scholarly journals Assessment of the Progression Risk of Chronic Lymphocytic Leukemia

2019 ◽  
pp. 38-43
Author(s):  
D. V. Kravchenko ◽  
Yu. I. Yarets ◽  
V. N. Martinkov ◽  
A. E. Silin ◽  
A. I. Svirnovsky
Keyword(s):  
Risk Assessment ◽  
Chronic Lymphocytic Leukemia ◽  
Disease Progression ◽  
Risk Group ◽  
Lymphocytic Leukemia ◽  
Low Risk ◽  
Assessment Model ◽  
Laboratory Parameters ◽  
Β2 Microglobulin ◽  
Progression Risk

Objective: to identify the interconnection of laboratory parameters with different courses of chronic lymphocytic leukemia (CLL) and to develop a comprehensive model for the assessment of the risk of the disease progression. Material and methods. The study included 127 patients with CLL whose laboratory parameters were evaluated (general and biochemical blood tests, β2-microglobulin, thymidinekinase, tissue polypeptide antigen (TPA), immunophenotypic markers, and also NOTCH1 gene mutations). Results. For the prediction of the course of the disease the most informative were such markers as β2-microglobulin, thymidinekinase, ZAP-70, CD38, and TPA. Based on the obtained data, a model of the risk assessment for CLL progression with high sensitivity and specificity was developed. The progressive-free survival (PFS) was evaluated in two groups of the patients of different risk (low and high) assigned to them according to the prognostic model. In the patients from the low-risk group PFS was determined to be 60 months, and in the high-risk group it was equal to 29.4 months. And it was found out that the patients without progression at the time of inclusion in the study with the presence of mutations of the NOTCH1 gene had a shorter PFS in comparison with the patients without mutations, which may indicate a link between the mutations of the NOTCH1 gene and the unfavorable prognosis for the disease progression. Conclusion . The integrated application of the prognostic factors in the form of a CLL progression risk assessment model allows to stratify CLL patients into high and low risk groups and to predict the probability and progression rate at the time of the diagnosis and during the treatment.

scholarly journals Prognostic factors for the progression of chronic lymphocytic leukemia

2020 ◽  
pp. 28-34
Author(s):  
D. V. Kravchenko ◽  
V. N. Martinkov ◽  
J. N. Pugacheva ◽  
Y. I. Yarets ◽  
A. E. Silin ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Chronic Lymphocytic Leukemia ◽  
Lymph Nodes ◽  
Disease Progression ◽  
Thymidine Kinase ◽  
Cox Regression ◽  
Lymphocytic Leukemia ◽  
Laboratory Parameters ◽  
Β2 Microglobulin ◽  
Selection Of

Objective: to determine a complex of the most significant prognostic factors in chronic lymphocytic leukemia (CLL) for the purpose of evaluation of the probability of the disease progression. Material and methods. The study included 127 CLL patients whose clinical and laboratory parameters (sizes of the lymph nodes, liver and spleen, general and biochemical blood tests, β2-microglobulin, thymidine kinase, tissue polypeptide antigen (TPA), immunophenotypic markers) had been evaluated at the setting of the diagnosis. As a result of a dynamic followup, the patients were divided into 2 groups: 71 patients who had been observed in the outpatient setting and had had no signs of CLL progression within 3 years of the followup (group 1), and 56 patients with clinical signs of the disease progression that had manifested themselves after 3 years of the followup (group 2). Results. The study has revealed statistically considerable differences (Mann-Whitney test) between the groups in the size of the lymph nodes, liver and spleen, in the Binet stages, leukocyte count, absolute values of lymphocytes, the counts of red blood cells, hemoglobin and platelets, as well as the levels of β2-microglobulin, thymidine kinase, TPA, and immunophenotypic markers of CD24, ZAP-70, and CD38 in the blood, which indicates the interconnection of the levels of these parameters at the setting of the diagnosis with subsequent rapid CLL progression. According to the results of the use of logistic regression and Cox regression analysis, 10 parameters showing the strongest interconnection between the progression and 3-year progression free survival (PFS) have been selected. The use of the step-by-step selection of variables has made it possible to formulate a qualitative Cox regression equation including 5 main parameters: β2-microglobulin, thymidine kinase, TPA, ZAP-70, and CD38, which is indicative of the possibility to use this combination of the markers to predict CLL progression. Conclusion: The prognostic value of the complex of the laboratory parameters (β2-microglobulin, thymidine kinase, TPA, ZAP-70, and CD38) has been determined to assess the probability of CLL progression at the setting of the diagnosis, which can be used for the determination of the management tactics and selection of the treatment scheme for these patients.

scholarly journals Progression and survival studies in early chronic lymphocytic leukemia

Blood ◽  
1991 ◽  
Vol 78 (4) ◽  
pp. 895-899 ◽  
Author(s):  
S Molica
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Disease Progression ◽  
Function Analysis ◽  
Linear Trend ◽  
Lymphocytic Leukemia ◽  
Clear Cut ◽  
Impact On Survival ◽  
History Of ◽  
Progression Risk ◽  
Survival Studies

To investigate the natural history of stage A chronic lymphocytic leukemia (CLL) we reviewed 84 such patients. Among 74 cases evaluable for disease progression, 22 (29.6%) progressed to more advanced clinical stages (9 to stage B, 13 to stage C); the actuarial estimation of such an event at 4 years was 30% (95% CI: 26.3% to 33.6%). Despite a linear trend toward an increasing risk (r = .92), the hazard function analysis showed a constant pattern of progression, suggesting a lack of correlation of such an event with time (r = .04). Furthermore, disease progression when analyzed as a time-dependent variable had a clear-cut impact on survival (P less than .001). With the aim of identifying a subgroup of patients with low probability of disease progression and death, we applied to our set of patients four different proposals for subclassifying stage A. All methods were similar in terms of sample size, 5-year survival rate, and disease progression risk, suggesting that the choice between different proposals is somewhat arbitrary. Whatever the criteria are for defining “smoldering” CLL, such patients (accounting in the present study for 20.5% of overall series and 46.7% of stage A patients) should not be treated until progression occurs.

scholarly journals Prediction of Outcome in Patients With Chronic Lymphocytic Leukemia Treated With Ibrutinib: Development and Validation of a Four-Factor Prognostic Model

2020 ◽  
pp. JCO.20.00979 ◽  
Author(s):  
Inhye E. Ahn ◽  
Xin Tian ◽  
David Ipe ◽  
Mei Cheng ◽  
Maher Albitar ◽  
...  
Keyword(s):  
High Risk ◽  
Chronic Lymphocytic Leukemia ◽  
Phase Ii ◽  
Prognostic Model ◽  
Risk Group ◽  
Machine Learning Algorithms ◽  
Lymphocytic Leukemia ◽  
Low Risk ◽  
Data Set ◽  
Increased Risk

PURPOSE Randomized trials established the superiority of ibrutinib-based therapy over chemoimmunotherapy in chronic lymphocytic leukemia. Durability of progression-free survival (PFS) with ibrutinib can vary by patient subgroup. Clinical tools for prognostication and risk-stratification are needed. PATIENTS AND METHODS Patients treated with ibrutinib in phase II and III trials provided the discovery data set and were subdivided into discovery and internal validation cohorts. An external validation cohort included 84 patients enrolled in our investigator-initiated phase II trial. Univariable analysis of 18 pretreatment parameters was performed using PFS and overall survival (OS) end-points. Multivariable analysis and machine-learning algorithms identified four factors for a prognostic model that was validated in internal and external cohorts. RESULTS Factors independently associated with inferior PFS and OS were as follows: TP53 aberration, prior treatment, β-2 microglobulin ≥ 5 mg/L, and lactate dehydrogenase > 250 U/L. Each of these four factors contributed one point to a prognostic model that stratified patients into three risk groups: three to four points, high risk; two points, intermediate risk; zero to one point, low risk. The 3-year PFS rates for all 804 patients combined were 47%, 74%, and 87% for the high-, the intermediate-, and the low-risk group, respectively ( P < .0001). The 3-year OS rates were 63%, 83%, and 93%, respectively ( P < .0001). The model remained significant when applied to treatment-naïve and relapsed/refractory cohorts individually. For 84 patients in the external cohort, BTK and PLCG2 mutations were tested cross-sectionally and at progression. The cumulative incidences of mutations were strongly correlated with the model. In the external cohort, Richter’s transformation occurred in 17% of the high-risk group, and in no patient in the low-risk group. CONCLUSION Patients at increased risk of ibrutinib failure can be identified at treatment initiation and considered for clinical trials.

scholarly journals Progression and survival studies in early chronic lymphocytic leukemia

Blood ◽  
1991 ◽  
Vol 78 (4) ◽  
pp. 895-899 ◽  
Author(s):  
S Molica
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Disease Progression ◽  
Function Analysis ◽  
Linear Trend ◽  
Lymphocytic Leukemia ◽  
Clear Cut ◽  
Impact On Survival ◽  
History Of ◽  
Progression Risk ◽  
Survival Studies

Abstract To investigate the natural history of stage A chronic lymphocytic leukemia (CLL) we reviewed 84 such patients. Among 74 cases evaluable for disease progression, 22 (29.6%) progressed to more advanced clinical stages (9 to stage B, 13 to stage C); the actuarial estimation of such an event at 4 years was 30% (95% CI: 26.3% to 33.6%). Despite a linear trend toward an increasing risk (r = .92), the hazard function analysis showed a constant pattern of progression, suggesting a lack of correlation of such an event with time (r = .04). Furthermore, disease progression when analyzed as a time-dependent variable had a clear-cut impact on survival (P less than .001). With the aim of identifying a subgroup of patients with low probability of disease progression and death, we applied to our set of patients four different proposals for subclassifying stage A. All methods were similar in terms of sample size, 5-year survival rate, and disease progression risk, suggesting that the choice between different proposals is somewhat arbitrary. Whatever the criteria are for defining “smoldering” CLL, such patients (accounting in the present study for 20.5% of overall series and 46.7% of stage A patients) should not be treated until progression occurs.

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