Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

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

Subjects

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Aricò M, Schrappe M, Hunger SP, Carroll WL, Conter V, Galimberti S et al. Clinical outcome of children with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia treated between 1995 and 2005. J Clin Oncol 2010; 28: 4755–4761.

    Article  Google Scholar 

  2. Gaynon PS, Trigg ME, Heerema NA, Sensel MG, Sather HN, Hammond GD et al. Children's Cancer Group trials in childhood acute lymphoblastic leukemia: 1983-1995. Leukemia 2000; 14: 2223–2233.

    Article  CAS  Google Scholar 

  3. Maloney KW, Shuster JJ, Murphy S, Pullen J, Camitta BA . Long-term results of treatment studies for childhood acute lymphoblastic leukemia: Pediatric Oncology Group studies from 1986–1994. Leukemia 2000; 12: 2276–2285.

    Article  Google Scholar 

  4. Pui CH, Evans WE . Treatment of acute lymphoblastic leukemia. N Engl J Med 2006; 354: 166–178.

    Article  CAS  Google Scholar 

  5. Aricò M, Valsecchi MG, Camitta B, Schrappe M, Chessells J, Baruchel A et al. Outcome of treatment in children with Philadelphia chromosome-positive acute lymphoblastic leukemia. N Engl J Med 2000; 342: 998–1006.

    Article  Google Scholar 

  6. Steinherz PG, Redner A, Steinherz L, Meyers P, Tan C, Heller G . Development of a new intensive therapy for acute lymphoblastic leukemia in children at increased risk of early relapse. The Memorial Sloan-Kettering-New York-II protocol. Cancer 1993; 72: 3120–3130.

    Article  CAS  Google Scholar 

  7. Bowman WP, Larsen EL, Devidas M, Linda SB, Blach L, Carroll AJ et al. Augmented therapy improves outcome for pediatric high risk acute lymphocytic leukemia: results of Children's Oncology Group trial P9906. Pediatr Blood Cancer 2011; 57: 569–577.

    Article  Google Scholar 

  8. Schultz KR, Aledo A, Bowman WP, Slayton WB, Sather H, Devidas M et al. Improved early event free survival (EFS) with tolerable toxicity in children with philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) with intensive imatinib mesylate with dose-intensive multiagent chemotherapy: Children's Oncology Group (COG) Study AALL0031. J Clin Oncol 2009; 27: 5175–5181.

    Article  CAS  Google Scholar 

  9. Yanada M, Takeuchi J, Sugiura I, Akiyama H, Usui N, Yagasaki F et al. Karyotype at diagnosis is the major prognostic factor predicting relapse-free survival for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia treated with imatinib-combined chemotherapy. Haematologica 2008; 93: 287–290.

    Article  Google Scholar 

  10. Towatari M, Yanada M, Usui N, Takeuchi J, Sugiura I, Takeuchi M et al. Combination of intensive chemotherapy and imatinib can rapidly induce high-quality complete remission for a majority of patients with newly diagnosed BCR-ABL-positive acute lymphoblastic leukemia. Blood 2004; 104: 3507–3512.

    Article  CAS  Google Scholar 

  11. Borowitz MJ, Pullen DJ, Shuster JJ, Viswanatha D, Montgomery K, Willman CL et al. Children's Oncology Group study. Minimal residual disease detection in childhood precursor-B-cell acute lymphoblastic leukemia: relation to other risk factors. A Children's Oncology Group study. Leukemia 2003; 17: 1566–1572.

    Article  CAS  Google Scholar 

  12. Borowitz MJ, Devidas M, Hunger SP, Bowman WP, Carroll AJ, Carroll WL et al. Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors: A Children's Oncology Group study. Blood 2008; 111: 5477–5485.

    Article  CAS  Google Scholar 

  13. Kaplan EL, Meier P . Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–481.

    Article  Google Scholar 

  14. Peto R, Peto J . Asymptotically efficient rank invariant test procedure. J Royal Stat Soc 1972; 135: 185–198.

    Article  Google Scholar 

  15. Bader P, Kreyenberg H, Henze GH, Eckert C, Reising M, Willasch A et al. ALL-REZ BFM Study Group. Prognostic value of minimal residual disease quantification before allogeneic stem-cell transplantation in relapsed childhood acute lymphoblastic leukemia: the ALL-REZ BFM Study Group. J Clin Oncol 2009; 27: 377–384.

    Article  Google Scholar 

  16. Raetz EA, Borowitz MJ, Devidas M, Linda SB, Hunger SP, Winick NJ et al. Reinduction platform for children with first marrow relapse of acute lymphoblastic Leukemia: A Children's Oncology Group Study[corrected]. J Clin Oncol 2008; 26: 3971–3978.

    Article  CAS  Google Scholar 

  17. Biondi A, Schrappe M, De Lorenzo P, Castor A, Lucchini G, Gandemer V et al. Imatinib after induction for treatment of children and adolescents with Philadelphia-chromosome-positive acute lymphoblastic leukaemia (EsPhALL): a randomised, open-label, intergroup study. Lancet Oncol 2012; 13: 936–945.

    Article  CAS  Google Scholar 

Download references

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.

Author information

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

Authors
  1. K R Schultz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A Carroll
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N A Heerema
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. W P Bowman
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A Aledo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. W B Slayton
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. H Sather
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M Devidas
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. H W Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. S M Davies
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. P S Gaynon
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. M Trigg
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. R Rutledge
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. D Jorstad
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. N Winick
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. M J Borowitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. S P Hunger
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. W L Carroll
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. B Camitta
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

from the Children’s Oncology Group

Corresponding author

Correspondence to K R Schultz.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2014.30

Keywords

This article is cited by

Search

Advanced search

Quick links