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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
Author(s) -
Molica Stefano,
Vitelli Gaetano,
Levato Domenico,
Giannarelli Diana,
Gandolfo Giuseppe Maria
Publication year - 2001
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(20010815)92:4<713::aid-cncr1374>3.0.co;2-o
Subject(s) - medicine , chronic lymphocytic leukemia , leukemia , disease , cd44 , immunology , oncology , cell , biology , genetics
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 stepwise 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. Cancer 2001;92:713–9. © 2001 American Cancer Society.