Unavailability of thymidine kinase does not preclude the use of German comprehensive prognostic index: results of an external validation analysis in early chronic lymphocytic leukemia and comparison with MD Anderson Cancer Center model

2015 ◽  
Vol 96 (1) ◽  
pp. 72-77 ◽  
Author(s):  
Stefano Molica ◽  
Diana Giannarelli ◽  
Rosanna Mirabelli ◽  
Luciano Levato ◽  
Antonio Russo ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Thymidine Kinase ◽  
External Validation ◽  
Prognostic Index ◽  
Lymphocytic Leukemia ◽  
Cancer Center ◽  
Md Anderson

scholarly journals The International Prognostic Index for Patients with Chronic Lymphocytic Leukemia Has the Higher Value in Predicting Overall Outcome Compared with the Barcelona-Brno Biomarkers Only Prognostic Model and the MD Anderson Cancer Center Prognostic Index

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Carolina Muñoz-Novas ◽  
María Poza-Santaella ◽  
Isabel González-Gascón y Marín ◽  
María Hernández-Sánchez ◽  
Ana-Eugenia Rodríguez-Vicente ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Prognostic Model ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Lymphocytic Leukemia ◽  
Cancer Center ◽  
Higher Power ◽  
Md Anderson ◽  
The One

In recent years, new prognostic indexes (PIs) for chronic lymphocytic leukemia (CLL), which include clinical, biological, and genetic variables, have been validated, highlighting the MD Anderson Cancer Center prognostic index (MDACC PI), the CLL-international prognostic index (CLL-IPI), and the Barcelona-Brno biomarkers only prognostic model. The aim of this study is to compare the utility of these PIs in a cohort of Spanish patients. A retrospective analysis of 696 unselected CLL patients newly diagnosed and previously untreated from different Spanish institutions was performed. The MDACC PI, the CLL-IPI, and the biomarkers only PI were applied to these patients, and a comparison of the three PIs was performed. With a median follow-up time of 46 months, 394 patients were alive and 187 had received treatment. The median overall survival (OS) was 173 months and the median time to first therapy (TTFT) was 32 months. Significant differences were obtained in OS and TTFT for all subgroups when applying these PIs, with the CLL-IPI being the one with the higherc-index (0.676 for OS and 0.757 for TTFT). The three PIs were able to discriminate patients in different prognostic subgroups. In our cohort, the CLL-IPI showed higher power in predicting TTFT and OS.

scholarly journals Comparative analysis of international prognostic index for chronic lymphocytic leukemia, progression-risk score, and MD Anderson Cancer Center 2011 score - a single center experience

2021 ◽  
pp. 47-47
Author(s):  
Biljana Mihaljevic ◽  
Vojin Vukovic ◽  
Natasa Milic ◽  
Teodora Karan-Djurasevic ◽  
Natasa Tosic ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Risk Score ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Lymphocytic Leukemia ◽  
Prognostic Models ◽  
Risk Scores ◽  
Cancer Center ◽  
Progression Risk ◽  
Md Anderson

Introduction/Objective. Prognostication of chronic lymphocytic leukemia (CLL) has been substantially improved in recent times. Among several prognostic models (PMs) focused on the prediction of time to first treatment (TTFT), Progression-Risk Score (PRS) and MD Anderson Cancer Center score 2011 (MDACC 2011) are the most relevant, while CLL-International Prognostic Index (CLL-IPI), although originally developed to predict overall survival (OS), is also being used to estimate TTFT. The aim of this study was to investigate CLL-IPI, PRS, and MDACC 2011 prognostic values regarding TTFT and OS. Methods. The analyzed cohort included 57 unselected Serbian CLL patients from a single institution, with the basic characteristics reflecting more aggressive disease than in general de novo CLL population. The eligible patients were assigned with investigated PMs, and TTFT and OS analyses were performed. Results. Patients with higher risk scores according to CLL-IPI, PRS, and MDACC 2011 underwent treatment significantly earlier than patients with lower risk scores (p = 0.002, p = 0.019, and p<0.001, respectively). In multivariate analysis, MDACC 2011 and CLL-IPI retained their significance regarding TTFT (p = 0.001 and p = 0.018, respectively), while PRS did not. CLL-IPI was the only significant predictor of OS both at the univariate (p = 0.005) and multivariate (p = 0.013) levels. Conclusion. CLL-IPI, PRS, and particularly MDACC 2011 are able to predict TTFT even in cohorts with more advanced-disease patients, while for prediction of OS, CLL-IPI is the only applicable among the three PMs. These results imply that prognostic models should be investigated in more diverse CLL populations, as it is in real-life setting.

scholarly journals Exclusion of SERUM Thymidine Kinase Does NOT Reduce the Predictive VALUE of a Comprehensive Prognostic INDEX in Chonic Lymphocytic Leukemia. Results of an External Validation on a Prospective Cohort of Patients with EARLY Disease

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4692-4692
Author(s):  
Stefano Molica ◽  
Diana Giannarelli ◽  
Luciano Levato ◽  
Mirabelli Rosanna ◽  
Massimo Gentile ◽  
...  
Keyword(s):  
Thymidine Kinase ◽  
Predictive Value ◽  
Conflicts Of Interest ◽  
External Validation ◽  
Prognostic Index ◽  
Lymphocytic Leukemia ◽  
C Statistic ◽  
Mutational Status ◽  
Significant Difference ◽  
German Model

Abstract A comprehensive prognostic index that includes clinical (i.e., age, sex, ECOG performance status), serum (i.e., B2-microglobulin, thymidine kinase) and molecular (i.e., IGVH mutational status, del 17p, del 11q) markers with independent prognostic value and combines them into a single risk score was recently developed by the German CLL Study Group (GCLLSG). We sought to externally validate this novel score in an independent, community-based cohort consisting of 338 patients with early chronic lymphocytic leukemia (CLL) who were registered on a prospective basis during 2006 to 2010 on an observational Italian database (O-CLL1 protocol; clinicaltrial. gov identifier NCT00917540). Because serum thymidine kinase was not available a slightly modified version of the German model based on 6 instead of 7 prognostic variables was used. According to clinical caracteristics of our patients (i.e., all with Binet stage A disease), a point score higher than 5, necessary for inclusion in the high-risk group, was found only in 2 cases. By German prognostic index, 62.9% of patients were scored as having low-risk CLL (score 0-2) whereas 37.1% had intermediate-risk CLL (score 3-5). This stratification translated into a significant difference in the time to first treatment (TTFT). In other words, the higher the score risk the shorter the TTFT [HR = 4.21; 95% C.I. (2.71-6.53) P<0.0001; (Fig 1)]. Interestingly, the prognostic index category remained a predictor of TTFT also when the analysis was restricted to 262 patients with Rai stage 0 disease [HR= 3.12; 95% C.I. (1.84-5.31);P <0.0001] The model proposed in 2007 by investigators at MD Anderson Cancer Center (MDACC) and barely based on traditional clinical parameters (i.e., age, gender, Rai substage, absolute lymphocyte count, number of involved nodal groups and B2-microglobulin) worked in predicting the TTFT [HR = 2,73; 95% C.I. (1.79-4.17); P<0.0001] in our patient cohort. In comparison to the MDACC score the German model provided similar results in terms of sensitivity (German score, 67%; MDACC score, 58.2; P = 0.28). However, both specificity (74% vs 65.4%; P=0.05) and accuracy (72.1% vs 63.5%; P=0.02) were significantly better with the German score. In order to investigate which prognostic model (i.e. German or MDACC score) provided a more accurate prediction of TTFT, a C-statistic analysis, considered a measure of concordance between observed and predicted time-dependent events, was performed. Interestingly, the C-statistic of the German score was 0.71 (range, 0.60-0.82), a value higher than c-statistic observed with MDACC score (c=0.65; range,0.53-0.78). In conclusion, we demonstrated that the German score works in predicting the TTFT of patients with early CLL also when a modified version which does not include serum thymidine kinase is utilized. These changes affected only partially the predictive value of model because C-statistic remained above 0.70, which is considered a necessary threshold of utility at the individual patient level. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Multivariable Model for Time to First Treatment in Patients With Chronic Lymphocytic Leukemia

2011 ◽  
Vol 29 (31) ◽  
pp. 4088-4095 ◽  
Author(s):  
William G. Wierda ◽  
Susan O'Brien ◽  
Xuemei Wang ◽  
Stefan Faderl ◽  
Alessandra Ferrajoli ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Chronic Lymphocytic Leukemia ◽  
Multivariable Analysis ◽  
Lymphocytic Leukemia ◽  
Cancer Center ◽  
Serum Lactate Dehydrogenase ◽  
Multivariable Model ◽  
Cervical Lymph Nodes ◽  
Mutation Status ◽  
Time To First Treatment

Purpose The clinical course for patients with chronic lymphocytic leukemia (CLL) is diverse; some patients have indolent disease, never needing treatment, whereas others have aggressive disease requiring early treatment. We continue to use criteria for active disease to initiate therapy. Multivariable analysis was performed to identify prognostic factors independently associated with time to first treatment for patients with CLL. Patients and Methods Traditional laboratory, clinical prognostic, and newer prognostic factors such as fluorescent in situ hybridization (FISH), IGHV mutation status, and ZAP-70 expression evaluated at first patient visit to MD Anderson Cancer Center were correlated by multivariable analysis with time to first treatment. This multivariable model was used to develop a nomogram—a weighted tool to calculate 2- and 4-year probability of treatment and estimate median time to first treatment. Results There were 930 previously untreated patients who had traditional and new prognostic factors evaluated; they did not have active CLL requiring initiation of treatment within 3 months of first visit and were observed for time to first treatment. The following were independently associated with shorter time to first treatment: three involved lymph node sites, increased size of cervical lymph nodes, presence of 17p deletion or 11q deletion by FISH, increased serum lactate dehydrogenase, and unmutated IGHV mutation status. Conclusion We developed a multivariable model that incorporates traditional and newer prognostic factors to identify patients at high risk for progression to treatment. This model may be useful to identify patients for early interventional trials.

scholarly journals High Serum Thymidine Kinase 1 Level Predicts Poorer Survival in Patients With Chronic Lymphocytic Leukemia

2010 ◽  
Vol 134 (3) ◽  
pp. 472-477 ◽  
Author(s):  
Sergej N. Konoplev ◽  
Herbert A. Fritsche ◽  
Susan O’Brien ◽  
William G. Wierda ◽  
Michael J. Keating ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Thymidine Kinase ◽  
High Serum ◽  
Lymphocytic Leukemia ◽  
Thymidine Kinase 1 ◽  
Serum Thymidine Kinase 1

scholarly journals Prognostic significance of immunoglobulin phenotype in B cell chronic lymphocytic leukemia

Blood ◽  
1985 ◽  
Vol 65 (2) ◽  
pp. 340-344 ◽  
Author(s):  
L Baldini ◽  
R Mozzana ◽  
A Cortelezzi ◽  
A Neri ◽  
F Radaelli ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Clinical Stage ◽  
Prognostic Significance ◽  
Prognostic Index ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Clinical Prognosis ◽  
Delta Type ◽  
Cell Chronic Lymphocytic Leukemia

Abstract Seventy-six consecutive untreated patients with B cell chronic lymphocytic leukemia (B-CLL) and classified according to Binet's staging system were studied at the clinical presentation. Several immunologic parameters (number of total and T circulating lymphocytes and their surface membrane immunoglobulin [Smlg] phenotypes and levels of serum Ig) were evaluated with the aim of identifying a biologic marker of prognostic relevance. In this series of persons, Binet staging confirmed its usefulness as a prognostic index (P less than .001). With regard to Smlg, they were mu-type in 41 cases (53.9%), mu- type plus delta-type in 29 cases (38.2%), alpha-type in one case, and not detectable in five cases. No correlations were found between clinical stage and immunoglobulin phenotype, although all but one patient in stage C showed mu-type Smlg alone. On analyzing the survival curves of our patients according to different Smlg phenotypes, we found that patients with only mu-type Smlg had a poorer prognosis (P less than .05) than those with mu-type plus delta-type; this difference was even more significant (P less than .01) in patients in stage A, whereas there were no statistical differences in those in stages B and C. Because the appearance of surface heavy chain of delta-type could be an expression of cell maturation, these results suggest that in B-CLL the presence of phenotypically more mature leukemic cells may correlate with better clinical prognosis, particularly in the early phase of the disease.

scholarly journals Prognostic impact of prevalent chronic lymphocytic leukemia stereotyped subsets: analysis within prospective clinical trials of the German CLL Study Group (GCLLSG)

Haematologica ◽  
2019 ◽  
Vol 105 (11) ◽  
pp. 2598-2607 ◽  
Author(s):  
Sonia Jaramillo ◽  
Andreas Agathangelidis ◽  
Christof Schneider ◽  
Jasmin Bahlo ◽  
Sandra Robrecht ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Chronic Lymphocytic Leukemia ◽  
Early Stage ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
Prognostic Impact ◽  
Advanced Stage ◽  
Multicenter Clinical Trials

Almost one-third of all patients with chronic lymphocytic leukemia (CLL) express stereotyped B cell receptor immunoglobulins (BcR IG) and can be assigned to distinct subsets, each with a particular BcR IG. The largest stereotyped subsets are #1, #2, #4 and #8, associated with specific clinicobiological characteristics and outcomes in retrospective studies. We assessed the associations and prognostic value of these BcR IG in prospective multicenter clinical trials reflective of two different clinical situations: i) early-stage patients (watch-and-wait arm of the CLL1 trial) (n=592); ii) patients in need of treatment, enrolled in 3 phase III trials (CLL8, CLL10, CLL11), treated with different chemo-immunotherapies (n=1861). Subset #1 was associated with del(11q), higher CLL international prognostic index (CLL-IPI) scores and similar clinical course to CLL with unmutated immunoglobulin heavy variable (IGHV) genes (U-CLL) in both early and advanced stage groups. IGHV-mutated (M-CLL) subset #2 cases had shorter time-to-first-treatment (TTFT) versus other M-CLL cases in the early-stage cohort (HR: 4.2, CI: 2-8.6, p<0.001), and shorter time-to-next-treatment (TTNT) in the advanced-stage cohort (HR: 2, CI: 1.2-3.3, p=0.005). M-CLL subset #4 was associated with lower CLL-IPI scores and younger age at diagnosis; in both cohorts, these patients showed a trend towards better outcomes versus other M-CLL. U-CLL subset #8 was associated with trisomy 12. Overall, this study shows that major stereotyped subsets have distinctive characteristics. For the first time in prospective multicenter clinical trials, subset # 2 appeared as an independent prognostic factor for earlier TTFT and TTNT and should be proposed for risk stratification of patients.

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