Peripheral Blood Lymphocyte Count Research Articles

Clinical characteristics of human recombination activating gene 1 mutations in 8 immunodeficiency patients with diverse phenotypes

Objective: To investigate the clinical characteristics of 8 immunodeficiency cases caused by human recombination activating gene 1 (RAG1) mutations, and to explore the relationship among genotypes, clinical manifestations and immunophenotypes. Methods: Clinical data were collected and analyzed from patients with RAG1 mutations who visited the Department of Clinical Immunology, Children's Hospital of Fudan University between October 2013 and June 2017. The data included clinical manifestations, immunophenotypes and genotypes. Results: A total of 8 patients were diagnosed with RAG1 deficiency (6 boys and 2 girls). The minimum age of onset was 2 months, and the maximum age was 4 months. The minimum age of diagnosis was 2 months, and the maximum age was 13 years. Four patients had a family history of infant death due to severe infections. Two cases were born to the same consanguineous parents. All cases had recurrent infections, including involvement of respiratory tract (8 cases), digestive tract (6 cases), urinary tract (1 case), and central nervous system (1 case). The pathogens of infection included bacteria, viruses and fungi. Rotavirus was found in 3 cases, cytomegalovirus (CMV) in 5 cases, bacillus Calmette-Guérin adverse reaction in 2 cases (1 of whom had a positive acid-fast smear from lymph node puncture fluid), fungal infection in 3 cases. One case had multiple nodular space-occupying lesions in lungs and abdominal cavity complicated with multiple bone destruction. The peripheral blood lymphocyte counts of all patients ranged between 0.1 ×10(9)/L and 3.3×10(9)/L (median, 0.65×10(9)/L). Eosinophilia was found in 3 cases (range, (0.48-1.69) ×10(9)/L). The patients were classified according to immunophenotype as severe combined immunodeficiency phenotype (4 cases), leaky severe combined immunodeficiency (2 cases), Omenn syndrome (1 case) and combined immunodeficiency (1 case) . Decreased serum IgG levels were found in 3 cases, increased serum IgM levels in 3 cases, increased serum IgE levels in 5 cases. RAG1 homozygous mutations were detected in 5 cases and RAG1 compound heterozygous mutations in 3 cases. Two novel mutations and six previously reported mutations were identified. Three cases were successfully treated with hematopoietic stem cell transplantation. Four cases died due to infections, and the 13 year-old patient was still under follow-up in the outpatient clinic. Conclusions: Different RAG1 gene mutations can lead to diverse clinical presentations and immune phenotypes. Clinicians should pay attention to the family history of infant death with severe infection. In that situation, immunological evaluation and gene detection should be performed as early as possible.

Fraction From Lycium barbarum Polysaccharides Reduces Immunotoxicity and Enhances Antitumor Activity of Doxorubicin in Mice.

The aim of the present study was to investigate whether fraction from Lycium barbarum polysaccharide (LBP) could reduce immunotoxicity and enhance antitumor activity of doxorubicin (Dox) in mice. A water-soluble LBP fraction, designated LBP3, was isolated from edible Chinese herbal Lycium barbarum and used in this study. To investigate the effect of LBP3 on Dox-induced immunotoxicity, tumor-free mice were used and treated with either normal saline, Dox, or Dox plus LBP3. To investigate the effect of LBP3 on antitumor activity of Dox, H22 tumor-bearing mice were used and treated with either normal saline, Dox, LBP3, or Dox plus LBP3. The results showed that LBP3 did not protect against the body weight loss caused by Dox, but it promoted the recovery of body weight starting at day 5 after Dox treatment in tumor-free mice. LBP3 also improved peripheral blood lymphocyte counts, promoted cell cycle recovery in bone marrow cells, and restored the cytotoxicity of natural killer cells. Furthermore, in H22 tumor-bearing mice, LBP3 enhanced antitumor activity of Dox and improved peripheral blood lymphocyte counts and the cytotoxicity of splenocytes. In brief, our results demonstrated that LBP3 could reduce the immunotoxicity and enhance antitumor activity of Dox.

Diagnosis and treatment of tuberculosis peritonitis in patients with maintenance hemodialysis

Objective To investigate the clinical characteristics and treatment strategies of patients with maintenance hemodialysis and tuberculous peritonitis. Methods The clinical data of maintenance hemodialysis 12 patients combined with tuberculous peritonitis were analyzed retrospectively. Results The pathogenesis of maintenance hemodialysis combined with tuberculous peritonitis was concealed, and history of tuberculosis in 4 cases (33%), 10 cases of peripheral blood lymphocyte count 2.5 g/dL, peritoneal effusion ADA>30 U/L in 9 cases (75%), all cases of peritoneal effusion LDH>90 U/L. All 12 patients received two (isoniazid and rifampicin) or triple (isoniazid, rifampicin and ethambutol) anti-tuberculosis treatment, daily single medication for 9 months. Ten patients were discharged with a better health condition. Conclusions Active anti-tuberculosis in the treatment of maintenance hemodialysis patients with tuberculous peritonitis can achieve better results. Key words: Renal Dialysis; Peritonitis, Tuberculous

Lymphocyte count in peripheral blood is not associated with the level of clinical response to treatment with fingolimod

BackgroundFingolimod is an efficient and safe drug for treating relapsing-remitting multiple sclerosis (RRMS). In vivo, fingolimod is phosphorylated and binds to “sphingosine-1-phosphate”(S1P) receptors that are expressed in a wide range of cells, including lymphocytes. Under the effect of fingolimod, lymphocytes are retained in lymphoid tissues through the regulation of S1P1 receptors. The aim of the present study was to assess whether the degree of lymphopenia was correlated to the positive treatment response of RRMS patients with fingolimod. MethodsData was sourced from the MSBase Registry. Patients were divided into two groups, according to the lymphocyte count on peripheral blood examination. Annualized Relapse Rate (ARR), time to first relapse and time to six-month confirmed disability progression were compared between groups. ResultsGroup one consisted of 202 patients who reached 750 lymphocytes/mm3 during treatment while the comparison group two included 101 patients who never reached less than 1000 lymphocytes/mm3 in peripheral blood during the observation period. There were no differences between groups in ARR, time to first relapse or time to six-month confirmed disability progression. ConclusionThe degree of lymphopenia in peripheral blood was not associated to the positive treatment response of fingolimod in RRMS patients.

Altered B-lymphopoiesis in mice with deregulated thrombopoietin signaling

Thrombopoietin (TPO) is the master cytokine regulator of megakaryopoiesis. In addition to regulation of megakaryocyte and platelet number, TPO is important for maintaining proper hematopoietic stem cell (HSC) function. It was previously shown that a number of lymphoid genes were upregulated in HSCs from Tpo−/− mice. We investigated if absent or enhanced TPO signaling would influence normal B-lymphopoiesis. Absent TPO signaling in Mpl−/− mice led to enrichment of a common lymphoid progenitor (CLP) signature in multipotential lineage-negative Sca-1+c-Kit+ (LSK) cells and an increase in CLP formation. Moreover, Mpl−/− mice exhibited increased numbers of PreB2 and immature B-cells in bone marrow and spleen, with an increased proportion of B-lymphoid cells in the G1 phase of the cell cycle. Conversely, elevated TPO signaling in TpoTg mice was associated with reduced B-lymphopoiesis. Although at steady state, peripheral blood lymphocyte counts were normal in both models, Mpl−/− Eµ-myc mice showed an enhanced preneoplastic phase with increased numbers of splenic PreB2 and immature B-cells, a reduced quiescent fraction, and augmented blood lymphocyte counts. Thus, although Mpl is not expressed on lymphoid cells, TPO signaling may indirectly influence B-lymphopoiesis and the preneoplastic state in Myc-driven B-cell lymphomagenesis by lineage priming in multipotential progenitor cells.

Change in lymphocyte to neutrophil ratio predicts acute rejection after heart transplantation.

Most immunosuppressive drugs provide targeted immunosuppression by selective inhibition of lymphocyte activation and proliferation. This study evaluated whether a change in the lymphocyte to neutrophil ratio (LNR) is related to acute rejection. In 74 cardiac transplant recipients peripheral blood lymphocyte and neutrophil counts were measured soon after (baseline) and three, six, and 12months after heart transplantation. The primary endpoint was the incidence of acute rejection. Significant acute rejection after heart transplantation occurred in 20 patients (27%) during a median follow-up of 49.4 [IQR 37.4-61.1] months. LNR significantly increased over time (0.1149±0.1354 at baseline, 0.2330±0.2266 at 3months, 0.2961±0.2849 at 6months, and 0.3521±0.2383 at 12months; P<0.001), especially during the first 3months in the group without acute rejection. The area under the curve of the change in LNR during the first three months (ΔLNR) for acute rejection was 0.565 (95% CI 0.420 to 0.710, P=0.380) on ROC curve analysis. The best cutoff value of Δ LNR to differentiate those with and without acute rejection was ≤0.046 by ROC curve analysis. Kaplan-Meier analysis revealed that the low ΔLNR group (≤0.046) had a significantly higher rate of acute rejection than the high ΔLNR group (>0.046) (37.5% vs. 19.0%, log-rank: P=0.0358). The low ΔLNR for the first 3months was an independent predictor of clinically significant acute rejection after adjusting for cytomegalovirus donor seropositive and recipient seronegative. The results of this study suggest that ΔLNR over the first 3months after heart transplantation is a strong and independent predictor of acute rejection after heart transplantation. ΔLNR can be used as an early biomarker for predicting of acute rejection after heart transplantation.

Nrf2-Knockout Protects from Intestinal Injuries in C57BL/6J Mice Following Abdominal Irradiation with γ Rays.

Radiation-induced intestinal injuries (RIII) commonly occur in patients who suffer from pelvic or abdominal cancer. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a key transcriptional regulator of antioxidant, and the radioprotective role of Nrf2 is found in bone marrow, lung, and intestine, etc. Here, we investigated the effect of Nrf2 knockout on radiation-induced intestinal injuries using Nrf2 knockout (Nrf2−/−) mice and wild-type (Nrf2+/+) C57BL/6J mice following 13 Gy abdominal irradiation (ABI). It was found that Nrf2 knockout promoted the survival of irradiated mice, protected the crypt-villus structure of the small intestine, and elevated peripheral blood lymphocyte count and thymus coefficients. The DNA damage of peripheral blood lymphocytes and the apoptosis of intestinal epithelial cells (IECs) of irradiated Nrf2−/− mice were decreased. Furthermore, compared with that of Nrf2+/+ mice, Nrf2 knockout increased the number of Lgr5+ intestinal stem cells (ISCs) and their daughter cells including Ki67+ transient amplifying cells, Villin+ enterocytes, and lysozyme+ Paneth cells. Nuclear factor-κB (NF-κB) was accumulated in the crypt base nuclei of the small intestine, and the mRNA expression of NF-κB target genes Bcl-2, uPA, and Xiap of the small intestine from irradiated Nrf2−/− mice were increased. Collectively, Nrf2 knockout has the protective effect on small intestine damage following abdominal irradiation by prompting the proliferation and differentiation of Lgr5+ intestinal stem cells and activation of NF-κB.

Leukocytic reaction as a marker of prepathological shifts in cases of benzene poisoning

Benzene is one of the most widespread environmental contaminants, which is able to reduce the body resistance even at low doses. Therefore, certain criteria should be developed that allow to identify the early stages of intoxication. With this objective in view, we studied the changes occurring in peripheral blood elements against the background of intoxication of the experimental animals with low doses of benzene. 36 experimental rabbits, divided into three groups, were used for the study. The rabbits in the first and second group were exposed accordingly to gradually increased and fluctuated concentrations of benzene, whereas the third group was used as the control group. Chronic exposure to benzene continued for 4 months. Determination of peripheral blood total leukocyte, eosinocyte, basocyte, neutrophil, lymphocyte and monocyte counts as well as their qualitative characterization (such as cell nucleus shape, existence of cytoplasmic grains and vacuoles and etc.) revealed that the study characteristics of the 1st group exhibit significant changes as compared to the control group. The maximal amplitudes of these changes were observed at the end of the third month. At the same time, left neutrophilic shift of regenerative type was observed, while the lymphocyte count reached the upper normal level. One month after the benzene exposure termination all indicators were normalized and returned to baseline and control levels. In the 2nd group, the total count of leukocytes and eozonocytes significantly increased one month after the beginning of the study. The rabbits within the group developed leukopenia by the end of the study. Not all indicators returned to baseline levels one month after termination of benzene exposure, which reflects the insufficiency of this period for the recovery after such scheme of exposure.

Eosinophil could predict the prognosis of patients with bloodstream infection: a retrospective analysis of 305 cases

To investigate the value of peripheral blood for the prognosis of patients with bloodstream infection. A retrospective analysis of patients with bloodstream infection was conducted in the intensive care unit (ICU) of Mianyang Central Hospital of Sichuan from January 2012 to October 2016. According to the 28-day survival, the patients were divided into survival group and death group. The white blood cell (WBC), neutrophils count (NEU), lymphocyte count (LYM), neutrophil/lymphocyte ratio (NLR), monocyte count (MO), eosinophil count (EO), basophil count (BA), hemoglobin (Hb), platelet count (PLT) and procalcitonin (PCT) in peripheral blood were recorded when patients were diagnosed with blood infection. Receiver operating characteristic curve (ROC), Kaplan-Meier survival analysis and Cox regression were used to evaluate the value of these risk factors for predicting the outcome. 305 patients were enrolled. 182 patients survived while 123 patients died during the 28-day period. (1) There was no significant difference in gender, age and comorbidities between the two groups. There was no significant difference in infection rate between the two groups except for fungal infection rate. The fungal infection rate in the death group was significantly higher than that in the survival group (9.8% vs. 3.3%, P = 0.019). (2) The LYM, MO, EO and PLT in the death group were significantly lower than those in the survival group [LYM (×109/L): 0.58 (0.29, 0.93) vs. 0.76 (0.44, 1.23), MO (×109/L): 0.47 (0.19, 0.80) vs. 0.58 (0.30, 0.94), EO (×109/L): 0.00 (0.00, 0.01) vs. 0.03 (0.01, 0.09), PLT (×1012/L): 89 (47, 148) vs. 126 (82, 186), all P < 0.05]. The NLR in the death group was significantly higher than that in the survival group [17.09 (7.60, 33.51) vs. 12.86 (6.51, 24.85), P < 0.05]. There was no significant difference in the WBC, NEU, BA, Hb and PCT between the two groups. (3) It was shown by ROC curve analysis that the maximum area under the ROC curve (AUC) of EO was 0.755. When the best cut-off value was 0.015×109/L as a predictor of death in 28 days, the sensitivity was 80.3%, and specificity was 64.7%. (4) It was shown by survival analysis that the 28-day survival rate in the patients with EO < 0.015×109/L was significantly lower than that of patients with EO > 0.015×109/L [38.3% (62/162) vs. 83.9% (120/143), χ 2 = 56.999, P = 0.000]. (5) It was shown by Cox regression that EO was the independent factor for 28-day survival (β = 1.466, χ 2 = 39.535, P = 0.000). Risk of death was 4.331 times greater in patients with EO < 0.015×109/L than in those with EO > 0.015×109/L [hazard ratio (HR) = 4.331, 95% confidence interval (95%CI) = 2.743-6.840]. Compared to other parameters in peripheral blood, EO has the best correlation with the prognosis of bloodstream infection. EO is the independent prognostic predictor for 28-day survival.

Neutrophil-Lymphocyte Ratio Is a Prognostic Marker in Patients with Locally Advanced (Stage IIIA and IIIB) Non-Small Cell Lung Cancer Treated with Combined Modality Therapy.

Neutrophil-lymphocyte ratio (NLR) is a measure of systemic inflammation that appears prognostic in localized and advanced non-small cell lung cancer (NSCLC). Increased systemic inflammation portends a poorer prognosis in cancer patients. We hypothesized that low NLR at diagnosis is associated with improved overall survival (OS) in locally advanced NSCLC (LANSCLC) patients. Records from 276 patients with stage IIIA and IIIB NSCLC treated with definitive chemoradiation with or without surgery between 2000 and 2010 with adequate data were retrospectively reviewed. Baseline demographic data and pretreatment peripheral blood absolute neutrophil and lymphocyte counts were collected. Patients were grouped into quartiles based on NLR. OS was estimated using the Kaplan-Meier method. The log-rank test was used to compare mortality between groups. A linear test-for-trend was used for the NLR quartile groups. The Cox proportional hazards model was used for multivariable analysis. The NLR was prognostic for OS (p < .0001). Median survival in months (95% confidence interval) for the first, second, third, and fourth quartile groups of the population distribution of NLR were 27 (19-36), 28 (22-34), 22 (12-31), and 10 (8-12), respectively. NLR remained prognostic for OS after adjusting for race, sex, stage, performance status, and chemoradiotherapy approach (p = .004). To our knowledge, our series is the largest to demonstrate that baseline NLR is a significant prognostic indicator in LANSCLC patients who received definitive chemoradiation with or without surgery. As an indicator of inflammatory response, it should be explored as a potential predictive marker in the context of immunotherapy and radiation therapy. Neutrophil-lymphocyte ratio measured at the time of diagnosis was associated with improved overall survival in 276 patients with stage IIIA and IIIB non-small cell lung cancer (NSCLC) treated with definitive chemoradiation with or without surgery. To our knowledge, our series is the largest to demonstrate that baseline neutrophil-lymphocyte ratio is a significant prognostic indicator in locally advanced NSCLC patients who received definitive chemoradiation with or without surgery. Neutrophil-lymphocyte ratio is an inexpensive biomarker that may be easily utilized by clinicians at the time of locally advanced NSCLC diagnosis to help predict life expectancy.

Low absolute peripheral blood CD4+ T-cell count predicts poor prognosis in R-CHOP-treated patients with diffuse large B-cell lymphoma

The absolute peripheral blood lymphocyte count at diagnosis is known to be a strong prognostic factor in patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), but it remains unclear as to which peripheral blood lymphocyte population is reflective of DLBCL prognosis. In this cohort, 355 patients with DLBCL treated with R-CHOP from 2006 to 2013 were analyzed. The low absolute CD4+ T-cell count (ACD4C) at diagnosis negatively correlated with the overall response rate and the complete response rate significantly (P<0.00001). An ACD4C<343 × 106/l had a significant negative impact on the 5-year progression-free survival and the overall survival as compared with an ACD4C⩾343 × 106/l (73.7% (95% confidence interval (CI)=66.7–79.5) versus 50.3% (95% CI=39.0–60.6), P<0.00001 and 83.3% (95% CI=77.1–88.0) versus 59.0% (95% CI=47.9–68.5), P<0.00000001, respectively). Multivariate analysis revealed that the ACD4C was an independent prognostic marker (hazard ratio=2.2 (95% CI=1.3–3.7), P<0.01). In conclusion, a low ACD4C at diagnosis served as an independent poor prognostic marker in patients with DLBCL.

Low prognostic nutritional index associated with cardiovascular disease mortality in incident peritoneal dialysis patients.

The prognostic nutritional index (PNI), a variable based on serum albumin concentration and total lymphocyte count in peripheral blood, is reported as a predictor of mortality in a variety of malignant tumor population. This study is aimed to evaluate whether PNI has prognostic value in patients on peritoneal dialysis (PD). This was a single-center, retrospective observational cohort study conducted in incident PD patients from January 1, 2006 to June 30, 2014, and followed until June 30, 2015. The associations of PNI levels with mortality were evaluated by Kaplan-Meier method and Cox proportional hazards models. A total of 345 patients were included in this study. Median PNI level at baseline was 40.7 (range: 18.8-75.5) for all patients. During follow-up, 59 (17.1%) died during follow-up, among which 31 (52.5%) were due to cardiovascular diseases (CVD). In crude analysis, the patients with low PNI had a significant increase risk of CVD and all-cause mortality [hazard ratio (HR) 3.07, 95% confidence interval (CI) 1.51-6.25 and HR 2.18, 95% CI 1.28-3.72, respectively)]. After adjusting age, Davies comorbidity score, hemoglobin and leukocytes, the patients with low PNI still had a significant increased risk of CVD mortality (HR 2.37, 95% CI 1.10-5.12). However, there was no significant difference in risk of all-cause mortality (HR 1.72, 95% CI 0.97-3.06). Low PNI at initiation of PD was independently associated with an increased CVD mortality.

MECHANISMS OF IMMUNOSUPPRESSION UPON FREQUENT ACUTE VIRAL RESPIRATORY INFECTIONS IN INFANTS AFTER NEONATAL CYTOMEGALOVIRUS INFECTION

Study objectives: To assess differential peripheral blood lymphocyte counts in infants three months of age who passed neonatal CMV infection. To examine the usability of the results for predicting frequent acute viral respiratory infections (AVRI) in the first year of life. Materials and methods: The study group included 69 infants of whom 54 passed severe neonatal CMV infection, and 15 were healthy according to conventional criteria. Among the 54 children, 30 suffered from frequent AVRI and 24 had no AVRI during the first year of life. CD markers were determined using flow cytofluorometry with a Beckman Coulter Epics XL II instrument. The following antibodies, which were purchased from Immunotest (France), were used: CD3, CD28, CD20, and CD40. Results: In all children after CMV infections in comparison with those who had no CMV infection,CD20+ and CD20+CD40+cell counts were increased.

Prognostic impact of intestinal wall thickening in hospitalized patients with heart failure

BackgroundIntestine-cardiovascular relationship has been increasingly recognized as a key factor in patients with heart disease. We aimed to identify the relationships among intestinal wall edema, cardiac function, and adverse clinical events in hospitalized heart failure (HF) patients. Methods and resultsAbdominal computed tomographic images of 168 hospitalized HF patients were retrospectively investigated for identification of average colon wall thickness (CWT) from the ascending to sigmoid colon. Relationships between average CWT and echocardiographic parameters, blood sampling data, and primary outcomes including readmission for deteriorated HF and all-cause mortality were evaluated. Among the echocardiographic parameters, lower left ventricular diastolic function was correlated with higher average CWT. In multivariate analysis, higher logarithmic C-reactive protein level, lower estimated glomerular filtration rate, lower peripheral blood lymphocyte count, higher E/E′ ratio, and extremely higher/lower defecation frequency were independently correlated with higher average CWT. Multivariate Cox-hazard analysis demonstrated that higher average CWT was independently related to higher incidence of primary outcomes. ConclusionIn hospitalized HF patients, increased CWT was associated with lower cardiac performance, and predicted poorer long-term clinical outcomes.

Absolute CD4+ T-Cell Count Predicts Survival in Diffuse Large B-Cell Lymphoma

IntroductionTumors deregulate immunological antitumor response, resulting in survival of tumor cells, which implicate the existence of immunological tolerance to tumors.CD4+ T cells activate tumor-specific cytotoxic CD8+ T cells via cytokines and they also can eliminate cancer in the absence of CD8+ T cell. Absolute CD4+ T-cell count(ACD4C)in biopsied specimen is known to correlate with therapeutic outcomes in DLBCL. In patients with solid cancer, CD4+ T cells decrease in the peripheral blood, whereas regulatory T cells (Tregs) increase in the peripheral blood.Tregshave a role to reduce antibody dependent cellular toxicity (ADCC) of rituximab against CD20+ B-cell malignancies. On the other hand,we and othersknow that absolute lymphocyte count in peripheral blood can predict survival of diffuse large B-cell lymphoma (DLBCL). It has been indefinite, however, which lymphocyte including CD4+ T cells in peripheral blood reflect the prognosis of DLBCL.MethodWe enrolled patients who were diagnosed with de novo DLBCL from 2006 until 2013, received R-CHOP, and followed up at Cancer Institute Hospital, Tokyo, Japan. We had measured absolute lymphocyte count, T-cell ratio, CD4+ T-cell ratio, and CD8+ T-cell ratio in these patients using pretreatment blood samples. Data were collected prospectively and recorded into a computerized database. All patientsgave written informed consent allowing the use of their medical record. The optimal cut-off values were made based on its utility as a marker for death using box plot, clinical important value from references, and receiver operating characteristic curve. Differences between the results of comparative tests were considered significant if the two-sided P value was less than 0.05.ResultsA total of 355 patients were diagnosed with de novo DLBCL.Baseline characteristics were following: median age was 65 (range 20-89), Patients aged over 60 were 243 (68%), male to female ratio was 1.2, ECOG PS ≥ 2 of 19 (5%), elevated LDH of 152 (43%), low ACD4C (< 350 x 106 /l) of 119 (34%), low ACD8C (< 300 x 106 /l) of 144 (41%), CD5+ DLBCL of 38 (11%), Ann Arbor stage III/IV of 145 (41%), and involved extranodal sites ≥ 2 of 93 (26%). Germinal center B cell (GCB) DLBCL was seen in 167 (53%), non-GCB DLBCL was seen in 148 (47%). Patients without evidence of death (n = 282) at last follow-up had a higher ACD4C (≥ 350 x 106 /l) at diagnosis than those with death (n = 73) (P < 0.0001). There was also markedly difference in absolute CD8+ T-cell count, but no difference in absolute B-cell count. At the median follow-up of 57 months, Kaplan-Meier method estimated that 5-year PFS was 78.1% in the high ACD4C group and 62.0% in the low ACD4C group (Figure 1A, log-rank P < 0.001), whereas 67.4% in the high ACD8C group and 41.6% in the low ACD8C group (P = 0.01). Furthermore, 5-year OS was 83.6% in the high ACD4C group and 64.5% in the low ACD4C group (Figure 1B, log-rank P < 0.001), whereas 56.2% in the high ACD8C group and 36.1% in the low ACD8C group (P < 0.01). An ACD4C < 350 x 106 /l was identified as an adverse prognostic marker in DLBCL by Cox hazard model (hazard ratio 1.9, P = 0.01). In addition, CD5+ DLBCL, PS ≥ 2, stage III/IV, and non-GCB DLBCL were identified as low ACD4C. Age > 60, extranodal diseases ≥ 2, and elevated LDH were not identified in this study. ACD4C had negative correlation with tumor burden, which was shown by Pearsonfs coefficient (correlation with LDH; r = -0.24, P < 0.0001) and Studentfs t-test (correlation with stage; P < 0.0001). Interestingly, low ACD4C affected OS only in the stage III/IV, non-GCB DLBCL, and high-IPI groups (fisherfs exact test P < 0.01). Baseline characteristics of the low ACD4C group showed higher rate of stage III/IV (P < 0.001), elevated LDH (P < 0.01), extranodal disease ≥ 2 (P < 0.001), soluble IL-2 receptor > 2000 U/l (P < 0.001), low serum albumin (P = 0.001), and beta2 microglobulin > 2 mg/dl (P < 0.001).ConclusionThis study demonstrates that ACD4C had a negative correlation with tumor burden and low ACD4C at diagnosis made worse prognosis of patients with DLBCL, in particular, those who had high tumor burden, non-GCB, or high IPI at diagnosis, suggestingTregsmight increase in peripheral blood in the low ACD4C group and might impair the ADCC of rituximab. [Display omitted] DisclosuresTerui:Yanssen: Honoraria. Mishima:Chugai: Consultancy. Nishimura:Chugai: Consultancy. Yokoyama:Chugai: Consultancy. Hatake:Meiji-Seika: Consultancy; Kyowa Kirin: Honoraria, Research Funding; Chugai: Research Funding; Otsuka: Consultancy.

Assessment of Measures to Reduce Infusion-Related Reactions in Patients with Chronic Lymphocytic Leukemia Treated with Obinutuzumab in the GREEN Study

Assessment of Measures to Reduce Infusion-Related Reactions in Patients with Chronic Lymphocytic Leukemia Treated with Obinutuzumab in the GREEN Study

Platelet Distribution Width as a Predictor of Metastasis in Gastric Cancer Patients.

There are few known predictors of gastric cancer (GC). In this study, we evaluated the relationship between peripheral blood parameters and disease in patients with GC. Our aim was to identify a predictor of the development of metastasis. Pretreatment peripheral blood parameters, including neutrophil, lymphocyte, and platelet counts; median platelet values (MPVs); and platelet distribution width (PDW), of patients diagnosed with GC were assessed. The independent T test was used in comparisons between two groups with a normal distribution, the Mann-Whitney U test in comparisons between two groups without a normal distribution, the Kruskal-Wallis test to compare more than two groups, and the Dunn's multiple comparison test to compare subgroups. A p value <0.05 was considered statistically significant. In GC patients, neutrophil and platelet counts, but not lymphocyte counts and MPVs, increased significantly with disease stage progression. Among patients who developed a metastasis during follow-up, the relationship between PDW and the risk of metastasis was statistically significant (p=0.04). Both lymphocyte and platelet levels had a statistically significant relationship to survival (p=0.04 and p=0.02, respectively). Our results showed that in patients with GC, PDW, one of the standard parameters measured in a complete blood count, is a predictor of metastasis. Therefore, the PDW may be an important consideration in the surgical and chemotherapeutic treatment planning of patients with GC. Treatment strategies should also take into account lymphocyte and platelet levels, both of which were shown to be significantly related to survival.

Protocolo de práctica asistencial de las linfocitosis crónicas

IntroductionChronic persistent lymphocytosis is the increase of the absolute lymphocyte count (usually> 4.800 / mm3) in peripheral blood. EtiologyLymphocytosis can be classified between clonal or reactive. DiagnosisThe diagnosis involves a complete medical history and some laboratory tests; peripheral blood smear is essential and other tests, as flow cytometry, can be also used to classify lymphocytosis (clonal or polyclonal). Once the cause is established, treatment and prognosis are those of the primary cause or clonal lymphoid blood disorder.

Impact of Demographics, Organ Impairment, Disease, Formulation, and Food on the Pharmacokinetics of the Selective S1P1 Receptor Modulator Ponesimod Based on 13 Clinical Studies.

Ponesimod is a selective, orally active sphingosine-1-phosphate receptor 1 modulator currently undergoing clinical evaluation for the treatment of multiple sclerosis (MS) in phase III clinical trials. Ponesimod dose-dependently reduces peripheral blood lymphocyte counts by blocking the egress of lymphocytes from lymphoid organs. A population pharmacokinetic (PK) analysis was performed based on pooled data from 13 clinical studies. Interindividual variability (IIV) and the impact of key demographic variables and other covariates on ponesimod exposure were assessed quantitatively. A two-compartment model with sequential zero/first-order absorption, including lag time, intercompartmental drug flow, and first-order clearance, adequately described the PK of ponesimod. Body weight, race, MS, psoriasis, hepatic impairment, drug formulation, and food were identified to significantly affect the concentration-time profile. The inclusion of these covariates into the model explained approximately 25% of the IIV in the PK of ponesimod. Model predictions indicated that the impact of the identified covariates on ponesimod steady-state exposure is within 20% of exposure, and thus within the margins of the IIV, with the exception of hepatic impairment. Changes up to threefold were predicted for severe cases of liver dysfunction. The rich data set enabled building a comprehensive population PK model that accurately predicts the concentration-time data of ponesimod. Covariates other than hepatic impairment were considered not clinically relevant and thus do not require dose adjustment. A potential dose adaptation can be conducted based on the final model.

Peripheral blood leukocyte populations and urinary neopterin during chemotherapy in patients with breast cancer

Abstract The aim of the present study was to investigate serial changes in urinary neopterin and the populations of peripheral blood lymphocytes in breast cancer patients treated with primary chemotherapy. Thirty patients with breast cancer, including 20 patients undergoing primary chemotherapy treated with the combination of doxorubicin and cyclophosphamide with sequential administration of paclitaxel-based therapy (cohort A), and 10 patients presenting for first-line therapy of metastatic disease and treated with the combination of bevacizumab, taxane and carboplatin (cohort M) were studied. Healthy female blood donors served as control group. Significant differences were observed in baseline relative and absolute counts of peripheral blood lymphocyte subpopulations between both patient cohorts and controls. Significant changes of peripheral blood lymphocyte subpopulations were also observed during the course of chemotherapy. However, no significant changes of urinary neopterin concentrations and no correlation between urinary neopterin and peripheral blood lymphocyte counts were observed. In conclusion, present data demonstrate the presence of significant differences in peripheral blood leukocyte phenotype in breast cancer patients even before the start of primary chemotherapy. Significant changes were observed during the course of chemotherapy.