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Neutropenia Associated With T-Cell Large Granular Lymphocyte
Leukemia: Long-Term Response to Cyclosporine Therapy Despite
Persistence of Abnormal Cells
Raman Sood,
Carleton C. Stewart,
Peter D. Aplan,
Hiroyuki Murai,
Pamela Ward,
Maurice Barcos, and
Maria R. Baer
From the Departments of Hematologic Oncology and Bone Marrow
Transplantation, the Division of Medicine, Laboratory of Flow
Cytometry, the Department of Pediatrics, the Department of Neurology,
Laboratory of Molecular Diagnostics, and the Department of Pathology,
Roswell Park Cancer Institute, Buffalo, NY.
T-cell large granular lymphocyte (T-LGL) leukemia is clinically
indolent, but is associated with severe neutropenia in approximately 50% of cases. The pathogenesis of the neutropenia is unclear. We
report reversal of severe neutropenia associated with T-LGL leukemia in
five patients treated with cyclosporine (CSA). All five had persistent
neutrophil counts below 0.5 × 109/L, two had
agranulocytosis, and four had recurrent 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 (TCR) gene rearrangements in two of two pretreatment blood samples studied. CSA was initiated at doses of 1 to 1.5 mg/kg orally every 12 hours, with subsequent dose adjustments based on trough serum levels.
Four patients attained normal neutrophil counts with CSA alone; one
required addition of low-dose granulocyte-macrophage colony-stimulating
factor. Time to attainment of 1.5 × 109/L neutrophils
ranged from 21 to 75 days. Attempts to taper and withdraw CSA resulted
in recurrent neutropenia. Three patients have maintained normal
neutrophil counts on continued CSA therapy for 2, 8, and 8.5 years. Two
patients died 1.7 and 4.6 years after initiation of CSA despite normal
neutrophil counts one of metastatic melanoma and one of complications
after aortofemoral bypass surgery. Despite resolution of neutropenia,
increased populations of T-LGL cells have persisted in all patients
during CSA therapy, as shown by morphology and flow cytometry and by
the presence of clonal TCR gene rearrangements in four patients'
posttreatment blood samples. We conclude that CSA is an effective
therapy for neutropenia associated with T-LGL leukemia, and that
resolution of neutropenia despite persistence of abnormal cells implies
that CSA may inhibit T-LGL secretion of yet unidentified mediators of
neutropenia.
Blood, Vol. 91 No. 9 (May 1), 1998:
pp. 3372-3378
© 1998 by The American Society of Hematology.
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