Patients affected by B-cell chronic lymphocytic leukemia (CLL) follow extremely variable clinical courses with overall survival times that range from months to decades. Clinical and biological factors with potential prognostic relevance have been searched in order to find markers that may help to refine outcome prediction for these individuals. Angiopoietin 2 (Ang2) is a pro-angiogenic factor which mRNA expression is increased in poor prognosis CLL patients. In order to better define the prognostic role of this molecule in CLL, we measured Ang2 plasmatic levels in 244 patients collected from several Italian centers, valuing associations with main established prognostic factors and clinical behavior. We observed variable plasmatic quantities of Ang2 (median value 1963 pg/ml, range 972-17281 pg/mL). We compared Ang2 amounts between different CLL prognostic subgroups and we found they were higher in cases with Binet stage B/C than A (p=0.002), in patients with unmutated Ig than mutated (p<0.0001) and in cases CD38 positive than negative (p=0.027). Moreover, we showed positive correlation between Ang2 plasmatic levels and b2 microglobulin (p<0.0001), LDH (p=0.029) and percentage of bone marrow lymphocytosis (p=0.030). Defining the best cut-off for Ang2 plasmatic levels in relation to time to first treatment (TTT), CLL patients were divided into Ang2 positive and Ang2 negative subset. Ang2 positive cases had shorter TTT than Ang2 negative (p=0.001): TTT was confirmed to be correlated with known established CLL prognostic factors. In bivariate analysis, Ang2 positive patients had shorter TTT than Ang-2 negative, even inside the subgroup with Binet stage B/C (p=0.005), with mutated Ig (p=0.010), CD38 negative (p=0.002), with low cytogenetic risk (p=0.005), with low CD49d (p<0.0001) and ZAP70 negative (p=0.006). In multivariate analysis with biological variables, plasmatic Ang2 resulted to be an independent prognostic factor for TTT as well as Ig mutational status and cytogenetic risk. In multivariate analysis with variables related to tumor burden, plasmatic Ang2 was an independent prognostic factor for TTT as well as Binet staging and b2 microglobulin. These data suggest that Ang2 plasmatic levels are associated with a progressive behavior of CLL and represent an independent factor predicting time to first treatment, allowing a more accurate prognostication and helping in a better managing of therapies for CLL patients.
PROGNOSTIC VALUE OF PLASMATIC LEVELS OF ANGIOPOIETIN 2 IN B-CELL CHRONIC LYMPHOCYTIC LEUKEMIA
RIGOLIN, Gian Matteo;CUNEO, Antonio;
2009
Abstract
Patients affected by B-cell chronic lymphocytic leukemia (CLL) follow extremely variable clinical courses with overall survival times that range from months to decades. Clinical and biological factors with potential prognostic relevance have been searched in order to find markers that may help to refine outcome prediction for these individuals. Angiopoietin 2 (Ang2) is a pro-angiogenic factor which mRNA expression is increased in poor prognosis CLL patients. In order to better define the prognostic role of this molecule in CLL, we measured Ang2 plasmatic levels in 244 patients collected from several Italian centers, valuing associations with main established prognostic factors and clinical behavior. We observed variable plasmatic quantities of Ang2 (median value 1963 pg/ml, range 972-17281 pg/mL). We compared Ang2 amounts between different CLL prognostic subgroups and we found they were higher in cases with Binet stage B/C than A (p=0.002), in patients with unmutated Ig than mutated (p<0.0001) and in cases CD38 positive than negative (p=0.027). Moreover, we showed positive correlation between Ang2 plasmatic levels and b2 microglobulin (p<0.0001), LDH (p=0.029) and percentage of bone marrow lymphocytosis (p=0.030). Defining the best cut-off for Ang2 plasmatic levels in relation to time to first treatment (TTT), CLL patients were divided into Ang2 positive and Ang2 negative subset. Ang2 positive cases had shorter TTT than Ang2 negative (p=0.001): TTT was confirmed to be correlated with known established CLL prognostic factors. In bivariate analysis, Ang2 positive patients had shorter TTT than Ang-2 negative, even inside the subgroup with Binet stage B/C (p=0.005), with mutated Ig (p=0.010), CD38 negative (p=0.002), with low cytogenetic risk (p=0.005), with low CD49d (p<0.0001) and ZAP70 negative (p=0.006). In multivariate analysis with biological variables, plasmatic Ang2 resulted to be an independent prognostic factor for TTT as well as Ig mutational status and cytogenetic risk. In multivariate analysis with variables related to tumor burden, plasmatic Ang2 was an independent prognostic factor for TTT as well as Binet staging and b2 microglobulin. These data suggest that Ang2 plasmatic levels are associated with a progressive behavior of CLL and represent an independent factor predicting time to first treatment, allowing a more accurate prognostication and helping in a better managing of therapies for CLL patients.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
