NEUTROPENIA ASSOCIATED WITH T-CELL LARGE GRANULAR LYMPHOCYTE LEUKEMIA- LONG-TERM RESPONSE TO CYCLOSPORINE THERAPY DESPITE PERSISTENCE OF ABNORMAL-CELLS

Citation
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
Citations number
46
Categorie Soggetti
Hematology
Journal title
BloodACNP
ISSN journal
00064971
Volume
91
Issue
9
Year of publication
1998
Pages
3372 - 3378
Database
ISI
SICI code
0006-4971(1998)91:9<3372:NAWTLG>2.0.ZU;2-O
Abstract
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.