Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Acute Myeloid Leukemia: Results of the AML BFM Study Group
Authors: Rettinger Eva , Hutter Martin , Karschen Birte , Antoniou Evangelia , Bader Peter , Beier Rita , Burkhardt Birgit , Creutzig Ursula , Escherich Gabriele , Klusmann Jan-Henning , Lang Peter , Niktoreh Naghmeh , Sauer Martin G. , Sendker Stephanie , Reinhardt Dirk , Waack Katharina 
Published: December 2024

Introduction:
The considerable success in the transplant field has changed transplant indications for pediatric acute myeloid leukemia (AML). However, the risk stratification for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1) and the importance of a remission with negative or low minimal residual disease before transplantation in relapsed/refractory diseases are still under discussion.
Patients:
This analysis critically evaluates and summarizes the role of allo-HSCT in treating children and adolescents with AML registered in the AML-BFM trials 2004 (EudraCT 2006-004710-41) and 2012 (EudraCT 2013-000018-39) and the AML-BFM 2012 registry spanning the years 2004 to 2019. This population-based study includes 381 pediatric patients diagnosed with various subtypes of AML (excluding Down syndrome, acute promyeloblastic leukemia, and treatment-related AML) in Germany from March 2004 to September 2017. The cohort consisted of 168 females (44%) and 213 males (56%), initially stratified into standard risk (SR, N=43, 11%), intermediate risk (IR, N=201, 53%), and high risk (HR, N=137, 36%) based on criteria regarding cytogenetics/molecular aberrations and response to treatment according to the Berlin-Frankfurt-Münster (BFM) study group, which changed over time.
Results:
Allo-HSCTs were performed between July 2004 and August 2018. The median age at the time of allo-HSCT was 8.9 years (range: 0.4-21.2 years). Donors included matched sibling donors (MSD, N=88, 27%), matched unrelated donors (MUD, N=200, 60%), haploidentical donors (N=41, 12%), and other mismatched donors (N=3, 1%). The remission status at the time of transplantation was as follows: CR1 (N=166, 44%), second or greater complete remission (≥CR2, N=136, 36%), or refractory diseases (NR) with or without leukemic blasts after the second course of induction (N=55, 14%; N=24, 6%). The median follow-up of the entire cohort was 7.7 years. The 4-year overall survival (OS) and disease-free survival (DFS) probabilities for the entire cohort were 71.5%±2.3% and 62.9%±2.5%, respectively. OS and DFS estimates improved over time, with 62.5%±3.1% and 56.4%±3.1% in the AML-BFM 2004 trial and 88.1%±2.9% and 74.9%±3.8% in the AML-BFM 2012 trial/registry analyzed together (p&lt;0.001 for both comparisons). Patients transplanted in CR1 (84.2%±2.8% and 73.4%±3.4%) showed significantly better OS and DFS compared to those transplanted in ≥CR2 (73.4%±3.8% and 65.4%±4.1%) and those in NR without (54.2%±10.2% and 50.0%±10.2%) or with evidence of leukemic blasts (35.9%±6.5% and 30.7%±6.2%; p&lt;0.001 for both comparisons). Notably, survival estimates between MSD (79.4%±4.3% and 73.9%±4.7%) and MUD (69.8%±3.3% and 62.4%±3.4%) were comparable and superior to haploidentical donors (60.7%±7.7% and 41.2%±7.7%; p=0.042 and p&lt;0.001).
Conclusion:
Paralleled by studies to optimize disease characteristics, risk stratification, pre-transplant treatment strategies, and successes in the transplant field, survival of patients with pediatric AML transplanted in ≥CR2 and even of those with relapsed/refractory disease has constantly improved, with survival rates now approaching up to 85% in CR1. This data emphasizes the inclusion of children and adolsecents with AML into clinical trials to further enhance treatment responses through novel promising drugs and to expand indications for allo-HSCT in CR1.