Treatment of stage II cutaneous T-cell lymphoma with interferon alfa-2a and extracorporeal photochemotherapy: A prospective controlled trial

Background: Both interferon alfa and extracorporeal photochemotherapy have been shown to be effective in primary cutaneous T-cell lymphomas (CTCLs). H owever, no prospective trial has been published on the combination of both treatments, although retrospective investigations suggested a better effica cy than For either interferon or extracorporeal photochemotherapy Objective: Our purpose was to evaluate the efficacy and toxicity of combine d interferon alfa-2a with extracorporeal photochemotherapy in a prospective controlled trial. Methods: A prospective controlled study was performed. Fourteen patients (a ll male) aged 38 to 72 years with CTCL of the mycosis fungoides type, stage IIa/lIb, and a 72-year-old male patient with a Ki-1 lymphoma were treated twice a month fur 6 months with extracorporeal photochemotherapy using oral 8-methoxypsoralen as photosensitizer in combination with interferon alfa-a a subcutaneously 3 times a a week in the maximal tolerable dosage tie, up t o 18 x 10(6) U). The effects were investigated by a skin score, staging, hi stologic score (density of the T-cell infiltrate; from 0 = absent to 3 = he avy), immunohistology, and laboratory investigations including total periph eral T-cell count, CD4/CD8 ratio, and soluble interleukin 2 receptor (sIL-2 R). Results: After 6 months, best response was a complete response (CR) in 4 pa tients, a partial response (PR) in 3, and a stable disease (SD) in 7 of 14 patients (overall response rate [CR + PR] 50%). In responders the time to b est response was 4.3 +/- 1.4 months. The skin score decreased from 22.5 +/- 8.1 to 15.1 +/- 11.0 (P <.001), the histologic score decreased from 2.57 /- 0.51 co 1.21 +/- 0.80 (P <.001). In the lesional skin the percentage of CD4 cells decreased from 75% to 51% (P =.038) and Ki-67-positive cells decr eased from 6.7% to 2.4% (P =.001). The total T-cell count/muL decreased fro m 1018.9 +/- 557.1 to 667.9 +/- 417.9 (P =.012), and the CD4/CD8 ratio also decreased from 1.88 +/- 0.92 to 1.51 +/- 0.67 (P =.038). The sIL-2R levels did not change significantly during the first 4 months of treatment. Among patients of stage IIa the response rate was 60% in contrast tu only 25% of those in stage IIb. Side effects were seen temporarily, ranging from grade 0 to grade 3. There was no need for additional therapy, but interferon dos e was decreased because of side effects. After 1 year of follow-up the tota l response race was 46.2% (6 of 13 patients): 5 of 9 with stage IIa (55.6%) and 1 of 4 with stage IIb (25.0%). Conclusion: These results indicate that patients with CTCL stage IIa can ac hieve a total response rate of 56% with combined interferon alfa-2a and ext racorporeal photochemotherapy. Responders seem to experience their best res ponse within the first 6 months of treatment. The treatment is well tolerat ed and does not cause severe side effects.