期刊
SCIENCE TRANSLATIONAL MEDICINE
卷 10, 期 440, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.aar5894
关键词
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资金
- Lubin Family Foundation
- NIH Specialized Program of Research Excellence [P50 CA9368305]
- NIH [R01CA203721, T32 AR007098, R01 AR063962, P30 AR069625]
- Societe Francaise de Dermatologie
- College des Enseignants de Dermatologie de France
- Association pour la Recherche contre le Cancer
- Fondation Rene Touraine
- Philippe Foundation
- Curing Cutaneous Lymphoma by Advancing Research, Innovation and Offering New Solutions grant from the Cutaneous Lymphoma Foundation
- Harvard Catalyst at the Harvard Clinical and Translational Science Center (National Center for Research Resources)
- Harvard Catalyst at the Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, NIH) [UL1 TR001102]
- Harvard University
Mycosis fungoides (MF), themost 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 b 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.
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