Repetitive Cycles of High-Dose Cytarabine Are Effective for Childhood Acute Myeloid Leukemia (AML): Long Term Outcome of the Children with AML Treated on Two Consecutive Trials of Tokyo Children's Cancer Study Group.

Abstract

Intensive chemotherapy has contributed to an improved survival in pediatric acute myeloid leukemia (AML). We here report the long term results of the two consecutive AML trials of Tokyo Children's Cancer Study Group; TCCSG M91-13 and M96-14. Between August 1991 and September 1998, a total of 216 eligible children with newly diagnosed AML entered either of the two trials. In M91-13 trial, patients received 3-drug induction therapy consisted of cytarabine, mitoxantrone, and etoposide, 4 courses of intensive consolidation chemotherapy including 2 courses with high-dose cytarabine. Subsequently, patients received another 4 courses of high-dose cytarabine containing consolidation chemotherapy, or autologous bone marrow or peripheral blood stem cell transplantation (A-BMT/PBSCT) instead. Allogeneic bone marrow transplantation (allo-BMT) was recommended for patients with HLA-matched family donor. In M96-14 trial, the last two courses of consolidation chemotherapy were omitted from the chemotherapy arm, and patients with FAB M3 were treated with all-trans-retinoic acid containing regimen. The remission induction rate, as a whole, was 81% and probability of 5-year overall survival and event-free survival were 62%±6% (95% confidence interval) and 56%±6% by Kaplan-Meier method, respectively. There were no significant differences in survivals among the three types of post-remission therapy (chemotherapy (n = 126), 64%±8%; allo-BMT (n = 34), 76%±14%; A-BMT/PBSCT (n = 32), 80%±13%). Although the number of consolidation chemotherapy courses were reduced from 8 to 6 in M96-14 trial, overall survival rate of each trial was similar (61%±8% vs. 64%±10%, P = 0.48). The overall survival rates of patients with low risk features, namely, t(8;21), inv(16), t(15;17) or FAB M3, and Down syndrome, were significantly better than that of the other patients (75%±9% vs. 55%±8%, P = 0.002). These results suggest that intensive high-dose cytarabine containing treatment was very effective for childhood AML regardless of types of post-remission therapy. As the chemotherapy courses could be safely reduced in number without compromising the results in the latter study, further optimization of AML therapy is required.