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Therapy

Comparison of the L10M consolidation regimen to an alternative regimen including escalating methotrexate/L-asparaginase for adult acute lymphoblastic leukemia: a Southwest Oncology Group Study

Leukemia volume 15, pages 208–216 (2001)Cite this article

Abstract

The effectiveness of intensive post-remission chemotherapy regimens for adult patients with acute lymphoblastic leukemia (ALL) is limited by both a high rate of disease recurrence and a substantial incidence of treatment toxicity. To evaluate a potentially more effective and less toxic approach, we conducted a multicenter phase III trial of consolidation therapies comparing the standard L10M regimen with one combining the brief, intensive L17M regimen and escalating methotrexate (MTX) and L-asparaginase (L-asp). Patients over age 15 with previously untreated ALL were eligible. Induction therapy included vincristine, prednisone, doxorubicin, cyclophosphamide and intrathecal methotrexate administered over 36 days. Patients who achieved complete remission (CR) were randomized to receive consolidation with either the L10M regimen or with DAT (daunomycin, cytosine arabinoside, 6-thioguanine) and escalating MTX and L-asp. The randomization was stratified by age, WBC and Ph chromosome status. Maintenance therapy was the same in both arms. Of 353 eligible patients, 218 (62%) achieved CR and 195 were randomized. The treatment arms did not differ significantly with respect to disease-free survival (DFS; P = 0.46) or overall survival (P = 0.39). Estimated DFS at 5 years was 32% (95% confidence interval (CI) 23–42%) in the L10M arm and 25% (95% CI 16–33%) in the DAT/MTX/L-asp arm. In each arm, 4% of patients died of toxicities (infection in all but one case). Infections and nausea/vomiting were somewhat more common in the L10M arm (occurring in 68% and 53% of patients respectively) than the DAT/MTX/L-asp arm (56% and 33%). The DAT/MTX/L-asp consolidation regimen was associated with some reduction in nonfatal toxicities, but no significant improvement in DFS, overall survival or non-relapse mortality when compared to the standard L10M regimen.

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Acknowledgements

This investigation was supported in part by the following PHS Cooperative Agreement grant numbers awarded by the National Cancer Institute, DHHS: CA32102, CA38926, CA04920, CA20319, CA46441, CA58686, CA16385, CA22433, CA35431, CA32734, CA42028, CA04919, CA46282, CA35281, CA58861, CA37981, CA46136, CA12213, CA46113, CA35261, CA27057, CA42777, CA35090, CA35128, CA35176, CA35119, CA45377, CA35178, CA58416, CA52654, CA13612, CA35262, CA12644, CA58348, CA45560, CA35192, CA45807, CA58415.

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Authors and Affiliations

  1. Puget Sound Oncology Consortium, Seattle, WA, USA

    SH Petersdorf & FR Appelbaum

  2. Southwest Oncology Group Statistical Center, Seattle, WA, USA

    KJ Kopecky

  3. St Jude Children's Research Hospital, Memphis, TN, USA

    DR Head

  4. University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

    DH Boldt

  5. Ohio State University Health Center, Columbus, OH, USA

    SP Balcerzak

  6. University of California, Davis, Sacramento, CA, USA

    T Wun

  7. University of Oklahoma Health Science Center, Oklahoma City, OK, USA

    V Roy

  8. Louisiana State University, New Orleans, LA, USA

    RW Veith

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Petersdorf, S., Kopecky, K., Head, D. et al. Comparison of the L10M consolidation regimen to an alternative regimen including escalating methotrexate/L-asparaginase for adult acute lymphoblastic leukemia: a Southwest Oncology Group Study. Leukemia 15, 208–216 (2001). https://doi.org/10.1038/sj.leu.2402006

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