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Acute Leukemias

High-risk childhood acute lymphoblastic leukemia in first remission treated with novel intensive chemotherapy and allogeneic transplantation

Leukemia volume 27, pages 1497–1503 (2013)Cite this article

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Abstract

Children with acute lymphoblastic leukemia (ALL) and high minimal residual disease (MRD) levels after initial chemotherapy have a poor clinical outcome. In this prospective, single arm, Phase 2 trial, 111 Dutch and Australian children aged 1–18 years with newly diagnosed, t(9;22)-negative ALL, were identified among 1041 consecutively enrolled patients as high risk (HR) based on clinical features or high MRD. The HR cohort received the AIEOP-BFM (Associazione Italiana di Ematologia ed Oncologia Pediatrica (Italy)–Berlin-Frankfurt-Münster ALL Study Group) 2000 ALL Protocol I, then three novel HR chemotherapy blocks, followed by allogeneic transplant or chemotherapy. Of the 111 HR patients, 91 began HR treatment blocks, while 79 completed the protocol. There were 3 remission failures, 12 relapses, 7 toxic deaths in remission and 10 patients who changed protocol due to toxicity or clinician/parent preference. For the 111 HR patients, 5-year event-free survival (EFS) was 66.8% (±5.5) and overall survival (OS) was 75.6% (±4.3). The 30 patients treated as HR solely on the basis of high MRD levels had a 5-year EFS of 63% (±9.4%). All patients experienced grade 3 or 4 toxicities during HR block therapy. Although cure rates were improved compared with previous studies, high treatment toxicity suggested that novel agents are needed to achieve further improvement.

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Acknowledgements

We thank Prof Martin Schrappe and the I-BFM for their support. This work was supported by the National Health and Medical Research Council of Australia, Cancer Council New South Wales, Steven Walter Children’s Cancer Foundation, Cancer Institute New South Wales and Leukemia Foundation.

Author contributions

Conception and design: LDP, GMM, MDN and RP. Administrative support: RS, AN, HG, SC, HM and VH. Provision of study materials or patients: LDP, RS, NCV, VHV, HB, ESJMB, RME, PMH, GJLK, ES, JD, TL, MDN, MH, TR, A, RS, RP and GMM. Collection and assembly of data: GMM, LDP, RS, AN, HG-K , NCV, VHV, HM, VH, MDN, MH, TR, FA and RP. Data analysis and interpretation: GMM, LDP, RS, AN, HG-K, NCV, VHV, SC, HM, VH, MDN, MH, TR, FA, RS and RP. Manuscript writing: GMM, LDP, RS, AN and RP. Final approval of manuscript: All the authors.

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Author notes

  1. G M Marshall and L Dalla Pozza: These authors contributed equally to this work.

Authors and Affiliations

  1. Children’s Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, UNSW, Sydney, New South Wales, Australia

    G M Marshall, R Sutton, N C Venn, T Law, M Haber & M D Norris

  2. Centre for Children’s Cancer and Blood Disorders, Sydney Children’s Hospital, Randwick, Sydney, New South Wales, Australia

    G M Marshall & H Mueller

  3. Children’s Hospital at Westmead, Sydney, New South Wales, Australia

    L Dalla Pozza, A Ng & S Cross

  4. The Dutch Childhood Oncology Group (DCOG) for the Dutch Childhood Leukemia Study Group and the Australian and New Zealand Children’s Haematology and Oncology Group (ANZCHOG), The Hague, The Netherlands

    H A de Groot-Kruseman & V de Haas

  5. Erasmus Medical Centre, Rotterdam, The Netherlands

    V H van der Velden, J van Dongen & R Pieters

  6. Emma Children Hospital AMC, University of Amsterdam, The Netherlands

    H van den Berg & E van der Schoot

  7. Beatrix Children's Hospital, University of Groningen, Groningen, The Netherlands

    E S J M de Bont

  8. Leiden University Medical Center, Leiden, The Netherlands

    R Maarten Egeler

  9. Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

    P M Hoogerbrugge

  10. VU University Medical Center, Amsterdam, The Netherlands

    G J L Kaspers

  11. Department of Hemato-oncology, Utrecht University Children's Hospital, Utrecht, The Netherlands

    M B Bierings

  12. Women’s and Children’s Hospital, Adelaide, South Australia, Australia

    T Révész

  13. John Hunter Children’s Hospital, Newcastle, New South Wales, Australia

    F Alvaro

  14. Mater Children’s Hospital, Brisbane, Queensland, Australia

    R Suppiah

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Correspondence to G M Marshall.

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Marshall, G., Dalla Pozza, L., Sutton, R. et al. High-risk childhood acute lymphoblastic leukemia in first remission treated with novel intensive chemotherapy and allogeneic transplantation. Leukemia 27, 1497–1503 (2013). https://doi.org/10.1038/leu.2013.44

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