Open AccessRandomized assessment of delayed intensification and two methods for parenteral methotrexate delivery in childhood B-ALL: Children’s Oncology Group Studies P9904 and P9905
Author(s) -
Naomi J. Winick,
Paul Martin,
Meenakshi Devidas,
Jonathan J. Shuster,
Michael J. Borowitz,
W. Paul Bowman,
Eric Larsen,
Jeanette Pullen,
Andrew J. Carroll,
Cheryl L. Willman,
Stephen P. Hunger,
William L. Carroll,
Bruce M. Camitta
Publication year - 2019
Publication title -
leukemia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.539
H-Index - 192
eISSN - 1476-5551
pISSN - 0887-6924
DOI - 10.1038/s41375-019-0642-2
Subject(s) - medicine , prednisone , methotrexate , randomization , minimal residual disease , gastroenterology , acute lymphocytic leukemia , induction chemotherapy , randomized controlled trial , leukemia , chemotherapy , lymphoblastic leukemia
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/m 2 ) vs. 4-h (2 g/m 2 ) 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.