Response-guided chemotherapy for pediatric acute myeloid leukemia without hematopoietic stem cell transplantation in first complete remission: Results from protocol DB AML-01

Background Children with acute myeloid leukemia (AML) have a 70% survival rate with treatment regimens containing high doses of cytarabine and anthracyclines and, in some, hematopoietic stem cell transplantation (allo‐HSCT).

Procedure In this multicenter Dutch–Belgian protocol (DB AML‐01), 112 children with de novo AML were included. Treatment was stratified according to day 15 bone marrow response after the first induction course. Poor responders received a second course without delay while good responders awaited hematological recovery. Patients achieving CR after two induction courses continued with three consolidation courses without HSCT in CR1.

Results The overall remission rate was 93.5%. After a median follow‐up of 4.1 years, three‐year event‐free survival (EFS) was 52.6% (95% CI, 42.9%–61.3%), three‐year cumulative incidence of relapse 39.7% (95% CI, 30.1%–49.0%), and three‐year overall survival (OS) 74.0% (95% CI, 64.8%–81.2%). Significantly more events occurred in patients with high WBC at diagnosis or FLT3‐ITD/NPM1‐WT, whereas core binding factor (CBF) leukemia had a significantly better EFS. KMT2A rearrangements and age > 10 years negatively impacted OS.

Conclusions DB AML‐01 response‐guided therapy results in a favorable OS, particularly for children with CBF leukemia, children younger than 10 years or with initial WBC counts below 100 × 109/L. Outcome of patients with FLT3‐ITD/NPM1‐WT remains poor and warrants alternative treatment strategies.