Thymidine kinase (TK), β-2-microglobulin (β2M) and soluble CD23 (sCD23) are among the most widely used soluble prognostic factors (sPFs) in patients with B-cell chronic lymphocytic leukemia (B-CLL). Aim of our study was the retrospective evaluation of a prognostic score mod- eled on their combination. We analysed the levels of these three sPFs in B-CLL patients, using available sera sampled at diagnosis and stored at –20°C. Of 254 patients, 150 were males (59%), median age at diagnosis was 66 years (range: 40-85) and Binet stage was A in 208 cases (82%), B in 36 (14%), and C in 10 (4%). Median follow-up was 77 months (14- 259). TK activity was measured by a radioenzymatic assay by Imm- munotech (Beckman-Coulter): the mean value of 80 healthy donors was 3.7 U/L +/- 2 (SD). sCD23 levels were measured by ELISA (Biosource International, Camarilla, CA, USA): the mean value of 30 healthy donors was 1.24 U/ml +/- 0.34 (SD). We set at 15 U/L the cut-off for significance for TK, at 85 U/ml that for sCD23 and at 3 mg/dl the one for b2M. In 156 patients we could also evaluate the expression of ZAP-70 by B-CLL cells by immunohistochemistry (clone 2F3.2, Upstate, Lake Placid NY, USA). Finally, we defined a score on the basis of the presence of an elevated value (0 = no factors; 1 = one elevated sPF; 2 = two or more elevated sPFs). All sPFs were associated with shorter TTP: TK>15 U/L: hazard ratio (HR) 3.3; 95% CI: 2.3-4.8; sCD23>85 U/mL: HR 6.11; 95% CI: 4.1- 9.0; B2M>3 mg/dL: 4.1; 95% CI: 2.8-5.9. Nevertheless, none of them was independent from most of other well-known risk factors, including ZAP-70 expression. 167 patients resulted score=0, 43 score=1, and 44 score=2. At the multivariate, score=2 proved independent from ZAP-70 expression, advanced stage, age, sex and lymphocyte count in predicting ear- lier progression (HR 1.82; 95% CI: 1.05-3.16) (Table 1). Score=2 also identified a subgroup at very high risk of progression among stage A, ZAP-70 negative patients, with median TTP of only 10 months (HR 2.56; 95% CI: 1.18-5.52). Score=2 was significantly associated with poorer OS only at the univariate analysis. The combined evaluation of TK, sCD23 and b2M levels is a simple and effective way to predict prog- nosis in B-CLL patients independently from other factors, including stage and ZAP-70. Funding. Supported by: Regione Veneto “Ricerca Sanitaria Final- izzata”; “Fondazione G. Berlucchi per la Ricerca sul Cancro”; AIRC - Associ- azione Italiana Ricerca sul Cancro; Fondazione CARIVERONA.
THE COMBINATION OF SERUM THYMIDINE KINASE, B-2-MICROGLOBULIN AND SOLUBLE CD23 AT DIAGNOSIS IS PREDICTIVE FOR PROGRESSION IN B-CELL CHRONIC LYMPHOCYTIC LEUKEMIA, INDEPENDENTLY FROM ZAP-70 EXPRESSION
ZANOTTI, ROBERTA;AMBROSETTI, Achille;SCUPOLI, Maria;LOVATO, Ornella;PERBELLINI, Omar;CHILOSI, Marco;PIZZOLO, Giovanni
2009-01-01
Abstract
Thymidine kinase (TK), β-2-microglobulin (β2M) and soluble CD23 (sCD23) are among the most widely used soluble prognostic factors (sPFs) in patients with B-cell chronic lymphocytic leukemia (B-CLL). Aim of our study was the retrospective evaluation of a prognostic score mod- eled on their combination. We analysed the levels of these three sPFs in B-CLL patients, using available sera sampled at diagnosis and stored at –20°C. Of 254 patients, 150 were males (59%), median age at diagnosis was 66 years (range: 40-85) and Binet stage was A in 208 cases (82%), B in 36 (14%), and C in 10 (4%). Median follow-up was 77 months (14- 259). TK activity was measured by a radioenzymatic assay by Imm- munotech (Beckman-Coulter): the mean value of 80 healthy donors was 3.7 U/L +/- 2 (SD). sCD23 levels were measured by ELISA (Biosource International, Camarilla, CA, USA): the mean value of 30 healthy donors was 1.24 U/ml +/- 0.34 (SD). We set at 15 U/L the cut-off for significance for TK, at 85 U/ml that for sCD23 and at 3 mg/dl the one for b2M. In 156 patients we could also evaluate the expression of ZAP-70 by B-CLL cells by immunohistochemistry (clone 2F3.2, Upstate, Lake Placid NY, USA). Finally, we defined a score on the basis of the presence of an elevated value (0 = no factors; 1 = one elevated sPF; 2 = two or more elevated sPFs). All sPFs were associated with shorter TTP: TK>15 U/L: hazard ratio (HR) 3.3; 95% CI: 2.3-4.8; sCD23>85 U/mL: HR 6.11; 95% CI: 4.1- 9.0; B2M>3 mg/dL: 4.1; 95% CI: 2.8-5.9. Nevertheless, none of them was independent from most of other well-known risk factors, including ZAP-70 expression. 167 patients resulted score=0, 43 score=1, and 44 score=2. At the multivariate, score=2 proved independent from ZAP-70 expression, advanced stage, age, sex and lymphocyte count in predicting ear- lier progression (HR 1.82; 95% CI: 1.05-3.16) (Table 1). Score=2 also identified a subgroup at very high risk of progression among stage A, ZAP-70 negative patients, with median TTP of only 10 months (HR 2.56; 95% CI: 1.18-5.52). Score=2 was significantly associated with poorer OS only at the univariate analysis. The combined evaluation of TK, sCD23 and b2M levels is a simple and effective way to predict prog- nosis in B-CLL patients independently from other factors, including stage and ZAP-70. Funding. Supported by: Regione Veneto “Ricerca Sanitaria Final- izzata”; “Fondazione G. Berlucchi per la Ricerca sul Cancro”; AIRC - Associ- azione Italiana Ricerca sul Cancro; Fondazione CARIVERONA.
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