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ACUTE LYMPHOBLASTIC LEUKEMIA

Outcomes in adolescent and young adult patients (16 to 30 years) compared to younger patients treated for high-risk B-lymphoblastic leukemia: report from Children’s Oncology Group Study AALL0232

Leukemia volume 36, pages 648–655 (2022)Cite this article

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Abstract

Adolescent and young adult (AYA) patients 16–30 years old with high-risk acute lymphoblastic leukemia (HR-ALL) have inferior outcomes compared to younger HR-ALL patients. AALL0232 was a Phase 3 randomized Children’s Oncology Group trial for newly diagnosed HR B-ALL (1–30 years). Between 2004 and 2011, 3154 patients enrolled with 3040 eligible and evaluable for induction. AYA patients comprised 20% of patients (16–21 years, n = 551; 22–30 years, n = 46). 5-year event-free survival and overall survival was 65.4 ± 2.2% and 77.4 ± 2.0% for AYA patients compared to 78.1 ± 0.9% and 87.3 ± 0.7% for younger patients (p < 0.0001). Five-year cumulative incidence of relapse was 18.5 ± 1.7% for AYA patients and 13.5 ± 0.7% for younger patients (p = 0.006), largely due to increased marrow relapses (14.0 ± 1.5% versus 9.1 ± 0.6%; p < 0.0001). Additionally, induction failure rate was higher in AYA (7.2 ± 1.1% versus 3.5 ± 0.4%; p < 0.001) and post-induction remission deaths were significantly higher in AYA (5.7 ± 1.0% versus 2.4 ± 0.3%; p < 0.0001). AALL0232 enrolled the largest number of AYA B-ALL patients to date, demonstrating significantly inferior survival and greater rates of treatment-related toxicities compared to younger patients. Although treatment intensification has improved outcomes in younger patients, they have not been associated with the same degree of improvement for older patients.

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Fig. 1
Fig. 2: 5-year Event-Free Survival and Overall Survival rates for AYA and younger patients with High-Risk BALL treated on COG AALL0232.

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Acknowledgements

This work was supported by NIH/NCI grants U24 CA196173, U10 CA98543, U10 CA180886, U10 CA098413, U10 CA180899, and the St. Baldrick’s Foundation. E.A.R. is a KiDS of NYU Foundation Professor at NYU Langone Health. M.L.L. is the UCSF Benioff Chair of Children’s Health and Deborah and Arthur Ablin Endowed Chair in Pediatric Molecular Oncology. S.P.H. is the Jeffrey E. Perelman Distinguished Chair in Pediatrics at The Children’s Hospital of Philadelphia. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Department of Pediatrics, Children’s Hospital of Wisconsin, Milwaukee, WI, USA

    Michael J. Burke

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

    Meenakshi Devidas

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

    Zhiguo Chen

  4. U.S. Army Medical Research and Materiel Command, Fort Detrick, MD, USA

    Wanda L. Salzer

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

    Elizabeth A. Raetz & William L. Carroll

  6. Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA

    Karen R. Rabin & Julie M. Gastier-Foster

  7. Department of Pathology, The Ohio State University School of Medicine, Columbus, OH, USA

    Nyla A. Heerema

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

    Andrew J. Carroll

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

    Michael J. Borowitz

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

    Brent L. Wood

  11. Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Naomi J. Winick

  12. Department of Pediatrics, Children’s Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Stephen P. Hunger

  13. Department of Pediatrics, Benioff Children’s Hospital and the Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CA, USA

    Mignon L. Loh

  14. Department of Pediatrics, Maine Children’s Cancer Program, Scarborough, ME, USA

    Eric C. Larsen

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Contributions

Conception and design: M.J.B., E.C.L., M.D., Z.C., W.L.S., M.L.L, J.M.G, N.J.W., S.P.H., W.L.C. Collection and assembly of data: M.J.B., E.C.L., M.D., Z.C., W.L.S., E.A.R., M.L.L., N.A.H., A.A.C., J.M.G., M.J.Bor., B.L.W., N.J.W., S.P.H., W.L.C. Data analysis and interpretation: M.J.B., E.C.L., M.D., Z.C., W.L.S., K.R.R., E.A.R., M.L.L., N.A.H., A.A.C., J.M.G., M.J.Bor., B.L.W., N.J.W., S.P.H., W.L.C. Manuscript writing: All authors. Final approval of manuscript: All authors.

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Correspondence to Michael J. Burke.

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Competing interests

M.J.B. has received honoraria from Shire Pharmaceuticals, Jazz Pharmaceuticals and Amgen. S.P.H. has received consulting fees from Novartis, honoraria from Jazz Pharmaceuticals and Amgen, and owns common stock in Amgen.

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Burke, M.J., Devidas, M., Chen, Z. et al. Outcomes in adolescent and young adult patients (16 to 30 years) compared to younger patients treated for high-risk B-lymphoblastic leukemia: report from Children’s Oncology Group Study AALL0232. Leukemia 36, 648–655 (2022). https://doi.org/10.1038/s41375-021-01460-6

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