Molecular genetic testing patterns for patients with newly diagnosed acute myeloid leukemia (AML) enrolled in the CONNECT MDS/AML disease registry.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 7022-7022 ◽  
Author(s):  
Daniel Aaron Pollyea ◽  
Tracy George ◽  
Kathryn M Foucar ◽  
Harry Paul Erba ◽  
Michael A. Thompson ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Genetic Testing ◽  
Molecular Genetic ◽  
Molecular Testing ◽  
Newly Diagnosed ◽  
Molecular Genetic Testing ◽  
Disease Registry ◽  
Nccn Guidelines ◽  
Recurrent Mutations ◽  
Testing Patterns

7022 Background: Recurrent mutations in AML-associated genes have prognostic value and may help guide treatment decisions. Molecular genetic testing patterns for AML in clinical practice are largely unknown. Previously the CONNECT MDS/AML Disease Registry (George et al. ASH 2016. Abstract 3548) showed suboptimal adherence to WHO 2008 recommendations for AML in a cohort of newly diagnosed (ND) AML patients (pts) in clinical practice. Here we report a detailed analysis of patterns of molecular genetic testing in pts with ND AML in community and academic settings. Methods: The CONNECT MDS/AML Disease Registry (NCT01688011) is a US prospective, observational cohort study of pts with ND AML (≥55 years) or MDS. Enrollment is ongoing. All clinical decisions are made by study clinicians. The current analysis evaluated the percentage of pts with AML with molecular genetic testing recommended by NCCN guidelines ( NPM1, FLT3-ITD, CEBPA, IDH1, IDH2, DNMT3A, and KIT). Chi-square tests evaluated effects of several variables on likelihood of molecular genetic testing. Results: Between 12 Dec 2013, and 8 Dec 2016 (data cutoff), 259 AML pts were enrolled at 86 sites. Molecular genetic testing was reported in 67% (173/259) of pts. Likelihood of testing varied, respectively, for academic vs community sites (76% [70/92] vs 62% [103/167], P= .018), normal vs abnormal karyotype (77% [79/103] vs 59% [79/133], P= .006), age < 65 vs ≥65 (83% [65/78] vs 60% [108/181], P= .0003), and Medicare vs other insurance (61% [83/137] vs 74% [90/122], P= .025). In pts with molecular genetic testing (n = 173), the mutations tested varied substantially. All of the NCCN-recommended molecular genetic tests were reported in 9% (15/173) of pts, including 8% (6/79) of those with normal karyotype. Of the 7 NCCN-recommended tests, NPM1 (77%) and FLT3-ITD (76%) were most often reported and DNM T3A least often (16%). Conclusions: Early data from the CONNECT MDS/AML Disease Registry reveal that despite molecular testing reported in 67% of ND AML pts, a majority do not receive guideline-recommended testing. This prospective registry is uniquely positioned to capture changes in testing patterns as guidelines are established.

scholarly journals Diagnostic and molecular testing patterns in patients with newly diagnosed acute myeloid leukemia in the Connect ® MDS/AML Disease Registry

eJHaem ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 58-68
Author(s):  
Daniel A. Pollyea ◽  
Tracy I. George ◽  
Mehrdad Abedi ◽  
Rafael Bejar ◽  
Christopher R. Cogle ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Molecular Testing ◽  
Newly Diagnosed ◽  
Disease Registry ◽  
Testing Patterns ◽  
Acute Myeloid

scholarly journals Comprehensive Geno- and Phenotyping in a Complex Pedigree Including Four Different Inherited Retinal Dystrophies

Genes ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 137
Author(s):  
Johannes Birtel ◽  
Martin Gliem ◽  
Kristina Hess ◽  
Theresa H. Birtel ◽  
Frank G. Holz ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Night Blindness ◽  
Molecular Genetic ◽  
Cone Dystrophy ◽  
Molecular Testing ◽  
Congenital Stationary Night Blindness ◽  
Molecular Genetic Testing ◽  
Inherited Retinal Dystrophies ◽  
Retinal Dystrophies ◽  
Novel Variant

Inherited retinal dystrophies (IRDs) are characterized by high clinical and genetic heterogeneity. A precise characterization is desirable for diagnosis and has impact on prognosis, patient counseling, and potential therapeutic options. Here, we demonstrate the effectiveness of the combination of in-depth retinal phenotyping and molecular genetic testing in complex pedigrees with different IRDs. Four affected Caucasians and two unaffected relatives were characterized including multimodal retinal imaging, functional testing, and targeted next-generation sequencing. A considerable intrafamilial phenotypic and genotypic heterogeneity was identified. While the parents of the index family presented with rod-cone dystrophy and ABCA4-related retinopathy, their two sons revealed characteristics in the spectrum of incomplete congenital stationary night blindness and ocular albinism, respectively. Molecular testing revealed previously described variants in RHO, ABCA4, and MITF as well as a novel variant in CACNA1F. Identified variants were verified by intrafamilial co-segregation, bioinformatic annotations, and in silico analysis. The coexistence of four independent IRDs caused by distinct mutations and inheritance modes in one pedigree is demonstrated. These findings highlight the complexity of IRDs and underscore the need for the combination of extensive molecular genetic testing and clinical characterization. In addition, a novel variant in the CACNA1F gene is reported associated with incomplete congenital stationary night blindness.

scholarly journals Glucose variability in pregnant women with newly diagnosed hyperglycemia

2020 ◽  
Vol 48 (7) ◽  
pp. 469-475
Author(s):  
M. A. Plekhanova ◽  
F. F. Burumkulova ◽  
V. A. Petrukhin ◽  
T. S. Budykina ◽  
A. E. Panov
Keyword(s):  
Diabetes Mellitus ◽  
Genetic Testing ◽  
Pregnant Women ◽  
High Performance ◽  
Molecular Genetic ◽  
Selection Criterion ◽  
Glycemic Variability ◽  
Glucose Variability ◽  
Newly Diagnosed ◽  
Molecular Genetic Testing

Background: High-performance parallel next-generation sequencing (NGS) allows for identification of various maturity-onset diabetes of the young (MODY) subtypes also during pregnancy. As this method is expensive and time-consuming, it has proposed to use various predictors for the diagnosis of mutation in the hexokinase (GCK)/MODY2 gene, helping to select the patients for subsequent molecular genetic testing. Hyperglycemia due to MODY2 is commonly newly diagnosed during pregnancy; therefore, there is a search for factors specific to this mutation in pregnant women.Aim: To evaluate blood glucose variability in pregnant women with newly diagnosed hyperglycemia at early gestation and to determine the threshold value of the glycemic variability coefficient for pregnant women with a mutation in the GCK/MODY2 gene.Materials and methods: This observational single center study included 41  pregnant women with newly diagnosed early hyperglycemia (not meeting the criteria for manifest diabetes mellitus). Molecular genetic testing was performed in all of them. According to its results, they were retrospectively categorized into two groups: with early gestational diabetes mellitus (GDM, no mutations) and with hyperglycemia related to a mutation in the GCK/MODY2 gene. A comparative analysis of glycemic variability in the two groups was performed. Sensitivity and specificity of the cutoff value for the coefficient of variability as a diagnostic marker of MODY2 were also calculated.Results: The pregnant women with GDM had significantly higher age and body mass index (BMI) than those with MODY2 (p<0.05). There were significant differences in venous fasting plasma glucose and glycated hemoglobin, with these parameters being higher in the pregnant women with MODY2 (p<0.05). In the patients with a  mutation in the GCK gene, hyperglycemia was diagnosed earlier and insulin therapy was started earlier during pregnancy than in those with GDM (p<0.05). The ROC analysis of the diagnostic accuracy of the variability coefficient showed that at the threshold CV (coefficient of variation) value of 20.8, the area under the curve was 0.742 (95% confidence intervals 0.597 to 0.888; p<0.005), with the sensitivity of 65% and the specificity of 65.4%.Conclusion: The calculated sensitivity of 65% and specificity of 65.4% for the CV of 20.8 do not allow for its use as an independent selection criterion for subsequent confirmation of MODY2. However, its combination with the A.J. Chakera criteria (BMI<25 kg/m2 and fasting glucose≥5.5  mmol with 68%  sensitivity and 96%  specificity) allows to clarify the category of pregnant women with newly detected early hyperglycemia, to whom the search for mutations in the GCK gene should be recommended.

scholarly journals Real-World Patterns of Molecular Genetic Testing Among Patients with Acute Myeloid Leukemia in US Community Oncology Settings

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4980-4980
Author(s):  
Roger Lyons ◽  
Sneha Sura ◽  
Srinivas Annavarapu ◽  
Jackie Kwong ◽  
Albert Fliss
Keyword(s):  
Genetic Testing ◽  
Targeted Therapies ◽  
Molecular Genetic ◽  
Outpatient Setting ◽  
Study Cohort ◽  
Inpatient Setting ◽  
Newly Diagnosed ◽  
Molecular Genetic Testing ◽  
Before And After ◽  
Refractory Aml

Abstract Introduction: Molecular genetic testing is essential to inform disease diagnosis, prognosis, and treatment selection for patients with acute myeloid leukemia (AML). The standard treatment is induction chemotherapy followed by post-remission consolidation therapy including chemotherapy and allogeneic hematopoietic stem cell transplantation. Since May 2017, targeted therapies such as midostaurin, ivosidenib, enasidenib, and gemtuzumab ozogamicin were introduced for the treatment of AML. The use of targeted therapies is driven in part by the results of molecular genetic testing. The aim of this study was to determine molecular genetic testing utilization among patients with AML before and after the introduction of targeted therapies in May 2017 within community oncology clinics. Methods: A retrospective observational cohort study was conducted using de-identified data from The US Oncology Network iKnowMed electronic health record database and chart review. The iKnowMed is an oncology-specific system that captures outpatient practice encounter history for patients under care, including (but not limited to) laboratory tests, diagnosis, therapy administration, line of therapy, staging, and performance status information. These structured data were supplemented by targeted chart review to capture unstructured data. All patients aged 18 years or older with newly diagnosed or relapsed/refractory AML who received treatment in The US Oncology Network from January 2014 through February 2019 were included in the study cohort. Patients enrolled in clinical trials were excluded. Patients were classified into two groups: those who received treatment prior to May 2017 and those who received it after May 2017. Molecular genetic testing included IDH1, IDH2, FLT3-ITD, FLT3-TDK and CD33 genes. We assessed the proportion of newly diagnosed or relapsed/refractory AML patients who received molecular genetic testing in the inpatient setting, outpatient setting and prior to treatment initiation before and after May 2017. Results: The study population consisted of 434 patients diagnosed with AML, of whom 313 had newly diagnosed and 121 had relapsed/refractory AML. The median age of the study cohort was 73 (interquartile range: 63.0, 79.0) years. Most of the study cohort were male (57.6%, n=250) and Caucasian (77.0%, n=334). Approximately 75% (235/313) of newly diagnosed patients (75.1%; 235/313) and 81.0% (98/121) of patients with relapsed/refractory AML had molecular genetic testing. The proportion of patients who had molecular genetic testing before and after May 2017 were similar for newly diagnosed AML patients (72.2% vs. 78.1%; p=0.2260) and relapsed/refractory AML patients (80.0% vs. 83.9%; p=0.6357). The proportion of newly diagnosed AML patients who received molecular genetic testing in the inpatient setting (18.5% vs. 23.8%; p=0.3403) and outpatient setting (49.4% vs. 51.0%; p=0.4223) did not change before and after May 2017. Likewise, among patients with relapsed/refractory AML, the proportion of molecular genetic testing in the inpatient setting (31.1% vs. 35.5%; p=0.8523) and outpatient setting (44.4% vs. 51.6%; p=0.7749) were similar before and after May 2017. In addition, the proportion of newly diagnosed AML patients (55.6% vs. 62.9%; p=0.3835) and relapsed/refractory AML patients (45.6% vs. 61.3%; p=0.3063) who received molecular genetic testing prior to AML treatment initiation did not change before and after May 2017. Time from test order date to test result availability was not significantly different before [mean (SD) =9.3 days (16.8)] and after May 2017 [mean (SD)=9.0 days (9.9)]. Conclusion: Introduction of targeted therapies for AML did not increase molecular genetic testing rates nor improve the turnaround time for test result availability in newly diagnosed and relapsed refractory AML patients by February 2019. Two out of 5 patients did not have molecular genetic testing performed prior to initiation of AML therapy after May 2017 when targeted therapies became available. Patients age, comorbidities and drug access issues may have contributed to under-utilization of molecular genetic testing. Further research is needed to identify barriers to molecular genetic testing in patients with AML. Disclosures Sura: McKesson Life Sciences: Current Employment. Annavarapu: McKesson Life Sciences: Current Employment. Kwong: Daiichi Sankyo, Inc: Current Employment. Fliss: Daiichi Sankyo, Inc: Current Employment.

scholarly journals Prostate Cancer, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology

2019 ◽  
Vol 17 (5) ◽  
pp. 479-505 ◽  
Author(s):  
James L. Mohler ◽  
Emmanuel S. Antonarakis ◽  
Andrew J. Armstrong ◽  
Anthony V. D’Amico ◽  
Brian J. Davis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Practice ◽  
Genetic Testing ◽  
Risk Stratification ◽  
Hormonal Therapy ◽  
Advanced Disease ◽  
Treatment Options ◽  
Molecular Testing ◽  
Nccn Guidelines ◽  
Localized Disease

The NCCN Guidelines for Prostate Cancer include recommendations regarding diagnosis, risk stratification and workup, treatment options for localized disease, and management of recurrent and advanced disease for clinicians who treat patients with prostate cancer. The portions of the guidelines included herein focus on the roles of germline and somatic genetic testing, risk stratification with nomograms and tumor multigene molecular testing, androgen deprivation therapy, secondary hormonal therapy, chemotherapy, and immunotherapy in patients with prostate cancer.

scholarly journals Diagnosing Paraproteinemic Keratopathy: A Case Report

2021 ◽  
pp. 337-343
Author(s):  
Eugenie Mok ◽  
Ka Wai Kam ◽  
Anthony J. Aldave ◽  
Alvin L. Young
Keyword(s):  
Optical Coherence Tomography ◽  
Genetic Testing ◽  
Serum Protein ◽  
Molecular Genetic ◽  
Anterior Segment ◽  
Protein Electrophoresis ◽  
Serum Protein Electrophoresis ◽  
Optical Coherence ◽  
Molecular Genetic Testing ◽  
Corneal Opacities

A 65-year-old man presented with bilateral, painless, progressive blurring of vision over 9 years. Slit-lamp examination revealed bilateral subepithelial corneal opacities in clusters located at the mid-periphery. Anterior segment optical coherence tomography, in vivo confocal microscopy (IVCM), serum protein electrophoresis, and molecular genetic testing were performed to evaluate the cause of corneal opacities. Anterior segment optical coherence tomography revealed a band-like, hyperreflective lesion in the Bowman layer and anterior stroma of both corneas. IVCM revealed hyperreflective deposits in the epithelium, anterior stroma, and endothelium. Serum protein electrophoresis identified the presence of paraproteins (immunoglobulin kappa), and molecular genetic testing revealed absence of mutations in the transforming growth factor beta-induced gene (<i>TGFBI</i>) and collagen type XVII alpha 1 gene (<i>COL17A1</i>). The ocular diagnosis of paraproteinemic keratopathy eventually led to a systemic diagnosis of monoclonal gammopathy of undetermined significance by our hematologist/oncologist. Paraproteinemic keratopathy is a rare differential diagnosis in patients with bilateral corneal opacities and therefore may be misdiagnosed as corneal dystrophy or neglected as scars. In patients with bilateral corneal opacities of unknown cause, serological examination, adjunct anterior segment imaging, and molecular genetic testing play a role in establishing the diagnosis.

scholarly journals Initial Diagnostic Workup of Acute Leukemia: Guideline From the College of American Pathologists and the American Society of Hematology

2017 ◽  
Vol 141 (10) ◽  
pp. 1342-1393 ◽  
Author(s):  
Daniel A. Arber ◽  
Michael J. Borowitz ◽  
Melissa Cessna ◽  
Joan Etzell ◽  
Kathryn Foucar ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Acute Leukemia ◽  
Lymphoblastic Leukemia ◽  
Molecular Genetic ◽  
Clinical Information ◽  
Molecular Genetic Testing ◽  
Acute Leukemias ◽  
Prognostic Evaluation ◽  
The Public ◽  
American Society

Context.— A complete diagnosis of acute leukemia requires knowledge of clinical information combined with morphologic evaluation, immunophenotyping and karyotype analysis, and often, molecular genetic testing. Although many aspects of the workup for acute leukemia are well accepted, few guidelines have addressed the different aspects of the diagnostic evaluation of samples from patients suspected to have acute leukemia. Objective.— To develop a guideline for treating physicians and pathologists involved in the diagnostic and prognostic evaluation of new acute leukemia samples, including acute lymphoblastic leukemia, acute myeloid leukemia, and acute leukemias of ambiguous lineage. Design.— The College of American Pathologists and the American Society of Hematology convened a panel of experts in hematology and hematopathology to develop recommendations. A systematic evidence review was conducted to address 6 key questions. Recommendations were derived from strength of evidence, feedback received during the public comment period, and expert panel consensus. Results.— Twenty-seven guideline statements were established, which ranged from recommendations on what clinical and laboratory information should be available as part of the diagnostic and prognostic evaluation of acute leukemia samples to what types of testing should be performed routinely, with recommendations on where such testing should be performed and how the results should be reported. Conclusions.— The guideline provides a framework for the multiple steps, including laboratory testing, in the evaluation of acute leukemia samples. Some aspects of the guideline, especially molecular genetic testing in acute leukemia, are rapidly changing with new supportive literature, which will require on-going updates for the guideline to remain relevant.

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