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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Winick, N; Martin, PL; Devidas, M; Shuster, J; Borowitz, MJ; Paul Bowman, W; Larsen, E; Pullen, J; Carroll, A; Willman, C; Hunger, SP; Carroll, WL; Camitta, BM

Published Date

  • April 2020

Published In

Volume / Issue

  • 34 / 4

Start / End Page

  • 1006 - 1016

PubMed ID

  • 31728054

Pubmed Central ID

  • 31728054

Electronic International Standard Serial Number (EISSN)

  • 1476-5551

Digital Object Identifier (DOI)

  • 10.1038/s41375-019-0642-2

Language

  • eng

Conference Location

  • England