Photopheresis is a leukapheresis-based therapy that utilizes 8-methoxypsoralen and ultraviolet A irradiation. Photopheresis is currently available at approximately 150 medical centers worldwide. Recent evidence suggests that this therapy used as a single agent may significantly prolong life, as well as induce a 50%-75% response rate among individuals with advanced cutaneous T cell lymphoma (CTCL). Furthermore, a 20%-25% complete response rate with photopheresis alone, or in combination with other biologic response modifiers, has been obtained at our institution among patients with Sezary syndrome. These complete responses have been characterized by the complete disappearance of morphologically atypical cells from the skin and blood. The use of sensitive molecular techniques has also confirmed the sustained disappearance of the malignant T cell clone from the blood of patients with complete responses. In addition to the treatment of CTCL, numerous reports indicate that photopheresis is a potent agent in the therapy of acute allograft rejection among cardiac, lung, and renal transplant recipients. Chronic graft versus host disease also appears to be quite responsive to photopheresis therapy. Likewise, there may also be a potential role for photopheresis in the therapy of certain autoimmune diseases that are poorly responsive to conventional therapy. The immunologic basis for the responses of patients with these conditions is likely due to the induction of anticlonotypic immunity directed against pathogenic clones of T lymphocytes. Treatment-induced apoptotic death of pathogenic T cells and activation of antigen presenting cells are postulated to have important effects in this therapeutic process.
Progression of cutaneous T-cell lymphoma (CTCL) is associated with profound defects in cell-mediated immunity and depressed production of cytokines, which support cell-mediated immunity. Because we have observed marked defects in interleukin-12 (IL-12) production in CTCL and because IL-12 is critical for antitumor cytotoxic T-cell responses, we initiated a phase I dose escalation trial with recombinant human IL-12 (rhIL-12) where patients received either 50, 100, or 300 ng/kg rhIL-12 twice weekly subcutaneously or intralesionally for up to 24 weeks. Ten patients were entered: 5 with extensive plaque, 3 with Sezary syndrome, and 2 with extensive tumors with large cell transformation. One patient with Sezary syndrome dropped out after 1 week for personal reasons. Subcutaneous dosing resulted in complete responses (CR) in 2 of 5 plaque and partial responses (PR) in 2 of 5 plaque, and 1 of 2 Sezary syndrome (overall response rate CR+PR 5 of 9, 56%). A minor response also occurred in 1 of 5 plaque patients. Intralesional dosing resulted in individual tumor regression in 2 of 2 patients. Biopsy of regressing lesions showed a significant decrease in the density of the infiltrate in all cases and complete resolution of the infiltrate among those with clinical lesion resolution. An increase in numbers of CD8-positive and/or TIA-1–positive T cells were observed on immunohistochemical analysis of skin biopsy specimens obtained from regressing skin lesions. Adverse effects of rhIL-12 on this regimen were minor and limited and included low-grade fever and headache. One patient discontinued rhIL-12 at week 6 because of depression. These results suggest that rhIL-12 may augment antitumor cytotoxic T-cell responses and may represent a potent and well-tolerated therapeutic agent for CTCL.
Periodontal tissue destruction and local IL-6 synthesis are associated with elevated serum IL-6 levels in transplant recipients. This may have serious implications in solid-organ transplant deterioration and chronic rejection.
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