Successful management of relapse is critical to improve outcomes of children with acute myeloid leukemia (AML). We evaluated response, survival and prognostic factors after a second relapse of AML. Among 1222 pediatric patients of the population-based AML-Berlin-Frankfurt-Munster (BFM) study group (2004 until 2017), 73 patients met the quality parameters for inclusion in this study. Central review of source documentation warranted the accuracy of reported data. Treatment approaches included palliation in 17 patients (23%), intensive therapy with curative intent (n = 46, 63%) and other regimens (n = 10). Twenty-five patients (35%) received hematopoietic stem cell transplantation (HSCT), 21 of whom (88%) had a prior HSCT. Survival was poor, with a five-year probability of overall survival (pOS) of 15 ± 4% and 31 ± 9% following HSCT (n = 25). Early second relapse (within one year after first relapse) was associated with dismal outcome (pOS 2 ± 2%, n = 44 vs. 33 ± 9%, n = 29; p < 0.0001). A third complete remission (CR) is required for survival: 31% (n = 14) of patients with intensive treatment achieved a third CR with a pOS of 36 ± 13%, while 28 patients (62%) were non-responders (pOS 7 ± 5%). In conclusion, survival is poor but possible, particularly after a late second relapse and an intensive chemotherapy followed by HSCT. This analysis provides a baseline for future treatment planning.

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

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

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

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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