Excellent Outcome of Risk Stratified Treatment for Childhood Acute Myeloid Leukemia-AML99 Trial. For the Japanese Childhood AML Cooperative Study Group.

Risk stratified treatment of childhood AML is important to improve the patient’s QOL. Analysis of the Japan cooperative study ANLL91 revealed that response to induction therapy, age at onset, initial WBC counts, and cytogenetics were prognostic factors. Based on these results and reports from other pediatric AML clinical trials, the Japan cooperative study AML99 was planned to test the concept of risk stratified treatment. Patients were stratified into 3 risk categories: low (t(8;21) and WBC <50000, age, 2 yrs without high risk(HR) factors (-7,5q-,Ph1,t(16;21), remission failure), intermediate (neither low nor high). Low risk (LR) patients were treated exclusively with chemotherapy regardless of the availability of donor for HSCT and all the HR patients were treated with HSCT. Intermediate risk (IR) patients with HLA-matched donor were treated with HSCT and those without donor were treated with chemotherapy. Induction therapy for patients with 2y≥ and WBC ≥ 100,000/μl was reinforced employing idarubicine (IDA). Of total, 240 newly diagnosed AML patients under the age of 15 were registered from January 2000 to December 2002. Those with Down syndrome and AML-M3 were treated with different chemotherapy regimens. Final analysis was conducted in March 2005. Remission induction therapy for 214 patients with <2y or WBC<100,000/μl, consisted of VP-16 (VP), cytarabine (CA) and mitoxantrone (MIT) (Induction A), whereas Induction B consisting of VP,CA and IDA was used in 26 patients. LR (109 patients) and IR patients without HLA- matched donor (69 patients) received 5 courses of intensification therapy consisted with VP, CA, MIT or IDA. HR (18 patients) and IR (24 patients) patients with HLA-matched donor received allogeneic HSCT after the 2nd course of intensification therapy. HR patients without HLA matched donor (15 patients) received unrelated HSCT. Complete remission rate (CR) was 94%: 95% for Induction A and 85% for Induction B. The 3-year overall survival(OS) +/− SE for all the patients was 79.2±5.2% and disease free survival(DFS) +/− SE was 65.4±6.2%. The 3-year OS and DFS in each risk group was 88.7% and 71.6% for LR, 79.0% and 60.0% for IR, and 58.3% and 58.3% for HR patients. The 3-year OS for patients who received HSCT after relapse was 60% for the LR, 42% for the IR, and 0% for the HR patients, respectively. These results suggest that IR patients should be treated with chemotherapy only and 50% of them can be rescued with HSCT even after relapse. We conclude that our stratification of children was optimal since OS for all the patients was satisfactory. Only 57 out of 240 patients (24%) received HSCT before relapse and consequently, a majority of children treated in this trial are supposed to enjoy an excellent QOL.