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Featured researches published by Katherine G. Evans.


Archives of Dermatology | 2010

Increased Programmed Death-1 Expression on CD4+ T Cells in Cutaneous T-Cell Lymphoma: Implications for Immune Suppression

Sara Samimi; Bernice M. Benoit; Katherine G. Evans; E. John Wherry; Louise C. Showe; Maria Wysocka; Alain H. Rook

OBJECTIVES To investigate the expression profile of programmed death-1 (PD-1) on T cells derived from patients with cutaneous T-cell lymphoma (CTCL), analyze a potential mechanism responsible for upregulation of PD-1, and assess the correlation between blockade of its signaling pathway and improvement in immunological function. DESIGN Translation research study. SETTING University medical center. PARTICIPANTS Patients with Sézary syndrome, patients with mycosis fungoides, and healthy volunteers. MAIN OUTCOME MEASURES Programmed death-1 expression on T cells by flow cytometry and interferon γ (IFN-γ) production by enzyme-linked immunosorbent assay. RESULTS We report significantly increased PD-1 expression on CD4(+) T cells from patients with Sézary syndrome compared with CD4(+) T cells from patients with mycosis fungoides and healthy volunteers. Both CD26(-) and CD26(+) populations of CD4(+) T cells demonstrated increased expression of PD-1, which was upregulated by the engagement of the T-cell receptor with anti-CD3/CD28 antibodies. In addition, blockade of the signaling pathway with blocking antibodies to PD-1 or its ligand PD-L1 led to an increase in the capacity to produce IFN-γ among some patients. Finally, longitudinal studies of 1 patient revealed a progressive decrease in PD-1 expression on CD4(+) T cells with improvement of clinical disease. CONCLUSION Our data imply that increased PD-1 expression in Sézary syndrome may play a role in attenuating the immune response and provide further insight into the immunosuppressive nature of CD4(+) T cells in Sézary syndrome and suggest another potential means of targeted therapy for these patients.


Current Opinion in Oncology | 2009

Update on treatment of cutaneous T-cell lymphoma

Jennifer M. Gardner; Katherine G. Evans; Amy Musiek; Alain H. Rook; Ellen J. Kim

Purpose of review Cutaneous T-cell lymphomas (CTCLs) are a heterogenous group of non-Hodgkins lymphomas characterized by atypical, skin-homing T lymphocytes and have varying prognoses depending on subtype and disease stage. Numerous therapeutic options exist; however, many patients experience refractory disease and novel treatments are needed. Recent findings This review will highlight selected advances in CTCL treatment over the past year (2007–2008). Discoveries regarding the pathophysiology of mycosis fungoides and Sézary syndrome, the two most common CTCL types, have led to an expansion of new treatments and an increase in experience with multimodality therapy continues to increase. A number of reports have examined both combination regimens of currently available CTCL therapies as well as treatments approved for other dermatologic or oncologic conditions. Also, several novel skin-directed treatments and systemic compounds have been studied in all CTCL stages as well as in treatment-refractory disease. Summary There remains a continued impetus to develop and amass experience with new therapeutic options for CTCL, particularly for patients with advanced stage and treatment-refractory disease.


Archives of Dermatology | 2011

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

Brian A. Raphael; Daniel B. Shin; Karen Rebecca Suchin; Kelly A. Morrissey; Carmela C. Vittorio; Ellen J. Kim; Jennifer M. Gardner; Katherine G. Evans; Camille E. Introcaso; Sara Samimi; Joel M. Gelfand; Alain H. Rook

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.


Archives of Dermatology | 2011

Fox-fordyce disease following axillary laser hair removal

Michael T. Tetzlaff; Katherine G. Evans; Danielle M. DeHoratius; Rochelle R. Weiss; George Cotsarelis; Rosalie Elenitsas

BACKGROUND Fox-Fordyce disease (FFD) is a relatively rare entity with a typical clinical presentation. Numerous studies have described unifying histopathological features of FFD, which together suggest a defect in the follicular infundibulum resulting in follicular dilation with keratin plugging, subsequent apocrine duct obstruction, and apocrine gland dilation, with eventual extravasation of the apocrine secretions as the primary histopathogenic events in the evolution of the disease. OBSERVATIONS We describe a case of FFD that developed in a 41-year-old woman 3 months after completing a series of axillary laser hair removal treatments, and we detail the clinical and histopathological changes typical for FFD. CONCLUSION Because defective infundibular maturation has been suggested to play a central role in the evolution of FFD, the close temporal relationship of laser hair therapy with the development of FFD suggests a causal role, which we continue to explore.


Journal of The American Academy of Dermatology | 2013

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

Rachel S. Klein; James D. Dunlop; Sara Samimi; Kelly A. Morrissey; Katherine G. Evans; Jennifer M. Gardner; Camille E. Introcaso; Carmela C. Vittorio; Alain H. Rook; B Micaily; Ellen J. Kim

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.


Journal of The American Academy of Dermatology | 2011

Validity assessment of the cutaneous T-cell lymphoma severity index to predict prognosis in advanced mycosis fungoides/Sézary syndrome.

Katherine G. Evans; Andrea B. Troxel; Barbara J. DeNardo; Camille E. Introcaso; Alain H. Rook; Ellen J. Kim

BACKGROUND There is a need for standardized quantitative disease assessment measures in mycosis fungoides/Sézary syndrome. In 2005, a cutaneous T-cell lymphoma (CTCL)-severity index (SI) that not only measures disease extent (on a scale of 0-75) independent of the classic TNM(B) staging system but can also be used to estimate individual 5-year survival (SR5) was reported. OBJECTIVE We sought to assess the generalizability of the CTCL-SI/SR5 equation (SR5 equation) to predict prognosis in our cohort of patients with advanced mycosis fungoides/Sézary syndrome (n = 50, photopheresis service, 1984-2001). METHODS TNM(B) staging, CTCL-SI score (based on skin involvement, presence of tumors, lymph node/visceral/blood involvement), and SR5 (SR5 equation = 124 - 2 × [CTCL-SI]%) at initial diagnosis were calculated retrospectively and compared with overall survival by the Kaplan-Meier method. The prognostic significance of TNM(B) staging versus the CTCL-SI was determined by Cox proportional hazards models and Brier scores. RESULTS Patients had stage IIA to IVA disease with a median actuarial overall survival of 58 months. By disease stage, the overall 5-year survival was 70% (stage IIA), 48% (stage IIB-IIIB), and 36% (stage IVA). In our cohort, the CTCL-SI itself was predictive of overall survival (P = .028) but the SR5 equation was not predictive of survival (Brier score of 0.29). LIMITATIONS Small sample size, single academic center population, and retrospective design are limitations. CONCLUSIONS The CTCL-SI is a relatively simple-to-use quantitative tool that measures disease activity in all compartments (skin, nodes, blood, viscera) and has prognostic significance in multivariate analysis. The CTCL-SI may be a useful adjunct to the TNM(B) staging for tracking disease activity quantitatively in all disease compartments (skin, nodes, blood, viscera) in clinical practice and trials, but the predictive ability of the SR5 equation needs further validation at other centers in larger groups of patients.


Archives of Dermatology | 2009

Vorinostat for the treatment of bullous pemphigoid in the setting of advanced, refractory cutaneous T-cell lymphoma

Jennifer M. Gardner; Katherine G. Evans; Steven C. Goldstein; Ellen J. Kim; Carmela C. Vittorio; Alain H. Rook

Histone deacetylase (HDAC) inhibitors represent a novel class of medication that is being targeted for use in the treatment of cancer. A member of this class, vorinostat, has recently been approved for the therapy of cutaneous T-cell lymphoma. Importantly, emerging data from animal studies have indicated that HDAC inhibitors may have the capacity to potently suppress the development of autoimmune disease. In this report, we describe a patient with advanced cutaneous T-cell lymphoma who developed refractory bullous pemphigoid (BP) and then experienced the rapid resolution of the BP following initiation of treatment with vorinostat. This observation may be broadly applicable to the treatment of other autoimmune skin diseases.


Clinical Lymphoma, Myeloma & Leukemia | 2010

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

Alain H. Rook; Bernice M. Benoit; Ellen J. Kim; Carmela C. Vittorio; Aleksandra Anshelevich; Brian A. Raphael; Camille E. Introcaso; Jennifer M. Gardner; Katherine G. Evans; Kelly A. Morrissey; Sara Samimi; Amy Musiek; Louise C. Showe; Mariusz A. Wasik; Maria Wysocka

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


Archives of Dermatology | 2012

Acute Onset of Leg Nodules in a Sporotrichoid Pattern—Quiz Case

Katherine G. Evans; Ronnie M. Abraham; Daniela Mihova; Xiaowei Xu; Dale Frank; Misha Rosenbach; Ellen J. Kim

An 83-year-old man with a history of diabetes and chronic obstructive pulmonary disorder (COPD) (taking prednisone, 5 mg/d) was admitted to our facility with a monthlong history of persistent right arm swelling, erythema, and pain. He had multiple prior admissions for this issue and was treated with oral and intravenous antibiotics for a suspected “cellulitis.” His skin symptoms worsened despite treatment, and he developed an extensive superimposed pustular eruption with sinus tracts involving the entire forearm and a portion of the upper arm (Figure 1). Workup included ultrasonography, which showed no fluid collection, and magnetic resonance imaging, which showed soft-tissue swelling without evidence of any underlying myositis or osteomyelitis. A Tzanck smear failed to show multinucleated giant cells. Punch biopsy specimens for culture and histopathologic analysis were obtained (Figure 2 and Figure 3). What is your diagnosis?


Journal of The American Academy of Dermatology | 2013

Romidepsin and interferon gamma: A novel combination for refractory cutaneous T-cell lymphoma

Sara Samimi; Kelly A. Morrissey; Sasha Anshelevich; Katherine G. Evans; Jennifer M. Gardner; Amy Musiek; Carmela C. Vittorio; Alain H. Rook; Ellen Kim

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Alain H. Rook

University of Pennsylvania

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Ellen J. Kim

University of Pennsylvania

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Sara Samimi

University of Pennsylvania

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Amy Musiek

University of Pennsylvania

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Bernice M. Benoit

University of Pennsylvania

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Brian A. Raphael

University of Pennsylvania

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