del(17p13.1) in Chronic Lymphocytic Leukemia Confers Poor Prognosis Even at Low Percentage Involvement and Increases Proportionately with Increase in Clonal Involvement.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2073-2073 ◽  
Author(s):  
Leslie A. Andritsos ◽  
Jeffrey Jones ◽  
Gerard Lozanski ◽  
Thomas S. Lin ◽  
Kristie A. Blum ◽  
...  
Keyword(s):  
Overall Survival ◽  
Chronic Lymphocytic Leukemia ◽  
Proportional Hazards ◽  
Chromosomal Abnormalities ◽  
Prognostic Significance ◽  
Continuous Variable ◽  
Cox Proportional Hazards ◽  
Lymphocytic Leukemia ◽  
Fish Analysis ◽  
Time To Progression

Abstract Background: The del(17p13.1) abnormality has been shown to have great prognostic significance in chronic lymphocytic leukemia (CLL), predicting a shorter time to progression and decreased overall survival when compared with other chromosomal abnormalities and a normal karyotype. We sought to assess the significance of low percentage del 17p in untreated patients with CLL. Patients and Methods: Patients with B-cell CLL who had received no prior therapy were eligible for evaluation. At the time of initial visit, baseline variables were collected including patient demographics, Rai stage, peripheral blood immunophenotyping, routine cytogenetic evaluation and FISH analysis (described below), and beta-2-microglobulin. Patients were followed for time to progressing (defined as need for first therapy) and overall survival. Cytogenetic and FISH analyses were performed according to standard laboratory methods. Probes for FISH were D12Z1 (12 centromere), TP53 del(17p13.1), del(11q22.3) and D13S319 del(13q14), (all from Abbott Molecular) and were used according to manufacturer directions. For each sample, 200 nuclei were analyzed per probe, 100 nuclei by each of two analysts. The association between percentage del(17p13.1) and time to progression, defined as time from FISH to initiation of treatment, was explored using Cox proportional hazards regression. For purposes of analysis, percentage del(17p13.1) was alternately considered as both a continuous and dichotomous variable (various cut points at 5% increments). Results: From August 2001 to February 2006, 54 untreated patients with CLL were found on initial evaluation to have del(17p13.1) ≥ 5% of nuclei analyzed. The median age was 61 (range 45–90), with 36 males and 18 females. At the time of initial FISH analysis, 14 patients had Rai stage 0 disease, 22 had Rai stage 1 disease, 10 had Rai stage 2 disease, and 8 had Rai stages 3 or 4 disease. 50 patients were evalualuable for time to progression and overall survival. Considered as a continuous variable, del(17p13.1) percent positive was associated with a significantly increased hazard for shorter time to progression. For each 10% increase in del(17p13.1) percentage, there was a 20% increase in the hazard for shorter time to disease progression [HR 1.20, 95%CI(1.05, 1.37), p=0.007]. Using alternative cutpoints for a positive test, del(17p13.1) percentage was associated with an increased hazard for TTP at all percentages greater than 10, an association that became statistically significant at 25%. Conclusion: del(17p13.1) in CLL predicts for shorter time to first treatment even at lower percentages, with the hazard ratio increasing with increasing percentage. Further study in a larger patient sample is warranted to determine whether del17p should be considered significant even at lower percentages not currently defined as “positive.” Figure Figure

Plasma thrombopoietin compared with immunoglobulin heavy-chain mutation status as a predictor of survival in chronic lymphocytic leukemia

Blood ◽  
2006 ◽  
Vol 108 (3) ◽  
pp. 1001-1006 ◽  
Author(s):  
Charles Koller ◽  
B. Nebiyou Bekele ◽  
Xian Zhou ◽  
Charles Park ◽  
Zeev Estrov ◽  
...  
Keyword(s):  
Overall Survival ◽  
Chronic Lymphocytic Leukemia ◽  
Heavy Chain ◽  
Proportional Hazards ◽  
Variable Region ◽  
Immunoglobulin Heavy Chain ◽  
Cox Proportional Hazards ◽  
Lymphocytic Leukemia ◽  
Mutation Status ◽  
Previously Treated

Abstract We investigated the association of plasma thrombopoietin (TPO) and overall survival in 127 patients with previously treated and previously untreated chronic lymphocytic leukemia (CLL). Higher levels of TPO were associated with advanced Rai stage (P < .001), higher levels of β2-microglobulin (β2-M) (P < .001), and the absence of mutation in the immunoglobulin heavy chain variable region (IgVH) (P < .001), and were inversely correlated with platelet count (P = .002). We found that TPO correlated strongly in a continuous manner with overall survival in both previously treated and untreated patients. The univariate Cox proportional hazard model demonstrated that high TPO levels were associated with shorter survival (P < .001), and multiple variable Cox proportional hazards regression analysis demonstrated that this was independent of the IgVH mutation status, β2-M, and Rai stage. Recursive partitioning showed that a cutoff point of 639 pg/mL separated the CLL patients into 2 major survival groups (P < .001). The effects of β2-M were masked by the effects of TPO in the patients with TPO levels higher than 639 pg/mL, but in the remainder, patients with β2-M level higher than 4.95 mg/L had significantly shorter survival than those with lower values. Plasma TPO and β2-M may be useful for the prediction of clinical behavior in CLL and may replace the need for the determination of IgVH mutation status.

CD23 Receptor Positivity Has No Prognostic Implication in Chronic Lymphocytic Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4397-4397
Author(s):  
Jahan Aghalar ◽  
Charles Chu ◽  
Rajendra N Damle ◽  
Che-Kai Tsao ◽  
Nina Kohn ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Overall Survival ◽  
Chronic Lymphocytic Leukemia ◽  
Prognostic Markers ◽  
Conflicts Of Interest ◽  
Prognostic Significance ◽  
Lymphocytic Leukemia ◽  
Mutation Status ◽  
Percent Positivity ◽  
Cd23 Expression

Abstract Abstract 4397 BACKGROUND Chronic Lymphocytic Leukemia (CLL) phenotypically expresses CD23, although the percentage of positive cells measured by flow cytometry is variable. We sought to analyze whether the percent of CD23 positive cells in the CLL clone correlates with time to treat (TTT), overall survival (OS) and prognostic markers CD38, ZAP-70, and IGHV mutation status. METHODS We retrospectively analyzed the flow cytometry data of 332 CLL patients on the gated population of cells that were CD5 and CD19 positive. Percentage positivity for CD23, CD38, and ZAP-70 was noted. CD38 and ZAP-70 were considered positive at cut-offs of >= 30% and >=20%, respectively. CD23 was considered negative at <30% and positive at >= 30%. IGHV sequence was determined from cDNA and then compared to germline to assess mutation status using IMGT/V-QUEST. The distributions of time from diagnosis until start of treatment and overall survival were stratified by CD23 positivity, estimated using the product limit method, and compared using the log rank test. Those who had expired without treatment or were alive and not treated at this time point were censored in the TTT analysis. Those who were still alive were censored in the OS analysis. Associations of CD23 positivity with IGHV mutation status, ZAP-70, and CD38 positivity were examined using the chi-square test. RESULTS Out of 332 patients, 25 had diminished CD23 expression (<30%) whereas 307 had normal CD23 expression (>30%). There was no difference in time until start of treatment or overall survival based on CD23 %positivity. CD23 %positivity showed no associations with IGHV mutation status, ZAP-70 or CD38 positivity. CONCLUSION CD23 percent positivity has no prognostic significance in CLL. There is no correlation between CD23 percent positivity and poor prognostic markers such as CD38, ZAP-70, or IGHV mutation status. Disclosures: No relevant conflicts of interest to declare.

CD38 Variation in Chronic Lymphocytic Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4576-4576
Author(s):  
Ryan D. Nipp ◽  
J. Brice Weinberg ◽  
Alicia D. Volkheimer ◽  
Evan D. Davis ◽  
Youwei Chen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Proportional Hazards Model ◽  
Prognostic Significance ◽  
Cox Proportional Hazards ◽  
Lymphocytic Leukemia ◽  
Cox Proportional Hazards Model ◽  
Rank Test ◽  
Cd38 Expression ◽  
Log Rank Test ◽  
Maximum Minimum

Abstract Abstract 4576 Background: Chronic lymphocytic leukemia (CLL) has a highly variable clinical course. Some patients require treatment early while others can be monitored without therapy. CD38 expression has been shown in multiple cohorts to have prognostic significance. An elevated percentage of CD38 positive CLL lymphocytes at the time of diagnosis is correlated with a more rapid need for therapy and a shorter overall survival. The extent to which CD38 varies during the course of CLL, including after therapy, has only been evaluated in a limited fashion. Methods: From a cohort of over 500 CLL patients at the Duke University and Durham VA Medical Centers, we selected 136 patients in whom we had measured CD38 expression by flow cytometry on two or more occasions. We determined the first, maximum, minimum, and range (maximum – minimum) CD38 values. We compared these values to other molecular prognostic markers using Wilcoxon tests and assessed the prognostic significance of these values using Cox proportional hazard models and Kaplan-Meier analyses. Results: Of the 136 patients, 70% were male and 88% Caucasian, with a median age of 60. The majority had low clinical stage at diagnosis—either Rai stage 0 (68%) or 1 (19%). Molecular prognostic markers were also generally favorable. Eighty-two (67%) patients had mutated IGHV status, 69 (51%) were ZAP70 negative, and 76 (63%) had either 13q deletion or normal cytogenetics, determined by fluorescent in situ hybridization. CD38 expression was measured a median of 5.5 times (2 – 19). The median time between the first and last CD38 measurements was 1206 days (81 – 4109). The median values were 6% (0.6 – 99) for maximum CD38, 1.5% (0 to 84.5) for minimum CD38, and 4.9% (0.2 to 95.3) for CD38 range. Maximum, minimum, and CD38 range were significantly lower in patients with mutated compared to unmutated IGHV status (p < 0.005 for all parameters, Wilcoxon rank sum test). Elevated maximum and CD38 range were significantly associated with a more rapid time to therapy (TTT) and shorter overall survival (OS) in a univariate Cox proportional hazards model (p < 0.03 for all, Wald test). In a multivariate Cox proportional hazards model including first CD38 and maximum CD38 values, only maximum CD38 remained statistically significant. We found that patients with high CD38 variation (CD38 range greater than the median) had significantly shorter TTT and OS than patients with low CD38 variation (p = 0.002 for both, log rank test). Using receiver operator characteristic analyses, we determined that the best cut-off for dichotomizing the first CD38 according to TTT and OS in the entire Duke/Durham VA CLL cohort was 11%. Using this cut-off, 15 patients (11%) converted from CD38 negative to CD38 positive. Using the standard 30% cut-off, 14 patients (10%) converted from CD38 negative to CD38 positive. Patients with a first CD38 measurement less than 11% and subsequent measurements above 11% had a favorable OS, similar to patients with low CD38 for all measurements (p = 0.002, log rank test). However, patients with a first CD38 measurement less than 30% who had subsequent measurements above 30% had an inferior OS, similar to patients with high CD38 for all measurements (p = 0.006, log rank test). Lastly, among 24 patients with CD38 measurements before and after first therapy, the percentage of CD38 positive cells increased in 19 patients (79%), with a median value of 3.2% before to 6.9% after therapy (p = 0.005, Wilcoxon signed rank test). Conclusions: CD38 values vary as patients transition across the disease trajectory. This variation appears to have prognostic significance, with high variation associated with faster time to first therapy and shorter overall survival. Additionally, in our cohort, a patient's maximum CD38 value had more prognostic significance than a single initial measurement. Thus, longitudinally measuring CD38 throughout the clinical course of CLL could aid in the management of CLL patients, refining the initial prognostic assessment, and improving patient counseling and decision making. Disclosures: No relevant conflicts of interest to declare.

Efficacy and Safety of Frontline Therapy with "FCR" Regimen for Chronic Lymphocytic Leukemia Outside Clinical Trials: Israeli CLL Study Group Experience

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5659-5659 ◽  
Author(s):  
Yair Herishanu ◽  
Neta Goldschmidt ◽  
Osnat Bairey ◽  
Rosa Ruchlemer ◽  
Riva Fineman ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Chronic Lymphocytic Leukemia ◽  
Dose Reduction ◽  
Lymphocytic Leukemia ◽  
Fish Analysis ◽  
Efficacy And Safety ◽  
Reduced Dose ◽  
Binet Stage ◽  
Frontline Therapy

Abstract The combination of fludarabine, cyclophosphamide and rituximab (FCR) is still currently regarded as the standard regimen for treatment of physically fit patients with chronic lymphocytic leukemia (CLL). This therapy can be associated with significant toxicity, and patient adherence to the protocol may often be difficult outside of clinical trials. This retrospective study aimed to evaluate the efficacy and safety of FCR therapy in the “real life” setting, with particular focus on the influence of dose reduction on treatment outcome. A total of 132 CLL patients (≤70 years of age) treated with FCR as frontline therapy from 10 medical centers, were reviewed. The majority of patients were males (73.5%, n=97) and younger than 60 years (78%, n=103). Eleven patients had Binet stage A (8.3%), 72 (54.5%) were stage B and 49 (37.1%) had Binet stage C. Results of FISH analysis were available for 99 patients, with high risk cytogenetics of del(11q) in 21 patients (21.2%) and del(17p) in 9 cases (9.1%). The majority (56.5%, n=74) received rituximab at a dose of 500mg/m2 and the rest 375mg/m2. Almost half of the patients (49.2%, n=65) were given a reduced dose of chemotherapy (<90% of the indicated dosage), while 23% (n=30) received 2/3 or less. Primary chemotherapy dose reduction was most commonly in accordance with the treating physician's judgment, while secondary dose modifications and less chemotherapy cycles were initiated mainly because of hematological toxicity. Most patients had a clinical complete response (69.8%, n=90) while only 10 (7.8%) failed to respond. Partial or non- responders were more commonly associated with lower pretreatment hemoglobin levels and platelet counts, Binet stage C, and presence of del(17p) and had also received lower doses of chemotherapy (p=0.024). The rituximab dose administered was not associated with differences in response rates (p=0.7). Reducing the dose of chemotherapy (≤2/3) was associated with an increase in risk of disease progression (HR 4.1, 95% CI 2.3-7.0, p<0.0001), resulting in a decrease in median progression free survival (PFS) from 46.9 months (for those receiving the full dose), to 15.8 months for patients given a reduced dose. In a multivariate analysis of PFS only a reduced dose of chemotherapy (≤2/3) and del(17) retained statistical significance, p=0.004 and p<0.0001, respectively. The median overall survival for the entire cohort was 99.5 months (95% CI 78.5-120.5). Del(17p) and failure to respond to treatment were independently associated with a worse overall survival (HR=9.2, 95% CI 2.0-41.8, p=0.004 and HR=15.1, 95% CI 3.2-72.0, p-0.001, respectively). The most commonly recorded severe adverse events included, at least one episode of infection or neutropenia in 25.8% and 24.2% of patients, respectively. Treatment related DAT+ autoimmune hemolysis occurred in 6.0% of the cases, late-onset neutropenia in 8.1%, Richter's transformation in 3% and therapy related MDS/AML in 2.3% of patients. In conclusion, it is apparent that outside of clinical trials treating physicians tend more readily to reduce doses of chemotherapy. Reduced doses of fludarabine and cyclophosphamide but not of rituximab, is significantly associated with a shorter PFS. Disclosures No relevant conflicts of interest to declare.

Prognostic relevance of neutrophil to lymphocyte ratio (NLR) before anti-PD1 therapy in metastatic melanoma patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21045-e21045
Author(s):  
Daniel Vilarim Araujo ◽  
Rafael Vanin de Moraes ◽  
Victor Aurelio Ramos Sousa ◽  
Mauro Daniel Spina Donadio ◽  
Aline Fusco Fares ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Metastatic Melanoma ◽  
Proportional Hazards ◽  
Checkpoint Inhibitors ◽  
Prognostic Significance ◽  
Multivariable Analysis ◽  
Continuous Variable ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Melanoma Patients

e21045 Background: Biomarkers to select the patients most likely to benefit from checkpoint inhibitors are urged. NLR is a simple way of measuring systemic inflammation and is an independent predictor of survival before Anti-CTLA4 therapy. We hypothesized if NLR is also a predictor of survival before Anti-PD1 therapy. Methods: We performed a retrospective review of the medical records of all consecutive metastatic melanoma patients who received Nivolumab treatment from January/2014 – February/2017, including 53 patients prospectively collected from an Expanded Access Program. Of 86 patients, 83 patients were included for demographic and efficacy analysis, and 74 had information about baseline pre-treatment NLR. We analyzed NLR as a continuous variable and categorised ≥ 5 vs. < 5. Kaplan-Meier method was used for survival analysis. Long-rank test compared categories and Cox proportional hazards regression model was used to assess the prognostic significance of baseline NLR in univariate and multivariable analysis. Results: Median PFS for the entire population was 6,407 months (3,28 – 9,52) and median OS was not reached (NR) with a median FU of 10,74 months. The median NLR ratio was 3,11 (0,87 – 19). 18 patients (24,3%) had a ≥ 5 NLR vs. 56 (75,7%) < 5. Median PFS for NLR ≥ 5 was: 2,3 (1,75 – 2,84) vs. 12,02 (5,11 – 18,93) for < 5 (HR = 3,11; IC95% 1,52 – 6,27; p = 0,001). Median OS ≥ 5: 3,05 (2,06 – 4,04) vs. NR for < 5 (HR = 5,88; IC95% 2,60 – 13,29; p = 0,001). NLR categorised remained statistically significant in multivariate analysis for PFS and NLR as a continuous variable remained statistically significant for both PFS and OS in multivariate analysis (Table 1). Conclusions: Baseline NLR is a rapid, simple, and cost-free predictor of survival before Anti-PD1 therapy. These results should be validated in a larger cohort of patients. [Table: see text]

The neutrophil to lymphocyte ratio as a prognostic factor among a diverse population with advanced pancreatic cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15729-e15729
Author(s):  
Michael Shusterman ◽  
Erin Jou ◽  
Andreas Kaubisch ◽  
Jennifer W. Chuy ◽  
Lakshmi Rajdev ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Metastatic Disease ◽  
Proportional Hazards ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Advanced Pancreatic Cancer ◽  
Cox Proportional Hazards ◽  
Neutrophil To Lymphocyte Ratio ◽  
Lymphocyte Ratio

e15729 Background: The neutrophil to lymphocyte ratio (NLR), a marker of systemic inflammatory response, has been suggested as a prognostic marker in patients with pancreatic adenocarcinoma (PAC). Black and Hispanic patients have been underrepresented in studies evaluating the significance of NLR in PAC. We investigated the prognostic significance of NLR in patients with advanced PAC treated at the Montefiore-Einstein Center for Cancer Care (MECCC) in the Bronx, NY. Methods: We included patients who were chemotherapy naive and treated for unresectable or metastatic PAC at MECCC between 2006 and 2015. Demographics, clinical characteristics and treatment data were collected. Overall survival was determined by the Kaplan-Meier method and Cox proportional-hazards models were built to assess survival differences adjusting for clinically relevant and statistically significant variables. Results: 201 patients were included in the study. Median age was 65 (range 32, 90). 52% were male. 41 were White (19%), 71 Black (33%), 71 Hispanic (33%), and 33 Other (15.3%). 66 (30.6%) had unresectable disease and 135 (62.5%) metastatic disease. An NLR ≥ 4 was associated with a worse OS compared to an NLR ≤ 4 (median 10 vs. 16.4 months; HR 1.895; 95% CI 1.390, 2.585; P < 0.0001). Predictors of worse OS on univariate analysis were ever smoker status (HR 1.365; P = 0.05), metastatic disease (HR 1.736; P = 0.001), and albumin ≤ 3.5 g/dL (HR 2.558; P< 0.0001). An NLR ≥ 4 on multivariate analysis remained significantly associated with worse OS (HR 1.665; 95% CI 1.188, 2.334; P = 0.003) after adjusting for age, gender, ever smoker status, metastatic disease, and albumin. Conclusions: In a cohort with significant minority patient representation, an NLR ≥ 4 was associated with significantly worse overall survival in patients with advanced pancreatic cancer. An elevated NLR in advanced PAC may be an important independent predictor to risk stratify patients and predict poor OS in future analyses.

scholarly journals Single-agent ibrutinib in RESONATE-2™ and RESONATE™ versus treatments in the real-world PHEDRA databases for patients with chronic lymphocytic leukemia

2019 ◽  
Vol 98 (12) ◽  
pp. 2749-2760 ◽  
Author(s):  
Gilles Salles ◽  
Emmanuel Bachy ◽  
Lukas Smolej ◽  
Martin Simkovic ◽  
Lucile Baseggio ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Real World ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Relative Effectiveness ◽  
Single Agent ◽  
Cox Proportional Hazards ◽  
Lymphocytic Leukemia ◽  
Cox Proportional Hazards Model ◽  
Treatment Naïve

AbstractAfter analyzing treatment patterns in chronic lymphocytic leukemia (CLL) (objective 1), we investigated the relative effectiveness of ibrutinib versus other commonly used treatments (objective 2) in patients with treatment-naïve and relapsed/refractory CLL, comparing patient-level data from two randomized registration trials with two real-world databases. Hazard ratios (HR) and 95% confidence intervals (CIs) were estimated using a multivariate Cox proportional hazards model, adjusted for differences in baseline characteristics. Rituximab-containing regimens were often prescribed in clinical practice. The most frequently prescribed regimens were fludarabine + cyclophosphamide + rituximab (FCR, 29.3%), bendamustine + rituximab (BR, 17.7%), and other rituximab-containing regimens (22.0%) in the treatment-naïve setting (n = 604), other non-FCR/BR rituximab-containing regimens (38.7%) and non-rituximab–containing regimens (28.5%) in the relapsed/refractory setting (n = 945). Adjusted HRs (95% CI) for progression-free survival (PFS) and overall survival (OS), respectively, with ibrutinib versus real-world regimens were 0.23 (0.14–0.37; p < 0.0001) and 0.40 (0.22–0.76; p = 0.0048) in the treatment-naïve setting, and 0.21 (0.16–0.27; p < 0.0001) and 0.29 (0.21–0.41; p < 0.0001) in the relapsed/refractory setting. When comparing real-world use of ibrutinib (n = 53) versus other real-world regimens in relapsed/refractory CLL (objective 3), adjusted HRs (95% CI) were 0.37 (0.22–0.63; p = 0.0003) for PFS and 0.53 (0.27–1.03; p < 0.0624) for OS. This adjusted analysis, based on nonrandomized patient data, suggests ibrutinib to be more effective than other commonly used regimens for CLL.

scholarly journals Percentage of Smudge Cells on Routine Blood Smear Predicts Survival in Chronic Lymphocytic Leukemia

2009 ◽  
Vol 27 (11) ◽  
pp. 1844-1849 ◽  
Author(s):  
Grzegorz S. Nowakowski ◽  
James D. Hoyer ◽  
Tait D. Shanafelt ◽  
Clive S. Zent ◽  
Timothy G. Call ◽  
...  
Keyword(s):  
Overall Survival ◽  
Chronic Lymphocytic Leukemia ◽  
Blood Smear ◽  
Early Stage ◽  
Continuous Variable ◽  
Lymphocytic Leukemia ◽  
Intact Cells ◽  
Cell Percentage ◽  
Blood Smears ◽  
The Relationship

PurposeSmudge cells are ruptured chronic lymphocytic leukemia (CLL) cells appearing on the blood smears of CLL patients. Our recent findings suggest that the number of smudge cells may have important biologic correlations rather than being only an artifact of slide preparation. In this study, we evaluated whether the smudge cell percentage on a blood smear predicted survival of CLL patients.Patients and MethodsWe calculated smudge cell percentages (ratio of smudged to intact cells plus smudged lymphocytes) on archived blood smears from a cohort of previously untreated patients with predominantly early-stage CLL enrolled onto a prospective observational study. The relationship between percentage of smudge cells, patient survival, and other prognostic factors was explored.ResultsBetween 1994 and 2002, 108 patients were enrolled onto the study and had archived blood smears available for review; 80% of patients had Rai stage 0 or I disease. The median smudge cell percentage was 28% (range, 1% to 75%). The percentage of smudge cells was lower in CD38+versus CD38–patients (P = .019) and in Zap70-positive versus Zap70-negative patients (P = .028). Smudge cell percentage as a continuous variable was associated with prolonged survival (P = .042). The 10-year survival rate was 50% for patients with 30% or less smudge cells compared with 80% for patients with more than 30% of smudge cells (P = .015). In multivariate analysis, the percentage of smudge cells was an independent predictor of overall survival.ConclusionPercentage of smudge cells on blood smear is readily available and an independent factor predicting overall survival in CLL.

scholarly journals Low preoperative serum ALB level is independently associated with poor overall survival in endometrial cancer patients

2020 ◽  
Author(s):  
Jia Lei ◽  
Yue Wang ◽  
Xiangqian Guo ◽  
Shuping Yan ◽  
Dimeng Ma ◽  
...  
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
Prognostic Factor ◽  
Proportional Hazards ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Cox Proportional Hazards ◽  
Independent Prognostic Factor ◽  
Poor Overall Survival ◽  
Preoperative Serum

Aim: To reveal the prognostic significance of serum albumin (ALB) concentration in endometrial cancer (EC) patients in China. Patients & methods: 345 EC patients were enrolled in a single center, and the preoperative serum ALB concentration were measured. Kaplan–Meier curve analysis and Cox proportional hazards regression model were performed to evaluate the associations between ALB concentration and overall survival (OS) of EC patients. Results: The EC patients with lower preoperative serum ALB concentration exhibited a significantly poorer OS (p < 0.05). Univariate analysis and multivariate analysis indicated that serum ALB concentration was an independent prognostic factor of unfavorable OS for EC patients. Conclusion: Our results showing that ALB concentration may serve as an independent prognostic factor for EC patients.

scholarly journals The impact of early discontinuation/dose modification of venetoclax on outcomes in patients with relapsed/refractory chronic lymphocytic leukemia: post-hoc analyses from the phase III MURANO study

Haematologica ◽  
2020 ◽  
pp. 0-0
Author(s):  
Anthony R. Mato ◽  
Jeff P. Sharman ◽  
Juliana M.L. Biondo ◽  
Mei Wu ◽  
Yong Mun ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Error Control ◽  
Proportional Hazards ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
Intention To Treat ◽  
Type 1 Error ◽  
The Impact

Fixed-duration venetoclax plus rituximab (VenR) has a manageable safety profile and improves survival in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). We present data from the phase III MURANO study on the impact of venetoclax modification or premature discontinuation on outcomes in patients with R/R CLL. Time-dependent Cox proportional hazards regression models, stratified by 17p deletion and risk status, evaluated the impact of venetoclax discontinuation/modification on investigator-assessed progression-free survival (PFS) and overall survival (OS). Analyses were performed retrospectively (without type-1 error control) in intention-to-treat patients from the VenR arm of MURANO. Overall, 140/194 (72%) patients in the VenR arm completed 2 years of therapy; 54/194 (28%) patients prematurely discontinued treatment. Inferior PFS was observed in patients prematurely discontinuing venetoclax for any reason (disease progression excluded; p

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