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To determine the efficacy of multimodality biologic response therapy for patients with cutaneous T-cell lymphoma (CTCL).Retrospective cohort study over a 14-year period.Tertiary care university hospital.A consecutive sample of patients was studied, all 47 of whom carried the clinical and laboratory diagnosis of CTCL: 68% of patients had stage III or IV disease, and 89% had circulating malignant T cells.All 47 patients received photopheresis for 6 or more cycles. Thirty-one patients received treatment with a combination of photopheresis and 1 or more systemic immunostimulatory agents, including interferon alfa, interferon gamma, sargramostim, or systemic retinoids for 3 or more months.Differences in pretreatment prognostic factors, response rates, and survival between patients receiving multimodality therapy and single-modality therapy or historical controls.A total of 79% of patients responded to therapy: 26% had complete remission, and 53% had a partial remission. Median survival from initiation of therapy was 74 months. Median survival for patients with stages III and IV and peripheral blood involvement was 55 months compared with 31 months for historical controls. Compared with the photopheresis monotherapy group, the patients receiving combination immunomodulatory therapy had a worse prognosis at the time of treatment initiation based on multiple prognostic factors. The positive response rates and median survival times were 84% and 74 months, respectively, compared with 75% and 66 months, respectively, for the combination immunomodulatory and photopheresis monotherapy groups (P =.47 for positive response rates and P =.51 for survival).Patients with advanced CTCL and multiple poor prognostic factors who receive treatment with combination immunomodulatory therapy experience higher clinical response rates and longer survival than historical controls. Although the group who received combination therapy had worse prognostic factors at baseline, they had better response rates and overall survival compared with those receiving photopheresis monotherapy.

Background: Peripheral eosinophilia occurs in a small subpopulation of patients with cutaneous T-cell lymphoma (CTCL) and denotes a poor prognosis. Clinical studies have suggested that the Sezary cell is a T H 2 type helper T cell that produces cytokines that enhance the differentiation and activation of eosinophils. Interferon alfa (IFN-α) and interleukin 12 are effective therapeutic agents for CTCL and other hematologic disorders. Objective: Our purpose was to determine the inhibitory activity of IFN-α and IL-12 on IL-5 production in vitro by peripheral blood mononuclear cells (PBMCs) obtained from patients with CTCL and eosinophilia. Methods: Suppression of IL-5 production by IFN-α and IL-12 was assessed by comparing IL-5 production by PBMCs from patients with Sezary syndrome and eosinophilia when cultured alone or in the presence of either IFN-α or IL-12. Results: A marked increase in IL-5 production by PBMCs from patients with Sezary syndrome and eosinophilia was observed. IL-5 production was markedly reduced when PBMCs were exposed to IFN-α or IL-12. Conclusion: These results suggest that IFN-α and perhaps IL-12 may produce a therapeutic response in patients with CTCL and eosinophilia through direct suppression of IL-5 production by malignant Sezary cells. (J Am Acad Dermatol 2001;44:28-32.)

Cutaneous T-cell lymphoma (CTCL) is a lymphoproliferative disorder characterized by skin invasion of clonally derived malignant CD4+ lymphocytes that phenotypically resemble mature T-helper (Th) cells. Sezary syndrome (SzS) represents an advanced form of CTCL associated with generalized erythroderma and involvement of the peripheral blood by the malignant cell population. We have previously demonstrated aberrant cytokine production by peripheral blood mononuclear cells (PBMCs) in SzS characterized by increased IL-4 and deficient IL-2 and IFN-gamma production, as well as increased expression of mRNA for IL-4 and IL-5 within active skin lesions, indicating that the clonal T-cell population is likely derived from the T-helper type 2 (Th2) subset of helper T lymphocytes. Furthermore, a variety of immune abnormalities have been observed in association with SzS that have been attributed to the cytokine abnormalities. Because IL-12 is a potent inducer of IFN-gamma production and causes the activation of cytotoxic lymphocytes, we assessed the production of IL-12 by PBMCs from SzS patients, and whether IL-12 could alter the unfavorable cytokine balance typical of SzS and, thus, possibly lead to correction of immune defects. In this review, we present our data, which indicate that patients with SzS exhibit marked defects in monocyte production of IL-12 p70. Moreover, in vitro culture of PBMC from SzS patients with recombinant IL-12 leads to reconstitution of normal IFN-gamma production and markedly enhances cell-mediated cytotoxicity.