methotrexate IV

The ABLE risk-stratification model can effectively differentiate prognostic subgroups in patients with PCNSL.

This pathway-informed approach identifies genetic contributors to methotrexate-induced mucositis and supports polygenic risk prediction. Our findings provide a foundation for individualized toxicity risk profiling and suggest potential therapeutic targets to mitigate treatment-limiting mucositis in pediatric oncology.

It was revealed that the lymphoma cells of both lymphoplasmacytic lymphoma/Waldenström macroglobulinemia and primary central nervous system lymphoma derived from a common cell possessing MYD88. The utility of adding chemotherapy for low-grade lymphoma in addition to therapy for primary central nervous system lymphoma is not clear. While lymphoplasmacytic lymphoma is a low-grade lymphoma that does not always require chemotherapy, combining treatment for lymphoplasmacytic lymphoma and primary central nervous system lymphoma may contribute to the effectiveness of both treatments.

P2, N=50, Not yet recruiting, Fred Hutchinson Cancer Center

P=N/A, N=20, Active, not recruiting, Ohio State University Comprehensive Cancer Center | Trial completion date: Nov 2025 --> Nov 2026 | Trial primary completion date: Sep 2025 --> Jan 2026

SIGNIFICANCE STATEMENT: This study identifies γ-glutamyl hydrolase/SLCO1B1/SLC19A1 polymorphisms as key predictors of methotrexate toxicity in Chinese acute lymphoblastic leukemia patients, whereas population pharmacokinetic reveals glomerular filtration rate-not genetics-drives clearance. Findings advocate for genotype-toxicity monitoring and glomerular filtration rate-based dosing to improve safety.

Among the 20 patients undergoing curative-intent treatment, most received less-intensive CNS-directed therapies, including R-CHOP with intrathecal chemotherapy or high-dose methotrexate...Our findings highlight the need for CNS-penetrant, intensified frontline strategies and support the investigation of Bruton's tyrosine kinase inhibitor-containing regimens in this population. Multicenter collaborative studies with standardized diagnostic and treatment approaches are essential to improve outcomes in synDLBCL.

Historically, high-dose methotrexate- or cytarabine-based chemotherapy, intrathecal therapy, and radiotherapy have been used; however, responses varied, and toxicity was considerable...Retrospective data support durable responses with ibrutinib, tirabrutinib, and zanubrutinib, while early findings suggest that non-covalent BTK inhibitors expand options for relapsed or refractory cases. Herein, we synthesize current evidence on epidemiology, pathophysiology, and diagnostic work-up. We also outline therapeutic recommendations integrating the genotype, disease pattern, and patient fitness and conclude with unmet needs and future directions.

Over subsequent years, she experienced multiple relapses, treated with bendamustine-rituximab and later lenalidomide, achieving remission...She received high-dose methotrexate, rituximab, and temozolomide with Stereotactic Body Radiotherapy (SBRT) for melanoma. Despite significant intracranial progression, she remained largely asymptomatic and prioritized quality of life, highlighting the challenges of individualized care in complex dual malignancies.

P3, N=91, Completed, Children's Oncology Group | Active, not recruiting --> Completed | Trial completion date: Dec 2028 --> Sep 2025

In conclusion, the R2-MTX regimen showed encouraging efficacy and a manageable safety profile in a small cohort of newly diagnosed PCNSL patients unsuitable for ASCT. These preliminary findings suggest that R2-MTX may be a promising therapeutic alternative, but validation in larger, prospective multicenter studies is warranted.

The patient underwent four cycles of rituximab and high-dose methotrexate, resulting in lesion resolution on follow-up MRI, with motor aphasia persisting. This case represents a rare instance of primary central nervous system lymphoma (PCNSL) initially presenting as CSDH, with progression to hematoma organization and brain herniation. This case provides new insights and experience in recognizing and managing rare clinical presentations of primary central nervous system lymphoma.