Interleukin-8 is not a predictive biomarker for the development of the acute promyelocytic leukemia differentiation syndrome.

BACKGROUND: Differentiation syndrome (DS) is the main life-threatening adverse event that occurs in acute promyelocytic leukemia (APL) patients treated with all-trans retinoic acid (ATRA). Cytokine imbalances have been reported to play role during the developing of acute promyelocytic leukemia differentiation syndrome (APL-DS). However, the relationship between the plasma cytokine levels and their prognostic value for the prediction of DS developing in patients with APL during the treatment with ATRA and anthracyclines has not been previously reported. METHODS: In this study, we followed an APL cohort (n = 17) over 7 days of ATRA therapy in DS (n = 6) and non-DS groups (n = 11). Interleukin (IL)-1ß, IL-6, IL-8, IL-10, IL-12p70 and TNF-α were measured in the peripheral blood plasma from 17 patients with APL and 11 healthy adult controls by using the cytometric bead array method. RESULTS: In non-DS patients, IL-8 plasma levels were significantly reduced in the seventh day of ATRA treatment (34.16; 6.99 to 147.11 pg mL- 1 in D0 vs. 10.9; 0 to 26.81 pg mL- 1 in D7; p = 0.02) whereas their levels did not discriminate between DS and non-DS development during the entire induction period (all p > 0.05 in D0, D3, and D7). No significant differences were found in IL-6 levels between groups (p > 0.05 in D0-D7). Other cytokines tested were all undetectable in patients with APL or healthy controls. CONCLUSIONS: We demonstrated that the modulation of IL-8 following ATRA treatment may occur regardless of the development of DS and, therefore, does not appear to be a predictive biomarker to monitor the APL-DS.

Procoagulant state after raloxifene therapy in postmenopausal women.

OBJECTIVE: To investigate the effects of raloxifene on the hemostatic system in postmenopausal women. DESIGN: A prospective longitudinal study. SETTING: Outpatient clinic of the Faculty of Medicine of Ribeirão Preto, Brazil. PATIENT(S): Sixteen postmenopausal women aged 56.8 +/- 5.9 years (mean +/- SD). INTERVENTION(S): Raloxifene hydrochloride (60 mg once daily) was administered orally for a period of 6 months. MAIN OUTCOME MEASURE(S): Plasma activities of coagulation factors (II, V, VII, VIII, IX, X, XI, XII, and fibrinogen), prothrombin-derived fragment 1+2, and activated protein C (APC) sensitivity ratio were measured at baseline and after 1, 3, and 6 months of treatment. RESULT(S): Factor VIII activity increased by 17.1% and 26.9% at 3 and 6 months of treatment, respectively, compared with baseline. Factor XI and FXII activities significantly increased by 10.9% and 43.1%, respectively, after 6 months compared with baseline. A significant reduction of APC sensitivity ratio also was observed after 6 months of treatment. CONCLUSION(S): A procoagulant state characterized by increased factor VIII, XI, and XII plasma levels and by reduced APC sensitivity was observed after raloxifene therapy in post-menopausal women.