Prognostic nomogram and index for overall survival in previously untreated patients with chronic lymphocytic leukemia

Blood ◽  
2007 ◽  
Vol 109 (11) ◽  
pp. 4679-4685 ◽  
Author(s):  
William G. Wierda ◽  
Susan O'Brien ◽  
Xuemei Wang ◽  
Stefan Faderl ◽  
Alessandra Ferrajoli ◽  
...  
Keyword(s):  
Overall Survival ◽  
Chronic Lymphocytic Leukemia ◽  
Prognostic Model ◽  
Clinical Decision Making ◽  
Early Stage ◽  
Lymphocytic Leukemia ◽  
Cox Proportional Hazards Model ◽  
Cancer Center ◽  
Early Stage Disease ◽  
Staging Systems

Abstract The clinical course for patients with chronic lymphocytic leukemia is extremely heterogeneous. The Rai and Binet staging systems have been used to risk-stratify patients; most patients present with early-stage disease. We evaluated a group of previously untreated patients with chronic lymphocytic leukemia (CLL) at initial presentation to University of Texas M. D. Anderson Cancer Center to identify independent characteristics that predict for overall survival. Clinical and routine laboratory characteristics for 1674 previously untreated patients who presented for evaluation of CLL from 1981 to 2004 were included. Univariate and multivariate analyses identified several patient characteristics at presentation that predicted for overall survival in previously untreated patients with CLL. A multivariate Cox proportional hazards model was developed, including the following independent characteristics: age, β-2 microglobulin, absolute lymphocyte count, sex, Rai stage, and number of involved lymph node groups. Inclusion of patients from a single institution and the proportion of patients younger than 65 years may limit this model. A weighted prognostic model, or nomogram, predictive for overall survival was constructed using these 6 characteristics for 5- and 10-year survival probability and estimated median survival time. This prognostic model may help patients and clinicians in clinical decision making as well as in clinical research and clinical trial design.

scholarly journals Prognostic importance of serum soluble CD23 level in chronic lymphocytic leukemia

Blood ◽  
1996 ◽  
Vol 88 (11) ◽  
pp. 4259-4264 ◽  
Author(s):  
M Sarfati ◽  
S Chevret ◽  
C Chastang ◽  
G Biron ◽  
P Stryckmans ◽  
...  
Keyword(s):  
Overall Survival ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Disease Progression ◽  
Early Stage ◽  
Lymphocytic Leukemia ◽  
Study Entry ◽  
Clinical Staging ◽  
Soluble Cd23

Abstract Prognosis of B-cell chronic lymphocytic leukemia (CLL) is based on clinical staging whose limitation is the failure to assess whether the disease will progress or remain stable in early stage (Binet A, or Rai 0, I, II) patients. We previously reported that soluble CD23 (sCD23), a protein derived from the B-cell membrane CD23 Ag, is selectively elevated in the serum of CLL patients. This prospective study assessed the predictive value of serum sCD23 level measured at study entry on the overall survival of all CLL patients and on disease progression of stage Binet A patients. Prognostic value of repeated measurements of sCD23 over time in stage A patients was also analyzed. One hundred fifty-three CLL patients were prospectively followed with a median follow-up of 78 months. Eight clinical or biological parameters were collected from the date of the first sCD23 measurement. At study entry, by Cox model, Binet staging (P = .0001) and serum sCD23 level (P = .03) appeared as prognostic factors for survival. Patients with sCD23 level above median value (> 574 U/mL) had a significantly worse prognosis than those with lower values (median survival of 53 v 100+ months, P = .0001). During follow-up, sCD23 doubling time increased by 3.2 the risk of death (P = .001). Among stage A patients (n = 100), sCD23 determination at study entry was the sole variable predictive of disease progression, patients with sCD23 level above 574 U/mL had a median time progression of 42 months versus 88 months for those with lower levels (P = .0001). Stage A patients who doubled their sCD23 level exhibited a 15-fold increased risk of progression (P = .0001) and, in addition, the sCD23 increase preceded by 48 months disease progression. We conclude that in CLL patients, serum sCD23 level provides significant additional prognostic information in terms of overall survival. Most interestingly, among early stage patients, sCD23 determination at diagnosis and during the course of the disease may help to the early identification of patients who will rapidly progress to upper stages.

scholarly journals CD49d Is The Strongest Flow Cytometry-Based Predictor Of Overall Survival In Chronic Lymphocytic Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 672-672 ◽  
Author(s):  
Pietro Bulian ◽  
Tait D Shanafelt ◽  
Chris Fegan ◽  
Antonella Zucchetto ◽  
Lilla Cro ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Overall Survival ◽  
Chronic Lymphocytic Leukemia ◽  
Research Funding ◽  
Early Stage ◽  
Cox Model ◽  
Univariate Analysis ◽  
Lymphocytic Leukemia ◽  
Bivariate Analysis ◽  
The Impact

Abstract Purpose Although CD49d is an unfavorable prognostic marker in chronic lymphocytic leukemia (CLL), definitive validation evidence is lacking. A worldwide multi-center analysis was performed using published and unpublished CLL series to evaluate the impact of CD49d as overall survival (OS) and treatment free survival (TFS) predictor. Patients and Methods A training/validation strategy was chosen to find the optimal CD49d cut-off. The hazard ratio (HR) for death and treatment imposed by CD49d was estimated by pooled analysis of 2,972 CLL, and Cox analysis stratified by center and stage was used to adjust for confounding variables. The importance of CD49d over other flow cytometry-based prognosticators (CD38, ZAP-70) was ranked by recursive partitioning. Results Patients with ≥30% of neoplastic cells expressing CD49d were considered CD49d+. The decrease in OS at 5 and 10-years among CD49d+ cases was 7% and 23% (decrease in TFS 26% and 25% respectively). The pooled HR of CD49d for OS was 2.5 (2.3 for TFS) in univariate analysis. This HR remained significant and of similar magnitude (HR=2.0) in a Cox model adjusted for clinical and biological prognosticators. Hierarchical trees including all cases, or restricted to early stage or patients ≤65 years, always selected CD49d as the most important flow-cytometry-based biomarker, with negligible additional prognostic information added by CD38 or ZAP-70. Consistently, by bivariate analysis, CD49d reliably identified patients' subsets with poorer outcome independent of CD38 and ZAP-70. Conclusions In this analysis of ∼3000 patients, CD49d emerged as the strongest flow cytometry-based predictor of OS and TFS in CLL. Disclosures: Shanafelt: Genentech: Research Funding; Glaxo-Smith-Kline: Research Funding; Cephalon: Research Funding; Hospira: Research Funding; Celgene: Research Funding; Polyphenon E International: Research Funding. Burger:Pharmacyclics: Research Funding.

Management of Chronic Lymphocytic Leukemia

2015 ◽  
pp. 164-175 ◽  
Author(s):  
Stephan Stilgenbauer ◽  
Richard R. Furman ◽  
Clive S. Zent
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Signaling Pathway ◽  
Early Stage ◽  
Lymphocytic Leukemia ◽  
Management Approach ◽  
Team Approach ◽  
Early Stage Disease ◽  
Asymptomatic Patients ◽  
Wide Range ◽  
Bcr Signaling

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) is usually diagnosed in asymptomatic patients with early-stage disease. The standard management approach is careful observation, irrespective of risk factors unless patients meet the International Workshop on CLL (IWCLL) criteria for “active disease,” which requires treatment. The initial standard therapy for most patients combines an anti-CD20 antibody (such as rituximab, ofatumumab, or obinutuzumab) with chemotherapy (fludarabine/cyclophosphamide [FC], bendamustine, or chlorambucil) depending on multiple factors including the physical fitness of the patient. However, patients with very high-risk CLL because of a 17p13 deletion (17p-) with or without mutation of TP53 (17p-/ TP53mut) have poor responses to chemoimmunotherapy and require alternative treatment regimens containing B-cell receptor (BCR) signaling pathway inhibitors. The BCR signaling pathway inhibitors (ibrutinib targeting Bruton's tyrosine kinase [BTK] and idelalisib targeting phosphatidyl-inositol 3-kinase delta [PI3K-delta], respectively) are currently approved for the treatment of relapsed/refractory CLL and all patients with 17p- (ibrutinib), and in combination with rituximab for relapsed/refractory patients (idelalisib). These agents offer great efficacy, even in chemotherapy refractory CLL, with increased tolerability, safety, and survival. Ongoing studies aim to determine the best therapy combinations with the goal of achieving long-term disease control and the possibility of developing a curative regimen for some patients. CLL is associated with a wide range of infectious, autoimmune, and malignant complications. These complications result in considerable morbidity and mortality that can be minimized by early detection and aggressive management. This active monitoring requires ongoing patient education, provider vigilance, and a team approach to patient care.

Early Ofatumumab Treatment For High-Risk, Treatment-Naive Patients With Chronic Lymphocytic Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5307-5307
Author(s):  
Nitin Jain ◽  
Michael J. Keating ◽  
Alessandra Ferrajoli ◽  
Marina Konopleva ◽  
Deborah A. Thomas ◽  
...  
Keyword(s):  
High Risk ◽  
Chronic Lymphocytic Leukemia ◽  
Delay Time ◽  
Early Stage ◽  
Lymphocytic Leukemia ◽  
Early Stage Disease ◽  
Tumor Lysis ◽  
Ighv Gene ◽  
Grade 3

Background Ofatumumab is a human IgG1-kappa monoclonal antibody that binds to CD20 on normal B cells and on B chronic lymphocytic leukemia cells, resulting in B cell lysis. Ofatumumab has single-agent activity in patients (pts) with refractory CLL (Wierda, JCO 2010). Pts with CLL who have early stage disease (Rai 0-II) but have high-risk prognostic markers such as deletion 17p or deletion 11q have an increased risk of disease progression. Currently, these pts are offered watch-and-wait approach. The objective of this Phase II study is to evaluate the efficacy of ofatumumab in treating these pts with the goal to delay time to first chemoimmunotherapy treatment. Methods Pts with CLL/SLL were eligible provided they had high-risk for progression based on the presence of at least one of the following features: Rai stage II, serum beta-2 microglobulin (β2M) ≥3 mg/L, absolute lymphocyte count ≥25,000/µL, unmutated (≤2%) IGHV gene or mutated IGHV3-21, ZAP70 positive, CD38 positive (≥ 30%), or 11q or 17p deletion by FISH. Pts having a 2008 IWCLL/NCI-WG indication for CLL treatment were not eligible. Pts with Rai stage III-IV CLL were not eligible. Ofatumumab 300 mg dose 1, then 1000 mg weekly for 7 additional weeks (8 doses) was administered. Response assessment, including bone marrow evaluation, was done at least 2 months after last dose of ofatumumab and pts were followed for progression-free survival and time to first chemoimmunotherapy. Results Twenty-five pts (9 women, 16 men) were enrolled so far. The median age was 59 yrs (range, 40-81). The baseline characteristics are listed in the Table. Fifty percent of pts had unmutated IGHV gene. Thirty-four percent of pts had high-risk cytogenetic by FISH analysis. The median follow-up on the study is 4.7 months (range, 0.5-26). Grade 3-4 adverse events included infusion reaction in 6 pts. Autoimmune hepatitis with grade 4 ALT, grade 4 AST, and grade 4 alkaline phosphatase elevations was seen in 1 pt. Other grade 3-4 toxicities included rash (1 pt), shingles (1 pt), and tumor lysis (1 pt). Tumor lysis was seen in the pt with the WBC count of 207 K/µL. Eighteen pts (7 too early) are evaluable for response. Responses are as follows: 6 CR, 3 nPR, 3 PR, and 6 with stable disease. Three pts have progressed at 18.8, 14.1 and 3.2 months after starting the study treatment; 2 pts had unmutated IGHV gene (FISH negative) and one pt had trisomy 12 (IGHV mutation status unknown). None of the pts with deletion 17p or deletion 11q have progressed. All pts are alive at this time. The median overall follow up time is 7.6 months (range, 1-28). Conclusions Ofatumumab is well tolerated in pts with early stage CLL and may delay time to first chemoimmunotherapy. Disclosures: Ferrajoli: GlaxoSmithKline: Research Funding.

scholarly journals Clinical significance of DNA methylation in chronic lymphocytic leukemia patients: results from 3 UK clinical trials

2019 ◽  
Vol 3 (16) ◽  
pp. 2474-2481 ◽  
Author(s):  
Tomasz K. Wojdacz ◽  
Harindra E. Amarasinghe ◽  
Latha Kadalayil ◽  
Alice Beattie ◽  
Jade Forster ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Overall Survival ◽  
Clinical Trials ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Early Stage ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
Prolonged Survival ◽  
Treatment Naïve

Abstract Chronic lymphocytic leukemia patients with mutated immunoglobulin heavy-chain genes (IGHV-M), particularly those lacking poor-risk genomic lesions, often respond well to chemoimmunotherapy (CIT). DNA methylation profiling can subdivide early-stage patients into naive B-cell–like CLL (n-CLL), memory B-cell–like CLL (m-CLL), and intermediate CLL (i-CLL), with differing times to first treatment and overall survival. However, whether DNA methylation can identify patients destined to respond favorably to CIT has not been ascertained. We classified treatment-naive patients (n = 605) from 3 UK chemo and CIT clinical trials into the 3 epigenetic subgroups, using pyrosequencing and microarray analysis, and performed expansive survival analysis. The n-CLL, i-CLL, and m-CLL signatures were found in 80% (n = 245/305), 17% (53/305), and 2% (7/305) of IGHV-unmutated (IGHV-U) cases, respectively, and in 9%, (19/216), 50% (108/216), and 41% (89/216) of IGHV-M cases, respectively. Multivariate Cox proportional analysis identified m-CLL as an independent prognostic factor for overall survival (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.24-0.87; P = .018) in CLL4, and for progression-free survival (HR, 0.25; 95% CI, 0.10-0.57; P = .002) in ARCTIC and ADMIRE patients. The analysis of epigenetic subgroups in patients entered into 3 first-line UK CLL trials identifies m-CLL as an independent marker of prolonged survival and may aid in the identification of patients destined to demonstrate prolonged survival after CIT.

Chronic Lymphocytic Leukemia

Hematology ◽  
2002 ◽  
Vol 2002 (1) ◽  
pp. 193-213 ◽  
Author(s):  
Neil E. Kay ◽  
Terry J. Hamblin ◽  
Diane F. Jelinek ◽  
Gordon W. Dewald ◽  
John C. Byrd ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Disease Progression ◽  
Early Stage ◽  
Diagnostic Procedures ◽  
Marrow Transplant ◽  
Lymphocytic Leukemia ◽  
Early Stage Disease ◽  
Prognostic Features ◽  
Stage Disease

Abstract This update of early stage B-cell chronic lymphocytic leukemia (B-CLL) embraces current information on the diagnosis, biology, and intervention required to more fully develop algorithms for management of this disease. Emphasis on early stage is based on the rapid advancement in our understanding of the disease parameters and our increasing ability to predict for a given early stage patient whether there is a need for more aggressive management. In Section I, Dr. Terry Hamblin addresses the nature of the disease, accurate diagnostic procedures, evidence for an early “preclinical” phase, the use of newer prognostic features to distinguish who will be likely to progress or not, and whether it is best to watch or treat early stage disease. In Section II, Dr. Neil Kay and colleagues address the biologic aspects of the disease and how they may relate to disease progression. Review of the newer insights into gene expression, recurring genetic defects, role of cytokines/autocrine pathways, and the interaction of the CLL B cell with the microenvironment are emphasized. The relationship of these events to both trigger disease progression and as opportunities for future therapeutic intervention even in early stage disease is also considered. In Section III, Dr. John Byrd and colleagues review the historical and now current approaches to management of the previously untreated progressive B-CLL patient. They discuss what decision tree could be used in the initial decision to treat a given patient. The use of single agents versus newer combination approaches such as chemoimmunotherapy are discussed here. In addition, the place of marrow transplant and some of the newer antibodies available for treatment of B-CLL are considered. Finally, a challenge to utilize our growing knowledge of the biology of B-CLL in the early stage B-CLL is proffered.

scholarly journals How to Improve the Definition of Chronic Lymphocytic Leukemia Outcome Using a Simple Flow Cytometric Score Based on CD49d and Homing Marker Expression

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5567-5567
Author(s):  
Valentina Giudice ◽  
Monia Rocco ◽  
Luca Pezzullo ◽  
Giancarlo Villani ◽  
Rosa Rosamilio ◽  
...  
Keyword(s):  
Early Stage ◽  
Lymphocytic Leukemia ◽  
Early Stage Disease ◽  
Cd38 Expression ◽  
Flow Cytometric ◽  
Stage Disease ◽  
Genetic Abnormalities ◽  
Staging Systems ◽  
Definition Of

Abstract The identification of new molecular markers in Chronic Lymphocytic Leukemia (CLL) allowed to better define prognosis and clinical outcome. The actual staging systems could estimate the prognosis, but not the rapidity of disease evolution. Neither the identification of new molecular markers did allow to foresee the evolution and clinical response, because discordant findings were mostly reported. The aim of the present study was (1) to confirm the independent prognostic role of CD49d as a single marker in CLL patients, (2) to investigate the relationship between CD49d and other well-established CLL-membrane predictor markers (CD5, CD11c, CD20 and CD38) or clinical staging systems and (3) to evaluate the role of an immunophenotypic score based on the flow-cytometric detection of CD5, CD11c, CD20, CD38 and CD49d in the work up of CLL staging. Heparinized whole blood was collected from 68 CLL patients for immunophenotyping using the following antibodies: anti kappa, anti-lambda, CD5, CD11c, CD19, CD20, CD23, CD38, CD45, CD49d. A scoring system was elaborated combining 5 membrane markers: CD5, CD11c, CD20, CD38 and CD49d. Antigens were divided in two groups, favorable (CD5 and CD20) and unfavorable (CD11c, CD38 and CD49d) prognostic markers, and the cut-off of positivity was chosen according to the literature (30% for CD5, CD11c, CD20 and CD38, and 45% for CD49d). A value of "0" or "1" ("2" only for CD49d positivity) was assigned according to antigen expression. Finally, we defined a favorable phenotype when the sum of all the cytometric features was equal or less than 2, conversely the unfavorable phenotype was defined for a sum equal or greater than 3 (between 3 and 6). Flow cytometric analysis showed high CD49d expression in CD19+ cells in 47% of patients (n=32), and high CD38 expression in 44% of subjects (n=30), simultaneously expressed in 28% of patients (n=19). The 19% (n=13) of all CLL patients were CD5-, and interestingly the 85% of them showed higher expression of CD49d. Linear correlation was found between CD49d and CD38 (r2=0.08772, p=0.0142), and between CD49d and CD20 expression (r2=0.2490, p<0.0001). For CD5, the opposite tendency was registered (r2=0.1944, p=0.0002). Strong negative correlation between higher CD49d expression and total lymphocyte count was found (Pearson r = -0.3577, r2=0.1279, p=0.0068), but not for hemoglobin level and platelet count. The statistical power of each parameter of the score was also calculated by Chi-square test and all markers displayed a statistically significant weight (p<0.0001). After assessed the prognostic power of each marker, we applied the score to staged patients. Forty patients (59%) had a Favorable Phenotype and 28 of them (70%) an early stage disease; in this group of patients, only 7.5% (n=3) showed CD49d high expression. The overall response rate (ORR) was of 58%. The other 28 patients (41%) showed an Unfavorable Phenotype and 21 of them (75%) had an early stage disease. In this arm, all subjects carried>45% of CD49d positive cells. Four patients with Unfavorable Phenotype received chemotherapy with an ORR of 25%. Furthermore, a small population (n=16) of our CLL cohort was also studied for genetic abnormalities using FISH technique. According to FISH analysis, 25% of studied patients were classifies as very low-risk and, interestingly, no one of them showed an Unfavorable Phenotype (only one patient carried CD49d as unique negative marker). In our cohort, 50% of patients were low-risk with no genetic abnormalities or +12, but 63% of them showed an Unfavorable Phenotype with high CD49d and CD38 expression in 100% and 60% of cases, respectively. Our data confirm the independent negative prognostic role of CD49d and suggest a stronger prognostic power compared to CD38 in the definition of CLL outcome, because of its complex activity as homing marker, signaling receptor and anti-apoptotic molecule. Thus, the prognostic significance of CD49d may be enhanced when considered in comparison with other established markers, as CD11c and CD38. In conclusion, our results propose the use of the CD49d marker in combination with other B-cell membrane antigens as an additional tool for routine diagnosis and risk-stratification of CLL patients. Identification of high-risk phenotype with a simple scoring method could improve the treatment of these patients, who could take advantage of the most recent molecular targeting therapies. Disclosures No relevant conflicts of interest to declare.

Flow Cytometric Detection of ZAP-70 in Chronic Lymphocytic Leukemia: Correlation With Immunocytochemistry and Western Blot Analysis

2007 ◽  
Vol 131 (1) ◽  
pp. 50-56
Author(s):  
Graham W. Slack ◽  
Juanita Wizniak ◽  
Laith Dabbagh ◽  
Xinzhe Shi ◽  
Pascal Gelebart ◽  
...  
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
Western Blot ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Early Stage ◽  
Lymphocytic Leukemia ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Specimen Processing

Abstract Context.—Expression of ZAP-70 in chronic lymphocytic leukemia (CLL) predicts worse clinical outcome in patients with early-stage disease. It has become important to include ZAP-70 in the immunophenotyping panel used to diagnose CLL, commonly performed by flow cytometry (FC). Nevertheless, the methodology used to detect ZAP-70 by FC has not been extensively evaluated. Objective.—To describe our FC method for detecting ZAP-70 in CLL and assess whether this assay is useful in estimating the ZAP-70 protein level in CLL cells. Design.—ZAP-70 expression was assessed by FC in 45 consecutive newly diagnosed CLL patients, and the results were correlated with those of immunocytochemistry and Western blot analysis. Results.—With &gt;25% ZAP-70–positive B cells as the cutoff, the FC results had a perfect concordance with those of immunocytochemistry (39/39, 100%) and Western blot analysis (7/7, 100%). The use of autofluorescence controls was found to be superior to other alternatives. Overall, 19 (42%) of 45 cases were ZAP-70 positive in our series. Since only 7 cases (16%) had &gt;20% to 30% ZAP-70–positive B cells, the cutoff of &gt;25% readily separated CLL into positive and negative groups in most cases. ZAP-70 positivity was significantly associated with atypical morphology but not other laboratory parameters evaluated. Conclusions.—With proper specimen processing and the use of directly fluorescence-conjugated anti–ZAP-70 antibody, one can readily incorporate ZAP-70 into the routine FC study panel for CLL. Our data suggest that FC is a rapid and useful method to estimate the ZAP-70 protein expression level in 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.

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