Nine of 10 patients tested had reduction in the frequency of malignant T cells in skin following resiquimod therapy. HTS of DNA from lesional skin before therapy and at 8 weeks was used to identify and quantify clonal malignant T cells. (A) The change in frequency of the malignant T-cell clone as a percentage of the total T-cell population is shown. Patients with a clinical CR (patients 3 and 8) and PR (all others) are indicated. Patient 11, a clinical PR, had eradication of the malignant clone at 8 weeks and patient 1, a clinical PR, had a 99.6% reduction in the malignant clone. Only patient 6 showed a slight increase in the malignant T-cell frequency. (B) The correlation of clinical SWAT scores with malignant T-cell clone frequency by HTS are shown. In general, clinical improvement lagged behind clearance of the malignant T-cell clone and in a subset of patients (11, 1, 5), clinical inflammation persisted despite complete or near eradication of the malignant clone.