Management of T-Cell Large Granular Lymphocyte Leukemia with Methotrexate or Cyclophosphamide

Background. T-Cell Large Granular Lymphocyte Leukemia (T-LGL Leukemia) is an extremely rare lymphoproliferative disorder which can originate from either mature T cells (CD3⁺) or natural killer cells (CD3^-). T-LGL leukemia is a slowly progressing disease, rarely presenting with an aggressive course and in general patients have prolonged survival. Treatment is commonly monotherapy with methotrexate (with or without prednisone), cyclosporine, or cyclophosphamide. Herein we review our experience with the management of T-LGL in the last 15 years.

Patients and Methods. We conducted a retrospective cohort study of all patients diagnosed with T-LGL at our center between 2000 and 2015. Patients were included if they had a positive study for T-Cell Receptor gene rearrangement. Response was evaluated using the criteria of Loughran et al (Leukemia 2015). Data was analyzed using descriptive statistics.

Results. We included 23 patients, (16 male). All of the patients were caucasian with the exception of two. The average age at diagnosis is 65.1 years. Patients were treated for symptomatic cytopenias or splenomegaly with transfusions and/or chemotherapy. Six patients did not need any treatment. Fourteen of the 23 patients were treated with oral methotrexate monotherapy. The methotrexate dose ranged from 5mg/week to 15mg/week orally. Seven patients had a complete response, 2 had a partial response, 3 patients failed treatment, 1 patient was not evaluable, and 1 was stable. Four patients were treated with methotrexate and prednisone. Two patients obtained a complete response, with 1 partial response, and 1 patient was not evaluable due to the short duration of the prescription. Nine patients were treated with oral cyclophosphamide at doses of 50mg or 100mg po daily. Four patients achieved a complete response, 2 patients achieved a partial response, while the other 3 patients did not respond. Only 2 patients were treated with oral cyclosporine, at 400mg/day and at 500mg/day. One patient failed treatment while the other is still on therapy. Two patients died while on the study at 22 and 42 months, both deaths were due to other illnesses not associated with T-LGL Leukemia. The median time since diagnosis for the remaining patients is 41 months.

Conclusion. T-LGL is a rare lymphoproliferative disorder. Most patients responded to simple oral therapy with methotrexate or cyclophosphamide and patients generally have prolonged survivals.