Comparison of clinical outcomes and prognostic utility of risk stratification tools in patients with therapy-related vs de novo myelodysplastic syndromes: a report on behalf of the MDS Clinical Research Consortium

Leukemia ◽  
2017 ◽  
Vol 31 (6) ◽  
pp. 1391-1397 ◽  
Author(s):  
A M Zeidan ◽  
N Al Ali ◽  
J Barnard ◽  
E Padron ◽  
J E Lancet ◽  
...  
2018 ◽  
Vol 18 (8) ◽  
pp. 528-532 ◽  
Author(s):  
Yazan Migdady ◽  
John Barnard ◽  
Najla Al Ali ◽  
David P. Steensma ◽  
Amy DeZern ◽  
...  

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21564-e21564
Author(s):  
Jesse D Troy ◽  
Carlos deCastro ◽  
Mary Ruth Pupa ◽  
Greg P. Samsa ◽  
Amy Pickar Abernethy ◽  
...  

e21564 Background: The National Comprehensive Cancer Network (NCCN) defines distress as an unpleasant emotional experience associated with the psychosocial complications of cancer. Patients with myelodysplastic syndromes (MDS) are at risk for distress given the largely incurable nature of this hematopoietic malignancy and its symptom burden, yet associations with clinical outcomes are unknown. Methods: We retrospectively reviewed patient-reported distress from ambulatory adult MDS patients visiting a single tertiary care medical center from July 2013-Sept 2015. Demographic, diagnostic, treatment, and comorbidity information were abstracted from records along with the NCCN Distress Thermometer (DT) and Problem List (PL). Survival was analyzed using the Kaplan-Meier method and Cox proportional hazards regression, controlling for age and risk stratification at diagnosis (Low or Intermediate/High Risk by IPSS, IPSS-R, or WPSS), ever use of therapy (hypomethylating agents/lenalidomide/growth factors/transfusions/chelation), Charlson comorbidity score, ever-report of fatigue, and frequency of fatigue. Results: We abstracted 376 DT (median = 1, range = 0-10) from 606 visits and 110 patients (median = 2 DT/patient, range = 1-16). NCCN guidelines suggest DT > = 4 should be evaluated for referral to specialty services to address unmet needs. Fifty-four patients (49%) had at least 1 DT > = 4 and 20 (18%) had 2 or more DT > = 4. Ninety-eight patients (89.1%) reported 1,379 problems during 23,613 person-days of follow-up (median = 4 problems/patient/visit, range = 1-23). The 5 most frequent were fatigue (181 times; 78 patients), pain (95 times; 46 patients), worry (80 times; 45 patients), sleep (78 times; 41 patients), and tingling hands/feet (68 times; 33 patients). After adjustment for risk stratification, a single-point increase on the DT was associated with an increased risk of death (HR = 1.18, 95% confidence interval: 1.01, 1.36). Conclusions: The distress burden is high inMDS, and patient-reported distress scores are associated with clinical outcomes after controlling for typical prognostic variables. Distress should be further studied as a marker of prognosis and of unmet needs in this population.


2021 ◽  
pp. 1-15
Author(s):  
Eva Pella ◽  
Afroditi Boutou ◽  
Marieta P. Theodorakopoulou ◽  
Pantelis Sarafidis

<b><i>Background:</i></b> Chronic kidney disease (CKD) is often characterized by increased prevalence of cardiovascular risk factors and increased incidence of cardiovascular events and death. Reduced cardiovascular reserve and exercise intolerance are common in patients with CKD and are associated with adverse outcomes. <b><i>Summary:</i></b> The gold standard for identifying exercise limitation is cardiopulmonary exercise testing (CPET). CPET provides an integrative evaluation of cardiovascular, pulmonary, hematopoietic, neuropsychological, and metabolic function during maximal or submaximal exercise. It is useful in clinical setting for differentiation of the causes of exercise intolerance, risk stratification, and assessment of response to relevant treatments. A number of recent studies have used CPET in patients with pre-dialysis CKD, aiming to assess the cardiovascular reserve of these individuals, as well as the effect of interventions such as exercise training programs on their functional capacity. This review provides an in-depth description of CPET methodology and an overview of studies that utilized CPET technology to assess cardiovascular reserve in patients with pre-dialysis CKD. <b><i>Key Messages:</i></b> CPET can delineate multisystem changes and offer comprehensive phenotyping of factors determining overall cardiovascular risk. Potential clinical applications of CPET in CKD patients range from objective diagnosis of exercise intolerance to preoperative and long-term risk stratification and providing intermediate endpoints for clinical trials. Future studies should delineate the association of CPET indexes, with cardiovascular and respiratory alterations and hard outcomes in CKD patients, to enhance its diagnostic and prognostic utility in this population.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Verena Schöning ◽  
Evangelia Liakoni ◽  
Christine Baumgartner ◽  
Aristomenis K. Exadaktylos ◽  
Wolf E. Hautz ◽  
...  

Abstract Background Clinical risk scores and machine learning models based on routine laboratory values could assist in automated early identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients at risk for severe clinical outcomes. They can guide patient triage, inform allocation of health care resources, and contribute to the improvement of clinical outcomes. Methods In- and out-patients tested positive for SARS-CoV-2 at the Insel Hospital Group Bern, Switzerland, between February 1st and August 31st (‘first wave’, n = 198) and September 1st through November 16th 2020 (‘second wave’, n = 459) were used as training and prospective validation cohort, respectively. A clinical risk stratification score and machine learning (ML) models were developed using demographic data, medical history, and laboratory values taken up to 3 days before, or 1 day after, positive testing to predict severe outcomes of hospitalization (a composite endpoint of admission to intensive care, or death from any cause). Test accuracy was assessed using the area under the receiver operating characteristic curve (AUROC). Results Sex, C-reactive protein, sodium, hemoglobin, glomerular filtration rate, glucose, and leucocytes around the time of first positive testing (− 3 to + 1 days) were the most predictive parameters. AUROC of the risk stratification score on training data (AUROC = 0.94, positive predictive value (PPV) = 0.97, negative predictive value (NPV) = 0.80) were comparable to the prospective validation cohort (AUROC = 0.85, PPV = 0.91, NPV = 0.81). The most successful ML algorithm with respect to AUROC was support vector machines (median = 0.96, interquartile range = 0.85–0.99, PPV = 0.90, NPV = 0.58). Conclusion With a small set of easily obtainable parameters, both the clinical risk stratification score and the ML models were predictive for severe outcomes at our tertiary hospital center, and performed well in prospective validation.


2021 ◽  
pp. 106505
Author(s):  
Marcus R. Johnson ◽  
Merritt Raitt ◽  
Aliya Asghar ◽  
Debra L. Condon ◽  
Danielle Beck ◽  
...  

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Jing-dong Zhou ◽  
Ting-juan Zhang ◽  
Zi-jun Xu ◽  
Zhao-qun Deng ◽  
Yu Gu ◽  
...  

AbstractThe potential mechanism of myelodysplastic syndromes (MDS) progressing to acute myeloid leukemia (AML) remains poorly elucidated. It has been proved that epigenetic alterations play crucial roles in the pathogenesis of cancer progression including MDS. However, fewer studies explored the whole-genome methylation alterations during MDS progression. Reduced representation bisulfite sequencing was conducted in four paired MDS/secondary AML (MDS/sAML) patients and intended to explore the underlying methylation-associated epigenetic drivers in MDS progression. In four paired MDS/sAML patients, cases at sAML stage exhibited significantly increased methylation level as compared with the matched MDS stage. A total of 1090 differentially methylated fragments (DMFs) (441 hypermethylated and 649 hypomethylated) were identified involving in MDS pathogenesis, whereas 103 DMFs (96 hypermethylated and 7 hypomethylated) were involved in MDS progression. Targeted bisulfite sequencing further identified that aberrant GFRA1, IRX1, NPY, and ZNF300 methylation were frequent events in an additional group of de novo MDS and AML patients, of which only ZNF300 methylation was associated with ZNF300 expression. Subsequently, ZNF300 hypermethylation in larger cohorts of de novo MDS and AML patients was confirmed by real-time quantitative methylation-specific PCR. It was illustrated that ZNF300 methylation could act as a potential biomarker for the diagnosis and prognosis in MDS and AML patients. Functional experiments demonstrated the anti-proliferative and pro-apoptotic role of ZNF300 overexpression in MDS-derived AML cell-line SKM-1. Collectively, genome-wide DNA hypermethylation were frequent events during MDS progression. Among these changes, ZNF300 methylation, a regulator of ZNF300 expression, acted as an epigenetic driver in MDS progression. These findings provided a theoretical basis for the usage of demethylation drugs in MDS patients against disease progression.


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