Updated Results of JALSG AML201 Study Comparing Intensified Daunorubicin with Idarubicin in Patients with De Novo Acute Myeloid Leukemia: Effect of Hematopoietic Stem Cell Transplantation.

We conducted a randomized study to determine whether the intensified daunorubicin (DNR) induction chemotherapy would be as effective as idarubicin (IDR) in adult acute myeloid leukemia (AML). From December 2001 to December 2005, 1064 newly diagnosed patients with de novo AML were registered and 1057 were eligible. Median age was 47 years old (range 15 to 64). The patients with AML excluding FAB-M3 were randomized to receive either increased dose of DNR (50 mg/m² daily for 5 days) or standard dose of IDR (12 mg/m² daily for 3 days), with cytarabine 100 mg/m² daily for 7 days by continuous intravenous infusion for induction chemotherapy. Complete remission (CR) was achieved in 407 patients (77.5%; 95% CI, 73.9% – 81.1%) in DNR group and 416 patients (78.2%; 74.7% – 81.7%) in IDR group (p = 0.79). After a median follow up of 48 months there was also no significant difference between the groups in the longer-time measures of efficacy: estimated overall survival at 5 years was 48.0% (95% CI: 43.3% – 52.8%) for DNR and 47.6% (42.8% – 52.4%) for IDR (p = 0.54); estimated relapse free survival at 5 years from CR was 40.7% (35.4% – 45.4%) for DNR and 40.6% (35.6% – 45.6%) for IDR (p = 0.97). The second purpose of this study was to evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-SCT) during the first CR in patients with intermediate or poor risk. If the patients other than CBF leukemia were in CR and had an HLA identical related donor, we recommended them to receive allo-SCT. Of the 823 patients that achieved CR, 132 (16.0%, madeian age, 37 years old; range, 15 – 61) received allo-SCT during the first CR: 72 patients, allo-SCT from a related donor and 60, from an unrelated donor. We examined the efficacy of SCT by comparing these patients with those who did not receive SCT using a matched-pair analysis method. We were able to select 95 pairs of patients by matching karyotype (MRC category), prognostic category established by JALSG, number and type (DNR or IDR) of induction therapy, post-remission therapy and age, that received (SCT pts) and did not receive SCT (non-SCT pts) during the first CR. Variables such as initial WBC count, diagnosis by FAB classification and myeloperoxidase positivity of blasts were comparable between the two groups. Estimated relapse free survival at 5 years from CR was 62.9% (52.5% – 73.3%) for SCT pts and 28.2% (20.6% – 35.8%) for non-SCT pts (p < 0.0001), and estimated overall survival at 5 years was 62.7% (51.5% – 73.8%) for SCT pts and 49.3% (40.6% – 58.1%) for non-SCT pts (p = 0.016). Estimated overall survival at 5 years was 47.0% (39.5% – 54.5%) in patients that received their first allo-SCT after relapse. It is noteworthy that many patients who suffered from relapse were also rescued by allo-SCT. We conclude that the long-term efficacy of the induction chemotherapy with increased dose of DNR and that with standard dose of IDR were comparable demonstrating high remission rate and fair overall survival. They are equally effective for the treatment of AML patients up to 64 years old. It is suggested that SCT during the first CR is recommended for patients that are categorized into the intermediate or poor risk group if a suitable donor is available.