NYMC Faculty Publications

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

Author Type(s)

Faculty

DOI

10.1097/MPH.0000000000000131

Journal Title

Journal of Pediatric Hematology/Oncology

First Page

353

Last Page

361

Document Type

Article

Publication Date

7-1-2014

Department

Pediatrics

Keywords

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

Disciplines

Medicine and Health Sciences

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.

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