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Dose intensification of methotrexate and cytarabine during intensified continuation chemotherapy for high-risk B-precursor acute lymphoblastic leukemia: POG 9406: a report from the Children's Oncology Group. J Pediatr Hematol Oncol 2014 Jul;36(5):353-61

Date

03/13/2014

Pubmed ID

24608079

Pubmed Central ID

PMC4120865

DOI

10.1097/MPH.0000000000000131

Scopus ID

2-s2.0-84903760629   6 Citations

Abstract

PURPOSE: To determine the efficacy and toxicity of higher dose versus standard dose intravenous methotrexate (MTX) and pulses of high-dose cytosine arabinoside with asparaginase versus standard dose cytosine arabinoside and teniposide during intensified continuation therapy for higher risk pediatric B-precursor acute lymphoblastic leukemia (ALL).

PATIENTS AND METHODS: From 1994 to 1999, the Pediatric Oncology Group conducted a randomized phase III clinical trial in higher risk pediatric B-precursor ALL. A total of 784 patients were randomized in a 2×2 factorial design to receive MTX 1 g/m versus 2.5 g/m and to cytosine arabinoside/teniposide versus high-dose cytosine arabinoside/asparaginase during intensified continuation therapy.

RESULTS: Patients receiving standard dose MTX had a 5-year disease-free survival (DFS) of 71.8±2.4%; patients receiving higher dose MTX had a 5-year DFS of 71.7±2.4% (P=0.55). Outcomes on cytosine arabinoside/teniposide (DFS of 70.4±2.4) were similar to higher dose cytosine arabinoside/asparaginase (DFS of 73.1±2.3%) (P=0.41). Overall survival rates were not different between MTX doses or cytosine arabinoside/teniposide versus cytosine arabinoside/asparaginase.

CONCLUSIONS: Increasing MTX dosing to 2.5 g/m did not improve outcomes in higher risk pediatric B-precursor ALL. Giving high-dose cytarabine and asparaginase pulses instead of standard dose cytarabine and teniposide produced nonsignificant differences in outcomes, allowing for teniposide to be removed from ALL therapy.

Author List

Tower RL, Jones TL, Camitta BM, Asselin BL, Bell BA, Chauvenet A, Devidas M, Halperin EC, Pullen J, Shuster JJ, Winick N, Kurtzberg J

Authors

Bruce M. Camitta MD Adjunct Professor in the Medicine department at Medical College of Wisconsin
Richard L. Tower MD Associate Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Antineoplastic Combined Chemotherapy Protocols
Asparaginase
Child
Cytarabine
Dose-Response Relationship, Drug
Female
Follow-Up Studies
Humans
Male
Methotrexate
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Prognosis
Remission Induction
Risk Factors
Survival Rate
Teniposide
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a