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A revised definition for cure of childhood acute lymphoblastic leukemia

Leukemia volume 28, pages 2336–2343 (2014)Cite this article

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Abstract

With improved contemporary therapy, we reassess long-term outcome in patients completing treatment for childhood acute lymphoblastic leukemia (ALL) to determine when cure can be declared with a high degree of confidence. In six successive clinical trials between 1984 and 2007, 1291 (84.5%) patients completed all therapies in continuous complete remission. The post-therapy cumulative risk of relapse or development of a second neoplasm and the event-free survival rate and overall survival were analyzed according to the presenting features and the three treatment periods defined by relative outcome. Over the three treatment periods, there has been progressive increase in the rate of event-free survival (65.2% vs 74.8% vs 85.1% (P<0.001)) and overall survival (76.5% vs 81.1% vs 91.7% (P<0.001)) at 10 years. The most important predictor of outcome after completion of therapy was the type of treatment. In the most recent treatment period, which omitted the use of prophylactic cranial irradiation, the post-treatment cumulative risk of relapse was 6.4%, death in remission 1.5% and development of a second neoplasm 2.3% at 10 years, with all relapses except one occurring within 4 years of therapy. None of the 106 patients with the t(9;22)/BCR-ABL1, t(1;19)/TCF3-PBX1 or t(4;11)/MLL-AFF1 had relapsed after 2 years from completion of therapy. These findings demonstrate that with contemporary effective therapy that excludes cranial irradiation, approximately 6% of children with ALL may relapse after completion of treatment, and those who remain in remission at 4 years post treatment may be considered cured (that is, less than 1% chance of relapse).

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Acknowledgements

This work was funded in part by the NCI grant CA21765, CA36401 and U01 GM92666, and the American Lebanese and Syrian Associated Charities (ALSAC).

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Authors and Affiliations

  1. Department of Oncology, St Jude Children’s Research Hospital, Memphis, TN, USA

    C H Pui, J T Sandlund, M M Hudson, R C Ribeiro, S Jeha, S C Howard, D Bhojwani, H Inaba, J E Rubnitz, M L Metzger & T A Gruber

  2. Department of Pathology, St Jude Children’s Research Hospital, Memphis, TN, USA

    C H Pui, S C Raimondi & J R Downing

  3. Department of Biostatistics, St Jude Children’s Research Hospital, Memphis, TN, USA

    D Pei & C Cheng

  4. Centre for Translational Medicine, National University of Singapore, Singapore, Singapore

    D Campana & E Coustan-Smith

  5. Department of Pediatrics, University of North Texas Health Science Center, Fort Worth, TX, USA

    W P Bowman

  6. Department of Bone Marrow Transplantation and Cellular Therapy, St Jude Children’s Research Hospital, Memphis, TN, USA

    W H Leung

  7. Department of Pharmaceutical Sciences, St Jude Children’s Research Hospital, Memphis, TN, USA

    M V Relling & W E Evans

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  1. C H Pui
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Correspondence to C H Pui.

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Author Contributions

CHP, CC, DP and WHL designed, analyzed and interpreted the study. DC, SCR and ECS performed the laboratory research. CHP, DC, WHL and WEE wrote the manuscript. CHP, JTS, WPB, MMH, RCR, SJ, SCH, DB, HI, JER, MLM and TAG provided clinical data. All authors critically reviewed the manuscript and gave their final approval.

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Pui, C., Pei, D., Campana, D. et al. A revised definition for cure of childhood acute lymphoblastic leukemia. Leukemia 28, 2336–2343 (2014). https://doi.org/10.1038/leu.2014.142

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