From the Research
Methotrexate is the first-line treatment for large granular lymphocytic leukemia (LGL leukemia), particularly for patients with symptomatic cytopenias, with a recommended dosing regimen of 10-15 mg/m² given weekly, either orally or parenterally, with folate supplementation (1 mg daily) to reduce side effects. This recommendation is based on the most recent and highest quality study available, which reported an overall response rate (ORR) of 86% with methotrexate therapy, with a median response duration of 20 months 1.
Key Points to Consider
- Methotrexate works in LGL leukemia by suppressing the abnormal proliferation of large granular lymphocytes through its immunomodulatory and anti-inflammatory properties, rather than through direct cytotoxicity 2.
- The medication is particularly effective for managing the autoimmune manifestations of LGL leukemia, including neutropenia, anemia, and rheumatoid arthritis-like symptoms 3.
- Common side effects include nausea, mouth sores, and liver function abnormalities, requiring regular monitoring of blood counts and liver enzymes 4.
- For patients who don't respond to methotrexate, alternative options include cyclophosphamide, cyclosporine, or targeted therapies depending on disease characteristics 5.
Important Considerations for Treatment
- The presence of a STAT3 mutation can impact the effectiveness of methotrexate therapy, with patients having a mutation tend to have a shorter treatment-free survival compared to those without a mutation 1.
- Pure red cell aplasia (PRCA) is a common complication in LGL leukemia and can respond well to methotrexate therapy 1.
- Methotrexate with or without prednisone is an effective initial therapy for patients with T-LGLL with wild-type STAT3 1.