Higher Absolute Neutrophil Count Research Articles

Gene Mutations in MDS Associating with Peripheral Blood Count Abnormalities

Recent data suggested that low levels of mutated myeloid genes could be detected in the peripheral blood of individuals with normal peripheral blood counts. While testing for MDS-related molecular abnormalities is not justified in individuals without a cytopenia, appreciating the linkage between abnormal peripheral blood counts and specific myeloid gene mutations would support the need for genetic testing. Furthermore, we found that approximately 50% of practicing hematologists and oncologists do not send MDS bone marrow specimens for conventional cytogenetic testing (Craig, et al. Leuk Res 2011), and even fewer order gene mutation profiling, despite the informative potential of results for diagnosis, prognosis and therapy. Hence, there is a gap in recognizing when to order genetic testing in MDS. To address this, bone marrow aspiration cells from patients with morphologically and clinically confirmed MDS were examined for genomic mutations by conventional cytogenetics and targeted next generation sequencing (NGS). Sequencing covered mutations in the following genes: TET2, SF3B1, ASXL1, DNMT3A, SRSF2, RUNX1, NRAS, ZRSR2, EZH2, ETV6, TP53, CBL, NPM1, JAK2, U2AF1, IDH1, KRAS, IDH2, FLT3, PTPN11, and SETBP1. The average depth of NGS was 10,000x and mutant allele frequency was >5%. Association between genomic mutations and peripheral blood counts were evaluated using the Kruskal-Wallis test. 147 patients with WHO-defined MDS were included in this study. 12/147 (8%) had very good cytogenetic risk disease, 104/147 (71%) were good risk, 22/147 (15%) were intermediate risk, 4/147 (3%) were poor risk, and 5/147 (3%) were very poor risk. Anemia was significantly associated with SF3B1 mutations (P=0.0017), while higher hemoglobin values were significantly associated with SRSF2 mutations (P=0.0051). Macrocytosis was associated with SF3B1 (P<0.0001) and ZRSR2 (P=0.0382) mutations. Thrombocytopenia (<100x109 /L) was associated with mutations in SRSF2 (P=0.0148), TP53 (P=0.0005), or U2AF1 (0.0434). Higher platelet counts were found in patients with SF3B1 mutations (P<0.0001). Higher total white blood cell counts (P<0.0001) and higher absolute neutrophil counts (P<0.0001) were noted in patients with SF3B1 mutations. Absolute monocyte counts were higher in patients with NRAS (P=0.0237) and SF3B1 (P=0.0122) mutations. TET2 mutations were associated with lower percentage of bone marrow blasts (P=0.0032). While patients with TP53 mutations tended to have higher IPSS-R score (P=0.0017), patients with SF3B1 mutations tended to have lower IPSS-R score (P=0.0133). Overall, patients with TP53 mutations were more likely to present with higher risk disease by IPSS-R than patients without TP53 mutations. In patients with MDS, certain myeloid gene mutations significantly associated with peripheral blood count abnormalities (Table 1). Genetic testing of bone marrow samples is warranted in MDS patients showing abnormal peripheral blood counts.Table 1Summary of Significant Associations Between Peripheral Blood Count Abnormalities and Myeloid Gene Mutations in Patients with MDS.Peripheral Blood Count AbnormalityGenetic MutationAnemiaSF3B1Higher HemoglobinSRSF2MacrocytosisSF3B1, ZRSR2Thrombocytopenia (<100x109 /L)SRSF2, TP53, U2AF1Higher Platelet CountSF3B1Higher Total WBC countSF3B1Higher Absolute Neutrophil Count (ANC)SF3B1Higher Absolute Monocyte Count (AMC)SF3B1, NRASLower % BM blastsTET2Lower IPSS-R scoreSF3B1Higher IPSS-R scoreTP53 DisclosuresCogle:OXiGENE: Research Funding.

High neutrophil to lymphocyte ratio measured before starting ipilimumab treatment is associated with reduced overall survival in patients with melanoma

There is an unmet need to identify markers predictive of response to ipilimumab in patients with melanoma because the number of responders to ipilimumab is low and its cost is very high. An increase in absolute lymphocyte count (ALC) or low neutrophil/lymphocyte ratio (NLR) just before the third infusion has been reported to be associated with better overall survival (OS). Our aim was to determine whether NLR measured before the first infusion was associated with OS. Data were collected on a consecutive series of 58 patients treated with ipilimumab in four hospitals, including 51 at stage M1c and four at stage M1b. The influences of the NLR and other factors such as lactate dehydrogenase (LDH), performance status, ALC, absolute neutrophil count (ANC) and corticosteroids on survival were studied. We also assessed this association with NLR categorized as a binary variable. The cut-off value for the NLR was determined with time-dependent receiver operating characteristic (ROC) analysis. Univariate and multivariate analyses were performed using Cox regression models. High NLR (≥) 4, high ANC LDH levels (>2), performance status ≥2, symptomatic brain metastases, and corticosteroids before week 1 were associated with poorer survival on univariate analysis. Using multivariate analysis, a significant association between high NLR (continuous variable) and poorer survival was demonstrated and remained significant after adjustment on potential confounders [hazard ratio (HR) = 1·21, 95% confidence interval (CI) 1·07-1·36]. NLR ≥4 was an independent prognostic factor (HR = 2·2, 95% CI 1·01-4·78). Intake of corticosteroids before week 1 was not an independent prognostic factor (HR = 1·28, 95% CI 0·54-3·06). High NLR (≥4) before initiating ipilimumab treatment in patients with metastatic melanoma is an independent prognostic indicator of poor survival.

Neutrophil and Lymphocyte Counts as Clinical Markers for Stratifying Low-Risk Prostate Cancer

IntroductionThe neutrophil-to-lymphocyte ratio (NLR) has emerged as a ubiquitous prognostic biomarker in cancer-related inflammation, specifically in patients with metastatic castration-resistant prostate cancer (PCa). We evaluated the clinical utility of the preoperative NLR, absolute neutrophil count (ANC), and absolute lymphocyte count (ALC) as a risk stratification tool for patients with low-risk PCa. Materials and MethodsWe identified 217 low-risk PCa patients with preoperative hematologic data who had met the criteria for active surveillance but had undergone robot-assisted radical prostatectomy at our institution from 2006 to 2015. Logistic regression models were constructed to determine whether the baseline NLR, ANC, and ALC were associated with upstaging, upgrading, and biochemical recurrence (BCR). Survival analyses were performed using the Kaplan-Meier method. ResultsOn multivariate analysis, a higher prostate-specific antigen level (odds ratio [OR], 1.554; 95% confidence interval [CI], 1.148-2.104), a greater number of positive cores (OR, 2.098; 95% CI, 1.043-2.104), and a higher ALC (OR, 4.311; 95% CI, 1.258-14.770) were associated with upstaging. More importantly, the 5-year biochemical recurrence-free survival was significantly lower in the high ANC group (ANC > 4.0 × 109/L) compared with that of the low ANC group (P = .011). The NLR was not associated with upstaging, upgrading, or BCR in our study cohort (P = .368, P = .573, and P = .504, respectively). The only significant association with upgrading was patient age (OR, 1.106; 95% CI, 1.043-1.173). ConclusionNLR was not useful in predicting adverse pathologic outcomes in our patients with low-risk PCa. However, relative neutrophilia and lymphocytosis might indicate an early manifestation of harboring a more aggressive PCa.

Monocyte Count and 30-Day Case Fatality in Intracerebral Hemorrhage.

Monocytes may contribute to secondary injury after intracerebral hemorrhage (ICH). We tested the association of absolute monocyte count with 30-day ICH case fatality in a multiethnic cohort. Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study is a prospective, multicenter, case-control study of ICH among white, black, and Hispanic patients. In 240 adults with nontraumatic ICH within 24 hours of symptom onset, we evaluated the influence of ICH score and complete blood count components on 30-day case fatality using generalized linear models. Mean age was 62.8 years (SD, 14 years); 61.7% were men, 33.3% black, and 29.6% Hispanic. Median ICH volume was 9.9 mL (interquartile range, 4.4-26.7). After adjusting for patient age and initial hemoglobin, higher total white blood cell count (P=0.0011), driven by higher absolute neutrophil count (P=0.002), was associated with larger ICH volume, whereas absolute monocyte count was not (P=0.15). After adjusting for age, Glasgow Coma Scale, ICH volume, location, and the presence or absence of intraventricular hemorrhage, baseline absolute monocyte count was independently associated with higher 30-day case-fatality (odds ratio, 5.39; 95% confidence interval, 1.87-15.49; P=0.0018), whereas absolute neutrophil count (odds ratio, 1.04; 0.46-2.32; P=0.93) and white blood cell count (odds ratio, 1.62; 0.58-4.54; P=0.36) were not. These data support an independent association between higher admission absolute monocyte count and 30-day case-fatality in ICH. Inquiry into monocyte-mediated pathways of inflammation and apoptosis may elucidate the basis for the observed association and may be targets for ICH neuroprotection.

Abstract T MP68: Validating the Association of Peripheral Monocyte Count with 30-Day Case-Fatality in Intracerebral Hemorrhage

Introduction: Preclinical models suggest an inflammatory response mediated by monocytes may contribute to secondary injury after intracerebral hemorrhage (ICH). We recently found an association of absolute monocyte count (AMC) with 30-day case fatality following ICH. We sought to validate this finding in an independent cohort of ICH patients. Hypothesis: AMC is independently associated with 30-day case-fatality following ICH. Methods: The Ethnic/Racial Variations of ICH (ERICH) study is a prospective, multi-center, case-control study of ICH among Caucasian, Black, and Hispanic patients. In 241 adult patients with nontraumatic ICH within 24 hours of symptom onset, demographic information, Glasgow Coma Scale (GCS), ICH volume, 30-day case-fatality, total white blood cell (WBC) count, absolute neutrophil count (ANC), AMC, and hemoglobin concentration were determined. Participating centers were requested to obtain WBC differentials on the 30 most recently enrolled cases. After receiving data on 411 subjects, we excluded 170 subjects whose initial WBC was &gt;24 hours from onset and in those where monocytes and neutrophils were not available, resulting in 241 cases for the analysis. Linear regression was used to evaluate factors associated with ICH volume (log transformed), and logistic regression for factors associated with 30-day case-fatality. Results: Mean age was 62.8 years (SD ± 14 years), 61.8% were men and 33.6% were Black. Median ICH volume was 9.7ml (IQR 4.3-26.7). After adjusting for patient age and initial hemoglobin, higher ANC (p= 0.001) and total WBC count (p=0.0005) were associated with larger ICH volume, whereas AMC was not (p=0.14). After adjusting for age, GCS, and ICH volume, baseline AMC was independently associated with higher 30-day case-fatality (OR 5.24, 95% CI 1.62-16.89, p=0.0056) whereas ANC (OR 0.85, CI 0.15-4.68, p=0.85) and WBC count (OR 0.58, CI 0.04-7.67, p=0.68) were not. Conclusions: In this independent cohort an association between higher admission monocytes and case fatality was corroborated independent of known clinical variables. This suggests a specific role of monocytes in secondary injury following ICH. Inflammatory and neuronal apoptotic pathways mediated by monocytes may be a target for neuroprotection in ICH.

Mutations in Histone Modulators and HOXA5 Methylation Levels Affects Survival in Azacitidine Treated MDS Patients

Introduction:Azacytidine (Aza) is first-line treatment for patients with higher-risk MDS but only around 50% of patients respond to therapy. Overall survival for this patient group is short and clinical decision-making tools are highly warranted. As Aza may improve survival also in patients with hematologic improvement or stable disease, survival may be a better response predictor than response rate.Methods:We evaluated the impact of clinical parameters (n=134), mutations (n=90) and DNA methylation profiles (n=42) on response and survival in a cohort of consecutive patients with higher-risk MDS treated with Aza. Targeted sequencing of 42 genes involved in myeloid disease and Illumina 450 methylation arrays were applied for mutational assessment and methylation profiling, respectively. The IWG criteria were used for response scoring.Results:Patients were eligible for analysis if they had received ≥1 dose of Aza. Median number of cycles given was 6 (range 1-29). Responses were scored as CR (22%), mCR (11%), PR (3%), HI (13%), SD (27%) and PD (13%). Fifteen patients (11%) were not evaluated for response due to early death. Disease duration was negatively associated with both response (p=0.035) and survival (p=0.001). Adverse cytogenetics and high absolute neutrophil count was associated with shorter survival (p=0.03 and p=0.02) but not with response.No single mutation or group of mutations was associated with response although there was a weak positive trend for TET2 and ASXL1. When using survival as endpoint, ASXL1 showed a strong trend towards prolonged survival (median 29 vs 14 months, p=0.07) and, importantly, the group of patients with any mutation in histone modulators (ASXL1, EZH2, MLL) had a significant longer survival (median 28 vs 13 months, p=0.01). This remained significant in the cox regression model (HR 0.3223 (0.16-0.70 95% CI); p=0.002). No other mutations or group of mutations were associated with survival. Interestingly, previously reported negative prognostic factors including RUNX1 (p=0.82), TP53 (p=0.54), and the number of mutations (p=0.37), were not associated with survival in this Aza-treated cohortDNA methylation profiling identified 233 differentially methylated regions (DMRs) between responders and non-responders, corresponding to 200 genes, including six HOX-genes, which were highly enriched for gene ontology pathways involved in development and differentiation. High methylation of HOXA5, the most significant DMR, was associated with prolonged survival (22 vs 12 months, p=0.03). We also studied the methylation level of HOXA5 in CD34+ cells from patients with high-risk MDS and sorted compartments during myeloid differentiation in normal bone marrow. The methylation profile in responding patients was closer to that of differentiated cells while non-responding cells were closer to progenitor cells.Discussion:Single mutations have a limited impact on response rates. Howver, we demonstrate a clear survival benefit for patients with mutations in histone modulators, which previously have been reported as negative prognostic factors (Bejar, NEJM 2013; Haferlach, Leukemia 2014). Moreover, several negative risk factors, such as RUNX1, TP53, and the number of mutations were neutralized by Aza. Histone modulation mutations may therefore be used in the clinical decision-making for higher-risk MDS. We demonstrate for the first time that methylation profiles in genes involved in differentiation and development differ between responders and non-responders and that hypermethylation of HOXA5 is positively associated with survival (p=0.03). Since methylation pattern in HOXA5 is linked to differentiation status, we hypothesize that non-responding patients are skewed towards more immature differentiation. [Display omitted] [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Peripheral Monocyte Count Is Associated with Case Fatality after Intracerebral Hemorrhage

Leukocytosis is associated with hemorrhage volume and early neurologic deterioration after intracerebral hemorrhage (ICH). We examined total white blood cell (WBC) count, absolute monocyte count (AMC), and absolute neutrophil count (ANC) as potential readily available prognostic biomarkers in human ICH. In a retrospective study, adult patients aged 18years or older who presented to 1 of 2 local hospitals with nontraumatic ICH from July 2008 to December 2009 within 12hours of symptom onset were identified. Demographics, Glasgow Coma Scale (GCS), ICH volume, ICH location, and 30-day case fatality rates were determined. Total WBC count, ANC, AMC, and hemoglobin concentration were determined. Linear and logistic regressions were used to evaluate factors associated with baseline ICH volume (log transformed) and 30-day case fatality, respectively. Of the 186 patients, mean (±SD) age was 67.3±14.8years; 51% were men and 22% were black. Median (interquartile range) ICH volume was 12.8 (4.9, 29.4) mL. After adjusting for patient age and initial hemoglobin, higher initial WBC count (P=.0009) and higher ANC (P=.006) were associated with higher ICH volume, whereas AMC was not (P=.4). After adjusting for patient age, GCS, intraventricular hemorrhage (+/-), stroke location, and ICH volume, baseline AMC was associated with greater odds of 30-day case fatality (odds ratio 2.26, 95% confidence interval 1.10-4.65, P=.03). The association of AMC with higher 30-day case fatality after ICH is hypothesis generating. Given the lack of association between presenting AMC and ICH volume, AMC may contribute to secondary injury after ICH (hematoma expansion and/or cerebral edema).

Tu1134 Layered Pattern of Enhancement and Retrodilation At Magnetic Resonance Enterography Predict the Outcome of Anti-TNF Alpha Therapy in Patients With Moderate-to-Severe Ileal Crohn's Disease

of 1-31. New/worse inflammation was found in 43.8% of CTs while any new/worse finding was found in 57.4%. PA+ occurred in 16.8% of CTs. Univariate analysis shows that younger and female patients were less likely to have I but not PA+. Steroid use did predict a higher probability of PA+ (OR 1.58, 95%CI 1.01-2.47) but not I (OR 1.01, 95%CI 0.70-1.44). Biologic agents and other immunosuppression did not predict either outcome. Among the labs, CRP was a good predictor of I and PA+ while ESR only predicted PA+. Higher absolute neutrophil count and lymphocyte count predicted both outcomes. The multivariable model for I had a c statistic of 0.68; a cutoff of 16% has a sensitivity of 99.6% and negative predictive value of 92.3%. The model for PA+ had better performance characteristics with a c statistic of 0.80; a cutoff of 5% has a sensitivity of 94.9% and a negative predictive value of 97.7%. Conclusions: Patients with CD are exposed to radiation frequently but have significant new/worse findings less than 60% of the time. Models with good negative predictive values predicting I and PA+ were identified. Automated use of these models could aid ER physicians in the decision to avoid CT scans in patients with low likelihood of a positive scan. Prospective studies are needed to validate these models and their utility in clinical practice.

Point prevalence of Pneumocystis pneumonia in patients with non-Hodgkin lymphoma according to the number of cycles of R-CHOP chemotherapy

R-CHOP chemotherapy composed of rituximab, cyclophosphamide, adriamycin, vincristine, and prednisolone which might increase the risk of Pneumocystis pneumonia in patients with non-Hodgkin lymphoma. We estimated the point prevalence of Pneumocystis pneumonia in non-Hodgkin lymphoma patients according to the number of R-CHOP cycles and investigated whether cytoreduction by chemotherapy is associated with Pneumocystis pneumonia development. We retrospectively established a cohort of patients who received R-CHOP for non-Hodgkin lymphoma in our institution. Using this cohort, we estimated the incidence rate and point prevalence of definite and probable Pneumocystis pneumonia. To assess factors associated with Pneumocystis pneumonia development several clinical variables, including absolute neutrophil and lymphocyte count at the time of non-Hodgkin lymphoma diagnosis and when the last R-CHOP cycle was administered, were compared between patients with and without Pneumocystis pneumonia. Of 713 patients in the cohort, 14 and 18 patients were diagnosed with definite and probable Pneumocystis pneumonia, respectively. The overall incidence of definite and definite plus probable PCP in NHL patients receiving R-CHOP were 2.0 % (14/713; 95 % CI, 1.1–3.3 %) and 4.5 % (32/713; 95 % CI, 3.2–6.4 %), respectively. This corresponded to 3.8 (95 % CI, 2.2–6.4) and 8.4 (95 % CI, 5.9–11.9) per 1000 persons. Many cases of Pneumocystis pneumonia (22/32, 68.7 %) developed after administration of the fourth R-CHOP cycle. However, there was no statistical difference in Pneumocystis pneumonia prevalence between patients receiving four or more cycles of R-CHOP and fewer than. Higher absolute neutrophil count (4,742/mm3 vs. 2,627/mm3; p < 0.01) was associated with Pneumocystis pneumonia development at the last R-CHOP cycle, while absolute lymphocyte count at the time of NHL diagnosis was not. Contrary to expectations, Pneumocystis pneumonia is not a frequent complication of R-CHOP treatment for non-Hodgkin lymphoma. Cytoreduction of R-CHOP might not be a risk factor of Pneumocystis pneumonia development. Universal prophylaxis against Pneumocystis pneumonia during R-CHOP treatment could not be strongly recommended.Electronic supplementary materialThe online version of this article (doi:10.1007/s00277-012-1592-1) contains supplementary material, which is available to authorized users.

Initial Characteristics of Kawasaki Disease With Cerebrospinal Fluid Pleocytosis in Febrile Infants

To distinguish between febrile infants with cerebrospinal fluid pleocytosis who are finally diagnosed with Kawasaki disease and those with enterovirus meningitis poses a diagnostic challenge. We compared clinical and laboratory features at admission between two groups of infants, aged 30-90 days, to identify markers of Kawasaki disease that initially presented as cerebrospinal fluid pleocytosis. During a 2-year period, 100 patients exhibiting cerebrospinal fluid pleocytosis were studied, including six (6.0%) with Kawasaki disease and 30 (30.0%) with enterovirus meningitis. A longer duration of fever before admission (P < 0.01), higher absolute neutrophil count (P < 0.01), increased C-reactive protein level (P < 0.01), pyuria (P = 0.02), and less prominent cerebrospinal fluid pleocytosis (P = 0.01) were identified as initial features of infants finally diagnosed with Kawasaki disease. No significant differences were evident in white blood cell count; platelet count; levels of hemoglobin, alanine aminotransaminase, aspartate aminotransferase, albumin, and sodium; cerebrospinal fluid chemistry; or presence of a rash. Our observations may offer early indicators of Kawasaki disease for timely diagnoses in febrile infants with cerebrospinal fluid pleocytosis.

Comparison of Two Inflammation-Based Prognostic Scores in Patients with Unresectable Advanced Gastric Cancer

Objectives: The objective of this study was to compare the usefulness of two inflammation-based prognostic scores, neutrophil to lymphocyte ratio (NLR) and modified Glasgow Prognostic Score (mGPS), assessed at diagnosis in stage IV advanced gastric cancer (AGC). Methods: We retrospectively reviewed the medical records of 104 patients with newly diagnosed metastatic AGC treated with palliative chemotherapy. Results: In the univariate analysis, the following variables were associated with shorter overall survival (OS): poor or undifferentiated histology (p = 0.013), more than 1 metastasis (p = 0.004), the presence of lymph node metastasis (p = 0.003), the presence of bone metastasis (p = 0.019), a lower albumin level (p < 0.001), elevated C-reactive protein (p < 0.001), a high absolute neutrophil count (p = 0.016), NLR ≥3 (p < 0.001) and higher mGPS (p < 0.001 and p = 0.007, respectively). In the multivariate analysis, high NLR and mGPS were independent prognostic factors for shorter OS (p = 0.037, p < 0.001 and p = 0.010, respectively), along with lymph node metastasis (p = 0.005) and histological subtype (p = 0.048). Conclusion: This study suggests that the inflammatory markers, NLR and mGPS, are independent prognostic factors for OS in patients with unresectable AGC treated with palliative chemotherapy.

Healthcare-Associated Infections at a Children's Cancer Hospital, 1983–2008

Little is known about the incidence and etiology of healthcare-associated infections in immunosuppressed children. Data collected prospectively between 1983 and 2008 were used to analyze changes in the rate, types of infection, and infecting organisms over time in patients treated at a children's cancer hospital. Neutropenia was evaluated as a risk factor. Over the 26-year study period, 1986 healthcare-associated infections were identified during 1653 hospitalizations. The infection rate decreased significantly from 5.6 to 2.0 infections per 100 discharges (P<.01) and from 9.0 to 3.7 infections per 1000 patient-days (P<.01). Bloodstream infections were the most common type of infection (32.7% of all infections). Staphylococci (46.4% of Gram-positive bacteria), Escherichia coli (36.7% of Gram-negative bacteria), and Candida spp. (68.7% of fungi) were the most common pathogens isolated. An absolute neutrophil count (ANC) nadir <100 per mm(3) was significantly associated (P<.0001) with an increased rate of infections compared with higher ANC nadirs. Despite a steady expansion in hospital capacity and patient encounters over the last 3 decades, rates of healthcare-associated infections decreased significantly at our hospital. These data suggest that sustained decreases in the rate of healthcare-associated infections in immunosuppressed children are possible. An ANC <100 per mm(3) is a risk factor for healthcare-associated infections in this population.

Immunosuppressive Therapy in Aplastic Anemia

To assess the response to antithymocyte globulin based immunosuppressive therapy (IST) in pediatric patients with idiopathic aplastic anemia. Thirty patients (19 boys and 11 girls) with aplastic anemia received antithymocyte globulin and cyclosporine. Twenty-two patients had severe and 8 had very severe aplastic anemia. Mean age of the patients was 9.19 ± 2.56y. Three patients died within 1mo of therapy, two due to sepsis and one due to intracranial hemorrhage. Twenty-seven patients were analyzed for response to therapy. Eight patients (29.7%) responded at 3mo: 3 complete response (CR) and 5 partial response (PR). Six mo after the therapy, overall response (OR) was seen in 9/27 (33.3%), with one more patient in no response group achieving partial response. At 1year, patients in CR maintained their status and 1 patient in PR group relapsed. He again achieved partial response with repeat course of ATG. Responders had significantly shorter duration of illness and higher absolute neutrophil count as compared to non responders to IST. None of the patients developed acute leukemia in the follow up. The treatment of aplastic anemia in pediatric patients is a challenging task. One third of the patients achieved overall response which included both complete and partial response.

Mycobacterial infections in adult patients with hematological malignancy

We retrospectively analyzed the clinical and microbiological characteristics of adult patients with hematological malignancy and nontuberculous mycobacteria (NTM) infections from 2001 to 2010. During the study period, 50 patients with hematological malignancy and tuberculosis (TB) were also evaluated. Among 2,846 patients with hematological malignancy, 34 (1.2%) patients had NTM infections. Mycobacterium avium-intracellulare complex (13 patients, 38%) was the most commonly isolated species, followed by M. abscessus (21%), M. fortuitum (18%), and M. kansasii (18%). Twenty-six patients had pulmonary NTM infection and eight patients had disseminated disease. Neutropenia was more frequently encountered among patients with disseminated NTM disease (p = 0.007) at diagnosis than among patients with pulmonary disease only. Twenty-five (74%) patients received adequate initial antibiotic treatment. Five of the 34 patients died within 30 days after diagnosis. Cox regression multivariate analysis showed that chronic kidney disease (p = 0.017) and neutropenia at diagnosis (p = 0.032) were independent prognostic factors of NTM infection in patients with hematological malignancy. Patients with NTM infection had higher absolute neutrophil counts at diagnosis (p = 0.003) and a higher 30-day mortality rate (15% vs. 2%, p = 0.025) than TB patients. Hematological patients with chronic kidney disease and febrile neutropenia who developed NTM infection had significant worse prognosis than patients with TB infection.

C-Reactive Protein for the Enhanced Evaluation of the Systemic Inflammatory Response Syndrome (SIRS)

Introduction: An elevation in the CRP may provide an early indication of developing SIRS with progression to sepsis that is more sensitive than the standard clinical criteria of fever (or hypothermia), tachypnea, tachycardia, and leukocytosis with neutrophilia (or neutropenia). The problem of false positive rate for SIRS resides mainly in the common occurance of tachypnea and tachycardia in presenting patients, and in the confounding presence of neutrophilia without reference to good measures of a left shift. The objective of this study was to investigate how using CRP as a marker to confirm the presence of early sepsis might reduce the false positive rate inherent in the defining SIRS criteria. Materials and Methods: One hundred sixty eight patients with leukocytosis greater than 12,000 associated with a high absolute neutrophil count were studied. Those that met the inclusion criteria were analyzed for CRP response. Results: A linear correlation between CRP elevation and the defining criteria for SIRS was found except there was no correlation with absolute neutrophil count.

Prevalence of Malaria Parasitemia among Human Immunodeficiency Virus (HIV) Seropositive Pregnant Women in Kwale, Delta State

A total of 196 pregnant women attending antenatal clinic in Kwale Central Hospital, were prospectively studied to determine their Human immunodeficiency virus status and Malaria parasitaemia from July 2006 to December 2008. Human immunodeficiency virus status and malaria parasitaemia were determined using (WHO) systems two and Field staining technique respectively. Malaria parasite was further confirmed with Geimsa staining technique. Haematocrit and Leishman staining techniques were used for full blood count determination. A prevalence rate of 8.2%,6.6% and 2.6% were observed for HIV, malaria parasite and HIV/ malaria parasite infections among the subjects examined respectively. Also, a prevalence rate of 31.3% was obtained for malaria parasite among HIV seropositive pregnant women with 60% and 40% malaria density respectively. The HIV/malaria positive subjects had reduced mean packed cell volume of 21.2%,mean total white blood cell count of 2900mm/3 and a high absolute neutrophil count. The adoption of routine malaria/HIV screening as parts of management policy to confirm co-infections and proper management of pregnant women in endemic areas is imperative, as discussed on the results of this study.KEYWORDS: Prevalence, Malaria, Human immunodeficiency virus, pregnancy

Average Absolute Neutrophil Count During Maintenance Chemotherapy In Latino Versus Non-Latino Caucasian Patients with Childhood Acute Lymphoblastic Leukemia

AbstractAbstract 3237Despite recent advances in the treatment of childhood acute lymphoblastic leukemia (ALL), Latino children consistently have survival rates approximately 10% lower than among Caucasians. The thiopurine, 6-mercaptopurine (6MP), is an essential component of ALL maintenance therapy; therefore differences in adherence, absorption, and/or the pharmacogenomics of 6MP metabolism may play a role in explaining their survival difference. The presence of one or more polymorphism of the enzyme thiopurine methyltransferase (TPMT) affects TPMT enzyme activity, and therefore sensitivity to 6MP. Genotype is commonly evaluated prior to initiating 6MP therapy, to identify patients at risk for significant myelosuppression who will require dose reductions, allowing patients to maintain targeted neutrophil counts while forming adequate concentrations of the metabolite thioguanine nucleotide (TGN). The TPMT phenotype reflects actual enzyme activity level, but it is less commonly measured prior to 6MP therapy, since results may be obscured by recent packed cell transfusions frequently given to patients at diagnosis. Most individuals (89%) inherit a normal TPMT genotype (wild type); however, there is significant heterogeneity of TPMT enzyme activity within this group. Recent data suggest that ALL patients who are genotypically normal, and have higher TPMT enzyme activity may have inferior survival compared to patients with lower TPMT enzyme activity. Higher activity may be associated clinically with a higher absolute neutrophil count (ANC) as higher TPMT enzyme activity is associated with the formation of more methylated metabolite and less TGN. Thus, we hypothesized that our Latino patients with wild type TPMT activity would have a skewed distribution of TPMT activity with higher activity than our non-Latino Caucasian population and that the absolute neutrophil count (ANC), which is used to dose adjust 6MP, would serve as a surrogate marker of TPMT enzyme activity.We conducted a retrospective analysis of all patients with ALL undergoing maintenance chemotherapy between 2005–2009 at Children's Medical Center of Dallas. All patients diagnosed with ALL between January 1, 2005 to August 1, 2009, who were self-described Latino and non-Latino Caucasian, and treated per a current COG treatment protocol, were included in this analysis. We recorded demographic information, diagnostic and risk stratification characteristics, all complete blood counts during maintenance therapy, 6MP and methotrexate dosing, and all coinciding infections and medications which could affect neutrophil counts. 134 patient records were analyzed. The nine patients known to have a heterozygous TPMT genotype were excluded; however, the 31 (25%) patients who had not been genotyped were included. Of those 125 patients, 68 (54%) were self-described Latino and 57 (46%) were non-Latino Caucasian. There was no significant difference in the average dose of 6-MP prescribed during maintenance therapy among Latino versus non-Latino Caucasians (445 mg/m2/week vs 426 mg/m2/week, p = 0.4), nor was there a significant difference in the average ANC for Latinos versus non-Latino Caucasians (2,199 vs 2,134, p = 0.6, by the Wilcoxon rank sum test). There was a wide range of enzyme activity in both Latino and non-Latinos Caucasian patients (17.4 - 60.6 EU/mL and 16.9 – 50.6 EU/mL, n = 32), with 3 Latino patients having activity levels > 50 EU/mL. In conclusion, this study did not demonstrate a difference in average ANC during maintenance therapy between Latino and non-Latino Caucasians in our Dallas population. Thus, if there were significant differences in either adherence or metabolism of 6MP secondary to a skew in TPMT activity, it was not detectable through an analysis of the average ANC during maintenance therapy. Enzyme activity was widely distributed in patients with wild type genetics, in both populations. Our study has many limitations, including small sample size, use of average ANC as a surrogate rather than direct measurements of TPMT enzyme activity, reliance on the medical record for definition of ethnicity, and possible inclusion of non-wild type patients who had not been genotyped. A larger prospective study is needed to directly evaluate TPMT enzyme activity in patients with known wild type genetics in order to elucidate the role of TPMT phenotypic variation in TPMT wild-type Latino patients. Disclosures:No relevant conflicts of interest to declare.

Occult Pneumonia in Infants With High Fever Without Source

The prevalence of pneumonia in infants with high fever without source (FWS; temperature, > or =39.0 degrees C) and a white blood cell (WBC) count greater than 20 x 10(9)/L (occult pneumonia) has been reported to be 20% before the introduction of the 7-valent pneumococcal conjugated vaccine (PCV7). This is the main reason for carrying out chest x-ray (CXR) on infants with high FWS. The aims of this study were to establish the prevalence of occult pneumonia in well-appearing infants with high FWS (temperature, > or =39.0 degrees C) and a WBC count greater than 20 x 10(9)/L in the era of PCV7 and to analyze the value of WBC, absolute neutrophil count (ANC), and C-reactive protein (CRP) level as predictors of the risk of occult pneumonia in these patients. We conducted a multicenter prospective study in 4 pediatric emergency departments including children younger than 36 months with FWS (temperature, > or =39.0 degrees C) and a WBC count higher than 20 x 10(9)/L on whom a CXR was performed in the absence of respiratory findings. Physicians completed a questionnaire when observing the infant, and the attending physician or, when in doubt, the radiologist interpreted the CXR. Multivariable binary logistic regression was used to estimate the adjusted relative influences of the aforementioned factors on the prevalence of radiological pneumonia. During an entire year (September 2006 to September 2007), we included 188 infants (aged 1-36 months; 56.2% were males) with high FWS and a WBC count greater than 20 x 10(9)/L (range, 20-44.7 x 10(9)/L) on whom a CXR was performed. Of the 188 chest radiographs obtained, 37 (19.7%) were interpreted by the radiologist. Consolidation in the chest radiographs was detected in 25 (13.3%). The probability of an infant with high FWS and WBC of 20 x 10(9)/L or greater having pneumonia was related to 3 of the studied variables: age, ANC, and serum CRP level. The incidence of pneumonia increased with age (odds ratio [OR] of 2.62 for infants >12 months; 95% confidence interval [95% CI], 1.04-6.60), CRP level greater than 100 mg/L (OR, 3.18; 95% CI, 1.19-8.51), and ANC greater than 20 x 10(9)/L (OR, 3.52; 95% CI, 1.37-9.06). White blood cell count was not predictive of occult pneumonia when ANC was taken into account. In the era of PCV7, the incidence of pneumonia in infants younger than 36 months with high FWS and WBC count greater than 20 x 10(9)/L seems to be lower than that previously reported. However, this is not a uniform group because the incidence of pneumonia increases in infants older than 12 months and with higher ANC and serum CRP level.

Rhinosinusitis in autologous and allogeneic bone marrow transplantation: a retrospective study on the performance of imaging studies on severity and prognostic evaluation

The objective of this work was to evaluate the diagnostic and prognostic performance of a traditional imaging staging system for rhinosinusitis in the bone marrow transplantation (BMT) scenario. A retrospective cohort study was carried out at a bone marrow transplantation referral center involving subjects who underwent allogeneic or autologous BMT from September 1st 2005 to September 31st 2007 and later evolved with rhinosinusitis during the BMT inpatient period. Patients who had a previous history of sinusal disease or otolaryngologic surgery were excluded from the study. Data concerning mortality, the treatment of rhinosinusitis and BMT outcomes were extracted from medical files. The collected parameters were compared to the Lund-Mackay tomographic staging system score which was calculated based on available tomography films of each patient. A total of 85 BMT were performed and 23 allogeneic and 14 autologous (43.5%) BMT patients evolved with rhinosinusitis during transplantation. A significant association with LMS was found for the absolute neutrophil count (ANC), with a higher ANC (>500/mm3) correlating with a higher LMS (Mean LMS for lower ANC 6.08 and higher ANC 9.71 points, p<0.05). Need for surgical management and post-BMT admissions, the resolution of the rhinosinusitis and overall mortality had no significant correlation with LMS. Patients with less than 500 neutrophils/mm3 are known to be prone to more severe infections, but paradoxically showed lower LMS when developing rhinosinusitis. However, there were no differences in the main outcomes between those with higher and lower LMS. This would possibly lead to an equivocal assumption of a less severe disease. Severely neutropenic patients are probably not able to mount an effective inflammatory response capable of inducing significant tomographic abnormalities. So, this imaging study would not be able to adequately evaluate the extent of sinusal involvement. We thus conclude that LMS is not an adequate staging system to evaluate the severity of BMT sinusal disease. Rev. Bras. Hematol. Hemoter.

Clinical, laboratory, and microbiological differences between children with simple or complicated mastoiditis

To assess clinical, laboratory, and microbiological differences between children with simple and complicated mastoiditis. Data on all children who were hospitalized at a tertiary center for acute mastoiditis over a 5-year period were collected from the computerized files. Findings were compared between those with simple mastoiditis vs. cases with intra- or extra-cranial complications. Of the 308 children with acute mastoiditis, 55 (17.9%) had complicated disease. This group was characterized by a significantly higher maximal fever at presentation and higher absolute neutrophil count and C-reactive protein level than the children with simple disease. There was no statistically significant between-group difference in age, history of otitis media, prior antibiotic treatment, days of illness before presentation, absolute leukocyte count, and platelet count. No difference was detected between the groups in the penicillin and ceftriaxone susceptibility of the Streptococcus pneumoniae isolates. High-grade fever, high absolute neutrophil count, and high C-reactive protein level may serve as clinical and laboratory markers of complicated mastoiditis. Children with these findings warrant close follow-up and perhaps, earlier surgical intervention.