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

Research output: Contribution to journalArticle

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
JournalLeukemia
DOIs
StateAccepted/In press - 1 Jan 2019

Fingerprint

Precursor Cell Lymphoblastic Leukemia-Lymphoma
Methotrexate
Residual Neoplasm
National Cancer Institute (U.S.)
Random Allocation
Prednisone
Pharmaceutical Preparations
Dexamethasone
Survival

Cite this

Winick, Naomi ; Martin, Paul L. ; Devidas, Meenakshi ; Shuster, Jonathan ; Borowitz, Michael J. ; Paul Bowman, W. ; Larsen, Eric ; Pullen, Jeanette ; Carroll, Andrew ; Willman, Cheryl ; Hunger, Stephen P. ; Carroll, William L. ; Camitta, Bruce M. / Randomized assessment of delayed intensification and two methods for parenteral methotrexate delivery in childhood B-ALL : Children’s Oncology Group Studies P9904 and P9905. In: Leukemia. 2019.
@article{88c0449de8ed48c0a02f9676a3838c93,
title = "Randomized assessment of delayed intensification and two methods for parenteral methotrexate delivery in childhood B-ALL: Children’s Oncology Group Studies P9904 and P9905",
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.",
author = "Naomi Winick and Martin, {Paul L.} and Meenakshi Devidas and Jonathan Shuster and Borowitz, {Michael J.} and {Paul Bowman}, W. and Eric Larsen and Jeanette Pullen and Andrew Carroll and Cheryl Willman and Hunger, {Stephen P.} and Carroll, {William L.} and Camitta, {Bruce M.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1038/s41375-019-0642-2",
language = "English",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Nature Publishing Group",

}

Randomized assessment of delayed intensification and two methods for parenteral methotrexate delivery in childhood B-ALL : Children’s Oncology Group Studies P9904 and P9905. / Winick, Naomi; Martin, Paul L.; Devidas, Meenakshi; Shuster, Jonathan; Borowitz, Michael J.; Paul Bowman, W.; Larsen, Eric; Pullen, Jeanette; Carroll, Andrew; Willman, Cheryl; Hunger, Stephen P.; Carroll, William L.; Camitta, Bruce M.

In: Leukemia, 01.01.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Randomized assessment of delayed intensification and two methods for parenteral methotrexate delivery in childhood B-ALL

T2 - Children’s Oncology Group Studies P9904 and P9905

AU - Winick, Naomi

AU - Martin, Paul L.

AU - Devidas, Meenakshi

AU - Shuster, Jonathan

AU - Borowitz, Michael J.

AU - Paul Bowman, W.

AU - Larsen, Eric

AU - Pullen, Jeanette

AU - Carroll, Andrew

AU - Willman, Cheryl

AU - Hunger, Stephen P.

AU - Carroll, William L.

AU - Camitta, Bruce M.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85075046448&partnerID=8YFLogxK

U2 - 10.1038/s41375-019-0642-2

DO - 10.1038/s41375-019-0642-2

M3 - Article

C2 - 31728054

AN - SCOPUS:85075046448

JO - Leukemia

JF - Leukemia

SN - 0887-6924

ER -