Experience With Bexarotene to Treat Cutaneous T-Cell Lymphomas: A Study of the Spanish Working Group of Cutaneous Lymphomas.

BACKGROUND AND OBJECTIVES: Bexarotene has been approved to treat advanced stage cutaneous T-cell lymphomas (CTCL) since 1999. However, very few data have been published on its long-term safety and efficacy profile. The aim of this study is to determine the tolerability to bexarotene and outcomes by collecting the 2nd largest case series to date on its long-term use vs CTCL. MATERIAL AND METHOD: This was a multicenter retrospective review of 216 patients with mycosis fungoides (174), or Sézary syndrome (42) on a 10-year course of bexarotene alone or in combination with other therapies at 19 tertiary referral teaching hospitals. RESULTS: A total of 133 men (62%) and 83 women (38%) were included, with a mean age of 63.5 year (27-95). A total of 45% were on bexarotene monotherapy for the entire study period, 22% started on bexarotene but eventually received an additional therapy, 13% were on another treatment but eventually received bexarotene while the remaining 20% received a combination therapy since the beginning. The median course of treatment was 20.78 months (1-114); and the overall response rate, 70.3%. Complete and partial response rates were achieved in 26% and 45% of the patients, respectively. Treatment was well tolerated, being the most common toxicities hypertriglyceridemia (79%), hypercholesterolemia (71%), and hypothyroidism (52%). No treatment-related grade 5 adverse events were reported. CONCLUSIONS: Our study confirms bexarotene is a safe and effective therapy for the long-term treatment of CTCL.

Prognostic factors in patients with primary cutaneous anaplastic large cell lymphoma: a multicentric, retrospective analysis of the Spanish Group of Cutaneous Lymphoma.

BACKGROUND: Reliable prognostic factors for patients with primary cutaneous anaplastic large cell lymphoma (PCALCL) are lacking. OBJECTIVE: To identify prognostic factors for specific survival in patients with PCALCL. METHODS: Using the convenience sampling method, patients with PCALCL diagnosed from May 1986 to August 2017 in 16 University Departments were retrospectively reviewed. RESULTS: One hundred eight patients were included (57 males). Median age at diagnosis was 58 years. All of them showed T1-3N0M0 stages. Seventy per cent of the cases presented with a solitary lesion, mostly at the limbs. Complete response rate after first-line treatment was 87%, and no advantage was observed for any of them (surgery, radiotherapy, chemotherapy or other approaches). Nodal and visceral progression rate was 11% and 2%, respectively. 5-year specific survival (SSV) reached 93%; 97% for T1 patients and 84% for T2/T3 patients (P = 0.031). Five-year SSV for patients developing early cutaneous relapse was 64%; for those with late or no relapse, 96% (P = 0.001). Estimated median SSV for patients showing nodal progression was 103 months (95% CI: 51-155 months); for patients without nodal progression, estimated SSV did not reach the median (P < 0.001). Nodal progression was an independent predictive parameter for shorter survival (P = 0.011). CONCLUSION: Multiple cutaneous lesions at presentation, early skin relapse and nodal progression portrait worse prognosis in patients with PCALCL.

First-line treatment in lymphomatoid papulosis: a retrospective multicentre study.

BACKGROUND: Data regarding response to treatment in lymphomatoid papulosis (LyP) are scarce. AIM: To assess the daily clinical practice approach to LyP and the response to first-line treatments. METHODS: This was a retrospective study enrolling 252 patients with LyP. RESULTS: Topical steroids, methotrexate and phototherapy were the most common first-line treatments, prescribed for 35%, 20% and 14% of the patients, respectively. Complete response (CR) was achieved in 48% of treated patients. Eczematous lesions significantly increased relative risk (RR) of not achieving CR (RR = 1.76; 95% CI 1.16-2.11). Overall median time to CR was 10 months (95% CI 6-13 months), and 78% of complete responders showed cutaneous relapse; both results were similar for all treatment groups (P > 0.05). Overall estimated median disease-free survival (DFS) was 11 months (95% CI 9-13 months) but DFS for patients treated with phototherapy was 23 months (95% CI 10-36 months; P < 0.03). Having the Type A LyP variant (RR = 2.04; 95% CI 0.96-4.30) and receiving a first-line treatment other than phototherapy (RR = 5.33; 95% CI 0.84-33.89) were significantly associated with cutaneous early relapse. Of the 252 patients, 31 (13%) had associated mycosis fungoides unrelated to therapeutic approach, type of LyP or T-cell receptor clonality. CONCLUSIONS: Current epidemiological, clinical and pathological data support previous results. Topical steroids, phototherapy and methotrexate are the most frequently prescribed first-line treatments. Although CR and cutaneous relapse rates do not differ between them, phototherapy achieves a longer DFS. Presence of Type A LyP and use of topical steroid or methotrexate were associated with an increased risk of early relapse.

Alopecia areata totalis and universalis: a multicenter review of 132 patients in Spain.

BACKGROUND: Alopecia areata totalis (AAT) and universalis (AAU) pose a therapeutic challenge. OBJECTIVE: To describe the clinical and epidemiological features, therapeutic response and prognostic factors in a large series of patients diagnosed with AAT and AAU. METHODS: This retrospective multicenter study included patients diagnosed with AAT/AAU with a minimum follow-up of 12 months. Response was assessed based on the regrowth of scalp hair. RESULTS: In all, 132 patients (92 women and 40 men) - 80 (61%) diagnosed with AAU and 52 (39%) diagnosed with AAT - were included. The median time between the presentation of alopecia areata (AA) and the development of extensive AA was 1 year and it was less than 4 years in 121 patients (91%). There was an initial response to treatment in 64% of patients, although only 14% presented a persistent response. Adverse side effects from the medications used were detected in 33% of patients. The prognostic factors associated with poor response were the presence of AAU and a positive family history of AA. CONCLUSIONS: Treatment of AAT and AAU is challenging. Although an initial regrowth may be achieved, the duration of response is usually short. There were no significant differences on the effectiveness or duration of response between the various systemic therapies.

Development of a liquid chromatographic method for the quantification of paromomycin. Application to in vitro release and ex vivo permeation studies.

We have developed a reversed phase high performance liquid chromatography pulsed amperometric detection (RPHPLC-PAD) method for the determination of paromomycin. It is sensitive, repeatable, and selective without the pretreatment step. Trifluoroacetic acid-water was utilized as the eluent and detected by PAD under NaOH alkaline conditions. The paromomycin detection limit (S/N=3.3) was 2µgmL(-1) and the quantification limit (S/N=10) was 6µgmL(-1). Coefficients of linear regression were higher than 0.99 for concentrations between 6.25 and 200µgmL(-1). The intra and inter-day precision (RSD) was less than 6.5%. The average recoveries were 97.53-102.01%. The proposed HPLC-PAD method presented advantageous performance characteristics and it can be considered suitable for the evaluation of paromomycin loaded nanogel formulation in ex vivo permeation and in vitro release studies.

[Subcutaneous adrenaline versus inhaled salbutamol in the treatment of childhood asthmatic crisis]. / Adrenalina subcutánea versus salbutamol inhalado en el tratamiento de la crisis asmática infantil.

As a bronchodilator, inhaled salbutamol has been shown to be as pharmacologically effective as epinephrine. However the use of the pressurised aerosol is difficult for pediatric patients (mainly under the age of six). The use of spacers (inhalation chambers) could solve this problem. This study was undertaken to compare the clinical effectiveness and toxicity of these two drugs and to try to establish dosage schedules of inhaled salbutamol with spacer in the treatment of acute asthma. The study population consisted of 100 children who were admitted to the emergency room at our hospital with acute asthma. One group receives 0.01 mg/kg of epinephrine (A) (maximum 0.3 mg), the other two groups received inhaled salbutamol (S-1 = 4 puffs and S-2 = 7 puffs) in a period of 20 minutes. Clinical effectiveness was measured by the score of Wood-Downes at 0, 30 and 60 minutes; and no statistical differences were observed between the three groups. The clinical effectiveness was similar in the three groups and the side effects (especially the increase of heart rate) was higher in epinephrine group. Inhaled salbutamol is as effective as subcutaneous epinephrine in management of children in acute bronchoconstricting episodes with less side effects.