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Biomedical subjects

Michel D'Incan

Publications and source records attributed to Michel D'Incan.

15 recordsLinked to original sources
PubMed2006

EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome.

Several reviews and guidelines on the management of mycosis fungoides and Sézary syndrome (MF/SS) have been published; however, treatment strategies for patients with MF/SS vary from institution to institution and no European consensus has yet been established. There are few phase III trials to support treatment decisions for MF/SS and treatment is often determined by institutional experience. In order to summarise the available evidence and review 'best practices' from each national group, the European Organisation for Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Task Force met in September 2004 to establish European guidelines for the treatment of MF/SS. This article reviews the treatment regimens selected for inclusion in the guidelines and summarises the clinical data for treatments appropriate for each stage of MF/SS. Guideline recommendations are presented according to the quality of supporting data, as defined by the Oxford Centre for Evidence-Based Medicine. Skin-directed therapies are the most appropriate option for early-stage MF/SS and most patients can look forward to a normal life expectancy. Patients with advanced disease should be encouraged to participate in clinical trials and maintenance of quality of life should be paramount.

Antineoplastic Agents↗
PubMed2005

Long-term disease-free survival in advanced melanomas treated with nitrosoureas: mechanisms and new perspectives.

BACKGROUND: Median survival of metastatic malignant melanoma is 6.0 to 7.5 months, with a 5-year survival of approximately 6.0%. Although long-term complete remissions are rare, few reports describe cases after chemotherapy. Fifty-three patients with metastatic melanoma were treated with Cystemustine, a chloroethyl nitrosourea (CENU) (60 or 90 mg/m2). CASE PRESENTATION: We describe 5 cases, presenting with complete response with long-term disease-free survival of long-term remission of 14, 12, 9, 7 and 6 years after Cystemustine therapy alone. CONCLUSION: Long-term survival has already been described in literature, but in all cases they have been obtained after chemotherapy associated with or followed by surgery. But despite these noteworthy and encouraging but also rare results, it appears essential to increase Cystemustine efficiency.

Adult↗
PubMed2005

Treatment of early-stage mycosis fungoides with twice-weekly applications of mechlorethamine and topical corticosteroids: a prospective study.

OBJECTIVE: To determine if a therapeutic regimen of twice-weekly applications of mechlorethamine hydrochloride and betamethasone dipropionate cream is effective in the treatment of early-stage mycosis fungoides while increasing cutaneous tolerance. DESIGN: Prospective nonrandomized study conducted from November 1999 to November 2002. SETTING: Eleven university or hospital dermatology departments in France. PATIENTS: Sixty-four consecutive patients with newly diagnosed early-stage mycosis fungoides (stage IA, n = 33; stage IB, n = 26; stage IIA, n = 5). INTERVENTIONS: Patients were treated with twice-weekly applications of a 0.02% aqueous solution of mechlorethamine followed by an application of betamethasone cream during a 6-month period. MAIN OUTCOME MEASURES: The primary end point was the rate of complete response during the treatment. Secondary end points were mean delay to achieve complete response, rate of severe cutaneous reactions of intolerance, and rate of relapse after achieving complete response. RESULTS: Thirty-seven patients (58%) had a complete response after a mean +/- SD treatment duration of 3.6 +/- 2.5 months: 20 (61%) of 33 patients with stage IA disease, 15 (58%) of 26 patients with stage IB disease, and 2 (40%) of 5 patients with stage IIA disease. Eighteen patients (28%) developed severe cutaneous reactions of intolerance that necessitated treatment discontinuation. Relapse was observed in 17 patients (46%) after a mean +/- SD time of 7.7 +/- 6.5 months. CONCLUSIONS: A regimen of twice-weekly applications of mechlorethamine and betamethasone cream is an effective treatment for early-stage mycosis fungoides. The decreased frequency of applications provides an advantage to the patient by being easy to use with limited adverse effects.

Administration, Topical↗
PubMed2005

Second-line chemotherapy of disseminated malignant melanoma with cystemustine at 60 mg/m2: a phase II trial.

Nitrosoureas possess some anti-tumor activity as a single agent in metastatic melanoma (MM). In a phase II trial, we evaluated the anti-tumor effects of cystemustine chemotherapy, a new nitrosourea, as a second-line treatment. Patients were required to have histologic evidence of disseminated MM and had failed in first-line chemotherapy. Treatment comprised cystemustine given at a dose of 60 mg/m every 2 weeks by a 15-min infusion. From February 1997 to September 1999, 22 patients (median age 66 years) were enrolled and were assessable. Two complete responses, one partial response, three stable diseases and 16 progressions were observed, giving an overall response rate of 13.6%. Median duration of response was 10 months (range 4-63). Median survival of responders and non-responders was 11 and 4 months, respectively. However, hematological toxicity, particularly thrombopenia, was a limiting factor for one-third of patients. We conclude that cystemustine at 60 mg/m is active in patients who progressed after one line of chemotherapy in advanced disease, and offers the possibility of complete responses and long durations of these responses.

Adolescent↗
PubMed2005

Blastic NK-cell lymphomas (agranular CD4+CD56+ hematodermic neoplasms): a review.

Blastic natural killer (NK) cell lymphoma (also termed CD4+CD56+ hematodermic neoplasm) is a recently described entity, with the first case reported in 1994. It was suggested initially that the disease originates from NK cells. Since 1994, single cases and a few small series have been published. In this review, data from the literature and a series of 30 cases from the French and Dutch study groups on cutaneous lymphomas are discussed. The major clinical, histopathologic, and phenotypic aspects of the disease and diagnostic criteria and data suggesting a plasmacytoid dendritic cell origin for the tumor cells are provided.

Adult↗
PubMed2004

Bcl-2 protein expression is the strongest independent prognostic factor of survival in primary cutaneous large B-cell lymphomas.

Bcl-2 protein expression has been associated with poor prognosis in patients with noncutaneous diffuse large B-cell lymphomas. In primary cutaneous large B-cell lymphomas, the location on the leg, the round-cell morphology defined as the predominance of centroblasts and immunoblasts over large centrocytes, and multiple skin lesions were identified as adverse prognostic factors. The prognostic value of bcl-2 protein expression has not been studied in large series of patients. We evaluated 80 primary cutaneous large B-cell lymphomas collected by the French Study Group on Cutaneous Lymphomas. The prognostic value of age, sex, number of lesions, cutaneous extent, location, serum lactate dehydrogenase (LDH) level, B symptoms, morphology, and bcl-2 protein expression was studied. The overall 5-year specific survival rate was 65%. In univariate analysis, advanced age, multiple skin lesions (n = 48), location on the leg (n = 25), round-cell morphology (n = 32), and bcl-2 expression (n = 39) were significantly related to death from lymphoma. In multivariate analysis, bcl-2 expression (P =.0003), multiple skin lesions (P =.004), and age remained independent prognostic factors. The 5-year specific survival rates in bcl-2-positive and bcl-2-negative patients were 41% and 89%, respectively (P <.0001). A new prognostic classification of primary cutaneous B-cell lymphoma should be based primarily on bcl-2 protein expression rather than the location of skin lesions.

Adult↗
PubMed2004

Downregulation of BRCA1 in A375 melanoma cell line increases radio-sensitivity and modifies metastatic and angiogenic gene expression.

The participation of BRCA1 (breast cancer 1) in DNA repair is well established, especially in mammary and ovarian cells. Our purpose was to develop a new in vivo radio-sensitizing therapy for melanoma. We therefore investigated the effect of downregulation of BRCA1 on irradiated melanoma cells using an anti-BRCA1 ribozyme. Our results show that BRCA1 downregulation increased radio-sensitivity of the A375 cell line, suggesting that BRCA1 could act as a caretaker in melanoma; however, as BRCA1 functions are not limited to maintaining genomic integrity but also regulate transcription and the cell cycle, we confirmed that the proliferative rate of BRCA1 downregulated clones did not change. We also demonstrate that: (1) among the major pro-angiogenic genes, FGF-2 was not increased before or after irradiation and vascular endothelial growth factor strongly inhibited after irradiation; (2) expression of two important metalloproteinases, matrix metalloproteinase 2 and 9, involved in melanoma metastasis were decreased before and after irradiation; (3) expression of their major inhibitor, tissue inhibitor of metalloproteinase, was mainly upregulated; and (4) that invasion of BRCA1 downregulated cells was modified. Together these data suggest that BRCA1 downregulation in melanoma cells did not make them more aggressive and could lead to new therapeutic strategies for this tumor, which is so difficult to control once metastasized.

Benzothiazoles↗
PubMed2004

CD158k/KIR3DL2 is a new phenotypic marker of Sezary cells: relevance for the diagnosis and follow-up of Sezary syndrome.

CD158k molecules belong to the family of killer cell immunoglobulin-like receptors (KIR) that are expressed on a minor population of circulating NK and CD8+ T lymphocytes. Here, we report a strong positive correlation between the percentage of CD158k+ blood lymphocytes analyzed by flow cytometry and the percentage of atypical circulating cells (Sezary cells) determined by cytomorphology in a large group of patients with Sezary syndrome. Moreover, we show that circulating CD4+CD158k+ lymphocytes correspond to the malignant clonal cell population. Our findings suggest that the CD158k marker could be a useful tool for the evaluation of the circulating tumoral burden and the follow-up of patients with Sezary syndrome.

Biomarkers, Tumor↗
PubMed2003

Extracorporeal photochemotherapy for graft versus host disease in pediatric patients.

Although worldwide experience with extracorporeal photochemotherapy (ECP) for GvHD treatment has grown enormously over the past decade, only a few pediatric centers have experience with ECP. Studies reporting clinical outcome in children with GvHD treated by ECP comprises a very limited number of patients with only few information described. This review article remain focused on the efficacy and the safety aspect of ECP in pediatric patients to provide information about the steps that should be taken to overcome the difficulties with ECP use in children with GvHD. Data concerning 19 children with acute GvHD and 54 children with chronic GvHD treated with ECP and reported so far have been considered. The principal reasons for the restriction in the use of ECP in children such as: (1) technical difficulties of leukapheresis procedures (venous access, hemodynamic, metabolic and hematological tolerance); and (2) the necessity of a specially adapted pediatric patient approach to improve the psychological tolerance of this treatment are discussed. The data of this retrospective review demonstrate that ECP is beneficial and well tolerated in children with GvHD. It can be safely used even in young children with low body weight and a poor performance status when it was performed by a qualified pediatric team. The observations concerning the response rate and onset suggest that in children with acute GvHD, ECP should be started early in the course of disease and employed over a relatively short period of time. As far as chronic GvHD is concerned, despite the fact that it is preferable to begin ECP early as second line therapy, it may also be beneficial in patients with late-stage disease.

Blood Component Removal↗
PubMed2002

123I-N-(2-diethylaminoethyl)-2-iodobenzamide: a potential imaging agent for cutaneous melanoma staging.

Melanoma is a neoplasia of dramatically increasing incidence that has a propensity to spread rapidly. Early detection is fundamental and patient management requires reliable, sensitive and reproducible staging methods, such as a single examination by planar scintigraphy or single-photon emission tomography (SPET) using a radiopharmaceutical with selectivity for melanoma tissue. Among iodobenzamides reported to possess an affinity for melanoma, a new compound, N-(2-diethylaminoethyl)-2-iodobenzamide (BZA(2)), was selected for a clinical trial in view of its pharmacokinetic experimental profile in melanoma-bearing mice. Planar whole-body scintigraphy using (123)I-BZA(2) was performed in 25 patients with histologically proven cutaneous melanoma. Performance was evaluated in two groups of patients with one or more documented secondary lesions ( n=13) or with no known secondary lesions ( n=12), and results were compared with those of conventional investigation techniques. No adverse clinical or biological events were recorded. Lesions were imaged by increased tracer uptake, and good quality images were obtained 4 h after administration. After a follow-up of more than 1 year, the overall results of (123)I-BZA(2) scintigraphy on a per patient basis showed a sensitivity of 100%, a specificity of 95%, a positive predictive value of 86% and a negative predictive value of 100%. The proven secondary lesions were imaged with a sensitivity of 100% and a specificity of 91%. In seven patients with suspected metastases, the absence of (123)I-BZA(2) uptake was confirmed as true negative, and in one patient without suspected metastases, (123)I-BZA(2) scintigraphy revealed a gastric lesion. Hence eight diagnoses would have been modified by (123)I-BZA(2) scintigraphy data. (123)I-BZA(2) allowed discrimination between benign and malignant lesions and, in the case of malignancies, between those of melanomatous origin and others. This compound, which is selective for melanoma tissue, appears promising for the staging and restaging of melanoma.

Adult↗
PubMed2002

A comparison of oral and topical corticosteroids in patients with bullous pemphigoid.

BACKGROUND: Bullous pemphigoid is the most common autoimmune blistering skin disease of the elderly. Because elderly people have low tolerance for standard regimens of oral corticosteroids, we studied whether highly potent topical corticosteroids could decrease mortality while controlling disease. METHODS: A total of 341 patients with bullous pemphigoid were enrolled in a randomized, multicenter trial and stratified according to the severity of their disease (moderate or extensive). Patients were randomly assigned to receive either topical clobetasol propionate cream (40 g per day) or oral prednisone (0.5 mg per kilogram of body weight per day for those with moderate disease and 1 mg per kilogram per day for those with extensive disease). The primary end point was overall survival. RESULTS: Among the 188 patients with extensive bullous pemphigoid, topical corticosteroids were superior to oral prednisone (P=0.02). The one-year survival rate was 76 percent in the topical-corticosteroid group and 58 percent in the oral-prednisone group. Disease was controlled at three weeks in 92 of the 93 patients in the topical-corticosteroid group (99 percent) and 86 of the 95 patients in the oral-prednisone group (91 percent, P=0.02). Severe complications occurred in 27 of the 93 patients in the topical-corticosteroid group (29 percent) and in 51 of the 95 patients in the oral-prednisone group (54 percent, P=0.006). Among the 153 patients with moderate bullous pemphigoid, there were no significant differences between the topical-corticosteroid group and the oral-prednisone group in terms of overall survival, the rate of control at three weeks, or the incidence of severe complications. CONCLUSIONS: Topical corticosteroid therapy is effective for both moderate and severe bullous pemphigoid and is superior to oral corticosteroid therapy for extensive disease.

Administration, Oral↗
PubMed2002

Successful extracorporeal photochemotherapy for chronic graft-versus-host disease in pediatric patients.

A total of 254 extracorporeal photochemotherapy (ECP) procedures were performed in 8 children (median age 10 years; range 5-15) with extensive resistant chronic graft-versus-host disease (GVHD). ECP was carried out in the pediatric environment using a Cobe Spectra separator and UV-MATIC irradiator. A peripheral venous with a single-lumen permanent central catheter access (69% of ECP-apheresis) or a dual-lumen permanent central catheter access (26% of ECP-apheresis) were used preferentially. A median platelet decrease of 17% (0-71) (p = 0.0001) and median hemoglobin level decrease of 15 g/L (0-31)(p = 0.0001) were noted following each ECP-apheresis. However, none of the patients had profound thrombocytopenia or anemia. Two minor episodes of catheter related-bacteriemia (Staphylococcus aureus) were noted (2310 catheter-days). A negative correlation was found between lymphocyte collection efficacy (median = 38%) and pre ECP-apheresis lymphocyte count (r = 0.4, p = 0.00001). The median of 5 x 10(7) lymphocytes/kg (0.1-50.10(7)/kg) was irradiated in each procedure. All patients are alive and well, and 7/8 experienced a dramatic improvement in their cutaneous status. Liver and gut disease resolved completely in 4/6 and 5/5 patients, respectively. In all patients, a concomitant immunosuppressive therapy was stopped (5/8) or considerably reduced (3/8). Five patients with more than 2 years follow-up after discontinuation of ECP are in remission with no immunosuppression treatment. They have normal growth rates and normal school and sport activity. Our study shows that ECP is beneficial, well tolerated, and can be safely used for chronic GVHD treatment even in young children with low body weight and a poor performance status. We believe that having a dedicated pediatric environment together with an experienced, motivated, and specifically pediatric team is of crucial importance for improving patient's acceptance of this long-term therapeutic program.

Adolescent↗
PubMedDate not supplied

Ichthyosiform mycosis fungoides.

Malignancy-associated acquired ichthyosis is well known, but the ichthyosiform subset of mycosis fungoides (MF) is rarely reported. We report on two patients with a clinical presentation for whom diagnosis of mycosis fungoides was established on histological grounds. In both cases, long term remission was obtained with non aggressive therapies. This rare condition must be added to newly described forms of MF with epidermal hyperplasia such as keratosis lichenoides chronica like MF and pilotropic MF.

Aged↗