tacrolimus and Mycosis-Fungoides

THE EFFICACY OF THE 308 NM EXCIMER LASER in the treatment of common psoriasis has been demonstrated. THE DOSES USED have progressively decreased, hence, limiting the adverse events that appear redhibitory with high doses. THE ADAPTATION OF THE DOSES not to the patients themselves but to each of the plaques treated should reduce the number of sessions and the cumulated close necessary to obtain clinical remission. THE 308 NM EXCIMER LASER is effective and tolerance is good in the treatment of vitiligo. It should be proposed for limited vitiligo and essentially of the "UV sensitive" areas, which have shown aesthetically correct percentage of repigmentation. THE PLACE AND INTEREST of its association with other treatments, notably with topical tacrolimus, remains to be defined. Although the results obtained in the treatment of vitiligo are promising, they have to be confirmed in larger cohorts and ensure the absence of median and long term side effects. This therefore limits its use in combined treatments in the context of controlled clinical traits. THE 30 NM EXCIMER LASER IS AN EFFECTIVE AND WELL TOLERATED TREATMENT in localised and non-nodular forms of mycosis fungoid (MF). Although the number of patients treated is limited, the clinical and histological cure observed demonstrates the interest of this new technique in the treatment of MF. These results must be confirmed in a greater number of patients. THE 308 NM EXCIMER LASER is an interesting therapeutic alternative in the treatment of plaques of alopecia areata, erosive oral lichen planus, post-surgical hypopigmentation, vergetures and localised forms of atopic dermatitis. Because of the sparcity of data and in the absence of long term follow-up, it must not be proposed in first intention.

Topics: Administration, Topical; Humans; Immunosuppressive Agents; Laser Therapy; Mycosis Fungoides; Phototherapy; Pilot Projects; Radiotherapy Dosage; Skin Diseases; Tacrolimus; Time Factors; Ultraviolet Therapy; Vitiligo

The calcineurin pathway is often activated in mycosis fungoides. We aimed to assess the activity and safety of topical pimecrolimus, a calcineurin inhibitor, in patients with early mycosis fungoides.. PimTo-MF was a single-arm, multicentre, phase 2 trial done at six medical centres in Spain. Patients (aged ≥18 years) had histologically confirmed early mycosis fungoides (stages IA-IIA) and an Eastern Cooperative Oncology Group performance status of 0-1. Key exclusion criteria included the use of concurrent treatments for mycosis fungoides, including sunbathing, topical or systemic corticosteroids, and other calcineurin inhibitors. Patients applied topical pimecrolimus 1% cream on their skin lesions twice daily for 16 weeks (1 g per 2% of body surface), with subsequent follow-up of 12 months. Dosage modifications were not allowed. To evaluate adherence to the treatment, patients were instructed to return all empty tubes to the hospital (as per drug accountability protocols). The primary endpoint was the overall response ratein the intention-to-treat population. PimTo-MF is registered with EudraCT, 2014-001377-14, and is complete.. Between March 1, 2015, and Sept 30, 2016, 39 patients were enrolled. All patients were assessable, with a median age of 51·5 years (IQR 45-62), and the population was predominantly male (24 male [62%], 15 female [38%]). Median follow-up after baseline was 5·7 years (IQR 5·7-6·2). 22 (56%) of 39 patients had an overall response (one complete response, 21 partial responses). Responses were observed across IA (14 [54%] of 26 patients) and IB (eight [73%] of 11 patients) clinical stages, but not IIA. Topical pimecrolimus was well tolerated and no patient required a dose reduction or discontinued treatment because of unacceptable drug-related toxicity. No patients were lost to follow-up or discontinued treatment. 13 (33%) of 39 patients reported adverse events; transitory mild burning or pruritus (grade 1) was the most common, seen in eight (21%) patients. In three (8%) of these patients, the burning or pruritus was considered related to treatment. No grade 4 or 5 adverse events were observed.. Pimecrolimus 1% cream seems active and safe in patients with early stage mycosis fungoides. Our findings should be taken with caution until long-term follow-up data are obtained that confirm the safety of this treatment. Further controlled clinical trials are warranted to confirm these results.. Instituto de Salud Carlos III and the European Regional Development Fund.. For the Spanish translation of the abstract see Supplementary Materials section.

Topics: Adolescent; Adult; Female; Humans; Male; Middle Aged; Mycosis Fungoides; Pruritus; Skin Neoplasms; Tacrolimus

Transformed mycosis fungoides (MF) and Sézary syndrome (SS) are currently incurable. We studied the safety and efficacy of total skin electron beam with allogeneic hematopoietic stem-cell transplantation (HSCT) in patients with cutaneous T-cell lymphoma (CTCL).. Nineteen patients with advanced CTCL (median age, 50 years; four prior therapies) underwent total skin electron beam radiation followed by allogeneic HSCT between July 2001 and July 2008. Sixteen patients were conditioned with fludarabine (125 mg/m(2)) and melphalan (140 mg/m(2)) plus thymoglobulin (for mismatched donors). Graft-versus-host disease (GVHD) prophylaxis was with tacrolimus/mini methotrexate.. Eighteen patients experienced engraftment, and one died as a result of sepsis on day 16. Median time to recovery of absolute neutrophil count (ANC) was 12 days. Fifteen achieved full donor chimerism, 12 had acute GVHD, and 12 were treated for chronic GVHD. The overall intent-to-treat response was 68%, and the complete response rate was 58%. Four of six patients died in complete remission as a result of bacterial sepsis (n = 2), chronic GVHD and fungal infection (n = 1), or lung cancer (n = 1); only two died as a result of progressive disease. Eight experienced relapse in skin; five regained complete response with reduced immunosuppression or donor lymphocyte infusions. Eleven of 13 are currently in complete remissions, with median follow-up of 19 months (range, 1.3 to 8.3 years). Median overall survival has not been reached.. Total skin electron beam followed by allogeneic stem-cell transplantation merits additional evaluation for a selected group of patients with refractory, advanced, cutaneous T-cell lymphoma with evidence for graft-versus-tumor effect.

Topics: Adult; Antibodies, Monoclonal; Antilymphocyte Serum; Disease Progression; Disease-Free Survival; Female; Graft vs Host Disease; Graft vs Tumor Effect; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Kaplan-Meier Estimate; Male; Melphalan; Methotrexate; Middle Aged; Mycosis Fungoides; Myeloablative Agonists; Recurrence; Sezary Syndrome; Tacrolimus; Time Factors; Transplantation Chimera; Transplantation Conditioning; Transplantation, Homologous; Treatment Outcome; Vidarabine; Whole-Body Irradiation; Young Adult

Mycosis fungoides (MF) in solid-organ transplant recipients (SOTRs) is rare, with limited data on disease characteristics.. The aim was to study the characteristics of MF in SOTRs with an emphasis on the immunosuppressive therapy.. A retrospective cohort of patients diagnosed with MF, who were also SOTRs, were followed at 3 cutaneous lymphoma outpatient clinics, between January 2010 and February 2022.. Ten patients were included (7 male; median ages at transplantation and at diagnosis of MF were 33 and 48 years, respectively; 40% were diagnosed before the age of 18 years). Median time from transplantation to diagnosis of MF was 8 years (range 0.5-22). Transplanted organs and immunosuppressive treatments included: liver (n = 5; 4 treated with tacrolimus, 1 with tacrolimus and prednisone), kidney (n = 3), liver and kidney (n = 1), and heart (n = 1), all treated with mycophenolic acid, tacrolimus, and prednisone. Nine had early-stage MF (IA - 4, IB - 5; 40% with early folliculotropic MF), treated with skin-directed therapies, in 2 combined with acitretin, achieving partial/complete response. One patient had advanced-stage MF (IIIA) with folliculotropic erythroderma, treated with ultraviolet A and narrow-band ultraviolet B with acitretin, achieving partial response. Immunosuppression was modified in 3. At last follow-up (median 4 years, range 1-8), no stage progression was observed; 5 had no evidence of disease, 5 had active disease (IA/IB - 4, III - 1).. MF in SOTRs is usually diagnosed at an early stage, with overrepresentation of folliculotropic MF, and of children. Immunosuppressive therapy alterations, not conducted in most patients, should be balanced against the risk of organ compromise/rejection. Disease course was similar to MF in immunocompetent patients, during the limited time of follow-up.

Topics: Acitretin; Adolescent; Child; Humans; Male; Mycosis Fungoides; Organ Transplantation; Prednisone; Retrospective Studies; Skin Neoplasms; Tacrolimus

Topics: Humans; Mycosis Fungoides; Skin Neoplasms; Tacrolimus

Topics: Humans; Mycosis Fungoides; Skin Neoplasms; Tacrolimus

Organ transplant recipients receiving immunosuppression have an increased risk of developing post-transplant lymphoproliferative diseases (PTLDs). Traditionally, PTLDs refer to Epstein-Barr virus (EBV)-induced B-cell lymphoma. However, post-transplant T-cell lymphoma may also occur and tends to have a poorer response to reduced immunosuppressive therapy. As such, additional therapy is often needed for post-transplant T-cell lymphoma, including post-transplant cutaneous T-cell lymphoma (PT-CTCL). We present only the third case of PT-CTCL occurring after liver transplantation. The patient was diagnosed with stage IB mycosis fungoides (MF). His lesions were refractory to multiple skin-directed therapies, and so he was given oral bexarotene 150 mg daily and his oral tacrolimus dose was decreased to 2 mg daily. Remarkably, his MF patches have demonstrated a complete response to oral bexarotene 75 mg daily without recurrence over 11 years of follow-up. He developed hypertriglyceridemia with bexarotene 150 mg, so his dose was decreased to 75 mg, without loss of response. Our report is the second to describe PT-CTCL demonstrating a long-term complete response to oral bexarotene. Given its anti-carcinogenic properties and favorable toxicity profile, oral bexarotene represents an appealing treatment option for PT-CTCL refractory to skin-directed therapies.

Topics: Administration, Oral; Anticarcinogenic Agents; Bexarotene; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Mycosis Fungoides; Skin Neoplasms; Tacrolimus; Tetrahydronaphthalenes; Treatment Outcome

Cutaneous T cell lymphomas (CTCLs) are a heterogenous group of lymphoproliferative disorders caused by clonally-derived, skin-invasive T cells. A variety of skin-directed and systemic therapies are available to treat mycosis fungoides/Sézary syndrome (MF/SS), the therapeutic choices of which are guided by the stage of disease. A 29-year-old man presented at our clinic with pruritic, erythematous macules located on the sternum and the lower back. Histological findings and immunohistochemistry studies showed patch stage MF. The patient was treated with tacrolimus ointment 0.1% twice daily for one month, achieving complete remission. Three months after the first episode a relapse was successfully treated with the same therapeutic regimen. Tacrolimus is an immunomodulatory macrolide that reduces the stimulatory capacity toward T cells and is therefore worth investigating as a treatment of CTCL. Topical tacrolimus has been related to an unknown effect with the risk for secondary malignancies including CTCL. Also, black box warnings have been proposed by the FDA for the topical calcineurin inhibitors. Nevertheless, our results in the treatment of early stage MF are in agreement with other unpublished data that have observed its efficacy. To our knowledge, there is no other case of patch type mycosis fungoides treated with tacrolimus ointment 0.1% in the medical literature.

Topics: Administration, Cutaneous; Adult; Diagnosis, Differential; Humans; Immunosuppressive Agents; Male; Mycosis Fungoides; Ointments; Severity of Illness Index; Skin Neoplasms; Tacrolimus