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

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

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

scholarly journals Identification of outcome-correlated cytokine clusters in chronic lymphocytic leukemia

Blood ◽  
2011 ◽  
Vol 118 (19) ◽  
pp. 5201-5210 ◽  
Author(s):  
Xiao-Jie Yan ◽  
Igor Dozmorov ◽  
Wentian Li ◽  
Sophia Yancopoulos ◽  
Cristina Sison ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Heavy Chain ◽  
Variable Region ◽  
Immunoglobulin Heavy Chain ◽  
Serum Levels ◽  
Lymphocytic Leukemia ◽  
Differentially Expressed ◽  
Prognostic Indicators ◽  
Mutation Status ◽  
Heavy Chain Variable Region

Abstract Individual cytokines and groups of cytokines that might represent networks in chronic lymphocytic leukemia (CLL) were analyzed and their prognostic values determined. Serum levels of 23 cytokines were measured in 84 patients and 49 age-matched controls; 17 levels were significantly elevated in patients. Unsupervised hierarchical bicluster analysis identified 3 clusters (CLs) of highly correlated but differentially expressed cytokines: CL1 (CXCL9, CXCL10, CXCL11, CCL3, CCL4, CCL19, IL-5, IL-12, and IFNγ), CL2 (TNFα, IL-6, IL-8, and GM-CSF), and CL3 (IL-1β, IL-2, IL-4, IL-15, IL-17, and IFNα). Combination scores integrating expression of CL1/CL2 or CL1/CL3 strongly correlated (P < .005) with time-tofirst-treatment and overall survival (OS), respectively. Patients with the worst course had high CL1 and low CL2 or CL3 levels. Multivariate analysis revealed that CL1/CL2 combination score and immunoglobulin heavy chain variable region mutation status were independent prognostic indicators for time-to-first-treatment, whereas CL1/CL3 combination score and immunoglobulin heavy chain variable region mutation status were independent markers for OS. Thus, we identified groups of cytokines differentially expressed in CLL that are independent prognostic indicators of aggressive disease and OS. These findings indicate the value of multicytokine analyses for prognosis and suggest therapeutic strategies in CLL aimed at reducing CL1 and increasing CL2/CL3 cytokines.

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

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

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

scholarly journals Preferential Usage of Specific Immunoglobulin Heavy Chain Variable Region Genes with Unmutated Profile and Advanced Stage at Presentation Are Common Features in Patients with Chronic Lymphocytic Leukemia from Senegal

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 19-19
Author(s):  
Abibatou Sall ◽  
Teresa Amato ◽  
Alessandro Gozzetti ◽  
Awa Oumar Touré ◽  
Saliou Diop ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Heavy Chain ◽  
Mononuclear Cells ◽  
Variable Region ◽  
Immunoglobulin Heavy Chain ◽  
Lymphocytic Leukemia ◽  
Peripheral Blood Mononuclear ◽  
Mutational Status ◽  
Igh Genes ◽  
Variable Region Genes

Introduction : Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in Western populations, being rarer in Asian and African people. It has been suggested that patients with CLL from Africa might have a more aggressive disease compared with Causasien patients. In this study, we aimed to identify genetic factors that may account for this difference Methods: We collected peripheral blood mononuclear cells (PBMCs) from a total of 75 patients with CLL, 25 from Senegal (Africa), and 50 from Siena. Since it is well known that there are differences in germline IGH repertoires between different populations, we also collected PBMCs from five healthy Senegalese individuals as control. We analyzed immunoglobulin heavy chain (IGH) genes mutational status by performing next-generation sequencing in these 2 groups of patients. Results: We found that Senegalese patients more frequently had adverse prognostic factors and an unmutated profile. Furthermore, we documented that IGHV1 (IGHV1-69), IGHD3, and IGHJ6 were significantly more frequent in Senegalese patients, whereas IGHV3-30 was common and limited to the Italian cohort. Stereotyped receptors commonly detected in the white population were not recorded in our Senegalese series. Conclusion: The different IGH repertoire we observed in the Senegalese cohort may reflect the diverse genetic and microenvironmental (ie, polymicrobial stimulation) background. Disclosures Gozzetti: Takeda: Honoraria; Amgen: Honoraria; Janssen: Honoraria, Research Funding.

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