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Rachel S Klein,
James D Dunlop,
Sara S Samimi,
Kelly A Morrissey,
Katherine G Evans,
Jennifer M Gardner, Camille E Introcaso,
Carmela C Vittorio,
Alain H Rook,
Bizhan Micaily,
Ellen J Kim
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ABSTRACT: 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 02/2013; · 3.99 Impact Factor
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International journal of dermatology 06/2012; 51(6):713-5. · 1.18 Impact Factor
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Brian A Raphael,
Daniel B Shin,
Karen R Suchin,
Kelly A Morrissey,
Carmela C Vittorio,
Ellen J Kim,
Jennifer M Gardner,
Katherine G Evans, Camille E Introcaso,
Sara S Samimi,
Joel M Gelfand,
Alain H Rook
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ABSTRACT: 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.
Retrospective cohort study.
Cutaneous T-cell lymphoma clinic at The Hospital at the University of Pennsylvania.
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.
Overall response to treatment was the main measurement of outcome.
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.
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 08/2011; 147(12):1410-5. · 4.76 Impact Factor
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Journal of the American Academy of Dermatology 05/2011; 64(5):986-7. · 3.99 Impact Factor
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ABSTRACT: 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.
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).
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.
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).
Small sample size, single academic center population, and retrospective design are limitations.
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.
Journal of the American Academy of Dermatology 02/2011; 64(4):682-9. · 3.99 Impact Factor
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Keith W Hamilton,
Peter L Abt,
Misha A Rosenbach,
Melissa B Bleicher,
Marc S Levine,
Jimish Mehta,
Susan P Montgomery,
Richard D Hasz,
Bartholomew R Bono,
Michael T Tetzlaff,
Shirly Mildiner-Early, Camille E Introcaso,
Emily A Blumberg
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ABSTRACT: Donor-derived Strongyloides stercoralis infection occurs rarely after transplantation, and the risk factors are not well understood. We present cases of two renal allograft recipients who developed Strongyloides hyperinfection syndrome after receipt of organs from a common deceased donor who received high-dose steroids as part of a preconditioning regimen.
The two renal transplant patients who developed Strongyloides hyperinfection syndrome are reported in case study format with review of the literature.
Microscopic examination of stool from one renal transplant patient and of tracheal and gastric aspirates from the other transplant patient revealed evidence of S. stercoralis larvae. Retrospective testing of serum from the deceased donor for Strongyloides antibodies by enzyme-linked immunosorbent assay was positive at 11.7 U/mL (Centers for Disease Control reference >1.7 U/mL positive). One patient was treated successfully with oral ivermectin. The other patient also had complete resolution of strongyloidiasis, but required a course of parenteral ivermectin because of malabsorption from severe gastrointestinal strongyloidiasis.
These case studies provide some of the best evidence of transmission of S. stercoralis by renal transplantation. Because of the high risk of hyperinfection syndrome and its associated morbidity and mortality, high-risk donors and recipients should be screened for Strongyloides infection, so that appropriate treatment can be initiated before the development of disease. This study indicates that parenteral ivermectin can be used safely and effectively in patients in whom severe malabsorption would preclude the effective use of oral formulation. These cases also suggest that reconsideration should be given for the safety of steroids in donor-preconditioning regimens.
Transplantation 02/2011; 91(9):1019-24. · 4.00 Impact Factor
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ABSTRACT: In 2008, the American Academy of Dermatology began sponsoring North American dermatology residents to travel to Botswana in sub-Saharan Africa and spend 4 to 6 weeks working with the Botswana-UPenn Partnership, the Baylor International Pediatrics AIDS Initiative, Princess Marina Hospital, and surrounding smaller district hospitals. During their time in Botswana, the residents staff the busy outpatient dermatology clinic and see adult and pediatric inpatients at Princess Marina Hospital in Gaborone, the capital city. The residents also travel to 4 rural hospitals to provide clinical services to patient and education to local health care providers. The program goals include providing direct care to the people of Botswana, capacity-building through dermatologic education for local clinicians, and educating the residents about delivering dermatologic care in resource-limited and culturally diverse settings and using teledermatology consulting services. Since the start of the program, more than 1500 patients have been seen, and 35 residents would have completed the program by the end of 2010.
Dermatologic clinics 01/2011; 29(1):63-7. · 1.29 Impact Factor
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ABSTRACT: Cutaneous manifestations of antiretroviral medications for HIV are common and potentially dangerous conditions encountered by dermatologists. Part II of this two-part series on the cutaneous effects of antiretroviral medications for HIV will discuss the four most recent classes of medications that have been developed and immune reconstitution syndrome--an important diagnostic consideration when evaluating a dermatologic patient who is taking antiretroviral medications.
Journal of the American Academy of Dermatology 10/2010; 63(4):563-9; quiz 569-70. · 3.99 Impact Factor
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ABSTRACT: Antiretroviral medications for the treatment of HIV are common drugs with diverse and frequent skin manifestations. Multiple new cutaneous effects have been recognized in the past decade. Dermatologists play an important role in accurately diagnosing and managing the cutaneous toxicities of these medications, thereby ensuring that a patient has as many therapeutic options as possible for life-long viral suppression. Part I of this two-part series on the cutaneous adverse effects of antiretroviral medications will discuss HIV-associated lipodystrophy syndrome, which can be seen as a result of many antiretroviral medications for HIV, and the specific cutaneous effects of the nucleoside reverse transcriptase inhibitors and protease inhibitors.
Journal of the American Academy of Dermatology 10/2010; 63(4):549-61; quiz 561-2. · 3.99 Impact Factor
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Alain H Rook,
Bernice Benoit,
Ellen J Kim,
Carmela C Vittorio,
Aleksandra Anshelevich,
Brian A Raphael, Camille E Introcaso,
Jennifer M Gardner,
Katherine G Evans,
Kelly Morrissey,
Sara Samimi,
Amy C Musiek,
Louise C Showe,
Mariusz A Wasik,
Maria Wysocka
Clinical lymphoma, myeloma & leukemia 09/2010; 10:S93-5.
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Archives of pediatrics & adolescent medicine 07/2010; 164(7):673. · 3.73 Impact Factor
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ABSTRACT: Long-term prognosis for advanced stages of cutaneous T-cell lymphoma may be beneficially altered with the use of multimodality therapy. However, refractory disease exists in which current therapeutic options fail to halt the progression of disease. We present 3 cases of refractory Sézary syndrome in which the combination of vorinostat and interferon gamma was well tolerated and produced significant clinical improvement. The potential immunologic basis for this is discussed.
Journal of the American Academy of Dermatology 08/2009; 61(1):112-6. · 3.99 Impact Factor
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ABSTRACT: Most cutaneous T-cell lymphomas demonstrate a malignant population with a CD4(+) phenotype. In rare cases, CD8(+) phenotypes have been described based on immunostaining of skin specimens. Although some CD8(+) lymphomas have an indolent course, others, such as CD8(+) epidermotropic cytotoxic T-cell lymphomas, are typically more aggressive. To our knowledge, involvement of peripheral blood or cerebrospinal fluid with a malignant population of CD8(+) cells demonstrated by flow cytometry and T-cell receptor gene rearrangement has not been previously described.
We describe a patient with a CD8(+) cutaneous T-cell lymphoma with an initially indolent course and early stage diagnosed on the basis of a skin biopsy specimen. However, when flow cytometry was performed looking specifically at CD8(+)/CD4(-) cells in the peripheral blood and cerebrospinal fluid, a malignant population of CD8(+)/CD4(-)/CD26(-)/CD7(-) cells was discovered.
It is important for prognosis and treatment to be able to identify CD8(+) epidermotropic cytotoxic T-cell lymphoma and separate it from other relatively indolent CD8(+) lymphomas. Furthermore, detection of an abnormal CD8(+)/CD26(-)/CD7(-) T-cell population within the peripheral blood has important prognostic and therapeutic implications. The use of flow cytometry looking for abnormal CD8(+) populations in the peripheral blood or cerebrospinal fluid can assist with this critical information.
Archives of dermatology 09/2008; 144(8):1027-9. · 4.76 Impact Factor
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Journal of the American Academy of Dermatology 08/2008; 59(3):536-7. · 3.99 Impact Factor
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Arthritis & Rheumatism 06/2008; 58(5):1552; author reply 1552-4. · 7.87 Impact Factor
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ABSTRACT: Total skin electron beam radiation is an effective therapy for palliation of the cutaneous symptoms of the most common types of cutaneous T-cell lymphomas, mycosis fungoides and Sézary syndrome. We report 4 cases of patients with Sézary syndrome who had significant improvement in their blood burden of malignant cells in addition to complete cutaneous responses to total skin electron beam therapy. The data from these 4 patients illustrate the potential for total skin electron beam to be used as both a skin and blood tumor debulking agent, and not merely as a palliation for skin symptoms.
Journal of the American Academy of Dermatology 05/2008; 58(4):592-5. · 3.99 Impact Factor
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ABSTRACT: Cutaneous T-cell lymphomas are a type of indolent non-Hodgkin's lymphoma where patients with limited skin disease can be successfully treated with a variety of skin-directed, systemic, and immunomodulating therapies, whereas durable remissions are difficult to achieve in patients with tumor, erythrodermic, or systemic disease. We describe a patient with cutaneous T-cell lymphoma and malignant cells constituting 99% of her peripheral blood lymphocytes who had a sustained complete response after an HLA-matched sibling allogeneic stem cell transplantation. We also review the current literature regarding both autologous and allogeneic stem cell transplantations for advanced stages of cutaneous T-cell lymphoma, discuss the importance of the graft-versus-tumor immunomodulatory effect in successful transplantations, and suggest that allogeneic stem cell transplantation deserves further consideration and study as a potential treatment for selected patients who are younger and at high risk.
Journal of the American Academy of Dermatology 05/2008; 58(4):645-9. · 3.99 Impact Factor
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ABSTRACT: Cutaneous Hodgkin's disease is a rare condition that usually occurs late in the course of Hodgkin's lymphoma. This rare condition is thought to have decreased in incidence in recent decades, likely owing to improved treatment of patients with Hodgkin's disease, who are receiving improved chemotherapy and radiation therapy, and the advent of peripheral blood stem cell transplantation. We present the case of a man who developed specific cutaneous Hodgkin's lymphoma 6 months after nonmyeloablative allogenic stem cell transplantation for his recurrent systemic disease. The patient's manifestation of relapse was cutaneous dissemination of the tumor, manifested by erythematous papules and ulcerated nodules. At the time of the cutaneous relapse he had minimal systemic disease. This case illustrates an example of this complication of Hodgkin's disease and stresses the importance of a timely diagnosis to direct appropriate therapy. A review of the literature demonstrates that the patient's lesion morphology and distribution are typical of specific manifestations of cutaneous Hodgkin's disease.
Journal of the American Academy of Dermatology 03/2008; 58(2):295-8. · 3.99 Impact Factor
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ABSTRACT: •
Cutaneous T-cell lymphomas are a group of extranodal non-Hodgkin’s lymphomas that present initially in the skin.
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The incidence of this condition is approximately 0.52–0.64/100,000 person-years.
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Cutaneous T-cell lymphomas usually present as indolent patches and plaques, but may also present with more aggressive tumors
or erythroderm. The survival is highly dependent on the stage of the disease.
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The diagnosis is made with clinical findings and histology. Staging of this disease is critical, and this may include history
and physical examination, blood tests, peripheral blood flow cytometry, and Sézary cell preparations, and scans for internal
involvement.
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Cell trafficking of malignant T cells into the skin and the epidermis is critical in the pathophysiology of this disease,
and involves chemokines and chemokine receptors.
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The immunology of this condition suggests that T-helper-2 (Th2) lymphocyte cytokine patterns are associated with the malignant
cells, and there is a progressive loss of cellular immunity with advancing disease.
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There are two major categories of treatments for this condition: skin-directed therapies or systemic therapies. Combination
therapies are effective and have immunomodulatory effects.
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Bone marrow transplantation is an emerging therapy for patients with advanced disease that is refractory to skin and systemic
therapy.
12/2007: pages 411-437;
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ABSTRACT: Nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis (NFD/NSF) is a fibrosing cutaneous disorder recently recognized to have systemic manifestations. The disease is characterized clinically by an acute onset of hardening and thickening of the skin of the extremities and trunk, often resulting in flexion contractures, and histologically by an increase in spindle-shaped cells, collagen, and sometimes mucin deposition in the dermis. The only common exposure amongst patients is acute or chronic renal failure. The pathophysiology of the disease remains to be elucidated, and there is currently no consistently effective treatment for this unremitting disease.
We report a case series of nine patients seen at the University of Pennsylvania between 1998 and mid-2004. The clinical, laboratory, and pathologic data of these patients are reviewed.
All patients had renal disease, received peritoneal or hemodialysis, and five had received at least one renal transplant. All patients had characteristic fibrotic cutaneous lesions involving the trunk, extremities, or both, and eight of the nine patients had scleral plaques. There were no other common findings amongst the histories, medications, or laboratory results of the patients.
Our report confirms the clinical and histologic characteristics of NFD that have been described previously, and raises new issues regarding the possible subtypes. A review of the current literature stresses that further basic science and translational studies are necessary to understand the disease mechanism and to propose effective therapy, and emphasizes the importance of recognizing the systemic effects of NFD.
International Journal of Dermatology 06/2007; 46(5):447-52. · 1.14 Impact Factor
