Microarray Analysis of the Effect of Cyclosporine Therapy on Gene Expression Patterns in Large Granular Lymphocytic Leukemia
- LGL leukemia is a low grade non-Hodgkins Lymphoma characterized by tissue invasion of
the marrow, spleen and liver
- Recurrent infections due to chronic neutropenia and transfusion-dependent anemia are
the principal causes for initiation of therapy
- Approximately 50% of patients treated with cyclosporine (CSA) respond to treatment. CSA
appears to correct the associated cytopenia without decreasing LGL numbers, suggesting
it may inhibit LGL secretion of yet unidentified mediators of neutropenia and anemia.
- Analysis of differential gene expression profiles in patients with LGL leukemia treated
with cyclosporine has the potential to detect as yet unidentified, therapeutic targets
and possibly provide predictors of CSA responsiveness.
- Identify changes in gene expression patterns induced by cyclosporine therapy in
patients with LGL leukemia
- Identify differences between responding and non-responding patients
-Patients with Large Granular Lymphocyte leukemia
- Patients will be treated with cyclosporine at a dose of 5-10mg/kg/day in divided doses,
with doses adjusted to maintain a therapeutic serum level between 200-400ng/ml. These
therapeutic levels shall be maintained for 3 months.
- Tumor response will be evaluated after 3 months therapy, the dose of CsA may then be
tapered to that required to sustain a response or discontinued if no evidence of
response, or after relapse.
- Blood sampling or Lymphapheresis for collection of circulating malignant cells will be
performed at a number of different time points. Gene expression profiling will be
carried out on Affymetrix microarrays to compare pretreatment and post-treatment
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Changes in Gene Expression Patterns
Differences (2 fold) in mean gene expression between pre-treatment and post treatment.
Baseline and 12 weeks
Thomas Waldmann, M.D.
National Cancer Institute, National Institutes of Health
United States: Federal Government
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