Toxicity
Toxicities for iCSN-R patients treated on AALL02P2 were those expected with 12 months of intensified systemic chemotherapy. There were 6 reports of avascular necrosis (AVN, three Grade 3, three Grade 2), however collection of these data began with a 2008 protocol amendment and may therefore have not included any occurrences of AVN prior to this time. Four patients came off therapy (1 in Induction and 3 prior to radiation) due to intolerable toxicity. These patients each experienced multiple toxicities, including Grade 4 myelosuppression, infection (Rubella, pseudomonas necrotizing fasciitis), peripheral neuropathy, and drug allergy. The most common combined Grade 3 and 4 toxicities reported were: febrile neutropenia (187), mucositis (30) diarrhea (22), hyperglycemia (21), anaphylaxis (20), dehydration (18), sepsis (7), and a thromboembolic event (6). In addition to the 2 Induction deaths, 4 deaths were reported as first events on treatment or within one month of end of treatment, including 3 patients from infectious causes (probable cytomegalovirus and Streptococcus pneumoniae sepsis,Escherichia coli bacteremia, Pseudomonas aeruginosasepsis), and 1 death at home of unknown cause.