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

Abstract

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.

Causes of early death and treatment‐related death in newly diagnosed pediatric acute myeloid leukemia: Recent experiences of the Dutch Childhood Oncology Group

“…Patients, aged 0 to 19 years, with AML, newly diagnosed between 1998 and 2014 and participating in one of the following DCOG protocols—ANLL‐97/MRC AML‐12 (ANLL97; 1998‐2002), AML‐15 (AML15; 2002‐2009), DB AML‐01 (DB01; 2009‐2014)—were eligible for inclusion. Written informed consent (IC) by the patient and/or parents/guardians for the use of information for study purposes (normally implemented in the overall IC of the applicable protocols) had to be present.…”

Nucleophosmin mutations confer an independent favorable prognostic impact in 869 pediatric patients with acute myeloid leukemia

“…Acute myeloid leukemia (AML) is a genetically heterogeneous disease that accounts for about 20% of pediatric leukemia. The overall 5-year survival rate for pediatric patients with AML has increased over time and is now in the range of 65-70% 1 . Most of the advances have been made by better risk classification, the implementation of excellent supportive care measures, and improvements in allogeneic hematopoietic stem cell transplantation 2 .…”

TARP is an immunotherapeutic target in acute myeloid leukemia expressed in the leukemic stem cell compartment

“…Despite initial clinical remission rates of 60-90%, 2,5,6 patients exhibit a high relapse risk and therapyrelated mortality, resulting in a 5-year overall survival of 30% in adult AML 1,3 and 65-70% in pediatric AML (pedAML). 5,8 Especially the prognosis of patients with fms-like tyrosine kinase receptor-3 internal tandem duplications (FLT3-ITD) remains extremely poor. 2,8,9 The high relapse rate is thought to arise from a chemotherapy-resistant cell fraction with unlimited self-renewal capacities, TARP is an immunotherapeutic target in acute myeloid leukemia expressed in the leukemic stem cell compartment cell transplantation, performed in high-risk (HR) patients or as salvage therapy, carries a high mortality and morbidity risk, 2,5 highlighting the need for alternative treatments.…”