Kelly A. Morrissey

High Clinical Response Rate of S ézary Syndrome to Immunomodulatory Therapies: Prognostic Markers of Response

OBJECTIVES To quantify response rates of Sézary syndrome (SS) to multimodality immunomodulatory therapy and to identify the important prognostic parameters that affect overall response to treatment. DESIGN Retrospective cohort study. SETTING Cutaneous T-cell lymphoma clinic at The Hospital at the University of Pennsylvania. PARTICIPANTS Ninety-eight patients who met the revised International Society for Cutaneous Lymphomas (ISCL) and the European Organization of Research and Treatment of Cancer (EORTC) criteria for the diagnosis of SS and were seen over a 25-year period at the University of Pennsylvania. Intervention Patients were treated with at least 3 months of extracorporeal photopheresis and 1 or more systemic immunostimulatory agents. MAIN OUTCOME MEASURES Overall response to treatment was the main measurement of outcome. RESULTS A total of 73 patients had significant improvement with multimodality therapy: 30% had complete response, with clearing of all disease (n = 29), and 45% had partial response (n = 44). At baseline, the complete response group had a lower CD4/CD8 ratio than the nonresponse group (13.2 vs 44.2) (P = .04) and a lower median percentage of CD4(+)/CD26(-) cells (27.4% vs 57.2%) (P = .01) and CD4(+)/CD7(-) cells (20.0% vs 41.3%) (P < .01). Median monocyte percentage at baseline was higher for patients who had a complete response than for nonresponders (9.5% vs 7.3%) (P = .02). The partial response group did not have any statistically significant variables compared with the nonresponse group. CONCLUSIONS In this large cohort study of patients with SS, a high clinical response rate was achieved using multiple immunomodulatory therapies. A lower CD4/CD8 ratio, a higher percentage of monocytes, and lower numbers of circulating abnormal T cells at baseline were the strongest predictive factors for complete response compared with nonresponse and warrant further examination in a larger cohort.

Allogeneic hematopoietic SCT for primary cutaneous T cell lymphomas

Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of non-Hodgkin lymphomas that are considered incurable. The role of allogeneic hematopoietic SCT (HSCT) in the treatment of CTCL is not well defined but may provide potent graft-vs-lymphoma (GVL) activity independent of the conditioning therapy. We present outcomes of 12 extensively-pretreated patients with CTCL who underwent allogeneic HSCT using, most commonly, a reduced intensity conditioning regimen. Median age at diagnosis of CTCL was 49 years, and median time to transplantation from diagnosis was 3.3 years. Transplantation induced and maintained CR in six patients with active disease, supporting the presence of a GVL effect. TRM was low, and 42% of patients were alive and disease-free a median duration of 22 months after transplant. Two patients showed strong and direct evidence of a GVL-effect with a direct response to withdrawal of immunosuppression or to donor leukocyte infusion. Our data show that HSCT can provide long-term disease control in patients with advanced CTCL, which otherwise was refractory to immunotherapy and chemotherapy.

Improvement in peripheral blood disease burden in patients with Sézary syndrome and leukemic mycosis fungoides after total skin electron beam therapy

BACKGROUND There is a paucity of effective therapies for patients with Sézary syndrome and advanced mycosis fungoides with peripheral blood involvement. Total skin electron beam (TSEB) radiation therapy is an extremely effective skin-directed therapy for these patients, but, until recently, it was thought not to signifcantly affect the peripheral blood malignant T-cell population. OBJECTIVE We conducted this study to determine if TSEB has therapeutic effect on the peripheral blood in patients with advanced mycosis fungoides and Sézary syndrome. METHODS All patients on stable medication regimens seen in our photopheresis facility who received TSEB therapy between January 2008 and October 2011 at Temple University Hospital, Philadelphia, PA, were analyzed retrospectively for improvement in the peripheral blood, as documented by flow cytometry. RESULTS Six of 11 patients achieved 50% or greater decrease in their peripheral blood malignant T-cell population after TSEB therapy, for an overall response rate of 55%. Within the group of patients who had a response in the skin, 67% also had a response in the peripheral blood. LIMITATIONS This analysis is limited in 3 ways. First, the sample described is small. Second, the results may be confounded by the fact that each patient was on other systemic therapies in addition to TSEB, albeit stable pre-existing regimens. The time interval between completion of TSEB therapy and repetition of flow cytometry was not standardized among patients, which may result in an underestimation of the overall response to TSEB therapy. CONCLUSION In patients with advanced mycosis fungoides and Sézary syndrome, the peripheral blood tumor burden may improve after treatment with TSEB.

Inhibition of cell-mediated immunity by the histone deacetylase inhibitor vorinostat: Implications for therapy of cutaneous T-cell lymphoma†

Several histone deacetylase inhibitors (HDACi), including vorinostat, have been approved for the therapy of cutaneous T-cell lymphoma (CTCL). Emerging data suggest that HDACi may exert immune suppressive effects which would be disadvantageous for therapy of CTCL. We describe a patient with Sezary syndrome who was monitored for drug-induced immunosuppression while undergoing treatment with vorinostat. Analysis of the patients natural killer cell function before and after initiation of treatment confirmed inhibition of this important cell-mediated immune function. In addition, the in vitro effects of vorinostat on the immunity of healthy volunteers confirmed that this class of drug can profoundly suppress multiple arms of the cellular immune response. These findings raise concerns of increased susceptibility to infection in this high-risk population.

Histopathology of the red lunula: new histologic features and clinical correlations of a rare type of erythronychia.

The lunula is the semi‐lunar shaped area seen at the proximal aspect of the nail unit. It is the most distal aspect of the nail matrix that can be visualized through the transparent nail plate. The term red lunula describes erythema that partially or completely replaces the normal white color of the lunula. Red lunulae have been associated with a number of dermatologic and systemic conditions. However, the etiology and histopathology of the red lunula have not been characterized. We report a case of red lunulae of the fingernails in an adult male. Histopathologic examination revealed an increased density of benign‐appearing and mildly dilated vascular channels present in the superficial papillary dermis of the nail matrix. To our knowledge, this is the first report of distinct pathologic findings seen on histologic examination of a red lunula. The increased vascularity of the lunula seen microscopically correlates with the clinically observed red color. These findings raise the possibility that systemic or local factors are responsible for angiogenesis within the nail unit in disorders associated with the red lunula.

Immune modulators as therapeutic agents for cutaneous T-cell lymphoma.

In choosing the ideal immune modulator, a number of factors should be considered. First, the agent should have the capacity to induce a robust antitumor immune response. The treatment should also directly produce high levels of apoptosis of the tumor cells. Finally, the ability to produce sustained immunologic memory against the tumor cells is of critical importance in an effort to produce prolonged clinical responses. A number of cytokines that are products of cells of the innate immune system, including interferon (IFN)-α, IFN-γ, and IL-12, meet at least 2 of the above criteria with IFN-α meeting all 3. IFN-α has been shown to produce high clinical response rates in

Psoralen plus ultraviolet A light may be associated with clearing of peripheral blood disease in advanced cutaneous T-cell lymphoma

This analysis found associations of tenderness, change in size, and, potentially, bleeding with type of lesion (SCC as compared with AK). Association of these symptoms with malignancy is not surprising as tumor growth may affect cutaneous nerves. Although symptoms may be an important clinical clue when evaluating a suspicious lesion, histopathologic evaluation remains the definitive method of distinguishing precancerous and malignant neoplasms.