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Treatment of large granular lymphocyte leukemia with oral low-dose
methotrexate
TP Loughran , PG Kidd and G Starkebaum
Veterans Affairs Medical Center, Syracuse, NY 13210.
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.
Volume 84,
Issue 7,
pp. 2164-2170,
10/01/1994
Copyright © 1994 by The American Society of Hematology
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