Search

The retinoid X receptor (RXR)-agonist bexarotene and the histone deacetylase inhibitor (HDACI) vorinostat are each established monotherapies for cutaneous T-cell lymphomas (CTCLs). We investigated the combination of HDACI and retinoic acid receptor (RAR)/RXR agonists in vitro and in a phase I, multicenter, open-label, two-part dose-escalation study. The combination of bexarotene with a HDACI in vitro leads to cooperative activation of gene transcription and reduction of cell viability in human tumor cell lines. The primary clinical objective was to determine the maximum tolerated dose (MTD) of bexarotene plus vorinostat in 23 patients with CTCLs. The MTD for part I was established at vorinostat 200 mg/day plus bexarotene 300 mg/m(2)/day. The MTD for part II was not reached. Four patients had an objective response and seven patients experienced pruritus relief. We conclude that concomitant administration of vorinostat and bexarotene is feasible only if lower doses of each drug are administered relative to the product label monotherapy doses.

Recently, several European centers of lymphoma diagnosis and research developed various polymerase chain reaction (PCR) methods for clonality analysis in suspect T-cell and B-cell proliferations (Biomed-2 Concerted Action). They have mainly been applied to frozen material of systemic B-cell and T-cell malignancies. Thus far, only limited data exist with regard to cutaneous T-cell lymphoma (CTCL) and paraffin-embedded material. Thus, we applied the Biomed-2 T-cell receptor (TCR) gamma and TCRbeta PCR as well as an in-house TCRgamma PCR to a collection of 107 archival skin samples (84 CTCL, 3 systemic TCL and 20 controls). As a result, the Biomed-2 TCRgamma PCR revealed 81% clonality, the in-house TCRgamma method revealed 86% clonality, and the Biomed-2 TCRbeta revealed 78% clonality in CTCL samples generating at least the 300 bp fragment in the Biomed-2 control PCR. We found clonal TCRbeta rearrangements in 5 of 17 CTCL samples that were polyclonal in the Biomed-2 TCRgamma PCR. By combining all Biomed-2 assays, one or more clonal rearrangements were detected in 87% of CTCL and in all 3 systemic TCLs. By combining all TCR PCR assays applied here, clonality was shown in 90% of the CTCL cases. In conclusion, we showed that the Biomed-2 TCR PCR worked well with DNA from paraffin-embedded tissue, revealing a high-clonality detection rate in CTCL, and thus should be highly recommended for routine molecular analysis. In addition, the performance of our in-house TCRgamma assay verifies our previously published findings on clonally expanded T-cells in CTCL.

Background: Mycosis fungoides (MF) represents the most common type of primary cutaneous T cell-lymphomas (CTCL), which are characterized by a clonally proliferation of malignant CD4+ lymphocytes in the skin., Objective: Skin-directed treatment regimens, like phototherapy and corticosteroids, are commonly used in early stages; systemic treatments and chemotherapies are used in advanced stages. Because conventional treatments usually end in a transient remission without curative results, there is a high need for new therapeutic strategies with acceptable side effects., Methods: Literature and reference research was done by using the data bank PubMed, and updates of ongoing studies were taken out of ASCO and ASH annual meeting abstracts., Results/conclusions: This article gives an overview of the various medications in current use, with emphasis on emerging drugs with novel therapeutic targets.

The lymph nodes are generally the first extracutaneous manifestation in patients with cutaneous T-cell lymphoma (CTCL); however, their early involvement is difficult to assess. The aim of our study was to define the diagnostic and prognostic value of T-cell clonality analysis for a more precise assessment of lymph node involvement in CTCL. T-cell clonality was determined by 2 independent polymerase chain reaction (PCR) assays, namely a recently developed T-cell receptor-beta (TCR-beta) PCR technique as well as an established TCR-gamma PCR. T-cell clonality was found in 22 of 22 lymph nodes with histologically detectable CTCL involvement as well as in 7 of 14 histologically noninvolved dermatopathic lymph nodes. The clonal T-cell populations in the lymph nodes were in all cases identical to those detected in the corresponding skin lesions, identifying them as the tumor cell population. T-cell clonality was not found in any of the 12 dermatopathic lymph nodes from 12 patients with inflammatory skin diseases. Clonal T-cell detection in 7 of 14 dermatopathic lymph nodes of patients with CTCL was associated with limited survival (74 months; confidence interval [CI], 66-82 months) as in patients with histologically confirmed lymph node involvement (41 months; CI, 35-47 months), whereas all patients without T-cell clonality in the lymph nodes (7 patients) were alive at the last follow-up. Thus, T-cell clonality analysis is an important adjunct in differentiating benign dermatopathic lymphadenitis from early CTCL involvement.

An unusual course was observed in a patient with indolent T-prolymphocytic leukaemia (T-PLL) who subsequently developed mycosis fungoides (Mf), lymphomatoid papulosis (LyP) and cutaneous CD30+ anaplastic large cell lymphoma (ALCL). Polymerase chain reaction analysis demonstrated identical monoclonal T-cell receptor-beta and -gamma gene rearrangements in all the different clinical entities. Furthermore, cytogenetic studies revealed the same aberrant clone with trisomy of chromosome 8 in T-PLL and ALCL cells. This unique observation suggests that in T-PLL, the leukaemic cells might undergo secondary transformation, subsequently resulting in different phenotypes of cutaneous T-cell lymphoma.