title: Extracorporeal photochemotherapy induces apoptosis of infiltrating lymphoid cells in patients with mycosis fungoides in early stages. A quantitative histological study.
abstract: 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 Sézary syndrome. Improvements have also been seen in patients with non-erythrodermic mycosis fungoides (MF) in the early stages, even when tumour cells are not detectable in the peripheral blood. In this study, we used ExP as a monotherapy in seven patients who had early stage (Ib) MF, and who were no longer responsive to or had contraindications for other therapies. We observed a clinical improvement in the disease after 12 months of treatment: one patient showed a complete response, five a partial response, and one remained stable. In each patient we compared skin biopsies of large plaque lesions before and after the treatment. We undertook a histological evaluation of the infiltrate. The lymphoid cell proliferation and death rates were quantified using the following parameters; lymphoid cell density (LCD), Ki67 + lymphoid cell nuclei percentage (Ki67 + Lcn percentage), and apoptotic index (AI). Significant decreases 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 decreased from 16.9 +/- 3.9 to 4.9 +/- 2.4, and the AI mean value increased from 0.05 +/- 0.03 to 2.41 +/- 1.54. Our results suggest a role for apoptosis in the improvement of the skin lesions and are in line with some reports on the mode of action of ExP. Although the way in which ExP works needs to be clarified further, it does seem to stimulate a CD8+ cell-mediated anticlonotypic activity against circulating pathogenic clones. Furthermore, a release of tumour necrosis factor alpha (TNF-alpha) by circulating monocytes has been demonstrated after ExP. Both are known to induce cell death by apoptosis.
authors.affiliation: Institute of Pathology, University of Siena, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Miracco
authors.forename: P
authors.initials: P
authors.lastname: Rubegni
authors.forename: G
authors.initials: G
authors.lastname: De Aloe
authors.forename: G
authors.initials: G
authors.lastname: D'Ascenzo
authors.forename: C
authors.initials: C
authors.lastname: Mazzatenta
authors.forename: M M
authors.initials: MM
authors.lastname: De Santi
authors.forename: M
authors.initials: M
authors.lastname: Fimiani
mesh_terms: D000368:Aged; D017209:Apoptosis; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000188:drug therapy* / Q000473:pathology; D017893:Photopheresis; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome