WBC Count In Patients Research Articles

Correlation of Plasma Cell Percentage and Monoclonal Gammapathies with Biochemical Parameters in Multiple Myeloma Patients: A Retrospective Study

Background: Multiple myeloma is characterized by the uncontrolled proliferation of monoclonal plasma cells in the bone marrow, leading to the production of non-functional intact immunoglobulin chains. This retrospective study aimed to investigate the correlation between plasma cell percentage (below 60% and above 60%) in different types of monoclonal gammapathies (IgA, IgG) and various biochemical parameters.Methods: This analysis was conducted at the Division of Biochemistry in the Malabar Cancer Centre, a tertiary care cancer center in Kerala, India. A total of 89 patient case reports were reviewed, and complete treatment data were available for 60 patients. The study aimed to evaluate the relationship between plasma cell percentage (below 60% and above 60%) in different types of monoclonal gammapathies (IgA, IgG) and various biochemical parameters. Results: The majority of the patients enrolled in the study were above 60 years of age, and more men were included than women. Among the parameters studied, a significant increase in plasma protein level was observed in the group with a plasma cell percentage below 60% and IgG type monoclonal gammapathy (P value = 0.014, p < 0.05). Additionally, there was a significant elevation in WBC count in patients with plasma cell percentage below 60% and IgG type MM when compared to IgA type MM patients (p = 0.023, p < 0.05). However, no significant changes were observed in plasma protein level, liver enzyme activity, renal function, serum electrolytes, CBC, and calcium level between patients with plasma cell percentages above and below 60% in multiple myeloma. Conclusion: This study found that only a few biochemical and hematological parameters showed significant deviations between plasma cell percentages above and below 60% in different types of monoclonal gammapathies in multiple myeloma patients.

Reduction in Opioid Use and Clinical Complications in Vitamin D Deficient Pediatric SCD Patients Following Vitamin D Replacement

Background: Hydroxyurea, the most common drug used to treat SCD patients, has several limitations: inadequate clinical benefit in 50% of adults, poor compliance, teratogenicity, marrow toxicity, and reduced fetal hemoglobin (HbF) induction over time. Thus, there is a need for additional treatment options. Vitamin D (vitD) could be a potential treatment option because it: 1) increases HbF and mean corpuscular volume, 2) reduces white cell (WBC) and platelet counts, and 3) is associated with increased morbidity in SCD patients. However, insufficient data demonstrating clinical benefits following vitD replacement prevents its routine use. To address this knowledge gap, we analyzed the change in emergency room visits/hospital admissions (admission rate), opioid use, clinical complications, HbF levels, and WBC count in pediatric SCD patients after vitD replacement. Methods: SCD patients 21 years and younger who received vitD at Texas Children's Hospital from 2007 to 2021 were included in this retrospective longitudinal study. Patients on chronic transfusions were excluded. Three-month data after an on-demand blood transfusion was also excluded from the analysis set as transfusion affects HbF levels temporarily. The study period included two years before vitD replacement (pre-vitD period, referent category ), vitD replacement period, and one year after cessation of vitD (post-vitD period). The patients with vitD levels < 30 ng/ml and ≥ 30 ng/ml were considered vitD deficient and not deficient, respectively. VitD levels or the vitD replacement status (pre-vitD, vitD, and post-vitD) were the exposure variables. Age and folic acid were considered potential confounders, and genotype and maximum tolerated dose of hydroxyurea (MTD) were effect modifiers. Hydroxyurea dose of ≥ 35 mg/kg/day or the dose that achieved absolute neutrophil count between 2000-4000/cmm was considered MTD. Statistical analyses: Two-level linear mixed model and Wilcoxon rank-sum tests were used. WBC, admission rate, and opioid use-related variables required log transformation to meet the model assumptions. A covariate was retained if its exclusion changed the beta coefficient of the exposure variable by over 10%. A backward selection method was used to derive a final model. P-values were adjusted for the multiple testing. Results: We analyzed 136 patients (male=68, average age=12.3 years, SCA=129) with a total of 534 clinic visits. The median follow-up was 3.5 years. 47.4% did not exhibit an elevation of vitD levels and 10.9% had a recurrence of deficiency despite an adequate replacement dose (median 2000 IU/day). Patients were on a stable dose of hydroxyurea (median: 19.9 mg/kg/day) during the study period. The reduction in hospital admissions, emergency room visits, infections, transfusions, and acute chest syndrome was higher during the vitD period than post-vitD period (Table1, Figure 1). The loss/reduction in benefits during the post-vitD period could be due to falling vitamin D levels and recurrence in 10.9% of patients. A comparable reduction in opioid use during the vitD and post-vitD replacement periods (81 vs.82%) suggests sustained benefit in pain reduction beyond the replacement period. (Table 1). Higher vitamin D levels were associated with higher HbF levels and lower WBC counts (Table1). There was a higher increase in HbF levels in patients at MTD (1.89% points) compared to the patients not at MTD (0.38% points) for each 10 ng/ml increase in vitD levels (p<0.01). Similarly, there was a higher reduction in WBC count in patients at MTD (15%) compared to the patients not at MTD (1%) (p<0.01). Conclusion: Our data show a statistically significant reduction in emergency visits/hospital admissions, opioid use, infections, transfusions, and acute chest syndrome following vitD replacement. The clinical improvement may be due to increased HbF levels and decreased WBC count observed with the increase in vitD levels. All subjects were on hydroxyurea; of note, subjects at MTD had a greater HbF response with vitD replacement than those not at MTD, suggesting an additive interaction between vitD and hydroxyurea. We, therefore, conclude that regular vitD screening followed by vitamin D replacement to achieve adequate vitamin D levels will likely reduce the public health burden of the SCD population significantly. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Comprehensive in Vitro Characterization of CXCR4WHIM variants to Decipher Genotype-Phenotype Correlations in WHIM Syndrome

▪Background: WHIM (Wart, Hypogammaglobulinemia, Infections, Myelokathexis) syndrome is a rare, autosomal-dominant primary immunodeficiency with neutropenia and lymphopenia. The clinical presentation may include recurrent infections, and increased susceptibility to human papillomavirus. In >80% of cases, WHIM syndrome is caused by heterozygous gain-of-function (GOF) mutations in C-X-C chemokine receptor 4 (CXCR4), with >12 variants reported in WHIM syndrome to date (nonsense [NS], frameshift [FS], and missense[MS]) spanning 27 C-terminal amino acids . These mutations cause hyperactivation of downstream signaling and retention of WBC in the bone marrow (McDermott D, et al. Immunol Rev. 2019;287(1):91-102; Beaussant S, et al. Orphanet J Rare Dis. 2012;7(71):1-14). To date, a comprehensive study characterizing the functional abnormalities caused by pathogenic CXCR4 mutations and correlating these measures with clinical presentation in patients has not been conducted. Here, we aimed to establish genotype-phenotype correlations for all known pathogenic variants using in vitro functional assays. These assays characterize CXCR4 receptor trafficking and downstream signaling, which will enable the long-term goal of assessing pathogenicity of novel CXCR4 variants of uncertain significance (VUS). We further aimed to assess the in vitro response of each variant to mavorixafor, an investigational CXCR4 antagonist.Methods: We used the CXCR4-negative K562 cell line as a model system to express all 14 known CXCR4 variants identified in patients diagnosed with WHIM syndrome (previous reports, ClinVar, and genetic screening initiatives [Invitae PATH4WARD]). The effects of the mutations on CXCR4 receptor trafficking (internalization and degradation), downstream signaling (Ca 2+ mobilization, cAMP inhibition, ERK and AKT activation), and chemotaxis were studied in parallel in a series of assays in cells stimulated with the natural ligand CXCL12. All in vitro functional parameters characterized were investigated for potential correlations with the clinical phenotypes reported for each variant, including disease manifestations and biomarkers.Results: The most conserved feature of the 14 CXCR4 variants was an impaired receptor internalization in response to CXCL12, evidenced by higher percentage of CXCR4 receptors remaining on the cell surface compared to untreated control, with truncated variants showing maximum impairment and the MS variant E343K being least affected. The decreased CXCR4 internalization correlated with both decreased CXCR4 degradation and increased cAMP inhibition. When stimulated with CXCL12, most variants demonstrated a higher amplitude and duration of ERK and AKT activation. Chemotactic responses to CXCL12 were diverse, depending on the variant sequence and subtype. While Ca 2+ mobilization was not enhanced compared to wild-type (WT) CXCR4-expressing cells in this assay, mavorixafor demonstrated inhibition of Ca 2+ mobilization in all CXCR4 mutant cells with a trend toward greater effect in the NS variants. In addition, both ERK and AKT activation decreased with increasing concentration of mavorixafor. Correlation analyses of the functional parameters in cells expressing mutated or WT CXCR4 and clinical manifestations or WBC counts in patients with these mutations revealed that the CXCR4 internalization defect strongly correlated with severity of peripheral blood cytopenias (ie, decreases in absolute neutrophil counts, and in CD3+ and CD4+ T-cell levels), which was paralleled by an increased susceptibility to recurrent infections. In addition, AKT hyperactivation correlated with lower IgA and decreased CD4+ T-cell levels (Figure).Conclusions: In the current study, we performed a detailed functional analysis of the entire spectrum of CXCR4 WHIM mutations known to date. In vitro CXCR4 receptor internalization correlates with WBC cytopenias and an increased susceptibility to recurrent infections in patients with CXCR4 GOF mutations. These data suggest that CXCR4 internalization and AKT activation may be used as key assays for the assessment of CXCR4 variant pathogenicity in vitro and potentially as WHIM-related disease biomarkers. Additionally, all tested CXCR4 variant cell lines were sensitive to mavorixafor at clinically relevant concentrations, rescuing defective GOF signaling toward that of WT CXCR4-expressing cells. [Display omitted] DisclosuresZmajkovicova: X4 Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Maier-Munsa: X4 Pharmaceuticals: Current Employment. Maierhofer: X4 Pharmaceuticals: Current Employment. Taveras: X4 Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Badarau: X4 Pharmaceuticals: Current equity holder in publicly-traded company, Ended employment in the past 24 months.

Study of Some Hematological and Biochemical Parameters in Children with Thalassemia in City of Karbala

This research including the study of some hematological and biochemical changes in children suffering thalassemia in the province of Karbala. To achieve this aim 50 samples was arranged in two groups first group include 40 patient with thalassemia male and female attending Imam Hussein medical city and second group include 10 healthy children as control. The results appear decrease in concentration of packed cell volume (PCV), Red Blood cell count and Hb. Also the results appear decrease in biochemical parameters represented by (GOT) and (GPT). While there is increase in WBC count in patients as compared with control. The result also shown that thalassemia mostly occurs in male than in female.

Impact of Non-Surgical Periodontal Treatment on Total WBC Count in Patients with Periodontitis

Background and objectives: Chronic periodontitis is an inflammatory disorders associated to the accumulation of microbial biofilm and the response of host to this accumulation. In our society the importance of total WBC counts has not yet been investigated with chronic periodontitis. The objective of this study was to investigate the impact of treatment on total WBC counts in subjects with chronic periodontitis. Materials and methods: A total of 50 subjects were selected for the study. Venous blood samples were taken at base line and 4 weeks after non-surgical periodontal therapy for the study group (group II), and one time for the control group (group I) to estimate total WBC counts. Clinical parameters such as Plaque Index, Gingival Index, probing pocket depth, the clinical attachment level for group II were measured. Results: The result of the present study shows a highly significant decrease of total WBC counts between group I and II before treatment P value=0.004. Our results indicate that there is a highly significant decrease of Gingival Index and probing pocket depth at base line compared with after treatment P value=0.003 and 0.000 respectively. Also, a significant decrease in Plaque Index and clinical attachment level at base line and 4 weeks following therapy P value=0.035 and 0.026 respectively. In addition, a significant decrease of total WBC counts at base line and 4 weeks following therapy P value=0.016. Statistical tests were done by standard program data processing (MS excel) paired t test. Conclusion: The present study concludes that total WBC counts were decreased after non- surgical periodontal therapy

Evaluation of oxidant and anti-oxidant balance in Behcet’s disease and its correlation with disease activity

Behcet’s disease (BD) is a multi-system, progressive disease which usually presents with oral aphthous and genital ulcers. It may involve other organs such as the eyes, joints, nervous and vascular systems. Although the origin of BD is unknown, it is proposed that immunological, viral, and toxic factors are responsible. The current study evaluated the oxidant/antioxidant balance (redox index) in Behcet’s disease and its correlation with disease activity. Thirty BD patients were enrolled in the study based on International Study Group (ISG 1992) criteria. An age- and gender-matched control group was selected from healthy hospital staff. In this study, 3, 3, 5, 5 tetramethylbenzene (TMB) was used to determine oxidant/antioxidant balance. In the first enzymatic reaction, TBM was oxidized to a colorful cation. In the second chemical reaction, the colorful cation was regenerated to a colorless substance. In such way, the redox index was achieved. The redox index was significantly higher in the BD group than in the healthy group (P=0.0140). The mean redox index varied significantly in different levels of disease activity and was higher in patients with a severe case in comparison with those with a moderate form (P=0.038). There was a positive correlation between disease activity and redox index (r=0.450; P=0.013). A positive correlation was observed between the redox index and the WBC count in patients (P=0.033). The findings of this study demonstrate the presence of oxidative stress in BD, and the severity of BD has a moderately positive correlation with the redox index.

To investigate the levels of plasma sp-selectin and the link between plasma sp-selectin levels and the circulating wbc count in patients with acute myocardial infarction (ami)

To investigate the levels of plasma sp-selectin and the link between plasma sp-selectin levels and the circulating wbc count in patients with acute myocardial infarction (ami)

Utility of 18F-FDG PET/CT for the diagnosis and staging of gallbladder carcinoma

Objective To investigate the value of 18F-FDG PET/CT combined with clinical data in the diagnosis of gallbladder carcinoma and to assess the role of 18F-FDG PET/CT in tumor staging. Methods 18F-FDG PET/CT and clinical data of 54 patients (28 males, 26 females, age range 18-82 years) with suspected gallbladder carcinoma from March 2009 to March 2014 were retrospectively analyzed. The results of histopathology and clinical follow-up were taken as golden standard. The diagnostic value of 18F-FDG PET/CT for gallbladder carcinoma was determined by the qualitative and quantitative methods. Serum CEA, CA19-9 and WBC count were evaluated for discriminating 18F-FDG-avid malignant and benign diseases. According to the final clinical staging, the role of 18F-FDG PET/CT for tumor staging was assessed. Data were analyzed by two-sample t test, χ2 test and McNemar test. Results (1) Gallbladder carcinoma was diagnosed in 27 cases and the gallbladder benign diseases in other 27 cases. 18F-FDG PET/CT showed positive results in 42 patients including true positive in 27 patients and false positive in other ones. When focal high uptake of 18F-FDG in the gallbladder and SUVmax of 6.6 in the lesions were used as the qualitative and quantitative standards, the diagnostic sensitivity, specificity, and accuracy of the two methods for gallbladder carcinoma were 100%(27/27) vs 81.5%(22/27), 44.4%(12/27) vs 70.4%(19/27), 72.2%(39/54) vs 75.9%(41/54), respectively (χ2=3.711 and 0.193, both P>0.05). There were no much difference for the positive rate of serum CEA and CA19-9 levels between the patients with early staged gallbladder carcinoma and those with 18F-FDG-avid benign diseases(χ2=0.529 and 0.045, both P>0.05). However, the rate of increased WBC count in patients with 18F-FDG-avid benign diseases was significantly higher than that in patients with early staged gallbladder carcinoma (14/15 vs 1/6, χ2=12.343, P<0.05). (2) Nearly 59.3% (16/27) patients with gallbladder carcinoma were upstaged due to the findings by whole body 18F-FDG PET/CT. The sensitivity, specificity of 18F-FDG PET/CT for diagnosing lymph node metastases and distant metastases were 18/19, 7/8 and 17/17, 9/10, respectively. Conclusions 18F-FDG PET/CT has low specificity for differentiating 18F-FDG-avid gallbladder benign disease and early staged gallbladder carcinoma, but it may be beneficial to the diagnosis that combining PET/CT with WBC count. 18F-FDG PET/CT is helpful for the staging of gallbladder carcinoma. Key words: Gallbladder neoplasms; Tomography, emission-computed; Tomography, X-ray computed; Diagnosis, differential; Neoplasm staging; Deoxyglucose

Leukapheresis in acute myeloid leukemia patients with hyperleukocytosis: A single center experience

Hyperleukocytosis is defined as WBC count above 100,000/mm3 in peripheral blood. Increased WBC count leads to leukocyte aggregation, increased blood viscosity, and consequently results in stasis in small blood vessels. Ultimate neurological, pulmonary, gastrointestinal complications, coagulopathy, and tumor lysis syndrome cause increase in morbidity and mortality. Leukapheresis is a treatment modality used for hyperleukocytosis. In patients presenting with hyperleukocytosis the indications for leukapheresis were accepted as having symptoms of leukostasis and prophylactic. Indications for leukapheresis in prophylactic group evaluated according to WBC count. We report a single center experience about leukapheresis in managing 31 AML patients with hyperleukocytosis. In addition to demographic characteristics, disease-related clinical and laboratory findings of the patients were recorded. Survival rates were also calculated. Ten patients were female. The most common of AML subtype was AML-M2. The median number of leukapheresis per patient was 2 and totally 60 leukapheresis cycles were performed in all patients. There was a significant decrease in WBC count and LDH level after leukapheresis as compared with the baseline values (p < 0.05). Early and total mortality were 16.1% and 58.0%, respectively. Alive and died patients were evaluated according to baseline WBC, LDH; increased WBC count and LDH level were found in died patients (p < 0.05). According to leukapheresis indications, patients were divided into two groups: 14 patients in symptomatic leukostasis, 17 patients in prophylaxis. No statistically significant differences were noted between both groups in leukapheresis effectiveness, mean survival time, early and total mortality rate (p > 0.05). None of our patients suffered serious side effects and tumor lysis syndrome during or after apheresis. Leukapheresis is an effective and safe approach to reduce WBC counts in patients with AML with hyperleukocytosis. Further evidence-based data obtained from larger sample sizes are required to better understand the impact of prophylaxis leukapheresis on early and total mortality of AML patients with hyperleukocytosis.

Does chronic alcohol use by HIV-infected patients on d4T/3TC/NVP drug regimen effect the HIV viral load and what is the therapeutic window of the drugs, CD4+ count and WBC count in patients with high viral load during the 9 months period of follow up?

The study investigated the effects of chronic alcohol use on HIV viral load in HIV-infected patients on d4T/3TC/ NVP drug regimen during 9 months follow up period. It also determined plasma drug concentrations of d4T, 3TC and NVP; CD4 + and WBC counts for patients with high HIV viral load. A case-control study using repeated measures with serial measurements was used. A total of 41 patients (20 alcohol group and 21 control group) were screened for alcohol use using WHO AUDIT tool and chronic alcohol use biomarkers. Blood sampling was done at 3 month intervals for a period of 9 months. HIV viral load was determined using Roche Amplicor HIV-1 monitor test, version 1.5 (Amplicor). The d4T, 3TC and NVP concentrations were determined by Shimadzu Class-VPTM HPLC Chromatography data system version 6.1. The CD4 + cell count was determined using FACSCalibur flow cytometer. T he WBC was determined using automated hematological Coulter CBC-5 Hematology Analyzer system. Results show that % patients with HIV viral load ≥400 copies/ml in control group was highest (23.8%, n=5) at 3 month while in chronic alcohol use group, it was at 0 month (35%, n=7) for both WHO AUDIT tool and chronic alcohol-use biomarkers groups. Generally patients with high viral load ≥400 copies/ml was observed in chronic alcohol use as compared to control group in both WHO AUDIT tool and biomarkers group despite of patients having high steady state d4T, 3TC and NVP plasma drug concentrations in circulation that is available to suppress HIV virus. The high viral load could be associated with the emergence of resistance of the HIV virus and these patients generally had a low CD4 + cell count. Some of these patients had no detectable d4T plasma drug concentrations in circulation and most of them with high viral load had sub-therapeutic NVP plasma drug concentrations in their blood circulation. Chronic ethanol use by HIV-infected patients on d4T/3TC/NVP drug regimen increased HIV viral load and the patients with high viral load had sub-therapeutic NVP plasma drug concentrations and some with undetectable d4T drug concentrations in their blood circulation.

Therapeutic leukapheresis in patients with leukostasis secondary to acute myelogenous leukemia

Leukostasis is a relatively uncommon but potentially catastrophic complication of acute myelogenous leukemia (AML). Prompt leukoreduction is considered imperative to reduce the high mortality rate in this condition. Leukapheresis, usually associated with chemotherapy, is an established approach to diminish blast cell counts. We report a single center experience in managing leukostasis with leukapheresis. Fifteen patients with leukostasis of 187 patients with AML (8.02%) followed at our institution were treated with leukapheresis associated with chemotherapy. The procedures were scheduled to be performed on a daily basis until clinical improvement was achieved and WBC counts were significantly reduced. Overall and early mortalities, defined as that occurred in the first 7 days from diagnosis, were reported. A high proportion of our patients with leukostasis (46.66%) had a monocytic subtype AML (M4/M5, according to French-American-British classification). The median overall survival was 10 days, despite a significant WBC reduction after the first apheresis procedure (from 200.7 × 10⁹/L to 150.3 × 10⁹/L). Almost half of patients (7/15) had an early death. Therapeutic leukapheresis, associated or not to chemotherapy, is an effective approach to reduce WBC counts in patients with AML and leukostasis; however, this therapeutic procedure does not appear to change significantly the sombre prognosis observed in the majority of patients with this complication. Other forms of treatment must be found to reduce the high mortality rate related to leukostasis.

Association of TET2 Alterations with NPM1 Mutations and Prognostic Value in De Novo Acute Myeloid Leukemia (AML).

Abstract 163In acute myeloid leukemia (AML), both cytogenetic and molecular abnormalities are strongly associated with prognosis. In particular, in cytogenetically normal AML (CN-AML), FLT3-ITD (internal tandem duplication) carries adverse prognostic factor whereas NPM1 or CEBPA mutations are associated with favorable outcome. Recently, mutations of the ten eleven translocation 2 gene (TET2) have been reported myeloid neoplasms. We evaluated the frequency and prognostic value of TET2 alterations, in a cohort of 111 de novo AML patients.We studied 111 patients aged between 15 years and 69 years with previously untreated de novo AML who had reached complete remission (CR) using intensive chemotherapy. 28 of them also received an allogenic bone marrow transplantation in first CR. Analysis of TET2 sequence variation was performed by direct sequencing of PCR products from 111 genomic DNA samples obtained at diagnosis. Frameshift and nonsense variations were all scored as mutation whereas missense mutations were retained when observed at diagnostic but absent in the CR paired sample obtained. Previously identified single nucleotide polymorphisms (SNP) were not considered. TET2 anomalies were numbered according to Genebank reference FM992369. Paired diagnosis and CR genomic DNAs were analyzed using Affymetrix Genome-Wide Human SNP Array 6.0 (Affymetrix, Santa Clara, CA). Data were analyzed using Gene Chip Genotyping Console 3.0.2 and Partek Genomics Suite (www.partek.com/). Comparisons were made by Fisher's exact test for binary variables and the Mann-Whitney‘s test for continuous variables. Disease Free Survival (DFS) and overall survival (OS) were calculated according to the Kaplan-Meier method. Comparisons regarding DFS and OS were performed with the log-rank test.24 acquired TET2 mutations were observed in 19 of the 111 (17%) de novo AML patients, suggesting the alteration of the two TET2 alleles in 5 patients. They included 21 different events: 6 frameshift, 7 non-sense and 11 missense mutations. Four of the missense mutations were located in conserved regions and 7 outside. All of them were detected in the diagnostic sample but were absent in the paired remission sample. Except for two missense mutations (S282F, T492S) both detected in two patients, no recurrent TET2 mutation was observed. Acquired mutations were spread over all exons. No case of uniparental disomy (UPD) was observed and only one patient presented a small deletion of 60Kb in the TET2 gene locus without TET2 mutation. No significant difference was observed between patients with or without TET2 alterations for gender, age, hemoglobin level, platelet count, FAB subtypes distribution and cytogenetics according to MRC classification, but there was a trend for higher WBC count in patients with TET2 alteration. No significant association was observed between TET2 mutations and FLT3 or CEBPA alterations. However, TET2 alterations were significantly associated with NPM1 mutations (p=0.032). In the entire patient cohort, no difference in DFS or OS was seen between patients with and without TET2 alteration. However, a significantly worse DFS was observed for patients presenting TET2 mutations within the subgroup of patients with NPM1 mutations (3y-DFS: 0% vs 66.4%, 95% CI [45.6–87.2], p=0.008) Considering both the favorable prognosis of NPM1 mutations without FLT3-ITD in CN-AML and the absence of clear association between FLT3-ITD and TET2 alterations in this study, prognostic value of the genotype characterized by NPM1 mutation without FLT3-ITD or TET2 alteration (NPM1+FLT3-ITD-TET2-) was compared to other patients within CN-AML group (N=54). NPM1+FLT3-ITD-TET2- patients showed a significantly better DFS and OS compared to other patients in CN-AML group (3y-DFS: 82.1%, 95% CI [59.1–100] vs 37.3%, 95% CI [20.2–54.3], p=0.01; 3y-OS: 80.8%, 95% CI [56.1–100] vs 42.3%, 95% CI [23.3–61.3], p=0.04).In conclusion, we observed point mutations of TET2 in 17% of patients, whereas TET2 deletion or UPD are very rare. In our study, TET2 mutations were clearly associated with NPM1 mutations and carried a negative prognostic impact in this subgroup. Screening for TET2 mutations may improve the characterization of CN-AML and help to identify within the low-risk subgroup with NPM1 mutation and without FLT3-ITD, patients at high risk of relapse. Disclosures:Fenaux:Celgene: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Ortho Biotech: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Cephalon: Honoraria, Research Funding; Merck: Honoraria, Research Funding; Novartis: Honoraria, Research Funding.

The changes of Hs-CRP and WBC count after percutaneous coronary intervention in different types of coronary heart diseases

Objective To investigate the regulation of High sensitive C-reactive protein (Hs-CRP) and WBC count in patients with coronary heart disease (CHD) by percutaneous transluminal intervention (PCI) and to discuss the mechanism of inflammatory reaction after coronary stenting. Methods 127 patients who received successful percutaneous transluminal coronary stenting, were divided into groups of stable angina (SAP), unstable angina (UAP), and acute myocardial infarction (AMI) according to their clinical types. Another 41 stable angina patients with more than 7o% of coronary artery tenosis who did not receive PCI served as control. Serum Hs-CRP levels and WBC count were determined before intervention, 3 days and 7 days post PCI and the data were analyzed statistically by t-test. Results There showed no difference in clinical baseline characteristics between groups. The serum Hs-CRP level and WBC count was gradually raised in the UAP and AMI group (how about SAP group, and had no difference in CAG group and SAP group). After PCI serum Hs-CRP levels and WBC counts were significantly higher in the SAP group than in the coronary angiography group (CAG) at 3 days and had no difference at 7 days. In the UAP and AMI group, the serum Hs-CRP level at 3 days and 7 days declined obviously, however serum WBC count did not decrease apparently. Conclusion The serum Hs-CRP level and WBC count elevate transiently after PCI. There are different inflammatory reactions in different types of coronary heart diseases after coronary stenting procedure.

The effect of chemotherapy (CT) and external beam radiotherapy (RT) on bone marrow (BM) toxicity of radionuclides in the treatment of bone metastases secondary to breast cancer

796 Background: Bone metastases are commonly seen in patients with metastatic breast cancer. Radionuclide therapy has been shown to alleviate the pain of bone metastases but may be associated with BM toxicity, particularly thrombocytopenia. Because many patients with breast cancer and bone metastases also receive CT and RT, we examined the effects of these other treatments on the BM of samarium (Sm)-153-EDTMP (Quadramet®). Methods: A retrospective review of patients (pts) with breast cancer and bone metastases who had received Sm-153-EDTMP was undertaken. Dates of CT and RT, as well as CT regimens were noted. Pre-and post-radionuclide platelet (PLT) and WBC counts were compared, as were the percent decreases in these parameters. Results: Forty-eight pts received 79 courses of Sm-153-EDTMP. Twenty-eight pts received 29 different chemotherapy regimens prior to treatment with Sm-153-EDTMP. Pre- and post-treatment data were available for 21 courses of Sm-153-EDTMP in 20 patients who received CT and RT and for 6 courses of Sm-153-EDTMP in 5 patients who received CT alone. For the entire cohort, the mean ± SEM baseline PLT count was 268 ± 12 x 103/μL, the mean nadir PLT count was 160 ± 10 x 103/μL and the mean percent (%) decrease in PLT count was 42%. The mean baseline WBC was 5.8 ± 0.23 x 103/μL, the mean nadir WBC was 3.7 ± 0.18 x 103/μL and the mean % decrease was 33%. The mean % decrease in PLT and WBC counts in patients receiving CT and RT was 45% and 41% respectively and the mean % decrease in PLT and WBC counts in patients receiving CT alone was 27% and 35%, respectively. The lowest nadir PLT count was 29 x 103/μL and the lowest nadir WBC was 1.3 x 103/μL. Median time to nadir was 28 days. Conclusions: Sm-153-EDTMP is well tolerated in patients with breast cancer who also receive CT and RT. BM toxicity is minimal with relatively small changes observed from pre-radionuclide levels of PLTs and WBCs. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Cytogen Corp.

The effect of chemotherapy (CT) and external beam radiotherapy (RT) on bone marrow (BM) toxicity of radionuclides in the treatment of bone metastases secondary to breast cancer

796 Background: Bone metastases are commonly seen in patients with metastatic breast cancer. Radionuclide therapy has been shown to alleviate the pain of bone metastases but may be associated with BM toxicity, particularly thrombocytopenia. Because many patients with breast cancer and bone metastases also receive CT and RT, we examined the effects of these other treatments on the BM of samarium (Sm)-153-EDTMP (Quadramet®). Methods: A retrospective review of patients (pts) with breast cancer and bone metastases who had received Sm-153-EDTMP was undertaken. Dates of CT and RT, as well as CT regimens were noted. Pre-and post-radionuclide platelet (PLT) and WBC counts were compared, as were the percent decreases in these parameters. Results: Forty-eight pts received 79 courses of Sm-153-EDTMP. Twenty-eight pts received 29 different chemotherapy regimens prior to treatment with Sm-153-EDTMP. Pre- and post-treatment data were available for 21 courses of Sm-153-EDTMP in 20 patients who received CT and RT and for 6 courses of Sm-153-EDTMP in 5 patients who received CT alone. For the entire cohort, the mean ± SEM baseline PLT count was 268 ± 12 x 103/μL, the mean nadir PLT count was 160 ± 10 x 103/μL and the mean percent (%) decrease in PLT count was 42%. The mean baseline WBC was 5.8 ± 0.23 x 103/μL, the mean nadir WBC was 3.7 ± 0.18 x 103/μL and the mean % decrease was 33%. The mean % decrease in PLT and WBC counts in patients receiving CT and RT was 45% and 41% respectively and the mean % decrease in PLT and WBC counts in patients receiving CT alone was 27% and 35%, respectively. The lowest nadir PLT count was 29 x 103/μL and the lowest nadir WBC was 1.3 x 103/μL. Median time to nadir was 28 days. Conclusions: Sm-153-EDTMP is well tolerated in patients with breast cancer who also receive CT and RT. BM toxicity is minimal with relatively small changes observed from pre-radionuclide levels of PLTs and WBCs. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Cytogen Corp.

Cerebrospinal fluid abnormalities in a phase III trial of Avonex® (IFNβ-1a) for relapsing multiple sclerosis

Background and objective: This report provides results of CSF analyses done in a subset of relapsing remitting MS patients participating in a placebo-controlled, double-blind, phase III clinical trial of IFNβ-Studies supported by the National Multiple Sclerosis Society (grants RG2019, RG2827),a (Avonex®, Biogen). The clinical trial demonstrated that IFNβ-1a treatment resulted in significantly reduced disability progression, annual relapse rate, and new brain lesions visualized by cranial magnetic resonance imaging. The objectives of the current study were to determine: (a) whether CSF abnormalities in MS patients correlated with disease or MRI characteristics, and (b) effects of IFNβ-1a therapy on these CSF abnormalities. Methods: CSF was analyzed from 262 (87%) of the 301 study subjects at entry into the clinical trial, and a second CSF sample was analyzed from 137 of these 262 subjects after 2 years of therapy. CSF cell counts, oligoclonal bands (OCB), IgG index, and free kappa light chains were measured using standard assays. Baseline CSF results were compared with demographic, disease, and MRI parameters. Differences in on-study relapse rate, gadolinium enhancement, and EDSS change according to baseline CSF status was used to determine the predictive value of CSF for subsequent clinical and MRI disease activity. Change in CSF parameters after 104 weeks were used to determine the effects of treatment. Results: (1) At study baseline, 37% of the subjects had abnormal CSF WBC counts, 61% had abnormal levels of CSF free kappa light chains, 84% had abnormal IgG index values, and 90% were positive for OCB. (2) Baseline IgG index, kappa light chains, and OCB showed weakly positive, statistically significant correlations with Gd-enhanced lesion volume and T2 lesion volume. WBC showed a statistically significant correlation with Gd-enhancing lesion volume but was uncorrelated with T2 lesion volume. (3) There was an associated between baseline CSF WBC counts and on-study clinical and MRI disease activity in placebo recipients. (4) IFNβ-1a treatment resulted in significantly reduced CSF WBC counts, but there was no treatment-related change in CSF IgG index, kappa light chains, or OCB, which remained relatively stable over time in both patient groups. Conclusions: The current study documents significant reductions in CSF WBC counts in patients treated with IFNβ-1a for 104 weeks. This finding is considered relevant to the therapeutic response, since CSF WBC counts were found to be positively correlated with subsequent clinical and MRI disease activity in placebo-treated relapsing MS patients.