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M Duvic

Publications and source records attributed to M Duvic.

At least 19 recordsLinked to original sources
PubMed2006

Minimizing adverse side-effects of oral bexarotene in cutaneous T-cell lymphoma: an expert opinion.

Bexarotene is an oral retinoid therapy that is effective for the treatment of early and advanced-stage cutaneous T-cell lymphoma (CTCL) in patients who have failed on other therapies. However, bexarotene treatment is associated with unavoidable side-effects, in particular hypertriglyceridaemia and hypothyroidism, which are manageable with adequate concomitant medications and are reversible on cessation of treatment. A pragmatic strategy for minimizing bexarotene-associated hypertriglyceridaemia and hypothyroidism is suggested, based on data from the studies with bexarotene in CTCL and on day-to-day experience with this agent in the clinical setting. The strategy anticipates that these common adverse events are likely to occur and recommends the early use of preventive therapy to lower triglycerides and elevate thyroid hormone levels in the blood, followed by subsequent monitoring, dose adjustment during bexarotene treatment, and titration of the daily bexarotene dose from 150 to 300 mg m(-2), which is optimal for most patients. When further information becomes available on how bexarotene interacts with lipid metabolism and thyroid function, the management approach suggested here may need to be changed.

Anticarcinogenic Agents↗
PubMed2003

Extracorporeal photopheresis therapy in the management of steroid-refractory or steroid-dependent cutaneous chronic graft-versus-host disease after allogeneic stem cell transplantation: feasibility and results.

We conducted a retrospective analysis of all allogeneic stem cell transplantation (ASCT) patients started on extracorporeal photopheresis (ECP) for the management of steroid-dependent (SD) or steroid-refractory (SR) cutaneous chronic graft-versus-host disease (cGVHD) following ASCT during a 36-month period (9/98-8/01). Only SD or SR patients who were treated by ECP after day 100 and who received at least 4 weeks of ECP were considered evaluable for this analysis. Out of 64 ASCT patients reviewed, 32 patients met the inclusion criteria. All 32 patients had been previously treated with systemic corticosteroids with 11 (34%) being SR and 21 (66%) SD. Cutaneous cGVHD was extensive in 28 patients (88%) and was accompanied by visceral (hepatic, gastrointestinal) cGVHD in 23 patients (72%). The 32 evaluated patients had received a median of three prior therapies before ECP, most commonly systemic corticosteroids, tacrolimus, and mycophenolate mofetil. Patients received a median of 36 ECP sessions (range 12-98) over a median of 5.3 months (range 1-28), with a median of six sessions per month. The complete response (CR) rate was 22% (n=7) and the partial response rate was 34% (n=11). In all, 28 patients were on systemic corticosteroid therapy at ECP initiation and 18 patients achieved 50% dose reduction while on ECP, yielding a 64% steroid-sparing response rate. Of seven CRs, five are ongoing. A total of 11 (34%) patients have died after ECP, with all cases due to visceral cGVHD or cGVHD-related infectious complications. All 21 surviving patients remain on at least some immunosuppressive cGVHD therapy (including ECP in eight). Overall, ECP displays a substantial response rate and, in particular, steroid-sparing activity in SR/SD extensive cutaneous cGVHD. However, most patients continue to require at least some chronic therapy and cGVHD-related morbidity and mortality remain high.

Adolescent↗
PubMed2003

Mycosis fungoides associated with malignant melanoma and dysplastic nevus syndrome.

BACKGROUND: The increased risk of second malignancies, including nonmelanoma skin cancers, in cutaneous T-cell lymphoma (CTCL) patients has been well documented. However, relatively few studies of malignant melanoma in CTCL patients have been reported. METHODS: A database of 250 CTCL patients registered over a 3-year period was searched to identify patients with diagnoses of both mycosis fungoides (MF) and malignant melanoma. RESULTS: We identified six cases of MF associated with malignant melanoma and one associated with dysplastic nevus syndrome, which is a marker of increased risk of melanoma. In four patients, melanoma was diagnosed along with or before MF. In the remaining two patients, MF was diagnosed prior to melanoma, although dysplastic nevi were noted at the time MF was diagnosed. These two patients received treatment for their MF (one with topical nitrogen mustard and another with radiation therapy and nitrogen mustard) prior to the histologic confirmation of melanoma. Six patients had early stages of MF (IA or IB), while one patient presented with simultaneous erythrodermic mycosis fungoides involving the lymph nodes as well as melanoma metastatic to the lymph nodes from an unknown primary. CONCLUSION: There is an elevated prevalence of malignant melanoma in MF patients compared to the general US population (P < 0.00001) with a relative risk of 15.3 for observing malignant melanoma in MF patients (95% confidence interval 7.0-33.8). Possible pathologic links between the two diagnoses include effects of mycosis fungoides therapies, immunosuppression secondary to mycosis fungoides, and genetic alterations in the p16 tumor suppressor protein.

Adult↗
PubMed2002

Trimetrexate in relapsed T-cell lymphoma with skin involvement.

PURPOSE: Methotrexate (MTX) is active against lymphomas, but transport or polyglutamylation mutations confer MTX resistance. Because trimetrexate (TMTX) enters cells by passive diffusion and is not polyglutamylated, its activity in relapsed T-cell lymphoma was investigated. PATIENTS AND METHODS: Eligible patients had histologically confirmed relapsed T-cell lymphoma involving the skin, had received more than one previous regimen, were older than 16 years, had normal organ function, and had no CNS disease or serious infections, including human immunodeficiency virus. TMTX (200 mg/m(2)) was given intravenously every 14 days without topical or systemic corticosteroids. Patients who responded received up to 12 doses. RESULTS: Twenty patients were assessable for response. Median age was 59 years (range, 45 to 87 years); 13 patients were men. Three patients had anaplastic large-cell lymphoma, 15 had mycosis fungoides or Sézary syndrome (14 with large-cell transformation), and two had peripheral T-cell lymphoma. Serum lactate dehydrogenase was high in 35%, and beta-2 microglobulin was more than 3.0 mg/L in 35% of patients. The median number of previous regimens was three (range, two to 15) and included MTX in five patients. Disease was refractory to the regimen immediately preceding TMTX in 85% of patients. Responses were complete in one and partial in eight patients (overall response rate, 45%). Two of five patients previously treated with MTX responded. Grade 3 or 4 mucositis was observed after 4%, infection after 3%, neutropenic fever after 6%, neutrophils less than 100/microL after 4%, and platelets less than 10,000/microL after 3% of TMTX doses. CONCLUSION: TMTX is active with acceptable toxicity in this population and merits further investigation.

Aged↗
PubMed2001

Bexarotene is effective and safe for treatment of refractory advanced-stage cutaneous T-cell lymphoma: multinational phase II-III trial results.

PURPOSE: Cutaneous T-cell lymphomas (CTCL) are malignancies of T cells appearing as skin lesions and are responsive to retinoid therapy. Safety and efficacy of a novel RXR-selective retinoid (rexinoid) bexarotene (Targretin, LGD1069; Ligand Pharmaceuticals Inc, San Diego, CA) was evaluated as a single-agent oral therapy administered once daily in an open-label study in patients with refractory advanced-stage CTCL. PATIENTS AND METHODS: Ninety-four patients with biopsy-confirmed CTCL in advanced stages (IIB-IVB) were enrolled at 26 centers. Fifty-six patients received an initial dose of 300 mg/m2/d oral bexarotene and 38 started at more than 300 mg/m2/d. RESULTS: Clinical complete and partial responses were reported by Primary End point Classification for the study in 45% (25 of 56) of patients enrolled at 300 mg/m2/d dosing. At more than 300 mg/m2/d, 55% (21 of 38) of patients responded, including 13% (five of 38) clinical complete. For the 300 mg/m2/d initial dose group, the rate of relapse after response was 36% and the projected median duration of response was 299 days. Improvements were also seen in overall body-surface area involvement, median index lesion surface area, adenopathy, cutaneous tumors, pruritus, and CTCL-specific quality of life. The most frequent drug-related adverse events included hypertriglyceridemia (associated rarely with pancreatitis), hypercholesterolemia, hypothyroidism, and headache. CONCLUSION: Bexarotene is the first in a novel class of pharmacologic agents, the RXR-selective retinoids, or rexinoids. Bexarotene is orally administered, safe, and generally well tolerated with reversible side effects, and is effective for the treatment of advanced, refractory CTCL.

Adult↗
PubMed2001

Pivotal phase III trial of two dose levels of denileukin diftitox for the treatment of cutaneous T-cell lymphoma.

PURPOSE: The objective of this phase III study was to determine the efficacy, safety, and pharmacokinetics of denileukin diftitox (DAB389IL-2, Ontak [Ligand Pharmaceuticals Inc, San Diego, CA]) in patients with stage Ib to IVa cutaneous T-cell lymphoma (CTCL) who have previously received other therapeutic interventions. PATIENTS AND METHODS: Patients with biopsy-proven CTCL that expressed CD25 on > or = 20% of lymphocytes were assigned to one of two dose levels (9 or 18 microg/kg/d) of denileukin diftitox administered 5 consecutive days every 3 weeks for up to 8 cycles. Patients were monitored for toxicity and clinical efficacy, the latter assessed by changes in disease burden and quality of life measurements. Antibody levels of antidenileukin diftitox and anti-interleukin-2 and serum concentrations of denileukin diftitox were also measured. RESULTS: Overall, 30% of the 71 patients with CTCL treated with denileukin diftitox had an objective response (20% partial response; 10% complete response). The response rate and duration of response based on the time of the first dose of study drug for all responders (median of 6.9 months with a range of 2.7 to more than 46.1 months) were not statistically different between the two doses. Adverse events consisted of flu-like symptoms (fever/chills, nausea/vomiting, and myalgias/arthralgias), acute infusion-related events (hypotension, dyspnea, chest pain, and back pain), and a vascular leak syndrome (hypotension, hypoalbuminemia, edema). In addition, 61% of the patients experienced transient elevations of hepatic transaminase levels with 17% grade 3 or 4. Hypoalbuminemia occurred in 79%, including 15% with grade 3 or 4 changes. Tolerability at 9 and 18 microg/kg/d was similar, and there was no evidence of cumulative toxicity. CONCLUSION: Denileukin diftitox has been shown to be a useful and important agent in the treatment of patients whose CTCL is persistent or recurrent despite other therapeutic interventions.

Adult↗
PubMed2001

Primary cutaneous non-Hodgkin's lymphoma of Ann Arbor stage I: preferential cutaneous relapses but high cure rate with doxorubicin-based therapy.

PURPOSE: Establish frequency, presenting features, response and relapse patterns, and outcome of primary cutaneous non-Hodgkin's lymphoma (PCNHL). PATIENTS AND METHODS: Review of untreated patients, older than 16 years, presenting between 1971 and 1993 with cutaneous lymphoma, not mycosis fungoides, and Ann Arbor stage I. RESULTS: We identified 46 patients, 27 males, with median age of 57 years. Treatment was radiotherapy in 10 patients, doxorubicin-based therapy in 33 patients that was followed by radiotherapy in 25 patients, and other combination with radiotherapy in one patient. The complete response rate was 95%. After a median follow-up of 140 months (range, 61 to 284 months), 18 patients have relapsed, and 14 have died from lymphoma. The first failure was exclusively cutaneous in 50% of relapses. For the 44 treated patients, progression-free survival (PFS; actuarial +/- SE) was 61% +/- 7% and survival was 58% +/- 9% at 12 years. For the 18 patients with diffuse large B-cell lymphoma, after doxorubicin-based regimens, PFS was 71% +/- 12% (P = .0003) versus 0% after radiotherapy; survival was 77% +/- 12% versus 25% +/- 22% (P = 004), respectively. For the nine patients with follicular center-cell lymphoma treated with combined modality, the 12-year PFS was 89% +/- 11% and survival 70% +/- 18%. CONCLUSION: PCNHL is rare, and its first relapse is exclusively cutaneous in 50% of patients. Patients with diffuse large B-cell lymphoma are curable with doxorubicin-based regimens but not with radiotherapy. Prospective studies in PCNHL should define the cytogenetics, the basis for cutaneous tropism, the prognosis of histologic subtypes, and the role of radiotherapy.

Adult↗
PubMed2001

Cutaneous T-cell lymphoma. New immunomodulators.

During the most recent decades, much knowledge has been gained concerning the immunologic and pathologic mechanisms of CTCL. The development of immunomodulators aimed at correcting aberrations in immunology and cellular growth and differentiation reflects this increased understanding. This review of the currently available immune-response modifying drugs shows that recombinant forms of natural cytokines and retinoids can be developed with tolerable toxicity profiles and substantial efficacy. Although milestone drugs such as bexarotene have been approved by the FDA- for treatment of CTCL, other agents such as IL-12 may also have a place in treatment of the disease. Even though unapproved, IFN-alpha may be the most active single immunomodulating agent against CTCL. It seems that further delineation of CTCL cytokine profile changes and immunologic aberrations are key in developing effective immunomodulators that are able to reverse these alterations.

Adjuvants, Immunologic↗
PubMed2001

Transient CD30+ nodal transformation of cutaneous T-cell lymphoma associated with cyclosporine treatment.

BACKGROUND: Mycosis fungoides (MF) may evolve from pre-existing chronic atopic or psoriasiform dermatitis and the histology can be equivocal. Early patch and plaque lesions of MF may evolve into tumors, disseminate to lymph nodes, bone marrow, and internal organs, and/or undergo transformation to a large cell size. METHODS: A patient with a history of "atopic dermatitis" followed by "psoriasis" rapidly developed exfoliative erythroderma and axillary lymphadenopathy following treatment with cyclosporine. At presentation, biopsy specimens of skin lesions and lymph nodes and staging were obtained. We present the treatment and follow-up of this patient and review the medical literature for similar cases. RESULTS: Multiple skin biopsy specimens from lesions revealed changes consistent with low-grade, cutaneous, T-cell lymphoma (MF) without evidence of large cell transformation and psoriasiform epidermal hyperplasia. CD30+ large cell transformation was present in the lymph node. Adenopathy and erythroderma resolved without systemic therapy following discontinuation of cyclosporine and treatment with psoralen/ultraviolet A (PUVA), isotretinoin, interferon-alpha, and antimicrobials. CONCLUSIONS: This case documents a close relationship between atopy, psoriasis, and the development of cutaneous T-cell lymphoma, and illustrates that an immunosuppressive agent, cyclosporine, can dramatically alter the course of the disease.

Adult↗
PubMed2001

A phase III, randomized, double-blind, placebo-controlled study of peldesine (BCX-34) cream as topical therapy for cutaneous T-cell lymphoma.

BACKGROUND: The purine nucleoside phosphorylase inhibitor peldesine is a new agent being evaluated as a T-cell inhibitor. OBJECTIVE: We attempted to determine the efficacy of peldesine (BCX-34) in a 1% dermal cream formulation as a treatment for cutaneous T-cell lymphoma (CTCL). METHODS: Ninety patients with patch and plaque phase CTCL, histologically confirmed by a referee dermatopathologist, were enrolled in a randomized, double-blind, placebo-controlled study. BCX-34 dermal cream 1% or the vehicle cream (as a placebo control) was applied twice daily to the entire skin surface for up to 24 weeks. Efficacy of the topical therapy was assessed in terms of complete or partial (> or = 50%) clearing of patches and plaques. RESULTS: Of the 89 patients able to be examined, 43 received BCX-34 and 46 received the placebo vehicle cream. One patient withdrew early and was not analyzed. The two groups were well balanced for potential prognostic factors. A total of 28% (12/43) of the patients treated with BCX-34 showed a response, but 24% (11/46) of patients who received vehicle also responded (P =.677). CONCLUSION: Although BCX-34 dermal cream 1% was not significantly better than the control as therapy for patch and plaque-phase CTCL, this appears to be the first published placebo-controlled trial evaluating treatment for CTCL. Whether the vehicle cream has more than a placebo therapeutic effect is unclear. The relatively high (24%) placebo response rate should be kept in mind in assessing other treatments for early-stage CTCL.

Administration, Cutaneous↗
PubMed2001

The role for interleukin-12 therapy of cutaneous T cell lymphoma.

Recent phase I and phase II trials using recombinant human interleukin-12 (rhIL-12) for cutaneous T cell lymphoma (CTCL) have been completed. Observations on 32 evaluable patients revealed an overall response rate approaching 50 percent. Biopsy of regressing lesions revealed an increase in numbers of CD8+ and/or TIA-1+ T cells. These results suggest that rhIL-12 may induce lesion regression by augmenting antitumor cytotoxic T cell responses. Future trials will be focused on strategies for further immune enhancement by the concomitant use of additional immune augmenting cytokines with rhIL-12.

Antigens, Differentiation, T-Lymphocyte↗
PubMed2001

The T-cell chemokine receptor CXCR3 is expressed highly in low-grade mycosis fungoides.

Three chemokines, Mig, IP-10, and I-TAC, are expressed highly in the epidermis. We examined the expression of the receptor for these chemokines, CXCR3, in cutaneous T-cell lymphoma. We compared CXCR3 expression with that of cutaneous lymphocyte antigen (CLA) and the activation marker CD30. CXCR3 was expressed by at least a subset of tumor lymphocytes in all 25 cases of low-grade mycosis fungoides (MF), with most cells positive in 20 cases. In progressed or transformed MF, CXCR3 expression was noted in 5 of 22 cases. In 4 of 5 MF cases with sequential biopsy specimens, large cell transformation was accompanied by loss of CXCR3 expression. In contrast, CLA was expressed in 35 of 42 MF cases with no significant differences in expression level between low-grade and transformed cases. In other lymphomas, CXCR3 was expressed in 4 of 4 cases of lymphomatoid papulosis, 3 of 4 cases of CD8+ cutaneous T-cell lymphoma, and 3 of 6 cases of systemic T-cell lymphoma in skin, but not in 10 cases of cutaneous anaplastic large cell lymphoma. CXCR3 expression was associated with epidermotropic T-cell tumors but was largely absent in dermal-based tumors. This phenotypic change likely influences the loss of epidermal localization.

Adolescent↗
PubMed2001

Absence of CD26 expression is a useful marker for diagnosis of T-cell lymphoma in peripheral blood.

We report flow cytometric characterization of surface CD26 expression in 271 peripheral blood samples from 154 patients evaluated for the presence of a T-cell lymphoproliferative disorder, primarily mycosis fungoides/Sézary syndrome (MF/SS). The presence of morphologically identifiable tumor cells on peripheral blood smears was the criterion for lymphomatous involvement. In 66 of 69 samples from 28 patients, we identified an abnormal CD26-/dim T-cell population that was distinct from the variable CD26 expression seen in normal peripheral blood T cells. This population was CD26- in 23 patients and weakly CD26+ in 5 patients. CD7 was more variably expressed in MF/SS tumor cells, allowing recognition of a distinct, quantifiable abnormal T-cell population in only 34 of 69 involved samples. An increased CD4/CD8 ratio and lower surface expression of CD4 in tumor cells also helped separate the CD26-/dim atypical population for quantification. In 35 blood samples from other types of T-cell tumors, tumor cells in 10 of 11 morphologically involved cases showed absent/dim CD26. Although capable of detecting abnormalities in most cases of MF/SS, CD7 expression does not provide as clear a separation of the neoplastic population and can be replaced by CD26 staining in routine peripheral blood flow cytometric screening of MF/SS patients.

Antigens, CD7↗
PubMed2001

Activation of HIV in human skin by ultraviolet B radiation and its inhibition by NFkappaB blocking agents.

To determine whether ultraviolet B (UVB) irradiation leads to activation of HIV in human skin, we conducted prospective and controlled studies in two academic medical centers in Texas from July 1995 to April 1999. HIV-positive patients with UV-treatable skin diseases were enrolled at each center, 18 subjects at one and 16 at the other. In one center, specimens from lesional and nonlesional skin biopsies were taken before and after sham- or UVB-irradiation administered in vivo or in vitro. In the other center, UVB phototherapy was administered three times weekly and specimens from skin biopsies were taken before and after 2 weeks (six treatments). Cutaneous HIV load was assessed using reverse transcriptase-polymerase chain reaction and reverse transcriptase-polymerase chain reaction in situ hybridization. UVB irradiation led to a 6-10-fold increase in the number of HIV in skin. To ascertain a role for nuclear factor kappa B (NFkappaB) in UVB-inducible HIV activation, two types of blockers, NFkappaB oligonucleotide decoy and sodium salicylate, were tested; each inhibited UVB-inducible HIV activation in skin partially. We conclude that UVB irradiation leads to increased numbers of HIV in human skin via processes that include release of cytoplasmic NFkappaB.

HIV↗