Language
English
Publication Date
3-1-2025
Journal
JCO Global Oncology
DOI
10.1200/GO-24-00591
PMID
40153690
PMCID
PMC12004980
PubMedCentral® Posted Date
3-28-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Purpose: Excellent survival for advanced (stages II with high lactate dehydrogenase, III, and IV) pediatric mature B-cell non-Hodgkin lymphoma (MB-NHL) has been achieved with intensive regimens, but adoption in sub-Saharan Africa is limited by inadequate supportive care. We provide real-world data on treating advanced MB-NHL with high-dose methotrexate (HD-MTX; ≥1,000 mg/m2/cycle) where real-time serum MTX monitoring is unavailable.
Methods: We identified two cohorts-a retrospective (January 2017-December 2020) cohort treated with 1,000 or 3,000 mg/m2/cycle of HD-MTX and a prospective (July 2022-July 2023) cohort-with a modified LMB96 protocol containing 3,000 mg/m2/cycle of HD-MTX. All doses of HD-MTX were given over 3 hours. Estimates of 12-month event-free survival (EFS) and overall survival (OS) were calculated with abandonment as an event. Clinical toxicity data were available for the prospective cohort.
Results: The retrospective cohort had 108 patients who received HD-MTX 1,000 mg/m2 (n = 98, 91%) or 3,000 mg/m2 per cycle. The 12-month EFS and OS were 39% (95% CI, 30 to 50) and 54% (95% CI, 44 to 64), respectively. HD-MTX at 3,000 mg/m2 had superior EFS: 69% (95% CI, 49 to 96) versus 33% (95% CI, 24 to 46), P = .004. The prospective cohort had 38 patients. Two ≥grade 3 mucositis, one acute kidney injury, and three treatment-related deaths (8%) occurred. Seven (18%) abandoned treatment. With a median follow-up of 14.5 months, 12-month EFS and OS were 45% (95% CI, 32 to 65) and 59% (95% CI, 45 to 79), respectively. Most relapses were stage IV: EFS 20% versus 51% (non-stage IV; P = .057). Severe malnutrition was associated with OS of 33% versus 58% (normal) or 76% (moderate; P = .055).
Conclusion: HD-MTX dosed at 3,000 mg/m2/cycle is feasible in low-resource settings where routine MTX monitoring is unavailable. Stage IV disease and severe malnutrition may contribute to poorer outcomes.
Keywords
Humans, Methotrexate, Malawi, Female, Male, Child, Retrospective Studies, Lymphoma, B-Cell, Adolescent, Child, Preschool, Prospective Studies, Drug Monitoring, Antimetabolites, Antineoplastic, Resource-Limited Settings
Published Open-Access
yes
Recommended Citation
Mzikamanda, Rizine R; Mulanje, Loviisa; McAtee, Casey L; et al., "High-Dose Methotrexate Usage Without Drug-Level Monitoring in Advanced Pediatric Mature B-Cell Non-Hodgkin Lymphoma in a Resource-Limited Setting in Malawi" (2025). Faculty, Staff and Students Publications. 6432.
https://digitalcommons.library.tmc.edu/baylor_docs/6432