Prognostic importance of serum soluble CD23 level in 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.

Serum insulin‐like growth factor is not elevated in patients with early B‐cell chronic lymphocytic leukemia but is still a prognostic factor for disease progression

“…Furthermore, our results contrast with those dealing with other markers in CLL, e.g. IL‐6, serum β 2 m, CD23, thymydine kinase (TK), where serum levels are elevated in the patient group (24–27). Several epidemiological studies have suggested that high serum levels of IGF‐1 may predispose to some types of cancer such as breast cancer in premenopausal women, colon cancer, and prostate cancer (28–30).…”

“…To identify patients at higher risk of DP a number of independent prognostic factors, such as LDT, soluble CD23, β 2 m, soluble VEGF and serum TK have been proposed in patients with early CLL (18, 24–27, 32). Immunoglobulin mutational status and CD38 expression can now discern on biological ground different CLL clinical outcomes and expression of ZAP‐70, as detected by flow‐cytometry, correlating with IgV H mutational status, DP and survival (33–37).…”

CLLU1 expression levels predict time to initiation of therapy and overall survival in chronic lymphocytic leukemia

“…Rai et al (3) and Binet et al (4), defines subgroups in which risk increases with stage, they are essentially observational, descriptive tools. Elevated levels of serum proteins, including soluble‐CD23 (5), β 2‐microglobulin (6) and thymidine‐kinase (7), have been associated with poor prognosis, and genetic defects in specific molecular pathways, involving p53 at 17p13, or ATM at 11q22 predict resistance to treatment and shortened survival in CLL (8, 9). A breakthrough in risk‐prediction was the demonstration that absence of somatic hypermutations in the rearranged variable regions of the immunoglobulin heavy chains ( IgV H ) genes of the CLL cells predicts for shortened survival, even within each clinical stage (10, 11).…”

Serum TK levels in CLL identify Binet stage A patients within biologically defined prognostic subgroups most likely to undergo disease progression

“…Serum markers, including beta‐2 microglobulin ( β 2 m), lactate dehyrogenase, soluble CD23 and serum thymidine kinase, all have been shown to predict progression and survival. However, their value has been limited either by the lack of a standard assay method, variable cut‐off points between series, or the lack of validation in prospective studies (22, 23).…”