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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 volume 33, pages 2144–2154 (2019)Cite this article

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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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Authors and 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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Steinherz, P.G., Seibel, N.L., Sather, H. et al. 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 33, 2144–2154 (2019). https://doi.org/10.1038/s41375-019-0422-z

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