Morbidity and mortality in patients with T large granular lymphocyte (T-
LGL) leukemia result from
infections acquired during severe
neutropenia. Optimum treatment for severe
neutropenia remains undefined. We conducted an uncontrolled but prospective study of low-dose oral
methotrexate, up to 10 mg/m2 weekly, in 10 patients with this disease. Therapeutic response was assessed by serial clinical evaluations and laboratory determinations including complete blood counts, lymphocyte phenotyping, and T-cell receptor gene rearrangement studies. A partial response was defined as a sustained increase in neutrophil count greater than 500/microL. A complete clinical remission was defined as achievement of a normal complete blood count and CD3+ LGL count. Previous
prednisone treatment in eight of these patients had produced one clinical remission and four partial responses; tapering of
prednisone in each of these patients resulted in recurrence of severe
neutropenia. Five patients in this study received both
methotrexate and tapering doses of
prednisone. Complete clinical remissions on
methotrexate were observed in five patients; an additional patient had a partial response. Molecular analyses of T-cell receptor gene rearrangement could not detect the abnormal clone in three of five patients achieving a complete clinical remission. Two weeks to 4 months of
therapy were needed before attaining a neutrophil count greater than 500/microL. Complete and partial responses have been maintained on
therapy, with a follow-up period ranging from 1.3 to 9.6 years. Low-dose oral
methotrexate therapy is an effective treatment for some patients with
LGL leukemia.