Randomized assessment of delayed intensification and two methods for parenteral methotrexate delivery in childhood B-ALL: Children’s Oncology Group Studies P9904 and P9905

Naomi Winick, Paul L. Martin, Meenakshi Devidas, Jonathan Shuster, Michael J. Borowitz, W. Paul Bowman, Eric Larsen, Jeanette Pullen, Andrew Carroll, Cheryl Willman, Stephen P. Hunger, William L. Carroll, Bruce M. Camitta

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Abstract

The delayed intensification (DI) enhanced outcome for patients with acute lymphoblastic leukemia (ALL) treated on BFM 76/79 and CCG 105 after a prednisone-based induction. Childrens Oncology Group protocols P9904/9905 evaluated DI via a post-induction randomization for eligible National Cancer Institute (NCI) standard (SR) and high-risk (HR) patients. A second randomization compared intravenous methotrexate (IV MTX) as a 24- (1 g/m2) vs. 4-h (2 g/m2) infusion. NCI SR patients received a dexamethasone-based three-drug and NCI HR/CNS 3 SR patients a prednisone-based four-drug induction. End induction MRD (minimal residual disease) was obtained but did not impact treatment. DI improved the 10-year continuous complete remission (CCR) rate; 75.5 ± 2.5% vs. 81.8 ± 2.2% p = 0.002, whereas MTX administration did not; 4-h 80.8 ± 1.9%; 24-h 81.4 ± 1.9% (p = 0.7780). Overall survival (OS) at 10 years did not differ with DI: 91.4 ± 1.6% vs. 90.9 ± 1.7% (p = 0.25) without but was higher with the 24-h MTX infusion; 4-h 91.1 ± 1.4%; 24-h 93.9 ± 1.2% (p = 0.0209). MRD predicted outcome; 10-year CCR 87.7 ± 2.2 and 82.1 ± 2.5% when MRD was <0.01% with/without DI (p = 0.007) and 54.3 ± 8% and 44 ± 8% for patients with MRD ≥ 0.01% with/without DI (p = 0.11). DI improved CCR for patients with B-ALL with and without end induction MRD.

Original languageEnglish
Pages (from-to)1006-1016
Number of pages11
JournalLeukemia
Volume34
Issue number4
DOIs
StatePublished - 1 Apr 2020

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Winick, N., Martin, P. L., Devidas, M., Shuster, J., Borowitz, M. J., Paul Bowman, W., Larsen, E., Pullen, J., Carroll, A., Willman, C., Hunger, S. P., Carroll, W. L., & Camitta, B. M. (2020). Randomized assessment of delayed intensification and two methods for parenteral methotrexate delivery in childhood B-ALL: Children’s Oncology Group Studies P9904 and P9905. Leukemia, 34(4), 1006-1016. https://doi.org/10.1038/s41375-019-0642-2