Survival Following Relapse in Children with Acute Myeloid Leukemia: A Report from AML-BFM and COG
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Mareike Rasche
1,*
,
Martin Zimmermann
2,
Emma Steidel
1,
Todd Alonzo
3,
Richard Aplenc
4,
Jean-Pierre Bourquin
5,
Heidrun Boztug
6,
Todd Cooper
7,
Alan S. Gamis
8,
Robert B. Gerbing
9,
Iveta Janotova
10,
Jan-Henning Klusmann
11,
Thomas Lehrnbecher
12, 
Nora Mühlegger
6,
Nils v. Neuhoff
1,
Naghmeh Niktoreh
1,
Lucie Sramkova
10,
Jan Stary
10,
Katharina Waack
1,
Christiane Walter
1,
Ursula Creutzig
2,
Michael Dworzak
6,
Gertjan Kaspers
13,14,
Edward Anders Kolb
15,† and
Dirk Reinhardt
1,†add
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1
Department of Pediatric Hematology-Oncology, Pediatrics III, University Hospital of Essen, 45147 Essen, Germany
2
Department of Pediatric Hematology and Oncology, Hannover Medical School, 30625 Hannover, Germany
3
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
4
Division of Oncology, The Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA
5
Division of Pediatric Hematology/Oncology, University Children’s Hospital Zurich, CH-8032 Zurich, Switzerland
6
St Anna Children’s Hospital and Children’s Cancer Research Institute, Department of Pediatrics, Medical University of Vienna, 1090 Vienna, Austria
7
Seattle Children’s Hospital, Seattle, WA 98105, USA
8
Children’s Mercy Hospitals and Clinics, Kansas City, MO 64108, USA
9
Children’s Oncology Group, Monrovia, CA 91016, USA
10
Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, 150 06 Prague, Czech Republic
11
Clinic for Pediatrics 1, Martin Luther University Halle-Wittenberg, 06108 Halle, Germany
12
Division for Pediatric Hematology and Oncology, Hospital for Children and Adolescents, University Hospital, Goethe University Frankfurt am Main, 60590 Frankfurt, Germany
13
Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands
14
Pediatric Oncology, Emma Children’s Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, 1105 AZ Amsterdam, The Netherlands
15
Nemours/Alfred I. du Pont Hospital for Children, Wilmington, DE 19803, USA
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cancers 2021, 13(10), 2336; https://doi.org/10.3390/cancers13102336
Submission received: 17 April 2021
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Revised: 5 May 2021
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Accepted: 7 May 2021
/
Published: 12 May 2021
(This article belongs to the Section Clinical Research of Cancer)
Simple Summary
Acute myeloid leukemia in children remains a difficult disease to cure despite intensive therapies that push the limits of tolerability. Though the intent of initial therapy should be the prevention of relapse, about 30% of all patients experience a relapse. Hence, relapse therapy remains critically important for survival. This retrospective analysis of two large international study groups (COG and BFM) was undertaken to describe the current survival, response rates and clinical features that predict outcomes. We demonstrate that children with relapsed AML may be cured with cytotoxic therapy followed by HSCT. High-risk features at initial diagnosis and early relapse remain prognostic for post-relapse survival. Current response criteria are not aligned with the standards of care for children, nor are the count recovery thresholds meaningful for prognosis in children with relapsed AML. Our data provide a new baseline for future treatment planning and will allow an updated stratification in upcoming studies.
Abstract
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.
