Single-center Series of Bone Marrow Biopsy-Defined Large Granular Lymphocyte Leukemia: High Rates of Sustained Response to Oral Methotrexate

Abstract Introduction Large granular lymphocyte (LGL) leukemia is a rare chronic lymphoproliferative disorder, with few large series reported to date. Series using stringent diagnostic criteria incorporating bone marrow biopsy (BMB), immunophenotyping, and T-cell receptor rearrangements are even scarcer. Patients and Methods The present study was a single-center series of 39 patients with LGL leukemia diagnosed using immunohistochemical analysis of BMB samples and flow cytometric and molecular data. Results With a median follow-up of 3.2 years (range, 1.0-15.1 years), 15 patients (38%) never required treatment. Of the remaining 24 patients requiring treatment, 13 were initially treated with prednisolone, for an overall response rate (ORR) of 84.6% and a median duration of response (DOR) of 13.5 months (range, 5.7-70.3 months). Of the 24 patients, 9 received oral low-dose weekly methotrexate as first-line therapy, with 8 (89%) achieving a hematologic response and a median DOR of 132.7 months (range, 6.7-180.5 months). Another 5 patients received methotrexate after prednisolone failure; all 5 responded, with a median DOR of 14 months (range, 4-96 months). Only 2 patients developed progression during methotrexate therapy, and 4 patients experienced responses lasting ≥ 5 years. Conclusion Single-agent oral methotrexate appears to be highly efficacious, resulting in long response durations and minimal toxicity.