Intensively Timed Induction (ITI) Chemotherapy in Adults with Acute Myelogenous Leukemia (AML).

The Children’s Cancer Group (CCG) demonstrated that children with AML have longer event free survival (EFS) and disease free survival (DFS), 42 +/− 7% and 55 +/− 9%, at a minimum of two years off of therapy when randomly assigned to ITI rather than standard chemotherapy (Woods, et al Blood 1996 Jun 15;87(12):4979–89). This led us to administer an almost identical regimen of ITI chemotherapy to 50 adults less than 50 years of age with untreated AML, excluding patients (pts) with inv16 or t(8;21). Each pt who remains alive in 1st complete remission (CR) has been followed for more than 3 years: the risk of relapse decreases sharply after this time (de Lima, et al. Blood 1997 Dec 15;90(12):4719–24). Daunorubicin 20 mg/m2/day intravenously (IV) on days 1–4 and 11–14, cytarabine 200 mg/m2/day IV on days 1–4 and 11–14, etoposide 100 mg/m2/day IV on days 1–4 and 11–14 and dexamethasone 6 mg/m2/day PO days 1–4 and 11–14 were given initially along with intrathecal cytarabine 70 mg on day 1 and 11 (DCTER regimen). G-CSF started on day 7 and continued until the ANC was more than 1000 for 2 days. The day 11 chemotherapy was given unless there was hypotension or clinical colitis. All pts started therapy in a protected environment. Pts in CR after the above chemotherapy repeated the induction course. After recovery, cytarabine 3 g/m2 every 12 hours for four doses was infused on days 0–3 and on days 12–15. L-asparaginase 6000 IU/m2 IV was given at hour 18 on days 3 and 15. The cytarabine and L-asparaginase were repeated upon recovery of the granulocyte count. The study was ongoing from 2/15/02 to 8/10/04. The 50 pts, median age 41 years, represented 62% of all pts eligible during this time period. Table 1 compares results in the 50 DCTER pts with the results in 35 non-core binding factor AML pts, median age 41 years, given idarubicin/cytarabine (IA) for induction and consolidation without intensive timing. The results in the IA pts treated from 1991–1993 were similar to those treated 1994–2001 (proportion alive in CR 16% and 19%). The lower CR rate in pts given DCTER reflected an increased death rate in the first 12 weeks after starting treatment. This was counterbalanced by a higher rate of potential cure, considering all 85 pts (95% confidence interval for the true difference [−.09, .34] suggesting that a difference of 26% is as plausible as no difference since .26 and 0 are each equidistant from the midpoint of the confidence interval). A larger cohort is needed to know if the higher early risk associated with DCTER is potentially justified by a better long-term prognosis.