Therapy, testing, and osteonecrosis on Total XV study. (A) Schema of sample collection, asparaginase and glucocorticoid dosing, and MRI screening. Blood samples were collected on consolidation day 15 and week 2, week 7, week 8, and week 12 of continuation phase of therapy. Prednisone was administered at 40 mg/m2 per day during remission induction. Dexamethasone was given at 12 mg/m2 per day (SR/HR arm) and 8 mg/m2 per day (LR) during continuation weeks 1 to 6 and 10 to 16; and at 8 mg/m2 per day for both treatment arms at weeks 7, 9, 17, and 19. Asparaginase was administered at 10 000 U/m2 per dose intramuscularly 3 times weekly for 6 to 9 doses during remission induction; those in SR/HR arms received 25 000 U/m2 per week from weeks 1 to 19; those in the LR arm received 10 000 U/m2 3 times weekly for 9 doses at weeks 7-9 and 17-19. MRI screens were scheduled to be performed at weeks 9-10 and 19-20. (B) Cumulative incidence of asymptomatic and symptomatic osteonecrosis. The top curve represents the first incidence of asymptomatic osteonecrosis in those whose worst grade was grade 1; and lower curve, the first incidence of symptomatic osteonecrosis in those who eventually developed grade 2 to 4 osteonecrosis.
