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

BACKGROUND. Although soluble CD44 (sCD44) is considered a reliable marker o f both tumor burden and disease activity, to the authors' knowledge, its pr edictive 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 CL L patients whose sera was taken at the time of diagnosis, stored at - 70 de greesC, and analyzed for the presence of standard sCD44 (sCD44(srd)) using a commercial enzyme-linked-immuno adsorbent-assay. The impact of the sCD44 level on the clinical outcome of the disease was assessed in 74 patients wi th early CLL (61 Binet Stage A patients and 13 asymptomatic Stage B patient s). 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 curr ent study. RESULTS. Patients with higher than median sCD44 levels (i.e., 642 ng/mL) ha d a more advanced clinical disease stage (P = 0.04), higher peripheral bloo d lymphocytosis (P = 0.006), and increased circulating levels of either lac tate dehydrogenase (P = 0.01) or beta (2)-microglobulin (P < 0.0001). In un ivariate analysis, seven of the nine parameters investigated predicted prog ression-free survival (PFS). In a stepwise multiple regression analysis, on ly 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 nonsmo ldering CLL, the sCD44 level distinguished two groups within the group of n onsmoldering 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 P FS 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 pr omising parameter for predicting the risk of disease progression in patient s with early CLL. Furthermore, sCD44 helps to refine the prognostic stratif ication of patients with either nonsmoldering CLL or Rai Stage I-II disease , thus enabling the identification of different prognostic subgroups in pat ients with early CLL. <(c)> 2001 American Cancer Society.