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Randomized Controlled Trial
. 2011 Jul 28;118(4):874-83.
doi: 10.1182/blood-2010-06-292615. Epub 2011 Apr 7.

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)

Barbara L Asselin  1 , Meenakshi Devidas, Chenguang Wang, Jeanette Pullen, Michael J Borowitz, Robert Hutchison, Steven E Lipshultz, Bruce M Camitta
Affiliations
Randomized Controlled Trial

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)

Barbara L Asselin et al. Blood. .

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.

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Figures

Figure 1
Figure 1
Patient enrollment in POG 9404.
Figure 2
Figure 2
Event-free and overall survival for all randomized patients.
Figure 3
Figure 3
Event-free survival based on diagnosis of T-ALL or T-NHL.
Figure 4
Figure 4
Event-free survival for all eligible patients according to methotrexate randomization and disease. (A) EFS curves based on treatment with (HDM) or without (no HDM) HDM. (B) EFS for T-ALL patients by treatment (HDM vs no HDM). (C) EFS for T-NHL patients by treatment (HDM vs no HDM).
Figure 5
Figure 5
Cumulative incidence (CI) of CNS relapse (isolated and concurrent with other sites) for patients according to methotrexate randomization. (A) CI for T-ALL patients. (B) CI for T-NHL patients. (C) CI for all patients.
See this image and copyright information in PMC

Comment in

  • Childhood T-all: it's time to move on.
    Whitlock JA, Silverman LB. Whitlock JA, et al. Blood. 2011 Jul 28;118(4):828-9. doi: 10.1182/blood-2011-05-348375. Blood. 2011. PMID: 21799094 No abstract available.

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