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Philadelphia chromosome-negative very high-risk acute lymphoblastic leukemia in children and adolescents: results from Children’s Oncology Group Study AALL0031

Leukemia volume 28, pages 964–967 (2014)Cite this article

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The Children’s Oncology Group (COG) AALL0031 study included very high-risk (VHR) pediatric acute lymphoblastic leukemia (ALL) patients who had an expected 5-year event-free survival ⩽45%. The chemotherapy regimen was based on previous strategies; eligible patients received 4 weeks of standard induction chemotherapy and then were enrolled on AALL0031, which included an intensive consolidation followed by a continuation regimen (Supplementary Figure 1).1 COG AALL0031 enrolled patients aged 1–21 years with VHR ALL from 14 October 2002 to 20 October 2006. Induction therapy was limited to a combination of vincristine, prednisone or dexamethasone, and asparaginase with or without daunomycin. VHR features included the following: (a) Philadelphia chromosome [t(9;22)(q34;q11.2)]; (b) hypodiploidy: defined as ⩽44 chromosomes or DNA index <0.81; (c) any rearrangement of the MLL gene in conjunction with a slow early response ⩾5% marrow blasts at day 15 and/or ⩾0.1% minimal residual disease (MRD) at the end of induction as detected by multiparameter flow cytometry;2, 3 and (d) induction failure (IF) defined as either >25% blasts (M3 marrow status) by histology at the end of 4 weeks of induction therapy or an M2 marrow (5–25% blasts) or MRD ⩾1% by flow cytometry at the end of induction followed by an M2 (or M3) marrow or MRD⩾1% after receiving two additional weeks of induction therapy (M2/M2 IFs). The therapy was identical to that presented in a previous publication on outcomes for Ph+ ALL patients,1 except that the Ph− patients received no imatinib (see Supplementary Figure 1).

Prior approval was obtained from the National Cancer Institute and the Institutional Review Boards of the COG member institutions. Informed consent was obtained in accordance with the Federal guidelines. Sixty-three hypodiploid (41) and IF (22) patients were enrolled in AALL0031 after 4 weeks of a three- or four-drug induction regimen for National Cancer Institute standard and high-risk ALL, respectively. Data on adverse events and clinically significant abnormal laboratory findings were collected using National Cancer Institute Common Terminology Criteria version 2.0. MRD was assessed by multiparameter flow cytometry.2 Samples were available from 46 of 63 (73%) patients at study entry. MRD high was defined as >0.01% and low as ⩽0.01%.

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References

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Acknowledgements

This study was supported by grants to the COG including CA98543, CA98413 and CA29139. SPH is the Ergen Family Chair in Pediatric Cancer. We sincerely thank Doojduen Villaluna, MS for invaluable statistical support, Tammie Eslinger, CCRP for outstanding protocol development and performance support, Laura Francisco, for data management, and Bernice Pasut, RN for diligent and thorough protocol development support.

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Authors and Affiliations

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

    K R Schultz

  2. Department of Biostatistics, Children’s Oncology Group Statistics and Data Center, The University of Florida, Gainesville, FL, USA

    M Devidas

  3. Division of Hematology/Oncology, Cook Children’s Medical Center, Fort Worth, TX, USA

    W P Bowman

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

    A Aledo

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

    W B Slayton

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

    H Sather, H W Zheng & S P Hunger

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

    S M Davies

  8. Division of Hematology/Oncology, Children’s Hospital Los Angeles, Los Angeles, CA, USA

    P S Gaynon

  9. Thomas Jefferson University, Philadelphia, PA, USA

    M Trigg

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

    R Rutledge

  11. Department of Pediatrics, MACC Fund Center for Cancer and Blood Disorders, Medical College of Wisconsin and Children's Hospital of Wisconsin, Milwaukee, WI, USA

    D Jorstad & B Camitta

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

    A J Carroll

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

    N Heerema

  14. Division of Hematology/Oncology, Department of Pediatrics, UT Southwestern Medical Center, Dallas, TX, USA

    N Winick

  15. Department Pathology, Johns Hopkins Hospital, Baltimore, MD, USA

    M J Borowitz

  16. 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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  17. S P Hunger
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  18. W L Carroll
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  19. B Camitta
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The Children’s Oncology Group

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Correspondence to K R Schultz.

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The authors declare no conflict of interest.

Additional information

List of where the study has been presented in part elsewhere: Schultz KR, Bowman P, Slayton WB, Aledo A, Devidas M, Sather H, Borowitz M, Davies S, Trigg M, Pasut B, Jorstad D, Eslinger T, Burden L, Wang CG, Rutledge R, Camitta B, Gaynon P, Carroll A, Heerema NA, Winick N, Hunger S, Carroll WL. Philadelphia chromosome-negative (Ph−) very high-risk (VHR) acute lymphoblastic leukemia (ALL) in children and adolescents: the impact of intensified chemotherapy on early event-free survival (EFS) in Children’s Oncology Group (COG) Study AALL0031. ASH 6–8 December 2008.

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Schultz, K., Devidas, M., Bowman, W. et al. Philadelphia chromosome-negative very high-risk acute lymphoblastic leukemia in children and adolescents: results from Children’s Oncology Group Study AALL0031. Leukemia 28, 964–967 (2014). https://doi.org/10.1038/leu.2014.29

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