NEUTROPENIA ASSOCIATED WITH T-CELL LARGE GRANULAR LYMPHOCYTE LEUKEMIA- LONG-TERM RESPONSE TO CYCLOSPORINE THERAPY DESPITE PERSISTENCE OF ABNORMAL-CELLS
R. Sood et al., NEUTROPENIA ASSOCIATED WITH T-CELL LARGE GRANULAR LYMPHOCYTE LEUKEMIA- LONG-TERM RESPONSE TO CYCLOSPORINE THERAPY DESPITE PERSISTENCE OF ABNORMAL-CELLS, Blood, 91(9), 1998, pp. 3372-3378
T-cell large granular lymphocyte (T-LGL) leukemia is clinically indole
nt, but is associated with severe neutropenia in approximately 50% of
cases. The pathogenesis of the neutropenia is unclear, We report rever
sal of severe neutropenia associated with T-LGL leukemia in five patie
nts treated with cyclosporine (CSA), All five had persistent neutrophi
l counts below 0.5 x 10(9)/L, two had agranulocytosis, and four had re
current infections. Increased populations of LGL were present in blood
and marrow, with a T-LGL immunophenotype (CD3(+)CD8(+)CD16(+/-)CD56(/-)CD57(+)) shown by multiparameter flow cytometry, and clonal T-cell
receptor (ICR) gene rearrangements in two of two pretreatment blood sa
mples studied. CSA was initiated at doses of 1 to 1.5 mg/kg orally eve
ry 12 hours, with subsequent dose adjustments based on trough serum le
vels. Four patients attained normal neutrophil counts with CSA alone;
one required addition of low-dose granulocyte-macrophage colony-stimul
ating factor. Time to attainment of 1.5 x 10(9)/L neutrophils ranged f
rom 21 to 75 days, Attempts to taper and withdraw CSA resulted in recu
rrent neutropenia. Three patients have maintained normal neutrophil co
unts on continued CSA therapy for 2, 8, and 8.5 years, Two patients di
ed 1.7 and 4.6 years after initiation of CSA despite normal neutrophil
counts-one of metastatic melanoma and one of complications after aort
ofemoral bypass surgery. Despite resolution of neutropenia, increased
populations of T-LGL cells have persisted in all patients during CSA t
herapy, as shown by morphology and flow cytometry and by the presence
of clonal TCR gene rearrangements in four patients' posttreatment bloo
d samples, We conclude that CSA is an effective therapy for neutropeni
a associated with T-LGL leukemia, and that resolution of neutropenia d
espite persistence of abnormal cells implies that CSA may inhibit T-LG
L secretion of yet unidentified mediators of neutropenia. (C) 1998 by
The American Society of Hematology.