Postremission Therapy in Adult Acute Myeloid Leukemia (AML): A Randomized Comparison of Intensified Consolidation Therapy without Maintenance Therapy Against Conventional Consolidation with Maintenance Therapy -JALSG AML-97 Trial-.

Between 1997 and 2001, JALSG conducted a randomized study to assess the optimal post remission therapy for adult AML in the first CR. The JALSG AML97 enrolled 809 previously untreated AML patients (pts) aged 15–64 yrs. Induction therapy consisted of cytarabine (100mg/m2 day1–7) and idarubicin (IDR 12mg/m2 day1– 3). If the patients did not achieve remission after the first induction therapy, the same therapy was given once more. Pts were categorized into good, intermediate or poor risk groups by risk factors based on the previous JALSG AML studies. All CR pts were randomized to receive either the intensified short course post remission regimen (arm A) or the conventional JALSG’s post remission regimen for AML including maintenance therapy (arm B). Arm A: 1) AraC 200mg/m2 day1–5+ Mitoxantrone (MTZ) 7mg/m2 day1–3, 2) AraC 200mg/m2 day1–5+Daunorubicin (DNR) 50mg/m2 day1–3, 3) AraC 200mg/ m2 day1–5+ Aclacinomycin (ACR) 20mg/m2 day1–5, 4) AraC 200mg/m2 day1–5+ Etoposide (ETP) 100mg/m2 day1–5 + Vincristine (VCR) 0.8mg/m2 day 8 + Vindesine (VDS) 2 mg/m2 day10. Arm B: 1) AraC 200mg/m2 day1–5 + MTZ 7mg/m2 day1–3, 2) Behenoyl AraC (BHAC) 200mg/m2 day1–7 + ETP 100mg/m2 day1–5 + DNR 50mg/m2 day1–3 + 6 mercptopurine (6MP) day1–7, 3) BHAC 200mg/m2 day1–7 + ACR 14mg/m2 day1–7, and then 6 courses maintenance therapy: 1) BHAC 170mg/m2 day1–5 + DNR 50mg/m2 day1,4+6MP day1–7, 2) BHAC 170mg/m2 day1–5 + MTZ 5mg/m2 day1–3, 3) BHAC 170mg/m2day1–5 + ETP 80mg/m2 day1,5,7 + VDS 2mg/m2 day1,8, 4) BHAC 170mg/m2 day1–5 + ACR 14mg/m2 day1–4 + 6MP day1–7, 5) BHAC 170mg/m2 day1–5 + DNR 50mg/m2 day1–4 + 6MP day1–7, 6) BHAC 170mg/m2 day1–5 + ETP 80mg/m2 day1,5,7 + VDS 2mg/m2 day1,8.

Result: Of the 809 pts registered, 789 pts (median age: 45 years) were evaluable. 621 pts (78.7%) achieved CR after one or two courses of induction therapy. The 5-year OS rate of arm A was 45.6% and of arm B 53.2% (p=0.3259). The 5-year DFS rate of CR patients was 34.8% in arm A and 28.9% in arm B (p=0.4978). Among the good risk group, the 5-year OS rate of arm A was 62.1% and of arm B 70.2% (p=0.5068), and the 5-year DFS rate of arm A was 53.4% and of arm B 42.0% (p=0.3719). Among the intermediate risk group, the 5-year OS rate of arm A was 35.6% and of arm B 45.5% (p=0.4776), and the 5-year DFS rate of arm A was 26.0% and of arm B 26.1% (p=0.9653). Among the poor risk group, the 5-year OS rate of arm A was 29.7% and of arm B was 33.4% (p=0.6523), and the 5-year DFS rate of arm A was 20.4% and of arm B was 13.5% (p=0.6339). In conclusion: JALSG’s conventional post remission therapy consisting of 3 courses of consolidation and 6 courses of maintenance therapy could be replaced by a shorter duration of intensified consolidation therapy.