Cytogenetics in Adult De Novo Acute Myeloid Leukemia: An Institutional Experience of a Predominantly Minority Population.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4484-4484
Author(s):  
Ebenezer Berko ◽  
David Osafo ◽  
Deimante Tamkus ◽  
Decebal S. Griza ◽  
Steven Sloan ◽  
...  
Keyword(s):  
Sample Size ◽  
De Novo ◽  
Small Sample Size ◽  
Small Sample ◽  
Minority Population ◽  
Intermediate Group ◽  
Cytogenetic Aberrations ◽  
Predominantly Minority ◽  
Institutional Experience ◽  
De Novo Aml

Abstract Cytogenetic findings at diagnosis correlate with prognosis in adult AML. Data have been largely derived from Caucasian populations. The purpose of this study was to define the frequency of cytogenetic abnormalities in de novo AML in a predominantly minority population and compare the data with that reported in the literature. We performed a retrospective review of cytogenetic findings at diagnosis in 40 adult AML patients diagnosed between 1999 and 2005. 17 African Americans, 11 Hispanics, 7 Caucasians, 1 Asian and 4 unknown ethnicity made up this population (72.5% minority). The age range was between 15 and 82 years. 28 patients (70%) were less than 55 years and 15 (37.5%) were less than 35 years of age. 75% of patients had abnormal karyotypes and 25% had normal karyotypes. Prognostic group categorization showed that 45% of patients were in the adverse group, 35% in the intermediate group and 20% in the favorable group. The most common cytogenetic finding was complex abnormalities occurring in 37.5% of patients. The frequency of complex abnormalities with adverse prognosis found in this predominantly minority population is higher than that reported in the literature (12% in SWOG/ECOG study; 6% in MRC AML 10 trial). Our study is limited by its small sample size. Further studies with a larger sample size would be needed to clarify the role of race/ethnicity in cytogenetic aberrations in AML.

Recurrent DNMT3A Mutations In Patients with Myelodysplastic Syndrome

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 608-608
Author(s):  
Matthew J. Walter ◽  
Dong Shen ◽  
Jin Shao ◽  
Li Ding ◽  
Marcus Grillot ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Bone Marrow ◽  
Myelodysplastic Syndrome ◽  
Sample Size ◽  
De Novo ◽  
Small Sample Size ◽  
Dna Methyltransferases ◽  
Small Sample ◽  
Mutation Status ◽  
Cd34 Cells

Abstract Abstract 608 Myelodysplastic syndrome (MDS) genomes are characterized by global DNA hypomethylation with concomitant hypermethylation of gene promoter regions compared to CD34+ cells from normal bone marrow samples. Currently, the underlying mechanism of altered DNA methylation in MDS genomes and the critical target genes affected by methylation remain largely unknown. The methylation of CpG dinucleotides in humans is mediated by DNA methyltransferases, including DNMT1, DNMT3A, and DNMT3B. DNMT3A and DNMT3B are the dominant DNA methyltransferases involved in de novo DNA methylation and act independent of replication, whereas DNMT1 acts predominantly during replication to maintain hemimethylated DNA. The function of these proteins in cancer cells is less well defined. Our group recently found that DNMT3A mutations are common in de novo acute myeloid leukemia (62/281 cases, 22%) and are associated with poor survival (Ley, et al, unpublished), providing a rationale for examining the mutation status of DNMT3A in MDS patients. MDS cases (n=150) were classified according to the French-American-British (FAB) system. The patients included refractory anemia (RA; n=67), RA with ringed sideroblasts (RARS; n=5), RA with excess blasts (RAEB; n=72), and RA with excess blasts in transformation (RAEB-T; n=6). The median International Prognostic Scoring System (IPSS) score was 1 (range 0–3), and the median myeloblast count was 4 (range 0–28%). We designed and validated 28 primer pairs covering the coding sequences and splice sites of all 23 exons for DNMT3A. Paired DNA samples were obtained from the bone marrow (tumor) and skin (normal) of each patient so that somatic mutations could be distinguished from inherited variants/polymorphisms. 17,120 reads were produced by capillary sequencing, providing at least 1X coverage for 82.6% of the target sequence (low/no coverage was obtained for 2 out of 28 amplicons). A semiautomated analysis pipeline was used to identify sequence variants and we restricted our analysis to nonsynonymous and splice site nucleotide changes. All mutations were confirmed by independent PCR and sequencing. We identified nonsynonymous DNMT3A mutations in 12/150 bone marrow samples (8% of cases). All the mutations were heterozygous (10 missense, 1 nonsense, 1 frameshift) and were computationally predicted (by SIFT and/or PolyPhen2) to have deleterious functional consequences. DNMT3A mRNA is expressed in normal CD34+ bone marrow cells and was expressed in all MDS patient samples tested (n=28), independent of mutation status. There was no difference in the expression level of total DNMT3A mRNA in CD34+ cells harvested from mutant (n=3) vs. non-mutant MDS samples (n=25). Amino acid R882, located in the methyltransferase domain of DNMT3A, was the most common mutation site, accounting for 4/12 mutations. The clinical characteristics of the 12 patients with DNMT3A mutations were similar to those of the 138 patients without mutations. Specifically, DNMT3A mutations were present in all MDS FAB subtypes (excluding CMML which was not tested) and in patients with IPSS scores ranging from 0–3. Mutations were not associated with a specific karyotype. In addition, there was no correlation between mutation detection and the myeloblast count of the banked bone marrow specimen, suggesting that mutations were not missed due to the cellular heterogeneity in the samples. We compared the overall (OS) and event-free survival (EFS) of the 12 patients with DNMT3A mutations vs. 138 patients without a mutation and observed a significantly worse OS in patients with mutations (p=0.02), with a median survival of 433 and 945 days, respectively. There was a trend towards worse EFS for patients with mutations (p=0.05). A multivariate analysis for outcomes could not be performed due to the small sample size of patients with mutations, indicating that a larger cohort from a clinical trial will be needed to properly address the affect of DNMT3A mutations on outcomes. The small sample size also precluded us from addressing whether the response to the hypomethylating agents 5-azacytidine or decitabine correlated with the mutation status of DNMT3A. If validated in larger cohort studies, we propose that DNMT3A mutation status could help risk stratify de novo MDS patients for more aggressive treatment early in their disease course. Disclosures: Westervelt: Novartis: Honoraria; Celgene: Honoraria, Speakers Bureau. DiPersio:Genzyme: Honoraria.

Application of Ultrasound Elastography for Assessing Intestinal Fibrosis in Inflammatory Bowel Disease: Fiction or Reality?

2020 ◽  
Vol 21 ◽  
Author(s):  
Roberto Gabbiadini ◽  
Eirini Zacharopoulou ◽  
Federica Furfaro ◽  
Vincenzo Craviotto ◽  
Alessandra Zilli ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Sample Size ◽  
Bowel Disease ◽  
Small Sample Size ◽  
Shear Wave Elastography ◽  
Small Sample ◽  
Ultrasound Elastography ◽  
Invasive Technique ◽  
Intestinal Fibrosis ◽  
Inflammatory Bowel

Background: Intestinal fibrosis and subsequent strictures represent an important burden in inflammatory bowel disease (IBD). The detection and evaluation of the degree of fibrosis in stricturing Crohn’s disease (CD) is important to address the best therapeutic strategy (medical anti-inflammatory therapy, endoscopic dilation, surgery). Ultrasound elastography (USE) is a non-invasive technique that has been proposed in the field of IBD for evaluating intestinal stiffness as a biomarker of intestinal fibrosis. Objective: The aim of this review is to discuss the ability and current role of ultrasound elastography in the assessment of intestinal fibrosis. Results and Conclusion: Data on USE in IBD are provided by pilot and proof-of-concept studies with small sample size. The first type of USE investigated was strain elastography, while shear wave elastography has been introduced lately. Despite the heterogeneity of the methods of the studies, USE has been proven to be able to assess intestinal fibrosis in patients with stricturing CD. However, before introducing this technique in current practice, further studies with larger sample size and homogeneous parameters, testing reproducibility, and identification of validated cut-off values are needed.

scholarly journals Confirming known planetary trends using a photometrically selected Kepler sample

2020 ◽  
Author(s):  
Jonah T Hansen ◽  
Luca Casagrande ◽  
Michael J Ireland ◽  
Jane Lin
Keyword(s):  
Sample Size ◽  
Robust Statistics ◽  
Narrow Band ◽  
Small Sample Size ◽  
Small Sample ◽  
Fitting Algorithm ◽  
Statistical Studies ◽  
The Rich ◽  
Host Stars ◽  
High Metallicity

Abstract Statistical studies of exoplanets and the properties of their host stars have been critical to informing models of planet formation. Numerous trends have arisen in particular from the rich Kepler dataset, including that exoplanets are more likely to be found around stars with a high metallicity and the presence of a “gap” in the distribution of planetary radii at 1.9 R⊕. Here we present a new analysis on the Kepler field, using the APOGEE spectroscopic survey to build a metallicity calibration based on Gaia, 2MASS and Strömgren photometry. This calibration, along with masses and radii derived from a Bayesian isochrone fitting algorithm, is used to test a number of these trends with unbiased, photometrically derived parameters, albeit with a smaller sample size in comparison to recent studies. We recover that planets are more frequently found around higher metallicity stars; over the entire sample, planetary frequencies are 0.88 ± 0.12 percent for [Fe/H] < 0 and 1.37 ± 0.16 percent for [Fe/H] ≥ 0 but at two sigma we find that the size of exoplanets influences the strength of this trend. We also recover the planet radius gap, along with a slight positive correlation with stellar mass. We conclude that this method shows promise to derive robust statistics of exoplanets. We also remark that spectrophotometry from Gaia DR3 will have an effective resolution similar to narrow band filters and allow to overcome the small sample size inherent in this study.

scholarly journals AB0543 CLINICAL CHARACTERISTICS OF A GROUP OF CHRONIC GRAFT-VERSUS-HOST DISEASE PATIENTS WITH POSITIVE AUTOIMMUNITY.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1568.1-1568
Author(s):  
M. E. Acosta ◽  
L. Gómez-Lechón ◽  
O. Compán ◽  
S. Pastor ◽  
C. A. Montilla-Morales ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Clinical Characteristics ◽  
De Novo ◽  
Small Sample Size ◽  
Small Sample ◽  
Eosinophilic Fasciitis ◽  
Ocular Involvement ◽  
Host Disease ◽  
Graft Versus Host ◽  
Multidisciplinary Consultation

Background:Graft-versus-host disease (GVHD) is a commonly severe multiorgan complication in patients undergoing allogeneic transplantation of hematopoietic progenitors. Its chronic form reflects a complex immune response with different degrees of inflammation, immune dysregulation and fibrosis. In some chronic graft-versus-host disease (cGVHD) patients, positive antibodies have been detected, which represent the presence of immune activity and suggest the possible involvement of B lymphocytes in the disease etiopathogenesis, but their clinical utility is controversial.Objectives:To describe the clinical characteristics of a group of cGVHD patients with positive autoimmunity treated in a multidisciplinary consultation of Rheumatology-Dermatology- Hematology of GVHD.Methods:Observational and retrospective study to describe the clinical characteristics of the patients with positive autoimmunity collected in the database of the multidisciplinary consultation of GVHD. The variables reviewed for this study, in addition to the demographic ones, were type of antibody, disease causing the transplant, presentation, severity and type of involvement. The statistical analysis was done with Epi-info 7.2.2.6.Results:Only 16 (16%) of the 100 patients included in the database had positive autoimmunity. Twelve (75%) tested positive to ANA, although 5 (31.25%) in a lower titer (1/80). The most common immunofluorescence pattern was the nucleolar in 88.89% (66.67% nucleolar and 22.22% nucleolar + cytoplasmic). Other antibodies detected were: 6 anti-Ro52, 2 anti-dsDNA, 1 anti-RP155, 1 anti-Fibrillarin, 1 anti-SAE1, 1 p-ANCA and 1 anti-NOR-90. The mean of age was 51.31±14.03 years. As for sex 4 (25%) were female and 12 (75%) were men. The most frequent disease that caused the transplant was acute myeloid leukemia (58.3%). Ten (62.5%) patients presented de novo cGVHD, 1 (6.25%) progressive and 5 (31.25%) quiescent. The time since receiving the transplant until the first visit was 14 to 79 months. Ten (62.5%) patients had nonspecific symptoms (arthralgia and myalgia), 2 (12.5%) edema, 8 (50%) contractures, 8 (50%) fasciitis and 6 (37.5%) eosinophilia. Eight (50%) patients had ocular involvement and 6 (37.5%) of the oral mucosa in the form of dry syndrome (Sjögren-like syndrome). Ten (62.5%) patients had limitation of joint mobility detected by the range of motion scale (ROM), of which 6 were mild and 4 moderate. Only 5 (31.25%) patients had general condition impairment. As for the skin involvement 10 (62.5%) patients had sclerodermiform involvement (8 of them being eosinophilic fasciitis- like), 2 (12.5%) lichenoid, and 3 (18.5%) mixed (sclerodermiform + lichenoid). Only 1 patient didn´t meet diagnostic criteria for GVHD. The sclerodermiform was the most common type of involvement in the positive ANA patients. Regarding the severity according to the of the American National Institute of Health (NIH) classification: 8 (50%) had serious affectation, 5 (31.25%) moderate and 2 (12.5%) mild, with 4 (25%) exitus.Conclusion:In our cohort of patients with cGVHD, serum detection of autoantibodies is uncommon, being the ANA with nucleolar pattern the most frequent. Although the small sample size does not allow correlations with the clinical variables it´s worth highlighting a greater positivity of autoantibodies in the sclerodermiform skin forms.References:[1]Kuzmina Z et al. Clinical significance of autoantibodies in a large cohort of patients with chronic graft-versus-host disease defined by NIH criteria. Am J Hematol. 2015 February; 90(2): 114–119.[2]Rhoades R, Gaballa S. The Role of B Cell Targeting in Chronic Graft-Versus-Host Disease, Biomedicines 2017, 5, 61: 2-10Disclosure of Interests:Maria Elisa Acosta: None declared, Luis Gómez-Lechón: None declared, Olga Compán: None declared, Sonia Pastor: None declared, Carlos A. Montilla-Morales: None declared, Olga Martínez González: None declared, Ana Isabel Turrión: None declared, Javier del Pino Grant/research support from: Roche, Bristol, Consultant of: Gedeon, Cristina Hidalgo: None declared

scholarly journals The use of diversity indices for local assessment of marine sediment quality

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shinya Hosokawa ◽  
Kyosuke Momota ◽  
Anthony A. Chariton ◽  
Ryoji Naito ◽  
Yoshiyuki Nakamura
Keyword(s):  
Community Structure ◽  
Sample Size ◽  
Small Sample Size ◽  
Benthic Communities ◽  
Sediment Quality ◽  
Diversity Indices ◽  
Small Sample ◽  
Species Density ◽  
Local Case ◽  
Two Indices

AbstractDiversity indices are commonly used to measure changes in marine benthic communities. However, the reliability (and therefore suitability) of these indices for detecting environmental change is often unclear because of small sample size and the inappropriate choice of communities for analysis. This study explored uncertainties in taxonomic density and two indices of community structure in our target region, Japan, and in two local areas within this region, and explored potential solutions. Our analysis of the Japanese regional dataset showed a decrease in family density and a dominance of a few species as sediment conditions become degraded. Local case studies showed that species density is affected by sediment degradation at sites where multiple communities coexist. However, two indices of community structure could become insensitive because of masking by community variability, and small sample size sometimes caused misleading or inaccurate estimates of these indices. We conclude that species density is a sensitive indicator of change in marine benthic communities, and emphasise that indices of community structure should only be used when the community structure of the target community is distinguishable from other coexisting communities and there is sufficient sample size.

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