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Acute Leukemias

Long-term follow-up of imatinib in pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia: Children's Oncology Group Study AALL0031

Leukemia volume 28, pages 1467–1471 (2014)Cite this article

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Abstract

We previously reported preliminary findings that post induction imatinib mesylate (340 mg/m2/day), in combination with intensive chemotherapy, resulted in outcomes similar to blood and marrow transplant (BMT) for pediatric patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). We now report 5-year outcomes of imatinib plus intensive chemotherapy in 91 children (1–21 years) with and without allogeneic BMT (N=91). We explore the impacts of additional chromosomal abnormalities and minimal residual disease (MRD) by flow cytometry on outcomes. The 5-year disease-free survival was similar for Cohort 5 patients, treated with chemotherapy plus imatinib (70%±12%, n=28), sibling donor BMT patients (65%±11%, n=21) and unrelated donor BMT patients (59±15%; P=0.60, n=13). Patients with additional cytogenetic abnormalities had worse outcomes (P=0.05). End induction (pre-imatinib) MRD was not prognostic for Cohort 5 or allogeneic BMT patients, although limited by small numbers. The re-induction rate following relapse was similar to other higher-risk ALL groups. Longer-term follow-up confirms our initial observation of substantially good outcomes for children and adolescents with Ph+ ALL treated with imatinib plus intensive chemotherapy with no advantage for allogeneic BMT.

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Acknowledgements

We sincerely thank Laura Francisco for invaluable data management support, Tammie Eslinger, CCRP, for outstanding protocol development and performance support and Bernice Pasut, RN, for diligent and thorough protocol development support. SPH is the Ergen Family Chair in Pediatric Cancer. This work was supported by grants CA98543 and CA29139.

Author contributions

Kirk R Schultz designed the research, performed the research, analyzed the data and wrote the paper. Andrew Carroll performed the research, analyzed the data and wrote the paper. Nyla A Heerema performed the research, analyzed the data and wrote the paper. W Paul Bowman designed the research, performed the research, analyzed the data and wrote the paper. Alexander Aledo designed the research, performed the research and wrote the paper. William B Slayton designed the research, performed the research and wrote the paper. Harland Sather designed the research, analyzed the data and wrote the paper. Meenakshi Devidas designed the research, analyzed the data and wrote the paper. Hao W Zheng analyzed the data. Stella M Davies designed the research and wrote the paper. Paul S Gaynon designed the research and wrote the paper. Michael Trigg designed the research and wrote the paper. Robert Rutledge designed the research and wrote the paper. Dean Jorstad designed the research and wrote the paper. Naomi Winick performed the research and wrote the paper. Michael J Borowitz performed the research, analyzed the data and wrote the paper. Stephen P Hunger designed the research, performed the research and wrote the paper. William L Carroll designed the research, performed the research and wrote the paper. Bruce Camitta designed the research, performed the research and wrote the paper.

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Authors and Affiliations

  1. Department of Pediatrics, Division of Hematology/Oncology/BMT British Columbia’s Children’s Hospital, University of British Columbia, Vancouver, BC, Canada

    K R Schultz

  2. University of Alabama at Birmingham, Birmingham, AL, USA

    A Carroll

  3. Department of Pathology, The Ohio State University, Columbus, OH, USA

    N A Heerema

  4. Cook Children's Medical Center, Hematology/Oncology Fort Worth, TX, USA

    W P Bowman

  5. Phyllis and David Komansky Center for Children's Health/Weill Cornell Medical Center, New York, NY, USA

    A Aledo

  6. Department of Pediatrics and University of Florida Shands Cancer Center, University of Florida College of Medicine, Gainesville, FL, USA

    W B Slayton

  7. Department of Preventative Medicine, University of Southern California, Los Angeles, CA, USA

    H Sather

  8. Department of Biostatistics, Children’s Oncology Group Statistics & Data Center, and the University of Florida, Gainesville, FL, USA

    M Devidas

  9. Children’s Hospital Colorado and the Department of Pediatrics University of Colorado School of Medicine, Ped. Hematology/Oncology/BMT, Aurora, CO, USA

    H W Zheng & S P Hunger

  10. Stem Cell Transplantation, Children’s Hospital Medical Center Cincinnati, Cincinnati, OH, USA

    S M Davies

  11. Hematology/Oncology Children’s Hospital Los Angeles, Los Angeles, CA, USA

    P S Gaynon

  12. Thomas Jefferson University, Philadelphia, PA, USA

    M Trigg

  13. Department of Radiation Oncology, Nova Scotia Cancer Centre and Dalhousie University, Halifax, NS, USA

    R Rutledge

  14. Department of Pediatrics, Midwest Children's Cancer Center, Medical College of Wisconsin and Children's Hospital of Wisconsin, Milwaukee, WI, USA

    D Jorstad & B Camitta

  15. Pediatric Hem/Onc, UT Southwestern Medical Center, Dallas, TX, USA

    N Winick

  16. Department of Pathology, Johns Hopkins Hospital, Baltimore, MD, USA

    M J Borowitz

  17. Department of Pediatrics, NYU Medical Center, New York, NY, USA

    W L Carroll

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  1. K R Schultz
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  2. A Carroll
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  3. N A Heerema
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  4. W P Bowman
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  7. H Sather
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  8. M Devidas
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  9. H W Zheng
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  10. S M Davies
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  11. P S Gaynon
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  14. D Jorstad
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  15. N Winick
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  16. M J Borowitz
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  17. S P Hunger
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  18. W L Carroll
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  19. B Camitta
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Correspondence to K R Schultz.

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Schultz, K., Carroll, A., Heerema, N. et al. Long-term follow-up of imatinib in pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia: Children's Oncology Group Study AALL0031. Leukemia 28, 1467–1471 (2014). https://doi.org/10.1038/leu.2014.30

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Keywords

  • imatinib mesylate
  • Philadelphia chromosome
  • acute lymphoblastic leukemia
  • toxicity
  • event-free survival
  • blood and marrow transplantation

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