tacrolimus and Lymphoma--T-Cell--Cutaneous

There is controversy regarding a potential increased risk of lymphoma in patients with atopic dermatitis (AD).. To assess the risk of lymphoma and the role of topical treatments in patients with AD.. A systematic literature search and a separate meta-analysis were performed on case control and cohort studies.. Of the 3979 articles retrieved, 24 references met the inclusion criteria. In cohort studies, the risk of lymphoma was slightly increased, with a relative risk (RR) of 1.43 (95% confidence interval [CI], 1.12-1.81). In case control studies, no significant increased risk of lymphoma was found, with an odds ratio (OR) of 1.18 (95% CI, 0.94-1.47). Severity of AD was a significant risk factor. Highly potent topical steroids were associated with an increased risk of lymphoma. For topical calcineurin inhibitors (TCIs), a significant association between tacrolimus and mostly skin lymphoma was found in 1 study.. Confusion between severe AD and cutaneous T-cell lymphoma may account for part of the increased risk of lymphoma in patients with AD.. This systematic literature review shows a slightly increased risk of lymphoma in patients with AD. Severity of AD appears to be a significant risk factor. The role of topical steroids and TCIs is unlikely to be significant.

Topics: Administration, Topical; Adrenal Cortex Hormones; Age Distribution; Calcineurin Inhibitors; Comorbidity; Dermatitis, Atopic; Female; Humans; Immunosuppressive Agents; Incidence; Lymphoma, T-Cell, Cutaneous; Male; Prognosis; Risk Assessment; Severity of Illness Index; Sex Distribution; Skin Neoplasms; Tacrolimus

Topics: Adult; Aged; Anti-Inflammatory Agents; Facial Dermatoses; Female; Humans; Hydroa Vacciniforme; Lymphoma, T-Cell, Cutaneous; Minocycline; Skin Neoplasms; Sunscreening Agents; Tacrolimus

Cutaneous T-cell lymphoma occurring in the context of posttransplant immunosuppression is rare, with 27 cases documented to date.. We report 2 new cases of posttransplant cutaneous T-cell lymphoma in patients treated at our institution. Both were male recipients of renal transplants who had undergone transplantation a mean of 5.3 years previously and were taking various multidrug immunosuppressive regimens, including cyclosporine, tacrolimus, mycophenolate mofetil, and prednisone.. These cases underscore the association of posttransplant cutaneous T-cell lymphoma with renal transplantation, cyclosporine and tacrolimus therapy, male sex, and later onset compared with B-cell posttransplant lymphoproliferative disease. Relative to the general population, the incidence of cutaneous T-cell lymphoma seems increased among transplant recipients receiving immunosuppressive medications.

Topics: Adult; Aged; Calcineurin Inhibitors; Cyclosporine; Humans; Immunosuppressive Agents; Kidney Transplantation; Lymphoma, T-Cell, Cutaneous; Male; Risk Factors; Sex Factors; Skin Neoplasms; Tacrolimus

A standard therapy for advanced cutaneous T-cell lymphomas has not yet been defined. Bexarotene is a new retinoid x receptor-specific retinoid that has been approved for systemic second-line therapy for cutaneous T-cell lymphomas in the USA and Europe. In order to evaluate the efficacy of bexarotene in cutaneous T-cell lymphomas, a pilot trial was initiated.. In a pilot project 10 patients with advanced cutaneous T-cell lymphomas, who had received a variety of previous treatments, were treated with bexarotene at the departments of dermatology in Münster, Minden and Charité Berlin, Germany. The patients received bexarotene at a dose of 300 mg/m2 body surface daily. According to the percentage of tumour reduction and affected body surface, the response rates were divided in complete and partial remission, stable disease and progressive disease. Laboratory parameters i.e. cholesterol, triglycerides transaminases, T3, T4, and TSH were screened regularly.. In 2 patients a short partial remission was achieved; however, after a few weeks progression followed. In 4 patients a lasting stabilisation was obtained. The other 4 patients showed a progressive disease during therapy. 6 patients developed hypertriglyceridemia with levels up to 2000 mg/dl; therapy had to be suspended in 3 patients because of these adverse drug events.. Weighing benefits and risks, bexarotene can at present not be recommended as standard therapy in the treatment of patients with progressive cutaneous lymphomas.

Topics: Adult; Aged; Aminoquinolines; Anticarcinogenic Agents; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bexarotene; Combined Modality Therapy; Cyclophosphamide; Disease Progression; Doxorubicin; Female; Humans; Imiquimod; Immunosuppressive Agents; Interferons; Lymphoma, T-Cell, Cutaneous; Male; Middle Aged; Neoplasm Staging; Pilot Projects; Prednisone; PUVA Therapy; Remission Induction; Skin; Skin Neoplasms; Tacrolimus; Tetrahydronaphthalenes; Time Factors; Treatment Outcome; Vincristine

Signaling through the interleukin 2 receptor (IL-2R) involves phosphorylation of several proteins including Jak3, STAT5, and, in preactivated cells, STAT3. In the present study, we examined the functional status of the IL-2R-associated Jak/STAT pathway in malignant T lymphocytes from advanced skin-based lymphomas: anaplastic large T-cell lymphoma (ALCL) and Sezary syndrome (SzS). Proliferation of three ALCL cell lines (PB-1, 2A, and 2B) was partially inhibited by rapamycin, a blocker of some of the signals mediated by IL-2R, but not by cyclosporin A, FK-506, and prednisone, which suppress signals mediated by the T-cell receptor. All the cell lines expressed on their surface the high-affinity IL-2R (alpha, beta, and gamma c chains). They showed basal, constitutive phosphorylation, and coassociation of Jak3, STAT5, and STAT3. Weak basal phosphorylation of IL-2R gamma c was also detected. In regard to SzS, peripheral blood mononuclear cells from 10 of 14 patients showed basal phosphorylation of Jak3, accompanied by phosphorylation of STAT5 in 9 patients, and STAT3 in 4 patients. However, in vitro overnight culture of SzS cells without exogenous cytokines resulted in markedly decreased Jak3 and STAT5 phosphorylation, which could be reversed by stimulation with IL-2. This indicates that the basal phosphorylation of Jak3 and STAT5 in freshly isolated SzS cells is induced rather than constitutive. The basal activation of the Jak/STAT pathway involved in IL-2R signal transduction in ALCL and SzS cells reported here suggests that this pathway may play a role in the pathogenesis of cutaneous T-cell lymphomas, although the mechanism (induced versus constitutive) may vary between different lymphoma types.

Topics: Cell Membrane; Cyclosporine; DNA-Binding Proteins; Humans; Immunosuppressive Agents; Janus Kinase 3; Lymphocyte Activation; Lymphoma, T-Cell, Cutaneous; Milk Proteins; Phosphorylation; Polyenes; Prednisone; Protein Binding; Protein-Tyrosine Kinases; Receptors, Interleukin-2; Sezary Syndrome; Signal Transduction; Sirolimus; STAT3 Transcription Factor; STAT5 Transcription Factor; Tacrolimus; Trans-Activators; Tumor Cells, Cultured