TREATMENT OF LARGE GRANULAR LYMPHOCYTE LEUKEMIA WITH ORAL LOW-DOSE METHOTREXATE

Morbidity and mortality in patients with T large granular lymphocyte ( T-LGL) leukemia result from infections acquired during severe neutrope nia. Optimum treatment for severe neutropenia remains undefined. We co nducted an uncontrolled but prospective study of low-dose oral methotr exate, up to 10 mg/m(2) weekly, in 10 patients with this disease. Ther apeutic response was assessed by serial clinical evaluations and labor atory determinations including complete blood counts, lymphocyte pheno typing, and T-cell receptor gene rearrangement studies. A partial resp onse was defined as a sustained increase in neutrophil count greater t han 500/mu L. A complete clinical remission was defined as achievement of a normal complete blood count and CD3(+) LGL count. Previous predn isone treatment in eight of these patient had produced one clinical re mission and four partial responses; tapering of prednisone in each of these patients resulted in recurrence of severe neutropenia. Five pati ents in this study received both methotrexate and tapering doses of pr ednisone. Complete clinical remissions on methotrexate were observed i n five patients; an additional patient had a partial response. Molecul ar analyses of T-cell receptor gene rearrangement could not detect the abnormal clone in three of five patients achieving a complete clinica l remission. Two weeks to 4 months of therapy were needed before attai ning a neutrophil count greater than 500/mu L. Complete and partial re sponses have been maintained on therapy, with a follow-up period rangi ng from 1.3 to 9.6 years. Low-dose oral methotrexate therapy is an eff ective treatment for some patients with LGL leukemia. (C) 1994 by The American Society of Hematology.