Impact of central nervous system involvement in adult patients with Philadelphia-negative acute lymphoblastic leukemia: a GRAALL-2005 study.

Whereas the prognosis of adult patients with Philadelphia-negative acute lymphoblastic leukemia (ALL) has greatly improved since the advent of pediatric-inspired regimens, the impact of initial central nervous system (CNS) involvement has not been formerly re-evaluated. We report here the outcome of patients with initial CNS involvement included in the pediatric-inspired prospective randomized GRAALL-2005 study. Between 2006 and 2014, 784 adult patients (aged 18-59 years) with newly diagnosed Philadelphia-negative ALL were included, of whom 55 (7%) had CNS involvement. In CNSpositive patients, overall survival was shorter (median 1.9 years vs. not reached, HR=1.8 [1.3-2.6], P<0.001). While there was no statistical difference in cumulative incidence of relapse between CNS+ and CNS- patients (HR=1.5 [0.9-2.5], P=0.11), non-relapse mortality was significantly higher in those with initial CNS disease (HR=2.1 [1.2-3.5], P=0.01). This increase in toxicity was mostly observed in patients randomized to the high-dose cyclophosphamide arm and in those who received allogeneic stem cell transplantation. Exploratory landmark analyses did not show any association between either cranial irradiation or allogeneic stem cell transplantation and outcome. Despite improved outcome in young adult ALL patients with pediatric-inspired protocols, CNS involvement is associated with a worse outcome mainly due to excess toxicity, without improved outcome with allogeneic SCT.

Serum anti-carbonic anhydrase antibodies and oxidant-antioxidant balance in patients with acute anterior uveitis.

PURPOSE: To study the existence of anti-carbonic anhydrase antibodies (anti-CA-I&II) in acute anterior uveitis (AAU) patients and to analyze the relationship between the levels of these antibodies and the total antioxidant capacity (TAC), total oxidant capacity (TOC), oxidative stress index (OSI), and malondialdehyde (MDA) level. METHODS: Forty-five AAU cases and 43 healthy controls were enrolled in this prospective study. RESULTS: The average anti-CA I and II antibody levels were 0.433 ± 0.306 and 0.358 ± 0.261 IU/mL, respectively, in the AAU group and 0.275 ± 0.147 and 0.268 ± 0.108 IU/mL, respectively, in the control group (p = 0.004 and p = 0.036, respectively). In addition, it was found that the TOC, OSI, and MDA levels in the AAU subjects were statistically significantly higher than those of the control subjects. CONCLUSIONS: These results suggest that autoimmune responses against CA I and CA II and an altered serum oxidant-antioxidant balance may be involved in the pathogenesis of AAU.