Association of Insurance Status and Marital Status with Outcomes of Patients with Chronic Lymphocytic Leukemia: A Population-Based Study

Introduction: Socioeconomic factors including insurance and marital status have impacts on the outcomes of cancer patients. Until now, there are few data regarding whether insurance status and marital status have effects on the outcomes of patients with chronic lymphocytic leukemia (CLL). In this study, the Surveillance, Epidemiology, and End Results (SEER) database was used to evaluate the prognostic roles of insurance and marital status in patients with CLL. Methods: Data from the SEER 18 Registries were used to conduct this study. Cases with newly-diagnosed CLL/small lymphocytic lymphoma (CLL/SLL) (International Classification of Diseases for Oncology, 3rd Edition [ICDO-3] codes 9823) in the time period between 2008 and 2015 were included. Exclusion criteria included history of cancer, unknown insurance status, unknown marital status, unknown survival data, unknown cause of death and survival months documented as 0. For each case we included age at the time of diagnosis, sex, marital status (married, divorced, single, widowed, unmarried or domestic partner, or separated), insurance status (Medicaid, insured, or uninsured), SEER cause-specific death classification, survival months and vital status. Survival curves were plotted by the Kaplan-Meier method and the log-rank test was used for comparison. P value was 2-sided and P<0.05 was considered to be statistically significant. All analyses were conducted using Graphpad Prism 6. Results: Atotal of 23,611 patients with CLL/SLL were included into the current analysis. The median follow-up was 34 months. We found that insurance status (uninsured or Medicaid) was significantly associated with decreased cancer-specific survival (CSS) (hazards ratio[HR]: 1.378, 95% confidence interval [CI]:1.251-1.664, P<0.0001) and overall survival (OS) (HR: 1.413, 95%CI:1.357-1.645, P<0.0001) (Figure 1A-B). Marital status (other than married) was also associated with decreased CSS (HR: 1.692, 95%CI:1.604-1.898, P<0.0001) and OS (HR: 1.791, 95%CI:1.757-1.968, P<0.0001) (Figure 1C-D). We then developed a prognostic index incorporating insurance status, marital status, and the well-known prognostic factor age (age≥65), with each risk factor being assigned 1 point. Four risk groups were generated: low (0), low-intermediate (1), high-intermediate (2), and high (3). The 5-year CSS rates for patients in low-risk, low-intermediate-risk, high-intermediate-risk, and high-risk subgroups were 94.2%, 85.8%, 77.7%, and 67.0%, respectively (P<0.0001) (Figure 1E). And the 5-year OS rates for patients in low-risk, low-intermediate-risk, high-intermediate-risk, and high-risk subgroups were 90.8%, 71.3 %, 55.7%, and 41.5%, respectively (Figure 1F) (P<0.0001). Conclusion: Insurance status and marital status have significant impacts on survival outcomes of patients with CLL/SLL. A 3-points prognostic index comprising insurance status, marital status and age could be used for risk stratification for patients with CLL/SLL. Figure 1 Disclosures No relevant conflicts of interest to declare.

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Detection Rate of Integrated Molecular and Cytogenetic Biomarker Testing for Chronic Lymphocytic Leukemia

Blood ◽

10.1182/blood-2021-152717 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4691-4691

Author(s):

Ramadevi Prathapam ◽

Najuma Maharjan ◽

Sheila B Powers ◽

Tracey Allen K Freitas ◽

Guoli Sun ◽

...

Keyword(s):

High Risk ◽

Chronic Lymphocytic Leukemia ◽

Prognostic Model ◽

Lymphocytic Leukemia ◽

Low Risk ◽

Intermediate Risk ◽

Clinical Value ◽

Trisomy 12 ◽

Biomarker Testing ◽

Testing Approach

Abstract Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in western countries and typically occurs in elderly individuals. There will be an estimated 21,250 newly diagnosed cases in the United States this year and 4,320 deaths. Due to the highly variable clinical course of this disease, prognostication and risk stratification methods are necessary for guiding decisions on clinical management. Integrated prognostic models incorporating laboratory testing for multiple molecular, cytogenetic, and other biomarkers have recently been proposed by major clinical guidelines to classify patients into risk subgroups. The current NCCN Guidelines for Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia describe such an integrated prognostic model known as the Rossi model that includes TP53, NOTCH1, SF3B1, and BIRC3 mutations along with the cytogenetic abnormalities detected by fluorescence in situ hybridization (FISH) to classify CLL patients into 4 distinct prognostic subgroups: high-risk (TP53 and/or BIRC3 abnormalities), intermediate-risk (NOTCH1 and/or SF3B1 mutations and/or deletion 11q), low-risk (trisomy 12 and wild-type for all genetic lesions), and very low-risk (deletion 13q only). The 10-year survival rates for these subgroups are 29%, 37%, 57%, and 69%, respectively. To assess the clinical value of an integrated biomarker testing approach, we analyzed results of 651 consecutive cases submitted to our clinical diagnostic laboratory for testing on our integrated panel of molecular and cytogenetic biomarkers for CLL. Our panel includes detection of genomic alterations by FISH (deletion 6q, 13q, 11q, 17p, trisomy 12, IGH rearrangement, and IGH/CCND1 translocation) and detection of sequence variants in BIRC3, BTK, MYD88, NOTCH1, PCLG2, SF3B1, and TP53 by next-generation sequencing (NGS). In total, 472 cases had positive findings by either FISH (90%) or NGS (46%) for a detection rate of 72.5%. Using the Rossi integrated prognostic model, 17.5% of cases fell into the high-risk subgroup, 20% of cases fell into the intermediate-risk subgroup, 43.5% of cases fell into the low-risk subgroup, and 19% of cases fell into the very low-risk subgroup. Importantly, among cases with positive FISH findings, 40.1% of cases also had positive molecular findings. In approximately 84% of cases belonging to the low-risk cytogenetic subgroups by FISH assessment alone, the incorporation of molecular findings resulted in reclassification into a higher-risk subgroup. Among the FISH-negative cases, 17% were classified as high-risk or intermediate-risk based on the molecular findings. Together, these findings support the clinical value of an integrative biomarker testing approach that includes both molecular and cytogenetic biomarkers to stratify CLL patients into risk subgroups to help guide decisions on clinical management. Disclosures Prathapam: Quest Diagnostics: Current Employment. Maharjan: Quest Diagnostics: Current Employment. Powers: Quest Diagnostics: Current Employment. Freitas: Quest Diagnostics: Current Employment. Sun: Quest Diagnostics: Current Employment. Tan: Quest Diagnostics: Current Employment. Gupta: Quest Diagnostics: Current Employment. Hucthagowder: Quest Diagnostics: Current Employment. Graham: Quest Diagnostics: Current Employment. Whitman: Quest Diagnostics: Current Employment. Khadgi: Quest Diagnostics: Current Employment. Daniel: Quest Diagnostics: Current Employment. Racke: Quest Diagnostics: Current Employment. Champion: Quest Diagnostics: Current Employment.

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External Validation On Biological Basis of New Prognostic Index in Early Asymptomatic Chronic Lymphocytic Leukemia (CLL) Patients: The Gruppo Italiano Studio Linfomi (GISL) Experience.

Blood ◽

10.1182/blood.v114.22.2375.2375 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2375-2375

Author(s):

Stefano Molica ◽

Sonia Fabris ◽

Giovanna Cutrona ◽

Massimo Gentile ◽

Emanuela Anna Pesce ◽

...

Keyword(s):

High Risk ◽

Chronic Lymphocytic Leukemia ◽

Risk Score ◽

Prognostic Index ◽

Lymphocytic Leukemia ◽

Low Risk ◽

Biological Parameters ◽

Cytogenetic Abnormalities ◽

Prognostic Relevance ◽

Binet Stage

Abstract Abstract 2375 Poster Board II-352 A prognostic index based on widely available clinical and laboratory features was recently proposed to predict survival in patients with previously untreated patients with chronic lymphocytic leukemia (CLL) by MD Anderson investigators. However, whether proposed clinical risk categories may surrogate new biological variables of prognostic relevance (i.e., mutational status of the IgVH gene regions, ZAP-70 or CD-38 expression, cytogenetic abnormalities) is unclear thus far. In a series of 160 asymptomatic Binet stage A patients enrolled in a Gruppo Italiano Studio Linfomi (GISL) multicentre trial designed to validate prospectively biological parameters in early CLL as well as to assess the impact on clinical outcome of an early versus delayed policy of treatment with subcutaneous alemtuzumab in the high biological risk, we evaluated whether clinical categories derived from newly proposed prognostic index reflected biological risk. Since the original prognostic index was derived from a database including cases with more advanced disease we used an optimal cutoff search to determine how to best split Binet stage A patients in different prognostic groups. To this purpose an independent patient cohort consisting of 310 Binet stage A patients included in a GIMEMA (Gruppo Italiano Malattie EMatologiche Maligne dell'Adulto) database was used. According to recursive partitioning (RPART) model, a classification tree was built that identified two subsets of patients who scored respectively: 0-3 (low risk) and 4-7 (high risk). Therefore, by prognostic index, 48.7% and 51.2% of 160 asymptomatic stage A patients, respectively, met criteria of low risk and high risk disease. In our prospective series high- risk score was more frequently associated with both unmutated IgVH status (P=0.009) and higher CD38-expression (P=0.002); in contrast only a trend towards an increased ZAP-70 expression could be found (P=0.06). As far as cytogenetic abnormalities are concerned, we observed that 11q deletion occurred more frequently among patients belonging to high-risk score (P=0.005), while cases with 13q deletion or trisomy 12 were homogeneously distributed among low- and high-risk patient category(P=0.151 and P=0.452, respectively). We did not consider suitable for correlation analysis 17p deletion since observed only in 2 out of 160 Binet stage A patients. In conclusion, our results demonstrate in a prospective cohort of patients with early CLL that clinical categories of a revised score index may surrogate biological parameters of prognostic relevance. The observation reinforces the revised IWCLL guidelines recommendations to assess the risk of CLL patients on clinical basis and to deserve biological studies to patients eligible for clinical trials. Disclosures: No relevant conflicts of interest to declare.

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Is the International Prognostic INDEX for CLL (CLL-IPI) Useful to Predict Time to First Treatment of Patients with EARLY Disease? Results of a Prospective Multicenter Analysis

Blood ◽

10.1182/blood.v126.23.498.498 ◽

2015 ◽

Vol 126 (23) ◽

pp. 498-498 ◽

Cited By ~ 1

Author(s):

Stefano Molica ◽

Diana Giannarelli ◽

Luciano Levato ◽

Rosanna Mirabelli ◽

Massimo Gentile ◽

...

Keyword(s):

High Risk ◽

Conflicts Of Interest ◽

Risk Group ◽

International Prognostic Index ◽

Prognostic Index ◽

Low Risk ◽

Intermediate Risk ◽

Early Disease ◽

Binet Stage ◽

Time To First Treatment

Abstract BACKGROUND: The CLL-IPI score is a large cooperative effort in which clinical data collected from 8 randomized trials were used to develop an internationally applicable prognostic index for CLL patients. The model includes 5 independent parameters that predict for overall survival such as age, clinical stage, del(17p) and/or TP53 mutation, IGHV mutation status and β2-microglobulin (B2M) level. A potential limitation for an extensive use of CLL-IPI is represented, however, by the fact that only 20% of patients included in the full analysis set had early disease. PATIENTS: The present analysis based on an observational multicenter CLL database including 337 Binet stage A patients (O-CLL1 protocol, clinicaltrial.gov identifier NCT00917540) was designed to assess the utility of the CLL-IPI score to predict time to first treatment (TTFT) in patients with early disease. RESULTS: Patients were followed up for a total of 2038 person-years (median, 42 months; range, 1-82 months), during which 91 (26.9%) experienced disease-progression requiring therapy according to 1996 IWCLL guidelines. The CLL-IPI score enabled Binet stage A patients to be divided into three subgroups [i.e., score 0-1, low-risk (n=229); score 2-3, intermediate-risk(n=99); score 4 or higher, high-risk (n=9)] that differed with respect to TTFT (P<0.0001). A comparative performance analysis between CLL-IPI and 2007 MD Anderson Cancer Center (MDACC) score, barely based on traditional clinical parameters (i.e., age, gender, Rai substage, absolute lymphocyte count, number of involved nodal groups and B2M), revealed that prediction of the TTFT was more accurate with the former. The c-statistic of the MDACC model was 0.62 (95% CI: 0.49-0.75) a level below than that of the CLL-IPI (c=0.70; 95% CI:0.58-0.81) and below the accepted 0.7 threshold necessary to have value at the individual patient level. These results are in keeping with the change in area under the receiver operating characteristic (ROC) curve (AUC) which increased from 0.646 (95% CI: 0.578-0.714) to 0.720 (95%CI:0.658-0.783) when moving from MDACC model to CLL-IPI score. Since the CLL-IPI score was originally derived from patients with active CLL enrolled in phase 3 trials we sought for different cut-off scores that better predict for TTFT in our patient cohort of early CLL. According to the recursive partitioning (RPART) analysis, a classification tree was built that identified three subsets of patients who scored 0 (low- risk,n=139), 1(intermediate-risk, n=90) and >1 (high-risk, n=108), respectively. The probability of remaining free from therapy at 5 years was 85% in the low-risk group, 68% in the intermediate-risk group and 47% in the high-risk group (P<0.0001)(Fig 1). Our revised IPI score remained a predictor of TTFT also when analysis was limited to 262 Rai stage 0 (P<0.0001) and 99 clinical monoclonal B-cell lymphocytosis (cMBL) cases (P=0.006). CONCLUSIONS: The results of this study confirm the utility of CLL-IPI score for predicting TTFT in a prospective cohort of community-based patients with early CLL at presentation. Our effort to adapt CLL-IPI score to patients with early disease meets the need to separate Binet stage A patients into different prognostic groups suitable for individualized follow-up programmes and possibly for early therapeutic interventions. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

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International prognostic score for asymptomatic early-stage chronic lymphocytic leukemia

Blood ◽

10.1182/blood.2019003453 ◽

2020 ◽

Vol 135 (21) ◽

pp. 1859-1869 ◽

Cited By ~ 7

Author(s):

Adalgisa Condoluci ◽

Lodovico Terzi di Bergamo ◽

Petra Langerbeins ◽

Manuela A. Hoechstetter ◽

Carmen D. Herling ◽

...

Keyword(s):

High Risk ◽

Chronic Lymphocytic Leukemia ◽

Risk Score ◽

Early Stage ◽

Prognostic Score ◽

Lymphocytic Leukemia ◽

Low Risk ◽

Intermediate Risk ◽

Early Stage Disease ◽

International Prognostic Score

Abstract Most patients with chronic lymphocytic leukemia (CLL) are diagnosed with early-stage disease and managed with active surveillance. The individual course of patients with early-stage CLL is heterogeneous, and their probability of needing treatment is hardly anticipated at diagnosis. We aimed at developing an international prognostic score to predict time to first treatment (TTFT) in patients with CLL with early, asymptomatic disease (International Prognostic Score for Early-stage CLL [IPS-E]). Individual patient data from 11 international cohorts of patients with early-stage CLL (n = 4933) were analyzed to build and validate the prognostic score. Three covariates were consistently and independently correlated with TTFT: unmutated immunoglobulin heavy variable gene (IGHV), absolute lymphocyte count higher than 15 × 109/L, and presence of palpable lymph nodes. The IPS-E was the sum of the covariates (1 point each), and separated low-risk (score 0), intermediate-risk (score 1), and high-risk (score 2-3) patients showing a distinct TTFT. The score accuracy was validated in 9 cohorts staged by the Binet system and 1 cohort staged by the Rai system. The C-index was 0.74 in the training series and 0.70 in the aggregate of validation series. By meta-analysis of the training and validation cohorts, the 5-year cumulative risk for treatment start was 8.4%, 28.4%, and 61.2% among low-risk, intermediate-risk, and high-risk patients, respectively. The IPS-E is a simple and robust prognostic model that predicts the likelihood of treatment requirement in patients with early-stage CLL. The IPS-E can be useful in clinical management and in the design of early intervention clinical trials.

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Mutational Characteristics and Changing Pattern from Idiopathic Cytopenia of Undetermined Significance to High-Risk Myelodysplastic Syndrome Stratified By IPSS-R

Blood ◽

10.1182/blood-2019-125236 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3009-3009

Author(s):

Eun-Ji Choi ◽

Young-Uk Cho ◽

Seongsoo Jang ◽

Chan-jeoung Park ◽

Han-Seung Park ◽

...

Keyword(s):

Bone Marrow ◽

High Risk ◽

Myelodysplastic Syndrome ◽

Rna Splicing ◽

Conflicts Of Interest ◽

Low Risk ◽

International Prognostic Scoring System ◽

Intermediate Risk ◽

Sequencing Data ◽

Undetermined Significance

Background: Unexplained cytopenia comprises a spectrum of hematological diseases from idiopathic cytopenia of undetermined significance (ICUS) to myelodysplastic syndrome (MDS). Revised International Prognostic Scoring System (IPSS-R) is the standard tool to assess risk in MDS. Here, we investigated the occurrence, characteristics, and changing pattern of mutations in patients with ICUS and MDS stratified by IPSS-R score. Methods: A total of 211 patients were enrolled: 73 with ICUS and 138 with MDS. We analyzed the sequencing data of a targeted gene panel assay covering 141 genes using the MiSeqDx platform (Illumina). The lower limit of variant allele frequency (VAF) was set to 2.0% of mutant allele reads. Bone marrow components were assessed for the revised diagnosis according to the 2016 WHO classification. Lower-risk (LR) MDS was defined as those cases with very low- or low-risk MDS according to the IPSS-R. Higher-risk (HR) MDS was defined as those cases with high- or very high-risk MDS according to the IPSS-R. Results: Patients with ICUS were classified as very low-risk (39.7%), low-risk (54.8%), and intermediate-risk (5.5%) according to the IPSS-R. Patients with MDS were classified as LR (35.5%), intermediate-risk (30.4%), and HR (34.1%). In the ICUS, 28 (38.4%) patients carried at least one mutation in the recurrently mutated genes in MDS (MDS mutation). The most commonly mutated genes were DNMT3A (11.0%), followed by TET2 (9.6%), BCOR (4.1%), and U2AF1, SRSF2, IDH1 and ETV6 (2.7% for each). IPSS-R classification was not associated with mutational VAF and the number of mutations in ICUS. In the 49 LR MDS, 28 (57.1%) patients carried at least one MDS mutation. The most commonly mutated genes were SF3B1 (20.4%), followed by TET2 (12.2%), U2AF1 (10.2%), DNMT3A (10.2%), ASXL1 (10.2%), and BCOR (6.1%). Higher VAF and number of mutations were observed in LR MDS compared to ICUS patients. In the 42 intermediate-risk MDS, 27 (64.3%) patients carried at least one MDS mutation. The most commonly mutated genes were ASXL1 (23.8%), followed by TET2 (21.4%), RUNX1 (16.7%), U2AF1 (14.3%), DNMT3A (14.3%), SF3B1 (9.5%), and SRSF2, BCOR, STAG2 and CBL (7.1% for each). In the 47 HR MDS, 36 (76.6%) patients carried at least one MDS mutation. The most commonly mutated genes were TET2 (25.5%), followed by DNMT3A (14.9%), TP53 (14.9%), RUNX1 (12.8%), U2AF1 (10.6%), ASXL1 (10.6%), and SRSF2 and KRAS (6.4% for each). As the disease progressed, VAF and number of the MDS mutations gradually increased, and mutations involving RNA splicing, histone modification, transcription factor or p53 pathway had a trend for increasing frequency. Specifically, ASXL1, TP53, and RUNX1 mutations were the most striking features in patients with advanced stage of the disease. Cohesin mutations were not detected in ICUS, whereas these mutations were detected at a relatively high frequency in HR MDS. Our data were summarized in Table 1. Conclusions: We demonstrate that on disease progression, MDS mutations are increased in number as well as are expanded in size. Furthermore, a subset of mutations tends to be enriched for intermediate- to HR MDS. The results of this study can aid both diagnostic and prognostic stratification in patients with unexpected cytopenia. In particular, characterization of MDS mutations can be useful in refining bone marrow diagnosis in challenging situations such as distinguishing LR MDS from ICUS. Disclosures No relevant conflicts of interest to declare.

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A Critical Analysis of Prognostic Factors in Patients with HTLV-1 Adult T-Cell Leukemia/Lymphoma: A Multicenter Clinicopathologic Experience and New Prognostic Score.

Blood ◽

10.1182/blood.v112.11.1784.1784 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1784-1784

Author(s):

Adrienne A. Phillips ◽

Iuliana Shapira ◽

Robert D. Willum ◽

Jasotha Sanmugarajah ◽

William B. Solomon ◽

...

Keyword(s):

T Cell ◽

High Risk ◽

Median Survival ◽

Risk Group ◽

Performance Status ◽

Recursive Partitioning ◽

Prognostic Index ◽

Low Risk ◽

Intermediate Risk ◽

A Performance

Abstract Purpose: Adult T-Cell Leukemia/Lymphoma (ATLL) is a rare aggressive Human T-cell Lymphotropic Virus Type-I (HTLV-I) associated peripheral T-cell neoplasm with 4 recognized clinicopathologic subtypes: acute, lymphomatous, chronic, and smoldering. Since the initial description of these variants, several studies have sought to identify additional prognostic factors. We assessed prognostic models already in use for aggressive non-Hodgkin lymphomas to develop a novel risk stratification scheme. Methods: Data regarding patients with ATLL were collected from 3 medical centers between 8/92 and 5/07. Descriptive statistics were used to assess categorical and continuous variables. Overall survival (OS) was defined as time from diagnosis to death. Survival curves for OS were estimated using the Kaplan-Meier method. Univariate associations between individual clinical factors and OS were evaluated using the log-rank test for categorical variables and the Cox model for continuous variables. Maximum logrank analysis was used to select the optimal cut-off for calcium. In order to develop a simple risk model and allow for interactions of factors independently associated with OS, we used recursive partitioning analysis. Results: 89 patients with ATLL were identified; 37 males (41.6%) and 52 females (58.4%) and median age 50 years (range 22 to 82). The acute subtype of ATLL predominated (68.5%), followed by lymphomatous (20.2%), chronic (6.8%) and smoldering (4.5%). Median OS for all sub-types was 24 weeks (range 0.9 to 315). According to the International Prognostic Index (IPI), 8 patients (9.1%) were classified as low risk, 11 patients (12.5 %) as low intermediate risk, 13 patients (14.8 %) as high intermediate risk, and 56 patients (63.6 %) as high risk, 1 patient could not be evaluated due to missing data. Median OS by IPI risk group was 271, 65, 31 and 16 weeks, respectively (p<0.01). The Prognostic Index for PTCL-U (PIT) could be determined in 68 patients; 10 patients (14.7 %) had a score of 0–1 (group 1), 19 patients (27.9 %) had a score of 2 (group 2), 31 patients (45.6 %) had a score of 3 (group 3), and 8 patients (11.8 %) had a score of 4 (group 4). Median OS by PIT risk group was 61.1, 28, 24, and 11.3 weeks respectively (p<0.01). A new risk model was developed using the variables of the IPI and PIT. In addition, calcium level at diagnosis was also included as it had independent prognostic value. Recursive partitioning of OS based on these variables gave a tree with 5 nodes, which fell into three risk categories: low risk patients with Stage I–II disease and a performance status <2; the medium risk group composed of two sets of patients: those with Stage III–IV disease with an ECOG performance status < 2 or those with an ECOG performance status ≥ 2 with calcium ≤ 11 mg/dL and age ≤ 60; and the high risk group (also comprising 2 sets of patients): those with a performance status ≥ 2 with calcium ≤ 11 mg/dL and age > 60 or those with a performance status ≥ 2 and calcium > 11 mg/dL. There were 10 patients (11.2%) in the low risk (median survival= 156.6 weeks), 31 (34.8%) in the intermediate risk (median survival = 45.4 weeks), and 48 (53.9%) in the high risk (median survival= 13 weeks) categories (p<0.01). Conclusion: This retrospective series confirms a poor outcome for North American patients with HTLV-1 related ATLL. Although the IPI and PIT identified subsets of patients, these models had liabilities. We propose a new prognostic model based on recursive partitioning analysis that successfully identifies three prognostic categories based on performance status, stage, age and calcium level at diagnosis in a more robust and distinct fashion. Table 1. Comparison of Prognostic Scores and Kaplan Meier Survival Estimates (%) of patients with ATLL International Prognostic Index (IPI) (n = 88) Prognostic Index for PTCL-U (PIT) (n = 68) ATLL Prognostic Score (APS) (n= 89) Time (wks) Low n= 8 Low-Intermed n= 11 High-Intermed n= 13 High n= 56 Group 1 n= 10 Group 2 n= 19 Group 3 N= 31 Group 4 n= 8 Low n= 10 Intermed n= 31 High n= 48 13 8 (100%) 10 (100%) 9 (75.5%) 31 (53.1%) 10 (100%) 13 (68.4%) 19 (66.3%) 3 (25.0%) 9 (100%) 27 (87.1%) 23 (46.4%) 26 8 (100%) 9 (90.0%) 6 (56.6%) 17 (31.1%) 10 (100%) 9 (51.3%) 13 (45.4%) 0 (0%) 9 (100%) 23 (77.0%) 9 (19.9%) 52 6 (75.0%) 6 (60.0%) 3 (28.3%) 9 (17.6%) 5 (50%) 5 (28.5%) 8 (30.7%) 0 (0%) 8 (88.9%) 13 (46.0%) 4 (8.8%) 78 5 (75.0%) 4 (40.0%) 2 (18.9%) 2 (4.0%) 4 (40%) 3 (17.1%) 2 (7.7%) 0 (0%) 7 (88.9%) 7 (24.8%) 0 (0%) 104 3 (56.2%) 3 (30.0%) 2 (18.9%) 2 (2.0%) 2 (30%) 3 (17.1%) 2 (3.8%) 0 (0%) 4 (61.0%) 6 (17.7%) 0 (0%) Median OS (wks) 271 65 31 16 61.1 28 24 11.3 156.6 45.4 13

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Chronic Lymphocytic Leukemia: Evaluation of Cytogenetic Markers as Prognostic Factors

Blood ◽

10.1182/blood.v116.21.4860.4860 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4860-4860

Author(s):

Jose Carda ◽

Patricia Sousa ◽

Patricia Olim ◽

Emília Magalhães ◽

Luis Rito ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factors ◽

Retrospective Study ◽

High Risk ◽

Chronic Lymphocytic Leukemia ◽

Progressive Disease ◽

Risk Group ◽

Staging System ◽

Lymphocytic Leukemia ◽

Intermediate Risk

Abstract Abstract 4860 Backgroud: Chronic lymphocytic leukemia (CLL) is one of the most frequent chronic lymphoproliferative disorders in Europe. It is characterized by persistent monoclonal lymphocitosis with localized or generalized lymphadenopathy. Despite the initial clinical presentation, it has a heterogeneous natural history, with the majority of patients living 10–12 years, but with some patients dying rapidly, within 2–3 years of diagnosis. Beside clinical prognostic factors, novel cytogenetic markers are recognized to be useful in predicting disease free and overall survival in CLL. AIMS: In a retrospective study throughout 10 years (1999-2009), we analyzed the clinical and biological presentation and compared the evolution and survival of patients with B-CLL using different cytogenetic markers. METHODS: We identified 112 cases (63 males and 49 females) of B-CLL with cytogenetic study by fluorescence in situ hybridization (FISH). RESULTS: Amongst 112 patients, the male to female (M/F) ratio was 1.3:1 and the median age was 70 (43-96) years. At diagnosis, the median lymphocyte count was 15.5 G/L (5.4-173). Fifty five patients (49%) had lymphadenopathies and seventeen (15%) had splenomegaly and/or hepatomegaly at presentation. By the revised Rai staging system seventy (63%) patients were included in low risk group, thirty (27%) in intermediate risk group and twelve (10%) in high risk group. The expression of ZAP-70 and CD38 by flow citometry was performed in 75 patients and revealed 13 (17%) patients CD38+ and 12 (16%) ZAP70+. The study of chromosomal aberrations with FISH showed thirty six patients (32%) with no abnormality, thirty six (32%) with isolated 13q deletion, fifteen (14%) with 12 trisomy, twelve (11%) with 11q deletion and thirteen (11%) with 17p deletion. Forty (36%) patients showed progressive disease in a median time of sixteen months (0-120), thirteen with 13qdel, seven with 17pdel and five with 12 trisomy. After treatment two patients showed progressive disease, six maintain a stable disease and thirty two obtain a remission, nine in complete remission. The Overall Survival (OS) at ten years was 70%. By the revised Rai staging system the OS at ten years was 80% for low risk, 70% for intermediate risk and all the high risk patients died during follow up. The OS at five years for the del13q-, 12 trisomy, del11q- and del17p- was 90%, 88%, 58% and 60%, respectively. SUMMARY: Chronic lymphocytic leukemia is currently considered a chronic disorder with a favourable outcome, but with a variable evolution to progressive disease. This retrospective study allowed the characterization of patient with CLL in our department and the acknowledgement that our results are quite similar to the published data. Disclosures: No relevant conflicts of interest to declare.

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Prognostic Factors and Outcomes in Allogeneic Hematopoietic Stem Cell Transplant Vs. Non-Transplant Chronic Lymphocytic Leukemia (CLL) Patients: A Comparative Analysis with the Leukemia/BMT Program of British Columbia (BC) and the BC Provincial CLL Database

Blood ◽

10.1182/blood.v124.21.2549.2549 ◽

2014 ◽

Vol 124 (21) ◽

pp. 2549-2549 ◽

Cited By ~ 2

Author(s):

Sebastian J. Swic ◽

Alexander G. T. MacPhail ◽

Chinmay B. Dalal ◽

Steven J.T. Huang ◽

Alina S. Gerrie ◽

...

Keyword(s):

Stem Cell ◽

High Risk ◽

Chronic Lymphocytic Leukemia ◽

Hematopoietic Stem Cell ◽

Conflicts Of Interest ◽

Early Recognition ◽

Lymphocytic Leukemia ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Long Term Outcome

Abstract Background: Chronic Lymphocytic Leukemia (CLL) patients (pts) have significant (sig) heterogeneity; survival ranges from decades to <5 years (yrs). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is promising treatment (tx) for high-risk pts. Ideally, predictive (pred) tools would allow clinicians to recognize such pts early, permitting transplant performance to maximize benefit and minimize procedure associated risk. Factors with significant (sig) pred capacity are not, however, entirely clarified. Moreover, limited studies compare CLL pts who have/have not received HSCT in terms of differences (diff) in characteristics (char) at diagnosis (dx), population (pop) composition and outcomes. This study evaluates pred factors for outcomes post allo-HSCT, and compares dx char between (bn) tx CLL pts who did /did not receive HSCT by evaluating a large pop-based CLL cohort (n= 1044) from the BC Provincial CLL Database (BCPCD). Methods: 102 CLL pts (71M, 31F) had consecutive allo-HSCT (01-91 to 03-13, L/BMT Program of BC). Median (med) age (range) at dx:HSCT was 50 (26-65):57 (32-68) yrs; med interval dx to HSCT 5.8 yrs (0.5 to 29). Most pts (78, 76%) received non-ablative therapy; (n=61 [60%] reduced-intensity fludarabine /busulfan [flu/bu] based [RIC], n=17 [17%] non-myeloablative flu-cyclophosphamide based [NMA]); 24 pts had myeloablative (MA) conditioning (CON). Donor status was 50% unrelated (UD) (51UD:51RD); 73M, 28 F. Results: With median (med) follow up (FU) (range) post allo-HSCT of 2 yrs (0.5-18); post dx of 9 yrs (1-38), 67 (50%) pts survive. 70 (69%) achieved CR post-HSCT a med of 187 (28-1274) days (d). 27 had CLL PROG a med of 339 (25-4367) d; 18 of 27 (67%) survive a med of 3 (0.5-18) yrs post HSCT. Factors pred OS post HSCT (KM p=; UVA HR=) (p<0.05) were: pre-HSCT FISH deletion 17p (del 17p) (0.005; 2.9), Dohner rank (0.02), HSCT specific comorbidity index (CoI) >3 vs. 0-2 (0.04; 2.5), HLA mismatched (MM) donor (0.03;2.3), pre-HSCT tx with alemtuzumab (alem) (0.005;3.0), CON (MA vs NMA or RIC) (0.046; 3.0), acute (A) graft vs host disease (GVHD) grade (g) 3-4 vs 0-2. (<0.001; 4.5), dn chim <90% (0.001; 5.2), abn FISH not clear post-HSCT (0.009; 2.6), yr of HSCT (pre- vs post-2010) (0.03; 3.13) and lack of CR post HSCT (<0.001; 10.5).The following sig pred for (OR; p=): >90% dn chim: no B symptoms at dx (2.5; 0.004), CON (RIC vs. NMA, (2.6; 0.006); clear FISH abn post-HSCT: CR post-HSCT (4.6; 0.004); CR post-HSCT: B symptoms at dx (0.4; 0.02), <=1 FISH abn (1.7; 0.045), rituximab (R) pre-HSCT (2.5; 0.001), clear FISH abn (2.5; 0.01), flu sensitivity (S) pre-HSCT (1.8; 0.03), S to last tx pre-HSCT (1.7; 0.03), CON (MA vs. RIC or NMA) (3.2; <0.001); PROG: Richter’s transformation ( Rich trans) pre-HSCT (3.5; 0.008), graft failure (3.3; 0.008), CoI >3 vs. 0-2 (6.9; 0.006), no R pre-HSCT (6.7; 0.01), CON (MA vs. NMA or RIC), (0.2; 0.03); NRM: pre-HSCT alem (2.7; 0.03), CoI >3 vs. 0-2 (2.7; 0.049), HLA MM (2.8; 0.01), CON (MA vs. rest) (3.0; 0.007), AGVHD g 3-4 vs. 0-2 (5.9; <0.001), FISH abn not clear (2.6; 0.04), and no CR (6.5; <0.001). Comparison bn allo-HSCT and BCPCD CLL pts showed sig diff at dx for Dohner FISH rank: more del 17p (23% vs.11%) and 11q (23% vs. 9%) in allo-HSCT pts (n=84 with pre-HSCT FISH); less +12 (13% vs. 17%), del 13q (24% vs.41%) or normal (22% vs 18%), p<0.001 than non-HSCT pts (n=952); Age at dx (med, range) was lower in HSCT (50, 26-65) vs non (62, 25-96), p<0.001; lymphocyte (lymph) count higher (14, 1-300 vs.11, 1-662, p=0.03), tx-free survival (TFS) from dx to 1st tx shorter at 0.75 (0-9.3) vs. 2.86 (0-20.6) yrs. Rich trans was more frequent in HSCT pts (8%) vs. non (3%), p=0.015.OS was sig better for HSCT pts (n=103) (med 17.6, SE 4.5, CI 95% 8.8-26) compared to non (n=494) (med 14.4, SE 1.1, CI 95% 12.1-16.6) (p=0.03). Conclusion: CLL allo-HSCT pts have sig diff than non including higher lymph at dx, shorter time to 1st tx, and higher risk FISH abn. 17p del remains high-risk with allo-HSCT. Pre-HSCT R increased post HSCT CR. Strategies to optimize post-HSCT CR and dn chim are important; these milestones are crucial to best outcome. PROG post-HSCT does not confer worse OS; rescue strategies are successful and deserve further study. Comparison of this large allo HSCT and pop-based BPCDB cohort indicate improved OS for allo-HSCT tx CLL pts vs. other, with a survival plateau. This data indicates early recognition of high-risk CLL patients for HSCT is likely to yield best long-term outcome. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

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Elevated Rates of Monoclonal Gammopathy in High-Risk Chronic Lymphocytic Leukemia Pedigrees

Blood ◽

10.1182/blood.v126.23.1449.1449 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1449-1449

Author(s):

Nicola J Camp ◽

Rosalie G Waller ◽

Cassandra Garner ◽

Guido J Tricot ◽

Michael Tomasson ◽

...

Keyword(s):

High Risk ◽

Chronic Lymphocytic Leukemia ◽

B Cell ◽

Monoclonal Gammopathy ◽

Conflicts Of Interest ◽

Lymphocytic Leukemia ◽

Clinical State ◽

Light Chains ◽

Solid Cancer ◽

Monoclonal Gammopathies

Abstract High-risk pedigrees can be a powerful design for disease gene discovery. Understanding tumor spectrum in high-risk pedigrees optimizes power for discovery, allows meaningful assessment of segregation and determination of familial risk. Many studies have observed that different hematological malignancies co-aggregate in families. In particular, we previously performed genealogical cluster analysis in the Utah Population Database and identified significant co-aggregation between chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). We have also determined that the frequency of the pre-clinical state, monoclonal B-cell lymphocytosis (MBL), is elevated in high-risk CLL pedigrees. Here, we explore evidence for monoclonal gammopathies in high-risk CLL pedigrees using serum immunoglobulin (Ig) biomarkers. Monoclonal gammopathies are characterized by a clonal expansion of plasma cells that secrete a monoclonal Ig. We used two serum biomarker tests to indicate the existence of clonal Ig proteins: Freelite™ and Hevylite™ immunoassays. These were performed on 498 frozen serum samples: 163 population controls; 97 MM/MGUS cases; 114 CLL cases (91 sporadic CLL and 23 from high-risk pedigrees); and 124 relatives in CLL pedigrees. Freelite detects and quantitates free light chains (κ and λ). Hevylite detects and quantitates specific immunoglobulins (IgA, IgG or IgM) bound to specific light chains. We determined monoclonality if either assay indicated an abnormal κ/λ ratio (specifically in conjunction with increased total Ig-type for Hevylite).The majority of monoclonality identified (92%) included restricted free lights chains. Those involving monoclonal Ig heavy chains only were all positively confirmed by standard serum protein and/or immunofixation electrophoresis. We observed a background of monoclonal gammopathy in our control samples (5/163, frequency =0.031), consistent with the advanced age of this comparison set (average 67y). As expected, monoclonal gammopathy was evident in the MM/MGUS cases (38/97, frequency=0.392, p=3.5×10-14), which increased to frequency=0.732, for abnormal κ/λ ratio considered without requiring increase of the specific Ig-type for Hevylite. The absence of complete identification is likely due to our samples being from prevalent cases at different treatment stages, in addition to non-secretory disease. The CLL cases (sporadic or pedigree) exhibited very similar rates of suggested monoclonal gammopathy (together 43/114, frequency=0.377, p=6.5×10-14). Pedigree relatives also exhibited evidence of clonal Ig proteins (9/124, frequency=0.073). The frequency across all relatives was not statistically different than the control set; however, the relatives were substantially younger than controls (minimum age 20y). When relatives were restricted to those over 49y (with average 67y), the frequency increased to 0.095 and became statistically increased compared to controls (p=0.028). The 9 relatives with monoclonality were: 1 non-Hodgkin lymphoma NOS, 1 MBL case, 2 solid cancer cases, and 5 relatives with no known cancer diagnoses. In conclusion, using sensitive Ig biomarkers we find that individuals in high-risk CLL pedigrees are at a greater risk of monoclonal gammopathy than the general population. This observation is consistent with previous clustering results indicating co-aggregation and a possible genetic etiologic overlap between CLL and MM. Furthermore, these Ig quantitative measures offer detailed phenotypes for all pedigree members, creating more informative pedigrees, increasing the power for gene identification. These measures offer an avenue for exploiting similarities across B-cell malignancies and have the potential to improve our ability to identify at-risk individuals. Disclosures No relevant conflicts of interest to declare.

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Serbian lymphoma study group: Demografic characteristics of 257 patients with follicular lymphoma

Vojnosanitetski pregled ◽

10.2298/vsp140115014s ◽

2015 ◽

Vol 72 (6) ◽

pp. 483-488

Author(s):

Olivera Simonovic ◽

Lana Macukanovic-Golubovic ◽

Bosko Andjelic ◽

Darko Antic ◽

Biljana Mihaljevic

Keyword(s):

High Risk ◽

Follicular Lymphoma ◽

International Prognostic Index ◽

Prognostic Index ◽

Treatment Decision ◽

Risk Groups ◽

Low Risk ◽

Intermediate Risk ◽

Prognostic Groups

Background/Aim. Follicular lymphoma (FL) is a B-cell tumor usually with indolent clinical course, yet in some cases the course of the disease can be very aggressive. The aim of the re-search was to determine distribution of patients into prognostic groups based on the International Prognostic Index (IPI) and Folicular Lymphoma International Prognostic Index (FLIPI) criteria, as well as to determine the importance of classifying patients into the prognostic groups, since this could potentially have the influence on selection of the treatment modality. Methods. The retrospective study was performed on 257 patients with follicular lymphoma diagnosed between January 2000 and April 2011. Results. Based on the IPI score, 153 (59.53%) patients had low risk, 57 (22.18%) low intermediate risk, 15 (5.84%) high intermediate risk, 9 (3.50%) high risk, whereas the classification of 23 patients diagnosed with FL remained with unknown risk according to the IPI. Based on the FLIPI prognostic index, 113 (43.97%) patients had low risk, 70 (27.24%) intermediate risk and 51 (19.84%) high risk, whereas the classification of 23 (8.95%) patients remained unknown. On the basis of the FLIPI 2 prognostic index, 48 (18.68%) patients had low risk, 145 (56.42%) intermediate risk and 41 (15.95%) high risk. The classification into prognostic groups for 23 (8.95%) patients remained unknown. According to the IPI, FLIPI and FLIPI 2 there were the patients that required treatment in all the risk groups. Conclusion. The FLIPI and FLIPI 2 effectively identify patients at high risk, thus helping in treatment decision for each single patient.

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