EXTRACORPOREAL PHOTOCHEMOTHERAPY INDUCES APOPTOSIS OF INFILTRATING LYMPHOID-CELLS IN PATIENTS WITH MYCOSIS-FUNGOIDES IN EARLY STAGES - A QUANTITATIVE HISTOLOGICAL STUDY

Extracorporeal photochemotherapy (ExP) is a well-tolerated new form of chemoimmunotherapy, which is considered to be effective for cutaneous T-cell lymphoma (CTCL) and the treatment of choice for Sezary syndrom e. Improvements have also been seen in patients with non-erythrodermic mycosis fungoides (MF) in the early stages, even when tumour cells ar e not detectable in the peripheral blood. In this study, we used ExP a s a monotherapy in seven patients who had early stage (Ib) MF, and who were no longer responsive to or had contraindications for other thera pies. We observed a clinical improvement in the disease after 12 month s of treatment: one patient showed a complete response, five a partial response, and one remained stable. In each patient we compared skin b iopsies of large plaque lesions before and after the treatment. We und ertook a histological evaluation of the infiltrate. The lymphoid cell proliferation and death rates were quantified using the following para meters: lymphoid cell density (LCD), Ki67+ lymphoid cell nuclei percen tage (Ki67+ Lcn percentage), and apoptotic index (AI). Significant dec reases in the lymphoid cell infiltrate and in cell proliferation, and a significant increase in AI were observed after therapy, The mean LCD decreased from 187 +/- 33 to 34 +/- 17.7, Ki67+ Lcn mean percentage d ecreased from 16.9 +/- 3.9 to 4.9 +/- 2.4, and the AI mean value incre ased from 0.05 +/- 0.03 to 2.41 +/- 1.54. Our results suggest a role f or apoptosis in the improvement of the skin lesions and are in line wi th some reports on the mode of action of ExP. Although the way in whic h ExP works needs to be clarified further, it does seem to stimulate a CD8+ cell-mediated anticlonotypic activity against circulating pathog enic clones. Furthermore, a release of tumour necrosis factor alpha (T NF-alpha) by circulating monocytes has been demonstrated after ExP, Bo th are known to induce cell death by apoptosis.