Management of the primary cutaneous lymphomas

Prince, H. Miles; McCormack, Christopher; Ryan, Gail; O'Keefe, Rod; Seymour, John F.; Baker, Chris I.

doi:10.1046/j.1440-0960.2003..x

Cited by 19 publications

(19 citation statements)

References 133 publications

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“…Effect on histone acetylation in mononuclear cells. Mononuclear cells were taken post-dose 1 at 3, 8,24, and 48 h, post-dose 2 at 48 h, and post-dose 3 at 72 h and whole-cell lysates were prepared in lysis buffer (Qiagen). Proteins (25 Ag) were separated by SDS-PAGE and Western blotting was done using anti-acetyl histone H3 and histone H4 antibodies (Upstate) and with anti -glyceraldehyde-3-phosphate dehydrogenase (Upstate) to control for protein loading.…”

Section: Methodsmentioning

confidence: 99%

Histone Deacetylase Inhibitor Panobinostat Induces Clinical Responses with Associated Alterations in Gene Expression Profiles in Cutaneous T-Cell Lymphoma

Ellis

Pan

Smyth

et al. 2008

Clinical Cancer Research

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274

196

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Purpose: Histone deacetylase inhibitors can alter gene expression and mediate diverse antitumor activities. Herein, we report the safety and activity of the histone deacetylase inhibitor panobinostat (LBH589) in cutaneous T-cell lymphoma (CTCL) and identify genes commonly regulated by panobinostat. Experimental Design: Panobinostat was administered orally to patients with CTCL on Monday, Wednesday, and Friday of each week on a 28-day cycle. A dose of 30 mg was considered excessively toxic, and subsequent patients were treated at the expanded maximum tolerated dose of 20 mg. Biopsies from six patients taken 0, 4, 8, and 24 h after administration were subjected to microarray gene expression profiling and real-time quantitative PCR of selected genes. Results: Patients attained a complete response (n = 2), attained a partial response (n = 4), achieved stable disease with ongoing improvement (n = 1), and progressed on treatment (n = 2). Microarray data showed distinct gene expression response profiles over time following panobinostat treatment, with the majority of genes being repressed. Twenty-three genes were commonly regulated by panobinostat in all patients tested. Conclusions: Panobinostat is well tolerated and induces clinical responses in CTCL patients. Microarray analyses of tumor samples indicate that panobinostat induces rapid changes in gene expression, and surprisingly more genes are repressed than are activated. A unique set of genes that can mediate biological responses such as apoptosis, immune regulation, and angiogenesis were commonly regulated in response to panobinostat. These genes are potential molecular biomarkers for panobinostat activity and are strong candidates for the future assessment of their functional role(s) in mediating the antitumor responses of panobinostat.

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Section: Methodsmentioning

confidence: 99%

Histone Deacetylase Inhibitor Panobinostat Induces Clinical Responses with Associated Alterations in Gene Expression Profiles in Cutaneous T-Cell Lymphoma

Ellis

Pan

Smyth

et al. 2008

Clinical Cancer Research

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274

196

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“…3,4 Furthermore, in 40% of patients with indolent CTCL, the disease can transform to a diffuse large cell phenotype carrying a particularly grave prognosis. 5,6 Therapy options for advanced-stage CTCL predominantly involve systemic approaches including immunomodulators such as interferon alpha, extracorporeal photopheresis (ECP), single or combination agent chemotherapy, oral retinoids, and immunotherapy such as alemtuzumab 6,7 or denileukin diftitox. 7,8 However, for patients with adverse prognostic factors, all of these approaches provide only limited-duration remissions, and the overall pattern is that of repeated relapse, and often death from complications of therapy or refractory disease.…”

mentioning

confidence: 99%

Graft-versus-lymphoma effect in refractory cutaneous T-cell lymphoma after reduced-intensity HLA-matched sibling allogeneic stem cell transplantation

Herbert

Spencer

Grigg

et al. 2004

Bone Marrow Transplant

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Summary:Cutaneous T-cell lymphomas (CTCL) are rare diseases that, in their advanced stages or in transformation, have a poor prognosis. Autologous stem cell transplantation (Au-SCT) after high-dose therapy has yielded disappointing results. Allogeneic transplantation (allo-SCT) provides the potential advantage of an immune-mediated graftversus-lymphoma (GVL) effect. Reduced-intensity allo-SCT potentially offers a GVL effect, but with diminished toxicity related to the induction regimen; however, published experience with this approach in CTCL is limited. We report a series of three patients (age 35-49) with advanced, refractory (n ¼ 2) or transformed (n ¼ 1) CTCL who underwent reduced-intensity allo-SCT in the context of active disease. All three survived the peritransplant period and, despite later having disease relapse, all exhibited evidence of a GVL effect. Relapses of the disease were in the context of immune suppression for graft-versus-host disease (GVHD), and when immune suppression was reduced, responses were regained. A comparison is made of these results to those in a review of the published literature to date. We conclude that while a GVL can be achieved for CTCL with reduced-intensity allogeneic transplantation, the clinical benefits are short lived and novel approaches are required to obtain sustained remissions.

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“…We found that patients with MF in tumor stage showed loss of CD3 and CD7, to those in patch and plaque stages and to patients with benign dermatoses. There are other reports on lower expression of CD7 [1,[24][25][26][27]. Most of authors state that deficiency of this antigen can represent a tool for diagnosis of MF [1,6,10].…”

Section: Discussionmentioning

confidence: 99%

“…Treating of the disease includes topical corticosteroids, phototherapy, topical chemotherapy, radiotherapy, retinoids (in IA to IIB stages) and systemic chemotherapy. Modern therapy for cutaneous Tcell lymphoma is based on the cellular and molecular pathways involved in the pathogenesis of CTCLs includes monoclonal antibodies and biological response modifiers (in IIB to IV stages) [1]. Recently it was reported that the use of allogenic stem cell transplantation can cause long-term durable remissions of more than 3 years in case of patients with CTCL [2].…”

mentioning

confidence: 99%

Immunoelectron microscopy in mycosis fungoides and benign dermatoses. Expression of CD3, CD4 and CD7 receptors

Grzanka

Placek²,

Sokołowska‐Wojdyło³

et al. 2010

neo

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Mycosis fungoides is an epidermotropic cutaneous T-cell lymphoma (CTCL).Specimens for presented study were taken from sixteen patients with MF confirmed by immunohistochemical methods and PCR and from nine patients with benign dermatoses. To demonstrate CD3, CD4 and CD7 antigens immunogold method was used. We saw morphological differences between lymphocytes from MF and benign dermatoses. In MF, CD3 and CD4 were present rather in form of clusters placed on the surface of cell. On the contrary -CD3 to CD7 distribution analysis showed that these antigens were present rather individually, however there were seen clusters as well. In MF tumor stage labelling decreased in following order: CD7, CD3 and CD4. We also found internalisation of studied antigens via the coated structures of the cell membrane -especially in tumor stage. In benign dermatoses the majority of all receptors was present on the cell membrane. Our work showed differences in localization of studied antigens, between MF stages, what can suggest their possible translocation in cells. We also found loss of CD3 and CD7 antigens in tumor stage what might be use as a diagnosis tool for this disease.

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Management of the primary cutaneous lymphomas

Cited by 19 publications

References 133 publications

Histone Deacetylase Inhibitor Panobinostat Induces Clinical Responses with Associated Alterations in Gene Expression Profiles in Cutaneous T-Cell Lymphoma

Histone Deacetylase Inhibitor Panobinostat Induces Clinical Responses with Associated Alterations in Gene Expression Profiles in Cutaneous T-Cell Lymphoma

Graft-versus-lymphoma effect in refractory cutaneous T-cell lymphoma after reduced-intensity HLA-matched sibling allogeneic stem cell transplantation

Immunoelectron microscopy in mycosis fungoides and benign dermatoses. Expression of CD3, CD4 and CD7 receptors

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