients with GATA2 deficiency into higher risk categories. In particular, patients harboring monosomy 7 had poorer survival outcomes than patients with normal cytogenetics or trisomy 8. Of note, all five patients with GATA2 deficiency and trisomy 1q successfully underwent HSCT. Clonal cytogenetic progression with the development of additional cytogenetic aberrations was a harbinger of myeloid progression and led to HSCT. In a cohort of four patients who underwent HSCT following progression to AML/CMML, there was only one survivor. Thus, HSCT is recommended in patients with GATA2 deficiency and intermediate or high-risk IPSS-R scores before the development of AML or CMML. DisclosuresNo relevant conflicts of interest to declare.

Low lymphocyte count and high monocyte count predicts poor prognosis of gastric cancer

BackgroundExisting data about the prognostic value of absolute count of blood cells in gastric cancer was limited. Thus, the present study aims to investigate the prognostic value of absolute count of white blood cell (WBC), neutrophil, lymphocyte, monocyte and platelet in gastric cancer patients.MethodsFrom September 2008 to March 2015, 3243 patients treated with radical gastrectomy were enrolled in the present study. Clinicopathological characteristics were recorded. The prognostic value of blood test in gastric cancer patients were analyzed.ResultsThere were 2538 male and 705 female. The median age was 58 years (range 20–90). The median follow-up time was 24.9 months (range 1–75). The 1-, 3- and 5-year overall survival rate was 88.9%, 65.8% and 57.2%, respectively. The optimal cut off value was 6.19 × 109/L for WBC (P = 0.146), 4.19 × 109/L for neutrophil (P = 0.004), 1.72 × 109/L for lymphocyte (P = 0.000), 0.51 × 109/L for monocyte (P = 0.019) and 260.0 × 109/L for platelet (P = 0.002), respectively. Neutrophil, lymphocyte, monocyte and platelet were risk factors for the prognosis of gastric cancer (all P < 0.05). However, only lymphocyte and monocyte were independent risk factors (both P < 0.05). Combination of lymphocyte and monocyte could increase the prognostic value for gastric cancer patients, especially in stage II/III gastric cancer patients.ConclusionsHigh absolute count of neutrophil, monocyte and platelet, and low absolute count of lymphocyte were associated with poor prognosis of gastric cancer. However, only lymphocyte and monocyte count were independent prognostic predictors. Combination of lymphocyte and monocyte count could further increase the predictive value for gastric cancer.

Risk stratification of castration-resistant prostate cancer patients treated with cabazitaxel.

Patient characteristics before administering the first cycle of cabazitaxel for metastatic castration-resistant prostate cancer (mCRPC) were collected to assess prognostic factors for overall survival (OS). Multivariate analysis revealed that prostate-specific antigen (PSA) ≥100 ng/ml prior to cabazitaxel treatment, visceral metastasis, and low absolute monocyte count were independent prognostic indicators for OS. The aim of the present study was to investigate prognostic biomarkers in patients treated with cabazitaxel among Japanese metastatic castration-resistant prostate cancer (mCRPC) patients. In this retrospective study, 45 patients with mCRPC treated with cabazitaxel were reviewed retrospectively. Clinicopathological factors and laboratory data before administering the first cycle of cabazitaxel were collected to assess the prognostic factors for overall survival (OS). Treatment was generally well tolerated, with a median of 5 cycles (range, 1-26). Median OS from the start of cabazitaxel treatment was 16.1 months (95% confidence interval 6.8-25.5). Univariate analysis revealed that poor performance status, visceral metastasis, hemoglobin <11 mg/dl, absolute monocyte count <400/µl, and prostate-specific antigen ≥100 ng/ml prior to cabazitaxel treatment (P=0.002) were significantly associated with shorter OS. Multivariate analysis revealed that PSA ≥100 ng/ml prior to cabazitaxel treatment, visceral metastasis, and absolute monocyte count <400/µl were independent prognostic indicators for OS. Based on the relative risk of death, patients with mCRPC before cabazitaxel therapy were divided into three risk groups: Low, intermediate, and high (P<0.001). In conclusion, the practical implications of our results may assist in tailoring the introduction of cabazitaxel.

The predictive value and the correlation of peripheral absolute monocyte count, tumor-associated macrophage and microvessel density in patients with colon cancer.

The tumor microenvironment plays a pivotal role in cancer progression. The purpose of the present study was designed to evaluate the predictive value of peripheral absolute monocyte count, tumor-associated macrophage, microvessel density, and to clarify the correlation between them in patients with colon cancer.A series of 216 patients with colon cancer were enrolled in this study. The peripheral absolute monocyte count was obtained from preoperative routine blood test. Tumor-associated macrophage and microvessel density were assessed on tissue microarray by immunohistochemistry.The one, three, five-year overall survival rate for the low absolute monocyte count group was 98.4%, 91.1%, 87.1%, respectively; and for the high absolute monocyte count group was 94.6%, 83.7%, 77.2%, respectively (P = .046). The one, three, five-year progression-free survival rate for the low absolute monocyte count group was 94.4%, 87.1%, 85.5%, respectively; and for the high absolute monocyte count group was 90.2%, 75.0%, 73.9%, respectively (P = .024). Univariate and multivariate analysis showed that there was a strong association between peripheral monocyte count and clinical outcome. The correlation between peripheral absolute monocyte count, tumor-associated macrophage, and microvessel density were not observed.The peripheral absolute monocyte count was an independent prognostic factor for overall survival and progression-free survival in colon cancer. The high absolute monocyte count was significantly associated with poor outcome.

A study of haematological profile of malaria in a tertiary care centre of western Uttar Pradesh, India

Background: Malaria is a major health problem in tropics with a high morbidity and mortality. Malaria causes wide spectrum of manifestation both clinical as well as hematological. A variety of haematological alterations like progressively increasing anaemia, thrombocytopenia, leucocytosis or leukopenia and rarely disseminated intravascular coagulopathy (DIC) have been reported in malaria. Though clinical manifestation has been widely studied but there is paucity of work in hematological abnormality.Methods: The hospital based observational study was conducted in the Department of Paediatrics, Shri Rammurti Smarak Insitute of Medical Sciences (SRMSIMS), Bareilly. Ninety-eight cases were positive for malaria by peripheral smear or by rapid diagnostic test for malaria or by both.Results: In the present study, prevalence of malaria found to be (11.6 %). Out of 98 cases, 60 were males, majority of cases belonged to 9-12 years of age, followed by 4-8 years of age. Male:Female ratio is 1.57:1. There was neutrophilic predominance and low monocyte count in cases positive for plasmodium falciparum malaria. All the patients had microcytic hypochromic anemia as per mean of MCV. In haematological profiles of malaria neutrophil and monocyte showed statistically significant variations (P value ≤0.001)Conclusions: Anemia is the most common hematological abnormality. There was neutrophilic predominance and low monocyte count in cases positive for malaria which is highly significant. All the patients had microcytic hypochromic anemia as per mean of MCV. Profound thrombocytopenia is very common in malaria.