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. 2021 May 12;13(10):2336.
doi: 10.3390/cancers13102336.

Survival Following Relapse in Children with Acute Myeloid Leukemia: A Report from AML-BFM and COG

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 , Dirk Reinhardt  1
Affiliations

Survival Following Relapse in Children with Acute Myeloid Leukemia: A Report from AML-BFM and COG

Mareike Rasche et al. Cancers (Basel). .

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.

Keywords: acute myeloid leukemia; childhood acute myeloid leukemia; pediatric; relapse; salvage therapy.

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Conflict of interest statement

D.R. has advisory roles for Celgene Corporation, Novartis, Bluebird Bio, Janssen, and receives research funding from CLS Behring and Roche. J.-H.K. has advisory roles for Bluebird Bio, Roche and Jazz Pharmaceuticals. J.-P.B. received travel support from Servier. All other authors have nothing to declare. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Figures

Figure 1
Figure 1
Overall survival at first relapse. (A) Five-year overall survival in patients with pediatric AML with diagnosed first relapse from 04/2009 until 07/2013 vs. 08/2013—12/2017. (B) Five-year overall survival in patients with pediatric AML with first relapse enrolled in the BFM registry compared to patients with first relapse enrolled in the previous I-BFM Relapse 2001/01 trial. (C) Five-year overall survival following relapse of patients enrolled on COG AAML0531 and COG AAML1031. (D) Five-year overall survival for first relapse patients in the COG cohort by year. Group 2018 until 2019 is excluded.
Figure 2
Figure 2
Prognostic factors for post-relapse survival. (A) Five-year overall survival of patients with early or late relapse defined as relapse within or after one year of initial diagnosis (BFM). (B) Five-year overall survival of patients with early or late relapse (COG). (C) Five-year overall survival in patients with first relapse based on the genetic risk profile of the initial diagnosis (BFM). (D) Five-year overall survival from relapse for AAML1031 and AAML0531 patients based on a retrospective classification by AAML1031 risk group definition (Table S1). (E) Five-year overall survival of patients based on the initial response to induction chemotherapy of the initial disease (BFM). Abbreviations: HR, high-risk. (F) Five-year overall survival according to residual disease detection at the end of one cycle of induction following initial diagnosis and treatment (COG).
Figure 3
Figure 3
Response and EFS at first relapse. (A) Five-year overall survival in patients with pediatric AML with first relapse based on the response to DNX-FLA(G) +/− FLA(G) comparing complete remission with complete (CR) and partial regeneration (CRp) and CRi vs. nonresponse and aplasia. (B) Five-year overall survival in patients with pediatric AML with first relapse based on the detailed response to DNX-FLA(G) +/− FLA(G). (C) Five-year event-free survival in all patients receiving DNX-FLA(G) +/− FLA(G) after first relapse. (D) Five-year event-free survival of patients with early or late relapse defined as relapse within or after one year of initial diagnosis. (E) Five-year event-free survival in patients with first relapse based on the risk profile of the initial diagnosis. (F) Five-year cumulative incidence of a second relapse in all patients receiving DNX-FLA(G) +/− FLA(G). The competing event is death. Abbreviations: HR, high-risk. DNX-FLA(G), liposomal daunorubicin, fludarabine, cytarabine with or without granulocyte-colony-stimulating factor. CR, complete remission; CRp, complete remission with partial regeneration; Cri, complete remission with incomplete recovery. See Table S1 for definitions.
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