Figure 4. HTS discriminates CTCL recurrences from benign inflammation, provides accurate assessment of responses to therapy and facilitates early diagnosis of disease recurrence in both the skin and blood of patients with CTCL.
(A-D) HTS distinguishes CTCL recurrences from benign inflammatory disease. Patient 247 had a history of stage IB CTCL, subsequently developed leukemic involvement and was treated with low dose alemtuzumab. Prior to therapy, TCRVβ HTS demonstrated a clear malignant clone in blood (A). The patient initially improved on alemtuzumab, then developed the skin eruption shown (B). Histopathology of the lesional skin was suggestive of a drug hypersensitivity reaction but a T cell dyscrasia could not be ruled out. HTS of blood and lesional skin showed clearance of the malignant T cell clone from blood and skin, confirming this was a benign inflammatory dermatitis (C). Bactrim was discontinued and the eruption completely resolved with topical steroids and narrow band UVB therapy. (D) Diverse populations of T cells remain within the skin of alemtuzumab treated patients. TCRVβ HTS of the skin of patient 247 while on alemtuzumab is shown. This patient had no circulating T or B cells but a diverse population of T cells remained in skin. (E-F) HTS allows longitudinal observation of disease activity over time and assesses responses to therapy. Patient 409, Stage IIA CTCL, was studied by HTS in 2012, after treatment with electron beam and brachytherapy and again in 2014, after initiation of gemcitabine. HTS demonstrated an identical clonal T-cell population in the skin at both time points, reduced but still frequent after gemcitabine therapy. The malignant clone (black circle) and three most frequent benign T cell clones (white circles) are shown. (G-H) HTS provides early diagnosis of disease recurrence. Patient 425 had recalcitrant stage IIB CTCL with CD30+ large cell transformation. She underwent stem cell transplantation (SCT) and appeared well until she developed a new right chest lesion 10 months after SCT (G). HTS prior to SCT demonstrated that presence of a malignant T cell clone (H). Biopsy of the lesion post SCT demonstrated recurrence of the same malignant T cell clone in the skin. The malignant T cell clone (black circles) and the three most frequent benign T cell clones (white circle) are shown. Subsequent withdrawal of systemic immunosuppression and narrowband UVB therapy induced a complete remission. (I) HTS allows accurate assessment of peripheral blood disease. HTS studies of 4 patients without CTCL, 12 patients with MF without evidence of blood disease (MF) and in 7 patients with leukemic disease (L-CTCL) with known blood involvement are shown. (test: Kruskal–Wallis one-way ANOVA with a Bonferroni-Dunn’s post test).