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ACUTE LYMPHOBLASTIC LEUKEMIA

Outstanding outcomes with two low intensity regimens in children with low-risk B-ALL: a report from COG AALL0932

Leukemia volume 37, pages 1375–1378 (2023)Cite this article

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A Correction to this article was published on 08 May 2023

This article has been updated

Acute lymphoblastic leukemia (ALL), the most common childhood malignancy, has excellent outcomes overall with contemporary therapy [1]. The combination of clinical features, sentinel genetic lesions, and day 8 peripheral blood and end of induction (EOI) bone marrow minimal residual disease (MRD) can be used to risk stratify patients based on risk of relapse [2, 3]. The Children’s Oncology Group (COG) retrospectively identified low-risk (LR) subsets of standard-risk (SR) B-ALL patients with 5-year event-free survival (EFS) > 95% and overall survival (OS) > 97% treated with a 3-drug induction and post-induction intensification strategies with either intermediate dose methotrexate (ID MTX) without anthracyclines or alkylating agents (P9904), or a COG-modified Berlin-Frankfurt-Muenster (BFM) approach (CCG-1991) [2, 4, 5]. COG AALL0932 was designed to prospectively confirm whether patients with low-risk (LR) B-ALL could achieve a 5-year disease-free survival (DFS) of ≥95% with either of two regimens previously associated with outstanding DFS and OS and limited short- and long-term toxicity.

AALL0932 enrolled patients with NCI SR (age 1–9.99 years, initial white blood cell count <50,000/microliter) B-ALL, all of whom received a 3-drug induction with dexamethasone, vincristine and pegaspargase [6]. MRD was assessed by multi-parameter flow cytometry performed in a central laboratory (prior to March 2017) or in a COG approved lab using a COG standardized analysis protocol (after March 2017). Following induction, LR patients were defined as those with favorable genetics (ETV6-RUNX1 fusion or trisomies of chromosomes 4 and 10); no steroid pre-treatment, unfavorable cytogenetics, Down syndrome (DS), central nervous system or testicular leukemia; and Day 8 peripheral blood (PB) and EOI bone marrow (BM) MRD < 0.01% (Supplementary Table 1) [6]. Consenting LR patients were randomized (1:1) to a P9904 based regimen that included 6 inpatient courses of ID MTX (1 g/m2/24 h with leucovorin rescue) without alkylating agents or anthracyclines (Arm LR-M), or a CCG-1991-based outpatient regimen with reduced frequency vincristine/dexamethasone pulses given during maintenance at 12 instead of the 4 week intervals used in CCG-1991 (Arm LR-C). Therapy details are provided in Supplementary Tables 2, 3 and 4. As of May 2015, the LR randomization was closed to new study enrollees and subsequent patients classified as LR came off therapy at EOI.

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Fig. 1: CONSORT diagram.
Fig. 2: Survival in LR B-ALL patients from EOI by randomized treatment arm.

Data availability

De-identified data will be submitted to and made available through the NCTN/NCORP Data Archive at https://nctn-data-archive.nci.nih.gov.

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Acknowledgements

Special thanks to all the patients and their families as well as the participating institutions, and study staff.

Funding

Supported by grants from National Cancer Institute grants to the Children’s Oncology Group (U10 CA98543, U10 CA98413, U10 CA180886, U10 CA180899, U24 CA114766, 1U24-CA196173) and by research funding from St. Baldrick’s Foundation and BD Biosciences.

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Authors and Affiliations

  1. Children’s National Health System, Washington, DC, USA

    Reuven J. Schore & Anne L. Angiolillo

  2. George Washington University School of Medicine and Health Sciences, Washington, DC, USA

    Reuven J. Schore & Anne L. Angiolillo

  3. Department of Biostatistics, Colleges of Medicine, Public Health & Health Professions, University of Florida, Gainesville, FL, USA

    John A. Kairalla & Cindy Wang

  4. Department of Global Pediatric Medicine, St Jude Children’s Research Hospital, Memphis, TN, USA

    Meenakshi Devidas

  5. Texas Children’s Cancer Center, Baylor College of Medicine, Houston, TX, USA

    Karen R. Rabin

  6. ImmunoGen, Inc., Boston, MA, USA

    Patrick Zweidler-McKay

  7. Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA

    Michael J. Borowitz

  8. Department of Laboratory Medicine, University of Washington, Seattle, WA, USA

    Brent Wood

  9. Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA

    Andrew J. Carroll

  10. Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH, USA

    Nyla A. Heerema

  11. St Jude’s Children’s Research Hospital, Memphis, TN, USA

    Mary V. Relling

  12. Hospital for Sick Children, Toronto, ON, Canada

    Johann Hitzler

  13. Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, USA

    Nina S. Kadan-Lottick

  14. Children’s Hospital Colorado and the Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA

    Kelly Maloney

  15. Department of Pediatrics and Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY, USA

    William L. Carroll & Elizabeth A. Raetz

  16. University of Texas Southwestern Medical Center, Dallas, TX, USA

    Naomi J. Winick

  17. Ben Towne Center for Childhood Cancer Research, Seattle Children’s Research Institute, Seattle, WA, USA

    Mignon L. Loh

  18. Department of Pediatrics, Seattle Children’s Hospital, University of Washington, Seattle, WA, USA

    Mignon L. Loh

  19. Department of Pediatrics and the Center for Childhood Cancer Research, the Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Stephen P. Hunger

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  1. Reuven J. Schore
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Contributions

RJS and ALA designed research, collected, and assembled data, analyzed and interpreted data and wrote the manuscript; JAK collected and assembled data, analyzed and interpreted data and wrote the manuscript; MD designed research, collected and assembled data, analyzed and interpreted data; KRR, PZM, MJB, BW designed research; collected and assembled data; AJC, NAH collected and assembled data; MVR designed research; JH, designed research, collected and assembled data, analyzed and interpreted data; NSKL, designed research; collected and assembled data; KM designed research, CW collected and assembled data, analyzed and interpreted data; WLC designed research; NJW, EAR, MLL, SPH designed research, collected and assembled data, analyzed and interpreted data and wrote the manuscript. All authors reviewed and approved the final manuscript and are accountable for all aspects of the work. RJS and ALA contributed equally as first authors.

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Correspondence to Reuven J. Schore.

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Competing interests

RJS has been on an advisory board and received honoraria from Jazz Pharmaceuticals; ALA has been on an advisory board and received honoraria from Jazz Pharmaceuticals. JAK has stock in Johnson & Johnson common stock. PZM employment at ImmunoGen. MJB has been on an advisory board and received honoraria from Amgen and received honoraria from Blueprint Medicines; BW has served as a consultant for Amgen and had received research funding from Celgene/Juno, Kite, Novartis, and Wugen; NSKL has a family member who is a consultant for Medtronic and Boston scientific; MVR and her institution receive investigator-initiated funding from Servier; EAR has received institutional research funding from Pfizer and serves on a DSMB for Celgene/BMS;SPH owns common stock in Amgen and has received honoraria from Amgen, Jazz and Servier.

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The original online version of this article was revised: Figure 2 has been corrected.

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Schore, R.J., Angiolillo, A.L., Kairalla, J.A. et al. Outstanding outcomes with two low intensity regimens in children with low-risk B-ALL: a report from COG AALL0932. Leukemia 37, 1375–1378 (2023). https://doi.org/10.1038/s41375-023-01870-8

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