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Madeleine Duvic

Publications and source records attributed to Madeleine Duvic.

At least 73 records · Page 4Linked to original sources
PubMed2003

Analysis of long-term outcomes of combined modality therapy for cutaneous T-cell lymphoma.

BACKGROUND: Although cutaneous T-cell lymphoma (CTCL), including mycosis fungoides (MF) and Sézary syndrome, is often responsive to treatment, few current therapies increase survival or consistently induce durable remissions, especially in advanced disease. OBJECTIVE: In an effort to improve treatment efficacy and outcome in CTCL, a combined modality protocol using 3 to 4 consecutive phases of therapy was initiated in 1987 at M.D. Anderson Cancer Center, Houston, Tex. METHODS: During a period of 15 years between 1987 and 2001, 95 patients with early-stage (Ia-IIa, n = 50) and late-stage (IIb-IVb, n = 45) MF were treated with subcutaneous interferon-alpha and oral isotretinoin, followed by total-skin electron beam therapy, and long-term maintenance therapy with topical nitrogen mustard and interferon-alpha. Patients with late-stage (IIb-IVb) disease also received 6 cycles of combination chemotherapy before electron beam therapy. RESULTS: Combined modality therapy yielded a response rate of 85% with a 60% complete response rate. Among 38 patients with early-stage disease and 18 patients with late-stage disease achieving complete response, 9 (24%) patients with early-stage MF and 3 (17%) patients with late-stage MF achieved sustained remissions lasting more than 5 years. The median disease-free survival (DFS) for early and late stages of disease was 62 and 7 months, with 5-year Kaplan-Meier estimated rates of 50% and 27%, respectively. Current median overall survival times on combined modality are 145 months for patients with early-stage disease and 36 months for those with late-stage disease. Death was attributable to CTCL disease in 17 (55%) of 31 cases. The Kaplan-Meier estimates for 5-year survival are 94% for early-stage and 35% for late-stage disease. Univariate survival analysis in this patient population reveals statistically significant associations of clinical stage with overall response rates (P =.02), DFS (P =.03), and overall survival (P <.0001); age with DFS (P =.001) and overall survival (P =.04); and T stage (P <.0001) and lactate dehydrogenase (P =.007) with overall survival. By multivariate analysis using a Cox proportional hazards model, only age was significantly associated with DFS (hazard ratio 2.9), and only stage with overall survival (hazard ratio 18.2). CONCLUSION: This nonrandomized and uncontrolled CTCL study gives supportive evidence that this multiphased combined modality regimen is well tolerated and may yield higher response rates and DFS than total-skin electron beam therapy alone, but provides no evidence for a change in survival.

Adult↗
PubMed2003

Retinoids: therapeutic applications and mechanisms of action in cutaneous T-cell lymphoma.

Retinoids, natural and synthetic derivatives of vitamin A, are biological regulators of differentiation, proliferation, apoptosis, and immune response. Retinoic-acid-receptor-selective 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 lymphoma (CTCL). Orally administered bexarotene, the first synthetic highly selective retinoid-X-receptor retinoid to be approved by the FDA 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. Bexarotene treatment induces apoptosis of CTCL cells with down-regulation of its receptors and of survivin, an inhibitor of apoptosis. Identification of new receptor subtype-selective retinoids, combination of various receptor-selective retinoids or other agents, and a new drug delivery system may improve the clinical efficacy of retinoids in the future.

Administration, Topical↗
PubMed2003

Bexarotene is a new treatment option for lymphomatoid papulosis.

BACKGROUND: Lymphomatoid papulosis (LyP) is a clonal T cell proliferation with large cell histology, a chronic course, and an increased risk of lymphoma. Bexarotene (Targretin) is an RXR-selective retinoid (rexinoid) approved for the cutaneous manifestations of cutaneous T cell lymphoma. OBJECTIVE: To determine whether bexarotene is effective in treating LyP. METHODS: Ten patients with chronic and symptomatic LyP were prospectively treated with oral (n = 3) or topical gel (n = 7) formulations of bexarotene. RESULTS: A favorable response to bexarotene treatment with decreased numbers or duration of lesions was seen in all with objective responses in 8 patients. CONCLUSIONS: Bexarotene may be an effective palliative treatment for LyP, warranting further controlled studies.

Administration, Oral↗
PubMed2003

Adult Langerhans cell histiocytosis limited to the skin.

BACKGROUND: The incidence of Langerhans cell histiocytosis (LCH) is 4-5 per million in children with only 30% of this number having an adult onset. While dermatological manifestations occur in as many as 50% of cases, disease limited to the skin is uncommon among reported cases of adult LCH. OBJECTIVES AND METHODS: To present 3 new cases of adult LCH and a review of the literature of isolated cutaneous LCH in adults. RESULTS: Three adults with scalp, vulvar and generalized LCH lesions had refractory responses to treatment. CONCLUSIONS: LCH may present with unusual cutaneous manifestations limited to the skin in adults. Optimal treatment has not yet been determined.

Adult↗
PubMed2003

Mycosis fungoides with follicular mucinosis displaying aggressive tumor-stage transformation : successful treatment using radiation therapy plus oral bexarotene combination therapy.

Follicular mucinosis is a tissue reaction pattern characterized by mucin deposition with follicular sebaceous units and is found as an idiopathic, primary, benign process (alopecia mucinosa), or as a secondary process due to inflammatory and neoplastic disorders (mycosis fungoides). When associated with follicular mucinosis, mycosis fungoides commonly pursues an aggressive course, often undergoing large-cell transformation, which is associated with resistance to therapy and poor prognosis. We present a case of mycosis fungoides with follicular mucinosis that was treated with incomplete courses of interferon, isotretinoin, and polychemotherapy with subsequent rapid progression to tumor-stage mycosis fungoides with large cell transformation and nodal and bone marrow involvement. In this setting, the patient was treated with local radiation therapy, total-skin electron beam therapy, and therapy and maintenance with the oral retinoid-X-receptor retinoid bexarotene, and achieved a durable complete remission.

Administration, Oral↗
PubMed2003

Atypical lymphoid infiltration occurring at the site of a healed varicella zoster infection.

Herpes zoster infection has been associated with a number of cutaneous reactions. The authors report the first case of a patient with an atypical epidermotropic lymphoid infiltrate that arose within skin previously affected by herpes varicella zoster. The differential diagnosis of such lesions and review of literature on previous cutaneous infiltrates occurring at sites of zoster infection are discussed

Aged↗
PubMed2002

A stable aberrant immunophenotype characterizes nearly all cases of cutaneous T-cell lymphoma in blood and can be used to monitor response to therapy.

BACKGROUND: Abnormal variations in the expression level of some commonly expressed T-cell antigens are a feature of many T-cell malignancies. METHODS: We sought to assess the frequency of such abnormal antigen expression by flow cytometry in peripheral blood (PB) samples from patients with mycosis fungoides (MF) and Sézary syndrome (SS). We correlated presence of morphologically identifiable tumor cells on PB smear with the frequency of abnormalities in the level of expression of CD3, CD4, CD7, CD8 and CD26. We also examined the degree of stability of these abnormal findings in tumor cells over the course of disease. The flow cytometric findings in 100 PB samples from 44 patients, including 38 who had multiple sequential PB samples (2-8 samples each), were assessed. RESULTS: Abnormalities were seen in the expression level of one or more T-cell markers in 41 cases (93%) including CD3 in 34% of patients, CD4 in 54%, CD26 in 86% and CD 45 in 40% (10 cases tested). In all but 2 cases, the abnormal T-cell immunophenotype remained similar over the course of treatment and correlated with the relative numbers of tumor cells counted on PB smear. CONCLUSIONS: Using a standard T-cell panel, stable phenotypically aberrant T-cell populations representing the tumor are detected in the vast majority of involved PB samples in MF/SS and can be used to monitor response to therapy.

Journal Article↗
PubMed2002

Cytomegalovirus seropositivity is significantly associated with mycosis fungoides and Sézary syndrome.

Although mycosis fungoides (MF) may arise through persistent antigen stimulation, cytomegalovirus (CMV) is not a known risk factor. To study the incidence of seropositivity to viral infections, we compared MF and Sézary Syndrome (SS) patients to healthy bone marrow donors and other historical control groups. Baseline screening serologies at baseline were performed on 116 biopsy-proven MF/SS patients at MD Anderson Cancer Center from 1992 to 2001 and on healthy bone marrow donors evaluated by the transplant service from 1988 to 2001. Antibodies to HTLV-I/II, HIV-1, EBV, and CMV were measured using standard enzyme-linked immunosorbent (ELISA) and membrane enzyme immunoassay (MEIA) assays. One hundred thirteen (97.4%) of all MF/SS patients had positive CMV IgG serologies at initial presentation. Early- and late-stage patients' seropositivity rates were significantly higher than healthy bone marrow donor controls (chi(2).05(df=1) = 71.79). By stage, 98.1% of early-stage MF patients (IA, IB, IIA; 52/53) and 96.8% of late-stage MF and SS patients (IIB-IVB; 61/63) were seropositive compared with healthy bone marrow donors whose seropositivity rate was 57.3% (757/1322). Because the rate of CMV seropositivity increases with age, a subset of cutaneous T-cell lymphoma (CTCL) patients 55 years or younger were compared to age-matched healthy donor controls; their seropositivity rate for CMV was also significantly higher (chi(2).05 05(df=1) = 20.4). EBV titers were positive by serology in 13 patients who were examined prospectively. CMV seropositivity is highly associated with MF and SS, even in the earliest stages of the disease, and is significantly higher than that of healthy and immunocompromised controls.

Adult↗
PubMed2002

Clonal heterogeneity in mycosis fungoides and its relationship to clinical course.

Mycosis fungoides (MF) is a cutaneous T-cell lymphoma characterized by multifocal disease and protracted clinical course. The few studies that have assessed T-cell receptor (TCR) gene rearrangements (GRs) present at different anatomic sites in MF have generally reported a common clone. We used a previously validated 4-color polymerase chain reaction (PCR) assay to assess the size and V-family usage of TCR-gamma GRs in 102 concurrent and/or sequential morphologically involved biopsy specimens (91 skin and 11 lymph nodes) from 39 MF patients. This assay detected TCR-gamma clonal GRs in 89 samples (87%) from 36 patients (92%). In 24 patients (77%), an identical clonal GR was present in at least 2 skin samples. However, in one third of these patients, additional different clonal GRs were also noted. Four patients (13%) had clonal GRs that were distinct in different skin samples. In 3 patients (10%), no GR was detected in any sample. In a comparison of lymph node and skin samples, 8 patients had the identical clonal GRs at both sites, 2 patients had different clonal GRs, and 1 patient had no GR identified at either site. Independent of clinical stage, patients who had the same GR detected in multiple concurrent biopsy specimens at the time of diagnosis were more likely to have progressive disease than those who had different GRs (P =.04). Four-color TCR-gamma PCR analysis can uncover multiple distinct clonal GRs in different samples consistent with multiclonal or oligoclonal disease in a significant proportion of MF patients. Demonstration of identical clonal GRs in multiple biopsy specimens at the time of diagnosis may provide prognostic information related to disease progression.

Adolescent↗
PubMed2002

Skin lesion classification using oblique-incidence diffuse reflectance spectroscopic imaging.

We discuss the use of a noninvasive in vivo optical technique, diffuse reflectance spectroscopic imaging with oblique incidence, to distinguish between benign and cancer-prone skin lesions. Various image features were examined to classify the images from lesions into benign and cancerous categories. Two groups of lesions were processed separately: Group 1 includes keratoses, warts versus carcinomas; and group 2 includes common nevi versus dysplastic nevi. A region search algorithm was developed to extract both one- and two-dimensional spectral information. A bootstrap-based Bayes classifier was used for classification. A computer-assisted tool was then devised to act as an electronic second opinion to the dermatologist. Our approach generated only one false-positive misclassification out of 23 cases collected for group 1 and two misclassifications out of 34 cases collected for group 2 under the worst estimation condition.

Humans↗
PubMed2002

Phase 1 and 2 trial of bexarotene gel for skin-directed treatment of patients with cutaneous T-cell lymphoma.

OBJECTIVE: To evaluate the safety, dose tolerance, and efficacy of topical bexarotene gel in patients with early-stage cutaneous T-cell lymphoma (CTCL). DESIGN: Phase 1 and 2, open-label, dose-escalation clinical trial of bexarotene gel. SETTING: Three university-based clinics. PARTICIPANTS: Sixty-seven adults with early-stage (TNM stages IA-IIA) CTCL. INTERVENTIONS: Bexarotene gel, 0.1%, 0.5%, and 1.0%, applied in incremental dose adjustments from 0.1% gel every day to 1.0% gel 4 times daily or the maximal tolerated dose. MAIN OUTCOME MEASURES: Patients were followed for efficacy and safety, and treatment continued as long as they benefited. Response (> or =50% improvement) was evaluated by the Physician's Global Assessment of cutaneous disease and by an overall severity assessment of cutaneous disease, including signs of CTCL and area involved. RESULTS: Most patients tolerated topical bexarotene at 1% gel twice daily for routine use. Adverse events were generally mild to moderate in severity and were confined to treatment sites. Treatment-limiting toxic effects were associated with skin irritation and increased with gel exposure. Patients achieved an overall response rate of 63% and a clinical complete response rate of 21%. Median projected time to onset of response was 20.1 weeks (range, 4.0-86.0 weeks), and the estimated median response duration from the start of therapy was 99 weeks. Patients with no previous therapy for mycosis fungoides responded at a higher rate (75%) than those who previously underwent topical therapies (67%). CONCLUSIONS: Bexarotene gel was well tolerated, was easily self-applied, and had a substantial response rate in treating patients with early-stage CTCL.

Adult↗
PubMed2002

Clinical and pathological spectrum of CD8-positive cutaneous T-cell lymphomas.

CD8+ T-cell lymphomas presenting in the skin are rare. We describe the clinical and histological features of 18 patients with CD8+ cutaneous T-cell tumors, which have been divided into four groups. Seven patients had precedent long histories of rashes, which progressively spread in a presentation similar to that of CD4+ mycosis fungoides (MF). Three patients had long-standing localized plaques consistent with a pagetoid reticulosis (PR) pattern. Two patients presented with erythroderma and had peripheral blood involvement consistent with a Sezary syndrome (SS) pattern and had rapidly progressive clinical courses. Six patients presented with cutaneous nodules of varying sizes and had variable outcomes, with two having rapidly progressive disease, two with indolent recurrences and a further two with complete responses to treatment. Histologically, 12 of the 18 cases showed an epidermotropic tumor infiltrate that was most marked in the three PR cases. Prominent periadnexal infiltration was seen in 11 cases. Similar to CD4+ MF, the skin-homing antigen, (cutaneous lymphocyte antigen: CLA), was strongly expressed in 13 of 16 tested cases. Expression of the cytotoxic granule protein granzyme B was noted in a majority of tumor cells in only three of 16 tested cases. We conclude that approximately half of CD8+ cutaneous T-cell lymphomas clinically and histologically resemble CD4+ MF/SS, whereas presentation as discrete nodular lesions are more common in CD8+ tumors as compared to those that express CD4.

Adult↗
PubMed2002

Interleukin-1 receptor antagonist allele 2 and familial alopecia areata.

Alopecia areata affects 1%-2% of the population and is hypothesized to be an autoimmune, organ specific T-cell mediated reaction directed against the human hair follicle. It is characterized by loss of hair in patches (alopecia areata) with progression in some individuals to total loss of scalp hair (alopecia totalis) or to loss of all scalp and body hair (alopecia universalis). The interleukin-1 receptor antagonist (IL-1RN) gene was found to be associated with more severe clinical outcome in several chronic inflammatory diseases, including alopecia areata. The IL-1RN*2 allele was found to be associated with alopecia areata severity in a British case-control study. In this paper, we analyzed alopecia areata probands in a family-based sample (n = 131 parent-offspring trios) to study the association between alleles of the IL-1RN and various phenotypes of alopecia areata. In considering all patients with any form of alopecia areata, no association was found with IL-1RN. IL-1RN*2 allele was not associated with alopecia totalis and alopecia universalis. A borderline association was observed between IL-1RN and patchy alopecia areata but it was not statistically significant (p =0.06). We also observed an association between IL1-RN*1 allele and patchy alopecia areata (p =0.045).

Alleles↗
PubMed2002

Update on erythrodermic cutaneous T-cell lymphoma: report of the International Society for Cutaneous Lymphomas.

Two conferences were sponsored by the International Society for Cutaneous Lymphomas (ISCL) to gain consensus on definitions and terminology for clinical use in erythrodermic cutaneous T-cell lymphoma (E-CTCL). Three subsets of E-CTCL were defined: Sézary syndrome ("leukemic phase" E-CTCL), erythrodermic mycosis fungoides (secondary E-CTCL that develops in patients with mycosis fungoides), and E-CTCL, not otherwise defined. The hematologic criteria recommended for Sézary syndrome are intended to identify patients with a worse prognosis compared with the other E-CTCL subsets and consist of one or more of the following: (1) an absolute Sézary cell count of 1000 cells/mm3 or more; (2) a CD4/CD8 ratio of 10 or higher caused by an increase in circulating T cells and/or an aberrant loss or expression of pan-T cell markers by flow cytometry; (3) increased lymphocyte counts with evidence of a T-cell clone in the blood by the Southern blot or polymerase chain reaction technique; or (4) a chromosomally abnormal T-cell clone. For staging purposes, it is proposed that these criteria define the B2 blood rating and that the B2 rating be considered equivalent to nodal involvement.

Dermatitis, Exfoliative↗