Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of CTCL

  • erythrodermic ctcl

  • Terms modified by CTCL

  • ctcl patient

  • Selected Abstracts

    Photodynamic Therapy of Cutaneous Lymphoma Using 5-Aminolevulinic Acid Topical Application

    Arie Orenstein MD
    Background. Photodynamic therapy (PDT) with topical application of 5-aminolevulinic acid (ALA) is a new and effective modality for treatment of superficial basal and squamous cell carcinomas. Objective. We present the kinetics of ALA-induced protoporphyrin IX (PP) accumulation and the results of ALA PDT treatment on two patients with different stages (stage I and stage III) of mycosis fungoides (MF)-type cutaneous T-cell lymphoma (CTCL). Methods. ALA-Decoderm cream was applied to the lesions for 16 hours. Spectrofluorescence measurements of PP accumulation were carried out before, during, and 1 hour after photoirradiation (580,720 nm) using the VersaLight system. Results. Different patterns of PP fluorescence kinetics were observed in patients with early and advanced stages of the disease. During photoirradiation the intensity of fluorescence decreased depending on the lesion thickness. One hour after the photoirradiation procedure no PP fluorescence was observed in the stage I MF lesion, while in the thick stage III MF lesions, PP fluorescence reappeared; after an additional 10,15 minutes of irradiation PP fluorescence disappeared. Complete response with excellent cosmetic results was observed in the stage I lesion after a single irradiation with a light dose of 170 J/cm2; in five stage III lesions, complete response was achieved after fractionated irradiation with a total light dose of 380 J/cm2 (follow-up at 27 and 24 months, respectively). Conclusion. The results showed a high response of both stage I and stage III MF lesions to ALA PDT. This modality appears to be very effective and can be used successfully for MF treatment. [source]

    Controversies in the management of the cutaneous T cell lymphomas

    John A. Zic
    ABSTRACT The primary cutaneous T cell lymphomas (CTCL) encompass all malignancies of the T cell where the skin is the primary organ of involvement. The diagnosis of a CTCL variant can be detoured by a number of obstacles including the slow evolution of the disease into a classic clinical and pathologic pattern. A realistic goal of early stage treatment is to reduce the likelihood of progression to a more advanced stage, not to achieve a cure. No studies have adequately compared the different systemic agents in patients with advanced CTCL so the clinician is left to act in the best interest of the patient with what evidence is available. When using the systemic agents, a "start low and go slow" strategy may offer patients several advantages. Dermatologists are uniquely trained to diagnose and to manage all but the most advanced stage patients with CTCL. [source]

    Treatment of cutaneous T-cell lymphoma with retinoids

    Chunlei Zhang
    ABSTRACT:, Retinoids are biologic regulators of differentiation, proliferation, apoptosis, and immune response. Retinoids (all- trans retinoic acid, 13- cis -retinoic acid, and the synthetic analogs isotretinoin, etretinate, and acitretin) have been used for years as monotherapy and/or in combination for treatment of cutaneous T-cell lymphomas (CTCL). Orally administered bexarotene, the first synthetic highly selective retinoid X receptor retinoid to be approved by the Food and Drug Administration for CTCL, was shown to be active against the cutaneous manifestations of all stages of CTCL. The topical gel formulation was also effective for early cutaneous manifestations of CTCL or as an adjunct to systemic or phototherapy. Use of retinoids in future long-term clinical trials and their eventual application in CTCL regiments will require strategies to decrease the side effects of existing retinoids, identify novel receptor subtype-selective retinoids with better therapeutic index, and explore biologically based synergistic combination therapies with other active agents. [source]

    Treatment planning in cutaneous T-Cell lymphoma

    Eric C. Vonderheid
    ABSTRACT:, Effective long-term management of cutaneous T-cell lymphoma (CTCL) requires administration of skin-directed therapies such as topically applied nitrogen mustard or photochemotherapy to achieve a complete response in clinically early disease (patch and thin-plaque-phase mycosis fungoides, MF) and often the concomitant administration of well-tolerated drugs with systemic effects such as interferon alfa, bexarotene, methotrexate or extracorporeal photopheresis in more advanced, but not highly aggressive/nontransformed disease (thick plaque or tumor phase MF or erythrodermic CTCL). The author's approach is provided as a guide for dermatologists in private practice. [source]

    About the cutaneous targets of bexarotene in CTCL patients

    Anne Chantal Knol
    Please cite this paper as: About the cutaneous targets of bexarotene in CTCL patients. Experimental Dermatology 2010; 19: e299,e301. Abstract:, There are several approved therapies for cutaneous T-cell lymphoma (CTCL). The retinoids are one of the major biologic response modifiers used in CTCL, producing good response rates but few complete responses. Bexarotene has been demonstrated to act on malignant T-cells by inducing their apoptosis, but nothing is known about its role on keratinocytes and Langerhans cells. Immunohistochemical analysis using CD1a, HLA-DR, ICAM-1 (activation markers), CD95 and CD40 (apoptosis markers) was conducted on frozen sections of bexarotene-exposed cutaneous explants and skin biopsy specimens from patients treated with bexarotene. None of the studied markers was significantly modulated both on cutaneous explants and on skin biopsy specimens after treatment with bexarotene, compared to controls. Langerhans cells and keratinocytes do not appear to play a central role in the therapeutic control of CTCL by bexarotene therapy. The main bexarotene's target thus remains T-cells by inducing their apoptosis, a mechanism that is different from the other retinoids used in CTCL. [source]

    Multilineage progression of genetically unstable tumor subclones in cutaneous T-cell lymphoma

    Albert Rübben
    Abstract:, Molecular analysis of solid malignant tumors has suggested multilineage progression of genetically unstable subclones during early stages of tumorigenesis as a common mechanism of tumor cell evolution. We have investigated whether multilineage progression is a feature of cutaneous T-cell lymphoma (CTCL). To identify individual tumor cell subclones, we determined the pattern of mutations within microsatellite DNA obtained from multiple histomorphologically confined tumor cell nests of mycosis fungoides (MF) and lymphomatoid papulosis (LyP) lesions. Tumor cells were isolated by laser microdissection, and allelotypes were determined at microsatellite markers D6S260, D9S162, D9S171, D10S215, TP53.PCR15, and D18S65. Nine cases of MF and one patient with anaplastic large cell lymphoma (ALCL) originating from LyP were analyzed at 277 different microdissected areas obtained from 31 individual lesions. Three specimens of cutaneous lichen planus microdissected at 26 areas served as the control tissue. Microsatellite instability in microdissected tissue [MSI(md-tissue)] was detected in tumor tissues of all CTCL patients. One hundred and fifty-seven of 469 analyzed polymerase chain reaction (PCR) amplifications contained mutated microsatellite alleles (34%). In lichen planus, MSI(md-tissue) was seen in only four of 76 PCR products (5%) (P < 0.0001). The distribution of allelotypes in tumor cells from different disease stages was consistent with multilineage progression in five MF cases, as well as in the LyP/ALCL patient. Our results suggest that CTCL may evolve by multilineage progression and that tumor subclones in MF can be detected in early disease stages by mutation analysis of microsatellite DNA obtained from multiple microdissected areas. [source]

    IL-15 and IL-16 overexpression in cutaneous T-cell lymphomas: stage-dependent increase in mycosis fungoides progression

    K. Asadullah
    Abstract: Cytokines are of major importance for the pathogenesis of cutaneous T-cell lymphomas (CTCL). Recent data suggested that IL-15 and IL-16 are survival/growth factors for the malignant T cells in these entities. To investigate the expression of IL-15 and IL-16 in mycosis fungoides (MF) and CD30+ pleomorphic T-cell lymphoma in vivo, we established a competitive RT-PCR technique. Analyzing skin biopsies from CTCL patients at different stages in comparison to psoriatic and healthy skin, we found IL-15 and IL-16 mRNA overexpression in both CTCL entities. Remarkably, there was some evidence for a stage-dependent increase during MF progression. We found only slight overexpression in early stage MF, when only few tumor cells are detectable within the infiltrates, whereas marked overexpression was found in more advanced lesions, which are characterized by a higher density of malignant cells. These results suggested that CTCL cells themselves might produce the cytokines. To further elucidate this hypothesis, two CTCL cell lines were analyzed but gave conflicting results. Therefore, the cellular origin of the IL-15 and IL-16 overexpression in CTCL remains unclear. Considering the significant overexpression of IL-15 and IL-16 and their biological capacities it is likely that these cytokines contribute to the tumor development. So, they might be involved in growth and skin homing of CTCL cells. [source]

    Cutaneous T-cell lymphoma-associated lung cancers show chromosomal aberrations differing from primary lung cancer

    Sonja Hahtola
    Cutaneous T-cell lymphoma (CTCL) patients have an increased risk of certain secondary cancers, the most common of which are lung cancers, especially small cell lung cancer. To reveal the molecular pathogenesis underlying CTCL-associated lung cancer, we analyzed genomic aberrations in CTCL-associated and reference lung cancer samples. DNA derived from microdissected lung cancer cells of five CTCL-associated lung cancers and five reference lung cancers without CTCL association was analyzed by comparative genomic hybridization (CGH). Fluorescent in situ hybridization (FISH), immunohistochemistry (IHC), and loss of heterozygosity (LOH) analysis were performed for selected genes. In CTCL-associated lung cancer, CGH revealed chromosomal aberrations characterizing both lung cancer and CTCL, but also losses of 1p, and 19, and gains of 4q and 7, hallmarks of CTCL. LOH for the CTCL-associated NAV3 gene was detected in two of the four informative primary lung cancers. FISH revealed increased copy number of the KIT gene in 3/4 of CTCL-associated lung cancers and 1/5 of primary lung cancers. PDGFRA and VEGFR2 copy numbers were also increased. IHC showed moderate KIT expression when the gene copy number was increased. CTCL-associated lung cancer shows chromosomal aberrations different from primary lung cancer, especially amplifications of 4q, a chromosome arm frequently deleted in the latter tumor type. Copy numbers and expression of selected genes in chromosome 4 differed between CTCL-associated and reference lung cancers. These preliminary observations warrant further prospective studies to identify the common underlying factors between CTCL and CTCL-associated lung cancer. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat. © 2007 Wiley-Liss, Inc. [source]

    Prognostic significance of the therapeutic targets histone deacetylase 1, 2, 6 and acetylated histone H4 in cutaneous T-cell lymphoma

    HISTOPATHOLOGY, Issue 3 2008
    L Marquard
    Aims:, Aberrant histone acetylation has been associated with malignancy and histone deacetylase (HDAC) inhibitors are currently being investigated in numerous clinical trials. So far, the malignancy most sensitive to HDAC inhibitors has been cutaneous T-cell lymphoma (CTCL). The reason for this sensitivity is unclear and studies on HDAC expression and histone acetylation in CTCL are lacking. The aim of this study was to address this issue. Methods and results:, The immunohistochemical expression of HDAC1, HDAC2, HDAC6, and acetylated H4 was examined in 73 CTCLs and the results related to histological subtypes and overall survival. HDAC1 was most abundantly expressed (P < 0.0001), followed by HDAC2; HDAC6 and H4 acetylation were equally expressed. HDAC2 (P = 0.001) and H4 acetylation (P = 0.03) were significantly more common in aggressive than indolent CTCL subtypes. In contrast, no differences were observed for HDAC1 and HDAC6. In a Cox analysis, elevated HDAC6 was the only parameter showing significant influence on survival (P = 0.04). Conclusions:, High expression of HDAC2 and acetylated H4 is more common in aggressive than indolent CTCL. HDAC6 expression is associated with a favorable outcome independent of the subtype. [source]

    Extracutaneous transformation into a high-grade lymphoma: a potential pitfall in the management of patients with Sézary syndrome

    Sonja Michaelis MD
    Background, Transformation into a high-grade lymphoma in cutaneous T-cell lymphoma (CTCL) occurs in approximately 25% of cases and is associated with an aggressive clinical course. Methods, We identified four cases of transformation of Sézary syndrome (SS) into pleomorphic T-cell lymphoma. Results, In all patients, transformation occurred first in the lymph nodes, an average of 43 months after the diagnosis of SS. These high-grade lymphomas were composed of CD30-positive (two patients) and CD30-negative (two patients) pleomorphic large cells. All patients died of lymphoma an average of 29 months after nodal transformation. Conclusion, Because of an apparently poorer prognosis, the early recognition of transformation, especially by lymph node biopsy, is important for adequate therapy. [source]

    Mycosis fungoides associated with malignant melanoma and dysplastic nevus syndrome

    J. A. Pielop MD
    Background The increased risk of second malignancies, including nonmelanoma skin cancers, in cutaneous T-cell lymphoma (CTCL) patients has been well documented. However, relatively few studies of malignant melanoma in CTCL patients have been reported. Methods A database of 250 CTCL patients registered over a 3-year period was searched to identify patients with diagnoses of both mycosis fungoides (MF) and malignant melanoma. Results We identified six cases of MF associated with malignant melanoma and one associated with dysplastic nevus syndrome, which is a marker of increased risk of melanoma. In four patients, melanoma was diagnosed along with or before MF. In the remaining two patients, MF was diagnosed prior to melanoma, although dysplastic nevi were noted at the time MF was diagnosed. These two patients received treatment for their MF (one with topical nitrogen mustard and another with radiation therapy and nitrogen mustard) prior to the histologic confirmation of melanoma. Six patients had early stages of MF (IA or IB), while one patient presented with simultaneous erythrodermic mycosis fungoides involving the lymph nodes as well as melanoma metastatic to the lymph nodes from an unknown primary. Conclusion There is an elevated prevalence of malignant melanoma in MF patients compared to the general US population (P < 0.00001) with a relative risk of 15.3 for observing malignant melanoma in MF patients (95% confidence interval 7.0,33.8). Possible pathologic links between the two diagnoses include effects of mycosis fungoides therapies, immunosuppression secondary to mycosis fungoides, and genetic alterations in the p16 tumor suppressor protein. [source]

    Vakzinationstherapie kutaner T-Zell-Lymphome

    Vaccination therapy for cutaneous T-cell lymphoma
    primary cutaneous T cell lymphomas (CTCL); vaccination; antigenic targets Zusammenfassung: Primär kutane T-Zell-Lymphome (CTCL) sind definiert als klonale Proliferation hautinfiltrierender T-Lymphozyten. Unabhängig von der Heterogenität dieser Krankheitsgruppe besteht derzeit keine kurative Therapiemöglichkeit, was zur Entwicklung verschiedener Behandlungsstrategien, einschließlich der Vakzination, führte. Dieser Artikel gibt eine Übersicht über den Entwicklungsstand der Vakzinationstherapie für Lymphome mit besonderer Rücksicht auf die CTCL. Da bisher kein universelles Tumorantigen identifiziert wurde, sind verschiedenste antigene Agenzien (komplette Tumorzellen, Idiotypen, Cancer/Testis-Antigene, Proteine aus tumorassoziierten Mutationen und Mimotope) hinsichtlich ihrer Eignung für die Vakzinationstherapie von CTCL untersucht worden. Die antigene Information dieser Präparationen kann dem körpereigenen Immunsystem über verschiedene Wege (Carrier) dargeboten werden, bisher sind dazu mit Tumorzellen fusionierte dendritische Zellen, Idiotyp-Proteine oder -Peptide sowie DNA- und RNA-Präparationen eingesetzt worden. Da die verwendeten Antigene allesamt schwache Immunogene darstellen, sind Adjuvanzien (dendritische Zellen, immunogene Peptide, Oligonukleotide, Zytokine, virale Vektoren) notwendig, um eine suffiziente Antigenpräsentation und Aktivierung des Immunsystems zu erreichen. Erste klinische Daten bestätigen die prinzipielle Wirksamkeit einer Vakzinationstherapie bei CTCL. Die große Anzahl bisher verwendeter Antigene, Carrier, Adjuvanzien und Applikationsschemen macht die Identifizierung eines optimalen Protokolls jedoch nahezu unmöglich. Da auch die Wechselwirkungen zwischen Lymphom und Immunsystem sehr komplex und nicht vollständig verstanden sind, ist bis zur Einführung der Vakzinationstherapie in die klinische Praxis noch großer Forschungsaufwand nötig. Summary: Primary cutaneous T,cell lymphomas (CTCL) are defined as clonal proliferation of skin-infiltrating T lymphocytes. Despite their heterogeneity, CTCL are generally incurable, which lead to the development of various treatment strategies including vaccination. Here, the attempts to vaccinate against lymphoma will be reviewed with special emphasis on CTCL. Since an universal tumour antigen is not available so far, different targets, including whole tumour cells, idiotypes, cancer/testis antigens, proteins derived from tumour-associated mutations, and mimotopes, have been investigated for their applicability in CTCL vaccination. The antigenic information can be delivered in different ways. So far, tumour cells fused to dendritic cells, idiotypic proteins/peptides and DNA/RNA preparations have been applied in lymphoma. Since most targets are weak immunogens, adjuvants and other helpers, including dendritic cells, immunogenic peptides and oligonucleotides, cytokines, and viral vectors, are required to enable proper presentation of the antigens and sufficient activation of the immune system. Although first data from CTCL patients prove the suitability of vaccination in CTCL therapy, the number of available antigens, carriers, adjuvants and application schemes creates a multitude of vaccine formulations and identification of the best-suited approach difficult. Furthermore, the relationship between lymphoma and the host immune system is complex and still not completely understood. In consequence, CTCL vaccination requires a lot of research to be done before its breakthrough. [source]

    Extracorporeal photopheresis reduces the number of mononuclear cells that produce pro-inflammatory cytokines, when tested ex-vivo

    John Bladon
    Abstract Extracorporeal photopheresis (ECP) has been shown to be clinically effective in the treatment of many T cell,mediated conditions. ECP's mechanism of action includes the induction of apoptosis and the release of pro-inflammatory cytokines. Recently, we have observed early lymphoid apoptosis, detectable immediately post ECP. We were interested to determine what influence ECP has on pro-inflammatory cytokine secretion at this early pre-infusion stage. Samples from 6 cutaneous T cell lymphoma (CTCL) and 5 graft versus host disease (GvHD) patients were taken pre ECP and immediately post ECP, prior to re-infusion. Following separation, the PBMCs were added to a cell culture medium and stimulated with PMA, Ionomycin, and Brefeldin A for 6 hours. Using flow cytometry, intracellular cytokine expression of IFN, and TNF, was determined in the T cell population. The monocytes were evaluated for IL6, IFN,, IL12, and TNF,. For both patient groups, the number of IFN,-expressing T cells fell significantly at re-infusion, whilst both T cell- and monocyte-expressing TNF, levels were reduced at re-infusion. All other cytokines tested showed no significant change post ECP. For GvHD, pro-inflammatory cytokines have a pathological role. Their down-regulation may have a direct clinical benefit. However, the reduction in the number of IFN,- and TNF,-expressing mononuclear cells means, at this early stage, it is unlikely that these cytokines assist in the removal of the malignant Th2 cells present in CTCL. J. Clin. Apheresis 17:177,182, 2002. © 2002 Wiley-Liss, Inc. [source]

    Lymphomatoid papulosis with CD1a+ dendritic cell hyperplasia, mimicking Langerhans cell histiocytosis

    Chris H. Jokinen
    Although CD1a+ dendritic cells (DC) in cutaneous T-cell lymphomas (CTCL) have been well documented, the presence of large numbers of DC within lymphoid infiltrates can pose a diagnostic difficulty. We present a case of a 70-year-old man with a 3-year history of recurrent red papules and plaques on the extremities and trunk that was referred to our institution, with the diagnosis of Langerhans cell histiocytosis. Skin biopsies showed a wedge-shaped cellular infiltrate in the superficial and deep dermis consisting of two cell populations. Most prominent were clusters of epithelioid cells with grooved nuclei and abundant eosinophilic cytoplasm, which stained with antibodies to CD1a and S-100. A second, less prominent population of atypical lymphocytes, some with enlarged, hyperchromatic and convoluted nuclei, were intermixed. The latter were positive for CD30, CD3 and CD5 and negative for CD20, CD34, CD68, ALK-1 and TdT. T-cell receptor gene rearrangement studies confirmed a clonal T-cell population, which with the clinical history was consistent with the diagnosis of lymphomatoid papulosis. While previous studies have shown an increased density of dermal DC in CTCL, we believe that this represents the first report of an unusually florid DC proliferation mimicking Langerhans cell histiocytosis and masking a lymphoproliferative disorder. [source]

    Extracorporeal photochemotherapy in patients with cutaneous T-cell lymphoma: is clinical response predictable?

    V Rao
    Abstract Background, Extracorporeal photochemotherapy (ECP) has been accepted as a standard therapy in cutaneous T-cell lymphomas (CTCL), a category of lymphomas mainly resistant to conventional therapies. Approximately one half of patients demonstrate a reduction in skin affliction by at least 50% within 12 months of therapy and are categorized as responders to ECP. Predictive criteria for selecting patients who will respond to ECP are lacking. Such criteria would however, be of great benefit. Objectives, This study compared T-cell clonality and serum levels of soluble interleukin-2 receptor (sIL-2R), lactate dehydrogenase (LD), neopterin, beta2-microglobulin (,2 -M) and granzyme B in CTCL patients in order to evaluate their potential usefulness as predictive markers. Patients/methods, Serum and T lymphocytes obtained from 16 patients with CTCL receiving ECP treatment were evaluated in an open retrospective study. Results, We found no evident correlation between detected T-cell clonality and response to ECP. The non-responding group had on average a higher level of serum sIL-2R. This difference was significant after 6 and 12 months of therapy, but not pretreatment. An individual reduction in serum sIL-2R, neopterin and ,2 -M during a 6-month course of ECP was well correlated to clinical remission. Conclusions, Seven out of 16 patients were classified as responders. Neither T-cell clonality nor any of the serum markers assessed pretreatment could reliably predict the response to ECP treatment. However, the individual relative changes in sIL-2R, neopterin and ,2 -M during 6 months of ECP treatment coherently displayed correlation to the clinical response, as assessed after 12 months of ECP treatment. [source]

    Cutaneous T-cell lymphoma

    EA Kotz
    ABSTRACT Cutaneous T-cell lymphoma (CTCL) is a neoplasm of helper T cells whose first manifestations usually appear in the skin. The various forms of CTCL are distinguished by both clinical features and histopathology. Early on, the diagnosis may be difficult to establish because of its numerous, and often non-specific, clinical presentations. Further, the pathological findings of early lesions may lack the diagnostic features observed in well-developed or advanced disease. The diagnosis of CTCL must be considered in any patient with a chronic, therapy-resistant condition of the skin. In patients with non-specific histological findings, a high index of suspicion and multiple biopsies may eventually lead to a diagnosis of CTCL. Once the diagnosis of CTCL is established, accurate staging is essential both for its effect on treatment decisions and for its prognostic value. In general, CTCL is a chronic, slowly progressive disease with a long evolution. The development of tumours is a poor prognostic sign, as is erythroderma. The Sezary syndrome is a distinct form of erythrodermic CTCL that is characterized by exfoliative erythroderma, lymphadenopathy, lymphocytosis, intense pruritus, and circulating large, abnormal lymphocytes (Sezary cells). When death does occur, it is most often due to septicemia. Treatment of CTCL must be tailored to the individual patient. The most commonly employed treatment options are photochemotherapy and topical chemotherapy. [source]

    Examination of mycosis fungoides for the presence of Epstein,Barr virus and human herpesvirus-6 by polymerase chain reaction

    E Erkek
    Abstract Background The aetiology of cutaneous T-cell lymphoma (CTCL) remains unknown despite numerous investigations. In recent years, retroviruses and human herpesviruses have been implicated to play a causal part in CTCL. Objective The aim of this study was to elucidate the possible aetiopathogenetic role of human herpesviruses (HHV) in mycosis fungoides (MF). Methods Polymerase chain reaction was used to study formalin-fixed, paraffin-embedded lesional skin biopsies from 92 subjects with MF to evidence possible presence of Epstein,Barr virus (EBV) and HHV-6. Results Biopsy specimens from nine subjects (9.8%) evidenced EBV DNA, whereas all except one of the subjects (1.1%) lacked HHV-6 DNA. Conclusions Although these findings do not support a primary aetiological role for EBV and HHV-6 in classical CTCL, the possibility remains that both viruses, particularly EBV, may act as potential cofactors in the development of CTCL. [source]

    CD8+ cutaneous T-cell lymphoma successfully treated with bexarotene: A case report and review of the literature,

    Srivalli Gopaluni
    CD8+ cutaneous T-cell lymphoma (CTCL) is a relatively rare subset of the non-Hodgkins lymphomas. Bexarotene has been FDA-approved for the treatment of CTCL, but previous studies have been conducted on CD4+ CTL and there have been no reports about its use in CD8+ CTCL. Herein, we report on a patient whose CD8+ CTCL completely responded to treatment with bexarotene. Am. J. Hematol., 2008. © 2008 Wiley-Liss, Inc. [source]

    Narrow-band ultraviolet B treatment for vitiligo, pruritus, and inflammatory dermatoses

    Sharam Samson Yashar
    Background: Narrow-band ultraviolet B (NB-UVB) therapy has been used successfully for the treatment of inflammatory and pigmentary skin disorders including atopic dermatitis, psoriasis, mycosis fungoides, polymorphous light eruption, and vitiligo. Methods: This is a retrospective review of the treatment outcomes of 117 consecutive patients with vitiligo, pruritus, and other inflammatory dermatoses, excluding those with psoriasis and CTCL, who were treated with NB-UVB between 1998 and 2001 at our institution. Results: Approximately 80% of all patients showed improvement in their condition. NB-UVB phototherapy was well tolerated, with no serious adverse effects. In patients with vitiligo, 6.4% had an abnormal thyroid-stimulating hormone level and 6.5% had anemia. Conclusion: NB-UVB may be considered as a viable therapeutic option in the treatment of vitiligo, pruritus, and other inflammatory dermatoses. Long-term adverse effects and cost,benefit analysis of NB-UVB therapy compared to other treatment modalities remain to be determined. [source]

    Efficacy of ultraviolet A1 phototherapy on the expression of bcl-2 in atopic dermatitis and cutaneous T-cell lymphoma in vivo: a comparison study

    F. Breuckmann
    Background/Purpose: Atopic dermatitis (AD) is characterized immunohistochemically by a high number of skin infiltrating T-helper cells (CD4 + ). In most cases cutaneous T-cell lymphoma (CTCL) is characterized by a malignant proliferation of CD4 + T-helper lymphocytes. The purpose of our study was to evaluate the extent of anti-apoptotic effects in patients suffering from AD or CTCL, respectively, which may contribute to the prolonged inflammation. Furthermore, we investigated whether medium-dose ultraviolet A1 (UVA1) phototherapy is able to modulate the expression of bcl-2 within the dermal inflammatory infiltrate. Methods: In order to enumerate bcl-2+ cells pre- and post-therapeutic punch skin biopsies of ten patients with AD and five patients with CTCL were stained immunohistochemically for features of apoptosis using a monoclonal antibody detecting bcl-2. Results: Both AD and CTCL sections revealed a high percentage of bcl-2+ cells within the dermal perivascular infiltrate before therapy. After the successful treatment using medium-dose UVA1 phototherapy this percentage could be decreased significantly. Conclusion: Both T-cell-derived skin diseases exhibit an increased pre-therapeutic number of bcl-2+ cells. After medium-dose UVA1 phototherapy the substantial improvement of the skin condition was linked to a significant decrease of the dermal bcl-2+ cell count. Moreover, we could demonstrate a remarkable correlation referring to the decrease and staining pattern of bcl-2 between these two groups as well as within each group. Because the bcl-2 protein is known to act as an apoptosis inhibitor, its pre-therapeutic increase may provide the persistent cutaneous inflammatory reaction in T-cell-derived skin diseases. Additionally, the post-therapeutic reduction of bcl-2+ cells might represent a key mechanism of medium-dose UVA1 phototherapy. [source]

    Proteomic patterns for classification of ovarian cancer and CTCL serum samples utilizing peak pairs indicative of post-translational modifications

    Chenwei Liu
    Abstract Proteomic patterns as a potential diagnostic technology has been well established for several cancer conditions and other diseases. The use of machine learning techniques such as decision trees, neural networks, genetic algorithms, and other methods has been the basis for pattern determination. Cancer is known to involve signaling pathways that are regulated through PTM of proteins. These modifications are also detectable with high confidence using high-resolution MS. We generated data using a prOTOFÔ mass spectrometer on two sets of patient samples: ovarian cancer and cutaneous t-cell lymphoma (CTCL) with matched normal samples for each disease. Using the knowledge of mass shifts caused by common modifications, we built models using peak pairs and compared this to a conventional technique using individual peaks. The results for each disease showed that a small number of peak pairs gave classification equal to or better than the conventional technique that used multiple individual peaks. This simple peak picking technique could be used to guide identification of important peak pairs involved in the disease process. [source]

    Epigenetic changes in cancer,

    APMIS, Issue 10 2007
    A cancer develops when a cell acquires specific growth advantages through the stepwise accumulation of heritable changes in gene function. Basically, this process is directed by changes in two different classes of genes: Tumor suppressor genes that inhibit cell growth and survival and oncogenes that promote cell growth and survival. Since several alterations are usually required for a cancer to fully develop, the malignant phenotype is determined by the compound status of tumor suppressor genes and oncogenes. Cancer genes may be changed by several mechanisms, which potentially alter the protein encoding nucleotide template, change the copy number of genes, or lead to increased gene transcription. Epigenetic alterations, which, by definition, comprise mitotically and meiotically heritable changes in gene expression that are not caused by changes in the primary DNA sequence, are increasingly being recognized for their roles in carcinogenesis. These epigenetic alterations may involve covalent modifications of amino acid residues in the histones around which the DNA is wrapped, and changes in the methylation status of cytosine bases (C) in the context of CpG dinucleotides within the DNA itself. Methylation of clusters of CpGs called "CpG-islands" in the promoters of genes has been associated with heritable gene silencing. The present review will focus on how disruption of the epigenome can contribute to cancer. In contrast to genetic alterations, gene silencing by epigenetic modifications is potentially reversible. Treatment by agents that inhibit cytosine methylation and histone deacetylation can initiate chromatin decondensation, demethylation and reestablishment of gene transcription. Accordingly, in the clinical setting, DNA methylation and histone modifications are very attractive targets for the development and implementation of new therapeutic approaches. Many clinical trials are ongoing, and epigenetic therapy has recently been approved by the United States Food and Drug Administration (US FDA) for use in the treatment of myelodysplastic syndrome (MDS) and primary cutaneous T-cell lymphoma (CTCL). [source]

    Infantile-onset cutaneous T-cell lymphoma

    A. Tsianakas
    Summary Background, Mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma (CTCL), is mainly a disease of the elderly. Objectives, To review paediatric CTCL cases reported in the literature, with a focus on the time between onset of symptoms and establishment of a correct diagnosis. Methods, A review of the literature was carried out and a case reported. Results, A total of 254 cases of CTCL have been reported in children aged < 16 years, 13 cases (< 1% of all reported cases) in children below the age of 2 years, and only seven cases (including ours) during the first year of life. CTCL was most prevalent in children aged 10,12 years. The delay between age of onset and establishment of diagnosis was largest in the youngest age group (0,3 years), and declined steadily thereafter, thus reflecting the increasing likelihood that CTCL is considered in the differential diagnosis of skin disorders with increasing age of the patient. Conclusions, The diagnosis of CTCL is frequently delayed in young children. It needs to be considered in chronic ,eczematous' skin lesions irrespective of the patient's age, and including infants. [source]

    Sézary syndrome associated with granulomatous lesions during treatment with bexarotene

    A. Ruiz-de-Casas
    Summary Sézary syndrome (SS) is a leukaemic variant of cutaneous T-cell lymphoma (CTCL). We report a patient with SS who developed granulomatous lesions. These lesions broke out during treatment with bexarotene when the disease had appeared to stabilize. After a partial clinical remission the disease showed rapid progression and finally led to the patient's death. This contradicts the initial assessment, which considered the granulomatous inflammation as a good prognostic factor in CTCL. [source]

    SEREX identification of new tumour-associated antigens in cutaneous T-cell lymphoma

    T.B. Hartmann
    Summary Background Cutaneous T-cell lymphoma (CTCL) is a clonal lymphoproliferative disorder of mainly CD4+ T cells, with primary manifestation in the skin. Objectives To detect new CTCL-associated antigens for immunological therapies and to define their specificity in terms of RNA expression and seroreactivity. Methods A newly constructed CTCL cDNA phage library was screened and cross-reactivities against the detected clones were tested using 15 mycosis fungoides and six Sézary syndrome sera. The mRNA expression of the identified genes was analysed by reverse transcription,polymerase chain reaction (RT,PCR) using 22 tumour tissues, nine cell lines and up to 29 different types of normal tissue. Results We identified nine different tumour antigens (HD-CL-01 to HD-CL-09) of which seven clones had high homology to genes with known functions. Several of these genes had previously been associated with cancer, namely inositol 1,4,5-triphosphate 5-phosphatase, vimentin, aldose reductase and elongation factor-1,. Variations in the deduced protein sequences were observed in three cases, mostly due to variations in protein length. The individual clones were recognized by up to 56% of patients' sera, while control sera were negative except in one case. Using RT,PCR, we found a frequent expression of these new tumour antigens in tumour specimens (26,100%). In contrast to humoral specificity, specific mRNA was also detected in selected normal tissues (29,89%). Conclusions SEREX (serological identification of antigens by recombinant expression cloning) identified multiple tumour-associated antigens in CTCL. The serological specificity and the high percentage of reactive sera of CTCL patients against several clones suggest these genes as potential targets for diagnostic and prognostic purposes. [source]

    Treatment of advanced mycosis fungoides/Sézary syndrome with fludarabine and potential adjunctive benefit to subsequent extracorporeal photochemotherapy

    P. Quaglino
    Summary Background Purine analogues [fludarabine monophosphate (FAMP); deoxycoformycin and 2-chlorodeoxyadenosine) and extracorporeal photochemotherapy (ECP) have been suggested to be active agents in advanced cutaneous T-cell lymphoma (CTCL) patients. Objectives To explore further the clinical efficacy and safety of FAMP monochemotherapy in advanced CTCL and to evaluate if the sequential association of ECP to FAMP in selected patients may improve the response rate (RR) and/or lengthen the remission duration. Patients and methods Forty-four CTCL patients [17 Sézary syndrome (SS); 26 mycosis fungoides (MF), stage IIB,IV or with peripheral blood involvement; one MF associated with lymphomatoid papulosis (LyP)] were enrolled in this pilot cohort study. All the patients received FAMP 25 mg m,2 5 days monthly; 19 patients (43·2%) underwent ECP after FAMP was discontinued. The majority of patients with erythrodermic CTCL or peripheral blood involvement underwent the combined FAMP,ECP schedule. Results After a median follow-up of 4·2 years, the overall FAMP RR was 29·5% (13/44); a higher RR was obtained in SS (35·3%) than in MF patients (25·9%). According to the treatment group, the RR of the FAMP,ECP group (63·2%) was significantly higher than that of the FAMP monotherapy group (24%; P = 0·021). No statistically significant difference was found in time-to-progression (TTP) or survival by therapy group, even if the TTP of the patients treated with the FAMP,ECP combination therapy was higher (median 13 vs. 7 months). A decrease or a normalization in the CD4+CD26, circulating subset was observed in responding patients, paralleling the reduction in the circulating Sézary cells. Conclusions FAMP confirms its clinical activity as a single agent in SS; conversely, FAMP results do not compare favourably with other therapeutic approaches for advanced stage MF patients. The sequential association of ECP after FAMP seems to increase the RR, even if future randomized studies are needed to confirm these results. [source]

    Molecular cytogenetic analysis of cutaneous T-cell lymphomas: identification of common genetic alterations in Sézary syndrome and mycosis fungoides

    X. Mao
    Summary Background Data on genome-wide surveys for chromosome aberrations in primary cutaneous T-cell lymphoma (CTCL) are limited. Objectives To investigate genetic aberrations in CTCL. Methods We analysed 18 cases of Sézary syndrome (SS) and 16 cases of mycosis fungoides (MF) by comparative genomic hybridization (CGH) analysis, and correlated findings with the results of additional conventional cytogenetics, fluorescent in situ hybridization (FISH) and allelotyping studies. Results CGH analysis showed chromosome imbalances (CIs) in 19 of 34 CTCL cases (56%). The mean ±,SD number of CIs per sample was 1·8 ± 2·4, with losses (1·2 ± 2·0) slightly more frequent than gains (0·6 ± 1·0). The most frequent losses involved chromosomes 1p (38%), 17p (21%), 10q/10 (15%) and 19 (15%), with minimal regions of deletion at 1p31p36 and 10q26. The commonly detected chromosomal gains involved 4/4q (18%), 18 (15%) and 17q/17 (12%). Both SS and late stages of MF showed a similar pattern of CIs, but no chromosomal changes were found in three patients with T1 stage MF. Of the 18 SS cases also analysed by cytogenetics, seven showed clonal chromosome abnormalities (39%). Five cases had structural aberrations affecting chromosomes 10 and 17, four demonstrated rearrangement of 1p and three revealed an abnormality of either 6q or 14q consistent with CGH findings. FISH analysis showed chromosome 1p and 17q rearrangements in five of 15 SS cases, and chromosome 10 abnormalities in four SS cases consistent with both the G-banded karyotype and the CGH results. In addition, allelotyping analysis of 33 MF patients using chromosome 1 markers suggested minimal regions of deletion at D1S228 (1p36), D1S2766 (1p22) and D1S397 (1q25). Conclusions These findings provide a comprehensive assessment of genetic abnormalities in CTCL and a rational approach for further studies. [source]

    Proapoptotic and antiapoptotic markers in cutaneous T-cell lymphoma skin infiltrates and lymphomatoid papulosis

    H. Nevala
    Background In cutaneous T-cell lymphoma (CTCL) lesions, both reactive T cells and malignant T cells intermingle. The disease progression is mostly slow. Recent evidence suggests that even if clinical remission is reached, malignant cells persist and a relapse follows sooner or later. To what extent tumour cell apoptosis occurs in the skin lesions either due to the reactive T cells or to therapeutic efforts is not known. Objectives To determine the extent of tumour cell apoptosis and the expression of proapoptotic and antiapoptotic markers in serial skin lesion samples from patients with CTCL, and to compare the findings with those in patients with lymphomatoid papulosis (LyP). Methods Thirty-four skin samples were obtained from 12 patients with CTCL at the time of diagnosis and at a mean of 1·6, 3 and 6 years later. The patients received psoralen plus ultraviolet A (PUVA), electron beam or cytostatic treatments. In addition, fresh post-treatment samples from three patients with CTCL undergoing PUVA therapy were obtained. For comparison, skin biopsies of five patients with LyP were studied. Immunohistochemical demonstration of the expression of the following markers was performed on formalin-fixed skin sections: Fas (CD95), Fas ligand (FasL), bcl-2, granzyme B, the tumour-suppressor protein PTEN and the effector caspase, caspase-3. The malignant cells were identified morphologically, and apoptotic cells were identified with the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling method on parallel sections. Results In untreated CTCL lesions, apoptotic lymphocytes were extremely rare, and no increase in the number of apoptotic cells was observed after any of the treatments used. In LyP, apoptotic cells were more frequent, comprising on average 5% of the infiltrate. The apoptosis-associated markers Fas, FasL, caspase-3 and granzyme B were expressed by morphologically neoplastic cells in CTCL and by large atypical cells in LyP, with no significant differences. However, only a few reactive cells in CTCL infiltrates expressed granzyme B while about 10% of the corresponding cells were positive in LyP. The expression of antiapoptotic bcl-2 was more frequent in CTCL than in LyP, while PTEN expression was high in both instances. The number of bcl-2+ cells tended to decrease after therapy. When comparing the findings between the first and the last samples, a decrease in the number of bcl-2+ cells and an increase in Fas+ cells was associated with disease progression, despite therapy, while the opposite was true for remissions. Conclusions Apoptosis was found to be a rare event in CTCL lesions irrespective of preceding therapy. During patient follow-up, no significant differences in the expression of apoptotic markers was observed while in most cases a lower level of antiapoptotic bcl-2 expression was observed after all types of therapies and in association with disease progression when compared with high expression in the untreated lesions. The absence of apoptosis and high expression of bcl-2 together with a low expression of apoptosis-inducing granzyme B in the reactive lymphocytes in CTCL could explain the chronic nature of the disease and the poor response to therapy, while the more frequent occurrence of granzyme B and apoptosis together with a lower level of expression of bcl-2 by the large atypical cells in LyP could contribute to the favourable outcome of the latter. [source]

    Significant impact of cutaneous T-cell lymphoma on patients' quality of life

    CANCER, Issue 10 2006
    Results of a 2005 National Cutaneous Lymphoma Foundation Survey
    Abstract BACKGROUND. Cutaneous T-cell lymphoma (CTCL) can have a profound impact on a patient's health-related quality of life; however, little is known about its actual impact. The authors evaluated patients' perspectives on the impact of CTCL on physical functioning, lifestyle, emotional well being, and satisfaction with treatment. METHODS. A 4-page, self-administered questionnaire was mailed and made available online in March 2005 to the entire United States membership of the Mycosis Fungoides Foundation (n = 930 members). Outcome measures were patients' perspectives on the psychosocial impact of CTCL and the management of their disease. RESULTS. The response rate was 68%, and 93.6% of respondents were white. The majority of respondents had mycosis fungoides (89%). Respondents were bothered by skin redness (94%) and by the extent of symptoms that affected their choice of clothing (63%). For most patients, the disease had a functional impact, rendering them tired or affecting their sleep. Health distress was reported by almost all respondents, with 94% reporting that they worried about the seriousness of their disease and 80% worrying about dying from the disease. Sixty-two percent of respondents reported that their disease made them feel unattractive, 85% reported that their treatment made their disease seem more manageable, but 61% reported that they felt burdened financially by their disease. CONCLUSIONS. The high response rate and patients' responses to the survey provided compelling evidence that patients believed CTCL had a profound and severe impact on their functioning, emotional, and social well being. A striking health distress was prevalent in almost all respondents. Although the majority of patients reported that treatments made their disease more manageable, a significant proportion reported that they felt burdened financially by their disease. Cancer 2006. © 2006 American Cancer Society. [source]

    Potential efficacy of the oral histone deacetylase inhibitor vorinostat in a phase I trial in follicular and mantle cell lymphoma

    CANCER SCIENCE, Issue 1 2010
    Takashi Watanabe
    Vorinostat (suberoylanilide hydroxamic acid, SAHA, Zolinza) is a histone deacetylase inhibitor with clinical activity in cutaneous T-cell lymphoma (CTCL). A phase I trial of oral vorinostat was conducted in Japanese patients with malignant lymphoma. Vorinostat 100 or 200 mg was administered twice daily for 14 consecutive days followed by a 1-week rest interval. Of 10 patients enrolled, four had follicular lymphoma (FL), two mantle cell lymphoma (MCL), two diffuse large B-cell lymphoma, and two CTCL (median age, 60 years; median number of prior regimens, 3). Vorinostat was well tolerated up to 200 mg with only one of six patients developing a dose-limiting toxicity (DLT; Grade 3 anorexia/hypokalemia). Common Grade 3 events were reversible neutropenia (30%), thrombocytopenia, and hypermagnesemia (20% each). The median number of treatment cycles was five (range, 1,36); two patients were continuing treatment. The overall response rate was 40%, with two complete responses/unconfirmed (CRu) and one partial response among FL patients and one CRu among MCL patients. One FL patient maintained CRu for 18.0 months. The median time to achieve CRu among the three patients was 8 months. These data suggest that further investigations of vorinostat in non-Hodgkin lymphoma, focusing on FL and MCL, are warranted. (Cancer Sci 2009) [source]