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 2020 Apr;34(4):1006-1016
Date
11/16/2019Pubmed ID
31728054Pubmed Central ID
PMC7749787DOI
10.1038/s41375-019-0642-2Scopus ID
2-s2.0-85075046448 (requires institutional sign-in at Scopus site) 8 CitationsAbstract
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.
Author List
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 BMMESH terms used to index this publication - Major topics in bold
AdolescentAntineoplastic Combined Chemotherapy Protocols
Asparaginase
Child
Child, Preschool
Cyclophosphamide
Cytarabine
Daunorubicin
Dexamethasone
Drug Administration Routes
Drug Administration Schedule
Female
Humans
Infant
Male
Mercaptopurine
Methotrexate
Neoplasm, Residual
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Prednisone
Random Allocation
Remission Induction
Survival Analysis
Time Factors
Treatment Outcome
Vincristine
Young Adult