Risk Stratification of DLBCL Patients According to NCCN-IPI in Our Hospital

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3030-3030
Author(s):  
Yasuhiro Kazuma ◽  
Kazunari Aoki ◽  
Yotaro Ochi ◽  
Yusuke Koba ◽  
Yoshimitsu Shimomura ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Multivariate Analysis ◽  
High Risk ◽  
Prognostic Factor ◽  
Risk Group ◽  
Risk Groups ◽  
Gi Tract ◽  
Extranodal Involvement ◽  
Ann Arbor ◽  
Risk Patients

Abstract Title Risk stratification of DLBCL patients according to NCCN-IPI in our hospital Background Recently, a robust prognostic tool termed enhanced International Prognostic Index (NCCN-IPI) for the rituximab era was reported. The aim of this study was to assess the usefulness of NCCN-IPI in risk discrimination and its suitability in clinical applications. Patients and Methods We retrospectively analyzed consecutive patients with de novo diffuse large B cell lymphoma (DLBCL) who were diagnosed and treated with R-CHOP or CHOP-like regimens between January 2004 and December 2013. Patients were required to be cancer-free for 5 years before diagnosis and had to have no prior documented history of indolent lymphoma. We stratified DLBCL patients using IPI and NCCN-IPI, and estimated overall survival (OS) in each risk group. The unadjusted probabilities of OS were estimated using the Kaplan-Meier(K-M) method. The log-lank test and multivariate Cox regression analysis were used to assess the prognostic values of each clinical variable. Results Three-hundred and seventy one patients were identified. The median age was 69 (20–93) years. The median follow-up time was 41 months. The numbers of patients with NCCN-IPI-defined low (L), low-intermediate (L-I), high-intermediate (H-I), and high (H) risk were 35 (9.4%), 125 (33%), 139 (37%), and 72(19%), respectively. The 3-year OS in each risk group was 93%, 89%, 70%, and 52%, respectively. NCCN-IPI was better for the discrimination of low- and high-risk groups (3-year OS, 93% vs 52%) than IPI (3-year OS, 87% vs 56%), and NCCN-IPI gave a better concordance index than IPI (c-Harrel = 0.678 vs 0.665). However, the discriminating power of NCCN-IPI was not as good as previously reported. In the multivariate analysis using the five independent variables of NCCN-IPI as covariates, age was not a significant factor in the <40, 40-60, and 61-75 age groups, and LDH ratio was not a significant factor between≤1 and >1-3 groups. Ann Arbor stage was not a significant factor either. Next, we examined extranodal involvement, which was a significant prognostic factor (HR, 2.3; p<0.001). Multivariate analysis, using age, LDH, performance status, stage, and extranodal involvement in major organs as covariates, lung (HR, 3.5; p<0.001) and bone marrow (HR, 1.8; p=0.048) involvement were significantly poor prognostic factors, and CNS (HR, 2.5; p=0.066) or GI tract (HR, 1.4; p=0.13) involvement adversely affected OS, although they were not significant factors. In contrast, liver involvement did not affect OS (HR, 0.87; p=0.70). We simplified the NCCN-IPI method by using a maximum of four scoring points for age (>75, 1pt), LDH ratio (>3, 1pt), extranodal disease (bone marrow, lung, CNS, or GI tract, but not liver, 1pt), and ECOG PS (≥2, 1pt) and not using Ann Arbor stage as a prognostic factor. Four distinct groups were formed based on K-M curves for OS: low (L, 0 pt), low-intermediate (L-I, 1pt), high-intermediate (H-I, 2pt), and high (H, 3-4 pt). Simplified NCCN-IPI better discriminated low- and high-risk groups (3-year OS, 93% vs 34%; c-Harrel = 0.705) than NCCN-IPI. When patient age was compared in each scoring system, high-risk patients were older in the NCCN-IPI (median age, 79 years old) and its simplified version (median age, 79 years old) than in IPI (median age, 72 years old). Conclusion NCCN-IPI showed better discrimination in our cohort than IPI. However, we found that the enhancement in predicting outcomes by including age and LDH was not as useful as previously reported, and stage and liver involvement was not an independent prognostic factor in our cohort. In the rituximab era, Ann Arbor stage is not a useful prognostic factor. Further validation and optimization of cut-off in each variable could improve the NCCN-IPI. The majority of the high risk patients evaluated by both NCCN-IPI and simplified NCCN-IPI were elderly, so innovative therapeutic approaches adjusted for age are required to improve the outcome of the high-risk group. To identify high-risk groups especially among younger patients, a refined scoring system including not only conventional clinical factors but also other factors such as biological markers will be required. Figure 1 Figure 1. Figure 2 Figure 2. Figure 3 Figure 3. Disclosures No relevant conflicts of interest to declare.

scholarly journals P0357VALIDATION OF THE ANCA RENAL RISK SCORE IN A LONDON COHORT: POTENTIAL IMPACT OF TREATMENT ON PREDICTION OUTCOME

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
PEK GHE TAN ◽  
Jennifer O'Brien ◽  
Megan Griffith ◽  
Marie Condon ◽  
Tom Cairns ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Score ◽  
Risk Group ◽  
Risk Groups ◽  
Renal Outcome ◽  
Combination Regimen ◽  
Renal Survival ◽  
Medium Risk ◽  
Risk Patients ◽  
Potential Impact

Abstract Background and Aims A renal risk score was recently developed to predict the risk of progression to end stage kidney disease (ESKD) in patients with ANCA-associated glomerulonephritis (ANCA-GN). The score defines three risk groups, each with distinct renal survival at 36 months: 68% of high-risk patients reaching ESKD, compared to 26% and 0% in the medium- and low-risk groups, respectively. The majority of patients (101/115) used to define the risk score were treated with IV cyclophosphamide and steroids. At our centre, we employ a combined low-dose IV cyclophosphamide, rituximab and oral corticosteroid induction regimen, with or without plasma exchange (PEX) depending on disease severity, for ANCA-GN. A recent cohort study suggested this combination regimen may lead to better renal survival. We thus hypothesized that choice of remission-induction treatment may affect prediction accuracy of the risk tool. We retrospectively test the validity of the ANCA renal risk score in patients with ANCA-GN treated at our centre. Method All patients with newly diagnosed, biopsy-proven ANCA-GN from 2006-19 were identified from local renal histopathology database. Patients with relapsing ANCA-GN, EGPA, other coexisting GN, or missing data on induction therapy or eventual renal outcome were excluded. ANCA-negative pauci-immune GN was included. Baseline demographics, ANCA serology, initial therapy and parameters in the ANCA risk score (including % normal glomeruli, % tubular atrophy and interstitial fibrosis (TAIF), and estimated glomerular filtration rate were collected. All patients were stratified using the risk tool and Kaplan Meier survival analysis was applied to examine the ESKD prediction. Subgroup analysis was then performed for patients who received the combination regimen of cyclophosphamide and rituximab. Results 178 patients with a median follow up of 44 month were included in the analysis. The median age was 62 years and 82 patients (46%) were female. 94(53%) were MPO-ANCA positive, 66(37%) PR3-ANCA positive, 15 (8%) ANCA-negative, and 3 (2%) were double PR3/MPO-ANCA positive. 148 (83%) patients received the combination regimen, and 45 had concurrent PEX. Total of 37 (21%) patients reached ESKD. 29 (78%) of these, developed ESKD within 36 months of initial diagnosis. Using the risk score, 64(36%), 76(43%) and 38(21%) patients were deemed low-, medium- and high-risk, respectively. Very distinct poor renal survival at 36 months was seen in high-risk group (55% reaching ESKD, p&lt;0.01), but was less apparent between low- (95%) and medium-risk (90%)(p=0.052) (Figure1); In the subgroup of patients treated with combination regimen without concurrent PEX, the high-risk subgroup continues to demonstrate poor renal survival at 36 months (60% ESKD), but renal survival between low- and medium-risk group were comparable (0 and 2% respectively, p=0.57) (Figure 2). Conclusion In our cohort, the ANCA Renal Risk Score reliably predicted rapid ESKD progression at 36-month in high-risk patients, but was less accurate for distinguishing patients with low-and medium-risk. The subgroup analysis suggested combined cyclophosphamide and rituximab therapy may have modified long-term renal outcome especially in the medium-risk cohort, influencing the accuracy of the prediction tool. Large multi-centre cohorts are required to further evaluate the potential impact of treatment on predicting outcome.

An Enhanced International Prognostic Index (IPI) for Patients with Diffuse Large B-Cell Lymphoma (DLBCL) in the Rituximab Era Using the National Comprehensive Cancer Network (NCCN) Database.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2656-2656
Author(s):  
Zheng Zhou ◽  
Alfred W. Rademaker ◽  
Leo I. Gordon ◽  
Ann S. LaCasce ◽  
Ann Vanderplas ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
High Risk ◽  
International Prognostic Index ◽  
Model Development ◽  
Prognostic Index ◽  
Risk Groups ◽  
Ratio Test ◽  
Validation Sample ◽  
Gi Tract

Abstract Abstract 2656 Introduction: The International Prognostic Index (IPI) was first developed in 1993 to risk stratify patients with aggressive Non-Hodgkin's lymphoma (NHL) for outcome prediction (Shipp, NEJM, 1993). Since the addition of rituximab to conventional CHOP chemotherapy for the treatment of DLBCL, there have been many efforts to validate the IPI as well as to improve upon the model's capacity to distinguish subgroups with discrete clinical outcomes, especially high-risk patients. Previous studies have focused on adding clinical or biologic prognostic factor(s) to the original model or regrouping the original IPI score (R-IPI; Sehn, Blood, 2007). We, therefore, built anew a modern IPI based solely on clinical factors available in the real world NCCN clinical database. Methods: Using the nationwide population-based NHL lymphoma database from NCCN, patients with newly diagnosed DLBCL enrolled between June 2000 and Dec. 2010 at 7 NCCN cancer centers were included with at least 1 year and up to 5 years of follow-up. Clinical characteristics including age, Ann Arbor stage, ECOG performance status, disease in extranodal sites (including positivity in bone marrow, CNS, liver/GI tract, lung, other sites and spleen), LDH, presence of bulky disease (>10 cm) as well as B symptoms were studied as potential predictors for model development using COX proportional hazards regression. IPI scores were assigned proportionally based on parameter estimates of the statistically significant predictors in the final COX model. Model selection and its comparison to the original IPI model were made based on Akaike Criteria (AIC) and the likelihood ratio test. Categorization of age and LDH was decided by testing the linearity assumption and Martingale residuals. Kaplan-Meier curves were plotted for stratified risk groups per the new and original IPI. Finally, both IPI models were compared using the initial randomly selected 15% validation sample. Results: There were 1,650 DLBCL patients with complete clinical information included for model development. The new IPI model consisted of similar component predictors but used a maximum of 8 scoring points by further categorizing age group into >40–60 (score of 1), >60–75 (score of 2) and >75 yrs (score of 3), and normalized LDH between >1–3 times (score of 1) and 33 times (score of 2) upper limit of normal. These categorizations minimized the Martingale residuals. Age effect was linear and 20-year increments fit the model best, whereas the effect of normalized LDH was not linear and reached plateau at a ratio of 3. Lymphomatous involvement either of bone marrow, CNS, Liver/GI tract or lung appeared as a stronger predictor (p<0.001) than number of extranodal sites (p=0.91). Four risk groups (Low, Low-intermediate, High-intermediate and High) were identified using the current IPI (Table 1) with enhanced discrimination power when compared with the original IPI and better global model fitting statistics, i.e. smaller AIC and significant likelihood ratio test (p<0.001). It was possible to identify a high risk group (score 3 6) with 5-year overall survival of 33% (95% CI: 22%–45%). Better model prediction was also shown in the validation sample. Conclusions: We were able to develop an enhanced IPI model for clinical prediction among previously untreated DLBCL cases by using patient level data from the NCCN NHL database. The NCCN-IPI demonstrates better risk stratification and identifies a poor risk subgroup with <50% 5-year overall survival in the current real-world clinical setting as compared to the original IPI model developed for aggressive lymphoma prior to the rituximab era. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Absolute Lymphocyte Count As an Independent Prognostic Factor of IPI and NCCN-IPI in DLBCL Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1636-1636 ◽  
Author(s):  
Kazuya Okada ◽  
Shinichi Ochi ◽  
Takashi Nagayama ◽  
Shogo Nabe ◽  
Kazuya Sakai ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
High Risk ◽  
Prognostic Factor ◽  
Lymphocyte Count ◽  
Blood Count ◽  
Absolute Lymphocyte Count ◽  
Independent Prognostic Factor ◽  
White Blood Count ◽  
High Risk Patients ◽  
Risk Patients

Abstract Background: Previous studies have shown that the absolute lymphocyte count (ALC) in peripheral blood at diagnosis may be an independent prognostic factor of IPI for patients with diffuse large B-cell lymphoma (DLBCL). In the rituximab era, the U.S. National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) was developed to improve the risk stratification of DLBCL in comparison to the existing IPI. Therefore, the aim of this study was to clarify the impact of ALC at diagnosis on event free survival (EFS) and overall survival (OS) on analysis performed with factors included in NCCN-IPI. Patients and methods: We retrospectively reviewed the ALC of 413 patients with newly diagnosed DLBCL treated with R-CHOP at our hospital between January 2005 and March 2013. Primary central nervous system lymphoma patients were excluded from this study. ALC was determined in all patients from complete blood count with differential white blood count at the time of diagnosis, and prior to therapy administration. EFS and OS were estimated according to the Kaplan-Meier method. Multivariate analysis was performed with the proportional hazard Cox model. Results: The median ALC was 1.2x10E9/L (range, 0.06-9.0). We set an ALC cut-point at 1.0x10E9/L based on previous studies. The median follow-up duration was 40 months. Baseline characteristics according to ALC (<1.0x10E9/L[n=145] and >1.0x10E9/L[n=268]) are summarized in Table1. Patients with ALC<1.0x10E9/L had a significantly poorer EFS and OS than patients with ALC>1.0x10E9/L (5-year EFS, 37.0% versus 68.9%, p<0.001; 5-year OS, 46.3% versus 80.0%, p<0.001). On multivariate analysis performed with factors included in IPI and NCCN-IPI, ALC remained an independent predictor of EFS (IPI: hazard ratio [HR] 1.95; 95% confidence interval [CI] 1.43-2.68; p<0.001, NCCN-IPI: HR 1.94; 95%CI 1.42-2.65; p<0.001) and OS (IPI: HR 2.35; 95%CI 1.61-3.42; p<0.001, NCCN-IPI: HR 2.29; 95%CI 1.57-3.33; p<0.001) (Table2). Importantly, within the poor R-IPI group, ALC distinguished patients with different 5-year EFS (24.4% versus 50.4%, p<0.001) and OS (35.7% versus 65.7%, p<0.001). For the high NCCN-IPI group also, ALC distinguished patients with different 5-year EFS (14.8% versus 39.8%, p<0.01) and OS (17.5% versus 54.5%, p<0.001) (Figure1). Conclusions: According to our results, ALC<1.0x10E9/L is an adverse prognostic factor and independent of IPI and NCCN-IPI. ALC might be more successful in identifying high-risk patients in which IPI and NCCN-IPI analysis was unrevealing. Our results suggest that other therapeutic strategies may be more effective in high-risk patients with DLBCL. Disclosures No relevant conflicts of interest to declare.

scholarly journals A Ferroptosis and Pyroptosis Molecular Subtype-Related Signature Applicable for Prognosis and Immune Microenvironment Estimation in Hepatocellular Carcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Junyu Huo ◽  
Jinzhen Cai ◽  
Ge Guan ◽  
Huan Liu ◽  
Liqun Wu
Keyword(s):  
High Risk ◽  
Risk Score ◽  
Risk Group ◽  
Molecular Subtype ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
Type I ◽  
Immune Microenvironment ◽  
Risk Patients

Background: Due to the heterogeneity of tumors and the complexity of the immune microenvironment, the specific role of ferroptosis and pyroptosis in hepatocellular carcinoma (HCC) is not fully understood, especially its impact on prognosis.Methods: The training set (n = 609, merged by TCGA and GSE14520) was clustered into three subtypes (C1, C2, and C3) based on the prognosis-related genes associated with ferroptosis and pyroptosis. The intersecting differentially expressed genes (DEGs) among C1, C2, and C3 were used in univariate Cox and LASSO penalized Cox regression analysis for the construction of the risk score. The median risk score served as the unified cutoff to divide patients into high- and low-risk groups.Results: Internal (TCGA, n = 370; GSE14520, n = 239) and external validation (ICGC, n = 231) suggested that the 12-gene risk score had high accuracy in predicting the OS, DSS, DFS, PFS, and RFS of HCC. As an independent prognostic indicator, the risk score could be applicable for patients with different clinical features tested by subgroup (n = 26) survival analysis. In the high-risk patients with a lower infiltration abundance of activated B cells, activated CD8 T cells, eosinophils, and type I T helper cells and a higher infiltration abundance of immature dendritic cells, the cytolytic activity, HLA, inflammation promotion, and type I IFN response in the high-risk group were weaker. The TP53 mutation rate, TMB, and CSC characteristics in the high-risk group were significantly higher than those in the low-risk group. Low-risk patients have active metabolic activity and a more robust immune response. The high- and low-risk groups differed significantly in histology grade, vascular tumor cell type, AFP, new tumor event after initial treatment, main tumor size, cirrhosis, TNM stage, BCLC stage, and CLIP score.Conclusion: The ferroptosis and pyroptosis molecular subtype-related signature identified and validated in this work is applicable for prognosis prediction, immune microenvironment estimation, stem cell characteristics, and clinical feature assessment in HCC.

scholarly journals Genomic profile of MYCN non-amplified neuroblastoma and potential for immunotherapeutic strategies in neuroblastoma

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Eunjin Lee ◽  
Ji Won Lee ◽  
Boram Lee ◽  
Kyunghee Park ◽  
Joonho Shim ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Risk Groups ◽  
High Risk Group ◽  
Genomic Feature ◽  
High Risk Patients ◽  
Dna Mismatch ◽  
Molecular Stratification ◽  
Recurrent Mutations ◽  
Risk Patients

Abstract Background MYCN amplification is the most important genomic feature in neuroblastoma (NB). However, limited studies have been conducted on the MYCN non-amplified NB including low- and intermediate-risk NB. Here, the genomic characteristics of MYCN non-amplified NB were studied to allow for the identification of biomarkers for molecular stratification. Methods Fifty-eight whole exome sequencing (WES) and forty-eight whole transcriptome sequencing (WTS) samples of MYCN non-amplified NB were analysed. Forty-one patients harboured WES and WTS pairs. Results In the MYCN non-amplified NB WES data, maximum recurrent mutations were found in MUC4 (26%), followed by RBMXL3 (19%), ALB (17%), and MUC16 and SEPD8 (14% each). Two gene fusions, CCDC32-CBX3 (10%) and SAMD5-SASH1 (6%), were recurrent in WTS analysis, and these fusions were detected mostly in non-high-risk patients with ganglioneuroblastoma histology. Analysis of risk-group-specific biomarkers showed that several genes and gene sets were differentially expressed between the risk groups, and some immune-related pathways tended to be activated in the high-risk group. Mutational signatures 6 and 18, which represent DNA mismatch repair associated mutations, were commonly detected in 60% of the patients. In the tumour mutation burden (TMB) analysis, four patients showed high TMB (> 3 mutations/Mb), and had mutations in genes related to either MMR or homologous recombination. Excluding four outlier samples with TMB > 3 Mb, high-risk patients had significantly higher levels of TMB compared with the non-high-risk patients. Conclusions This study provides novel insights into the genomic background of MYCN non-amplified NB. Activation of immune-related pathways in the high-risk group and the results of TMB and mutational signature analyses collectively suggest the need for further investigation to discover potential immunotherapeutic strategies for NB.

Utilization patterns and clinical outcomes of rasburicase administration according to tumor risk stratification

2019 ◽  
Vol 26 (3) ◽  
pp. 529-535 ◽  
Author(s):  
Parisa R Khalighi ◽  
Kylee L Martens ◽  
Andrew A White ◽  
Shan Li ◽  
Emily Silgard ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Tumor Lysis Syndrome ◽  
Kidney Injury ◽  
Risk Groups ◽  
High Risk Group ◽  
Adherence To Guidelines ◽  
Tumor Lysis ◽  
Risk Patients ◽  
Utilization Patterns

Purpose Current guidelines for tumor lysis syndrome management recommend rasburicase for high-risk patients. Adherence to guidelines has not been well studied, and the correlation between uric acid reduction and clinically relevant outcomes, such as acute kidney injury, remains unclear. Our study aims to describe rasburicase utilization patterns and outcomes in cancer patients with varying risks for tumor lysis syndrome. Methods In this retrospective cohort study, we included cancer inpatients who received rasburicase for tumor lysis syndrome management at two affiliated academic hospitals from 2009 to 2015. Patients were classified by tumor lysis syndrome risk categories prior to drug administration. Primary outcomes included acute kidney injury incidence and renal recovery. Secondary outcomes included uric acid nadir, mortality, and hospital length-of-stay. Results Among 164 patients, 42 (26%) had high-, 63 (38%) had intermediate-, and 59 (36%) had low-risk for tumor lysis syndrome. A total of 94 patients (57%) had existing renal dysfunction prior to rasburicase use. This occurred more frequently in low- (68%) compared to intermediate- (57%) and high- (43%) risk patients ( p = 0.044). A greater proportion of patients in the high-risk group (78%) had renal recovery when compared to the intermediate- (61%) or low- (45%) risk groups ( p = 0.056). Despite a similar length of stay, the high-risk group had a significantly lower 30-day mortality (10%) when compared to intermediate- (25%) or low- (32%) risk groups ( p = 0.029). Conclusions Our results suggest that rasburicase may be frequently prescribed to treat hyperuricemia unrelated to tumor lysis syndrome in cancer patients. Improved education and adherence to guidelines may improve clinical and economic outcomes associated with rasburicase administration.

Varying Importance of Prognostic Factors in Subgroups of Myelodysplastic Syndromes Defined by Blast Count, Cytogenetic Risk Group, or WHO Classification.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2776-2776
Author(s):  
Andrea Kuendgen ◽  
Corinna Strupp ◽  
Kathrin Nachtkamp ◽  
Barbara Hildebrandt ◽  
Rainer Haas ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
High Risk ◽  
Research Funding ◽  
Risk Group ◽  
Univariate Analysis ◽  
Risk Groups ◽  
High Risk Group ◽  
Intermediate Risk ◽  
Blast Count

Abstract Abstract 2776 Poster Board II-752 Introduction: We wondered whether prognostic factors have similar relevance in different subpopulations of MDS patients. Methods: Our analysis was based on patients with primary, untreated MDS, including 181 RA, 169 RARS, 649 RCMD, 322 RSCMD, 79 5q-syndromes, 290 RAEB I, 324 RAEB II, 266 CMML I, 64 CMML II, and 209 RAEB-T. The impact of prognostic variables in univariate analysis was compared in subpopulations of patients defined by medullary blast count, namely <5%, ≥5% (table), ≥10%, and ≥20% (not shown), as well as 3 subpopulations defined by the cytogenetic risk groups according to IPSS (table). Multivariate analysis of prognostic factors was performed for cytogenetically defined subgroups and WHO-subtypes. Results: Strong prognostic factors in all blast-defined subgroups were hemoglobin, transfusion dependency, increased WBC, age, and LDH. However, all variables became less important in patients with ≥20% blasts (RAEB-T) and increased WBC was rare. Platelet count and cytogenetic risk groups were relevant in patients with <5%, ≥5%, and ≥10% marrow blasts, but not in RAEB-T. Marrow fibrosis was important in patients with <5% or ≥5% blasts, but not ≥10%. Gender and ANC <1000/μl were significant only in patients with a normal blast count. Furthermore, we looked for the effect of the karyotypes, relevant for IPSS scoring (-Y, del5q, del20q, others, del7q/-7, complex), and found a comparable influence on survival, irrespective whether patients had < or ≥5% marrow blasts. In subpopulations defined by cytogenetic risk groups, several prognostic factors were highly significant in univariate analysis, if patients had a good risk karyotype. These included hemoglobin, sex, age, LDH, increased WBC, transfusion need, and blast count (cut-offs 5%, 10%, and 20%). In the intermediate risk group only LDH, platelets, WBC, and blasts were significant prognostic factors, while in the high risk group only platelets and blast count remained significant. Multivariate analysis was performed for the cytogenetic risk groups and for subgroups defined by WHO subtypes. The analysis considered blast count (</≥5%), hemoglobin, platelets, ANC, cytogenetic risk group, transfusion need, sex, and age. In the subgroup including RA, RARS, and 5q-syndrome, LDH, transfusion, and age in descending order were independent prognostic parameters. In the RCMD+RSCMD group, karyotype, age, transfusion, and platelets were relevant factors. In the RAEB I+II subgroup, the order was hemoglobin, karyotype, age, and platelets, while in CMML I+II only hemoglobin had independent influence. In RAEB-T none of the factors examined was of independent significance. Looking at cytogenetic risk groups, in the favorable group, several variables independently influenced survival, namely transfusion, blasts, age, sex, and LDH (in this order). Interestingly, in the intermediate and high risk group, only blast count and platelets retained a significant impact. Conclusion: Univariate analysis showed prognostic factors (except ANC) included in IPSS and WPSS are relevant in most subgroups defined by marrow blast percentage. However, they all lose their impact if the blast count exceeds 20%. Regarding cytogenetic risk groups, several prognostic factors lose their influence already in the intermediate risk group. This underscores the prognostic importance of MDS cytogenetics. Multivariate analysis showed MDS subpopulations defined by WHO types also differ with regard to prognostic factors. In particular, CMML and RAEB-T stand out against the other MDS types. Disclosures: Kuendgen: Celgene: Honoraria. Hildebrandt:Celgene: Research Funding. Gattermann:Novartis: Honoraria, Participation in Advisory Boards on deferasirox clinical trials. Germing:Novartis, Celgene: Honoraria, Research Funding.

Impact of Stratification of Comorbidities on Nutrition Indices and Survival in Patients on Continuous Ambulatory Peritoneal Dialysis

2009 ◽  
Vol 29 (2_suppl) ◽  
pp. 153-157 ◽  
Author(s):  
Narayan Prasad ◽  
Amit Gupta ◽  
Archana Sinha ◽  
Anurag Singh ◽  
Raj Kumar Sharma ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
High Risk ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Risk Group ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
Comorbid Illness ◽  
Medium Risk ◽  
Risk Patients

Background Case-mix comorbidities and malnutrition influence outcome in continuous ambulatory peritoneal dialysis (CAPD) patients. In the present study, we analyzed the influence of stratified comorbidities on nutrition indices and survival in CAPD patients. Patients and Methods We categorized 373 CAPD patients (197 with and 176 without diabetes) into three risk groups: low—age under 70 years and no comorbid illness; medium—age 70 – 80 years, or any age with 1 comorbid illness, or age under 70 years with diabetes; high—age over 80 years, or any age with 2 comorbid illnesses. We then compared nutrition indices and malnutrition by subjective global assessment (SGA) between the three groups. Survival was compared using Kaplan–Meier survival analysis. Results Mean daily calorie and protein intakes in the low-risk group (21 ± 6.7 Kcal/kg, 0.85 ± 0.28 g/kg) were significantly higher than in the medium- (17.6 ± 5.2 Kcal/kg, 0.79 ± 0.25 g/kg) and high-risk (17.5 ± 6.1 Kcal/kg, 0.78 ± 0.26 g/kg) groups ( p = 0.001 and p = 0.04 respectively). Relative risk (RR) of malnutrition was less in the low-risk group (103/147, 70.06%) than in the medium-risk group [135/162, 83.3%; RR: 2.0; 95% confidence interval (CI): 2.1 to 3.4; p = 0.01] or the high-risk group (54/64, 84.4%; RR: 2.3; 95% CI: 2.1 to 4.9; p = 0.03). Mean survivals of patients in the low-, medium-, and high-risk groups were 51 patient–months (95% CI: 45.6 to 56.4 patient–months), 43.3 patient–months (95% CI: 37.8 to 48.7 patient–months), and 29.7 patient–months (95% CI: 23 to 36.4 patient–months) respectively (log-rank: 35.9 patient–months; p = 0.001). The 1-, 2-, 3-, 4-, and 5-year patient survivals in the low-, medium-, and high-risk groups were 96%, 87%, 79%, 65%, and 56%; 89%, 67%, 54%, 43%, and 34%; and 76%, 48%, 31%, 30%, and 30% respectively. Conclusions Intake of calories and protein was significantly lower in the medium-risk and high-risk groups than in the low-risk group. Survival was significantly better in low-risk patients than in medium- and high-risk patients.

Integrative prognostic risk score in acute myeloid leukemia with normal karyotype

Blood ◽  
2011 ◽  
Vol 117 (17) ◽  
pp. 4561-4568 ◽  
Author(s):  
Frederik Damm ◽  
Michael Heuser ◽  
Michael Morgan ◽  
Katharina Wagner ◽  
Kerstin Görlich ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Risk Score ◽  
Myeloid Leukemia ◽  
Risk Group ◽  
Normal Karyotype ◽  
Risk Groups ◽  
Risk Of Death ◽  
Risk Patients ◽  
Acute Myeloid

Abstract To integrate available clinical and molecular information for cytogenetically normal acute myeloid leukemia (CN-AML) patients into one risk score, 275 CN-AML patients from multicenter treatment trials AML SHG Hannover 0199 and 0295 and 131 patients from HOVON/SAKK protocols as external controls were evaluated for mutations/polymorphisms in NPM1, FLT3, CEBPA, MLL, NRAS, IDH1/2, and WT1. Transcript levels were quantified for BAALC, ERG, EVI1, ID1, MN1, PRAME, and WT1. Integrative prognostic risk score (IPRS) was modeled in 181 patients based on age, white blood cell count, mutation status of NPM1, FLT3-ITD, CEBPA, single nucleotide polymorphism rs16754, and expression levels of BAALC, ERG, MN1, and WT1 to represent low, intermediate, and high risk of death. Complete remission (P = .005), relapse-free survival (RFS, P < .001), and overall survival (OS, P < .001) were significantly different for the 3 risk groups. In 2 independent validation cohorts of 94 and 131 patients, the IPRS predicted different OS (P < .001) and RFS (P < .001). High-risk patients with related donors had longer OS (P = .016) and RFS (P = .026) compared with patients without related donors. In contrast, intermediate-risk group patients with related donors had shorter OS (P = .003) and RFS (P = .05). Donor availability had no impact on outcome of patients in the low-risk group. Thus, the IPRS may improve consolidation treatment stratification in CN-AML patients. Study registered at www.clinicaltrials.gov as #NCT00209833.

scholarly journals Genomic profile of MYCN non-amplified neuroblastoma and potential for immunotherapeutic strategies in neuroblastoma

2020 ◽  
Author(s):  
Eunjin Lee ◽  
Ji Won Lee ◽  
Boram Lee ◽  
Kyunghee Park ◽  
Joonho Shim ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Risk Groups ◽  
High Risk Group ◽  
Genomic Feature ◽  
High Risk Patients ◽  
Dna Mismatch ◽  
Recurrent Mutations ◽  
Whole Transcriptome Sequencing ◽  
Risk Patients

Abstract Background MYCN amplification is the most important genomic feature in neuroblastoma (NB). However, limited studies have been conducted on the MYCN non-amplified NB including low- and intermediate-risk NB. Here, the genomic characteristics of MYCN non-amplified NB were studied to allow for the identification of biomarkers for molecular stratification.Results Fifty-eight whole exome sequencing (WES) and 48 whole transcriptome sequencing (WTS) samples of MYCN non-amplified NB were analysed. Forty-one patients harboured WES and WTS pairs. In the MYCN non-amplified NB WES data, maximum recurrent mutations were found in MUC4 (26%), followed by RBMXL3 (19%), ALB (17%), and MUC16 and SEPD8 (14% each). Two gene fusions, CCDC32-CBX3 (10%) and SAMD5-SASH1 (6%), were recurrent in WTS analysis, and these fusions were detected mostly in non-high-risk patients with ganglioneuroblastoma histology. Analysis of risk-group-specific biomarkers showed that several genes and gene sets were differentially expressed between the risk groups, and some immune-related pathways tended to be activated in the high-risk group. Mutational signatures 6 and 18, which represent DNA mismatch repair (MMR) associated mutations, were commonly detected in 60% of the patients. In the tumour mutation burden (TMB) analysis, four patients showed high TMB (> 3 mutations/Mb), and had mutations in genes related to either MMR or homologous recombination. Excluding four outlier samples with TMB > 3 Mb, high-risk patients had significantly higher levels of TMB compared with the non-high-risk patients.Conclusions This study provides novel insights into the genomic background of MYCN non-amplified NB. Activation of immune-related pathways in the high-risk group and the results of TMB and mutational signature analyses collectively suggest the need for further investigation to discover potential immunotherapeutic strategies for NB.

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