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This vicious circle is then fed with reduced copper metallation of SOD1, decreasing its enzymatic function on the one hand and upregulating oxidative stress-induced SOD1 on the other

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Results from the CCG-1961 trial for high-risk ALL, which included patients with T-ALL, showed that an augmented Berlin-Frankfurt-Münster (BFM) regimen with a single delayed intensification course produced the best results for patients with morphological rapid response to initial induction therapy (estimated 5-year EFS rate, 83%).[9,10] With this approach, patients with a presenting WBC count greater than 200,000 had similar outcomes to those with a WBC count of less than 200,000.[11][Level of evidence B1] Overall results from POG-9404 and CCG-1961 were similar, although POG-9404 used a higher cumulative dose of anthracyclines and cranial radiation therapy for every patient, while CCG-1961 used cranial radiation therapy only for patients with slow morphological response.[10,5] Among children with NCI standard-risk T-ALL treated on the CCG-1952, COG-1991, and POG-9404 trials, the 7-year EFS rates were comparable with those of patients treated with the CCG regimens that used significantly less anthracycline in a less intensive chemotherapy backbone without the prophylactic cranial irradiation included in POG-9404.[12] However, the patients with NCI standard-risk T-ALL had an inferior EFS and OS compared with patients with NCI standard-risk B-ALL treated with the same regimens on the CCG-1952 and COG-1991 trials.[12] In the COG, children with T-ALL are not treated on the same protocols as children with B-ALL