relapse prediction
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The paper presents a framework for early identification of prodromal syndromes od mania or depression in bipolar disorder. The framework may mitigate relapses and improve patient functioning. The methodology consists of long-term actigraphy monitoring and simplified self-assessment tool to determine manic or depression events. Eight patients were involved in the feasibility study, spanning period of 150 months, resulting in 17 relapses and 3 hospitalizations in total. We concluded that the most promising parameter extracted from actigraphy recording is a circadian rhythm's interdaily stability. Using developed trend analysis applied on interdaily stability parameter, we achieved sensitivity and specificity about 65, resp. 68. We hypothesized that this performance is both mainly due to missing values in data and due to small amount of relapses.
- MeSH
- aktigrafie * MeSH
- algoritmy MeSH
- bipolární porucha * patofyziologie MeSH
- chronická nemoc MeSH
- cirkadiánní rytmus MeSH
- dospělí MeSH
- lidé MeSH
- pohyb fyziologie MeSH
- průzkumy a dotazníky MeSH
- recidiva MeSH
- spánek fyziologie MeSH
- studie proveditelnosti MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
Central nervous system (CNS) relapse carries a poor prognosis in diffuse large B-cell lymphoma (DLBCL). Integrating biomarkers into the CNS-International Prognostic Index (CNS-IPI) risk model may improve identification of patients at high risk for developing secondary CNS disease. CNS relapse was analyzed in 1418 DLBCL patients treated with obinutuzumab or rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone chemotherapy in the phase 3 GOYA study. Cell of origin (COO) was assessed using gene-expression profiling. BCL2 and MYC protein expression was analyzed by immunohistochemistry. The impact of CNS-IPI, COO, and BCL2/MYC dual-expression status on CNS relapse was assessed using a multivariate Cox regression model (data available in n = 1418, n = 933, and n = 688, respectively). High CNS-IPI score (hazard ratio [HR], 4.0; 95% confidence interval [CI], 1.3-12.3; P = .02) and activated B-cell‒like (ABC) (HR, 5.2; 95% CI, 2.1-12.9; P = .0004) or unclassified COO subtypes (HR, 4.2; 95% CI, 1.5-11.7; P = .006) were independently associated with CNS relapse. BCL2/MYC dual-expression status did not impact CNS relapse risk. Three risk subgroups were identified based on the presence of high CNS-IPI score and/or ABC/unclassified COO (CNS-IPI-C model): low risk (no risk factors, n = 450 [48.2%]), intermediate risk (1 factor, n = 408 [43.7%]), and high risk (both factors, n = 75 [8.0%]). Two-year CNS relapse rates were 0.5%, 4.4%, and 15.2% in the respective risk subgroups. Combining high CNS-IPI and ABC/unclassified COO improved CNS relapse prediction and identified a patient subgroup at high risk for developing CNS relapse. The study was registered at www.clinicaltrials.gov as #NCT01287741.
- MeSH
- difúzní velkobuněčný B-lymfom farmakoterapie genetika patologie MeSH
- dospělí MeSH
- incidence MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru diagnóza epidemiologie genetika MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mutace * MeSH
- nádorové biomarkery genetika MeSH
- nádory centrálního nervového systému farmakoterapie genetika sekundární MeSH
- následné studie MeSH
- prediktivní hodnota testů MeSH
- protokoly protinádorové kombinované chemoterapie terapeutické užití MeSH
- protoonkogenní proteiny c-bcl-2 genetika MeSH
- protoonkogenní proteiny c-myc genetika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
PURPOSE: Renal cell carcinoma belongs among the deadliest malignancies despite great progress in therapy and accessibility of primary care. One of the main unmet medical needs remains the possibility of early diagnosis before the tumor dissemination and prediction of early relapse and disease progression after a successful nephrectomy. In our study, we aimed to identify novel diagnostic and prognostic biomarkers using next-generation sequencing on a novel cohort of RCC patients. METHODS: Global expression profiles have been obtained using next-generation sequencing of paired tumor and non-tumor tissue of 48 RCC patients. Twenty candidate lncRNA have been selected for further validation on an independent cohort of paired tumor and non-tumor tissue of 198 RCC patients. RESULTS: Sequencing data analysis showed significant dysregulation of more than 2800 lncRNAs. Out of 20 candidate lncRNAs selected for validation, we confirmed that 14 of them are statistically significantly dysregulated. In order to yield better discriminatory results, we combined several best performing lncRNAs into diagnostic and prognostic models. A diagnostic model consisting of AZGP1P1, CDKN2B-AS1, COL18A1, and RMST achieved AUC 0.9808, sensitivity 95.96%, and specificity 90.4%. The model for prediction of early relapse after nephrectomy consists of COLCA1, RMST, SNHG3, and ZNF667-AS1 and achieved AUC 0.9241 with sensitivity 93.75% and specificity 71.07%. Notably, no combination has outperformed COLCA1 alone. Lastly, a model for stage consists of ZNF667-AS1, PVT1, RMST, LINC00955, and TCL6 and achieves AUC 0.812, sensitivity 85.71%, and specificity 69.41%. CONCLUSION: In our work, we identified several lncRNAs as potential biomarkers and developed models for diagnosis and prognostication in relation to stage and early relapse after nephrectomy.
- MeSH
- karcinom z renálních buněk * diagnóza genetika chirurgie MeSH
- lidé MeSH
- lokální recidiva nádoru diagnóza genetika chirurgie MeSH
- nádorové biomarkery genetika MeSH
- nádory ledvin * diagnóza genetika chirurgie MeSH
- nefrektomie MeSH
- regulace genové exprese u nádorů MeSH
- RNA dlouhá nekódující * genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Znovuobjevení či nárůst autologní krvetvorby po alogenní transplantaci hematopoetických buněk bývá spojen s počínajícím relapsem akutní myeloidní leukemie, nicméně význam mikrochimérismu (podílu autologních buněk pod hranicí 1 %) není jednoznačný. Byly porovnávány výsledky fragmentační analýzy (FA) a kvantitativní PCR v reálném čase (RQ-PCR). Hodnoty získané z obou analýz byly konfrontovány s klinickým stavem pacientů: kompletní remise, molekulární relaps, hematologický relaps. Zatímco RQ-PCR analýza periferní krve predikovala hematologický relaps ve 12 případech z 13 (92 %), s mediánem předpovědi 34 dnů (0–322 dní), byla FA úspěšná pouze v pěti případech (38 %) (medián předpovědi 0 dní, 0–154 dní) (p = 0,002). RQ-PCR předcházela FA v 10 případech, s mediánem dřívější předpovědi 35 dní (interval 6–168 dní). RQ-PCR dále zachytila dalších 4 z 6 časných hematologických relapsů (do jednoho roku po transplantaci), mimo dosah senzitivity FA. Kombinace vyšetření periferní krve a kostní dřeně navíc potvrdilo 9 molekulárních relapsů z 9. RQ-PCR se jeví jako citlivá a spolehlivá metoda stanovení mikrochimérismu, jehož dynamika umožňuje zachycení počátku relapsu a umožňuje tak časnou klinickou intervenci.
The reoccurrence or increase in autologous hematopoiesis after allogeneic stem cell transplantation has been linked with incipient leukemia relapse, however, importance of such emergency regarding microchimerism (chimerism under 1% of autologous cells) remains controversial. We compared conventional PCR of minisatellite, microsatellite, or sex specific regions followed by fragment analysis (FA) with real-time quantitative PCR (RQ-PCR) of insertion/deletion and sex polymorphism. Chimerism values obtained from both analyses were compared with the status of the disease (continuous complete remission, molecular relapse, hematological relapse, HR). Whereas RQ-PCR analysis of microchimerism predicted full HR in 12/13 cases (92%) with median of 34 days (0-322 days), the conventional FA was successful only in 5/13 cases (38%) (median 0 days, interval 0-154 days; p = 0.002). RQ-PCR surpassed FA in 10 cases with median of earlier prediction of relapse of 35 days (interval 6-168 days). Besides this, RQ-PCR detected other 4/6 HR until one year after transplantation, beyond the sensitivity of FA. Further, RQ-PCR examination of peripheral blood in combination with bone marrow confirmed all 9 molecular relapses previously detected due to a specific molecular marker. We conclude, that RQ-PCR is sensitive and reliable method of microchimerism analysis that can predict impending relapse and allows therefore earlier clinical intervention in comparison with another, less sensitive method.
BACKGROUND: Characteristics at clinically isolated syndrome (CIS) examination assist in identification of patient at highest risk of early second attack and could benefit the most from early disease-modifying drugs (DMDs). OBJECTIVE: To examine determinants of second attack and validate a prognostic nomogram for individualised risk assessment of clinical conversion. METHODS: Patients with CIS were prospectively followed up in the MSBase Incident Study. Predictors of clinical conversion were analysed using Cox proportional hazards regression. Prognostic nomograms were derived to calculate conversion probability and validated using concordance indices. RESULTS: A total of 3296 patients from 50 clinics in 22 countries were followed up for a median (inter-quartile range (IQR)) of 1.92 years (0.90, 3.71). In all, 1953 (59.3%) patients recorded a second attack. Higher Expanded Disability Status Scale (EDSS) at baseline, first symptom location, oligoclonal bands and various brain and spinal magnetic resonance imaging (MRI) metrics were all predictors of conversion. Conversely, older age and DMD exposure post-CIS were associated with reduced rates. Prognostic nomograms demonstrated high concordance between estimated and observed conversion probabilities. CONCLUSION: This multinational study shows that age at CIS onset, DMD exposure, EDSS, multiple brain and spinal MRI criteria and oligoclonal bands are associated with shorter time to relapse. Nomogram assessment may be useful in clinical practice for estimating future clinical conversion.
- MeSH
- demyelinizační nemoci farmakoterapie patologie MeSH
- dospělí MeSH
- imunosupresiva terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- nomogramy * MeSH
- prognóza MeSH
- progrese nemoci MeSH
- proporcionální rizikové modely MeSH
- recidiva MeSH
- rizikové faktory MeSH
- roztroušená skleróza patologie MeSH
- věk při počátku nemoci MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
Accurate risk assignment in childhood acute lymphoblastic leukaemia is essential to avoid under- or over-treatment. We hypothesized that time-series gene expression profiles (GEPs) of bone marrow samples during remission-induction therapy can measure the response and be used for relapse prediction. We computed the time-series changes from diagnosis to Day 8 of remission-induction, termed Effective Response Metric (ERM-D8) and tested its ability to predict relapse against contemporary risk assignment methods, including National Cancer Institutes (NCI) criteria, genetics and minimal residual disease (MRD). ERM-D8 was trained on a set of 131 patients and validated on an independent set of 79 patients. In the independent blinded test set, unfavourable ERM-D8 patients had >3-fold increased risk of relapse compared to favourable ERM-D8 (5-year cumulative incidence of relapse 38·1% vs. 10·6%; P = 2·5 × 10-3 ). ERM-D8 remained predictive of relapse [P = 0·05; Hazard ratio 4·09, 95% confidence interval (CI) 1·03-16·23] after adjusting for NCI criteria, genetics, Day 8 peripheral response and Day 33 MRD. ERM-D8 improved risk stratification in favourable genetics subgroups (P = 0·01) and Day 33 MRD positive patients (P = 1·7 × 10-3 ). We conclude that our novel metric - ERM-D8 - based on time-series GEP after 8 days of remission-induction therapy can independently predict relapse even after adjusting for NCI risk, genetics, Day 8 peripheral blood response and MRD.
- MeSH
- akutní lymfatická leukemie krev genetika mortalita MeSH
- dítě MeSH
- hodnocení rizik MeSH
- kojenec MeSH
- lidé MeSH
- míra přežití MeSH
- prediktivní hodnota testů MeSH
- předškolní dítě MeSH
- přežití bez známek nemoci MeSH
- recidiva MeSH
- regulace genové exprese u leukemie * MeSH
- stanovení celkové genové exprese * MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
Early relapse (ER) following Autologous Hematopoietic Cell Transplantation (AHCT) confers a poor prognosis. We therefore developed a novel scoring system to predict ER. A total of 14,367 AHCT-1 patients were transplanted between 2014 and 2019, and were conditioned with Melphalan 200 mg/m2 (Mel200) (n = 7228; 2014-2017) (training cohort); Mel200 (n = 5616; 2018-2019) or Mel140 (n = 1523; 2018-2019) (validation cohorts). PFS-12 and the Cumulative Incidence of Relapse at 12 months were 84.1% and 14.7% (training Mel200), 87.2% and 11.6% (validation Mel200), and 80.3% and 16.9% (validation Mel140), respectively. The points in the risk score were: 0, 1,2 for ISS stages I, II, and III; Disease status: 0 (CR/VGPR); 1 (PR); 2 (SD/MR); 4 (Relapse/Progression); and 1 for Karnofsky ≤ 70. The distribution of scores: 0 (24%), 1 (33.9%), 2 (29.6 %), 3 (9.5%), and ≥4 (2.7%). The score separated PFS-12, with the lowest risk group (n = 1752) having a PFS-12 of 91.7% and the highest risk group (n = 195) 57.1%. This also applied in cytogenetically high-risk patients. If the pre-score baseline risks are 15% (standard risk) and 25% (high-risk), a score of ≥4 confers calculated risks of 38% and 54%, respectively. This novel EBMT ER score, therefore, allows for the identification of five discrete prognostic groups.
- MeSH
- DNA virů krev MeSH
- dospělí MeSH
- Hodgkinova nemoc diagnóza patologie virologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- prediktivní hodnota testů MeSH
- prognóza MeSH
- recidiva MeSH
- senioři MeSH
- virová nálož MeSH
- virus Epsteinův-Barrové genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
- práce podpořená grantem MeSH
