Institutional members access full text with Ovid®

Share this article on:

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

Journal of Pediatric Hematology/Oncology: July 2014 - Volume 36 - Issue 5 - p 353–361
doi: 10.1097/MPH.0000000000000131
Original Articles

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.

*MACC Fund Center for Cancer and Blood Disorders, Medical College of Wisconsin and Children’s Hospital of Wisconsin, Milwaukee, WI

Department of Biostatistics, Colleges of Medicine and Public Health and Health Professions

††Department of Health Outcomes and Policy and Clinical and Translational Science Institute, College of Medicine, University of Florida

Children’s Oncology Group, Department of Biostatistics, Gainesville, FL

Department of Pediatrics, Golisano Children’s Hospital at University of Rochester Medical Center, Rochester

#New York Medical College, Valhalla, NY

§Department of Pediatrics, Georgia Health Sciences University, Augusta, GA

Department of Pediatrics, Charleston Division, West Virginia University, Charleston, WV

**Department of Pediatric Hematology/Oncology, University of Mississippi Medical Center, Jackson, MS

‡‡Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX

§§Pediatric Blood and Marrow Transplant Program, Duke University Medical Center, Durham, NC

Supported by the following NIH grants: COG Chairs grant U10CA98543; POG Statistical Center grant U10CA30969; COG Statistics and Data Center grant U10CA98413.

The authors declare no conflict of interest.

Reprints: Richard L. Tower, MD, MACC Fund Center for Cancer and Blood Disorders, Medical College of Wisconsin, MFRC 3018, 8701 Watertown Plank Road, Milwaukee, WI 53226 (e-mail:

Received July 22, 2013

Accepted January 24, 2014

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