Tool Predicts Deadly Form of Mycosis Fungoides

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 develops progressive and fatal disease and because outcomes can be so different, early identification of this high-risk population is an urgent unmet clinical need. If identified early, patients with this aggressive form of MF may be eligible for a stem cell transplant to cure the disease, but once MF progresses and becomes treatment-resistant, it is nearly impossible to achieve the complete remission required for a successful stem cell transplant.

Scientists from the Brigham and Women’s Hospital (Boston, MA, USA) and their colleagues 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. They compared these data to the results in an independent validation cohort of 101 CTCL patients (87 with MF).

The team used high-throughput DNA sequencing, a technique that allowed them to sequence massive amounts of DNA at once, producing a snapshot of the TCRB genes from a large number of cells at the site of the lesion. The team could use this to measure “tumor clone frequency (TCF)” – the percentage of T cells that are clones of the mutated MF lymphoma T cells. An elevated TCF predicted the likelihood of progression and overall survival of patients with MF with high sensitivity and specificity.

The team found that in early-stage patients, a TCF of more than 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.

Thomas S. Kupper, MD, a professor of Dermatology and senior author of the study, said, “Under the microscope, benign T cell and MF T cells are hard to distinguish. However, every T cell has a unique DNA sequence of its T cell receptor, which we can detect by high-throughput DNA sequencing. High throughput DNA sequencing and calculations of TCF allow us to make predictions that would never before have been possible. As a physician who has treated patients with this disease for decades, I am excited to be involved with work that so directly and profoundly affects the care and management of these patients.” The study was published on May 9, 2018, in the journal Science Translational Medicine.

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