The effect of changes in the treatment paradigm for chronic lymphocytic leukemia: A tumor registry study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 16000-16000
Author(s):  
S. Waheed ◽  
B. McClune ◽  
F. Buadi ◽  
K. Wright ◽  
D. Przepiorka
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Household Income ◽  
Census Data ◽  
Lymphocytic Leukemia ◽  
P Value ◽  
Study Cohort ◽  
Term Survival ◽  
Tumor Registry ◽  
Treatment Paradigm ◽  
Time Periods

16000 Background: In the early 1990s, several new agents became available for treatment of chronic lymphocytic leukemia (CLL), leading to a shift in the treatment paradigm with the hope of improving long-term survival. To determine if that outcome has been achieved, we performed a retrospective analysis of survival of patients in our community. Methods: The hospital tumor registry was queried to identify patients with CLL diagnosed 1980 to 2004. Zip code at diagnosis was used to assign a median household income based on census data. Survival was estimated by the method of Kaplan and Meier. Comparisons between the two groups were made by chi square. Hazard ratios for mortality were calculated in a Cox proportional hazard model using a backward stepping procedure retaining factors having a p-value < 0.1. Results: There were 192 patients with a diagnosis of CLL for analysis. The study cohort was comprised of 58% males and 42% females of median age 67 years (range, 39–96 years) at diagnosis. Fifty-three (28%) were <60 years of age, 29% were 60–69 years old, 26% were 70–79 years old, and 18% were >79 years at diagnosis. The group was 71% caucasian and 29% African American. Seventy-five (39%) patients had a household income greater than the median for the state, and the remainder had lesser incomes. There was a significant increase in the proportion of African Americans diagnosed >1990 compared to those diagnosed ≤1990 (40% vs 19%, p = 0.002), but there were no differences between time periods in gender, age, age category or income category. On multivariate analysis, factors predicting mortality differed between time periods as shown in the table. Median survival was 4.0 years for all patients, 3.9 years for the early group and 4.1 years for the later group (p = NS). Conclusion: We conclude that with changes in the treatment paradigm for CLL, gender and race are no longer prognostic for mortality, and the relative hazard for death is less amongst those 60–69 years and >79 years old, but there is no difference in survival for patients overall. [Table: see text] No significant financial relationships to disclose.

scholarly journals No improvement in long-term survival over time for chronic lymphocytic leukemia patients in stereotyped subsets #1 and #2 treated with chemo(immuno)therapy

Haematologica ◽  
2017 ◽  
Vol 103 (4) ◽  
pp. e158-e161 ◽  
Author(s):  
Panagiotis Baliakas ◽  
Mattias Mattsson ◽  
Anastasia Hadzidimitriou ◽  
Eva Minga ◽  
Andreas Agathangelidis ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Term Survival ◽  
Long Term Survival ◽  
Over Time

The impact of Agent Orange exposure on prognosis and management in patients with chronic lymphocytic leukemia: a National Veteran Affairs Tumor Registry Study

2017 ◽  
Vol 59 (6) ◽  
pp. 1348-1355 ◽  
Author(s):  
Craig Mescher ◽  
David Gilbertson ◽  
Nicole M. Randall ◽  
Gobind Tarchand ◽  
Julie Tomaska ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Agent Orange ◽  
Registry Study ◽  
Tumor Registry ◽  
Veteran Affairs ◽  
The Impact

scholarly journals V H mutation status, CD38 expression level, genomic aberrations, and survival in chronic lymphocytic leukemia

Blood ◽  
2002 ◽  
Vol 100 (4) ◽  
pp. 1410-1416 ◽  
Author(s):  
Alexander Kröber ◽  
Till Seiler ◽  
Axel Benner ◽  
Lars Bullinger ◽  
Elsbeth Brückle ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Expression Level ◽  
Chain Gene ◽  
P Value ◽  
Prognostic Impact ◽  
Survival Times ◽  
Mutation Status ◽  
Cd38 Expression ◽  
Genomic Aberrations

In chronic lymphocytic leukemia (CLL), biologic risk factors such as immunoglobulin variable heavy chain gene (VH) mutation status, CD38 expression level, and genomic aberrations have recently been identified, but the relative prognostic impact of the individual parameters is unknown. In the current study, we analyzed VH mutation status by polymerase chain reaction and sequencing (n = 300), genomic aberrations by fluorescence in situ hybridization (+3q, 6q−, +8q, 11q−, +12q, 13q−, t(14q), 17p−) (n = 300), and CD38 expression by triple-color FACS (CD5, CD19, CD38) (n = 157) in a unicentric CLL cohort. The prognostic influence of VH mutation rate and CD38 expression level was tested by maximally selected log-rank statistics. A corrected P value (Pcor) for a cutoff level allowing the best separation of 2 subgroups with different survival probabilities was identified at 97% VH homology (95% confidence interval [CI], 96%-98% homology,Pcor &lt;.001) and at 7% CD38 expression (95% CI, 20%-71% expression, Pcor = .02). In univariate analyses, unmutated VH genes and high CD38 expression levels predicted for shorter survival times. The overall incidence of genomic aberrations was similar in theVH unmutated and VHmutated subgroups. High-risk genomic aberrations such as 17p− and 11q− occurred almost exclusively in the VHunmutated subgroup, whereas favorable aberrations such as 13q− and 13q− as single abnormalities were overrepresented in theVH mutated subgroup. In multivariate analysis, unmutated VH, 17p deletion, 11q deletion, age, WBC, and LDH were identified as independent prognostic factors, indicating a complementary role of VH mutation status and genomic aberrations to predict outcome in CLL.

Free Light Chains, Monoclonal Proteins, and Chronic Lymphocytic Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4697-4697 ◽  
Author(s):  
Rosa Ruchlemer ◽  
Constantine Reinus ◽  
Esther Paz ◽  
Ahuva Cohen ◽  
Natalia Melnikov ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Light Chain ◽  
Lymphocytic Leukemia ◽  
Light Chains ◽  
P Value ◽  
Advanced Stage ◽  
Free Light Chains ◽  
Monoclonal Protein ◽  
Low Levels ◽  
Monoclonal Proteins

Abstract Monoclonal proteins(MPs) can frequently be detected in the serum/urine of chronic lymphocytic leukemia(CLL) patients. Serum free light chains(FLC) assays can detect MPs in the absence of M bands on immunofixation(IMF).An abnormal FLC ratio indicates excess of one light chain type suggesting clonality.We evaluated fresh serum/urine samples from 34 CLL patients at various stages of disease by quantitative nephelometric assay,IMF and FLC assay.Median age was 66 yrs(43–87),M:F 1.9:1 and median time from diagnosis 41.5 mos(5–288). 45% had advanced stage and 39% prior treatment with 1–7 therapies.Only 2 patients had mild renal failure.Serum immunoglobulins were normal/low in 94% of patients:IgG (171–1580 mg/l, median 803 mg/l), IgA(<25–310 mg/l, median 88 mg/l),IgM(<18–290 mg/l, median 38 mg/l), irrespective of the presence of a monoclonal protein. 71% of patients had evidence of abnormal immunoglobulin synthesis: by IMF alone (8),IMF and FLC(10) or FLC alone(8).Abnormal FLC ratios were more frequently associated with advanced stage disease and increased κ chains(see table 1). Abnormal FLC ratios(< 0.26 or >1.65) were measured in 18(53%) patients, 8 of whom did not have MPs by IMF. Two advanced stage patients had abnormal FLC ratios due to very low levels of a single light chain, most probably reflecting secondary hypogammaglobulinemia due to CLL and/or chemotherapy.Abnormal FLC ratios reverted to normal after 1 course of chemotherapy(FC+/−R) in 3 patients despite persistence of minimal residual disease(MRD).FLC were of the same type as expressed on the surface of CLL cells, with discrepancies observed in 5 patients.BM biopsy staining for light chains revealed IgAκ MGUS in addition to λ chain restricted CLL in one patient, but was noncontributory in the other 4. Conclusions: Neither IMF nor the FLC assay alone could detect all MPs. Normal FLC ratios do not exclude the presence of MPs. The FLC ratio should be interpreted with caution in CLL patients with advanced disease and hypogammaglobulinemia. Monoclonal bands and abnormal FLC ratios can be detected despite normal or low levels of serum immunoglobulins in CLL patients. The significance of these monoclonal gammopathies in CLL is not clear and warrants further study in a larger group of patients. Discrepancies between surface immunoglobulins and serum/urine MPs might suggest the presence of an additional condition:ex. MGUS. FLC may not be a sensitive measure of MRD. Normal FLC ratio Abnormal FLC ratio P value *median No. patients 16(47%) 18(53%) M:F 1.3:1 3.5:1 NS Age* 62.5 yrs(49–73) 68 yrs(43–87) NS Time from CLL diagnosis* 25.3 mos(0–282) 59 mos(0–210) NS Adv stage(Rai III/IV-Binet C) 25% 66.7% 0.018 Untreated 62% 50% NS CLL:κ:λ restriction 7:8(0.88:1) 11:6(1.8:1) NS Monoclonal protein 8(50%) 10(56%) NS Increased freeκ no. 8 15 0.043 Freeκ level* 19.6(4.5–200) 39.2(2.9–386) 0.0064 Increased freeλ no 4 3 NS Free λ level* 19.3(12.4–146) 15.4(0.1–517) NS Serum β 2m* 3.1(1.8–6.7) 4.3(2.2–10.2) NS Zap70≥20 86% 36% 0.002 CD38≥30 44% 44% NS 17pdel/11qdel 40% 44% NS

Richter Transformation of Chronic Lymphocytic Leukemia: Incidence, Risk Factors and Outcome

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3179-3179 ◽  
Author(s):  
Sina Alipour ◽  
Heather Leitch ◽  
Linda M Vickars ◽  
Lynda M Foltz ◽  
Paul F Galbraith ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Lymphocyte Count ◽  
Rare Complication ◽  
Univariate Analysis ◽  
Lymphocytic Leukemia ◽  
Age At Diagnosis ◽  
P Value ◽  
Prior Therapy ◽  
Electronic Database Search ◽  
Baseline Characteristics

Abstract Richter transformation (RT) is a rare complication of chronic lymphocytic leukemia (CLL). There is little information in the literature about its risk and outcome. In this study we assessed the incidence, presenting characteristics and outcomes of patients (pts) with CLL who developed RT. 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, 24 pts (5%) developed RT. Presenting features included B-symptoms (17%), lymph node enlargement (58%), progressive cytopenia (29%), hypercalcemia (4%), and spleno/hematomegaly (13%). The median age at diagnosis of CLL and RT were 64 y (range 33–80 y) and 67 y (range 48–81 y) respectively. The median time to transformation from CLL diagnosis was 61 months (range 1–257 m). Twenty one patients (88%) had been previously treated for CLL. Seventeen patients (71%) had received &gt;1 prior therapy. The median lymphocyte count at diagnosis was 12 ×109/L (range 4–120 ×109/L). Six patients (25%) are still alive with a median follow up of 38 m (range: 3–66 m). The only predictive factor for better survival post-transformation on univariate analysis was age of less than 60 y at CLL diagnosis (p=0.01). Other factors such as CLL Rai stage, lymphocyte count at diagnosis were not predictive for survival. This group of patients was compared with randomly selected group of patients with CLL but did not have RT. The baseline characteristics of the groups are presented in the table. No significant differences were found between the two groups in terms of gender, age at diagnosis, Rai stage or median lymphocyte count at diagnosis. The 5 and 10 year OS for the RT group were 76% and 39% compared to 93% and 84% for the CLL group (p= 0.002), respectively. In summary, RT significantly shortens the survival of CLL patients. There were no obvious predictive factors for RT in CLL pts at diagnosis. Table: Baseline characteristics of Richter and CLL groups. Parameter Richter group (%) CLL group (%) P value Number 24 37 Sex: M/F (ratio) 16/8 (2:1) 22/15 (1.5:1) 0.052 Age at Diagnosis: Median (range) 64 (33–80) 60 (37–85) 0.6 Rai stage at diagnosis: 0, 1+2, 3+4 7, 16,1 (29, 67, 4) 23, 14, 0 (62, 38, 0) 0.3 Median lymphocyte count at diagnosis (range) 12 ×109/1 (4–120) 8 × 109/1 (5–394) 0.056 Fig: OS of pts with RT compared with CLL pts and no RT Fig:. OS of pts with RT compared with CLL pts and no RT

Vegf and bFGF Single-Nucleotide Polymorphisms In Chronic Lymphocytic Leukemia: Impact On Susceptibility

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5287-5287
Author(s):  
Sandra Ballester ◽  
Begoña Pineda ◽  
Eduardo Tormo ◽  
Blanca Navarro ◽  
Ariadna Perez ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Conflicts Of Interest ◽  
Expression Patterns ◽  
Lymphocytic Leukemia ◽  
P Value ◽  
Nucleotide Polymorphisms ◽  
Exact Test ◽  
Cd38 Expression ◽  
Mutational Status ◽  
The Individual

Abstract Background B-cell chronic lymphocytic leukemia (B-CLL) is a heterogeneous disease with a highly variable clinical outcome. Recent studies have identified a number of different molecular prognostic markers (including mutational status of the IgVH gene, ZAP70 and CD38 expression) that allow to discriminate patients in prognostic subgroups. However, different expression patterns of angiogenic factors as VEGF, VEGFR1 and bFGF have been related with B-CLL susceptibility and treatment requirements. We have analyzed the polymorphisms: -710 C/T in VEGFR1, rs1109324, rs1547651, rs3025039 (936C/T) and rs833052 in VEGF and rs1449683 (223 C/T) in bFGF in order to determine the possible association with susceptibility in B-CLL. Methods Peripheral blood samples from 230 B-CLL patients and 476 healthy controls were genotyped using probes TaqMan SNP Genotyping Assays. Samples were providing from the Hospital Clinic of Valencia. Four SNPs in the VEGF gene, one SNP in the bFGF gene and one SNP in the VEGFR1 gene were evaluated. Statistical analysis was performed using SNPStats program (Catalan Institute of Oncology) and Fisher's exact test was applied to evaluate the significance. Results We have observed an increased frequency of the T allele in the rs1449683 SNP [OR 1.62 (95% CI: 0.98-2.66) p-value =0.063] and in the rs1547651 SNP [OR 0.72 (95% CI: 0.51-1.03), p-value=0.072] in our B-LLC patients when compared to control subjects. Moreover we observed that T allele carriers of rs3025039 (VEGF) have a significant protective effect concerning this disease [OR 0.59 (95% CI: 0.39-0.89) p-value=0.009]. Conclusion Our data indicate an increased frequency of the T allele in polymorphisms rs1449683 (bFGF) and rs1547651 (VEGF) in the group of patients, which possibly account for the individual susceptibility to develop B-CLL. On the other hand the data provided suggest that the T allele of VEGF rs3025039 is likely important genetic marker of susceptibility to B-CLL. Further studies regarding the role of pro-angiogenic markers in B-CLL would be beneficial to help elucidate pathogenic pathways in this disease. Disclosures: No relevant conflicts of interest to declare.

Chronic Lymphocytic Leukemia: State of the Art and Beyond

2014 ◽  
Vol 12 (5S) ◽  
pp. 801-803
Author(s):  
John C. Byrd
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Kinase Inhibitors ◽  
State Of The Art ◽  
Lymphocytic Leukemia ◽  
Newly Diagnosed ◽  
Treatment Standard ◽  
Genetic Features ◽  
Treatment Paradigm ◽  
Genomic Studies ◽  
Poor Outcomes

In the treatment of chronic lymphocytic leukemia (CLL), select genomic studies can assist in risk stratification of newly diagnosed patients. Chemoimmunotherapy targeting CD20 offers a survival advantage in symptomatic patients both with and without these high-risk genetic features, though patients with del(17p13.1) have poor outcomes and require specific intervention. Obinutuzumab plus chlorambucil is a treatment standard for untreated elderly patients and is superior to rituximab plus chlorambucil. In the setting of relapsed CLL, the new kinase inhibitors have the potential to completely change the treatment paradigm of CLL.

scholarly journals The role of combined fludarabine, cyclophosphamide and rituximab chemoimmunotherapy in chronic lymphocytic leukemia: current evidence and controversies

2016 ◽  
Vol 8 (3) ◽  
pp. 99-105 ◽  
Author(s):  
Alan P. Skarbnik ◽  
Stefan Faderl
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Standard Of Care ◽  
Current Treatment ◽  
Lymphocytic Leukemia ◽  
Current Evidence ◽  
Treatment Paradigm

Chemoimmunotherapy (CIT) has become a cornerstone in the treatment of patients with chronic lymphocytic leukemia (CLL). The combination of fludarabine, cyclophosphamide and rituximab (FCR) has emerged as the standard of care for therapy of previously untreated patients with CLL who are younger than 65 years and have no significant comorbidities. In this article, we review the role of FCR in the current treatment paradigm for CLL.

Paving the way for new agents; is standard chemotherapy part of the treatment paradigm for chronic lymphocytic leukemia in the future?

2016 ◽  
Vol 9 (7) ◽  
pp. 679-693 ◽  
Author(s):  
Anna Maria Frustaci ◽  
Marco Montillo ◽  
Paola Picardi ◽  
Maddalena Mazzucchelli ◽  
Roberto Cairoli ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Standard Chemotherapy ◽  
New Agents ◽  
The Future ◽  
Treatment Paradigm ◽  
The Way

scholarly journals Other Cancers in Long-Term Survivors of Chronic Lymphocytic Leukemia: Incidence and Prognostic Relevance

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3323-3323 ◽  
Author(s):  
Lorenzo Falchi ◽  
Michael Keating ◽  
Susan Lerner ◽  
Xuemei Wang ◽  
Kplola Y Elhor Gbito ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Chronic Lymphocytic Leukemia ◽  
Conflicts Of Interest ◽  
Observation Time ◽  
Lymphocytic Leukemia ◽  
P Value ◽  
Prognostic Impact ◽  
Long Term Survivors

Abstract Introduction. The clinical course of chronic lymphocytic leukemia (CLL) is mostly indolent. About one third of the patients are managed with lifelong watch-and-wait (WW) and those who receive therapy often achieve a durable remission. As a result, the majority of patients with CLL will live with their disease for long periods of time, and be exposed to several complications, including the occurrence of other cancers (OC). Patients with CLL may have an increased incidence in OC. Published reports indicate an incidence of 3-27%, mostly in treated patients, however, very little is known on OC in patients with CLL not requiring therapy. Furthermore, observation time in published studies is limited to <5 years, and the incidence of OC in patients followed for longer than 10 years is unknown. We, therefore, studied the incidence and prognostic impact of OC in treatment-naïve patients with CLL followed for ≥10 years. Methods. We reviewed our database and identified all patients with CLL untreated at the time of referral. We selected long-term survivors (LTS), defined as patients with a follow-up ≥10 years, and analyzed the incidence and prognostic impact of OC in this population. Non-melanoma skin cancers were excluded since these were diagnosed and treated promptly in virtually all cases and felt not to have prognostic impact. Standardized incidence ratios (SIR) were calculated for OC occurring after the diagnosis of CLL that were reportable to the Surveillance, Epidemiology and End Results program.The estimated overall survival (OS) according to the presence of OC was plotted considering OC as a time-dependent covariate. Results. We identified 797 LTS of CLL seen at our institution between 1957 and 2003. Median age was 56 years (24-88). 57% of patients were males. Median follow-up for the entire population is 154 months (120-485). We recorded 383 OC in 286 (36%) patients. 76/286 (26%) patients had >1 OC (62 had 2 OC, 10 had 3, 2 had 4, 1 had 5 and 1 had 6).The firstOC preceded or was diagnosed concomitantly with CLL in 100 patients (35%), while in the remaining 186 (65%) it occurred later during the course of the disease. 570 patients (71%) required treatment for CLL. Median time to treatment was 18 months (0-454). In treated patients, the cumulative frequency of OC was 205/570 (36%) and in WW patients 81/227 (36%). The SIR for all OC was 1.2 (p = .034). Males and patients younger than 60 years had a significantly higher incidence of OC (SIR 1.31 and 1.27, respectively). Among OC types, secondary leukemia, melanoma and head and neck cancers had the highest observed-to-expected ratio. Surprisingly, lung, digestive tract, and bladder cancer had a lower-than-expected incidence (table). 474 patients (59%) are alive. 222/570 (39%) treated patients and 101/227 (44%) WW patients have died. The median OS was longer in patients without OC (279 months) vs. those with OC (189 months). Independent predictors of shorter survival in multivariate analysis included higher creatinine, the presence of OC, and older age. Discussion. This is the first study to address the incidence of OC in LTS of CLL, including WW patients. In our population, the frequency of OC is similar in treated and WW patients. Although the incidence of OC in LTS of CLL is higher compared to matched general population, the incidence of lung, digestive and bladder cancer is lower than expected. Reasons of this finding remain to be identified.The occurrence of OC is an independent predictor of shorter survival, thus constituting a relevant competing risk of mortality in LTS of CLL. Variable Observed Expected Person-years SIR (O/E) 95% CI for O/E P -value Overall 148 123.34 10956 1.20 1.01 – 1.40 0.034 Male 96 73.4 5885 1.31 1.06 – 1.58 0.013 Female 52 49.93 5071 1.04 0.78 – 1.36 0.67 Age ≥60 years 60 54.33 3416 1.10 0.84 – 1.42 0.44 Age <60 years 88 69.02 7540 1.27 1.02 – 1.57 0.027 OC type Prostate 28 25.92 11809 1.08 0.72 – 1.56 0.64 Lung 20 29.08 11942 0.69 0.42 – 1.06 0.04 Breast 19 18.60 11855 1.02 0.62 – 1.59 0.96 Melanoma 16 4.23 11926 3.78 2.16 – 6.14 0.00 Leukemia 15 4.27 12009 3.51 1.96 – 5.79 0.00 Non-Hodgkin lymphoma 6 6.38 11996 0.94 0.34 – 2.05 1.00 Digestive 16 40.4 11937 0.40 0.23 – 0.64 0.00 Colon 8 19.42 11972 0.41 0.18 – 0.81 0.006 Pancreas 2 4.83 12024 0.41 0.05 – 1.49 0.18 Rectal 3 8.69 12011 0.34 0.07 – 1.00 0.05 Bladder 3 11.18 11993 0.27 0.05 – 0.78 0.009 Multiple Myeloma 2 1.98 12012 1.01 0.12 – 3.64 1.00 Lip 3 0.02 12015 150 31.00 – 438.5 0.00 Salivary gland 2 0.03 12026 66.66 8.00 – 240.06 0.00 Disclosures No relevant conflicts of interest to declare.

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