Department of Dermatology, Brigham and Women's Hospital, and the Center for Cutaneous Oncology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, MA 02115, USA.
Center for Hematologic Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Sci Transl Med. 2018 May 9;10(440). doi: 10.1126/scitranslmed.aar5894.
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 () 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 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），最常见的皮肤 T 细胞淋巴瘤（CTCL），是一种皮肤归巢记忆 T 细胞的恶性肿瘤。大多数 MF 病例表现为早期（I 期 A/B 期，局限于皮肤），这些患者通常具有慢性、惰性的临床病程。然而，一小部分早期病例会发展为进行性和致命性疾病。由于结局可能如此不同，早期识别这种高危人群是一个迫切的未满足的临床需求。我们评估了下一代高通量 T 细胞受体 β 基因（）皮肤活检的 DNA 测序在预测 15 年纵向观察性临床研究中 208 例 CTCL（177 例 MF）患者的发现队列中的进展和生存中的应用。我们将这些数据与来自独立验证队列的 101 例 CTCL 患者（87 例 MF）的结果进行了比较。通过高通量测序测量的病变皮肤中的肿瘤克隆频率（TCF）是 CTCL 和 MF 患者无进展和总生存的独立预后因素。在早期患者中，皮肤中的 TCF>25%是比任何其他既定预后因素（IB 期比 IA 期、斑块存在、高血乳酸脱氢酶浓度、大细胞转化或年龄）更强的进展预测因子。因此，TCF 可能能够准确预测早期 MF 的疾病进展。早期识别进展风险高的患者可能有助于识别那些在疾病变得难治之前可能受益于同种异体造血干细胞移植的候选者。
