-
[show abstract]
[hide abstract]
ABSTRACT: Dendritic cells (DCs) are potent antigen-presenting cells that help orchestrate the innate and adaptive immune systems to induce tolerance and immunity. They are diversified in their phenotypes, stages of maturation, degrees of activation, and functions. Several subtypes of DCs exist among human lymphoid tissues, non-lymphoid tissues, and in peripheral blood. In the skin, three types of DCs are described: Langerhans cells (LCs), dermal dendritic cells (DDCs), and plasmacytoid dendritic cells (pDCs). In the peripheral blood, myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells are well described. Dysfunctional DCs are found in many autoimmune disorders, allergies, and cancers. In this paper, we focus on DCs as related to cutaneous T cell lymphomas (CTCLs). Abnormal DC number and defective DC function are found in the blood of patients with advanced stage Sézary syndrome (SS), a leukemic variant of CTCLs. Extracorporeal photopheresis (ECP), an effective therapy for erythrodermic CTCLs, is thought to work by inducing apoptosis of tumor cells and monocytes-derived DCs. DC vaccination has been carried out successfully in some patients with CTCLs when combined with immune modifiers like toll like receptor agonists, which may enhance the function of DCs. However, DCs may perform a dual role in the pathogenesis of CTCLs. Immature DCs (langerhans cells) could promote the survival of malignant T cells. Further understanding of DCs and their role in CTCLs can help us to uncover the pathogenesis of this disease and to further explore the therapeutic uses of DCs.
Giornale Italiano di Dermatologia e Venereologia 04/2011; 146(2):103-13.
-
[show abstract]
[hide abstract]
ABSTRACT: Alopecia areata (AA) is an organ-specific autoimmune disease characterized by folliculotropic T-cell infiltrates around anagen-stage hair follicles. The role of T helper (Th)1 and Th2 cytokines in the pathogenesis of AA have not been established.
To determine whether serum cytokine profiles define the severity of the AA phenotype or are affected by co-existent atopy.
In total, 17 serum cytokines were measured and compared in 269 patients with AA of varying severity with and without atopy and 18 unrelated controls.
Of the 269 patients with AA, 96% had active disease and 54% were atopic. The disease phenotype was transient patchy AA in 27 patients, persistent patchy AA in 89 and alopecia totalis or alopecia universalis in 153. Levels of Th1, interleukin (IL)-1 receptor antagonist (ra) and IL-8 levels were higher in all patients with AA than in controls. IL-1alpha, IL-12 and tumour necrosis factor-alpha levels were higher in patients with AA and atopy than in patients with AA without atopy.
Increased Th1 serum cytokines (IL-2, IL-12 and interferon-gamma) and IL-1ra levels are associated with AA regardless of disease severity or the presence of atopy.
Clinical and Experimental Dermatology 10/2009; 35(4):409-16. · 1.20 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To determine incidence and risk factors for developing lymphoma in patients with lymphomatoid papulosis (LyP), and to identify putative triggers amenable to treatment.
The prognostic effect of severity of LyP, viral infection by history or serology, beta-2-microglobulin level, lactic dehydrogenase (LDH) level, and CD4 : CD8 ratio were evaluated using logistic regression models. Responses to prophylactic or palliative treatment were assessed.
In total, 84 patients (38 men, 46 women, median age at diagnosis 48.5 years) were identified. Of these, 34 (40%) were also diagnosed with one or more lymphomas: 16 (19%) had mycosis fungoides, 15 (17%) had primary cutaneous anaplastic large-cell lymphoma (pcALCL), 2 had both MF and pcALCL, and 1 had MF with large cell transformation and 1 had peripheral T-cell lymphoma. Of the 61 people presenting with LyP alone, only 11 (18%) subsequently developed lymphoma, with a median onset of 17.6 years (95% CI: 4, not obtained). Men were 2.5 times more likely than women to develop lymphoma (P = 0.04). Exposure to Epstein-Barr virus (EBV) was associated with an increase in incidence of 4.8 times (P = 0.16). Treatment for a putative infectious trigger resulted in improvement for 15 of 24 patients (63%).
Referral bias may explain the higher (40%) incidence of lymphoma in this population of LyP patients, compared with the 10-20% incidence commonly cited in the literature. In the subset of patients presenting with LyP alone, only 18% later developed lymphoma. Male patients or patients with prior EBV infection may have a higher risk for developing lymphoma, and some patients improved with treatment of putative infectious triggers.
Clinical and Experimental Dermatology 02/2009; 34(5):576-81. · 1.20 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Mycosis fungoides (MF) and Sézary syndrome (SS), variants of cutaneous T-cell lymphoma, may arise from antigen-driven clonal expansion and accumulation of helper-memory T cells. Superantigens from Staphylococcus aureus can stimulate T cells.
(i) To determine the prevalence of S. aureus carriage in nares and skin in patients with MF/SS compared with historical rates in other conditions. (ii) To determine whether eradication of S. aureus carriage is associated with clinical improvement. Methods Skin and nares cultures were performed prospectively. Patients with positive nares and skin cultures were treated with oral antibiotics and intranasal mupirocin 2% and samples were taken for reculturing at 3 days, 4 weeks and 8 weeks. An exact binomial test was used to compare the carriage rates among different groups.
Among 106 patients with MF/SS, 67 (63%) had skin colonization and 57 (54%) had nasal colonization. Staphylococcus aureus was isolated from 44 patients, 33 (31%) each from skin and nares. Colonization was highest in erythrodermic SS (48%), similar to atopic dermatitis (64%), and lowest in MF without erythroderma (26%), psoriasis (21%), and the general population (10%). Oral and topical antibiotics eradicated S. aureus colonization in nares in 28 of 33 (85%) patients and in MF skin lesions in 30 of 33 (91%) patients at 4-8 weeks, with rapid clinical improvement seen in 58% of S. aureus-colonized patients.
Staphylococcal carriage in nares and skin lesions of patients with MF is similar to that in atopic dermatitis. Eradication of staphylococci from the skin is possible with treatment and was associated with clinical improvement.
British Journal of Dermatology 08/2008; 159(1):105-12. · 3.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Sezary syndrome (SS) is a T-cell lymphoproliferative disorder involving the blood, skin and lymph nodes associated with erythroderma. Other cutaneous manifestations of SS include palmoplantar keratoderma, ectropion, and alopecia. Two clinical patterns of SS can be defined: “secondary” SS arising from systemic spread of long-standing mycosis fungoides (MF) and “primary” SS with a much shorter prodromal phase characterized by pruritus, xerosis and scaling culminating in erythroderma. Most previous studies examining the histological features of SS have not distinguished between these two different clinical patterns, and have emphasized that the histological features of SS mostly resemble those of typical MF, including epidermotropism and/or band-like superficial dermal lymphoid infiltrates. In this study, we have concentrated on the histological findings of primary SS and correlated them with the clinical and hematologic parameters at the time of skin biopsy. We note that dermal perivascular lymphoid infiltrates predominate in a majority of primary SS cases, raising the differential diagnosis of benign dermatoses, rather than resembling the classical pattern of MF. This impression is further complicated by commonly observed epidermal changes such as spongiosis, acanthosis and parakeratosis that are likely secondary to tumor-associated pruritus and secondary lichenification.
Journal of Cutaneous Pathology 06/2008; 32(1):85 - 85. · 1.56 Impact Factor
-
N Apisarnthanarax,
M Donato,
M Körbling,
D Couriel,
J Gajewski,
S Giralt,
I Khouri,
C Hosing,
R Champlin, M Duvic,
P Anderlini
[show abstract]
[hide abstract]
ABSTRACT: 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.
Bone Marrow Transplantation 04/2003; 31(6):459-65. · 3.75 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 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.
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.
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.
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.
International Journal of Dermatology 02/2003; 42(2):116-22. · 1.14 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 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.
International journal of dermatology 01/2003; 42(2):116 - 122. · 1.18 Impact Factor
-
A H Sarris,
A Phan, M Duvic,
J Romaguera,
P McLaughlin,
O Mesina,
K King,
L J Medeiros,
G Z Rassidakis,
B Samuels,
F Cabanillas
[show abstract]
[hide abstract]
ABSTRACT: 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.
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.
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.
TMTX is active with acceptable toxicity in this population and merits further investigation.
Journal of Clinical Oncology 07/2002; 20(12):2876-80. · 18.37 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 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.
Photochemistry and Photobiology 01/2002; 74(6):805-10. · 2.41 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The treatment of cutaneous T-cell lymphoma (CTCL) is continually evolving, as new and emerging drugs are added to the growing arsenal of CTCL therapy. The availability of newly approved investigational therapies, such as bexarotene, denileukin diftitox (DAB389- IL2), monoclonal antibodies and novel chemotherapeutic agents, adds complexity to decisions on the management and treatment of CTCL patients. In formulating a treatment plan, therapeutic options are best approached through consideration of overall clinical staging (stage IA-IVB) and skin staging (T1-T4), which affect prognosis and the characteristics of each individual patient's disease. This article will present and discuss the optimal therapeutic agents for all clinical stages of CTCL patients, based on currently available and investigational agents.
Expert Review of Anti-infective Therapy 11/2001; 1(3):403-20. · 2.65 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 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.
Dermatologic Clinics 11/2001; 19(4):737-48. · 2.16 Impact Factor
-
A H Rook,
M H Zaki,
M Wysocka,
G S Wood, M Duvic,
L C Showe,
F Foss,
M Shapiro,
T M Kuzel,
E A Olsen,
E C Vonderheid,
R Laliberte,
M L Sherman
[show abstract]
[hide abstract]
ABSTRACT: 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.
Annals of the New York Academy of Sciences 10/2001; 941:177-84. · 3.15 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 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.
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.
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.
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.
International Journal of Dermatology 09/2001; 40(8):505-11. · 1.14 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma (CTCL) and arises from the accumulation and clonal proliferation of epidermotropic, CD4+/CD45RO+ (helper/memory) T lymphocytes. Loss of CD8+ CTLs within MF lesions is associated with poor prognosis and disease progression. Because T-lymphocyte apoptosis is controlled mainly through the Fas/Fas ligand (FasL) pathway and tumor cells may escape immune surveillance by expressing FasL, triggering apoptosis of tumor-infiltrating T lymphocytes, we studied the role of this system in MF. T-cell subsets, Fas/FasL expression, and apoptosis were evaluated in normal and lesional skin biopsy specimens from 21 patients with all stages of MF and in cultured CTCL cell lines (MJ, HUT78, and HH) using immunohistochemistry, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and Western blotting. MF lesions and paired, clinically "normal," uninvolved skin showed increased numbers of both TUNEL-positive epidermal keratinocytes (n = 13; F = 31.146; P < 0.01, ANOVA) and dermal lymphocyte infiltrates (n = 13; F = 15.825, P < 0.01, ANOVA) compared with the normal control skin. FasL expression was highest in lesional epidermal keratinocytes, in CTCL tumor cell lines, and in dermal tumor lymphocytes in MF lesions compared with uninvolved skin. FasL colocalized with CD45RO+ cells. CD8+ cells in or adjacent to CD45RO+ cells were positively labeled by TUNEL for apoptosis. In addition, CD8+ cell numbers were decreased in areas in which FasL+ tumor cells were abundant (2.01 +/- 0.86%) compared with non-FasL expressing areas (13.53 +/- 3.54%; P < 0.02). These results suggest that a potential mechanism of tumor immune escape in MF is FasL-mediated apoptosis of infiltrating CD8+ CTLs.
Clinical Cancer Research 09/2001; 7(9):2682-92. · 7.74 Impact Factor
-
Archives of Dermatology 09/2001; 137(8):1071-2. · 3.89 Impact Factor
-
Journal of the American Academy of Dermatology 09/2001; 45(2):318. · 3.99 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 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.
American Journal of Clinical Pathology 07/2001; 115(6):885-92. · 2.60 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The purine nucleoside phosphorylase inhibitor peldesine is a new agent being evaluated as a T-cell inhibitor.
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).
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.
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).
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.
Journal of the American Academy of Dermatology 06/2001; 44(6):940-7. · 3.99 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 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.
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.
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.
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.
Journal of Clinical Oncology 06/2001; 19(9):2456-71. · 18.37 Impact Factor
