High expression of nucleoside transporter hENT1 predicts a worse event-free survival in relapsed/refractory Hodgkin lymphoma patients treated with gemcitabine, vinorelbine, and liposomal doxorubicin—A CALGB 59804 correlative study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7581-7581
Author(s):  
R. Lai ◽  
E. D. Hsi ◽  
J. Mackey ◽  
S. Jung ◽  
J. L. Johnson ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Liposomal Doxorubicin ◽  
Cox Regression ◽  
Nucleoside Analogs ◽  
Hazard Ratio ◽  
High Expression ◽  
Event Free Survival ◽  
Fixed Tissue ◽  
Free Survival ◽  
Cox Regression Analysis

7581 Background: CALGB 59804 was a phase I/II trial of gemcitabine, vinorelbine, and liposomal doxorubicin (GVD) for pts with relapsed Hodgkin lymphoma (HL). Overall response rate (RR) was 70% (manuscript in review). Plasma membrane nucleoside transporters such as hENT1 are important in transporting nucleoside analogs into cells to exert their pharmacologic effects. We hypothesized high hENT1 expression would predict better RR and outcome in pts treated with GVD. Methods: 58 of 91 pts enrolled in CALGB 59804 had sufficient tissue for study; 31 relapse biopsies and 27 initial diagnosis biopsies. Expression of hENT1 was evaluated by immunohistochemistry in formalin fixed tissue and scored independently by two hematopathologists (RL and EH) blinded to the clinical outcomes. Positivity for hENT1 was defined as >25% of Reed-Sternberg (RS) cells expressing hENT1. Expression was correlated with clinical factors, including IPS at relapse, as well as the overall (OS) and event-free survival (EFS). Results: Expression of hENT1 in RS cells was heterogeneous among cases. 28/58 cases (48%) were hENT1-positive. hENT1-expression was not associated with age, gender, stage, IPS (≤2 or >2), or maximum toxicity grade (≤2 or >2). Compared to hENT1-negative pts, hENT1-positive pts were less likely to have complete or partial response (19/30, 63% versus 22/28, 76%, P=0.20, chi square). hENT1 expression was not significantly associated with OS (P=0.18). Univariate log-rank analysis showed hENT1 positivity and IPS >2 correlated significantly with a lower EFS (P=0.05, and P=0.03, respectively). Multivariate Cox regression analysis confirmed that IPS >2 and hENT1 positivity were independent predictors of EFS (Hazard ratio 2.16, 95%CI 1.08–4.35, P=0.03; and Hazard ratio 2.10, 95% CI 1.06–4.19, P=0.03, respectively). P-values are two-sided. Conclusions: Contrary to our hypothesis, there is an inverse relationship between EFS and hENT1 expression in relapsed HL pts treated with GVD. High expression of hENT1 did not identify gemcitabine-sensitive disease, but may identify a biologically aggressive and/or treatment refractory subtype of HL. No significant financial relationships to disclose.

scholarly journals Relationship between Plasma Endocan Level and Clinical Outcome of Chinese Peritoneal Dialysis Patients

2019 ◽  
Vol 44 (5) ◽  
pp. 1259-1270 ◽  
Author(s):  
Peter Yam-Kau Poon ◽  
Jack Kit-Chung Ng ◽  
Winston Wing-Shing Fung ◽  
Kai-Ming Chow ◽  
Bonnie Ching-Ha Kwan ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Clinical Outcome ◽  
Cardiovascular Event ◽  
Cox Regression ◽  
Event Free Survival ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Reactive Protein ◽  
Inflammatory Conditions ◽  
Serum Crp

Background: Endocan is associated with endothelial dysfunction. In peritoneal dialysis (PD) patients, cardiovascular disease is a common cause of mortality. We examined the relationship between serum endocan level and clinical outcome of PD patients. Methods: We recruited 193 new PD patients (118 males, mean age 58.8 ± 11.6 years). Serum endocan levels were determined and stratified into tertile 1 (lowest) to 3 (highest). Nutritional status, arterial pulse wave velocity (PWV) and serum C-reactive protein (CRP) levels were measured. The patients were followed for at least 4 years for clinical outcomes. Results: For the whole cohort, patients with higher serum endocan levels had lower serum albumin and subjective global assessment score, higher carotid-femoral PWV, and higher serum CRP. For patients with suboptimal blood pressure (BP) control, cardiovascular event-free survival was 95.0, 95.5, and 78.5% for tertiles 1, 2, and 3 at 60 months respectively (p = 0.019). Multivariate Cox regression analysis showed that serum endocan level was an independent predictor of cardiovascular event-free survival. No association with cardiovascular event-free survival was found for patients with adequate BP control (95.0, 92.3, and 100% for tertile 1, 2, and 3 at 60 months, respectively, p = 0.6). Conclusions: Higher serum endocan level is associated with unfavourable nutritional, arterial and inflammatory conditions in PD patients. In patients with suboptimal BP control, higher serum endocan is also associated with worse cardiovascular outcome.

scholarly journals Prognostic roles of microRNA 143 and microRNA 145 in colorectal cancer: A meta-analysis

2019 ◽  
Vol 34 (1) ◽  
pp. 6-14 ◽  
Author(s):  
Chenyao Li ◽  
Guoqiang Yan ◽  
Libin Yin ◽  
Tao Liu ◽  
Chao Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Hazard Ratio ◽  
High Expression ◽  
Cochrane Library ◽  
Event Free Survival ◽  
Free Survival ◽  
High Event ◽  
Low Expression

Background: A systematic analysis was conducted to clarify the relationship between miR-143/145 and the prognosis of colorectal cancer. Materials and methods: We searched four databases: PubMed, EMBASE, Web of Science, and the Cochrane Library. We extracted and estimated the hazard ratios for survival outcomes, which compared low and high expression levels of miR-143/145 in colorectal cancer patients in the available studies. Each individual hazard ratio was used to calculate the pooled hazard ratio. Results: A total of 17 articles including 5128 patients were ultimately included. The results showed that there was no significant difference between low expression and high expression of miR-143 in the overall survival of colon cancer patients. However, low expression of miR-143 was significantly associated with high event-free survival (hazard ratio (HR) 0.6; 95% confidence interval (CI) 0.40, 0.88). Low expression of miR-145 was associated with poor prognosis of patients (HR 1.92; 95% CI 1.45, 2.54); those with low expression of miR-145 were at 1.92-fold higher risk for short-term overall survival than those with high expression of miR-145. MiR-145 was an unfavorable factor for the prognosis of colorectal cancer. There were no significant differences between low expression of miR-145 and high expression of miR-143 in event-free survival. Conclusion: miR-143 and miR-145 have promising prognostic value for colorectal cancer. Low expression of miR-143 can predict high event-free survival, and low expression of miR-145 can predict poor overall survival.

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<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<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<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<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<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 CCT6A, a Novel Prognostic Biomarker for Ewing's Sarcoma

2020 ◽  
Author(s):  
Jie Jiang ◽  
Chong Liu ◽  
Guoyong Xu ◽  
Tuo Liang ◽  
Chaojie Yu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Ewing Sarcoma ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
High Expression ◽  
P Value ◽  
Event Free Survival ◽  
Free Survival ◽  
Cox Regression Analysis

Abstract Background: Ewing's sarcoma (ES) is the second most prevalent malignancy among bone tissue tumors, and there is no adequate prognosis biomarker. The protein encoded by CCT6A is a molecular chaperone. Early studies have suggested that CCT6A is involved in the development of many cancers, however, there is no clear evidence of a role for CCT6A in ES.Methods: In this study, we performed a bioinformatics analysis of 32 Ewing sarcoma specimens from the GSE17618 dataset for differences in gene expression and overall survival, event-free survival, and gene expression in different subgroups. Results: After three screenings, we identified CCT6A as highly correlated with Ewing's sarcoma prognosis. Survival analysis showed low overall survival (OS) for CCT6A high expression (P=0.024). On the other hand, Cox regression analysis showed that CCT6A expression, event-free survival (EFS), and age were strongly associated with the prognosis of Ewing sarcoma, identified as independent poor prognostic biomarkers. (CCT6A: P=0.015; Age: P-value=0.026; EFS: P-value=0.001). Conclusion: The expression level of CCT6A is strongly associated with the prognosis of Ewing's sarcoma. High expression of the CCT6A gene may serve as a biomarker for poor prognosis in patients with Ewing's sarcoma.

scholarly journals Elevated CDK5R1 predicts worse prognosis in hepatocellular carcinoma based on TCGA data

2020 ◽  
Author(s):  
Zhili Zeng ◽  
Zebiao Cao ◽  
Enxin Zhang ◽  
Haifu Huang ◽  
Ying Tang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Regression Analysis ◽  
Cox Regression ◽  
Hazard Ratio ◽  
Gene Set Enrichment Analysis ◽  
High Expression ◽  
Rapid Progression ◽  
Raw Data ◽  
Cox Regression Analysis ◽  
Free Interval

Background: Hepatocellular carcinoma (HCC) is a malignant tumor with rapid progression, high recurrence rate and poor prognosis. The objective of our investigation was to explore the prognostic value of CDK5R1 in HCC. Methods: The raw data of HCC raw data were downloaded from The Cancer Genome Atlas (TCGA) database. The Wilcoxon signed-rank test, Kruskal-Wallis test and logistic regression were applied to investigate the relevance between the CDK5R1 expression and clinicopathologic characteristics in HCC. Kaplan-Meier and Cox regression analysis were employed to examine the association between clinicopathologic features and survival. Gene set enrichment analysis (GSEA) was applied to annotate the biological function of CDK5R1. Results: CDK5R1 was highly expressed in HCC tissues. The high expression of CDK5R1 in HCC tissues was significantly associated with tumor status (P=0.00), new tumor event (P=0.00), clinical stage (P=0.00), topography (P=0.00). Elevated CDK5R1 had significant correlation with worse overall survival (OS) (P=7.414e−04), disease-specific survival (DSS) (P=5.642e−04), disease-free interval (DFI) (P=1.785e−05), and progression-free interval (PFI) (P=2.512e−06). Besides, univariate and multivariate Cox regression analysis uncovered that increased CDK5R1 can independently predict adverse OS (P=0.037, hazard ratio [HR]=1.7 (95% CI [1.0-2.7])), DFI (P=0.007, hazard ratio [HR]=3.0 (95% CI [1.4-6.7])), PFI (P=0.007, hazard ratio [HR]=2.8 (95% CI [1.3-5.9])). GSEA disclosed that notch signaling pathway and non-small cell lung cancer were prominently enriched in CDK5R1 high expression phenotype. Conclusions: Increased CDK5R1 may act as a promising independent prognostic factor of poor survival in HCC.

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.

Prognostic Significance of Blasts in the Cerebrospinal Fluid Without Pleiocytosis or a Traumatic Lumbar Puncture in Children With Acute Lymphoblastic Leukemia: Experience of the Dutch Childhood Oncology Group

2006 ◽  
Vol 24 (15) ◽  
pp. 2332-2336 ◽  
Author(s):  
D. Maroeska W.M. te Loo ◽  
Willem A. Kamps ◽  
Anna van der Does-van den Berg ◽  
Elisabeth R. van Wering ◽  
Siebold S.N. de Graaf
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lumbar Puncture ◽  
Cox Regression ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Event Free Survival ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Significant Difference

Purpose To determine the significance of blasts in the CSF without pleiocytosis and a traumatic lumbar puncture in children with acute lymphoblastic leukemia (ALL). Patients and Methods We retrospectively studied a cohort of 526 patients treated in accordance with the virtually identical Dutch protocols ALL-7 and ALL-8. Patients were classified into five groups: CNS1, no blasts in the CSF cytospin; CNS2, blasts present in the cytospin, but leukocytes less than 5/μL; CNS3, blasts present and leukocytes more than 5/μL. Patients with a traumatic lumbar puncture (TLP; > 10 erythrocytes/mL) were classified as TLP+ (blasts present in the cytospin) or TLP− (no blasts). Results Median duration of follow-up was 13.2 years (range, 6.9 to 15.5 years). Event-free survival (EFS) was 72.6% (SE, 2.5%) for CNS1 patients (n = 304), 70.3% (SE, 4.7%) for CNS2 patients (n = 111), and 66.7% (SE, 19%) for CNS3 patients (n = 10; no significant difference in EFS between the groups). EFS was 58% (SE, 7.6%) for TLP+ patients (n = 62) and 82% (SE, 5.2%) for TLP− patients (n = 39; P < .01). Cox regression analysis identified TLP+ status as an independent prognostic factor (risk ratio, 3.5; 95% CI, 1.4 to 8.8; P = .007). Cumulative incidence of CNS relapses was 0.05 and 0.07 in CNS1 and CNS2 patients, respectively (not statistically significant). Conclusion In our experience, the presence of a low number of blasts in the CSF without pleiocytosis has no prognostic significance. In contrast, a traumatic lumbar puncture with blasts in the CSF specimen is associated with an inferior outcome.

CCT6A, a novel prognostic biomarker for Ewing's sarcoma

2020 ◽  
Author(s):  
Jie Jiang ◽  
Chong Liu ◽  
Guoyong Xu ◽  
Tuo Liang ◽  
Chaojie Yu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Ewing Sarcoma ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
High Expression ◽  
P Value ◽  
Event Free Survival ◽  
Free Survival ◽  
Cox Regression Analysis

Abstract Background Ewing's sarcoma (ES) is the second most prevalent malignancy among bone tissue tumors, and there is no adequate prognosis biomarker. The protein encoded by CCT6A is a molecular chaperone. Early studies have suggested that CCT6A is involved in the development of many cancers, however, there is no clear evidence of a role for CCT6A in ES. Methods In this study, we performed a bioinformatics analysis of 32 Ewing sarcoma specimens from the GSE17618 dataset for differences in gene expression and overall survival, event-free survival, and gene expression in different subgroups. Results After three screenings, we identified CCT6A as highly correlated with Ewing's sarcoma prognosis. Survival analysis showed low overall survival (OS) for CCT6A high expression (P = 0.024). On the other hand, Cox regression analysis showed that CCT6A expression, event-free survival (EFS), and age were strongly associated with the prognosis of Ewing sarcoma, identified as independent poor prognostic biomarkers. (CCT6A: P = 0.015; Age: P-value = 0.026; EFS: P-value = 0.001). Conclusion The expression level of CCT6A is strongly associated with the prognosis of Ewing's sarcoma. High expression of the CCT6A gene may serve as a biomarker for poor prognosis in patients with Ewing's sarcoma.

The Childhood Hodgkin International Prognostic Score (CHIPS) for Predicting Event Free Survival in Pediatric and Adolescent Hodgkin Lymphoma,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3649-3649 ◽  
Author(s):  
Cindy Schwartz ◽  
Lu Chen ◽  
Louis Constine ◽  
Suzanne Wolden ◽  
Frank G Keller ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Conflicts Of Interest ◽  
Prognostic Score ◽  
Early Response ◽  
Intermediate Risk ◽  
Event Free Survival ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Excellent Outcome ◽  
International Prognostic Score

Abstract Abstract 3649 Purpose: To develop a method for predicting Event Free Survival (EFS) in Hodgkin Lymphoma (HL) using clinical factors known at diagnosis. Background: Although early response as measured by CT and/or PET scan has proven useful in the allocation of patients to therapy (eg. eliminating radiation or augmenting chemotherapy) (D Friedman, ASH 2010), stratification at diagnosis may allow earlier modification of treatment approach. The International Prognostic Score (D. Hasenclever, N Engl J Med, 1998) has been used effectively in adults with advanced stage disease, but includes predictors that may not be applicable to the pediatric and adolescent population. 1721 patients with intermediate risk HL (excludes IA and IIA without bulk disease and IIIB/IVB) were treated on AHOD0031, a Children's Oncology Group study using a dose dense, response based algorithm. 770 patients who were randomized or assigned to receive the same treatment (4 ABVE-PC and IFRT) serve as the basis for this report. Methods: Patients <21 years with intermediate risk HL were eligible for COG AHOD0031. The study evaluated the tailoring of treatment by early response to 2 ABVE-PC. Rapid early response (RER) was a 2-dimensional tumor reduction of >60% after 2 cycles of ABVE-PC. Complete response (CR) was a >80% 2-diminsional reduction by CT, and resolution of nuclear imaging abnormalities. RER who achieved CR after 2 additional ABVE-PC were randomized to +/− 21Gy. Slow early responders (SER) were randomized to +/− DECA in addition to the 4 ABVE-PC/21 Gy. Cox regression analysis was used to evaluate potential predictors of EFS (gender, age, race, stage, mediastinal mass, B symptoms, hemoglobin, sedimentation rate, albumen, histology). Continuous variables were dichotomized by clinical significance or quartiles of the population. Multivariable predictive modeling was performed using univariate predictors with a p<0.25. In instances of collinearity, the most robust variable was used. A stepwise selection algorithm was used to identify predictors with a p<0.15. Results: Four predictors (stage 4, large mediastinal adenopathy, albumen<3.5 and fever) were identified as predictive of adverse EFS. Since the Hazard Ratios were similar, the CHIPS (Childhood Hodgkin IPS) score was devised that gave 1 point for each of the 4 adverse predictors. EFS based on score was found to predict an excellent outcome of nearly 90% for those with CHIPS 0 or 1 (N=589) vs. 78% or 62% for those with CHIPS 2 or 3 respectively (N= 141 and 32). Conclusion: The CHIPS score identifies a subset of patients accounting for 22% of an intermediate risk population who are predicted to have an EFS <80%. Early augmentation of therapy may improve outcome for this cohort. After further validation of this approach in historical cohorts, future studies will evaluate the utility of the CHIPS in additional cohorts of newly diagnosed patients. Disclosures: No relevant conflicts of interest to declare.

Diagnostic Cerebrospinal Fluid Examination in Children With Acute Lymphoblastic Leukemia: Significance of Low Leukocyte Counts With Blasts or Traumatic Lumbar Puncture

2003 ◽  
Vol 21 (2) ◽  
pp. 184-188 ◽  
Author(s):  
Britta Bürger ◽  
Martin Zimmermann ◽  
Georg Mann ◽  
Joachim Kühl ◽  
Lutz Löning ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lumbar Puncture ◽  
Cox Regression ◽  
Lymphoblastic Leukemia ◽  
Cranial Irradiation ◽  
Event Free Survival ◽  
Cns Involvement ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Leukocyte Counts

Purpose: To determine the significance of leukemic blasts or traumatic lumbar puncture (TLP) in diagnostic CSF of children enrolled in the Berlin-Frankfurt-Münster (BFM) Acute Lymphoblastic Leukemia–BFM-95 trial. Patients and Methods: A total of 2,021 patients were retrospectively evaluated according to initial central nervous system (CNS) status. Patients were classified as follows: CNS1 (CNS negative, n = 1,605), CNS2 (≤ 5 WBC/μL CSF with blasts, n = 103), CNS3 (CNS positive, n = 58), TLP+ (TLP with blasts, n = 135), or TLP− (TLP without blasts, n = 111). Patients with CNS2 and TLP+ status were eligible for two additional doses of intrathecal (IT) methotrexate (MTX). CNS3 patients received additional IT MTX and cranial irradiation (18 Gy). Results: CNS2, CNS3, and TLP+ groups contained a higher percentage of patients with unfavorable characteristics. Cox regression analysis identified TLP+ and CNS3 status as prognostically significant (CNS3): risk ratio (RR) = 2.3; 95% confidence interval [CI], 1.4 to 3.6; P = .0005; TLP+: RR = 1.5; 95% CI, 1.02 to 2.2; P = .04. Overall 5-year event-free survival (EFS) is 79%, for CNS1 it is 80%, and for TLP− it is 83%. CNS2 patients have an EFS of 80%, but the cumulative incidence of relapses with CNS involvement is higher compared with CNS1 patients (0.10 v 0.04). TLP+ patients have a significantly reduced EFS (73%, P = .003) because of an increased incidence of CNS relapses. CNS3 patients suffer from more systemic and CNS relapses (EFS 50%). Conclusion: CNS2 patients have the same prognosis as patients with CNS1 status, whereas the EFS of TLP+ patients is inferior to CNS1 but superior to CNS3 patients (P = .001). Both subgroups may have benefitted from additional IT MTX.

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