TY  - JOUR
A1  - Rasche, Mareike
A1  - Zimmermann, Martin
A1  - Steidel, Emma
A1  - Alonzo, Todd
A1  - Aplenc, Richard
A1  - Bourquin, Jean-Pierre
A1  - Boztug, Heidrun
A1  - Cooper, Todd
A1  - Gamis, Alan S.
A1  - Gerbing, Robert B.
A1  - Janotova, Iveta
A1  - Klusmann, Jan-Henning
A1  - Lehrnbecher, Thomas
A1  - Mühlegger, Nora
A1  - Neuhoff, Nils von
A1  - Niktoreh, Naghmeh
A1  - Sramkova, Lucie
A1  - Stary, Jan
A1  - Waack, Katharina
A1  - Walter, Christiane
A1  - Creutzig, Ursula
A1  - Dworzak, Michael
A1  - Kaspers, Gertjan
A1  - Kolb, Edward Anders
A1  - Reinhardt, Dirk
T1  - Survival following relapse in children with Acute Myeloid leukemia: a report from AML-BFM and COG
T2  - Cancers
N2  - 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.
KW  - acute myeloid leukemia
KW  - relapse
KW  - childhood acute myeloid leukemia
KW  - pediatric
KW  - salvage therapy
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62114
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-621140
SN  - 2072-6694
VL  - 13
IS  - 10, art. 2336
SP  - 1
EP  - 14
PB  - MDPI
CY  - Basel
ER  -