Skip Navigation LinksHome > July 2014 - Volume 36 - Issue 5 > Dose Intensification of Methotrexate and Cytarabine During I...
Journal of Pediatric Hematology/Oncology:
doi: 10.1097/MPH.0000000000000131
Original Articles

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

Tower, Richard L. MD; Jones, Tamekia L. PhD; Camitta, Bruce M. MD; Asselin, Barbara L. MD; Bell, Beverly A. MD; Chauvenet, Allen MD, PhD; Devidas, Meenakshi PhD; Halperin, Edward C. MD; Pullen, Jeanette MD; Shuster, Jonathan J. PhD; Winick, Naomi MD; Kurtzberg, Joanne MD

Collapse Box


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/m2 versus 2.5 g/m2 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/m2 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.

Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.


Article Tools


Article Level Metrics

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.

Connect With Us


For additional oncology content, visit LWW Oncology Journals on Facebook.