Alfa Thalassemia Intermedia (HbH disease): How the New Information Provided by the Routine Hematology Analysers May Help in Its Differential Diagnosis or Flagging

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5180-5180
Author(s):  
Susanna Barella ◽  
Ramon Simon-Lopez ◽  
Nicola Di Gaetano ◽  
Renzo Galanello
Keyword(s):  
Research Funding ◽  
Roc Analysis ◽  
Dna Analysis ◽  
Point Mutations ◽  
Control Group ◽  
Thalassemia Intermedia ◽  
Gene Encoding ◽  
New Information ◽  
Best Parameters ◽  
Hbh Disease

Abstract Abstract 5180 Alpha-thalassemia (α-thalassemia) has two clinically significant forms: hemoglobin Bart hydrops fetalis (Hb Bart) syndrome and hemoglobin H (HbH) disease. HbH disease is characterized by microcytic hypochromic hemolytic anemia, hepatosplenomegaly, mild jaundice, and sometimes thalassemia-like bone changes. Diagnostic of Alfa Thalassemia: Classic testing for α-thalassemia includes: hematologic testing of red blood cell indices, peripheral blood smear, supravital stain to detect RBC inclusion bodies, and qualitative and quantitative hemoglobin analysis. HBA1, the gene encoding α1-globin, and HBA2, the gene encoding α2-globin, are the two genes most commonly associated with α-thalassemia. Molecular genetic testing of HBA1 and HBA2 detects deletions in about 90% and point mutations in about 10% of affected individuals. Objective: Recently have been developed new parameters and information in the new automated hematology analyzer called DxH8008™ from Beckman Coulter as @MSCV, @RSF, @MAF, @LHD% and many morphological parameters for RBC and Reticulocytes calles Cell Population Data. All this parameters may be used to create flagging for laboratory use only (LUO) or Research use only (RUO). The purpose of this study is to investigate the possible use or utility of this new information for the screening/flagging of Alfa Thalassemia. Patient and Methods: We have collected 129 patients with Alfa Thalassemia Intermedia (HbH disease). All of them were confirmed by red cell morphology, Hgb Electroforesis, cromatography in liquid phase in human whole blood for the determination of Hemoglobin A2, F, A1c, and identification of abnormal hemoglobins and DNA analysis (DNA Analysis by GAP-PCR). We have compared these patients with a control group (184 individuals) and with other anemias (see Table 1). Results: Using ROC analysis, the best parameters differentiating the HbH Disease from the normals were: RDW (AUC 1. 000), @LHD(AUC 1. 000), @MAF(AUC 1. 000), @MCNRET (AUC 1. 000), MCV (AUC 0. 999), @MCRET (AUC 0. 999), @RSF (AUC 0. 998), HGB (AUC 0. 996), @MSCV (AUC 0. 995). Using ROC analysis, the best parameters differentiating the HbH Disease from other anemias (excluding normals) were: @LHD(AUC 0. 957), @MCNRET (AUC 0. 946), @MCRET (AUC 0. 902), @MAF(AUC 0. 873), MCV (AUC 0. 869). Using logistic regression we found a discrminant function that permits to differentiate/flag perfectly the patients with HbH disease from other anemias, and of course from normals: AUC 0. 996) Sensitivity: 91. 47% Specificity 94. 68% with a percent of cases correctly classified of: 93. 67 %. Disclosures: Simon-Lopez: Beckman Coulter: @LHD, @MAF, @RSF, @LHD, @MAF, @RSF Patents & Royalties, Employment. Di Gaetano:Instrumentation Laboratory spa: Work for a distributor of Beckman Coulter Instruments in Italy Other. Galanello:Novartis: Research Funding, Speakers Bureau; Apopharma: Research Funding, Speakers Bureau; Ferrokin: Research Funding.

Alfa Thalassemia Heterozygous: How the New Information Provided by the Routine Hematology Analysers May Help in Its Differential Diagnosis or Flagging

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5183-5183
Author(s):  
Susanna Barella ◽  
Ramon Simon-Lopez ◽  
Nicola Di Gaetano ◽  
Renzo Galanello
Keyword(s):  
Research Funding ◽  
Roc Analysis ◽  
Dna Analysis ◽  
Molecular Genetic ◽  
Point Mutations ◽  
Control Group ◽  
Gene Encoding ◽  
New Information ◽  
Thalassemia Trait ◽  
Best Parameters

Abstract Abstract 5183 Carriers of α°-thalassemia (α-thalassemia trait) show microcytosis, hypochromia, and normal percentages of HbA2 and HbF. Carriers of α + -thalassemia (α-thalassemia silent carrier) have either a silent hematologic phenotype or present with a moderate thalassemia-like hematologic picture. Homozygosity for α + -thalassemia results in an α°-thalassemia (α-thalassemia trait) hematologic phenotype. Diagnostic of Alfa Thalassemia Heterozygous: Classic testing for α-thalassemia includes: hematologic testing of red blood cell indices, peripheral blood smear, supravital stain to detect RBC inclusion bodies, and qualitative and quantitative hemoglobin analysis. HBA1, the gene encoding α1-globin, and HBA2, the gene encoding α2-globin, are the two genes most commonly associated with α-thalassemia. Molecular genetic testing of HBA1 and HBA2 detects deletions in about 90% and point mutations in about 10% of affected individuals. Objective: Recently have been developed new parameters and information in the new automated hematology analyzer called DxH8008™ from Beckman Coulter as @MSCV, @RSF, @MAF, @LHD% and many morphological parameters for RBC and Reticulocytes calles Cell Population Data. All this parameters may be used to create flagging for laboratory use only (LUO) or Research use only (RUO). The purpose of this study is to investigate the possible use or utility of this new information for the screening/flagging of Alfa Thalassemia Heterozygous. Patient and Methods: We have collected 48 patients with Alfa Thalassemia Heterozygous All of them were confirmed by red cell morphology, Hgb Electroforesis, cromatography in liquid phase in human whole blood for the determination of Hemoglobin A2, F, A1c, and identification of abnormal hemoglobins and DNA analysis (DNA Analysis by GAP-PCR). We have compared these patients with a control group (184 individuals) and with other anemias (see Table 1). Results: Using ROC analysis, the best parameters differentiating the Alfa Thalassemia Heterozygous from the normals were: MCV (AUC 0. 963), @RSF (AUC 0. 936), @MSCV (AUC 0. 912), RDW (AUC 0. 848), @MAF(AUC 0. 845), @LHD(AUC 0. 829). Using ROC analysis, the best parameters differentiating the Alfa Thalassemia Heterozygous from other anemias (excluding normals) were: RDW (AUC 0. 885), @MAF(AUC 0. 857), @MCNRET (AUC 0. 832). Disclosures: Simon-Lopez: Beckman Coulter: @LHD, @MAF, @RSF, @LHD, @MAF, @RSF Patents & Royalties, Employment. Di Gaetano:Instrumentation Laboratory spa: Work for a distributor of Beckman Coulter Instruments in Italy Other. Galanello:Ferrokin: Research Funding; Apopharma: Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau.

Beta Thalassemia Trait: How the New Information Provided by the Routine Hematology Analysers May Help in Its Differential Diagnosis or Flagging

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5186-5186
Author(s):  
Susanna Barella ◽  
Ramon Simon-Lopez ◽  
Nicola Di Gaetano ◽  
Renzo Galanello
Keyword(s):  
Research Funding ◽  
Roc Analysis ◽  
Dna Analysis ◽  
Population Data ◽  
Beta Thalassemia ◽  
Control Group ◽  
Target Cells ◽  
New Information ◽  
Thalassemia Trait ◽  
Best Parameters

Abstract Abstract 5186 Introduction: Beta Thalassemia (β-thalassemia) is one of the more common hemoglobinopathies worldwide, being the heterozygous variant, called Beta Thalassemia Trait, a benign variant, but important to diagnose, for genetic counseling, trying to avoid the homozygous variant, called major. Diagnostic of Beta Thalassemia Trait: Classic testing for β-thalassemia includes: hematologic testing of red blood cell indices, peripheral blood smear (prewsence of target cells and RBC with basophilic stippling, etc.), and qualitative and quantitative hemoglobin analysis. Have been proposed too Discriminant functions, like the one published many years ago, by England and Fraser. Objective: Recently have been developed new parameters and information in the new automated hematology analyzer called DxH8008™ from Beckman Coulter as @MSCV, @RSF, @MAF, @ LHD% and many morphological parameters for RBC and Reticulocytes calles Cell Population Data. All this parameters may be used to create flagging for laboratory use only (LUO) or Research use only (RUO). The purpose of this study is to investigate the possible use or utility of this new information for the screening/flagging of Beta Thalassemia Trait. Patient and Methods: We have collected 30 patients with Beta Thalassemia Trait. All of them were confirmed by red cell morphology, Hgb Electroforesis, cromatography in liquid phase in human whole blood for the determination of Hemoglobin A2, F, A1c, and identification of abnormal hemoglobins and DNA analysis (DNA Analysis by GAP-PCR). We have compared these patients with a control group (184 individuals) and with other anemias (see Table 1). Results: Using ROC analysis, the best parameters differentiating the Beta Thalassemia Trait from the normals were: MCV (AUC 1. 000), MRV (AUC 0. 999), @MAF(AUC 0. 999), @MCNRET (AUC 0. 997), RDW (AUC 0. 957), HGB (AUC 0. 915), RBC(AUC 0. 912). Using ROC analysis, the best parameters differentiating the Beta Thalassemia Trait from other anemias (excluding normals) were: RDW-SD (AUC 0. 937), DF Eng-Fra (AUC 0. 779), RDW (AUC 0. 766), RBC (AUC 0. 734) Disclosures: Simon-Lopez: Beckman Coulter: @LHD, @MAF, @RSF, @LHD, @MAF, @RSF Patents & Royalties, Employment. Di Gaetano:Instrumentation Laboratory spa: Work for a distributor of Beckman Coulter Instruments in Italy Other. Galanello:Ferrokin: Research Funding; Apopharma: Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau.

Hereditary Spherocytosis: How the New Information Provided by the Routine Hematology Analysers May Help in Its Differential Diagnosis or Flagging

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5163-5163
Author(s):  
Susanna Barella ◽  
Ramon Simon-Lopez ◽  
Nicola Di Gaetano ◽  
Renzo Galanello
Keyword(s):  
Research Funding ◽  
Roc Analysis ◽  
Hereditary Spherocytosis ◽  
Osmotic Fragility ◽  
Peripheral Blood Smear ◽  
Band 3 ◽  
Screening Tests ◽  
New Information ◽  
Related Proteins ◽  
Best Parameters

Abstract Abstract 5163 Introduction: Hereditary Spherocytosis (HS) is one of the most common inherited hemolytic anemias. Many of them are autosomal dominant, being about 25% of the cases transmitted recessively. Diagnostic of HS: Classic testing for HS includes: Hematologic testing of red blood cell indices (RDW, MCHC, Reticulocyte count), peripheral blood smear (presence of spherocytes), osmotic fragility and Eosin-5-maleimide binding to band 3 and Rh-related proteins forms that may be used as screening tests for hereditary spherocytosis. Objective: Recently have been developed new parameters and information in the new automated hematology analyzer called DxH8008™ from Beckman Coulter as @MSCV (@Mean Sphered Cell Volume), @RSF, @MAF, @ LHD%. All this parameters may be used to create flagging for laboratory use only (LUO) or Research use only (RUO). The purpose of this study is to investigate the possible use or utility of this new information for the screening/flagging of Hereditary Spherocytosis. There are previous studies showing the possible benefit of using MCV minus @MSCV for the detection/flagging of cases with spherocytes. Patient and Methods: We have collected 28 patients with Hereditary Spherocytosis. All of them were confirmed by red cell morphology, osmotic fragility and Eosin-5-maleimide binding to band 3 and Rh-related proteins forms. Results: Using ROC analysis, the best parameters differentiating the Hereditary Spherocytosis from the normals were: RET% (AUC 0. 996), MCV - @MSCV (AUC 0. 996), @MSCV (AUC 0. 969), RDW(AUC 0. 892), MCHC (AUC 0. 860), HGB (AUC 0. 787). Using ROC analysis, the best parameters differentiating the Hereditary Spherocytosis from other anemias (excluding normals)were: MCV - @MSCV (AUC 0. 991), MCHC (AUC 0. 987), RET% (AUC 0. 857). Disclosures: Simon-Lopez: Beckman Coulter: @LHD, @MAF, @RSF, @LHD, @MAF, @RSF Patents & Royalties, Employment. Di Gaetano:Instrumentation Laboratory spa: Work for a distributor of Beckman Coulter Instruments in Italy Other. Galanello:Novartis: Research Funding, Speakers Bureau; Apopharma: Research Funding, Speakers Bureau; Ferrokin: Research Funding.

scholarly journals Genotypes of the Gene Encoding the Membrane Transporter SLC22A4 Are Associated with Molecular Relapse-Free Survival after Discontinuation of Imatinib Therapy in Patients with Chronic Myeloid Leukemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1647-1647
Author(s):  
Katerina Machova ◽  
Ali Albeer ◽  
Vaclava Polivkova ◽  
Katerina Vlcanova ◽  
Alice Fabarius ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Research Funding ◽  
Dna Analysis ◽  
University Hospital ◽  
Molecular Response ◽  
Imatinib Treatment ◽  
Gene Encoding ◽  
Factors Affecting ◽  
Prognostic Analysis ◽  
Pre Treatment

Introduction: The single nucleotide polymorphism (SNP) rs460089 (G/C) located in the promotor of SLC22A4 (transporter hOCTN1) was identified as a prognostic factor for the outcome of chronic myeloid leukaemia patients treated with imatinib first line (Jaruskova et al. JECCR 2017). Patients with GC genotype had significantly higher probability of achievement of sustained major molecular response (MMR, BCR-ABL≤0.1% IS) as compared with patients with GG. We investigated differences in the outcome after imatinib cessation in EURO-SKI patients according to the genotypes of the SNP rs460089. Methods: DNA analysis was performed by TaqMan SNP genotyping assay using StepOnePlus RQ-PCR System (Thermofisher Scientific). In addition to the inclusion criteria defined for prognostic analysis in Saussele et al. (Lancet Oncology 2018), all patients with interferon pre-treatment were excluded. Data on sex, duration of IM treatment, of deep molecular response and age at time of imatinib discontinuation as well as molecular status at 6 months thereafter were available for 178 patients. Logistic regression was used to investigate factors affecting MMR maintenance at 6 months. Level of significance was 0.05. Results: Of 178 patients, 106 (60%) maintained MMR 6 months after imatinib stop. GC genotype was identified in 64 patients, GG in 96 and CC in 18. Most beneficial for MMR maintenance was genotype GC (72%, 95% confidence interval (CI): 60-82%), followed by CC (61%, CI: 38-80%) and GG (51%, CI: 41-61%). Overall, the SNP rs460089 was associated with MMR maintenance (p=0.0335) with a significantly higher odds ratio (OR) for maintenance for GC genotype vs. GG (2.451, CI: 1.247-4.819, p=0.0093) but not for CC vs. GG (1.507, CI: 0.539-4.216, p=0.4343). Only duration of TKI treatment was significant (OR: 1.157, CI: 1.014-1.319, p=0.0303) when added to genotypes in multiple regression. The OR of GC vs. GG was slightly modified to 2.311 (1.164-4.588, p=0.0166). Conclusions: Based on observed data we suppose that the GC genotype of the SNP rs460089 is associated with sufficient intracellular concentration of imatinib allowing more efficient targeting of CML cells during the treatment. This resulted in a higher proportion of patients who sustained MMR after imatinib stop as compared with patients with GG. Longer duration of imatinib treatment increased the probability of MMR maintenance after imatinib cessation also in patients with GG. The frequency of CC was low and outcome in between GC and GG. The SNP rs460089 may provide an independent prognostic factor for molecular response maintenance after imatinib cessation. Supported by MZCR 00023736. Disclosures Machova: Novartis: Consultancy; BMS: Consultancy, Research Funding; Incyte: Consultancy. Fabarius:Novartis: Research Funding. Brümmendorf:Pfizer: Consultancy, Research Funding; University Hospital of the RWTH Aachen: Employment; Merck: Consultancy; Ariad: Consultancy; Novartis: Consultancy, Research Funding; Janssen: Consultancy. Burchert:Novartis: Research Funding. Mustjoki:BMS: Honoraria, Research Funding; Novartis: Research Funding; Pfizer: Research Funding. Mayer:AOP Orphan Pharmaceuticals AG: Research Funding. Žáčková:Bristol Myers Squibb: Consultancy; Angelini: Consultancy; Incyte: Consultancy; Novartis: Consultancy. Panayiotidis:Bayer: Other: Support of clinical trial. Richter:Novartis: Consultancy; Pfizer: Consultancy, Research Funding. Hjorth-Hansen:BMS: Research Funding; Pfizer: Consultancy, Research Funding; Austrian Orphan Pharma: Consultancy, Research Funding. Saussele:Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Pfizer: Honoraria; Incyte: Honoraria, Research Funding.

scholarly journals CD77 levels over enzyme replacement treatment in Fabry Disease Family (V269M)

2018 ◽  
Vol 40 (4) ◽  
pp. 333-338
Author(s):  
Ester Miranda Pereira ◽  
Adalberto Socorro da Silva ◽  
Raimundo Nonato da Silva ◽  
José Tiburcio Monte Neto ◽  
Fernando F. do Nascimento ◽  
...  
Keyword(s):  
Fabry Disease ◽  
Cell Types ◽  
Control Group ◽  
Gene Encoding ◽  
Peripheral Blood Mononuclear ◽  
Enzyme Replacement ◽  
Replacement Treatment ◽  
Promising Tool ◽  
Potential Marker ◽  
Different Cell Types

ABSTRACT Introduction: Fabry disease (FD) is a disorder caused by mutations in the gene encoding for lysosomal enzyme α-galactosidase A (α-GAL). Reduced α-GAL activity leads to progressive accumulation of globotriaosylceramide (Gb3), also known as CD77. The recent report of increased expression of CD77 in blood cells of patients with FD indicated that this molecule can be used as a potential marker for monitoring enzyme replacement therapy (ERT). Objective: The purpose of this study was to evaluate the CD77 levels throughout ERT in FD patients (V269M mutation). Methods: We evaluated the fluctuations in PBMC (peripheral blood mononuclear cell) membrane CD77 expression in FD patients undergoing ERT and correlated these levels with those observed in different cell types. Results: A greater CD77 expression was found in phagocytes of patients compared to controls at baseline. Interestingly, the variability in CD77 levels is larger in patients at baseline (340 - 1619 MIF) and after 12 months of ERT (240 - 530 MIF) compared with the control group (131 - 331 MFI). Furthermore, by analyzing the levels of CD77 in phagocytes from patients throughout ERT, we found a constant decrease in CD77 levels. Conclusion: The increased CD77 levels in the phagocytes of Fabry carriers together with the decrease in CD77 levels throughout ERT suggest that measuring CD77 levels in phagocytes is a promising tool for monitoring the response to ERT in FD.

scholarly journals A Cam Shaped Femur Might Be A Risk Factor for ACL Injuries

2018 ◽  
Vol 6 (7_suppl4) ◽  
pp. 2325967118S0013
Author(s):  
Thomas Rudolf Pfeiffer ◽  
Jeremy M. Burnham ◽  
Ajay C. Kanakamedala ◽  
Jonathan Daniel Hughes ◽  
James J. Irrgang ◽  
...  
Keyword(s):  
Acl Reconstruction ◽  
Injury Risk ◽  
Roc Analysis ◽  
Femoral Condyle ◽  
Academic Medical Center ◽  
Acl Injury ◽  
Control Group ◽  
Acl Injuries ◽  
Increased Risk ◽  
The Mean

Objectives: Bony morphologic characteristics have been demonstrated to increase the risk of anterior cruciate ligament (ACL) injury. While posterior femoral condyle condylar offset is an aspect of distal femoral bony morphology that has been reported to influence range of motion and other aspects of knee joint kinematics, it remains unclear whether this characteristic influences the risk of ACL injury. The purpose of the study was to examine the relationship between distal femoral morphology and risks of ACL injury, reconstruction failure, and contralateral ACL injury. It was hypothesized that increased posterior femoral condylar depth, quantified as the cam ratio, would correlate with increased risk of primary ACL injuries, ACL reconstruction failures, and contralateral ACL injuries. Methods: Consecutive patients undergoing evaluation for knee complaints at an academic medical center from 2012-2016 with minimum 24-month follow-up were retrospectively reviewed. Subjects were stratified into four groups: a control group consisting of patients with no ACL injuries and three groups of patients with a primary ACL injury, failed ACL reconstruction, or previous ACL injury with subsequent contralateral ACL injury. Using lateral radiographs, the ratio of posterior condylar depth over total condylar distance was defined as the cam ratio. Analysis-of-variance (ANOVA) and post-hoc testing were used to test for differences in the mean tomahawk ratio between study groups (p<0.05). Receiver Operating Characteristic (ROC) analysis was performed to determine the optimal cam ratio cut-off for detecting increased risk for ACL injury. Results: One hundred and seventy-five patients met inclusion criteria. The mean cam ratios in the control, primary ACL injury, failed ACL reconstruction, and contralateral ACL injury groups were 61.1% (± 2.1), 64.2% (± 3.8), 64.4% (± 3.6), and 66.9% (± 4.0), respectively. Patients with a primary ACL injury, failed ACL reconstruction, or contralateral ACL injury had a significantly higher cam ratio compared to the control group (p<0.008). ROC analysis demonstrated a cam ratio of 63% or greater to be associated with an increased risk for ACL injury with a sensitivity of83% and a specificity of 71%. Conclusion: The data from this study show that an increased posterior femoral condylar depth, or cam ratio, might be associated with increased risk of ACL injury, including primary ACL injury, failed ACL reconstruction, and contralateral ACL injury. The data from this study may help clinicians identify patients at greater risk of ACL injury and re-injury. Future prospective studies will be helpful in investigating the mechanism by which an increased cam ratio increases ACL injury risk and potential strategies to mitigate the increased risk posed by this bony characteristic.

scholarly journals Platelet and Immune Characteristics of Patients with Immune Thrombocytopaenia Non Responders to Therapeutic Treatments

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1089-1089
Author(s):  
Elena Monzón Manzano ◽  
Raul Justo Sanz ◽  
Diana Hernández ◽  
Teresa Álvarez Roman ◽  
Ihosvany Fernandez-Bello ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Immune Response ◽  
Sialic Acid ◽  
Research Funding ◽  
Caspase 3 ◽  
Mononuclear Cells ◽  
Ricinus Communis ◽  
The Other ◽  
Control Group ◽  
Platelet Surface

Introduction: Mechanisms leading to diminished platelet counts in immune thrombocytopaenia (ITP) appear to be multifactorial: autoantibodies, autoreactive CD8+ cytotoxic T cells, enhanced apoptosis and loss of sialic acid which mediates platelet clearance through the Ashwell-Morell receptors present in hepatocytes. Differential involvement of each of them might condition the ability of patients with ITP to respond to treatments. We aimed to examine platelet features and the immunological state of patients with ITP who do not respond to any treatment to detect the unique characteristics of this group. Methods: This was an observational, prospective and transversal study. Patients with chronic primary ITP were included: 28 ITP patients without treatment for at least 6 months (UT-ITP); 36 responders to agonists of thrombopoietin receptors (TPO-RA); and 14 ITP patients who did not respond to first- and second-line treatments (NR-ITP). A healthy control group (n=104) was also included in the study. Active caspase-3, -7, -8 or -9 were determined by flow cytometry using CaspaTag kits (Millipore, Madrid, Spain) in PRP diluted with HEPES-buffer containing 2 mM Ca2+ and 2 mM Gly-Pro-Arg-Pro (Sigma-Aldrich, Madrid, Spain) to prevent fibrin formation . Platelet surface glycan exposure was analysed by determining the binding of lectins by flow cytometry. To do so, washed platelets were incubated with 1 μg/ml Alexa fluor 488-conjugated wheat germ agglutinin lectin (WGA, Invitrogen, Spain) or with 1 μg/ml FITC-conjugated Ricinus communis agglutinin (RCA, Vector Labs, UK). WGA binds to sialic acid and N-acetylglucosaminyl residues, and RCA is a galactose-specific legume lectin which binding serves as an indirect measurement of the loss of sialic acid. Peripheral blood mononuclear cells (PBMCs) subsets were analysed by flow cytometry using specific antibodies. Experimental data was analysed using SPSS 9.0 software (SPSS Inc., Chicago, IL). Results: Platelets from TPO-RA treated and from NR-ITP patients had increased caspase-3, -7, -8 and -9 activities (Figure 1A). Platelets from NR-ITP patients exposed less sialic acid and more N-acetylglucosaminyl residues than the other groups (Figure 1B). Binding of WGA and RCA correlated with caspase activities (Table 1). Distribution of lymphocytes, monocytes and natural killer cells is shown in Table 1. NR-ITP patients had an increased proportion of B lymphocyte (LB), maybe due to a significant rise in the fraction of naive LB cells, and a diminution in LTreg subset. Whereas classical monocytes was increased, nonclassical monocyte fraction was decreased in the UT-ITP and NR-ITP groups. NR-ITP patients also presented an increased CD16+CD56bright cells fraction and a diminished NK CD16+CD56dim subset. TPO-RA-treated patients seemed to recover an immune homeostasis similar to healthy controls (monocyte and NK cells subset distribution and LTreg count similar to control group). It is of interest to note the relationship between loss of sialic acid from platelet surface glycans and Tregs count: the most reduced surface exposure of sialic acid, the less Treg count (Figure 2). Conclusions: Platelets from NR-ITP patients had more signs of apoptosis and a different composition of surface glycans, accompanied by a diminished LTreg population, a higher LB naïve percentage, and an increased CD16+CD56bright cells fraction in circulation, indicating a severe deregulation of the immune system. Since an inverse correlation was observed between loss of sialic acid and LTreg count, a potential relationship between glycan composition on the platelet surface and immune response is suggested, positing terminal sugar moieties of the glycan chains as aetiopathogenic agents in ITP. On the other hand, TPO-RA appears to have a beneficial effect on immune response. Nevertheless, one of the limitations of our study was that patients were recruited once the response to TPO-RA was achieved; therefore, a longitudinal study would provide more information regarding TPO-RA effects. This work was supported by grants from the FIS-FONDOS FEDER (PI15/01457, NB). NVB holds a Miguel Servet tenure track grant from FIS-FONDOS FEDER (CP14/00024). Disclosures Álvarez Roman: Roche: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Takeda: Research Funding; NovoNordisk: Consultancy, Speakers Bureau; CSL Behring: Consultancy, Speakers Bureau; Sobi: Consultancy, Speakers Bureau. Fernandez-Bello:Novartis, Pfizer, ROCHE, Stago: Speakers Bureau. Martín:SOBI: Research Funding; Novartis, Pfizer, ROCHE, Novo Nordisk: Speakers Bureau. Rivas Pollmar:Novartis, Pfizer, ROCHE, Novo Nordisk: Speakers Bureau; SOBI: Research Funding. Canales:Novartis: Honoraria; Takeda: Speakers Bureau; iQone: Honoraria; Sandoz: Honoraria; Celgene: Honoraria; SOBI: Research Funding; Karyopharm: Honoraria; F. Hoffmann-La Roche Ltd: Honoraria, Speakers Bureau; Gilead: Honoraria; Janssen: Honoraria, Speakers Bureau. Jimenez-Yuste:Bayer, CSL Behring, Grifols, Novo Nordisk, Octapharma, Pfizer, Roche, Sobi, Shire: Consultancy, Honoraria, Other: reimbursement for attending symposia/congresses , Research Funding, Speakers Bureau. Butta:Novartis: Consultancy; Roche, Pfizer: Speakers Bureau.

scholarly journals Board Game as an Educational Game Media to an Effort to Change the Attitude of Dengue Prevention in School-Aged Children

2019 ◽  
Vol 1 (2) ◽  
pp. 1-9
Author(s):  
Vivi Leona Amelia ◽  
Agus Setiawan ◽  
Sukihananto Sukihananto
Keyword(s):  
Dengue Fever ◽  
Age Groups ◽  
Water Storage ◽  
Educational Game ◽  
Control Group ◽  
Board Game ◽  
School Aged Children ◽  
New Information ◽  
Quasi Experimental ◽  
Dengue Prevention

Background: Indonesia is the second highest country for dengue prevalence, and the cases has rapidly increased in the last 45 years. Compared to other age groups, the age group of children is the highest dengue fever prevalence. The attitude of dengue prevention is important for child which related to their skill to preventing the dengue fever by themselves. A game is one of the way to teach the children for a new information, it is also including the dengue prevention material Objective: This study want to identify the attitude of the children about dengue prevention and develop an educational game to teach a new information about dengue prevention. Methods: This study uses quasi-experimental design with pre and posttest with control group. The participants are a school-aged children with age 10-12 years old. With total 92 participants, and 46 for each group. Results: The results show a significantly increasing score at children attitude of dengue prevention before and after intervention except the strategy to closing the water storage (p=0.008), the other strategy that gets a significantly increasing such as fever and fever management (p=0.000), draining the water storage (p=0.001), checking the water storage (p=0.000), recycling (p=0.000), chemistry agent (p=0.000), biology agent (p=0.000), self protection (p=0.001), immune system (0.000). There are different attitude between control and intervention groups (p=0.000). Conclusion: The conclusion is the dengue board game can be an educational game media to give dengue prevention information to children, also can improving the attitude of dengue prevention.   Keywords: Board Game, Dengue Prevention Strategy, School-Aged Children

scholarly journals Favorable Long-Term Outcomes after Daratumumab Discontinuation in AL Amyloidosis Patients Achieving Deep Responses

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1884-1884 ◽  
Author(s):  
Alfred Chung ◽  
Gregory P. Kaufman ◽  
Surbhi Sidana ◽  
David Iberri ◽  
Erik Eckhert ◽  
...  
Keyword(s):  
Disease Progression ◽  
Board Of Directors ◽  
Median Duration ◽  
Research Funding ◽  
Control Group ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Advisory Committees ◽  
Free Interval ◽  
Significant Difference

Daratumumab (DARA) is a CD38-targeted antibody FDA-approved for the treatment of multiple myeloma (MM) and its efficacy has recently been demonstrated in the treatment of AL amyloidosis. DARA is conventionally given indefinitely until evidence of disease progression or intolerance for the treatment of MM. In AL amyloidosis, the optimal duration of therapy is not known, and patients may be treated indefinitely on maintenance, extrapolating from MM data. However, the plasma cell burden observed in AL amyloidosis is often lower than in MM, and thus certain patients achieving deep responses may have durable responses with time-limited treatment. Outcomes for patients who are observed after DARA discontinuation are not known. We report the outcomes of patients at our institution who received time-limited DARA. A retrospective analysis of AL amyloidosis patients treated at Stanford University from 2016 to 2019 with DARA monotherapy and dexamethasone for at least 2 months was performed, and patients who subsequently had DARA discontinued for reasons other than disease progression or lack of response were selected for the study. Hematologic responses were assessed by consensus guidelines. Duration on and off therapy were explored, along with time-to-next treatment or death (TTNT), defined as the time from DARA initiation to restarting/switching therapy or death. An exploratory analysis comparing TTNT between the study population and a control cohort who achieved hematologic CR and were maintained on DARA was conducted with the Kaplan-Meier method and log-rank testing. 67 patients received at least 2 months of DARA monotherapy and dexamethasone; among these, 15 patients discontinued therapy for reasons other than disease progression and were included. Median age was 66 years old and median lines of prior therapies was 4 (range: 1 - 6). Baseline difference between involved and uninvolved free light chains (dFLC) prior to DARA initiation was 2.6 mg/dL (range: 0 - 16.8 mg/dL). 10 of 15 patients had cardiac involvement with median NT-proBNP of 1982 pg/mL and 9 of 15 patients had renal involvement with median 24-hour proteinuria of 6.2 g and eGFR of 32 mL/min/1.73m2 at DARA initiation. Median duration from starting to stopping DARA was 7.8 months (range: 2 - 21 months). Median duration from achieving best hematologic response to stopping DARA was 3 months (range: 0 - 17 months). Reasons for discontinuation included: patient preference (5), fatigue/body aches (4), infection (2), other active medical comorbidities (3), and lack of perceived further benefit (1). At DARA discontinuation, median dFLC was 0.1 mg/dL (range: 0 - 2.2 mg/dL) and there were 12 hematologic CR, 1 VGPR, 1 PR, and 1 not assessable for response. Outcomes for all 15 patients are shown in Figure 1. The median treatment-free interval was 17.5 months (range: 5 - 34 months); estimated 2-year TTNT-free survival was 83% (95% CI: 61 - 100%). All 14 evaluable patients eventually achieved CR. 3 patients restarted DARA for rising dFLC, and all 3 patients demonstrated response to retreatment (2 achieving CR and 1 near PR with ongoing follow-up). There were 2 deaths. One patient with severe baseline cardiac amyloidosis developed sudden rise in dFLC after treatment-free interval of 21 months; although he rapidly achieved hematologic CR on retreatment, he died of heart failure within 2 months of restarting DARA. The other patient developed therapy-related AML while off therapy and underwent allogenic stem cell transplant but died of leukemia (censored for AL amyloidosis outcomes at transplant). There was no significant difference in the TTNT between the study group and a control group of 16 patients who achieved CR and were on continuous maintenance (Figure 2; p=0.807). AL amyloidosis patients achieving deep responses with DARA can have favorable outcomes after treatment discontinuation, including a long treatment-free interval. Although our sample size is small, the outcomes of these patients appeared comparable to those achieving CR on continuous DARA maintenance, and patients were able to regain responses when retreatment was necessary. These results suggest that DARA may be safely discontinued in patents achieving deep hematologic responses, which has significant implications for quality of life and financial burden of treatment. Future studies evaluating time-limited versus continuous DARA maintenance after achievement of deep responses are warranted. Disclosures Kaufman: Janssen: Other: travel/lodging, Research Funding. Liedtke:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; IQVIA/Jazz: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech/Roche: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celator: Research Funding; Caelum: Membership on an entity's Board of Directors or advisory committees; BlueBirdBio: Research Funding; Amgen/Onyx: Consultancy, Honoraria, Research Funding; Agios: Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Daratumumab for treatment of AL amyloidosis

scholarly journals Financial Incentives to Increase Stool Collection Rates for Microbiome Studies in Adult Bone Marrow Transplant Patients

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5775-5775
Author(s):  
Jillian C. Thompson ◽  
Yi Ren ◽  
Kristi M. Romero ◽  
Meagan V. Lew ◽  
Amy T. Bush ◽  
...  
Keyword(s):  
Financial Incentives ◽  
Research Funding ◽  
Intervention Group ◽  
Outpatient Setting ◽  
Historical Control Group ◽  
Historical Control ◽  
Categorical Variables ◽  
Control Group ◽  
Continuous Variables ◽  
Stool Samples

Introduction: Dysbiosis of the gut microbiome during hematopoietic stem cell transplantation (HCT) is associated with adverse post-transplant outcomes such as graft-versus-host disease, bloodstream infections, and mortality. In order to learn more about the role of the microbiome in HCT in adverse clinical outcomes, researchers collect stool samples from patients at various time points throughout HCT. However, unlike blood samples or skin swabs, stool collection requires active subject participation, particularly in the outpatient setting, and may be limited by patient aversion to handling stool. By providing study participants with compensation for their stool samples, we hypothesize that we can significantly increase stool collection rates. Methods: We performed a prospective cohort study on the impact of financial incentives on stool collection rates for microbiome studies. The intervention group consisted of allogeneic (allo)-HCT patients from 05/2017-05/2018 who were compensated with a $10 gas gift card for each stool sample. The intervention group was compared to a historical control group consisting of allo-HCT patients from 11/2016-05/2017 who provided stool samples before the incentive was implemented. To control for potential changes in collections over time, we also compared a contemporaneous control group of autologous (auto)-HCT patients from 05/2017-05/2018 with a historical control group of auto-HCT patients from 11/2016-05/2017; neither auto-HCT groups were compensated. Allo-HCT patients were required to give samples at pre-HCT, day 0 (the day of HCT), and days 7, 14, 21, 30, 60, and 90 post-HCT. Auto-HCT patients were required to give samples at pre-HCT and days 7, 14, and 90 post-HCT. Collection rates were defined as the number of samples provided divided by the number of time points for which we attempted to obtain samples. Patient characteristics were summarized by proportions for categorical variables and median with interquartile ranges for continuous variables. Chi-square tests or Fisher's exact tests were used to compare categorical variables, as appropriate, and Wilcoxon Rank Sum tests or t-tests were used to compare continuous variables, as appropriate. This study was approved by the Duke Institutional Review Board, and informed consent was obtained from all patients. Results: There were 35 allo-HCT patients in the intervention group, 19 allo-HCT patients in the historical control group, 142 auto-HCT patients in the contemporaneous control group, and 75 auto-HCT patients in the historical control group. Groups were similar with regard to baseline demographics such as age, race, and gender. While allo-HCT patients were more likely to have leukemia and auto-HCT patients were more likely to have lymphoma and multiple myeloma, there were no differences in disease rates across the study periods. Allo-HCT patients in the intervention group had significantly higher average overall collection rates when compared to the historical control group allo-HCT patients (80% vs 37%, p<0.001), as well has significantly higher average outpatient collection rates (84% vs 23%, p<0.001) and average inpatient collection rates (71% vs 46%, p=0.04). In contrast, there were no significant differences in overall average collection rates between the auto-HCT patients in the contemporaneous control and historical control group (36% vs 32%, p=0.28), as well as the average outpatient collection rates (30% vs 28%, p=0.54) and the average inpatient collection rates (46% vs 59%, p=0.25). Discussion: Our results demonstrate that even a modest incentive can significantly increase collection rates. Use of a contemporaneous control group to account for potential differences in stool collection rates over time strengthens our finding that financial incentives increase stool collection rates. Furthermore, the significant increase in collection rates in the outpatient setting highlights the role of the incentive when patient participation is needed, as opposed to the inpatient setting in which the nurse assists with collection. While this study uses a specialized HCT patient population, these results may be generalizable to future studies and aid other researchers in obtaining stool samples needed for future microbiome studies. Disclosures Peled: Seres Therapeutics: Other: IP licensing fees, Research Funding. van den Brink:Acute Leukemia Forum (ALF): Consultancy, Honoraria; Juno Therapeutics: Other: Licensing; Merck & Co, Inc.: Consultancy, Honoraria; Seres Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Therakos: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Flagship Ventures: Consultancy, Honoraria; Evelo: Consultancy, Honoraria; Jazz Pharmaceuticals: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Magenta and DKMS Medical Council: Membership on an entity's Board of Directors or advisory committees. Sung:Novartis: Research Funding; Merck: Research Funding; Seres: Research Funding.

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