Prognostic Impact of Genetic Characterization in the GIMEMA LAM99P Study for Newly Diagnosed Adult AML. Relevance of Combined Analysis of Conventional Karyotyping, FLT3 and NPM Mutational Status.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 226-226
Author(s):  
G. Saglio ◽  
Francesco Lo Coco ◽  
A. Cuneo ◽  
F. Pane ◽  
G. Rege Cambrin ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
High Risk ◽  
Genetic Characterization ◽  
High Risk Group ◽  
Low Risk ◽  
Prognostic Impact ◽  
Intermediate Risk ◽  
Mutational Status ◽  
Molecular Studies ◽  
The Impact

Abstract Between 1998 and 2002, 509 patients with AML (median age 46 yrs, range 15–60) were enrolled in the multicenter LAM99P study of the Italian GIMEMA group. To better evaluate the clinical impact of genetic characterization, all patients received a uniform protocol and diagnostic samples were centralised for cytogenetic and molecular studies. Therapy consisted of HU pre-treatment (2g/m2 for 5 days) followed by induction with DNR (50 mg/m2 d 1, 3, 5), cytarabine (100 mg/m2 d 1–10) and etoposide (100 mg/m2 d 1–5) and consolidation with cytarabine (500 mg/m2/q12 hrs d 1–6) and DNR (50 mg/m2 d 4–6). After consolidation, eligible patients with an identical HLA donor were to receive allogeneic SCT and the remaining peripheral blood autologous SCT. Cytogenetic and molecular genetic characterization (including analysis of major fusion genes, FLT3 and NPM status) was available in 397 (78%) patients. Compared to previous GIMEMA studies, the possibility to collect samples during the 5d of HU pretreatment considerably improved genetic characterization and in particular centralised karyotyping by overcoming the problem of sampling and shipment over the w-end. After induction, 269/397 (68%) patients achieved CR. For induction response, conventional K identified 3 distinct risk groups as follows: low risk (inv. 16 and t8;21), intermediate (normal K and other anomalies not comprised in the high risk group) and high risk (t3;3, inv.3, t9;22, 11q23, 5/7 abnormalities complex K,) with CR rates of 92%, 67% and 39%, respectively (P<.0001). NPM mutations were significantly associated with older age, higher WBC, normal K and FLT3-ITD. CR rates in NPM+ (mutated) vs. NPM- (wildtype) groups were 76% vs. 60% for the whole population and 81% vs, 61% for patients in the normal K group (P<.001 for both comparisons). Multivariate analysis for CR indicated that low risk K and NPM+ were independent factors favorably affecting CR achievement while FLT3 status had no significant impact on CR. The analysis of prognostic factors for DFS and OS was carried out in 269 patients in CR (median follow-up of 39 mos.) and multivariate analysis performed after adjusting for unfavorable factors (WBC count). Multivariate analysis of variables influencing OS showed the following: low vs intermediate K, P=.0005; high vs intermediate K, P<.0001; FLT3+ vs. FLT3−, P=.06. Multivariate analysis for DFS showed: low risk vs. intermediate risk K, p=.01; high risk vs. intermediate risk K, p= .03; FLT3+ vs. FLT3-, p=.0002. NPM status did not significantly influence DFS in either the whole population or in the normal K group. In particular, there was no difference in the DFS rates among patients NPM+ and NPM- in the normal K/FLT3- group while in the normal K/FLT3+ group there was a trend (p=.06) for lower relapse rate for NPM+ patients as compared to NPM- ones. These results highlight the relevance of combining cytogenetic and molecular studies in the diagnostic work up of AML and confirm the impact of karyotype on all outcome estimates as well as of FLT3 status on DFS. As to NPM mutations, these appear a favorable predictor of CR achievement. Further investigations in large clinical trials are needed to assess the prognostic value of NPM mutations on outcome in AML with normal karyotype.

The International Prognostic Scoring System for Waldestrom’s Macroglobulinemia (ISSWM) Is Applicable in Patients Treated with Rituximab-Based Regimens.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3615-3615
Author(s):  
Meletios Athanasios Dimopoulos ◽  
Efstathios Kastritis ◽  
Dimitra Gika ◽  
Sossana Delimpassi ◽  
Konstantinos Zervas ◽  
...  
Keyword(s):  
High Risk ◽  
Alkylating Agents ◽  
Single Agent ◽  
Primary Treatment ◽  
High Risk Group ◽  
Low Risk ◽  
International Prognostic Scoring System ◽  
Intermediate Risk ◽  
Number Of Patients ◽  
The Impact

Abstract Introduction: An ISSWM was recently proposed (Morel et al, ASH 2006), which was based on a large number of patients treated primarily with alkylating agents and /or nucleoside analogues. The ISSWM based on 5 adverse covariates wich defined 3 risk groups: low, intermediate and high risk with 5-years survival rates of 87%, 68% and 36% respectively. In our current analysis, we assessed the impact of this system in patients with WM who received primary treatment with rituximab-based regimens. Patients and methods: Ninety-three previously untreated, symptomatic patients who received treatment either with single agent rituximab (21 patients) or with the combination of dexamethasone, rituximab, and cyclophosphamide (72 patients) were classified according to the ISSWM, which is based on 5 adverse covariates: age&gt; 65 years, hemoglobin ≤11.5 g/dl, platelet count ≤ 100 x 109/L, β2- microglobulin &lt;3mg/L, serum monoclonal protein concentration &gt;70g/L. Low risk is defined by the presence of ≤ 1 adverse characteristics except age, high risk by the presence of &gt;2 adverse characteristics and intermediate risk by the presence of 2 adverse characteristics or age &gt;65 years. Results: The disease features of the 93 patients were typical of symptomatic WM: age &gt; 65 years in 63%, males 65%, B-symptoms in 22%, splenomegaly in 29%, lymphadenopathy in 34%. 15% of patients were rated as low risk, 65% as intermediate risk and 20% as high risk. Criteria for initiation of therapy included cytopenia, hyperviscosity, constitutional symptoms, organomegaly or IgM-related disorders. Overall, 62% of patients were alive at 6 years. Median survival was not reached for low and intermediate risk and was 38 months for high risk patients (p=0.006). There was a clear separation of the survival curves in the three groups. At the time of last follow-up the percentage of patients alive was 100%, 82% and 58% for patients classified as low, intermediate and high-risk group respectively. Conclusions: The recently proposed ISSWM is applicable in patients with WM who receive primary treatment with rituximab-based regimens and may serve as a basis to compare outcomes in different studies.

scholarly journals SARS-CoV-2 Seroprevalence in Healthcare Workers in Germany: A Follow-Up Study

2021 ◽  
Vol 18 (9) ◽  
pp. 4540
Author(s):  
Johannes Korth ◽  
Benjamin Wilde ◽  
Sebastian Dolff ◽  
Jasmin Frisch ◽  
Michael Jahn ◽  
...  
Keyword(s):  
High Risk ◽  
Healthcare Workers ◽  
Risk Group ◽  
Close Contact ◽  
Virus Transmission ◽  
High Risk Group ◽  
Low Risk ◽  
University Hospital ◽  
Intermediate Risk ◽  
Igg Antibody

SARS-CoV-2 is a worldwide challenge for the medical sector. Healthcare workers (HCW) are a cohort vulnerable to SARS-CoV-2 infection due to frequent and close contact with COVID-19 patients. However, they are also well trained and equipped with protective gear. The SARS-CoV-2 IgG antibody status was assessed at three different time points in 450 HCW of the University Hospital Essen in Germany. HCW were stratified according to contact frequencies with COVID-19 patients in (I) a high-risk group with daily contacts with known COVID-19 patients (n = 338), (II) an intermediate-risk group with daily contacts with non-COVID-19 patients (n = 78), and (III) a low-risk group without patient contacts (n = 34). The overall seroprevalence increased from 2.2% in March–May to 4.0% in June–July to 5.1% in October–December. The SARS-CoV-2 IgG detection rate was not significantly different between the high-risk group (1.8%; 3.8%; 5.5%), the intermediate-risk group (5.1%; 6.3%; 6.1%), and the low-risk group (0%, 0%, 0%). The overall SARS-CoV-2 seroprevalence remained low in HCW in western Germany one year after the outbreak of COVID-19 in Germany, and hygiene standards seemed to be effective in preventing patient-to-staff virus transmission.

P3609Temporal trends of the management and outcomes of patients after myocardial infarction according to the risk for recurrent cardiovascular events

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Grinberg ◽  
T Bental ◽  
Y Hammer ◽  
A R Assali ◽  
H Vaknin-Assa ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
High Risk ◽  
Cardiovascular Events ◽  
Risk Group ◽  
Temporal Trends ◽  
High Risk Group ◽  
Low Risk ◽  
Intermediate Risk ◽  
High Risk Patients ◽  
Risk Patients

Abstract Background Following Myocardial Infarction (MI), patients are at increased risk for recurrent cardiovascular events, particularly during the immediate period. Yet some patients are at higher risk than others, owing to their clinical characteristics and comorbidities, these high-risk patients are less often treated with guideline-recommended therapies. Aim To examine temporal trends in treatment and outcomes of patients with MI according to the TIMI risk score for secondary prevention (TRS2°P), a recently validated risk stratification tool. Methods A retrospective cohort study of patients with an acute MI, who underwent percutaneous coronary intervention and were discharged alive between 2004–2016. Temporal trends were examined in the early (2004–2010) and late (2011–2016) time-periods. Patients were stratified by the TRS2°P to a low (≤1), intermediate (2) or high-risk group (≥3). Clinical outcomes included 30-day MACE (death, MI, target vessel revascularization, coronary artery bypass grafting, unstable angina or stroke) and 1-year mortality. Results Among 4921 patients, 31% were low-risk, 27% intermediate-risk and 42% high-risk. Compared to low and intermediate-risk patients, high-risk patients were older, more commonly female, and had more comorbidities such as hypertension, diabetes, peripheral vascular disease, and chronic kidney disease. They presented more often with non ST elevation MI and 3-vessel disease. High-risk patients were less likely to receive drug eluting stents and potent anti-platelet drugs, among other guideline-recommended therapies. Evidently, they experienced higher 30-day MACE (8.1% vs. 3.9% and 2.1% in intermediate and low-risk, respectively, P<0.001) and 1-year mortality (10.4% vs. 3.9% and 1.1% in intermediate and low-risk, respectively, P<0.001). During time, comparing the early to the late-period, the use of potent antiplatelets and statins increased among the entire cohort (P<0.001). However, only the high-risk group demonstrated a significantly lower 30-day MACE (P=0.001). During time, there were no differences in 1-year mortality rate among all risk categories. Temporal trends in 30-day MACE by TRS2°P Conclusion Despite a better application of guideline-recommended therapies, high-risk patients after MI are still relatively undertreated. Nevertheless, they demonstrated the most notable improvement in outcomes over time.

scholarly journals The Impact of Preoperative Risk on the Association between Hypotension and Mortality after Cardiac Surgery: An Observational Study

2020 ◽  
Vol 9 (7) ◽  
pp. 2057
Author(s):  
Vanja Ristovic ◽  
Sophie de Roock ◽  
Thierry G. Mesana ◽  
Sean van Diepen ◽  
Louise Y. Sun
Keyword(s):  
Cardiac Surgery ◽  
Risk Factor ◽  
High Risk ◽  
Hospital Mortality ◽  
Risk Group ◽  
High Risk Group ◽  
Group Care ◽  
Intermediate Risk ◽  
Intraoperative Hypotension ◽  
The Impact

Background: Despite steady improvements in cardiac surgery-related outcomes, our understanding of the physiologic mechanisms leading to perioperative mortality remains incomplete. Intraoperative hypotension is an important risk factor for mortality after noncardiac surgery but remains relatively unexplored in the context of cardiac surgery. We examined whether the association between intraoperative hypotension and in-hospital mortality varied by patient and procedure characteristics, as defined by the validated Cardiac Anesthesia Risk Evaluation (CARE) mortality risk score. Methods: We conducted a retrospective cohort study of consecutive adult patients who underwent cardiac surgery requiring cardiopulmonary bypass (CPB) from November 2009–March 2015. Those who underwent off-pump, thoracic aorta, transplant and ventricular assist device procedures were excluded. The primary outcome was in-hospital mortality. Hypotension was categorized by mean arterial pressure (MAP) of <55 and between 55–64 mmHg before, during and after CPB. The relationship between hypotension and death was modeled using multivariable logistic regression in the intermediate and high-risk groups. Results: Among 6627 included patients, 131 (2%) died in-hospital. In-hospital mortality in patients with CARE scores of 1, 2, 3, 4 and 5 was 0 (0%), 7 (0.3%), 35 (1.3%), 41 (4.6%) and 48 (13.6%), respectively. In the intermediate-risk group (CARE = 3–4), MAP < 65 mmHg post-CPB was associated with increased odds of death in a dose-dependent fashion (adjusted OR 1.30, 95% CI 1.13–1.49, per 10 min exposure to MAP < 55 mmHg, p = 0.002; adjusted OR 1.18 [1.07–1.30] per 10 min exposure to MAP 55–64 mmHg, p = 0.001). We did not observe an association between hypotension and mortality in the high-risk group (CARE = 5). Conclusions: Post-CPB hypotension is a potentially modifiable risk factor for mortality in intermediate-risk patients. Our findings provide impetus for clinical trials to determine if hemodynamic goal-directed therapies could improve survival in these patients.

An Automated and Quantitative Protein Expression-Based Classification System to Identify High Risk Multiple Myeloma Patients

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 735-735
Author(s):  
Alex Klimowicz ◽  
Paola Neri ◽  
Adnan Mansoor ◽  
Anthony Magliocco ◽  
Douglas A. Stewart ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
High Risk ◽  
Protein Expression ◽  
Classification System ◽  
Risk Group ◽  
Univariate Analysis ◽  
High Risk Group ◽  
Group Classification ◽  
Low Risk ◽  
High Expression

Abstract Background: Autologous stem cell transplantation (ASCT) has dramatically improved the survival of myeloma patients; however, this approach has significant toxicities and nearly 25% of MM patients progress within one year from their transplant. While gene expression profiling-based (GEP) molecular classification has permitted the identification of unresponsive high-risk patients, these approaches have proven too costly and complex to translate into clinical practice. Less expensive and more readily available methods are needed clinically to identify, at the time of diagnosis, MM patients who may benefit from more aggressive or experimental therapies. While protein-based tissue arrays offer such alternative, biases introduced by the “observer-dependent” scoring methods have limited their wide applicability. Methods: We have designed a simplified, fully automated and quantitative protein expression based-classification system that will allow us to accurately predict survival post ASCT in a cost effective and “observer-independent” manner. We constructed tissue microarrays using diagnostic bone marrow biopsies of 82 newly diagnosed MM patients uniformly treated with a dexamethasone based induction regimen and frontline ASCT. Using the HistoRx PM-2000 quantitative immunohistochemistry platform, coupled with the AQUA analysis software, we have examined the expression of the following proteins: FGFR3 which is associated with t(4;14), cyclin B2 and Ki-67 which are associated with cellular proliferation, TACI which is associated with maf deregulation, and phospho-Y705 STAT3 and p65NF-κB, which are associated with myeloma cell growth and survival. For FGFR3, patients were divided into FGFR3 positive and negative groups based on hierarchical clustering of their AQUA score. For all other proteins examined, based on AQUA scores, the top quartiles or quintiles of patients were classified as high expression groups. Based on the univariate analysis, patients were further classified as “High Risk” MM if they had been identified as high expressers of either TACI, p65NF-κB or FGFR3. The Kaplan-Meier method was used to estimate time to progression and overall survival. Multivariate analysis was performed using the Cox regression method. Results: 82 patients were included in this study. In univariate analysis, FGFR3 and p65NF-κB expression were associated with significantly shorter TTP (p=0.018 and p=0.009) but not OS (p=0.365 and p=0.104). TACI expression levels predicted for worse OS (p=0.039) but not TTP (p=0.384). High expression of Ki67 or phospho-Y705 STAT3 did not affect survival. Of the 82 cases, 67 were included in the multivariate analysis since they had AQUA scores available for all markers: 26 (38.8%) were considered as High Risk by their AQUA scores and had significantly shorter TTP (p=0.014) and OS (p=0.006) compared to the Low Risk group. The median TTP for the Low and High Risk groups was 2.9 years and 1.9 years, respectively. The 5-years estimates for OS were 60.6% for the High Risk group versus 83.5% for the Low Risk group. Multivariate analysis was performed using del13q and our risk group classification as variables. Both our risk group classification and del13q were independent predictors for TTP, having 2.4 and 2.3 greater risk of relapse, respectively. Our risk group classification was the only independent predictor of OS with the High Risk group having a 5.9 fold greater risk of death. Conclusions: We have found that the expression of FGFR3, TACI, and p65NF-κB, in an automated and fully quantitative tissue-based array, is a powerful predictor of survival post-ASCT in MM and eliminates the “observer-dependent” bias of scoring TMAs. A validation of this “High Risk” TMA based signature is currently underway in larger and independent cohorts. Figure Figure

Spliceosome Mutations Involving SRSF2, SF3B1 and U2AF35 in World Health Organization Defined Chronic Myelomonocytic Leukemia; Prevalence, Clinical Correlates and Prognosis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1711-1711
Author(s):  
Mrinal M. Patnaik ◽  
Terra L Lasho ◽  
Christy Finke ◽  
Curtis A Hanson ◽  
Janice M Hodnefield ◽  
...  
Keyword(s):  
High Risk ◽  
Chronic Myelomonocytic Leukemia ◽  
Low Risk ◽  
World Health ◽  
Prognostic Impact ◽  
Intermediate Risk ◽  
Free Survival ◽  
Clinical Correlates ◽  
Significant Difference ◽  
Myelomonocytic Leukemia

Abstract Abstract 1711 Background: Mutations in genes of the splicing machinery, such as SF3B1, SRSF2 and U2AF35 are common in patients with myelodysplastic syndromes [MDS] (Nature 2011;478:64) and chronic myelomonocytic leukemia [CMML] (Haematologica 2012;Epub). In MDS, SRSF2 gene mutations are an independent risk factor for shortened over-all (OS) and leukemia-free survival (LFS) (Blood 2012;119:3578). In MDS with ring sideroblasts (RS), SF3B1 mutations have a high prevalence (∼50%), but do not influence either, the OS or the LFS (Blood 2012;119:569). We carried out this study to evaluate the prevalence, clinical correlates and prognosis of the aforementioned spliceosome mutations in CMML. Methods: The study included 227 patients with WHO defined CMML who were seen at the Mayo Clinic from 1997 through 2007. All patients underwent bone marrow (BM) examination and cytogenetic evaluation at diagnosis. DNA was interrogated in the three most frequent spliceosome genes with somatic mutations; SRSF2, SF3B1 and U2AF35. Results I: Prevalence and clinical correlates Among the 227 study patients, 153 (67%) were male, median age was 71 years (range, 17–90 years) and 192 (85%) met the WHO criteria for CMML-1. Ninety (40%) patients had SRSF2 mutations (86% CMML-1), 13 (6%) had SF3B1 mutations (75% CMML-1) and 20 (9%) had U2AF35 mutations (95% CMML-1). One-hundred and twenty three (54%) patients had at least one of three spliceosome mutations (86% CMML-1). Mutational hot spots were P95 for SRSF2 (P95L-n=36/H-n=32/R-n=13/A-n=1), K700E (n=7) and H662Q (n=2) for SF3B1, and Q157 (Q157R-n=5/P-n=5/G-n=1) and S34F (n=7) for U2AF35. Seven patients (54%) with SF3B1 mutations had ≥1% RS, with 5 (38%) showing ≥15% RS. Mutations involving all three spliceosome genes were mutually exclusive. The cytogenetic distribution based on the Spanish risk stratification system (Haematologica 2011;96:375) was; SRSF2 mutations: 69 (77%) low risk, 11 (12%) intermediate risk, and 10 (11%) high risk (+8-n=3, del/monosomy 7-n=2, monosomal karyotype-n=5); SF3B1 mutations: 8 (62%) low risk and 5 (38%) intermediate risk; U2AF35 mutations: 15 (75%) low risk, 3 (15%) intermediate risk and 2 (10%) high risk (p=0.89). The distribution of mutations according to the MD Anderson prognostic scoring system [MDAPS] (Blood 2002;99:840) was; SRSF2 - low-n=41, intermediate-1-n=26, intermediate-2-n=18, high-n=5, SF3B1- low-n=7, intermediate-1-n=3, intermediate-2-n=2, high-n=1, and U2AF35- low-n=11, intermediate-1-n=5, intermediate-2-n=3, high-n=1 (p=0.73). There was no statistically significant difference, among the three mutation groups, in prognostically relevant parameters, including gender distribution, median age, hemoglobin values, platelet counts, peripheral blood (PB) and BM blast counts, absolute neutrophil counts (ANC) and absolute monocyte counts (AMC). The only notable difference was that patients with the SF3B1 mutation had a lower median white blood cell count (p=0.04) and a lower absolute lymphocyte count (p=0.045). Results II: Prognostic impact of spliceosome mutations At a median follow-up of 15 months, 166 (73%) deaths and 33 (14.5%) leukemic transformations were documented. Median survivals for patients with mutations involving SRSF2, SF3B1 and U2AF35 were 24, 17 and 12 months, respectively. In univariate analysis, the presence of SRSF2 (p=0.67), SF3B1 (p=0.96) or U2AF35 (p=0.49) mutations had no prognostic impact on OS. Similarly, none of the three spliceosome mutations affected LFS; corresponding p values were 0.55 for SRSF2, 0.9 for SF3B1 and 0.38 for U2AF35 mutations respectively. We then examined possible prognostic value of having none of these mutations (n=104) vs otherwise (n=123) and the results were once again negative (p=0.87). Conclusions: SRSF2 is the most frequently mutated spliceosome gene in CMML, but neither it nor SF3B1 or U2AF35 mutations affect overall or leukemia-free survival in CMML. Furthermore, the current study suggests limited genotype-phenotype association, save for the already established association between SF3B1 mutations and RS. Disclosures: No relevant conflicts of interest to declare.

Application of a Validated Predictive Model for Venous Thromboembolism in Cancer to Patients with Multiple Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 534-534
Author(s):  
Natasha Catherine Edwin ◽  
Jesse Keller ◽  
Suhong Luo ◽  
Kenneth R Carson ◽  
Brian F. Gage ◽  
...  
Keyword(s):  
High Risk ◽  
Research Funding ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Intermediate Risk ◽  
Discriminative Ability ◽  
Blood Institute ◽  
C Statistic

Abstract Background Patients with multiple myeloma (MM) have a 9-fold increased risk of developing venous thromboembolism (VTE). Current guidelines recommend pharmacologic thromboprophylaxis in patients with MM receiving an immunomodulatory agent in the presence of additional VTE risk factors (NCCN 2015, ASCO 2014, ACCP 2012). However, putative risk factors vary across guidelines and no validated VTE risk tool exists for MM. Khorana et al. developed a VTE risk score in patients with solid organ malignancies and lymphoma (Blood, 2008). We sought to apply the Khorana et al. score in a population with MM. Methods We identified patients diagnosed with MM within the Veterans Health Administration (VHA) between September 1, 1999 and December 31, 2009 using the International Classification of Diseases (ICD)-03 code 9732/3. We followed the cohort through October 2014. To eliminate patients with monoclonal gammopathy of undetermined significance and smoldering myeloma, we excluded patients who did not receive MM-directed therapy within 6 months of diagnosis. We also excluded patients who did not have data for hemoglobin (HGB), platelet (PLT) count, white blood count (WBC), height and weight, as these are all variables included in the Khorana et al. risk model. Height and weight were assessed within one month of diagnosis and used to calculate body mass index (BMI). We measured HGB, PLT count, and WBC count prior to treatment initiation: within two months of MM diagnosis. A previously validated algorithm, using a combination of ICD-9 code for VTE plus pharmacologic treatment for VTE or IVC filter placement, identified patients with incident VTE after MM diagnosis (Thromb Res, 2015). The study was approved by the Saint Louis VHA Medical Center and Washington University School of Medicine institutional review boards. We calculated VTE risk using the Khorana et al. score: We assigned 1 point each for: PLT ≥ 350,000/μl, HGB < 10 g/dl, WBC > 11,000/μl, and BMI ≥ 35 kg/m2. Patients with 0 points were at low-risk, 1-2 points were considered intermediate-risk and ≥3 points were termed high-risk for VTE. We assessed the relationship between risk-group and development of VTE using logistic regression at 3- and 6-months. We tested model discrimination using the area under the receiver operating characteristic curve (concordance statistic, c) with a c-statistic range of 0.5 (no discriminative ability) to 1.0 (perfect discriminative ability). Results We identified 1,520 patients with MM: 16 were high-risk, 802 intermediate-risk, and 702 low-risk for VTE using the scoring system in the Khorana et al. score. At 3-months of follow-up, a total of 76 patients developed VTE: 27 in the low-risk group, 48 in the intermediate-risk group, and 1 in the high-risk group. At 6-months of follow-up there were 103 incident VTEs: 41 in the low-risk group, 61 in the intermediate-risk group, and 1 in the high-risk group. There was no significant difference between risk of VTE in the high- or intermediate-risk groups versus the low-risk group (Table 1). The c-statistic was 0.56 at 3-months and 0.53 at 6-months (Figure 1). Conclusion Previously, the Khorana score was developed and validated to predict VTE in patients with solid tumors. It was not a strong predictor of VTE risk in MM. There is a need for development of a risk prediction model in patients with MM. Figure 1. Figure 1. Disclosures Carson: American Cancer Society: Research Funding. Gage:National Heart, Lung and Blood Institute: Research Funding. Kuderer:Janssen Scientific Affairs, LLC: Consultancy, Honoraria. Sanfilippo:National Heart, Lung and Blood Institute: Research Funding.

Utilization of oncotype DX in node-negative, ER-positive breast cancer patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 11067-11067 ◽  
Author(s):  
H. Patel ◽  
K. Hook ◽  
C. Kaplan ◽  
R. Davidson ◽  
A. DeMichele ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Oncotype Dx ◽  
Intermediate Risk ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Node Negative ◽  
Er Positive

11067 Background: The 21 gene RT-PCR assay Oncotype DX (Genomic Health, CA) stratifies patients into low, intermediate and high risk for systemic recurrence. The objective of this study was to examine the patterns of use of Oncotype DX in a single institution. Methods: All patients who had ODX testing requested by the University of Pennsylvania were identified and recurrence scores (RS) obtained. Patient and tumor characteristics, as well as treatment administered, were obtained by chart review for analysis. Results: 100 ODX tests were ordered between 1/1/05–11/30/06. RS results classified 51% of breast cancers as low risk, 38% intermediate risk, and 11% high risk. Characteristics of the tumors of the overall population and by RS group are shown in Table . 99% of patients received hormonal therapy. Of the low risk patients, only one patient was treated with chemotherapy (2%) while 34% of the intermediate risk group and 80% of the high risk group received chemotherapy. Notably, only 4/100 patients with ODX were under age 35 and 17/100 had tumors over 2cm. Conclusions: In this series, ODX use is accelerating. The results of the ODX tests appear to be used clinically as demonstrated by the very low use of chemotherapy in the low risk group. Comparison to the overall population of ER positive, node negative patients seen at this institution is underway. [Table: see text] No significant financial relationships to disclose.

Identification of Novel Tumor Microenvironment-Related Long Non-coding RNAs to Predict the Prognosis for Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Shenglan Huang ◽  
Jian Zhang ◽  
Dan Li ◽  
Xiaolan Lai ◽  
Lingling Zhuang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
High Risk ◽  
Tumor Microenvironment ◽  
Cox Regression ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Clinicopathological Parameters ◽  
Kaplan Meier ◽  
The Impact

Abstract Introduction: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with poor prognosis. Tumor microenvironment (TME) plays a vital role in the tumor progression of HCC. Thus, we aimed to analyze the association of TME with HCC prognosis, and construct an TME-related lncRNAs signature for predicting the prognosis of HCC patients.Methods: We firstly assessed the stromal/immune /Estimate scores within the HCC microenvironment using the ESTIMATE algorithm based on TCGA database, and its associations with survival and clinicopathological parameters were also analyzed. Then, different expression lncRNAs were filtered out according to immune/stromal scores. Cox regression was performed to built an TME-related lncRNAs risk signature. Kaplan–Meier analysis was carried out to explored the prognostic values of the risk signature. Furthermore, we explored the biological functions and immune microenvironment feathers in high- and low risk groups. Lastly, we probed the association of the risk signature with the treatment responses to immune checkpoint inhibitors (ICIs) in HCC by comparing the immunophenoscore (IPS).Results: Stromal/immune /Estimate scores of HCC patients were obtained based on the ESTIMATE algorithm. The Kaplan-Meier curve analysis showed the high stromal/immune/ Estimate scores were significantly associated with better prognosis of the HCC patients. Then, six TME-related lncRNAs were screened for constructing the prognosis model. Kaplan-Meier survival curves suggested that HCC patients in high-risk group had worse prognosis than those with low-risk. ROC curve and Cox regression analyses demonstrated the signature could predict HCC survival exactly and independently. Function enrichment analysis revealed that some tumor- and immune-related pathways associated with HCC tumorigenesis and progression might be activated in high-risk group. We also discovered that some immune cells, which were beneficial to enhance immune responses towards cancer, were remarkably upregulated in low-risk group. Besides, there was closely correlation of immune checkmate inhibitors (ICIs) with the risk signature and the signature can be used to predict treatment response of ICIs.Conclusions: We analyzed the impact of the tumor microenvironment scores on the prognosis of patients with HCC. A novel TME-related prognostic risk signature was established, which may improve prognostic predictive accuracy and guide individualized immunotherapy for HCC patients.

Incidence and Prognostic Impact of Gene Mutations in Older Patients with AML Treated in the ALFA-9801 Study.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1525-1525
Author(s):  
Aline Renneville ◽  
Sylvie Castaigne ◽  
Sylvie Chevret ◽  
Laura Llopis ◽  
Nathalie Philippe ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Older Patients ◽  
Gene Mutations ◽  
Significant Prognostic Factor ◽  
Prognostic Impact ◽  
Npm1 Mutation ◽  
Younger Patients ◽  
Mutational Status ◽  
Cebpa Mutations ◽  
The Impact

Abstract Introduction: The impact of gene mutations, i.e. poor-prognosis FLT3 internal tandem duplications (ITDs) and good-prognosis NPM1 or CEBPA mutations, has been welldocumented in several recent reports dealing with younger patients with acute myeloid leukemia (AML). As these mutations were associated with cytogenetically normal (CN) AML, most of these reports focused on CN-AML patients. Both FLT3-ITD and NPM1 mutations were also associated with higher WBC. The objective of the present study was to evaluate the incidence, correlations, and prognostic value of these mutations in older patients with the disease. Methods: The French ALFA group has screened a total of 583 patients, including 333 younger patients (15–50 years) treated in the ALFA-9802 trial and 250 older patients (50–70 years) treated in the ALFA-9801 trial. The older ALFA-9801 trial included 468 patients with previously untreated de novo AML and studied the role of idarubicin (IDA) as compared to high-dose daunorubicin (DNR) as well as interleukine-2 as a maintenance therapy (C. Pautas et al. ASH 2007, abstract #162). Comparison between the 250 patients tested for mutations in that trial and the 218 patients not tested showed no differences in age, sex ratio, FAB classification, bone marrow blasts percentage, randomization arm, and performance status at entry in the study. There was, however, a higher rate of patients with intermediate cytogenetics (p=.01) or increased WBC (p=.01) in the former subgroup. Results: Median age of the 250 patients tested was 60 years. Cytogenetics was studied in 232 patients (12 favorable, 174 intermediate, 46 unfavorable). One hundred twenty-two patients (49%) had CN-AML. CR rate was 67.5% and estimated 4-year OS was 26% (95% CI, 20–33). Incidences of FLT3-ITD, NPM1, and CEBPA mutations were 37/250 (15%), 64/249 (26%), and 20/249 (8%), respectively. These incidences were very similar than in the younger ALFA-9802 population [50/329 (15%), 76/321 (24%), and 24/316 (8%), respectively]. In these older AML patients, the correlation between increased WBC and FLT3-ITD (p&lt;.001) or NPM1 mutation (p&lt;.001) was still observed. Conversely, NPM1 mutations only (p&lt;.001), but not FLT3-ITDs (p=.10) or CEBPA mutations (p=.99), were significantly associated with CN-AML. In the whole group of 249 patients with either normal or abnormal karyotype tested for all mutations, 46 were NPM1+/FLT3-ITDwt, 19 FLT3-ITD+/NPM1wt, 18 FLT3-ITD+/NPM1+, and 166 NPM1wt/FLT3-ITDwt. CR rate was 87%, 84%, 56%, and 75% and median OS was 20.5, 18.6, 6.0, and 14.6 months, respectively. In the 20 CEBPA+ patients, CR rate was 80% and median OS was 22.8 months. In the group of 122 CN-AML patients tested for all mutations, 36 were NPM1+/FLT3-ITDwt, 8 FLT3-ITD+/NPM1wt, 15 FLT3-ITD+/NPM1+, and 63 NPM1wt/FLT3- ITDwt. CR rate was 92%, 87.5%, 60%, and 78% and median OS was 20.5, 16.9, 7.0, and 16.8 months, respectively. In the 10 CEBPA+ patients, CR rate was 80% and median OS was not reached. In multivariate analysis including age, WBC, cytogenetics (favorable versus others), and gene mutational status (NPM1+ or CEBPA+ if FLT3-ITDwt versus others), a pejorative effect of age (p=.02) and WBC (p&lt;.001), but a protective effect of mutational status (HR= 0.66, p=.05) and favorable cytogenetics (HR=0.43, p=.06) was observed in the whole patient population. Nevertheless, estimated 4-year OS was only 37% (95% CI, 23–50) in patients with a favorable mutational status. In those with CNAML and a favorable mutational status, estimated 4-year OS reached only 40% (95% CI, 23–56). In this subgroup of patients with CN-AML, WBC was the only significant prognostic factor identified in multivariate analysis (p&lt;.001). Conclusion: This study conducted in a large cohort of patients aged 50 to 70 years and prospectively treated in the same trial showed that gene mutational status still affect the outcome of older patients with AML. Mutation incidences are in the same range than in younger patients. Nevertheless, their impact on OS appeared to be less marked than in younger patients, probably due to the worse general outcome observed in these older patients.

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