Systemically disseminated
cutaneous T-cell lymphoma is generally resistant to
chemotherapy and
radiotherapy. We tested a treatment involving the extracorporeal photoactivation of biologically inert
methoxsalen (8-methoxypsoralen) by ultraviolet A energy to a form that covalently cross-links
DNA. After
oral administration of
methoxsalen, a lymphocyte-enriched blood fraction was exposed to ultraviolet A (1 to 2 J per square centimeter) and then returned to the patient. The combination of ultraviolet A and
methoxsalen caused an 88 +/- 5 percent loss of viability of target lymphocytes, whereas the
drug alone was inactive. Twenty-seven of 37 patients with otherwise resistant
cutaneous T-cell lymphoma responded to the treatment, with an average 64 percent decrease in cutaneous involvement after 22 +/- 10 weeks (mean +/- SD). The responding group included 8 of 10 patients with lymph-node involvement, 24 of 29 with exfoliative
erythroderma, and 20 of 28 whose disease was resistant to standard
chemotherapy. Side effects that often occur with standard
chemotherapy, such as bone marrow suppression, gastrointestinal erosions, and
hair loss, did not occur. Although the mechanism of the beneficial effect is uncertain, an immune reaction to the infused damaged cells may have restricted the activity of the abnormal T cells. This preliminary study suggests that
extracorporeal photochemotherapy is a promising treatment for widespread
cutaneous T-cell lymphoma.