Clinical characteristics, risk factors and long-term outcome of 114 patients with folliculotropic mycosis fungoides.

Folliculotropic mycosis fungoides (FMF) is a distinct variant of mycosis fungoides (MF) where atypical T-cells invade the hair follicles. The objective was to assess the clinical features, risk factors for progression, long-term outcome and response to treatment modalities in a large cohort of FMF patients. We, therefore, conducted a single-center retrospective study, reviewing 114 patients with FMF seen from 1987 to 2015 at the cutaneous T-cell lymphoma clinic of the MD Anderson Cancer Center. The mean age at diagnosis of FMF was 57.1 ± 13.5 years. The male to female ratio was 1.2:1. MF stage IA (n = 50, 43.9%) was the most common diagnosed stage, followed equally by stages IB and IIB (n = 23, 20.2%, respectively). Eighty-six patients (75.4%) suffered from pruritus. Concomitant hair loss was observed in 37 (32.5%) subjects. The median number of different treatment modalities used per patient was 4 (range 1-12). Low-dose radiation was beneficial in clearing therapy refractory lesions. The overall survival was influenced by several factors, including advanced age (>65), late stages and the presence of large cell transformation (LCT). Thirty-three of 113 patients (29.2%) progressed to more advanced stages and 26 (23.0%) died, with the cause of death being MF in 11 (9.7%) subjects. In conclusion, patients with FMF have a worse overall 10-year survival rate compared with other MF variants. Several factors, including stage, advanced age and the presence of LCT impact survival. Multiple different treatment approaches may be needed to achieve a good clinical response and to prevent disease progression.

Phase 2 trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) for refractory cutaneous T-cell lymphoma (CTCL).

The activity and safety of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid, SAHA) were evaluated in patients with refractory cutaneous T-cell lymphoma (CTCL). Group 1 received vorinostat 400 mg daily, group 2 received vorinostat 300 mg twice daily for 3 days with 4 days rest, and group 3 received vorinostat 300 mg twice daily for 14 days with 7 days rest followed by 200 mg twice daily. Treatment continued until disease progression or intolerable toxicity. The primary objective was to determine the complete and partial response (PR) rate. Time to response (TTR), time to progressive disease (TTP), response duration (DOR), pruritus relief, and safety were determined. Thirty-three patients who had received a median of 5 prior therapies were enrolled. Eight patients achieved a PR, including 7 with advanced disease and 4 with Sézary syndrome. The median TTR, DOR, and TTP for responders were 11.9, 15.1, and 30.2 weeks, respectively. Fourteen of 31 evaluable patients had pruritus relief. The most common drug-related AEs were fatigue, thrombocytopenia, diarrhea, and nausea. The most common grade 3 or 4 drug-related AEs were thrombocytopenia and dehydration. Vorinostat demonstrated activity in heavily pretreated patients with CTCL. The 400 mg daily regimen had the most favorable safety profile and is being further evaluated.

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

Treatment of cutaneous T cell lymphoma: current status and future directions.

The treatment of cutaneous T cell lymphoma (CTCL), which includes mycosis fungoides and Sezary syndrome, has been in a state of continual change over recent decades, as new therapies are constantly emerging in the search for more effective treatments for the disease. However, prognosis and survival of patients with CTCL remains dependent upon overall clinical stage (stage IA-IVB) at presentation, as well as response to therapy. Past therapies have been limited by toxicity or the lack of consistently durable responses, and few treatments have been shown to actually alter survival, especially in the late stages of disease. Even aggressive chemotherapy has not been shown to improve overall survival compared to conservative sequential therapy in advanced disease, and adds the risk of immunosuppressive complications. Over the last decade, extracorporeal photopheresis has been the only single treatment that has been shown to improve survival in patients with Sezary syndrome, although its true efficacy and place in combination therapy remain unclear. Much of the focus of current research has been on combinations of skin-directed therapies and biological response modifiers, which improve response rates. The results of various trials over the years have also brought into favor the use of post-remission maintenance therapy with topical corticosteroids, topical mechlorethamine (nitrogen mustard), interferon-alpha, or phototherapy to prevent disease relapse. Recent novel developments in CTCL therapy include oral bexarotene, a retinoid X receptor-selective retinoid that has activity in all stages of CTCL, and the topical gel formulation of bexarotene, which plays a role in treating localized lesions. US Food and Drug Administration (FDA)-approved, oral systemic bexarotene has the advantage of a 48% overall response rate at a dosage of 300 mg/m(2)/day, and avoids immunosuppression and risk of central line and catheter-related infectious complications that are associated with other systemic therapies. Monitoring of triglycerides and use of concomitant lipid-lowering agents and thyroid replacement is required in most patients. Also recently FDA-approved, denileukin diftitox is the first of a novel class of fusion toxin proteins and is selective for interleukin-2R (CD25+) T cells, targeting the malignant T cell clones in CTCL. Denileukin diftitox is associated with capillary leak syndrome in 20 to 30% of patients, which may be ameliorated by hydration and corticosteroids. Higher response rates are possible by combining bexarotene with "statin" drugs and active CTCL therapies. Studies are being conducted on combining bexarotene and denileukin diftitox with other modalities. Biological response modifier therapies that are in current or future investigational trials include topical tazarotene, pegylated interferon, interleukin-2, and interleukin-12. At the forefront of systemic chemotherapy development, pegylated liposomal doxorubicin, gemcitabine, and pentostatin appear to have the greatest potential for success in CTCL therapy. Bone marrow transplantation, which is currently limited by the risk of graft-versus-host disease, offers the greatest potential for disease cure. Further developments for CTCL may include more selective immunomodulatory agents, vaccines, and monoclonal antibodies.