Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2021 Jul:151:175-189.
doi: 10.1016/j.ejca.2021.03.034. Epub 2021 May 16.

Risk factors and outcomes in children with high-risk B-cell precursor and T-cell relapsed acute lymphoblastic leukaemia: combined analysis of ALLR3 and ALL-REZ BFM 2002 clinical trials

Cornelia Eckert  1 , Catriona Parker  2 , Anthony V Moorman  3 , Julie Ae Irving  3 , Renate Kirschner-Schwabe  4 , Stefanie Groeneveld-Krentz  5 , Tamas Révész  6 , Peter Hoogerbrugge  7 , Jeremy Hancock  8 , Rosemary Sutton  9 , Guenter Henze  5 , Christiane Chen-Santel  10 , Andishe Attarbaschi  11 , Jean-Pierre Bourquin  12 , Lucie Sramkova  13 , Martin Zimmermann  14 , Shekhar Krishnan  15 , Arend von Stackelberg  5 , Vaskar Saha  16
Affiliations
Free article
Multicenter Study

Risk factors and outcomes in children with high-risk B-cell precursor and T-cell relapsed acute lymphoblastic leukaemia: combined analysis of ALLR3 and ALL-REZ BFM 2002 clinical trials

Cornelia Eckert et al. Eur J Cancer. 2021 Jul.
Free article

Abstract

Aim: Outcomes of children with high-risk (HR) relapsed acute lymphoblastic leukaemia (ALL) (N = 393), recruited to ALLR3 and ALL-REZ BFM 2002 trials, were analysed. Minimal residual disease (MRD) was assessed after induction and at predetermined time points until haematopoietic stem cell transplantation (SCT).

Methods: Genetic analyses included karyotype, copy-number alterations and mutation analyses. Ten-year survivals were analysed using Kaplan-Meier and Cox models for multivariable analyses.

Results: Outcomes of patients were comparable in ALLR3 and ALL-REZ BFM 2002. The event-free survival of B-cell precursor (BCP) and T-cell ALL (T-ALL) was 22.6% and 26.2% (P = 0.94), respectively, and the overall survival (OS) was 32.6% and 28.2% (P = 0.11), respectively. Induction failures (38%) were associated with deletions of NR3C1 (P = 0.002) and BTG1 (P = 0.03) in BCP-ALL. The disease-free survival (DFS) and OS in patients with good vs poor MRD responses were 57.4% vs 22.6% (P < 0.0001) and 57.8% vs 32.0% (P = 0.0004), respectively. For BCP- and T-ALL, the post-SCT DFS and OS were 42.1% and 56.8% (P = 0.26) and 51.6% and 55.4% (P = 0.67), respectively. The cumulative incidences of post-SCT relapse for BCP- and T-ALL were 36.9% and 17.8% (P = 0.012) and of death were 10.7% and 25.5% (P = 0.013), respectively. Determinants of outcomes after SCT were acute graft versus host disease, pre-SCT MRD (≥10-3), HR cytogenetics and TP53 alterations in BCP-ALL.

Conclusion: Improvements in outcomes for HR ALL relapses require novel compounds in induction therapy to improve remission rates and immune targeted therapy after induction to maintain remission after SCT.

Trial registration: ALLR3: NCT00967057; ALL REZ-BFM 2002: NCT00114348.

Keywords: Acute lymphoblastic leukaemia; High-risk; Minimal residual disease; Outcomes; Stem cell transplantation.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article.

Publication types

MeSH terms

Substances

Associated data