Treatment of Cutaneous T-Cell Lymphoma by Extracorporeal Photochemotherapy

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. (N Engl J Med 1987; 316:297–303.) STUDIES in rodents have shown that intravenous infusion of syngeneic cells from in vitro expanded autoreactive clones of T cells can induce experimental autoimmune thyroiditis, encephalomyelitis, or arthritis. 1 However, if cells from the same T-cell clones are lethally damaged and then infused into syngeneic mice or rats, the recipient animal becomes resistant to induction of the disease by subsequent infusion of viable autoreactive T cells. 2 , 3 These findings suggested that an induced clone-specific immune reaction might limit the activity of an aberrant population of T cells and raised the possibility that similar results might be obtained in humans with diseases mediated . . .