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Acute lymphoblastic leukemia

Treatment of higher risk acute lymphoblastic leukemia in young people (CCG-1961), long-term follow-up: a report from the Children’s Oncology Group

Leukemia (2019) | Download Citation

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Abstract

Children’s Cancer Group CCG-1882 improved outcome for 1–21-year old with high risk acute lymphoblastic leukemia and Induction Day 8 marrow blasts ≥25% (slow early responders, SER) with longer and stronger post induction intensification (PII). This CCG-1961 explored alternative PII strategies. We report 10-year follow-up for patients with rapid early response (RER) and for the first time details our experience for SER patients. A total of 2057 patients were enrolled, and 1299 RER patients were randomized to 1 of 4 PII regimens: standard vs. augmented intensity and standard vs. increased length. At the end of interim maintenance, 447 SER patients were randomized to idarubicin/cyclophosphamide or weekly doxorubicin in the delayed intensification phases. The 10-year EFS for RER were 79.4 ± 2.4% and 70.9 ± 2.6% (hazard ratio = 0.65, 95% CI 0.52–0.82, p < 0.001) for augmented and standard strength PII; the 10-year OS rates were 87.2 ± 2.0% and 81.0 ± 2.2% (hazard ratio = 0.64, 95% CI 0.48–0.86, p = 0.003). Outcomes remain similar for standard and longer PII, and for SER patients assigned to idarubicin/cyclophosphamide and weekly doxorubicin. The EFS and OS advantage of augmented PII is sustained at 10 years for RER patients. Longer PII for RER patients and sequential idarubicin/cyclophosphamide for SER patients offered no advantage. CCG-1961 is the platform for subsequent COG studies.

Key points

  • In all, 2057 high risk ALL patients had a 5- and 10-year EFS of 71.8 ± 1.1% and 68.5 ± 1.5%.The 10-year EFS rate for rapid early responders was 79.4%.

  • EFS for slow responders was 70.2% and 65.3% at 5 and 10 years. Advantage of augmented intensification seen at 5 years, was sustained at 10 years.

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Acknowledgements

We wish to thank Ms. Damaris Morales for secretarial support. The funding for the research was under the auspices of the Childrens Oncology Group and the various NIH grants: NIH grants CA13539, CA 30969, U10 CA98543, U10 CA98413, U10 CA180886, and U10 CA180899.

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Affiliations

  1. Memorial Sloan Kettering Cancer Center, New York, NY, USA

    • Peter G. Steinherz
  2. Children’s National Health System, George Washington University School of Medicine and Health Sciences, Washington, DC, USA

    • Nita L. Seibel
  3. Children’s Oncology Group, Los Angeles, CA, USA

    • Harland Sather
    •  & Xinxin Xu
  4. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    • Lingyun Ji
  5. Department of Biostatistics, University of Florida, Gainesville, FL, USA

    • Meenakshi Devidas
  6. Children’s Hospital of Los Angeles, Los Angeles, CA, USA

    • Paul S. Gaynon

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The authors declare that they have no conflict of interest.

Corresponding author

Correspondence to Peter G. Steinherz.

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https://doi.org/10.1038/s41375-019-0422-z