Post-relapse therapy remains critical for survival in children with acute myeloid leukemia (AML). We evaluated survival, response and prognostic variables following relapse in independent cooperative group studies conducted by COG and the population-based AML-BFM study group. BFM included 197 patients who relapsed after closure of the last I-BFM relapse trial until 2017, while COG included 852 patients who relapsed on the last Phase 3 trials (AAML0531, AAML1031). Overall survival at 5 years (OS) was 42 ± 4% (BFM) and 35 ± 2% (COG). Initial high-risk features (BFM 32 ± 6%, COG 26 ± 4%) and short time to relapse (BFM 29 ± 4%, COG 25 ± 2%) predicted diminished survival. In the BFM dataset, there was no difference in OS for patients who had a complete remission with full hematopoietic recovery (CR) following post-relapse re-induction compared to those with partial neutrophil and platelet recovery (CRp and CRi) only (52 ± 7% vs. 63 ± 10%, p = 0.39). Among 90 patients alive at last follow-up, 87 had received a post-relapse hematopoietic stem cell transplant (HSCT). OS for patients with post-relapse HSCT was 54 ± 4%. In conclusion, initial high-risk features and early relapse remain prognostic. Response assessment with full hematopoietic recovery following initial relapse therapy does not predict survival. These data indicate the need for post-relapse risk stratification in future studies of relapse therapies.

Children's Mercy Hospitals and Clinics Kansas City MO 64108 USA

Children's Oncology Group Monrovia CA 91016 USA

Clinic for Pediatrics 1 Martin Luther University Halle Wittenberg 06108 Halle Germany

Department of Pediatric Hematology and Oncology 2nd Faculty of Medicine Charles University and University Hospital Motol 150 06 Prague Czech Republic

Department of Pediatric Hematology and Oncology Hannover Medical School 30625 Hannover Germany

Department of Pediatric Hematology Oncology Pediatrics 3 University Hospital of Essen 45147 Essen Germany

Department of Preventive Medicine Keck School of Medicine University of Southern California Los Angeles CA 90033 USA

Division for Pediatric Hematology and Oncology Hospital for Children and Adolescents University Hospital Goethe University Frankfurt am Main 60590 Frankfurt Germany

Division of Oncology The Children's Hospital of Philadelphia Philadelphia PA 19104 USA

Division of Pediatric Hematology Oncology University Children's Hospital Zurich CH 8032 Zurich Switzerland

Nemours Alfred 1 du Pont Hospital for Children Wilmington DE 19803 USA

Pediatric Oncology Emma Children's Hospital Amsterdam UMC Vrije Universiteit Amsterdam 1105 AZ Amsterdam The Netherlands

Princess Máxima Center for Pediatric Oncology 3584 CS Utrecht The Netherlands

Seattle Children's Hospital Seattle WA 98105 USA

St Anna Children's Hospital and Children's Cancer Research Institute Department of Pediatrics Medical University of Vienna 1090 Vienna Austria

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