Median White Blood Cell Count Research Articles

Clinical Characteristics and Prognosis of Acute Myeloid Leukemia with FLT3-ITD Mutation

To investigate the clinical characteristics of acute myeloid leukemia(AML) patients with FLT3-ITD(Fms-like tyrosine kinase3, intenal tandem duplication) mutation and their response to treatment. Retrospective analysis of 128 newly diagnosed AML (except type M3) patients was performed between January 2014 and July 2017. Patients were divided into FLT3-ITD mutated group and non-mutated group. Mutation detection was carried out by using polymerase chain reaction(PCR) and gene sequencing analysis. Standard 3 + 7 or CAG regimen were taken as the first induction chemotherapy, 4 cases received sorafenib, overall survival (OS) was calculated by Kaplan-Meier. Ninety-seven patients can be evaluable for clinical data available; 4 patients were FLT3-TKD mutated, which accounted for 4.1%; 19 patients were FLT3-ITD mutated, which accounted for 19.59%(19/97). Median white blood cell count (WBC), percentage of peripheral blasts and LDH value were significantly higher in FLT3-ITD group than those in non-mutated group [64.65(1.07-587.92)×109/L vs 39.68 (0.45-203.81) ×109/L](P<0.01), [69.62(16-99)% vs 36.35(0-92) %](P<0.01 ) and [LDH 526(124-2 729)U/L vs 265(20-1977)U/L](P<0.05), respectively. The frequency of coexisting NPM1 mutation was higher in FLT3-ITD group than that in non-mutated group [36.8(7/19)% vs 6.8 (5/74) %](P<0.01). The CR+PR was lower in FLT3-ITD group than that in non-mutated group [31.6(6/19)% vs 64.9 (48/74)%](P<0.05). OS in FLT3-ITD group was significantly shorter than that in non-mutated group (5 vs 18 months)(P<0.05). There is no significant difference in OS between FLT3-ITD concomitant with and without NPM1 mutation groups(5 vs 5 months)(P>0.05). The median OS was 13 months for the FLT3-ITD patients taking sorafenib. The FLT3-ITD is a common mutation in AML, FLT3-ITD mutated AML is more likely concomitant with NPM1 mutation with higher number of WBC, percentage of peripheral blasts and LDH value, thus CR is low after the 1st treatment and survival is poor.

The Biology of Chronic Myelogenous Leukemia in Childhood and Young Adolescents: An Indian Perspective

Abstract Objective: The purpose of this study was to determine the clinical, biological, and molecular characteristics at diagnosis in children and adolescents with chronic myelogenous leukemia (CML) in the Indian scenario at our tertiary patient care center. Subjects and Methods: We evaluated 51 children and adolescents with CML registered at our clinic, from January 2007 to December 2015. The mean and median of various parameters were calculated using a Microsoft excel sheet and SPSS software version 16. Results: The median age of presentation in children was 16 years; 92.2% of them were older than 10 years, with a higher prevalence in boys than girls (gender ratio 2.6:1). The symptoms at presentation were fatigue, fever, awareness of mass due to splenomegaly, and bleeding manifestations. One patient presented with Bell's palsy. Markedly raised leukocyte counts were present in 29.4% patients (median white blood cell count &gt;400 × 109/L). Most of the patients presented in the chronic phase of the disease, four each were in accelerated phase and blast crisis, respectively. Majority of patients were categorized as intermediate risk as per Sokal and Hansford score. About 60.7% of these pediatric patients fell in low-risk category as per European Treatment and Outcome Study score at baseline. A predominance of transcript P210-b3a2 (68%) was observed in the children who were studied for the type of chimeric BCR-ABL mRNA. Conclusions: This is one of the most recent reported series of CML in children and adolescents from India highlighting the difference in presentation from adults; mainly hepatomegaly, bleeding manifestations, and higher leukocyte count. Presence of b3a3 transcript of p210 breakpoint of BCR-ABL was more common in children (68%) than b2a2 transcript (32%) when compared to adults as recently described in a study from India, which may explain the differences at presentation.

Juvenile Myelomonocytic Leukemia in Turkey: A Retrospective Analysis of Sixty-five Patients.

Objective:This study aimed to define the status of juvenile myelomonocytic leukemia (JMML) patients in Turkey in terms of time of diagnosis, clinical characteristics, mutational studies, clinical course, and treatment strategies.Materials and Methods:Data including clinical and laboratory characteristics and treatment strategies of JMML patients were collected retrospectively from pediatric hematology-oncology centers in Turkey.Results:Sixty-five children with JMML diagnosed between 2002 and 2016 in 18 institutions throughout Turkey were enrolled in the study. The median age at diagnosis was 17 months (min-max: 2-117 months). Splenomegaly was present in 92% of patients at the time of diagnosis. The median white blood cell, monocyte, and platelet counts were 32.9x109/L, 5.4x109/L, and 58.3x109/L, respectively. Monosomy 7 was present in 18% of patients. JMML mutational analysis was performed in 32 of 65 patients (49%) and PTPN11 was the most common mutation. Hematopoietic stem cell transplantation (HSCT) could only be performed in 28 patients (44%), the majority being after the year 2012. The most frequent reason for not performing HSCT was the inability to find a suitable donor. The median time from diagnosis to HSCT was 9 months (min-max: 2-63 months). The 5-year cumulative survival rate was 33% and median estimated survival time was 30±17.4 months (95% CI: 0-64.1) for all patients. Survival time was significantly better in the HSCT group (log-rank p=0.019). Older age at diagnosis (>2 years), platelet count of less than 40x109/L, and PTPN11 mutation were the factors significantly associated with shorter survival time.Conclusion:Although there has recently been improvement in terms of definitive diagnosis and HSCT in JMML patients, the overall results are not satisfactory and it is necessary to put more effort into this issue in Turkey.

Clinical Efficacy of Decitabine Combined with or without Cytarabine-based Low Dose Regimen for Senile patients with Acute Myeloid Leukemia

To investigate the therapeutic effectiveness and side effects of decitabine combined with or without cytarabine-based low dose regimen for acute myeloid leukemia in geratic patients. Clinical data of 8 geratic patients (aged over 70 years) suffered from acute myeloid leukemia from September 2009 to March 2012 were analyzed retrospectively, including age, sex, peripheral blood and bone marrow characteristics and so on. These patients were treated by an 1-hour intravenous infusion of decitabine 20 mg/m2 per day for 5 consecutive days every 4 weeks combined with or without low dose regimen dominantly consisting of cytarabine 20 mg per day as subcutaneous injection for seven consecutive days. The therapeutic effectiveness and side-effects were evaluated. Among 8 patients, incinding 3 males and 5 females aged between 71-84 years old, their median white blood cell count was 31.2(1.38-179)× 109/L, and median bone marrow blast cell ratio was 42.7(23-94)% at the initial diagnosis.The median treatment courses was 2.5 (1-20).After treatment by this protocol,2 patients achieved complete remission(CR) (25%), 2 patients achieved partial remission (PR)(25%), 3 were not relieved, and 1 died, thus the overall response rate reached to 50% (4/8). The median overall survival time was 9.5 (2-36) months, and the overall survival time of 3 patients reached 1 year or more. The main side-effects of treatment were grade III-IV of myelosuppression (87.5%) and pneumonia (50%). Decitabine combined with or without cytarabine-based low dose regimen is promising for the treatment of geriatric acute myeloid leukemia, thus improving the overall response rate, and prolonging overall survival time.

Clinical and laboratory features of urinary tract infections in young infants.

ABSTRACTIntroduction:Urinary tract infection (UTI) is the most common serious bacterial infection in young infants. Signs and symptoms are often nonspecific.Objectives:To describe clinical, demographic and laboratory features of UTI in infants ≤ 3 months old.Methods:Cross-sectional study of infants ≤ 3 months old with UTI diagnosed in a pediatric emergency department, for the period 2010-2012. UTI was defined as ≥ 50,000 colony-forming units per milliliter of a single uropathogen isolated from bladder catheterization. Paired urinalysis and urine culture from group culture-positive and group culture-negative were used to determine the sensitivity and specificity of pyuria and nitrite tests in detecting UTI.Results:Of 519 urine cultures collected, UTI was diagnosed in 65 cases (prevalence: 12.5%); with male predominance (77%). The most common etiologies were Escherichia coli (56.9%), Klebsiella pneumoniae (18.5%) and Enterococcus faecalis (7.7%). Frequent clinical manifestations were fever (77.8%), irritability (41.4%) and vomiting (25.4%). The median temperature was 38.7°C. The sensitivity of the nitrite test was 30.8% (95%CI:19.9-43.4%), specificity of 100% (95%CI:99.2-100%). Pyuria ≥ 10,000/mL had a sensitivity of 87.7% (95%CI:77.2-94.5%), specificity of 74.9% (95%CI:70.6 -78.8%). The median peripheral white blood cell count was 13,150/mm3; C-reactive protein levels were normal in 30.5% of cases.Conclusions:The male: female ratio for urinary tract infection was 3.3:1. Non-Escherichia coli etiologies should be considered in empirical treatment. Fever was the main symptom. Positive nitrite is highly suggestive of UTI but has low sensitivity; whereas pyuria ≥ 10,000/mL revealed good sensitivity, but low specificity. Peripheral white blood cell count and C-reactive protein concentration have limited usefulness to suggest UTI.

Bone Marrow Characterization in Sickle Cell Disease: Inflammation and Stress Erythropoiesis Lead to Suboptimal CD34 Recovery Compared to Normal Volunteer Bone Marrow

IntroductionGene therapy for sickle cell disease (SCD) requires modification of a high number of long term engrafting hematopoietic stem cells (LT-HSCs) sufficient to sustain production of the gene of interest at levels capable of overcoming the pathogenic HbSS phenotype. Unlike β-Thalassemia, the inflammatory bone marrow (BM) environment and stress erythropoiesis associated with SCD may have significant impacts on HSC quality and yield necessary for disease amelioration. Important work to optimize gene therapy through improvement in gene transfer efficiency, editing strategies, or transplant conditioning can only improve gene therapy in SCD if enough autologous HSCs are LT-HSCs, thus characterization of SCD BM and CD34+ HSCs is required. Collection type, storage, and delays in processing may further impact CD34+ recovery and should be investigated as a strategy to maximize LT-HSC recovery.MethodsTwenty milliliters of BM from subjects with SCD (HbSS genotype) and normal volunteers was collected in different anticoagulants (Heparin, ACD-A) and processed immediately(day 0) or stored at 40C and processed the following day(day 1). After isolation via Ficoll density gradient centrifugation, the mononuclear (MN) layer was stained with antibodies against inflammatory markers (CD36, CD35, CD11b, CD62L, CD62P), non-MN cells (GPA, CD66b, CD41/61), or processed for CD34+ selection using a magnetic microbead CD34+ selection kit and stained for CD34, CD45, and GPA expression. Data were analyzed by conventional and imaging flow cytometry, the latter confirming post-CD34+ selection flow data and demonstrating antibody intensity as a characterization of HSC heterogeneity and progenitor lineage. Complete blood count and hemoglobin (Hb) electrophoresis were obtained at the time of BM collection. Statistical analyses were performed using unpaired t-tests.ResultsBM was collected from 18 subjects (16 with SCD; 11M; age 21-41 years). Median Hb (8.6 vs. 13.5 gm/dL, p<0.01) and white blood cell count (8.8 vs. 4.2 K/mcL, p<0.05) differed significantly between SCD and non-SCD subjects. Median percent sickle Hb in SCD subjects was 62%. Inflammatory markers and contamination with red cell and platelet markers in the post-Ficoll MN layer were higher in SCD vs. non-SCD BM regardless of anticoagulant (CD35 24% vs. 13%, p<0.05; CD36 22% vs. 11%, p<0.05; CD62P 16% vs. 3%, p<0.05; GPA 16% vs. 4%, p<0.05; CD41/61 19% vs. 3%, p<0.05), and trended higher on day 1 in SCD BM in both anticoagulants, significantly in Heparin (GPA 23% vs. 33% on day 1, p<0.05). Total CD45 expression was lower in SCD vs. non-SCD BM in both anticoagulants (p<0.05) and on day 0 (p<0.05) and 1 (p<0.01), with Amnis data confirming a higher CD34+CD45- population in SCD BM (4 ± 2% vs. 0.5 ± 0.3%, p<0.05). While there was no significant difference in total CD34+ cell count between SCD and non-SCD BM after selection post-Ficoll, there was a trend for lower CD34+ count in SCD in both anticoagulants (2.6x10^5 vs. 4.7x10^5, p=0.1). SCD CD34+ cells were characterized by higher GPA expression (28 ± 5% vs. 13 ± 3% in non-SCD BM, p<0.01) that worsened in Heparin on day 1 (22 ± 6.3% vs. 35 ± 12.4%, p<0.05). Image cytometry confirmed a majority of GPA expression in SCD BM is from single cell CD34+CD45+GPA+ and CD34+CD45-GPA+ HSCs in addition to red cell aggregates, with an increase in CD34+CD45-GPA+ HSCs on day 1 (10 ± 5% vs. 0.6 ± 0.2 % on day 0, p<0.05). Furthermore, the percentage of CD34hi HSCs was lower in SCD vs. non-SCD BM, with >50% SCD HSCs characterized as CD34dim (56% vs. 4% in non-SCD BM, p<0.001). Lastly, the purity of CD34+ selection worsened from day 0 to day 1 in SCD BM in heparin (94% vs. 68 ± 8%, p<0.05) and ACD-A (88% vs. 68 ± 0.7%, p<0.05).ConclusionsSCD BM is characterized by increased inflammation and cell contamination in the MN layer regardless of anticoagulant that worsens over time in Heparin more significantly than in ACD-A. Compared to non-SCD BM, CD34+ HSC yield post-Ficoll is lower in SCD subjects, and is characterized by a larger proportion of CD34+CD45+GPA+ and CD34+CD45-GPA+ HSCs that rise with delays in processing. This indication of early differentiation along the erythroid lineage, with more than 50% of HSCs losing CD34+ intensity suggesting they are not LT-HSCs, suggests suppression of inflammation and stress erythropoiesis, combined with early cell processing may be critical for maximal HSC recovery necessary for successful gene therapy in SCD. [Display omitted] DisclosuresLuo:bluebird bio Inc.: Employment. Pierciey:bluebird bio: Employment.

Leukapheresis in 15 patients weighing 20 kg or less: A single centre experience

The application of apheresis equipment to perform leukapheresis (LK) in low weight paediatric patients is logistically complex and lacking of largest clinical performing experiences, meanwhile, the benefit from LK is controversial. In this study, 15 children with acute lymphoblastic leukemia(ALL)and acute myeloid leukemia (AML) and hyperleukocytosis were treated with the COBE Spectra apheresis system in the general paediatric ward by the staff from the department of Blood Transfusion. 26 LK procedures were performed. 12 patients (80%) were performed with peripheral veins, others (20%) with femoral veins. Median age, body weight of the patients was 4 years (range from1year 10 month to 7 years) and 15kg (range from10 to 20kg). The median white blood cell (WBC) count of pre-first-LK was 289×109/L (range from 108×109/L to 579×109/L). The median decrease in WBC count after each LK was 34% (range from 14% to 54%), and overall decrease in WBC after completion of LK procedures was 45% (range from 15% to 70%). All of the patients had no further signs of leukostasis and achieved marked reductions in WBC counts. Only minor clinical adverse events were attributable to LK. With adequate monitoring and experienced team, LK is a safe and may be a beneficial leukoreduction method in small patients weighing 20kg or less with ALL and AML.

Neuroborreliosis in Swedish Children: A Population-based Study on Incidence and Clinical Characteristics

Borrelia burgdorferi is a common cause of bacterial meningitis, but there are very few studies on incidence in Europe. The aim of this study was to report the incidence and symptoms of neuroborreliosis in Swedish children. Medical records of children (< 15 years) treated for neuroborreliosis 2002-2014 were studied retrospectively. The patients were identified in the computerized registers of discharge diagnoses at the Departments of Pediatrics and Infectious Diseases in Gothenburg, Borås, Trollhättan and Halmstad using International Classification of Diseases 10 diagnosis codes G51.0, G01.9 and/or A69.1. Of those, patients with symptoms compatible with neuroborreliosis and a white blood cell count in cerebrospinal fluid ≥ 7 cells/mm with ≥ 80% mononuclear cells were included. Only children living in the city of Gothenburg and 10 surrounding municipalities were included. Five hundred forty-eight children were included. The median age was 7 (1-14) years. The total incidence for the 13-year-period was 2.8/10,000 and remained unchanged during the period. The incidence was significantly higher in rural (4.0/10,000) than in urban municipalities (2.1/10,000). The most common presenting symptoms were headache (n = 335), fatigue (n = 330) and cranial nerve palsies (n = 329). The median duration of symptoms before admittance was 4.0 days for facial palsy and 14.0 days for other symptoms (P < 0.001). The median white blood cell count in cerebrospinal fluid was 129 (7-1069) cells/mm. This study is the largest so far in a pediatric population. The incidence of neuroborreliosis was higher than in previous European reports. This might be explained by increased Borrelia awareness, the distribution of tick population in Sweden, and the possibility that Swedish children more frequently play outdoors.

Changes in the haematological parameters of HIV-1 infected children at 6 and 12 months of antiretroviral therapy in a large clinic cohort, North-Central Nigeria

BackgroundPrior to commencing antiretroviral therapy (ART), haematological abnormalities are a common occurrence in individuals diagnosed with human immunodeficiency virus (HIV). In the course of receiving ART, these abnormalities usually improve. We determined the prevalence of haematological abnormalities in children diagnosed with HIV-1 and the changes in haematological parameters that occur after 6 and 12 months of being on ART. MethodsA cross-sectional study of HIV-1 infected children aged 2 months to 15 years, between July 2005 and March 2013, at the paediatric HIV clinic of the Jos University Teaching Hospital, Jos. Median values of repeated measures were compared using the Wilcoxon signed-rank sum test. ResultsThe prevalence of anaemia, thrombocytopenia and leukopenia among the 941 children studied, prior to ART was 6.4%, 7.0% and 8.6%. Median (IQR) haemoglobin (Hb) levels increased from 10 g/dL (9–11 g/dL) at baseline to 11 g/dL (10–12 g/dL) and 11 g/dL (10–12 g/dL) at 6 and 12 months of ART (P<0.001 and P<0.001), respectively, a 10% increase in both cases. Also, platelet count increased from a median of 327×103/μL (243–426×103/μL) at baseline to 333×103/μL (266–408×103/μL) at 6 months and 339×103/μL (267–420×103/μL) at 12 months, representing a 1.8% and 3.7% increase, respectively. The median total white blood cell count decreased from 7.4×103/μL (5.3–9.9×103/μL) at baseline to 5.9×103/μL (4.6–8.0×103/μL) and 5.8×103/μL (4.5–7.5×103/μL) at 6 and 12 months of ART (P<0.001 and P<0.001), a 20.3% and 21.6% decrease, respectively. ConclusionDuring the 12 months of ART, children in our cohort had significant improvements in haematological parameters such as haemoglobin levels and platelet counts, which would suggest an early positive response to ART.

The kinetics of white blood cell and the predictive factors of leukocytosis under oral or intravenous arsenic as the first-line treatment for acute promyelocytic leukemia

ObjectiveWe aimed to compare the kinetics of white blood cell (WBC) and explore predictive factors of leukocytosis in non-high-risk acute promyelocytic leukemia (APL), with oral arsenic plus all-trans retinoic acid (ATRA) or intravenous arsenic trioxide (ATO) plus ATRA as a first-line treatment. MethodsThe absolute count, doubling time and peak time of WBC were analyzed in 64 newly diagnosed non-high-risk APL patients who were treated with different induction regimens containing either oral Realgar-indigo naturalis formula (RIF) (n=35) or ATO (n=29). The end points were the dynamic changes of the WBC counts during induction. The time points started at day 1 and were selected over 3-day intervals for 28days. ResultsAmong the 64 included patients, the median initial and peak WBC counts were 1.78×109/L (range 0.31–9.89) and 12.16×109/L (range 1.56–80.01), respectively. The incidence of differentiation syndrome was 9.38%. The dynamic changes in leukocytosis showed a single peak wave in all the patients, and the median time to peak was 10 (range 2–26) days. A higher WBC count was observed in the RIF group than in the ATO group after 10days of treatment (9.22×109/L vs. 4.10×109/L, p=0.015). Patients with the peak WBC count >10×109/L had a shorter WBC doubling time compared to patients with a lower peak WBC (RIF group 4days vs. 7days, p=0.001; ATO group 4.5days vs. 23days, p=0.002). Univariate and multivariable analyses showed that the doubling time of WBC is an independent factor for the peak WBC count. ConclusionDifferent kinetics of WBC proliferation were observed during induction with oral arsenic plus ATRA and ATO plus ATRA. The doubling time of WBC is an important independent factor for predicting the peak WBC count.

Red blood cell distribution width is useful in discriminating adult onset Still's disease and sepsis within 24 hours after hospitalization.

Background/AimsRed blood cell distribution width (RDW) is a value representing the heterogeneity in the size of red blood cell, and it is usually used in distinguishing types of anaemia. Recently, it was reported that it could reflect the burden of inflammation in diverse diseases and their prognosis. Hence, in this study, we investigated whether RDW may contribute to discriminating adult onset Still’s disease (AOSD) from sepsis in serious febrile patients within 24 hours after hospitalization. MethodsWe reviewed the medical records and enrolled 21 AOSD patients, 27 sepsis patients and 30 matched healthy controls. We collected at least two laboratory results of variables including RDW within 24 hours after hospitalization, and we calculated their mean values. ResultsSepsis patients showed the significantly increased median white blood cell count, compared to AOSD patients (14,390.0/mm3 vs. 12,390.0/mm3 , p = 0.010). The median RDW in sepsis patients was higher than that in AOSD patients (15.0% vs. 13.3%, p = 0.001), and furthermore, the median RDW in both patient-groups was significantly higher than that in healthy controls. In contrast, the median ferritin level in sepsis patients was lower than that in AOSD patients (544.0 mg/dL vs. 3,756.6 mg/dL, p = 0.001). In multivariate analysis, RDW ≥ 14.8% (odds ratio, 17.549) and ferritin < 2,251.0 mg/dL (odds ratio, 32.414) independently suggested sepsis more than AOSD in patients initially presenting with fever requiring hospitalization. ConclusionsRDW might be a rapid and helpful marker for a differential diagnosis between AOSD from sepsis at an early phase.

Neutrophil Recovery in Breast Cancer Patients Receiving Docetaxel-Containing Chemotherapy with and without Granulocyte Colony-Stimulating Factor Prophylaxis

Objective: The primary outcome of the current study is, whether there is a protective effect of prior chemotherapy or of prior granulocyte colony-stimulating factor (G-CSF) on the next cycle blood cell counts. Methods: Hematologic toxicity was evaluated, based on a randomized phase III study in breast cancer patients (n = 167) with >20% risk of febrile neutropenia. The primary endpoint was the nadir blood cell counts for patients treated with G-CSF given during all 6 chemotherapy cycles or limited to the first 2 chemotherapy cycles only. Results: For the present analyses, 47 patients were eligible. In the G-CSF 1-6 arm, the median white blood cell count (WBC) and absolute neutrophil count (ANC) nadir slowly decreased from 10.8 × 10⁹/L in cycle 1 to 7.5 × 10⁹/L in cycle 6 and from 7.1 × 10⁹/L to 5.5 × 10⁹/L, respectively. The median WBC nadir in the G-CSF 1-2 arm decreased from 1.2 × 10⁹/L in cycle 3 to 0.9 × 10⁹/L in cycle 6 and the ANC nadir showed a grade 4 neutropenia of 0.1 × 10⁹/L in cycles 3-6. All patients had ANC recovery to normal levels (≥1.5 × 10⁹/L) without delay on day 1 of the next cycle. Conclusion: We conclude that there is no protective effect of prior G-CSF or prior chemotherapy use on nadir blood cell counts in subsequent cycles.

Age- and sex-related changes in hematological parameters in healthy Malawians.

AimThe aim of the study was to determine how values for white blood cell (WBC) counts, hemoglobin (Hb), hematocrit (Hct), mean corpuscular volume (mcv), and platelet counts vary with age and sex in healthy Malawians.MethodsWe recruited 660 (316 male and 344 female) participants in 12 different age groups. An ethylenediaminetetraacetic acid-anticoagulated blood sample collected from each participant was analyzed using a hematological analyzer.ResultsWBC counts decreased with age with the lowest counts observed in the 20 to <60 years old group. Median WBC counts for 20 to <60 year old females (5.9×109/L) were significantly higher than those for men (4.7×109/L; p=0.015) of the same age. Hb and Hct increased between 5 and 10 years in males and 10 and 15 years in females to adult levels. Males aged 5 to <10 years had significantly higher Hb (13.05 g/dL) and Hct (42.50%) compared to females of the same age (10.40 g/dL and 32.55%, respectively; p<0.0001 for both parameters). Platelet counts in males, which were highest between 3 and 5 years (376×109/L), decreased to lowest counts among 5 to <10 year olds (238×109/L), while in females these decreased from 402×109/L in 6 to <10 years olds to 226×109/L in 10 to <15 year olds. mcv median values were high in neonates reaching a nadir at 13–18 months and then increased throughout life. Females aged 0 to <6 months had significantly higher mcv values (81.85 fL) than males of the same age (69.3 fL; p<0.0001).ConclusionThis study provides hematological values according to age and sex that are suitable for reference use in studies among Malawian subjects.

Low white blood cell count is independently associated with chronic kidney disease progression in the elderly: the CKD-ROUTE study.

Elevated white blood cell (WBC) count is a well-known predictor of chronic kidney disease (CKD) progression. However, elderly patients commonly fail to develop a high WBC count in response to several diseased states and may instead present a low WBC count. Therefore, we hypothesized that low WBC count, in addition to high WBC count, is associated with CKD progression in the elderly. We conducted a prospective cohort study using 3-year follow-up data from the CKD Research of Outcomes in Treatment and Epidemiology study. In the present study, participants aged over 60years with pre-dialysis CKD stages G2-G5 were eligible. Patients were stratified into three groups according to WBC count using tertiles (T). The primary outcome was a composite of end-stage renal disease and a 50% reduction in estimated glomerular filtration rate. Data were analyzed using Cox proportional hazard models with adjustments for covariates. We enrolled 697 patients (males, 69%). The median WBC count was 6100cells/µl (T1, <5400, n= 222; T2, 5400-6900, n= 235; T3, ≥6900, n=240). During a median follow-up of 868days, the primary outcome was observed in 170 patients, whereas 54 patients died. T1 and T3 had significantly higher hazard ratios (HR) than T2 (T1, HR 1.69, 95% confidence interval 1.14-2.51; T3, HR 1.63, 95% confidence interval 1.10-2.41). Moreover, T1 had a significantly higher adjusted HR (1.54, 95% confidence interval 1.00-2.37). Low WBC count is independently associated with CKD progression in the elderly.

Variability in hematology of white-spotted bamboo sharks (Chiloscyllium plagiosum) in different living environments.

Elasmobranch hematology continues to reveal new peculiarities within this specialized field. This report compares total hematologic values from the same white-spotted bamboo sharks (Chiloscyllium plagiosum) housed in different environments. We compared the hemograms one year apart, using a standardized Natt-Herrick's technique. The total white blood cell (WBC) counts of the sharks were statistically different between the two time points (initial median total WBC count = 18,920 leukocytes/μl, SD = 8,108; 1 year later total WBC count = 1,815 leukocytes/μl, SD = 1,309). The packed cell volumes were additionally found to be statistically different (19%, SD = 2.9 vs. 22%, SD = 2.0). Analysis revealed the only differences between the time points were the temperature and stocking densities at which these sharks were housed. This report emphasizes the need for a thorough understanding of the husbandry of an elasmobranch prior to interpretation of a hemogram and suggests that reference intervals should be created for each environment.

Prevalence of Malaria Parasitaemia and Its Association with ABO Blood Group in Jos, Nigeria

Malaria is a disease associated with high morbidity and mortality especially among children and other high risk groups. Certain ABO blood group is thought to be protective of severe malaria. Determining the prevalence of malaria parasitaemia among asymptomatic individuals and its association with ABO blood grouping could be a step to further studies to understand the immunity of Malaria. A cross sectional study in which one hundred and seven asymptomatic, consenting individuals in malaria endemic Jos, Nigeria, were recruited into the study. Demographic data and blood samples were taken for the determination of ABO blood group and for thin and thick blood film for malaria parasite detection. The asexual parasite density (asp/µl) was also determined. Of the 107 individuals studied, there were 30(28.0%) males and 77(72.0%) females. The mean age of study participants was 26.2±6.3 years. The predominant blood group was O 48(44.9%), followed by B 33(30.8%), A 21(19.6%) and AB 5(4.7%) respectively. The prevalence of Malaria parasitaemia was 40(37.4%). The mean parasite density was 241.0± 69 asp/µl. There was a significant association between Malaria parasitaemia and ABO blood group (P 0.016, 0.03 and 0.026 respectively) The median WBC count of Malaria infected individuals was significantly higher than the median WBC count of those subjects without parasitaemia, (P<0.01). There was a positive correlation between the total White blood cell count (WBC) count and asexual parasite density, although only 35.4% was attributable to the WBC (r2=0.354, P<0.0001). In conclusion, the prevalence of Malaria parasitaemia in our cohort is comparatively low to southern parts of Nigeria. Although there was relative spread of parasitaemia across all blood groups, the highest rate was observed among blood group A and in females. We recommend that available malaria interventions should be directed at all individuals but with particular emphasis on Blood group A and females. Large studies are required to validate our findings, and to elucidate the socio-demographic and immunologic mechanisms involved in the apparent protection.

TP53 mutation does not confer a poor outcome in adult patients with acute lymphoblastic leukemia who are treated with frontline hyper-CVAD-based regimens.

Tumor protein 53 (TP53) mutations are uncommon in adult patients with acute lymphoblastic leukemia (ALL) and predict a poor outcome. TP53 mutation analysis was performed in 164 newly diagnosed adult patients with ALL using a combination of targeted amplicon-based next-generation sequencing and Sanger sequencing. TP53 mutations were detected in 25 patients (15%), with a median allelic frequency of 42.2% (range, 5.6%-93.8%). The majority of mutations were single-nucleotide variants of missense type and involved the DNA-binding domain. TP53-mutated (TP53mut ) ALL was found to be significantly associated with older age, lower median white blood cell and platelet counts, lower frequency of Philadelphia chromosome and a higher frequency of low hypodiploid karyotype compared with ALL with wild-type TP53 (TP53wt ). To evaluate the prognostic effect of TP53 mutations, the authors selected 146 patients with B-cell immunophenotype ALL (24 with TP53mut and 122 with TP53wt ) who were uniformly treated with frontline hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD)-based regimens; >90% of these individuals also received a monoclonal antibody. Over a median follow-up duration of 15 months, there was no significant difference in the median overall survival, event-free survival, and duration of complete remission noted between patients with TP53mut ALL and those with TP53wt ALL. Hyper-CVAD-based regimens appear to negate the poor prognostic impact of TP53 mutations in patients with adult B-cell immunophenotype ALL. Cancer 2017;123:3717-24. © 2017 American Cancer Society.

Outcome and Clinical Significance of Immunophenotypic Markers Expressed in Different Treatment Protocols of Pediatric Patients With T-ALL in Developing Countries.

T-cell acute lymphoblastic leukemia (T-ALL) accounts for about 15% of pediatric ALL. With wider use of intensive chemotherapy, the prognosis for childhood T-ALL has improved. Further gains in treatment outcome will likely require methods to identify patients who continue to fail on contemporary protocols. This study aimed to evaluate pediatric patients with T-ALL at 2 different Arabic cancer centers regarding their clinicopathologic, immunophenotypic, and cytogenetic features and outcome. This retrospective study included all children with T-ALL treated between 2003 and 2013 at 2 oncology centers in the Middle East. Patients were divided into (group I) treated with Berlin-Frankfurt-Münster (BFM)-90 treatment protocol between February 2003 and June 2007 and (group II) includes all patients treated thereafter by the Total Therapy Study XIII protocol for high-risk ALL. This study included 103 patients with a median age of 8.9 years. The male to female ratio was 2.6:1. The median initial white blood cell count was 123× 109/L. Central nervous system leukemia was detected in 15%. The early T-cell precursor (ETP)-ALL phenotype was found in 16.5%. The 5-year overall survival was 20.7% ± 67.5% and 72.9% ± 5.7% (P< .01); the 5-year disease-free survival was 47.1% ± 13.8% and 77.3% ± 6.0% (P= .023); and the 5-year event-free survival was 28.6% ± 12.1% and 71.1% ± 6.2% (P= .003) for group I and II, respectively. The outcome of patients with T-ALL significantly improved in patients who received the treatment protocol of ALL with high-risk criteria. This protocol eliminates the bad outcomes effect of several clinical and immunophenotypic markers. Patient with the ETP-ALL phenotype had a nonsignificant inferior outcome compared with the non-ETP-ALL group.

Cerebrospinal Fluid Cytokines Correlate With Aseptic Meningitis and Blood-Brain Barrier Function in Neonatal-Onset Multisystem Inflammatory Disease: Central Nervous System Biomarkers in Neonatal-Onset Multisystem Inflammatory Disease Correlate With Central Nervous System Inflammation.

To evaluate proinflammatory cytokines and leukocyte subpopulations in the cerebrospinal fluid (CSF) and blood of patients with neonatal-onset multisystem inflammatory disease (NOMID) after treatment, and to compare inflammatory cytokines in the CSF and blood in 6 patients treated with 2 interleukin-1 (IL-1) blockers-anakinra and canakinumab. During routine follow-up visits between December 2011 and October 2013, we immunophenotyped the CSF of 17 pediatric NOMID patients who were treated with anakinra, and analyzed CSF cytokine levels in samples obtained at baseline and at 3-5-year follow-up visits and compared them to samples from healthy controls. CSF levels of IL-6, interferon-γ-inducible 10-kd protein (IP-10/CXCL10), and IL-18 and monocyte and granulocyte counts significantly decreased with anakinra treatment but did not normalize to levels in the controls, even in patients fulfilling criteria for clinical remission. CSF IL-6 and IL-18 levels significantly correlated with measures of blood-brain barrier function, specifically CSF protein (r = 0.75 and r = 0.81, respectively) and albumin quotient (r = 0.79 and r = 0.68, respectively). When patients were treated with canakinumab versus anakinra, median CSF white blood cell counts and IL-6 levels were significantly higher with canakinumab treatment (10.2 cells/mm3 versus 3.7 cells/mm3 and 150.7 pg/ml versus 28.5 pg/ml, respectively) despite similar serum cytokine levels. CSF leukocyte subpopulations and cytokine levels significantly improve with optimized IL-1 blocking treatment, but do not normalize. The correlation of CSF IL-6, IP-10/CXCL10, and IL-18 levels with clinical laboratory measures of inflammation and blood-brain barrier function suggests that they may have a role as biomarkers in central nervous system (CNS) inflammation. The difference in inhibition of CSF biomarkers between 2 IL-1 blocking agents, anakinra and canakinumab, suggests differences in efficacy in the intrathecal compartment, with anakinra being more effective. Our data indicate that intrathecal immune responses shape CNS inflammation and should be assessed in addition to blood markers.

Abstract WP211: Prognostic Significance of White Blood Cell Count in Acute Ischemic Stroke With Nonvalvular Atrial Fibrillation: The SAMURAI-NVAF Study

Background and Purpose: White blood cell count (WBC), a marker of the atherosclerotic burden, has reportedly been a predictor of poor outcome in the general stroke population. The purpose of this study was to clarify associations between WBC on admission and outcomes among patients having acute ischemic stroke with nonvalvular atrial fibrillation (NVAF), that was principally cardioembolic. Methods: Of those enrolled in the multicenter observational Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI)-NVAF study, acute ischemic stroke/TIA patients (within 7 days of onset) with NVAF with premorbid modified Rankin Scale (mRS) score of 0-2 were included in the analysis. WBC on admission was categorized into quartiles. Associations between WBC count and major disability or death (mRS score of 3-6) at 90 days and 2 years were analyzed using logistic and proportional odds regression models. Results: A total of 789 patients were studied (306 women, 76.2±9.5 years old, the median NIHSS score was 6 [IQR, 2-16], the median WBC count was 6700 [IQR, 5475-8300], the median mRS score at 90 days was 2 [IQR, 1-4], the median mRS score at 2 years was 2 [IQR, 0-5]). WBC had a significant linear association with major disability or death at 90 days (adjusted odds ratio [OR] for highest versus lowest quartile 3.53; 95% confidence interval [CI] 2.07-6.13; P for trend&lt;0.001). Associations were similar for the outcome at 2 years (adjusted OR for highest versus lowest quartile 2.16; 95% CI 1.31-3.56; P for trend&lt;0.001). Conclusions: Higher WBC count on admission seems to predict a short- and long-term poor outcome in acute ischemic stroke patients with NVAF. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01581502.