Analysis of the Serum Free Light Chain Ratio and Its Prognostic Value in a Cohort of Patients with Chronic Lymphocytic Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2631-2631
Author(s):  
Chaim Shustik ◽  
Stephen Harding ◽  
Keyue Ding ◽  
Liting Zhu ◽  
Laura Z. Rassenti ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Prognostic Value ◽  
Cox Regression ◽  
Lymphocytic Leukemia ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Serum Free ◽  
Mutational Status ◽  
Igvh Mutational Status ◽  
Baseline Factors

Abstract Abstract 2631 Poster Board II-607 Introduction The measurement of immunoglobulin serum free light chains (sFLC) has prognostic value in the spectrum of plasma cell dyscrasias and has been evaluated in other B-cell malignancies. Its utility as a biomarker of potential prognostic value in B-CLL ( chronic lymphocytic leukemia ) was previously reported in a study of 259 patients in whom 39% had an abnormal sFLC ratio which was associated with a shorter time to first treatment and poor survival (Pratt et al. BJH. 2008). The objective of the present analysis was to identify if these findings are applicable to a previously untreated population of 125 patients accrued to NCIC CTG trial CL2 treated in a uniform manner and characterized for cytogenetic abnormalities, ZAP-70 expression and IgVH mutational staus. Patients & Methods Sera from 125 untreated patients, previously enrolled in a non-randomised, non-blinded, phase II study evaluating the efficacy of oral fludarabine (NCIC CTG CL2 trial), were analysed retrospectively. Median age was 61 yrs (range: 33–92) and 39% patients (49) were female. Rai staging system - Stage I: n=30, II: n=54, III: n=19, IV: n=22. Kaplan-Meier survival curves and log-rank test were used in summarizing and comparing survival distributions between sFLC ratio normal and abnormal groups, and COX regression analysis adjusting for prespecified baseline factors of ZAP-70, IGVH mutational status, sFLC and b2M were also performed to compare the two groups. Results 83/125 (66%) patients showed an abnormal sFLC ratio (<0.26 or >1.65). Table 1 summarises the results. b2M was the only baseline factor showing a statistically significant association with the sFLC ratio (p=0.01). A total of 33 patients died over the course of the study (21 had an abnormal sFLC ratio vs 12 with a normal sFLC ratio), including 20 deaths attributed to the disease and/or its treatment (13 with abnormal sFLC ratios vs 7 with normal sFLC ratios). No statistically significant difference was found, either for overall survival (OS) or for treatment free survival (TFS) between patients with normal and abnormal sFLC ratios. However, patients with abnormal sFLC ratios did show a borderline significantly worse progression free survival (PFS) (HR= 1.48, 95% C.I. 0.97 – 2.28, p = 0.07), even after adjustment for pre-specified baseline factors (HR = 1.48, 95% C.I. 0.94 -2.34, p = 0.09). Furthermore, in patients with mutated IGVH, those with with an abnormal sFLC ratio had a significantly shorter PFS (HR = 2.76, 95% V.I. 1.1 – 6.9, p=0.02). COX regression analysis for OS found that age (> 65yrs), gender (male), and stage (III or IV) were poor prognostic factors. sFLC ratios were not significantly associated with response rates (60% vs. 69%, p = 0.33) Conclusions 1) In this study of patients with untreated CLL with an indication for therapy, the frequency of an abnormal sFLC ratio is higher than previously reported i.e. 66% vs 44% (Martin et al. Trans Res. 2007) and 39% (Pratt et al. BJH. 2009). 2) The relation between IgVH mutational status and sFLC ratio needs further investigation. 3) The role of sFLC ratio as a prognostic biomarker in CLL should be evaluated in prospective trials of therapy in CLL. Disclosures: No relevant conflicts of interest to declare.

Abnormal Serum Free Light Chain Ratios Are Associated with Earlier Time to First Treatment and Poor Survival in Patients with Chronic Lymphocytic Leukaemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3141-3141
Author(s):  
Guy Pratt ◽  
Graham Mead ◽  
Supratik Basu ◽  
Abe Jacobs ◽  
Roger Holder ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Lymphocytic Leukemia ◽  
Female Ratio ◽  
Cox Regression Analysis ◽  
Serum Free ◽  
Kaplan Meier ◽  
Mutational Status ◽  
Time To First Treatment

Abstract Introduction: Serum free light chains (sFLC) have prognostic significance in plasma cell disorders. In B-cell chronic lymphocytic leukemia (CLL), a small study found 8/18 (44%) of patients to have abnormal FLC ratios but no assessment of prognostic value was published. The aim of the present study was to determine whether abnormal serum FLC concentrations are indicative of a poor prognosis in CLL patients. Methods: Sera were analysed from 381 previously diagnosed CLL patients (Stage A 307; B 30; C 26; 18 missing; male: Female Ratio 1.6:1, mean age 71 (29–98)) with samples taken before their first treatment (303) or after treatment (78). The study was approved by the Birmingham Heart of England NHS Trust Review Board. Patients were described using the Binet staging system and measured for prognostic markers including CD38, Zap70, mutational status, β2M and FLC. Kaplan Meier survival curves and Cox proportional hazards regression (age, sex, CD38, Zap 70, mutational status, β2M and sFLC) were calculated using SPSS v14. Results: 147/381 (39%) patient sera had abnormal sFLC ratios. Kaplan Meier analysis of all deaths showed abnormal ratios were significantly associated with worse survival (n=350, p&lt;0.001). Analysis of deaths attributed to CLL (n=30) also indicated that an abnormal FLC ratio was predictive of shorter survival (p=0.001). However, for deaths not attributed to CLL (n=32), the FLC ratio was not significantly predictive of outcome (p=0.112). For Cox regression analysis (n=228) of deaths attributed to CLL only, three significant, independent, prognostic factors were identified: CD38 (p&lt;0.001), abnormal ratio (p&lt;0.001) and Stage (p=0.027). Analysis of the untreated patient population (n=303), using Kaplan Meier analysis of time to first treatment, found that an abnormal lambda ratio (p=0.04) but not an abnormal kappa ratio (p=0.443) predicted earlier treatment. For patients with an abnormal lambda ratio, the mean time to first treatment was 38 months earlier than those patients with a normal ratio. Cox regression analysis (n=171) of time to first treatment, found 4 significant, independent factors predicting earlier treatment: Zap70 (p&lt;0.001), Age (p&lt;0.001), abnormal sFLC ratio (p=0.001) and Stage (p=0.027). Conclusions: As shown in other monoclonal gammopathies, abnormal sFLC ratios were associated with poorer outcomes in patients with CLL. Furthermore, in an untreated population, patients with an abnormal lambda sFLC ratio required earlier treatment, indicating a pathological mechanism which is as yet unclear but which warrants further investigation.

scholarly journals Ring Sideroblasts and SF3B1 Mutations in Myelodysplastic Syndromes (MDS): Are They Two Faces of the Same Coin? a Study on Behalf of the MDS Clinical Research Consortium (MDS CRC)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4321-4321
Author(s):  
Rami S. Komrokji ◽  
John Barnard ◽  
David P Steensma ◽  
Amy E. DeZern ◽  
Gail J. Roboz ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Myelodysplastic Syndromes ◽  
Research Funding ◽  
Somatic Mutations ◽  
Cox Regression ◽  
Hazard Ratio ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Mutational Status ◽  
Hazard Ratios

Abstract Introduction Recurrent somatic mutations in SF3B1, a gene encoding a spliceosome component, have been identified in patients (pts) with myelodysplastic syndromes (MDS). SF3B1 mutations (MT) are more commonly detected in pts with ring sideroblast (RS) morphology and are associated with favorable outcome. The proposed 2016 World Health Organization (WHO) MDS classification categorizes pts with >5% RS and SF3B1 MT as MDS with RS, in contrast to prior WHO classifications which required ≥15% RS regardless of genotype. In this study, we explored the prognostic value of RS and SF3B1 MT and assessed the validity of the new proposal. Methods We identified 471 pts with MDS and known SF3B1 mutational status from MDS CRC institutions. RS were assessed as present or absent (RS +/-) based on bone marrow aspirate reports (n=157); in cases where quantitative data on RS% were available (n=41), pts were grouped in the 5-15% RS group or > 15% RS group. Survival was calculated from time of diagnosis. Cox regression analysis was used to estimate hazard ratios for overall survival (OS) and AML free survival (AFS), which was defined as time to death or AML transformation, respectively. Chi-squared and Wilcoxon tests were used to test for differences in categorical and continuous distributions, respectively. Results: Among 471 pts with known SF3B1 mutational status, 76 (16%) had MT. Pts with MT had lower-risk International Prognostic Scoring System (IPSS) scores compared to SF3B1 wild-type (WT; 79% vs 57%, p < .001). Among pts with MT, 50% had RS + compared to 19% RS + in the WT group (p < .001). MT were independently associated with better OS (HR 0.48, p= .001) and longer AFS (HR 0.5, p <.005) after adjusting for age and IPSS. We compared outcomes of four groups: WT/RS-, MT/RS-, WT/RS+, and MT/ RS +. Adjusting for age and IPSS, pts with MT/RS + had the best outcome, with hazard ratios for AFS of 4.2 for WT/RS- vs. MT/RS+ (p =.018), 4.1 for MT/RS- vs. MT/RS+ (p =.045), and 5.1 for WT/RS+ vs. MT/RS+ (p= .01). We compared 7 pts with 5-15% RS to 22 pts with >15% RS. Among patients with RS 5-15%, 4/7 pts (57%) were classified as MDS with excess blasts compared to 24% for those RS >15% (p=.09). Pts with 5-15% RS were more likely to be thrombocytopenic (5/7, 71%) compared to >15% RS (29%, p=.04). One patient (14%) with 5-15% RS had MT compared to 12 (55%) pts with > 15% RS, p= .06. In Cox regression analysis using the RS 5-15% group as the reference, the hazard ratio for RS > 15% for AFS was 0.26 (p = .034) and the hazard ratio for MT for AFS was 0.08 (p= .002). Conclusions SF3B1 somatic mutations in MDS are commonly associated with RS, better OS and longer AML-free survival. Patients with RS and MT had a significantly better outcome than those with either isolated RS or MT, or neither. These data support incorporation of SF3B1 mutation status into the WHO classification regardless of RS percent, though with differentiation for those with RS and MT. Disclosures Komrokji: Novartis: Consultancy, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Consultancy; Boehringer-Ingelheim: Research Funding. Roboz:Cellectis: Research Funding; Agios, Amgen, Amphivena, Astex, AstraZeneca, Boehringer Ingelheim, Celator, Celgene, Genoptix, Janssen, Juno, MEI Pharma, MedImmune, Novartis, Onconova, Pfizer, Roche/Genentech, Sunesis, Teva: Consultancy.

Predictive Value of Gene Expression with Respect to IgVH Mutational Status and Survival in Chronic Lymphocytic Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1913-1913
Author(s):  
Mars B. Van’t Veer ◽  
Anne Brooymans ◽  
Anton W. Langerak ◽  
Wilfried J. Graveland ◽  
Kirsten Van Lom ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Predictive Value ◽  
Cox Regression ◽  
Lymphocytic Leukemia ◽  
P Value ◽  
Mrna Levels ◽  
Cox Regression Analysis ◽  
Mutational Status ◽  
Igvh Mutational Status ◽  
Prediction Of Prognosis

Abstract Background: Chronic Lymphocytic Leukemia (CLL) has a variable clinical course, of which IgVH mutational status of the malignant B cells is a strong independent predictor for outcome. Objective: We studied the expression of 5 different genes for their value to predict IgVH mutational status and overall survival (OS). Methods: mRNA levels were quantified by real time PCR in lymphoprep separated but unsorted blood samples from 110 morphologically and fenotypically characterised CLL patients for the following genes: ZAP70, lipoprotein lipase (LPL), ADAM29, KIAA0610 and nRIP1. Expression levels were compared wih respect to IgVH mutational status (mutation = % germline < 98%), using logistic regression and with respect to OS (= time from day of laboratory tests to death due to any cause), using Cox regression analysis. Results: The predictive value of the expression of these 5 genes for IgVH mutational status is shown in table 1. Each of these genes showed to be an independent marker for the prediction of IgVH mutational status. LPL as a single marker was the best predictor for mutation. These factors taken together had a high predictive value towards mutational IgVH status (area under ROC curve = 0.93). table 1 N Odds ratio P value ZAP70 no 85 1 (>5.2) yes 25 0.098 0.002 LPL no 73 1 (>0.04) yes 37 0.029 <0.001 ADAM29 no 73 1 (>30) yes 37 6.61 0.012 KIAA0610 no 81 1 (>0.25) yes 29 0.19 0.045 NRIP1 no 88 1 (>10) yes 22 48.73 0.008 The predictive value of IgVH mutation and the expression of these 5 genes for OS is shown in table 2. From the six parameters tested, IgVH mutational status and LPL were predictors for OS at a significant level of 5%, while ZAP70 was of borderline significance. table 2 Conclusion: measured in unsorted CLL samples, all genes, and especially LPL, had predictive value towards the presence of IgVH mutation. Expression of LPL and absence of mutation were adverse prognostic factors for survival. Thus, the replacement of the assessment of both IgVH mutational status and ZAP70 by assessment of LPL levels for the prediction of prognosis in CLL patients may be considered. N survival at 24months P value mutation no 36 70% yes 44 93% 0.041 ZAP70 no 66 87% yes 18 70% 0.078 LPL no 55 94% yes 29 66% 0.001 ADAM29 no 57 84% yes 27 84% 0.486 KIAA0610 no 63 88% yes 21 71% 0.133 NRIP no 71 81% yes 13 100% 0.167

Identification and Validation of a Seven m6A-related lncRNAs Signature Predicting Prognosis of Ovarian Cancer

2021 ◽  
Author(s):  
Yan Li ◽  
Xiaoying Wang ◽  
Yue Han ◽  
Xun Li
Keyword(s):  
Ovarian Cancer ◽  
Regression Analysis ◽  
Correlation Analysis ◽  
Prognostic Value ◽  
Cox Regression ◽  
Risk Group ◽  
Pearson Correlation ◽  
Regression Analyses ◽  
Cox Regression Analysis ◽  
Pearson Correlation Analysis

Abstract Background: Long non-coding RNAs (lncRNAs) play an important role in angiogenesis, immune response, inflammatory response and tumor development and metastasis. m6 A (N6 - methyladenosine) is one of the most common RNA modifications in eukaryotes. The aim of our research was to investigate the potential prognostic value of m6A-related lncRNAs in ovarian cancer (OC).Methods: The data we need for our research was downloaded from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. Pearson correlation analysis between 21 m6A regulators and lncRNAs was performed to identify m6A-related lncRNAs. Univariate Cox regression analysis was implemented to screen for lncRNAs with prognostic value. A least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox regression analyses was used to further reduct the lncRNAs with prognostic value and construct a m6A-related lncRNAs signature for predicting the prognosis of OC patients. Results: 275 m6A-related lncRNAs were obtained using pearson correlation analysis. 29 m6A-related lncRNAs with prognostic value was selected through univariate Cox regression analysis. Then, a seven m6A-related lncRNAs signature was identified by LASSO Cox regression. Each patient obtained a riskscore through multivariate Cox regression analyses and the patients were classified into high-and low-risk group using the median riskscore as a cutoff. Kaplan-Meier curve revealed that the patients in high-risk group have poor outcome. The receiver operating characteristic curve revealed that the predictive potential of the m6A-related lncRNAs signature for OC was powerful. The predictive potential of the m6A-related lncRNAs signature was successfully validated in the GSE9891, GSE26193 datasets and our clinical specimens. Multivariate analyses suggested that the m6A-related lncRNAs signature was an independent prognostic factor for OC patients. Moreover, a nomogram based on the expression level of the seven m6A-related lncRNAs was established to predict survival rate of patients with OC. Finally, a competing endogenous RNA (ceRNA) network associated with the seven m6A-related lncRNAs was constructed to understand the possible mechanisms of the m6A-related lncRNAs involed in the progression of OC.Conclusions: In conclusion, our research revealed that the m6A-related lncRNAs may affect the prognosis of OC patients and identified a seven m6A-related lncRNAs signature to predict the prognosis of OC patients.

P4369Direct comparison of prognostic value of echocardiographic parameters of right ventricular dysfunction in normotensive patients with acute pulmonary embolism

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
K Kurnicka ◽  
M Ciurzynski ◽  
L Hobohm ◽  
A Thielmann ◽  
B Sobkowicz ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Regression Analysis ◽  
Prognostic Value ◽  
Acute Pulmonary Embolism ◽  
Ventricular Dysfunction ◽  
Cox Regression ◽  
Clinical Course ◽  
Right Ventricular Dysfunction ◽  
Cox Regression Analysis ◽  
Echocardiographic Parameters

Abstract Background Although various echocardiographic parameters of right ventricular dysfunction (RVD) were reported to be of prognostic value in normotensive patients with acute pulmonary embolism (APE), an optimal definition of RVD on echocardiography is missing. Purpose We performed a direct comparison of prognostic value of RV/LV ratio, TAPSE, and TRPG/TAPSE for complicated clinical course that included: in-hospital APE related mortality, hemodynamic collapse or rescue thrombolysis. Methods Prospective cohorts of APE patients normotensive at admission, managed according to the ESC Guidelines 2014 were merged in a collaborative database. Transthoracic echocardiography was performed at admission, as soon as possible. All studied parameters were available in each patient. AUC in ROC analysis were assessed for each parameter and were compared between them. Multivariable Cox regression analysis was performed to assess the combination of echo-parameters. Results Overall, 490 pts were included in the study (229F), aged 64±18 years. Clinical endpoint occurred in 31 pts including 8 APE related deaths. AUC for SAE of RV/LV, TAPSE and TRPG/TAPSE were similar (Figure 1). TAPSE <16mm compared to other echo-parameters showed the highest PPV and NPV (Table 1). Cox regression analysis including SBP, HR, age, elevated troponin and echo-parameters showed that only blood pressure, RV/LV >1 and TAPSE <16mm were identified as independent predictors of outcome (HR 0.98 (95% CI: 0.96–0.99), p=0.03; 2,53 (95% CI: 1.2–5.7), p<0.03 and 3,76 (95% CI: 1.74–8.11), p<0.001). Table 1. Predictive values of proposed cut offs of echocardiographic parameters Parameter Sensitivity Specificity PPV NPV TAPSE <16mm 52% 85% 18% 96% RV/LV >1.0 74% 63% 12% 95% TAPSE<20 & TRPG/TAPSE >4.5 10% 94% 10% 94% Figure 1 Conclusions Although all TAPSE, RV/LV ratio and TRPG/TAPSE showed similar performance for prognosticating of in-hospital outcome in normotensive PE patients, TAPSE<16mm showed the highest predictive value for identification of patients at risk of complicated clinical course.

Prognostic Impact of Cytogenetics and Early Response and Efficacy of Sequential High-Dose AraC and Idarubicin (S-HAI) in Patients with Refractory and Relapsed Acute Myeloid Leukemia (AML): Results of a Prospective Study.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 871-871
Author(s):  
Wolfgang Kern ◽  
Hubert Serve ◽  
Peter Staib ◽  
Christa Kerschgens ◽  
Anett Matylis ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Prospective Study ◽  
Cox Regression ◽  
High Dose ◽  
Prognostic Impact ◽  
Prognostic Parameters ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
A Prospective Study ◽  
Refractory Aml

Abstract Management of patients with refractory and relapsed AML needs optimization. We performed a prospective study in these patients aiming at 1) the definition of the anti-leukemic efficacy of the S-HAI regimen; and 2) the evaluation of the prognostic impact of cytogenetic aberrations at relapse in the context of other prognostic parameters. Treatment consisted of AraC 1 g/sqm q 12 h days 1, 2, 8, and 9 and idarubicin 10 mg/sqm days 3, 4, 10, and 11. AraC was given at 3 g/sqm in patients under age 60 with refractory AML or relapse after CR1 <6 months. Fludarabine was given according to randomization at 15 mg/sqm 4 h before each dose of AraC. Between May 1996 and February 2004 306 patients were randomized, 261 are fully evaluable. The patients′ characteristics were median age 55 years (range, 18-83); refractory AML/relapse with CR1<6 months/relapse with CR1 >6 months 13%/25%/62%; cytogenetics at relapse favorable/intermediate/unfavorable/not available 7%/44%/24%/25%; secondary AML 7%. Median duration of neutropenia <1000/μl was 37 days. Non-hematologic side effects III°/IV° included diarrhea (21%), mucositis (19%), nausea/vomiting (17%), hyperbilirubinemia (12%), and bleeding (8%). Encontered infections were pneumonia 51%, FUO 41%, bacteremia 28%, abdominal 23%, and catheter-related 16%. Response rates were CR 39%, partial remission 7%, persistent leukemia 36%, early death 18%. Median event-free survival (EFS) was 2.4 months, meidan relapse-free survival was 5.9 months, and median overall survival was 6.2 months. In 38% of patients a change of karyotype between diagnosis and relapse occurred. In general, cytogenetics (CG) at relapse had a higher prognostic impact as compared to CG at diagnosis and therefore was included in the following analyses of prognostic parameters. CR rate was significantly related to duration of CR1 (CR1 0 months 29%; CR1 <6 months 14%; CR1 >6<18 months 52%; CR1 >18 months 56%; p<0.0001) and CG at relapse (favorable CG 85%; intermediate CG 44%; unfavorable CG 21%; p<0.0001) but not to age < vs. >60 years (40% vs. 39%). EFS and OS were significantly related to duration of CR1 (p=0.0001 and p=0.0004) and CG at relapse (p=0.0002 and p=0.0009). Logistic regression analysis revealed CG at relapse (p=0.006) as well as duration of CR1 (p=0.004) being independently related to CR rate. Cox regression analysis revealed CG at relapse (p=0.001) and duration of CR1 (p=0.014) being independently related to EFS. CG at relapse was the only parameter independently related to OS (p=0.001). The inclusion of the therapy-dependent parameter, residual bone marrow blasts at day 18 (day 18 blasts), revealed day 18 blasts being independently related to CR rate, EFS, and OS. These data indicate that 1) the S-HAI regimen confers a significant anti-leukemic efficacy in patients with relapsed and refractory AML unless unfavorable CG are present; and 2) CG at relapse is the most important prognostic parameter in these patients and day 18 blasts may be used to early identify treatment failure and guide the decision about alternative treatment approaches.

Translocations Involving the IGH@locus Occur In 3.7% of Chronic Lymphocytic Leukemia and Are Associated with Unmutated IGHV Status and a Shorter Time to Treatment: A Study on 2,135 Cases

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3596-3596
Author(s):  
Claudia Haferlach ◽  
Frank Dicker ◽  
Susanne Schnittger ◽  
Wolfgang Kern ◽  
Torsten Haferlach
Keyword(s):  
Multivariate Analysis ◽  
Regression Analysis ◽  
Chronic Lymphocytic Leukemia ◽  
Cox Regression ◽  
Lymphocytic Leukemia ◽  
Employment Equity ◽  
Mutation Status ◽  
Cox Regression Analysis ◽  
Igh Locus ◽  
Equity Ownership

Abstract Abstract 3596 Introduction: Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with a variable clinical course and a large spectrum of treatment options. Based on FISH data, a prognostic classification system has been established with 13q deletions as sole abnormality associated with a favorable prognosis and 17p and 11q deletions correlating with an unfavorable outcome. Recently, the combined evaluation of FISH data, IGHV mutation status and chromosome banding analysis (CBA) revealed that the impact of distinct genetic parameters differs with respect to overall survival (OS) and time to treatment (TTT). Thus far only few data is available on less frequent genetic abnormalities such as 14q deletions and translocations involving the IGH@ locus (tIGH). Therefore, we analyzed CLL with tIGH in detail with respect to frequency, partner genes and impact on prognosis. Methods/Patients: 78 CLL cases with tIGH were identified from 2,135 CLL sent to our laboratory for diagnostic work-up. All cases had been evaluated by immunphentotyping, FISH and CBA. Result: The most frequent tIGH was t(14;19)(q32;q13) (BCL3, n=21) followed by t(14;18)(q32;q21) (BCL2, n=19), t(8;14)(q24;q32) (CMYC, n=7) and t(11;14)(q13;q32) (CCND1, n=6). In the remaining 25 cases 5 recurrent translocations (t(2;14)(p13;q32), n=3; t(4;14)(p16;q32), FGFR3, n=2; t(11;14)(p15;q32), n=2; t(14;17)(q32;q25), n=2; and t(7;14)(q21;q32), n=2) were observed while the remaining 14 translocations were identified in single cases only. In 9/78 cases (11.5%) the tIGH was the sole abnormality. Recurrent additional chromosome abnormalities were +12 (n=7), del(13q) (n=9), del(11q) (n=3). A 17p deletion was observed in 1 case. In two cases tIGH was present only in a subclone and was a secondary abnormality occurring in addition to an del(11q) and a +12, respectively. CLL with tIGH were compared to 401 CLL without tIGH comprising all other genetic subgroups (subdivided according to Döhner et al.: del(17p) n=26, del(11q) n=42, +12 n=42, “normal” n=88, del(13q) sole n=177 and del(14q) n=26). An unmutated IGHV status was more frequent in CLL with tIGH as compared to all others (26/46 (54.3%) vs 128/353 (36.3%); p=0.023). For 53 cases with tIGH and all cases of the non-tIGH cohort clinical follow-up data was available. Median OS was 143.8 months (mo) in CLL with tIGH and 72.9 mo in patients with del(17p) while it was not reached in all other subgroups. In Cox regression analysis only del(17p) and mutated IGHV status were significantly associated with OS (p<0.0001, relative risk (RR)=7.0; p=0.014, RR=0.38). Median TTT was as follows: total cohort: 60.9 mo; tIGH: 27.8 mo; del(17p): 58.9 mo; del(11q): 19.7 mo; +12: n.r.; “normal” 63.9 mo; del(13q) sole: 83.0 mo and del(14q): 21.0 mo. In univariate Cox regression analysis the following parameters were significantly associated with shorter TTT: tIGH (p=0.004, RR=1.82), del(11q) (p<0.0001, RR=2.55), and del(14q) (p=0.007, RR=2.1), while del(13q) sole and mutated IGHV status were associated with longer TTT (p<0.0001, RR=0.40; p<0.0001, RR=0.23). In multivariate analysis including tIGH, del(11q), del(14q) and del(13q) sole all parameters retained their impact on TTT. However, if IGHV mutation status was included in the model only the mutated IGHV mutation status retained an impact on TTT (p<0.0001, RR=0.26). Next, patients with tIGH were subdivided according to their partner genes. Median OS was not reached in all subgroups, while median TTT was as follows: t(11;14): 101.2 mo, t(14;18): 47.9 mo, t(14;19): 11.0 mo, t(8;14): 18.5 mo and other partner genes: 27.8 mo. In univariate Cox regression analysis only t(14;19) was significantly associated with shorter TTT (p<0.001, RR=3.1). Including t(14;19) into multivariate analysis revealed a significant impact of both mutated IGHV mutation status and t(14;19) on TTT (p<0.0001, RR=0.286; p=0.004, RR=3.60). Conclusion: Translocations involving the IGH@ locus occur at low frequency in CLL. They are associated with unmutated IGHV status and a shorter TTT. TTT is especially short in cases with t(14;19). The prognostic impact of t(14;19) is independent of IGHV mutation status. In contrast CLL with t(11;14) and t(14;18) are neither associated with shorter OS nor shorter TTT. This data supports the application of CBA in CLL in order to identify all clinically relevant chromosomal aberrations, including those not detected by routine FISH analysis. Disclosures: Haferlach: MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Dicker:MLL Munich Leukemia Laboratory: Employment. Schnittger:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Kern:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership.

Hypercvad for Treatment of Adult Acute Lymphocytic Leukemia: The Moffitt Cancer Center Experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4241-4241
Author(s):  
Kendra L. Sweet ◽  
Robert M. Crescentini ◽  
Jennifer L. Cultrera ◽  
Jeffrey E Lancet ◽  
Rami S. Komrokji
Keyword(s):  
Overall Survival ◽  
Regression Analysis ◽  
T Cell ◽  
Acute Lymphocytic Leukemia ◽  
Cox Regression ◽  
Philadelphia Chromosome ◽  
Lymphocytic Leukemia ◽  
Cancer Center ◽  
Cox Regression Analysis ◽  
Frontline Therapy

Abstract 4241 Background: Acute lymphocytic leukemia (ALL) incidence is approximately 4000 cases per year in the USA. Several standard induction regimens are used upfront for the treatment of ALL. The HyperCVAD regimen is currently a widely used upfront treatment option for adult ALL patients based on pioneer work at MD Anderson Cancer Center (MDACC). Here we present our experience with the HyperCVAD regimen treating ALL at Moffitt Cancer Center (MCC), representing the largest cohort treated with this regimen outside MDACC. Methods: Patients who were diagnosed and treated at MCC with ALL were identified through the MCC Total Cancer Care database. Individual charts were reviewed. All patients treated with the HyperCVAD regimen frontline were included in this analysis. The HyperCVAD regimen was administered as originally described at MDACC. Philadelphia positive patients were treated with addition of tyrosine kinase inhibitors (TKI) (imatinib or dasatinib). Descriptive data are reported, t-test was used to compare continuous variables, chi square test for categorical variables, Kaplan Meier curves were used for overall survival (OS). Log rank test was used to compare survival times between groups. Cox regression analysis was used for multivariable analysis. All analyses were conducted using SPSS version 19.0 Results: Between 1/1/2002 and 6/30/2011, 100 ALL patients were treated with HyperCVAD at MCC. The median age was 45 years (range 18–83), 26 were above age of 60 years and 26 were below age of 30 years. Sixty three percent were male and 37% were female. Sixty five percent were white, 6% were African America, 7% were Hispanic and 22% were described as other. B-Cell ALL accounted for 83% of patients, while the other 17% had T-Cell origin. Of the 100 patients, 23% of patients were Philadelphia chromosome positive, while 72% were negative, and in 5% karyotype was unknown. Splenomegaly was present at diagnosis in 18% of patients, while 17% presented with lymphadenopathy. Twenty-three percent of patients presented with a WBC of 50,000 or greater. CNS disease was noted in 9% of patients at diagnosis. Seventy-six percent achieved a complete response (CR), while 12% had refractory disease. Response to frontline was not documented in 12% of patients. The median overall survival was 27 months (95% CI 15.6–38.3). In univariable analysis, no difference in outcome was observed based on gender, race, Philadelphia chromosome positivity, B or T-cell origin, presence of lymphadenopathy, splenomegaly, WBC >50,000 or CNS disease at presentation. Age was a significant prognostic factor. The median OS for patients <60 years old was 34 months (95% CI 20.8–47.), and 16 months for patients >60 years old (95% CI 6.9–25.1) (p= 0.006) (figure-1) The median OS was higher in patients who achieved CR with frontline chemotherapy. OS was 34 months (95% CI 22.5–45.4) compared to 13 months in patients who did not achieve CR after frontline (95% CI 7.3–18.7) (p=< 0.005). Thirty-eight patients proceeded to allogeneic SCT. The median OS was 40 months in patients who proceeded to allogeneic SCT compared with 16 months in patients who did not (p=0.002). In Cox regression analysis, achieving CR with frontline induction, and allogeneic SCT were statistically significant independent variables for OS for adult patients with ALL. The odds ratio was 3.4 in patients achieving CR with frontline therapy, and 3.1 in patients who underwent allogeneic SCT. Conclusion: To our knowledge, this cohort represents the largest group of ALL patients treated outside MDACC with HyperCVAD based regimens, with similar overall results in the setting of tertiary centers. Achievement of CR after frontline therapy, and undergoing allogeneic SCT were statistically significant prognostic indicators. The outcome of elderly patients (age >60) was inferior. In the elderly population there were lower rates of CR and less number of patients proceeded to allogeneic SCT. The outcome in Philadelphia chromosome positive ALL has improved with the introduction of TKI’s and allogeneic SCT. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Evaluation of pulse wave velocity for predicting major advanced cardiovascular events in patients with chronic myocardial infarction

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
Z Meiszterics ◽  
T Simor ◽  
R J Van Der Geest ◽  
N Farkas ◽  
B Gaszner
Keyword(s):  
Myocardial Infarction ◽  
Regression Analysis ◽  
Cardiovascular Events ◽  
Pulse Wave ◽  
Cox Regression ◽  
Event Free Survival ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Kaplan Meier

Abstract Introduction Increased aortic pulse wave velocity (PWV) as a strong predictor of major advanced cardiovascular events (MACE) has a prognostic relevance in patients after myocardial infarction (MI). Several non-invasive methods have been proposed for the assessment of arterial stiffness, but the PWV values show significant differences according to the applied techniques. Cardiac magnetic resonance imaging (CMR) provides an accurate method to measure PWV and infarct size in patients after MI. Purpose Calculated PWV values of CMR based phase-contrast (PC) and invasively validated oscillometric methods were compared in this prospective observational study. We aimed to evaluate the cut-off PWV values for each method, while MACE predicted and validated the prognostic value of high PWV in post-infarcted patients in a 6-year follow-up. Methods 3D aortic angiography and PC velocity imaging was performed using a Siemens Avanto 1,5 T CMR device. Oscillometric based Arteriograph (AG) was used to assess PWV using direct body surface distance measurements. The comparison between the two techniques was tested. Patients received follow-up for MACE comprising all-cause death, non-fatal MI, ischemic stroke, hospitalization for heart failure and coronary revascularization. Event-free survival was analysed using Kaplan-Meier plots and log-rank tests. Univariable and multivariable Cox regression analysis was performed to identify outcome predictors. Results 75 patients (56 male, 19 female, average age: 56±13 years) referred for CMR were investigated, of whom 50 had coronary artery disease (CAD) including 35 patients with previous MI developing ischaemic late gadolinium enhancement (LGE) pattern. AG and CMR derived PWV values were significantly correlated (rho: 0,343, p&lt;0,05), however absolute PWV values were significantly higher for AG (median (IQR): 10,4 (9,2–11,9) vs. 6,44 (5,64–7,5); p&lt;0,001). Bland Altman analysis showed an acceptable agreement with a mean difference of 3,7 m/s between the two measures. In patients with CAD significantly (p&lt;0,01) higher PWV values were measured by AG and CMR, respectively. During the median follow-up of 6 years, totally 69 MACE events occurred. Optimized PWV cut-off values for MACE prediction were calculated (CMR: 6,47 m/s; AG: 9,625 m/s) by receiver operating characteristic analysis. Kaplan-Meier analysis in both methods showed a significantly lower event-free survival in case of high PWV (p&lt;0,01, respectively). Cox regression analysis revealed PWV for both methods as a predictor of MACE (PWV CMR hazard ratio (HR): 2,6 (confidence interval (CI) 1,3–5,1), PWV AG HR: 3,1 (CI: 1,3–7,1), p&lt;0,005, respectively). Conclusions Our study showed good agreement between the AG and CMR methods for PWV calculation. Both techniques are feasible for MACE prediction in postinfarcted patients. However, different AG and CMR PWV cut-off values were calculated to improve risk stratification. FUNDunding Acknowledgement Type of funding sources: None. Agreement between the two methods Kaplan-Meier event curves for MACE

scholarly journals Elevated expression of FGB predicts poor survival in lung adenocarcinoma patients with tobacco exposure

2019 ◽  
Author(s):  
Xu-gang Hu ◽  
De-min Jiao ◽  
You-liang Si ◽  
Jun Chen ◽  
Xia-li Tang ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Lung Adenocarcinoma ◽  
Prognostic Value ◽  
Cox Regression ◽  
Normal Lung ◽  
Tobacco Exposure ◽  
Survival Analyses ◽  
Cox Regression Analysis ◽  
Elevated Expression ◽  
Km Plotter

Abstract Background: Tobacco exposure is the most important risk factor for the occurrence and death of lung cancer. Fibrinogen beta chain (FGB), the most abundant coagulation factor in plasma, is putatively involved in tumor progression. This study aimed to evaluate the expression pattern and prognostic value of FGB in lung adenocarcinoma with tobacco exposure. Methods: FGB expression in lung adenocarcinoma (LUAD) and corresponding normal lung tissues was compared in The Cancer Genome Atlas (TCGA) database. Stratified analysis was conducted to investigate the expression of FGB in LUAD patients with different tobacco exposure. Kaplan-Meier analysis and Cox-regression analysis were performed to evaluate the prognostic significance of FGB. The same survival analyses were conducted in the KM plotter database to validate the prognostic value of FGB. Results: FGB expression was significantly increased in LUAD tissues than in normal tissues (P<0.001). The FGB expression in smoker group was higher than those in non-smoker group (P<0.001). High FGB expression was associated with advanced N stage (P=0.033) and TNM stage (P=0.046). The smoker group possessed higher level of FGB both in LUAD patients without (P=0.003) or (P =0.045) with lymph node metastasis. However, in early TNM stages, the smoker group showed elevated expression of FGB compared with non-smoker group (P=0.0004), and in advanced TNM stages, there was no significant difference between the two groups (P=0.350). In survival analyses, patients with high FGB expression had remarkably worse overall survival (P=0.007) and progression-free survival ((P=0.007) than those with low FGB expression. In smoker group, high level of FGB expression predicted worse OS (P=0.003) and PFS (P=0.029). Cox-regression analysis indicated that FGB was an independent prognostic factor for LUAD patients’ OS (HR= 1.616, P=0.017) and PFS (HR= 1.710, P=0.028). In smoking group, FGB also served as a promising prognostic biomarker for OS (HR= 1.806, P=0.027) and PFS (HR= 2.181, P=0.013). Similar survival curves were generated in the KM plotter cohort. Conclusions: Our study demonstrated that elevated expression of FGB may identify an aggressive subgroup in LUAD with tobacco exposure and serve as an independent prognostic indicator in these patients.

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