Mycosis fungoides (MF), the most common cutaneous T cell lymphoma (CTCL) is a malignancy of skin-tropic memory T cells. Most MF cases present as early stage (stage I A/B, limited to the skin), and these patients typically have a chronic, indolent clinical course. However, a small subset of early-stage cases develop progressive and fatal disease. Because outcomes can be so different, early identification of this high-risk population is an urgent unmet clinical need. We evaluated the use of next-generation high-throughput DNA sequencing of the T cell receptor β gene (TCRB) in lesional skin biopsies to predict progression and survival in a discovery cohort of 208 patients with CTCL (177 with MF) from a 15-year longitudinal observational clinical study. We compared these data to the results in an independent validation cohort of 101 CTCL patients (87 with MF). The tumor clone frequency (TCF) in lesional skin, measured by high-throughput sequencing of the TCRB gene, was an independent prognostic factor of both progression-free and overall survival in patients with CTCL and MF in particular. In early-stage patients, a TCF of >25% in the skin was a stronger predictor of progression than any other established prognostic factor (stage IB versus IA, presence of plaques, high blood lactate dehydrogenase concentration, large-cell transformation, or age). The TCF therefore may accurately predict disease progression in early-stage MF. Early identification of patients at high risk for progression could help identify candidates who may benefit from allogeneic hematopoietic stem cell transplantation before their disease becomes treatment-refractory.

蕈样肉芽肿 (MF) 是最常见的皮肤 T 细胞淋巴瘤 (CTCL) 是皮肤嗜性记忆 T 细胞的恶性肿瘤。大多数 MF 病例表现为早期（IA/B 期，仅限于皮肤），这些患者通常具有慢性、惰性的临床过程。然而，一小部分早期病例会发展为进行性和致命的疾病。由于结果可能如此不同，因此早期识别这一高危人群是一项紧迫的未满足的临床需求。我们评估了 T 细胞受体 β 基因 ( TCRB ) 的下一代高通量 DNA 测序的使用) 在一项为期 15 年的纵向观察临床研究中，在病变皮肤活检中预测 208 名 CTCL 患者（177 名 MF）的发现队列中的进展和存活率。我们将这些数据与 101 名 CTCL 患者（87 名 MF）的独立验证队列的结果进行了比较。通过TCRB的高通量测序测量病变皮肤中的肿瘤克隆频率 (TCF)基因，尤其是 CTCL 和 MF 患者的无进展生存期和总生存期的独立预后因素。在早期患者中，皮肤 TCF > 25% 比任何其他已确定的预后因素（IB 期与 IA 期、斑块的存在、高血乳酸脱氢酶浓度、大细胞转化或年龄）更能预测进展）。因此，TCF 可以准确预测早期 MF 的疾病进展。早期识别具有高进展风险的患者可以帮助识别可能在其疾病变得难以治疗之前从异基因造血干细胞移植中受益的候选人。