Prognosis of Binet stage A chronic lymphocytic leukemia patients: the strength of routine parameters

Blood ◽  
2010 ◽  
Vol 116 (22) ◽  
pp. 4588-4590 ◽  
Author(s):  
Rémi Letestu ◽  
Vincent Lévy ◽  
Virginie Eclache ◽  
Fanny Baran-Marszak ◽  
Dominique Vaur ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Prognostic Index ◽  
Progression Free Survival ◽  
Cost Effective ◽  
Lymphocytic Leukemia ◽  
Free Survival ◽  
Cd38 Expression ◽  
Recent Developments ◽  
Binet Stage

Recent developments in the management of chronic lymphocytic leukemia (CLL) patients have made necessary the availability of dependable prognostic factors. We have developed a prognostic index derived from the multivariate analysis of 339 stage A patients at diagnosis, exhaustively studied for classical and recent predictive markers. Only 4 biologic parameters were found to be independent predictors of progression-free survival (PFS): serum thymidine kinase (sTK), lymphocytosis, β2-microglobulin, and CD38 expression. Two groups were distinguishable: cases with no or 1 risk factor (among whom 85% did not progress after 7 years), and cases with 2 or more factors showing a median PFS of 20 months. Finally, we propose an easy, fast, cost-effective strategy for a trustworthy prognostication in stage A patients, who currently represent more than 80% of the CLL population, allowing physicians to adapt follow-up individually.

scholarly journals Chemoimmunotherapy With Fludarabine and Rituximab Produces Extended Overall Survival and Progression-Free Survival in Chronic Lymphocytic Leukemia: Long-Term Follow-Up of CALGB Study 9712

2011 ◽  
Vol 29 (10) ◽  
pp. 1349-1355 ◽  
Author(s):  
Jennifer A. Woyach ◽  
Amy S. Ruppert ◽  
Nyla A. Heerema ◽  
Bercedis L. Peterson ◽  
John G. Gribben ◽  
...  
Keyword(s):  
Overall Survival ◽  
Chronic Lymphocytic Leukemia ◽  
Variable Region ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
Free Survival ◽  
Mutational Status ◽  
Long Term Follow Up

Purpose The addition of rituximab to fludarabine-based regimens in chronic lymphocytic leukemia (CLL) has been shown to produce high response rates with extended remissions. The long-term follow-up of these regimens with respect to progression, survival, risk of secondary leukemia, and impact of genomic risk factors has been limited. Methods We report the long-term follow-up of the chemoimmunotherapy trial CALGB 9712 from the Cancer and Leukemia Group B, for which treatment regimen was previously reported, to examine end points of progression-free survival (PFS), overall survival (OS), impact of genomic features, and risk of therapy-related myeloid neoplasm (t-MN). Results A total of 104 patients were enrolled on this study and now have a median follow-up of 117 months (range, 66 to 131 months). The median OS was 85 months, and 71% of patients were alive at 5 years. The median PFS was 42 months, and 27% were progression free at 5 years. An estimated 13% remained free of progression at almost 10 years of follow-up. Multivariable models of PFS and OS showed that immunoglobulin heavy chain variable region mutational status was significant for both, whereas cytogenetic abnormalities were significant only for OS. No patient developed t-MN before relapse. Conclusion Long-term follow-up of CALGB 9712 demonstrates extended OS and PFS with fludarabine plus rituximab. Patients treated with fludarabine plus rituximab administered concurrently or sequentially have a low risk of t-MN. These long-term data support fludarabine plus rituximab as one acceptable first-line treatment for symptomatic patients with CLL.

scholarly journals Ofatumumab maintenance prolongs progression-free survival in relapsed chronic lymphocytic leukemia: final analysis of the PROLONG study

2019 ◽  
Vol 9 (12) ◽  
Author(s):  
Marinus van Oers ◽  
Lukas Smolej ◽  
Mario Petrini ◽  
Fritz Offner ◽  
Sebastian Grosicki ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Lymphocytic Leukemia ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Third Line ◽  
Grade 3 ◽  
Third Line Treatment

AbstractWe report the final analysis of the PROLONG study on ofatumumab maintenance in relapsed chronic lymphocytic leukemia (CLL). In all, 480 patients with CLL in complete or partial remission after second- or third-line treatment were randomized 1:1 to ofatumumab (300 mg first week, followed by 1000 mg every 8 weeks for up to 2 years) or observation. Median follow-up duration was 40.9 months. Median progression-free survival was 34.2 and 16.9 months for ofatumumab and observation arms, respectively, (hazard ratio, 0.55 [95% confidence interval, 0.43–0.70]; P < 0.0001). Median time to next treatment for ofatumumab and observation arms, respectively, was 37.4 and 27.6 months (0.72 [0.57–0.91]; P = 0.0044). Overall survival was similar in both arms; median was not reached (0.99 [0.72–1.37]). Grade ≥ 3 adverse events occurred in 62% and 51% of patients in ofatumumab and observation arms, respectively, the most common being neutropenia (23% and 10%), pneumonia (13% and 12%) and febrile neutropenia (6% and 4%). Up to 60 days after the last treatment, four deaths were reported in the ofatumumab arm versus six in the observation arm, none considered related to ofatumumab. Ofatumumab maintenance significantly prolonged progression-free survival in patients with relapsed CLL and was well tolerated.

Impact of Biological Variables on Need of Treatment in B-CLL: Study of 347 Patients in a Single Institution

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4188-4188
Author(s):  
Mj Garcia-Rodriguez ◽  
Raquel de Paz ◽  
M. Canales ◽  
M. Morado ◽  
F. Hernandez-Navarro
Keyword(s):  
Lymphocytic Leukemia ◽  
Clinical Staging ◽  
Free Survival ◽  
Cd38 Expression ◽  
Biological Variables ◽  
Positive Expression ◽  
Binet Stage ◽  
The Moment ◽  
The Impact

Abstract Background: Chronic lymphocytic leukemia (CLL) has an extremely variable clinical course. Some patients have a rapid and fatal evolution, and die earlier after diagnosis, whereas others have an indolent disease, and live for 10–20 years without symptoms. Ray and Binet system have been classically considered standard clinical staging method, but have a recognised limitation to identify the real risk to start treatment in patients with initial stage of disease (Rai 0–2, Binet A). Objetive: Our objective was to evaluate the impact of biological variables (cytogenetic analyses and CD38 and ZAP70 expression) independently of Rai and Binet stage at diagnosis, in the need of treatment. Moreover we analyzed the treatment-free survival at 12 and 60 months. Patients and methods: Our study includes 347 patients with B-CLL, 167 men and 180 women, with a median age of 70 years (range 35–97 years) who were retrospectively analyzed. All patients were diagnosed in our center during a period of 20 years, on the basis of a clinical examination as well as morphological and immunological criteria. Chromosomal abnormalities were studied using FISH cytogenetic methodology in 79.3% of patients. Patients with normal karyotype or single abnormality of 13q-, were considered in the group of favourable prognosis. Patients with other abnormalities such as trisomy 12, 17p- and 11q-, were considered as high risk of progression. CD38 expression was analyzed by flow cytometry in 90.2% of patients. A cut-off ≥30% was defined to distinguish positive and negative expression. ZAP70 expression was studied in 64.8% and we considered positive a cut-off ≥20%. Results: 78.9% of patients were classified by FISH in the good risk prognosis group. CD38 positive expression was detected in the 24.6% and ZAP70 was positive in the 56%. When we analysed the biological characteristics of treated patients we observed that they expressed CD38, ZAP70 and unfavourable karyotype more frequently than total population studied. These differences were more significant than the relationship with Rai and Binet stage. At 12 months of follow-up, we found that only 21% of patients with CD38 negative expression need treatment versus 40% of patients with positive expression. 25% of patients with ZAP-70 negative expression and 35% of ZAP-70 positive expression need treatment at this moment. 27% of patients with favourable kariotype and 29% of patients with unfavourable cytogenetic were treated (Figure 1). At 5 years since the moment of diagnostic, these differences were more significant. 82% of patients with CD38 positive expression need treatment versus 64% of patients with CD38 negative expression; 80% of patients with unfavourable cytogenetic need treatment versus 64% of patients with favourable kariotype. No differences were found in the two groups of the ZAP70 expression (Figure 1). Conclusions: We observed that biological markers, fundamentally CD38 expression, predict need of treatment. The percentage of treated patients was significantly higher in the group of CD38 positive expression at the moment of diagnosis. The follow-up of our patients shows that the treatment-free survival is lower in patients with CD38 positive expression, so this marker could be used to predict need of treatment and separate those cases of smouldering B-CLL that no need to be observed so intensively in which the best option of treatment is “watch and wait”. Figure 1. Treatment-free survival in 347 patients with B-CLL according to karyotype, CD38 and ZAP70 expression. Figure 1. Treatment-free survival in 347 patients with B-CLL according to karyotype, CD38 and ZAP70 expression.

scholarly journals Autologous and allogeneic stem cell transplantations for poor-risk chronic lymphocytic leukemia

Blood ◽  
2005 ◽  
Vol 106 (13) ◽  
pp. 4389-4396 ◽  
Author(s):  
John G. Gribben ◽  
David Zahrieh ◽  
Katherine Stephans ◽  
Lini Bartlett-Pandite ◽  
Edwin P. Alyea ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Chronic Lymphocytic Leukemia ◽  
Human Leukocyte ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Matched Sibling

We report here on the long-term follow-up on 162 patients with high-risk chronic lymphocytic leukemia (CLL) who have undergone hematopoietic stem cell transplantation (SCT) at a single center from 1989 to 1999. Twenty-five patients with human leukocyte antigen (HLA)-matched sibling donors underwent T-cell-depleted allogeneic SCT, and 137 patients without HLA-matched sibling donors underwent autologous SCT. The 100-day mortality was 4% for both groups, but later morbidity and mortality were negatively affected on outcome. Progression-free survival was significantly longer following autologous than allogeneic SCT, but there was no difference in overall survival and no difference in the cumulative incidence of disease recurrence or deaths without recurrence between the 2 groups. At a median follow-up of 6.5 years there is no evidence of a plateau of progression-free survival. The majority of patients treated with donor lymphocyte infusions after relapse responded, demonstrating a significant graft-versus-leukemia effect in CLL. From these findings we have altered our approach for patients with high-risk CLL and are currently exploring the role of related and unrelated allogeneic SCT following reduced-intensity conditioning regimens.

CD38 Expression above 20% Predicts Disease Progression in Chronic Lymphocytic Leukemia and Is a Useful Prognostic Marker Where Cytogenetic and Molecular Markers Are Not Available

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4190-4190
Author(s):  
Sina Alipour ◽  
Heather Leitch ◽  
Linda M Vickars ◽  
Lynda M Foltz ◽  
Paul F Galbraith ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Disease Progression ◽  
Lymphocyte Count ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
Disease Stage ◽  
Free Survival ◽  
Cd38 Expression

Abstract The prognostic significance of CD38 expression and the cut off value has not been fully investigated. As CD38 is readily available test in patients with chronic lymphocytic leukemia (CLL), we investigated its role in prediction of disease progression when a cut off value of 20% is used. Progression free survival (PFS) was defined as the time from diagnosis to first treatment or last follow up. An electronic database search of pts with CLL who presented at St Paul’s Hospital between 1969 and 2007 was performed. Among 465 pts with CLL, 161 pts (35%) had their CD38 expression measured by flow cytometry. CD38 expression and its association with other prognostic factors such as age, Rai stage, lymphocyte count at diagnosis, gender and other immunophenotypic makers were analyzed. Out of 161 pts, positive CD38 expression (&gt;20%) was found in 36 patients (22%). Comparing the baseline characteristics of the CLL pts with CD38+ and negative disease, we found CD38 positivity more common in male pts than in female pts (p=0.03). Also patients with CD38 positive disease tend to present with more advanced stage disease (p=0.056). Progression free survival at 2, 5 and 10y for the CD38+ CLL pts was 89%, 61% and 41% respectively compared with 95%, 81% and 62% for the CD38 negative group (p=0.03). Univariate analysis revealed the following factors as significant or marginally significant for disease progression: CD38+ (p=0.03), male gender (p=0.07), Rai stage (p&lt;0.0001), lymphocyte count above 20 ×109/l at diagnosis (p&lt;0.0001), CD5 expression &lt;10% (p=0.01). On multivariate analysis, only disease stage at diagnosis (p&lt;0.0001) and CD38 expression above 20% (p=0.04) retained significant and were predictive for disease progression. We conclude that CD38 expression above 20% at the time of diagnosis can be prognostically useful and predicts for disease progression and along with Rai staging can provide inexpensive tool to follow and monitor patients with CLL. Table: Characteristics of patients with CLL based on CD38 ≥20% and &lt;20% Parameter CD38 ≥20% (%) CD38&lt;20% (%) p value* *for differences between the groups. Number 36 125 Sex: M/F (ratio) 22/14 (1.6:1) 66/60 (1.1:1) 0.03 Age above 60 y 21 (58) 81 (65) 0.2 Rai stage: 0, 1+2, 3+4 20, 11, 5 (55, 31, 14) 100, 17, 1 (80, 14, 0) 0.056 Lymphocyte count above 20×109/l 9 (25) 23 (18) 0.3 CD5 &lt;10% 6 (16) 29 (23) 0.3 Fig: Progression free survival for patients with CLL based on CD38 expression, cut off level 20%. Fig:. Progression free survival for patients with CLL based on CD38 expression, cut off level 20%.

Acalabrutinib ± obinutuzumab versus obinutuzumab + chlorambucil in treatment-naïve chronic lymphocytic leukemia: Elevate-TN four-year follow up.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7509-7509
Author(s):  
Jeff Porter Sharman ◽  
Miklos Egyed ◽  
Wojciech Jurczak ◽  
Alan Skarbnik ◽  
John M. Pagel ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Progressive Disease ◽  
Progression Free Survival ◽  
Complete Response ◽  
Lymphocytic Leukemia ◽  
Free Survival ◽  
Early Results ◽  
Treatment Naïve ◽  
Group A

7509 Background: Early results from ELEVATE-TN (NCT02475681) at a median follow-up of 28.3 mo demonstrated superior efficacy of acalabrutinib (A) ± obinutuzumab (O) compared with O + chlorambucil (Clb) in patients (pts) with treatment-naïve (TN) chronic lymphocytic leukemia (CLL) (Sharman et al. Lancet 2020;395:1278-91). Results from a 4-year update are reported here. Methods: Pts received A±O or O+Clb. Crossover to A monotherapy was permitted in pts who progressed on O+Clb. Investigator-assessed (INV) progression-free survival (PFS), INV overall response rate (ORR), overall survival (OS), and safety were evaluated. Results: 535 pts (A+O, n=179; A, n=179; O+Clb, n=177) were randomized with a median age of 70 y; 63% had unmutated IGHV and 9% del(17p). At a median follow-up of 46.9 mo (range, 0.0–59.4; data cutoff: Sept 11, 2020), the median PFS was not reached (NR) for A+O and A pts vs 27.8 mo for O+Clb pts (both P<0.0001). In pts with unmutated IGHV, the median PFS was NR (A+O and A) vs 22.2 mo among O+Clb pts (both P<0.0001). In pts with del(17p), the median PFS was NR (A+O and A) vs 17.7 mo for O+Clb ( P<0.005). Estimated 48-mo PFS rates were 87% for A+O, 78% for A, and 25% for O+Clb. Median OS was NR in any treatment arm with a trend towards significance in the A+O group (A+O vs O+Clb, P=0.0604); estimated 48-mo OS rates were 93% (A+O), 88% (A), and 88% (O+Clb). ORR was significantly higher with A+O (96.1%; 95% CI 92.1–98.1) vs O+Clb (82.5%; 95% CI 76.2–87.4; P<0.0001); ORR with A was 89.9% (95% CI 84.7–93.5; P=0.035 vs O+Clb). Complete response/complete response with incomplete hematologic recovery (CR/CRi) rates were higher with A+O (26.8%/3.9%) vs O+Clb (12.4%/0.6%); 10.6%/0.6% had CR/CRi with A. Common adverse events (AEs) and AEs of interest are shown in the Table. Overall treatment discontinuation rates were 25.1% (A+O), 30.7% (A), and 22.6% (O+Clb); the most common reasons were AEs (12.8%, 12.3%, 14.7%, respectively) and progressive disease (4.5%, 7.8%, 1.7%). Most pts (77.4%) completed O+Clb treatment. Conclusions: With a median follow-up of 46.9 mo (̃4y), the efficacy and safety of A+O and A monotherapy was maintained, with an increase in CR since the interim analysis (from 21% to 27% [A+O] and from 7% to 11% [A]) and low rates of discontinuation.[Table: see text]

scholarly journals Relationship between Progression-Free Survival and Overall Survival in Chronic Lymphocytic Leukemia

2012 ◽  
Vol 23 ◽  
pp. ix350
Author(s):  
C. Beauchemin ◽  
J.B. Johnston ◽  
M. Lapierre ◽  
F. Aissa ◽  
J. Lachaine
Keyword(s):  
Overall Survival ◽  
Chronic Lymphocytic Leukemia ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
Free Survival
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