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.