Circulating sCD138 and Some Angiogenesis-Involved Cytokines Help to Anticipate the Disease Progression of Early-Stage B-Cell Chronic Lymphocytic Leukemia

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.

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Elevated serum levels of soluble CD44 can identify a subgroup of patients with early B-cell chronic lymphocytic leukemia who are at high risk of disease progression

Cancer ◽

10.1002/1097-0142(20010815)92:4<713::aid-cncr1374>3.0.co;2-o ◽

2001 ◽

Vol 92 (4) ◽

pp. 713-719 ◽

Cited By ~ 18

Author(s):

Stefano Molica ◽

Gaetano Vitelli ◽

Domenico Levato ◽

Diana Giannarelli ◽

Giuseppe Maria Gandolfo

Keyword(s):

High Risk ◽

Chronic Lymphocytic Leukemia ◽

B Cell ◽

Disease Progression ◽

Elevated Serum ◽

Serum Levels ◽

Lymphocytic Leukemia ◽

Soluble Cd44 ◽

Risk Of Disease ◽

Cell Chronic Lymphocytic Leukemia

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Dynamics of microvesicle generation in B-cell chronic lymphocytic leukemia: implication in disease progression

Leukemia ◽

10.1038/leu.2016.217 ◽

2016 ◽

Vol 31 (2) ◽

pp. 350-360 ◽

Cited By ~ 18

Author(s):

J Boysen ◽

M Nelson ◽

G Magzoub ◽

G P Maiti ◽

S Sinha ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

B Cell ◽

Disease Progression ◽

Lymphocytic Leukemia ◽

Cell Chronic Lymphocytic Leukemia

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Combined analysis of ZAP-70 and CD38 expression as a predictor of disease progression in B-cell chronic lymphocytic leukemia

Leukemia ◽

10.1038/sj.leu.2403707 ◽

2005 ◽

Vol 19 (5) ◽

pp. 750-758 ◽

Cited By ~ 148

Author(s):

R Schroers ◽

F Griesinger ◽

L Trümper ◽

D Haase ◽

B Kulle ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

B Cell ◽

Disease Progression ◽

Lymphocytic Leukemia ◽

Combined Analysis ◽

Cd38 Expression ◽

Cell Chronic Lymphocytic Leukemia

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Chronic Lymphocytic Leukemia

Hematology ◽

10.1182/asheducation-2002.1.193 ◽

2002 ◽

Vol 2002 (1) ◽

pp. 193-213 ◽

Cited By ~ 37

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.

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Regulatory T-cells in B-cell chronic lymphocytic leukemia: their role in disease progression and autoimmune cytopenias

Leukemia & Lymphoma ◽

10.3109/10428194.2012.728287 ◽

2012 ◽

Vol 54 (5) ◽

pp. 1012-1019 ◽

Cited By ~ 30

Author(s):

Deepesh P. Lad ◽

Subhash Varma ◽

Neelam Varma ◽

Man Updesh Singh Sachdeva ◽

Parveen Bose ◽

...

Keyword(s):

T Cells ◽

Chronic Lymphocytic Leukemia ◽

Regulatory T Cells ◽

B Cell ◽

Disease Progression ◽

Lymphocytic Leukemia ◽

Autoimmune Cytopenias ◽

Cell Chronic Lymphocytic Leukemia

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High incidence of serum monoclonal Igs detected by a sensitive immunoblotting technique in B-cell chronic lymphocytic leukemia

Blood ◽

10.1182/blood.v84.4.1216.bloodjournal8441216 ◽

1994 ◽

Vol 84 (4) ◽

pp. 1216-1219 ◽

Cited By ~ 1

Author(s):

A Beaume ◽

A Brizard ◽

B Dreyfus ◽

JL Preud'homme

Keyword(s):

Chronic Lymphocytic Leukemia ◽

B Cell ◽

Light Chain ◽

Early Stage ◽

Lymphocytic Leukemia ◽

Cell Functions ◽

Lymphocyte Surface ◽

Light Chain Type ◽

Cell Chronic Lymphocytic Leukemia ◽

Chain Type

In a prospective study in 65 untreated patients with early-stage B-cell chronic lymphocytic leukemia (B-CLL), serum monoclonal Igs (moIg) were evidenced in 80% of cases by a sensitive immunoblotting procedure. These low-abundance moIg were generally undetectable by immunoelectrophoresis and individual sera often contained several of them. Their kappa/lambda ratio was close to 1 instead of 2.8 for the lymphocyte surface Igs. A monoclonal IgM of the same light-chain type as the lymphocyte surface IgM was found in 26 sera only. The distribution of the heavy-chain classes and subclasses and light-chain types of the serum moIg was similar to those observed in aging (with a higher incidence and no correlation with age in B-CLL) and conditions with defective T-cell functions. Using a specific filter affinity- transfer assay, rheumatoid factors were detected in 58.5% of sera. However, homogeneous anti-IgG antibodies corresponding to a monoclonal IgM of the same light-chain type as the surface IgM were found in 10 patients only. These data suggest that the majority of discrete serum moIg in B-CLL are not secretion products of the leukemic clones and likely result from the immunodeficiency state inherent in the disease.

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