scholarly journals Clinical Staging and Flowcytomteric CD38 and Zap 70 Prognostic Indicators in Sudanese Patients with Chronic Lymphocytic Leukemia

2020 ◽  
Author(s):  
Enaam Abdelrhman Abdelgader ◽  
Nada Hassan Eltayeb ◽  
Tasniem Ahmed Eltahir ◽  
Osama Ali Altayeb ◽  
Eman Abbass Fadul ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Stage Iv ◽  
Cross Sectional Study ◽  
Lymphocytic Leukemia ◽  
Clinical Staging ◽  
Prognostic Indicators ◽  
P Value ◽  
Cross Sectional ◽  
Cd38 Expression ◽  
Staging Systems

Background: The clinical course of chronic lymphocytic leukemia is highly variable. The determination of ZAP70 and CD38 is increasingly utilized as prognostic factor for chronic lymphocytic leukemia. The aim of conducting this study was to investigate the frequency of CD38 and ZAP70 expression among Sudanese Chronic lymphocytic leukemia (CLL) patients and to relate them to the Binet and Rai clinical staging systems. Method: A total of 93 patients (mean age; 62.29 ± 11.68, sd) were enrolled in this cross-sectional study. CD38 and ZAP70 expression levels were measured with four color flowcytometry using the cut-off values of 20% for ZAP70 and 30% for CD38 expression. Staging was assessed by using clinical examination and CBC for all patients. Data were analyzed using the Statistical Package for Social science for Windows (SPSS), version 22. Results: There were 93 CLL patients and the median age of the group was 63 years (36–95 years). About 71% of the patients presented with lymphadenopathy, 53.8% with splenomegaly, 73.1% with anemia, and 45.2% with thrombocytopenia. There was higher frequency of Binet stage C and Rai stage IV (62 [66.6%] patients and 34 [36.5%] patients, respectively). In addition, CD38 and ZAP70 showed higher frequency among Binet and Rai advance stages. ZAP70 and CD38 positivity were detected in 21 patients (22.6%) and 31 patients (33.3%), respectively. There was no statistically significant association between ZAP70 and CD38 and clinical staging systems (P-value > 0.05). Conclusion: No significant association was observed between Flowcytometric (CD38 and Zap70) Prognostic Indicators and clinical staging systems. Keywords: chronic lymphocytic Leukemia, Flowcytometry, ZAP70, CD38, clinical staging systems

Ig V Gene Mutation Status and CD38 Expression As Novel Prognostic Indicators in Chronic Lymphocytic Leukemia

Blood ◽  
1999 ◽  
Vol 94 (6) ◽  
pp. 1840-1847 ◽  
Author(s):  
Rajendra N. Damle ◽  
Tarun Wasil ◽  
Franco Fais ◽  
Fabio Ghiotto ◽  
Angelo Valetto ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Gene Mutation ◽  
Lymphocytic Leukemia ◽  
Prognostic Indicators ◽  
Risk Category ◽  
Mutation Status ◽  
Cd38 Expression ◽  
Staging Systems ◽  
V Genes ◽  
V Gene

Abstract Cellular immunophenotypic studies were performed on a cohort of randomly selected IgM+ B-chronic lymphocytic leukemia (B-CLL) cases for which Ig VH and VL gene sequences were available. The cases were categorized based on V gene mutation status and CD38 expression and analyzed for treatment history and survival. The B-CLL cases could be divided into 2 groups. Those patients with unmutated V genes displayed higher percentages of CD38+ B-CLL cells (≥30%) than those with mutated V genes that had lower percentages of CD38+ cells (<30%). Patients in both the unmutated and the ≥30% CD38+ groups responded poorly to continuous multiregimen chemotherapy (including fludarabine) and had shorter survival. In contrast, the mutated and the <30% CD38+ groups required minimal or no chemotherapy and had prolonged survival. These observations were true also for those patients who stratified to the Rai intermediate risk category. In the mutated and the <30% CD38+ groups, males and females were virtually equally distributed, whereas in the unmutated and the ≥30% CD38+ groups, a marked male predominance was found. Thus, Ig V gene mutation status and the percentages of CD38+B-CLL cells appear to be accurate predictors of clinical outcome in B-CLL patients. These parameters, especially CD38 expression that can be analyzed conveniently in most clinical laboratories, should be valuable adjuncts to the present staging systems for predicting the clinical course in individual B-CLL cases. Future evaluations of new therapeutic strategies and drugs should take into account the different natural histories of patients categorized in these manners.

Clinical significance of CD38 expression in chronic lymphocytic leukemia

Blood ◽  
2001 ◽  
Vol 98 (9) ◽  
pp. 2633-2639 ◽  
Author(s):  
Giovanni Del Poeta ◽  
Luca Maurillo ◽  
Adriano Venditti ◽  
Francesco Buccisano ◽  
Anna Maria Epiceno ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Clinical Outcome ◽  
B Cell ◽  
Progression Free Survival ◽  
Cell Number ◽  
Tumor Burden ◽  
Lymphocytic Leukemia ◽  
Clinical Staging ◽  
Cd38 Expression ◽  
Staging Systems

Abstract B-cell chronic lymphocytic leukemia (B-CLL) follows heterogeneous clinical courses, and several biological parameters need to be added to the current clinical staging systems to predict which patients will experience an indolent or an aggressive outcome. This study analyzed CD38 expression by flow cytometry and soluble APO1/Fas (sAPO1/Fas), Bcl-2 (sBcl-2), and CD23 (sCD23) proteins by immunoenzymatic methods to evaluate their effect on the clinical course of 168 unselected B-CLL patients. Intermediate/high risk modified Rai stages were characterized by a higher CD38+ B-cell number (P = .0002) and higher sCD23 levels (P < .0001). Moreover, CD38+ B-cell percentages were significantly and directly associated both with β2-microglobulin and sCD23 concentrations (P < .0001 and P = .002, respectively). Both a higher tumor burden (lymphadenopathy/splenomegaly) and a lymphocyte doubling time less than 12 months were significantly associated with higher CD38+ percentages (P < .0001 and P = .0001, respectively). With regard to clinical outcome, progression-free survival was significantly longer (75% versus 37% at 5 years; P = .00006) in patients with lower CD38+ B-cell percentages. Furthermore, the risk of partial or no response to fludarabine increased with increasing CD38 expression (P = .003), and a shorter overall survival (50% versus 92% at 8 years; P < .00001) characterized patients with more than 30% CD38+ B-cell number. The predictive value of CD38 expression was maintained among the patients within the Rai intermediate risk group and was confirmed in multivariate analysis. Thus, the percentage of CD38+ B cells appears to be an accurate predictor of clinical outcome and therefore could be used to indicate when more novel chemotherapeutic approaches are needed.

scholarly journals Comparison between LDH with Zap-70 and CD38 as prognostic Markers in Chronic Lymphocytic Leukemia Sudanese patients - A Pilot Study in Khartoum State

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Yassmin Hassan Mohammed ◽  
Salma Hussein Elhassan ◽  
Mariam Abbas Ibrahim ◽  
May Mohammed Ali ◽  
Nuha Eljaili Abubaker ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Prognostic Markers ◽  
Computer Software ◽  
Cross Sectional Study ◽  
Lymphocytic Leukemia ◽  
Poor Correlation ◽  
P Value ◽  
Cross Sectional ◽  
Dehydrogenase Enzyme ◽  
Program Version

Background:  Several prognostic markers are used in clinical stages of Chronic Lymphocytic Leukemia (CLL); including lactate dehydrogenase enzyme (LDH), CD38 and Zeta associated protein kinase (ZAP70). This study aimed to compare LDH with ZAP70 and CD38 as prognostic markers in Sudanese patients with CLL. Materials and Methods: Fifty newly diagnosed patients with CLL were enrolled in this cross-sectional study, the age of patients ranged between 36 - 85 years, with mean of 62 years. Of total patients; there were 34 males (68%) and 16 females (32%). Blood samples were obtained and LDH measurement was done by using Dirui CS-T240 automated analyzer while CD38 and ZAP-70 were measured by flowcytometry. Data were analyzed by statistical package for social science (SPSS) computer software program version 21. Results: The present study revealed a significant association between LDH and Rai staging (p. value= 0.002), when LDH compared with ZA-70 and CD38 as reference prognostic markers; poor correlation between CD38 and LDH was found (R2= 0.086, P value= 0.034) and no correlation between LDH level and ZAP-70 expression (R2= 000, P value= 0.960). In conclusion: According to the outcomes of this study; ZAP-70 and CD38 cannot be substituted by LDH as a prognostic marker.

Ig V Gene Mutation Status and CD38 Expression As Novel Prognostic Indicators in Chronic Lymphocytic Leukemia

Blood ◽  
1999 ◽  
Vol 94 (6) ◽  
pp. 1840-1847 ◽  
Author(s):  
Rajendra N. Damle ◽  
Tarun Wasil ◽  
Franco Fais ◽  
Fabio Ghiotto ◽  
Angelo Valetto ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Gene Mutation ◽  
Lymphocytic Leukemia ◽  
Prognostic Indicators ◽  
Risk Category ◽  
Mutation Status ◽  
Cd38 Expression ◽  
Staging Systems ◽  
V Genes ◽  
V Gene

Cellular immunophenotypic studies were performed on a cohort of randomly selected IgM+ B-chronic lymphocytic leukemia (B-CLL) cases for which Ig VH and VL gene sequences were available. The cases were categorized based on V gene mutation status and CD38 expression and analyzed for treatment history and survival. The B-CLL cases could be divided into 2 groups. Those patients with unmutated V genes displayed higher percentages of CD38+ B-CLL cells (≥30%) than those with mutated V genes that had lower percentages of CD38+ cells (<30%). Patients in both the unmutated and the ≥30% CD38+ groups responded poorly to continuous multiregimen chemotherapy (including fludarabine) and had shorter survival. In contrast, the mutated and the <30% CD38+ groups required minimal or no chemotherapy and had prolonged survival. These observations were true also for those patients who stratified to the Rai intermediate risk category. In the mutated and the <30% CD38+ groups, males and females were virtually equally distributed, whereas in the unmutated and the ≥30% CD38+ groups, a marked male predominance was found. Thus, Ig V gene mutation status and the percentages of CD38+B-CLL cells appear to be accurate predictors of clinical outcome in B-CLL patients. These parameters, especially CD38 expression that can be analyzed conveniently in most clinical laboratories, should be valuable adjuncts to the present staging systems for predicting the clinical course in individual B-CLL cases. Future evaluations of new therapeutic strategies and drugs should take into account the different natural histories of patients categorized in these manners.

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.

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.

CD38 expression and immunoglobulin variable region mutations are independent prognostic variables in chronic lymphocytic leukemia, but CD38 expression may vary during the course of the disease

Blood ◽  
2002 ◽  
Vol 99 (3) ◽  
pp. 1023-1029 ◽  
Author(s):  
Terry J. Hamblin ◽  
Jenny A. Orchard ◽  
Rachel E. Ibbotson ◽  
Zadie Davis ◽  
Peter W. Thomas ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Surrogate Marker ◽  
Variable Region ◽  
Lymphocytic Leukemia ◽  
Prognostic Indicators ◽  
Cd38 Expression ◽  
Immunoglobulin Variable Region

Abstract Although the presence or absence of somatic mutations in the immunoglobulin variable region (IgVH) genes in chronic lymphocytic leukemia (B-CLL) identifies subtypes with very different prognoses, the assay is technically complex and unavailable to most laboratories. CD38 expression has been suggested as a surrogate marker for the 2 subtypes. IgVHmutations and CD38 expression in 145 patients with B-CLL with a long follow-up were compared. The 2 assays gave discordant results in 41 patients (28.3%). Multivariate analysis demonstrated that Binet stage,IgVH mutations and CD38 were independent prognostic indicators. Median survival time in patients whose cells had unmutated IgVH genes and expressed CD38 was 8 years; in those with mutated IgVHgenes not expressing CD38, it was 26 years. For those with discordant results, median survival time was 15 years. Thus, although CD38 expression does not identify the same 2 subsets as IgVHmutations in CLL, it is an independent risk factor that can be used with IgVH mutations and clinical stage to select patients with B-CLL with the worst prognoses. Using cryopreserved cells taken at intervals during the course of the disease, however, changes of CD38 expression over time were demonstrated in 10 of 41 patients. Causes of the variation of CD38 expression require further study. Additional prospective studies are required for comparing CD38 expression with other prognostic factors and for taking sequential measurements during the course of the disease.

scholarly journals ZAP-70 expression is associated with increased CD4 central memory T cells in chronic lymphocytic leukemia: cross-sectional study

2018 ◽  
Vol 40 (4) ◽  
pp. 317-325 ◽  
Author(s):  
Rodolfo Patussi Correia ◽  
Flávia Amoroso Matos e Silva ◽  
Nydia Strachman Bacal ◽  
Paulo Vidal Campregher ◽  
Nelson Hamerschlak ◽  
...  
Keyword(s):  
T Cells ◽  
Chronic Lymphocytic Leukemia ◽  
Memory T Cells ◽  
Cross Sectional Study ◽  
Central Memory ◽  
Lymphocytic Leukemia ◽  
Sectional Study ◽  
Cross Sectional ◽  
Central Memory T Cells

scholarly journals Clinical staging of chronic lymphocytic leukemia

Blood ◽  
1975 ◽  
Vol 46 (2) ◽  
pp. 219-234 ◽  
Author(s):  
KR Rai ◽  
A Sawitsky ◽  
EP Cronkite ◽  
AD Chanana ◽  
RN Levy ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Median Survival ◽  
Prognostic Significance ◽  
Stage Iv ◽  
Staging System ◽  
Lymphocytic Leukemia ◽  
Stage Ii ◽  
Stage Iii ◽  
Clinical Staging ◽  
Survival Times

A method of clinical staging of chronic lymphocytic leukemia (CLL) has been proposed which is based on the concept that CLL is a disease of progressive accumulation of nonfunctioning lymphocytes: stage O, bone marrow and blood lymphocytosis only; stage 1, lymphocytosis with enlarged nodes; stage II, lymphocytosis with enlarged spleen or liver or both; stage III, lymphocytosis with anemia; and stage IV:lymphocytosis with thrombocytopenia. Analysis of 125 patients. in the present series showed the following median survival times (in months) from diagnosis: stage 0, is greater than 150; stage I 101; stage II, 71; stage III, 19; stage IV, 19, The median survival for the entire series was 71 mo. The prognostic significance of the stage remained even after adjustment was made for age and sex. However, both sex and age were shown to be poor predictors of survival after adjustment for stage. The method of staging proved to be a reliable predictor of survival whether used at diagnosis or during the course of the disease. The proposed staging system was an equally accurate indicator for survival when applied to two other previously published studies of large series of patients.

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