Overall survival in erythrodermic cutaneous T‐cell lymphoma: an analysis of prognostic factors in a cohort of patients with erythrodermic cutaneous T‐cell lymphoma

Vidulich, Kelley A.; Talpur, Rakhshandra; Bassett, Roland L.; Duvic, Madeleine

doi:10.1111/j.1365-4632.2009.03771.x

Cited by 111 publications

(70 citation statements)

References 46 publications

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“…124 It appears that the overall prognosis of SS/erythrodermic MF (E-CTCL) is improving; and in a recent report of 124 patients with E-CTCL, there was a median OS of 5.1 years (range, 0.4-18.6 years). 125 When patients were stratified according to Sézary cell (SC) counts, the median OS was 7.6 years for patients with less than 1000 SC/L versus 2.4 years for those with more than 10 000 SC/L. In multivariate analysis, advanced age and elevated lactate dehydrogenase were the strongest predictors of a poor prognosis.…”

Section: Sé Zary Syndromementioning

confidence: 99%

How I treat mycosis fungoides and Sézary syndrome

Prince

Whittaker

Hoppe

2009

Blood

135

109

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The most common subtypes of primary cutaneous T-cell lymphomas are mycosis fungoides (MF) and Sézary syndrome (SS). The majority of patients have indolent disease; and given the incurable nature of MF/SS, management should focus on improving symptoms and cosmesis while limiting toxicity. Management of MF/SS should use a “stage-based” approach; treatment of early-stage disease (IA-IIA) typically involves skin directed therapies that include topical corticosteroids, phototherapy (psoralen plus ultraviolet A radiation or ultraviolet B radiation), topical chemotherapy, topical or systemic bexarotene, and radiotherapy. Systemic approaches are used for recalcitrant early-stage disease, advanced-stage disease (IIB-IV), and transformed disease and include retinoids, such as bexarotene, interferon-α, histone deacetylase inhibitors, the fusion toxin denileukin diftitox, systemic chemotherapy including transplantation, and extracorporeal photopheresis. Examples of drugs under active investigation include new histone deacetylase inhibitors, forodesine, monoclonal antibodies, proteasome inhibitors, and immunomodulatory agents, such as lenalidomide. It is appropriate to consider patients for novel agents within clinical trials if they have failed front-line therapy and before chemotherapy is used.

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Section: Sé Zary Syndromementioning

confidence: 99%

How I treat mycosis fungoides and Sézary syndrome

Prince

Whittaker

Hoppe

2009

Blood

135

109

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“…[13][14][15][16][17][18][19][20] However, none of these markers is directly associated with the tumor phenotype of the SS cells and they seem to be mere markers of risk or, at best, the result of some deregulated mechanisms. Here we describe, for the first time, the prognostic significance of two antigens directly related to T-cell function, and thus possibly involved in the pathogenesis of SS.…”

Section: Discussionmentioning

confidence: 99%

“…4,5,11,12 Previous studies of prognostic indicators in SS showed that circulating Sézary cell count, high CD4/CD8 ratio, advanced age, high lactate dehydrogenase serum level and a high white blood cell count were associated with an unfavorable outcome. [13][14][15][16][17][18][19][20] Up to now, scanty data have been provided concerning possible associations between the immunophenotype of circulating CD4 + T cells and survival in SS. As for other hematologic malignancies, 21,22 it is important to clarify the prognostic relevance of activation of homing receptors expressed by circulating CD4 + T cells in SS, since these markers might be directly linked to the pathogenesis and outcome of the disorder.…”

Section: Introductionmentioning

confidence: 99%

The role of 9-O-acetylated ganglioside D3 (CD60) and 4 1 (CD49d) expression in predicting the survival of patients with Sezary syndrome

Scala

Abeni²,

Pomponi³

et al. 2010

Haematologica

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BackgroundSézary syndrome is a rare and very aggressive leukemic variant of cutaneous T-cell lymphoma characterized by extensive skin involvement and a malignant circulating CD4 + T-cell clone which homes to the skin, over-expresses CD60, and lacks CD7, CD26 and CD49d. So far prognostic markers in this disease are limited to treatment with systemic steroids, age, serum lactate dehydrogenase, and a white blood cell count of 20¥10 9 /L or higher: no other biological marker with prognostic value, especially related to malignant cells, has been described. Design and MethodsWe used flow activated cell sorting analysis to compare the distribution of the T-cell receptor-Vβ repertoire and several surface molecules (CD7, CD26, CD49d and CD60) within the circulating CD4 + T-cell population in 62 patients with Sézary syndrome, 180 with mycosis fungoides, 6 with B-cell lymphomas, and 19 with chronic eczema. We calculated the 5-year overall survival of patients with Sézary syndrome after first hospital admission using Kaplan-Meier product-limit estimates and hazard ratios from the Cox proportional hazards model. ResultsWe found that both higher number of CD60 + and lower number of CD49d + cells within circulating CD4 + T cells at disease presentation were significantly associated with a lower probability of survival. An exceedingly high risk of death was observed for patients with a combination of a high proportion of CD4 /L) (hazard ratio = 12.303, 95% confidence interval 1.5-95.9; P<0.02). In addition, a skewed usage of T-cell receptor-Vβ subfamilies was observed in the circulating T-cell clone for 61.9% of all patients with Sézary syndrome, T-cell receptor-Vβ 2 and 5.1 subfamilies being the most frequently represented (42.8%), followed by T-cell receptor-Vβ 12 and 13.1. ConclusionsIn this study we showed that up-regulation of CD60 and down-regulation of CD49d on circulating CD4 + T cells are two useful markers for predicting a very poor outcome in patients with Sézary syndrome.Key words: TCR-Vβ repertoire, CD60, CD49d, survival rate, Sézary syndrome. Haematologica 2010;95(11):1905-1912. doi:10.3324/haematol.2010 This is an open-access paper.The role of 9-O-acetylated ganglioside D3 (CD60) and α4β1 (CD49d) expression in predicting the survival of patients with Sézary syndrome

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“…We have previously shown that the median overall survival in patients with erythrodermic CTCL is 5.1 years, with the strongest predictive factors being elevated serum lactate dehydrogenase, advanced age, and the absolute Sézary cell count. 4 The association of CTCL with increased class II HLA-DR5 and DQB*03 alleles suggests that the disease may arise in the setting of aberrant antigen stimulation or a genetic predisposition as seen with other autoimmune skin diseases. 5 Mutations in T cells may promote both T cell accumulation via defects in the Fas/Fas ligand death pathway 6 and attraction to the skin via mutations in skin-homing molecules.…”

Section: Cutaneous T-cell Lymphomamentioning

confidence: 99%

Trends in the treatment of cutaneous T-cell lymphoma – critical evaluation and perspectives on vorinostat

Rangwala¹,

Duvic²,

Zhang³

2012

BLCTT

Self Cite

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Epigenetic modification with small molecule histone deacetylase inhibitors has been a promising new anti-neoplastic approach for various solid and hematological malignancies, particularly cutaneous T-cell lymphoma (CTCL). Oral vorinostat was the first histone deacetylase inhibitor approved to enter the clinical oncology market for treating CTCL patients who have progressive, persistent, or recurrent disease after failing two systemic therapies. In two phase II clinical trials, oral vorinostat was found to be safe and effective at a dose of 400 mg/day, with an overall response rate of 24%-30% in heavily pretreated patients with advanced CTCL, including those with large-cell transformed mycosis fungoides and Sézary syndrome. About half of CTCL patients receiving vorinostat also experienced substantial relief in pruritus and thus a marked improvement in quality of life. A subsequent follow-up study reported long-term safety and clinical benefits of vorinostat in patients with refractory CTCL, regardless of previous treatment failures. The most frequent side effects of vorinostat include gastrointestinal symptoms, fatigue, and thrombocytopenia. These adverse reactions are dose-related and reversible upon cessation of therapy. Preclinical studies have supported the therapeutic potential of vorinostat by demonstrating in vitro and in vivo anti-tumor activities against CTCL, including selective induction of apoptosis in malignant T cells, inhibition of angiogenesis, suppression of signal transducer and activator of transcription proteins, and up-regulation of pro-apoptotic proteins. Identification of biomarkers of response and resistance will help select CTCL patients most likely to benefit from treatment and guide the design of effective combination therapies.

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Overall survival in erythrodermic cutaneous T‐cell lymphoma: an analysis of prognostic factors in a cohort of patients with erythrodermic cutaneous T‐cell lymphoma

Abstract: Serum LDH and age were the strongest predictive factors for OS in E-CTCL.

Cited by 111 publications

References 46 publications

How I treat mycosis fungoides and Sézary syndrome

How I treat mycosis fungoides and Sézary syndrome

The role of 9-O-acetylated ganglioside D3 (CD60) and 4 1 (CD49d) expression in predicting the survival of patients with Sezary syndrome

Trends in the treatment of cutaneous T-cell lymphoma – critical evaluation and perspectives on vorinostat

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Overall survival in erythrodermic cutaneous T‐cell lymphoma: an analysis of prognostic factors in a cohort of patients with erythrodermic cutaneous T‐cell lymphoma

Abstract: Serum LDH and age were the strongest predictive factors for OS in E-CTCL.

Cited by 111 publications

References 46 publications

How I treat mycosis fungoides and Sézary syndrome

How I treat mycosis fungoides and Sézary syndrome

The role of 9-O-acetylated ganglioside D3 (CD60) and 4 1 (CD49d) expression in predicting the survival of patients with Sezary syndrome

Trends in the treatment of cutaneous T-cell lymphoma &ndash; critical evaluation and perspectives on vorinostat

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Product

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Trends in the treatment of cutaneous T-cell lymphoma – critical evaluation and perspectives on vorinostat