Edelson R, Berger C, Gasparro F, Jegasothy B, Heald P, Wintroub B, Vonderheid E, Knobler R, Wolff K, Plewig G
N Engl J Med. 1987 Feb 5;316(6):297-303. doi: 10.1056/NEJM198702053160603.
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.
系统性播散性皮肤T细胞淋巴瘤通常对化疗和放疗耐药。我们测试了一种治疗方法,即通过紫外线A能量将生物惰性的甲氧沙林(8-甲氧基补骨脂素)体外光活化成一种能与DNA共价交联的形式。口服甲氧沙林后,将富含淋巴细胞的血液成分暴露于紫外线A(每平方厘米1至2焦耳),然后回输给患者。紫外线A和甲氧沙林的联合使用导致靶淋巴细胞活力丧失88±5%,而单独使用该药物则无活性。37例其他治疗方法均耐药的皮肤T细胞淋巴瘤患者中有27例对该治疗有反应,在22±10周(平均±标准差)后皮肤受累平均减少64%。有反应的患者组包括10例有淋巴结受累患者中的8例、29例有剥脱性红皮病患者中的24例以及28例对标准化疗耐药患者中的20例。标准化疗常见的副作用,如骨髓抑制、胃肠道糜烂和脱发,均未出现。虽然有益效果的机制尚不确定,但对输注的受损细胞的免疫反应可能限制了异常T细胞的活性。这项初步研究表明,体外光化学疗法是广泛皮肤T细胞淋巴瘤的一种有前景的治疗方法。