Faculty Collaboration Database

Effectiveness of high-dose methotrexate in T-cell lymphoblastic leukemia and advanced-stage lymphoblastic lymphoma: a randomized study by the Children's Oncology Group (POG 9404). Blood 2011 Jul 28;118(4):874-83

Date

04/09/2011

Pubmed ID

21474675

Pubmed Central ID

PMC3292437

DOI

10.1182/blood-2010-06-292615

Scopus ID

2-s2.0-79961016780 (requires institutional sign-in at Scopus site)   146 Citations

Abstract

The Pediatric Oncology Group (POG) phase 3 trial 9404 was designed to determine the effectiveness of high-dose methotrexate (HDM) when added to multi-agent chemotherapy based on the Dana-Farber backbone. Children with T-cell acute lymphoblastic leukemia (T-ALL) or advanced lymphoblastic lymphoma (T-NHL) were randomized at diagnosis to receive/not receive HDM (5 g/m² as a 24-hour infusion) at weeks 4, 7, 10, and 13. Between 1996 and 2000, 436 patients were enrolled in the methotrexate randomization. Five-year and 10-year event-free survival (EFS) was 80.2% ± 2.8% and 78.1% ± 4.3% for HDM (n = 219) versus 73.6% ± 3.1% and 72.6% ± 5.0% for no HDM (n = 217; P = .17). For T-ALL, 5-year and 10-year EFS was significantly better with HDM (n = 148, 5 years: 79.5% ± 3.4%, 10 years: 77.3% ± 5.3%) versus no HDM (n = 151, 5 years: 67.5% ± 3.9%, 10 years: 66.0% ± 6.6%; P = .047). The difference in EFS between HDM and no HDM was not significant for T-NHL patients (n = 71, 5 years: 81.7% ± 4.9%, 10 years: 79.9% ± 7.5% vs n = 66, 5 years: 87.8% ± 4.2%, 10 years: 87.8% ± 6.4%; P = .38). The frequency of mucositis was significantly higher in patients treated with HDM (P = .003). The results support adding HDM to the treatment of children with T-ALL, but not with NHL, despite the increased risk of mucositis.

Author List

Asselin BL, Devidas M, Wang C, Pullen J, Borowitz MJ, Hutchison R, Lipshultz SE, Camitta BM

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

Adolescent
Antineoplastic Agents
Antineoplastic Combined Chemotherapy Protocols
Child
Child, Preschool
Disease-Free Survival
Female
Humans
Infant
Male
Methotrexate
Mucositis
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Prognosis
Proportional Hazards Models
Young Adult