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

Stefano Molica, Gaetano Vitelli, Domenico Levato, Diana Giannarelli, Giuseppe Maria Gandolfo

Research output: Contribution to journalArticle

Abstract

BACKGROUND. Although soluble CD44 (sCD44) is considered a reliable marker of both tumor burden and disease activity, to the authors' knowledge, its predictive and prognostic value in B-cell chronic lymphocytic leukemia (CLL) has not been addressed to date. METHODS. The authors studied 94 previously untreated CD5-positive B-cell CLL patients whose sera was taken at the time of diagnosis, stored at - 70 °C, and analyzed for the presence of standard sCD44 (sCD44 std) using a commercial enzyme-linked-immunoadsorbent-assay. The impact of the sCD44 level on the clinical outcome of the disease was assessed in 74 patients with early CLL (61 Binet Stage A patients and 13 asymptomatic Stage B patients). Because the time to disease progression appears to predict the survival time of patients with CLL, it was used as a surrogate endpoint in the current study. RESULTS. Patients with higher than median sCD44 levels (i.e., 642 ng/mL) had a more advanced clinical disease stage (P = 0.04), higher peripheral blood lymphocytosis (P = 0.006), and increased circulating levels of either lactate dehydrogenase (P = 0.01) or β 2-microglobulin (P <0.0001). In univariate analysis, seven of the nine parameters investigated predicted progression-free survival (PFS). In a step-wise multiple regression analysis, only 2 parameters provided independent prognostic information regarding PFS: Rai substages (0 vs. I-II) (P = 0.002) and serum sCD44 levels > 642 ng/mL (P = 0.01). When added to the classification of smoldering CLL versus nonsmoldering CLL, the sCD44 level distinguished two groups within the group of nonsmoldering Stage A patients; patients with a sCD44 level > 642 ng/mL had a median PFS of 36 months, whereas patients with a sCD44 level <642 ng/mL experienced a longer PFS (median had not been reached at 8 years of follow-up). Furthermore, serum levels of sCD44 defined two different patterns of PFS within the group of patients with Rai disease Stages I-II (P = 0.01). CONCLUSIONS. An increased serum level of sCD44 can be considered to be a promising parameter for predicting the risk of disease progression in patients with early CLL. Furthermore, sCD44 helps to refine the prognostic stratification of patients with either nonsmoldering CLL or Rai Stage I-II disease, thus enabling the identification of different prognostic subgroups in patients with early CLL.

Original languageEnglish
Pages (from-to)713-719
Number of pages7
JournalCancer
Volume92
Issue number4
DOIs
Publication statusPublished - Aug 15 2001

Fingerprint

B-Cell Chronic Lymphocytic Leukemia
Disease Progression
Serum
Lymphocytosis
Immunosorbents
Tumor Burden
L-Lactate Dehydrogenase
Biomarkers

Keywords

  • Disease progression
  • Early chronic lymphocytic leukemia (CLL)
  • Progression-free survival (PFS)
  • Soluble CD44

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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. / Molica, Stefano; Vitelli, Gaetano; Levato, Domenico; Giannarelli, Diana; Gandolfo, Giuseppe Maria.

In: Cancer, Vol. 92, No. 4, 15.08.2001, p. 713-719.

Research output: Contribution to journalArticle

@article{83ce50c2f89b459fbe68c0e92f8c7b79,
title = "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",
abstract = "BACKGROUND. Although soluble CD44 (sCD44) is considered a reliable marker of both tumor burden and disease activity, to the authors' knowledge, its predictive and prognostic value in B-cell chronic lymphocytic leukemia (CLL) has not been addressed to date. METHODS. The authors studied 94 previously untreated CD5-positive B-cell CLL patients whose sera was taken at the time of diagnosis, stored at - 70 °C, and analyzed for the presence of standard sCD44 (sCD44 std) using a commercial enzyme-linked-immunoadsorbent-assay. The impact of the sCD44 level on the clinical outcome of the disease was assessed in 74 patients with early CLL (61 Binet Stage A patients and 13 asymptomatic Stage B patients). Because the time to disease progression appears to predict the survival time of patients with CLL, it was used as a surrogate endpoint in the current study. RESULTS. Patients with higher than median sCD44 levels (i.e., 642 ng/mL) had a more advanced clinical disease stage (P = 0.04), higher peripheral blood lymphocytosis (P = 0.006), and increased circulating levels of either lactate dehydrogenase (P = 0.01) or β 2-microglobulin (P <0.0001). In univariate analysis, seven of the nine parameters investigated predicted progression-free survival (PFS). In a step-wise multiple regression analysis, only 2 parameters provided independent prognostic information regarding PFS: Rai substages (0 vs. I-II) (P = 0.002) and serum sCD44 levels > 642 ng/mL (P = 0.01). When added to the classification of smoldering CLL versus nonsmoldering CLL, the sCD44 level distinguished two groups within the group of nonsmoldering Stage A patients; patients with a sCD44 level > 642 ng/mL had a median PFS of 36 months, whereas patients with a sCD44 level <642 ng/mL experienced a longer PFS (median had not been reached at 8 years of follow-up). Furthermore, serum levels of sCD44 defined two different patterns of PFS within the group of patients with Rai disease Stages I-II (P = 0.01). CONCLUSIONS. An increased serum level of sCD44 can be considered to be a promising parameter for predicting the risk of disease progression in patients with early CLL. Furthermore, sCD44 helps to refine the prognostic stratification of patients with either nonsmoldering CLL or Rai Stage I-II disease, thus enabling the identification of different prognostic subgroups in patients with early CLL.",
keywords = "Disease progression, Early chronic lymphocytic leukemia (CLL), Progression-free survival (PFS), Soluble CD44",
author = "Stefano Molica and Gaetano Vitelli and Domenico Levato and Diana Giannarelli and Gandolfo, {Giuseppe Maria}",
year = "2001",
month = "8",
day = "15",
doi = "10.1002/1097-0142(20010815)92:4<713::AID-CNCR1374>3.0.CO;2-O",
language = "English",
volume = "92",
pages = "713--719",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "4",

}

TY - JOUR

T1 - 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

AU - Molica, Stefano

AU - Vitelli, Gaetano

AU - Levato, Domenico

AU - Giannarelli, Diana

AU - Gandolfo, Giuseppe Maria

PY - 2001/8/15

Y1 - 2001/8/15

N2 - BACKGROUND. Although soluble CD44 (sCD44) is considered a reliable marker of both tumor burden and disease activity, to the authors' knowledge, its predictive and prognostic value in B-cell chronic lymphocytic leukemia (CLL) has not been addressed to date. METHODS. The authors studied 94 previously untreated CD5-positive B-cell CLL patients whose sera was taken at the time of diagnosis, stored at - 70 °C, and analyzed for the presence of standard sCD44 (sCD44 std) using a commercial enzyme-linked-immunoadsorbent-assay. The impact of the sCD44 level on the clinical outcome of the disease was assessed in 74 patients with early CLL (61 Binet Stage A patients and 13 asymptomatic Stage B patients). Because the time to disease progression appears to predict the survival time of patients with CLL, it was used as a surrogate endpoint in the current study. RESULTS. Patients with higher than median sCD44 levels (i.e., 642 ng/mL) had a more advanced clinical disease stage (P = 0.04), higher peripheral blood lymphocytosis (P = 0.006), and increased circulating levels of either lactate dehydrogenase (P = 0.01) or β 2-microglobulin (P <0.0001). In univariate analysis, seven of the nine parameters investigated predicted progression-free survival (PFS). In a step-wise multiple regression analysis, only 2 parameters provided independent prognostic information regarding PFS: Rai substages (0 vs. I-II) (P = 0.002) and serum sCD44 levels > 642 ng/mL (P = 0.01). When added to the classification of smoldering CLL versus nonsmoldering CLL, the sCD44 level distinguished two groups within the group of nonsmoldering Stage A patients; patients with a sCD44 level > 642 ng/mL had a median PFS of 36 months, whereas patients with a sCD44 level <642 ng/mL experienced a longer PFS (median had not been reached at 8 years of follow-up). Furthermore, serum levels of sCD44 defined two different patterns of PFS within the group of patients with Rai disease Stages I-II (P = 0.01). CONCLUSIONS. An increased serum level of sCD44 can be considered to be a promising parameter for predicting the risk of disease progression in patients with early CLL. Furthermore, sCD44 helps to refine the prognostic stratification of patients with either nonsmoldering CLL or Rai Stage I-II disease, thus enabling the identification of different prognostic subgroups in patients with early CLL.

AB - BACKGROUND. Although soluble CD44 (sCD44) is considered a reliable marker of both tumor burden and disease activity, to the authors' knowledge, its predictive and prognostic value in B-cell chronic lymphocytic leukemia (CLL) has not been addressed to date. METHODS. The authors studied 94 previously untreated CD5-positive B-cell CLL patients whose sera was taken at the time of diagnosis, stored at - 70 °C, and analyzed for the presence of standard sCD44 (sCD44 std) using a commercial enzyme-linked-immunoadsorbent-assay. The impact of the sCD44 level on the clinical outcome of the disease was assessed in 74 patients with early CLL (61 Binet Stage A patients and 13 asymptomatic Stage B patients). Because the time to disease progression appears to predict the survival time of patients with CLL, it was used as a surrogate endpoint in the current study. RESULTS. Patients with higher than median sCD44 levels (i.e., 642 ng/mL) had a more advanced clinical disease stage (P = 0.04), higher peripheral blood lymphocytosis (P = 0.006), and increased circulating levels of either lactate dehydrogenase (P = 0.01) or β 2-microglobulin (P <0.0001). In univariate analysis, seven of the nine parameters investigated predicted progression-free survival (PFS). In a step-wise multiple regression analysis, only 2 parameters provided independent prognostic information regarding PFS: Rai substages (0 vs. I-II) (P = 0.002) and serum sCD44 levels > 642 ng/mL (P = 0.01). When added to the classification of smoldering CLL versus nonsmoldering CLL, the sCD44 level distinguished two groups within the group of nonsmoldering Stage A patients; patients with a sCD44 level > 642 ng/mL had a median PFS of 36 months, whereas patients with a sCD44 level <642 ng/mL experienced a longer PFS (median had not been reached at 8 years of follow-up). Furthermore, serum levels of sCD44 defined two different patterns of PFS within the group of patients with Rai disease Stages I-II (P = 0.01). CONCLUSIONS. An increased serum level of sCD44 can be considered to be a promising parameter for predicting the risk of disease progression in patients with early CLL. Furthermore, sCD44 helps to refine the prognostic stratification of patients with either nonsmoldering CLL or Rai Stage I-II disease, thus enabling the identification of different prognostic subgroups in patients with early CLL.

KW - Disease progression

KW - Early chronic lymphocytic leukemia (CLL)

KW - Progression-free survival (PFS)

KW - Soluble CD44

UR - http://www.scopus.com/inward/record.url?scp=0035880701&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035880701&partnerID=8YFLogxK

U2 - 10.1002/1097-0142(20010815)92:4<713::AID-CNCR1374>3.0.CO;2-O

DO - 10.1002/1097-0142(20010815)92:4<713::AID-CNCR1374>3.0.CO;2-O

M3 - Article

C2 - 11550139

AN - SCOPUS:0035880701

VL - 92

SP - 713

EP - 719

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 4

ER -