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Long-term follow-up of short intensive multiagent chemotherapy without high-dose methotrexate (‘Orange’) in children with advanced non-lymphoblastic non-Hodgkin's lymphoma: a Children's Cancer Group Report

Leukemia volume 16, pages 594–600 (2002)Cite this article

Abstract

Despite prolonged therapy (18 months), children with advanced non-lymphoblastic, non-Hodgkin's lymphoma (NHL) treated on previous Children's Cancer Group (CCG) trials achieved less than a 60% 5-year event-free survival (EFS). In this study we piloted a shorter but more intensive protocol (‘Orange’) to determine the feasibility, safety, and efficacy of this alternative treatment approach. Thirty-nine children received a CHOP-based induction, etoposide/ifosfamide consolidation, DECAL (dexamethasone, etoposide, cisplatin, cytosine arabinoside (Ara-C) and L-asparaginase) intensification, and either one or two similar but less intense maintenance courses. Patients were stratified to standard-risk (5 months) vs high-risk (7 months) treatment. High risk was defined as either bone marrow disease, CNS disease, mediastinal mass ⩾ one-third thoracic diameter at T5 and/or LDH ⩾2 times institutional upper limits of normal. All other patients were considered to be standard risk. Results were compared with the previous CCG NHL study (CCG-503). Sixteen and 23 patients were considered standard- vs high-risk, respectively. The 5-year EFS and overall survival (OS) were 77 ± 7% and 80 ± 7%, respectively. The 5-year EFS and OS were significantly better in the standard- vshigh-risk subgroups (100% vs 61 ± 11%) (P < 0.003) and (100% vs 65 ± 11%) (P < 0.01), respectively. Lactate dehydrogenase (LDH) ⩾2 × normal (NL) was associated with significantly poorer outcomes (LDH ⩾2 × NL vs <2 × NL) (5-year EFS: 55 ± 12% vs 100%) (P < 0.0004). This CCG hybrid regimen, ‘Orange’, of short and more intensive therapy resulted in a significant improvement in outcomes compared with the previous CCG trial of more prolonged but less intense therapy. This regimen that deletes high-dose methotrexate, if confirmed in a larger trial, could be considered as an alternative treatment approach in children without high tumor burdens (LDH <2 × NL) and Murphy stage III disease.

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Acknowledgements

The authors would like to thank Linda Rahl, Shaun Mason, and Lucia Noll for their editorial assistance in the preparation of this manuscript. Grant support from the Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Department of Health and Human Services. Contributing Children's Cancer Group investigators, institutions, and grant numbers are given in the Appendix.

Table 4 Appendix: Participating principal investigators – Children's Cancer Group
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Authors and Affiliations

  1. Children's Hospital of New York, Columbia University, New York, NY, USA

    MS Cairo & E Morris

  2. Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    MD Krailo

  3. Children's Hospital of Denver, Denver, CO, USA

    M Morse

  4. Mott Children's Hospital, University of Michigan, Ann Arbor, MI, USA

    RJ Hutchinson

  5. Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA

    RE Harris

  6. University of Utah Medical Center, Salt Lake City, UT, USA

    CR Kjeldsberg

  7. Beth Israel Hospital, Boston, MA, USA

    ME Kadin

  8. Montefiore Medical Center, Bronx, NY, USA

    E Radel

  9. Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    LJ Steinherz

  10. New York University, New York, NY, USA

    JL Finlay

  11. Children's Hospital of Philadelphia, Philadelphia, PA, USA

    AT Meadows

Authors
  1. MS Cairo
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  2. MD Krailo
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  3. M Morse
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  4. RJ Hutchinson
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  5. RE Harris
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  6. CR Kjeldsberg
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Additional information

Presented in part at the American Society of Hematology (ASH), San Francisco, CA, 2000

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Cairo, M., Krailo, M., Morse, M. et al. Long-term follow-up of short intensive multiagent chemotherapy without high-dose methotrexate (‘Orange’) in children with advanced non-lymphoblastic non-Hodgkin's lymphoma: a Children's Cancer Group Report. Leukemia 16, 594–600 (2002). https://doi.org/10.1038/sj.leu.2402402

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