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Background Mycosis fungoides (MF) and Sézary syndrome (SS) are chronic malignant diseases that typically necessitate diverse strategies to achieve remission. Systemic interferon (IFN)-α (subtypes 2a and 2b) has been used to treat MF/SS since 1984; however, its production was recently stopped. The recombinant pegylated (PEG) form of IFN-α-2a remains the only alternative IFN treatment, although it has not been approved for use in MF/SS. Objectives To assess the effectiveness and safety of PEG-IFN-α-2a in monotherapy and in combination with other treatments using time to next treatment (TTNT) as a measure of clinical therapeutic benefit in a real-world setting. Methods We conducted an international, multicentre retrospective study of patients with MF and SS (of any stage) treated with PEG-IFN-α-2a from July 2012 to February 2022. Patients were included across 11 centres in 10 countries. The primary endpoints were to determine the TTNT of PEG-IFN-α-2a and adverse events (AEs) in MF/SS. Results In total, 105 patients were included [mean (SD) age 61 (13.1) years]; 42 (40.0%) had stage IA–IIA and 63 (60.0%) had stage IIB–IVB disease. PEG-IFN-α-2a was combined with other therapies in 67 (63.8%) patients, most commonly with extracorporeal photopheresis (36%) and bexarotene (22%). Patients with stage I–IIA disease achieved an overall response rate (ORR) of 57%; the ORR in those with stage IIB–IVB disease was 51%. Combination treatment resulted in a median TTNT of 10.4 months (range 0.6–50.7) vs. 7.0 months (range 0.7–52.4) for those who received monotherapy (P < 0.01). Overall, the mean (SD) TTNT was 9.2 (10.6) months and the ORR was 53.3% (n = 56). A complete response was seen in 13% of patients and a partial response in 40%. AEs were described in 68.6% (n = 72) of patients. Flu-like symptoms (n = 28; 26.7%), lymphopenia (n = 24; 22.9%) and elevated liver function (n = 10; 9.5%) were the most frequently reported. Grade 3–4 AEs were reported in 23 (21.9%) patients, mostly related to myelosuppression. Conclusions PEG-IFN-α-2a for MF/SS resulted in an ORR of 53.3% and a mean (SD) TTNT of 9.2 (10.6) months. Combination regimens were superior to monotherapy and doses of 180 µg PEG-IFN-α-2a weekly were related to a higher ORR. [ABSTRACT FROM AUTHOR]

Dear Editor, Mogamulizumab is an anti-CCR4 antibody that was investigated in the phase 3 MAVORIC study (NCT01728805) of adult patients with previously treated mycosis fungoides (MF) or Sézary syndrome (SS).1 In the primary analysis (December 31, 2016 cutoff), progression-free survival (PFS) and confirmed global overall response rate were significantly better with mogamulizumab compared with vorinostat. As expected, the patients with the longest exposure to mogamulizumab had higher rates of TEAEs than the overall safety population but also showed acceptable disease control, suggesting that TEAEs were generally manageable and patients were able to stay on treatment. Long-term disease control and safety with the anti-CCR4 antibody mogamulizumab: Post-hoc analyses from the MAVORIC trial of patients with previously treated cutaneous T-cell lymphoma. [Extracted from the article]

Mycosis fungoides (MF), the most common form of primary cutaneous T-cell lymphoma, is a disease typically with an indolent course that is initially characterized by localized patches and plaques. In the early stages of the disease, treatment involves skin-directed therapies (SDTs) such as topical corticosteroids and retinoids. Chlormethine gel (also known as mechlorethamine) was the first SDT purposely developed to treat MF and is currently endorsed by international guidelines for the treatment of adult patients with MF as a first-line therapy. While chlormethine is an efficacious therapy, its usage may be complicated by the development of cutaneous reactions at the sites of application. Herein, we discuss the supportive guidelines for MF and the suitability of chlormethine as a therapeutic option in patients with MF. In addition, we present real-world experience on the use of chlormethine gel from clinics in the USA, Israel, and France with the aim of demonstrating the efficacy of chlormethine gel in routine clinical practice and outlining strategies that are being used to manage emergent cutaneous reactions. [ABSTRACT FROM AUTHOR]

Summary: Cutaneous T‐cell lymphomas (CTCLs) have a chronic, relapsing course, and the most common subtypes are mycosis fungoides and Sézary syndrome. The disease causes visible skin alterations and can also cause alopecia, pruritus and pain, all of which can impact patients' health‐related quality of life (HRQoL). The goal of treatment is to reduce symptoms and prevent disease progression. However, treatment recommendations are often based on low levels of evidence due to the lack of well‐designed randomised clinical trials and treatment guidelines, and approved drugs vary considerably across different countries and regions. Currently, available treatments rarely lead to durable remissions and eventually become less effective, meaning patients often require multiple therapy changes. Skin‐directed therapies (SDTs) are first‐line treatments for early‐stage CTCL, whereas systemic therapies may be needed for early‐stage disease that does not respond to SDT or for advanced‐stage disease. However, patients can experience significant side‐effects with these treatments or may be unable to tolerate them. Hence, there is an unmet need for effective therapies with good safety profiles for the treatment of early‐ and late‐stage CTCL. Here, we review current treatment guidelines, investigational and approved treatments, the impact of CTCL on patients' HRQoL, and the treatment of pruritus. [ABSTRACT FROM AUTHOR]

Background: IPH4102 is a first-in-class monoclonal antibody targeting KIR3DL2, a cell surface protein that is expressed in cutaneous T-cell lymphoma, and predominantly in its leukaemic form, Sézary syndrome. We aimed to assess the safety and activity of IPH4102 in cutaneous T-cell lymphoma.Methods: We did an international, first-in-human, open-label, phase 1 clinical trial with dose-escalation and cohort-expansion parts in five academic hospitals in the USA, France, the UK, and the Netherlands. Eligible patients had histologically confirmed relapsed or refractory primary cutaneous T-cell lymphoma, an Eastern Cooperative Oncology group performance score of 2 or less, were aged 18 years or older, and had received at least two previous systemic therapies. Ten dose levels of IPH4102, administered as an intravenous infusion, ranging from 0·0001 mg/kg to 10 mg/kg, were assessed using an accelerated 3 + 3 design. The primary endpoint was the occurrence of dose-limiting toxicities during the first 2 weeks of treatment, defined as toxicity grade 3 or worse lasting for 8 or more days, except for lymphopenia. Global overall response by cutaneous T-cell lymphoma subtype was a secondary endpoint. Safety and activity analyses were done in the per-protocol population. The study is ongoing and recruitment is complete. This trial is registered with ClinicalTrials.gov, number NCT02593045.Findings: Between Nov 4, 2015, and Nov 20, 2017, 44 patients were enrolled. 35 (80%) patients had Sézary syndrome, eight (18%) had mycosis fungoides, and one (2%) had primary cutaneous T-cell lymphoma, not otherwise specified. In the dose-escalation part, no dose limiting toxicity was reported and the trial's safety committee recommended a flat dose of 750 mg for the cohort-expansion, corresponding to the maximum administered dose. The most common adverse events were peripheral oedema (12 [27%] of 44 patients) and fatigue (nine [20%]), all of which were grade 1-2. Lymphopenia was the most common grade 3 or worse adverse event (three [7%]). One patient developed possibly treatment-related fulminant hepatitis 6 weeks after IPH4102 discontinuation and subsequently died. However, the patient had evidence of human herpes virus-6B infection. Median follow-up was 14·1 months (IQR 11·3-20·5). A confirmed global overall response was achieved in 16 (36·4% [95% CI 23·8-51·1]) of 44 patients, and of those, 15 responses were observed in 35 patients with Sézary syndrome (43% [28·0-59·1]).Interpretation: IPH4102 is safe and shows encouraging clinical activity in patients with relapsed or refractory cutaneous T-cell lymphoma, particularly those with Sézary syndrome. If confirmed in future trials, IPH4102 could become a novel treatment option for these patients. A multi-cohort, phase 2 trial (TELLOMAK) is underway to confirm the activity in patients with Sézary syndrome and explore the role of IPH4102 in other subtypes of T-cell lymphomas that express KIR3DL2.Funding: Innate Pharma. [ABSTRACT FROM AUTHOR]

Background: Cutaneous T-cell lymphomas are rare non-Hodgkin lymphomas with substantial morbidity and mortality in advanced disease stages. We compared the efficacy of mogamulizumab, a novel monoclonal antibody directed against C-C chemokine receptor 4, with vorinostat in patients with previously treated cutaneous T-cell lymphoma.Methods: In this open-label, international, phase 3, randomised controlled trial, we recruited patients with relapsed or refractory mycosis fungoides or Sézary syndrome at 61 medical centres in the USA, Denmark, France, Italy, Germany, the Netherlands, Spain, Switzerland, the UK, Japan, and Australia. Eligible patients were aged at least 18 years (in Japan, ≥20 years), had failed (for progression or toxicity as assessed by the principal investigator) at least one previous systemic therapy, and had an Eastern Cooperative Oncology Group performance score of 1 or less and adequate haematological, hepatic, and renal function. Patients were randomly assigned (1:1) using an interactive voice web response system to mogamulizumab (1·0 mg/kg intravenously on a weekly basis for the first 28-day cycle, then on days 1 and 15 of subsequent cycles) or vorinostat (400 mg daily). Stratification was by cutaneous T-cell lymphoma subtype (mycosis fungoides vs Sézary syndrome) and disease stage (IB-II vs III-IV). Since this study was open label, patients and investigators were not masked to treatment assignment. The primary endpoint was progression-free survival by investigator assessment in the intention-to-treat population. Patients who received one or more doses of study drug were included in the safety analyses. This study is ongoing, and enrolment is complete. This trial was registered with ClinicalTrials.gov, number NCT01728805.Findings: Between Dec 12, 2012, and Jan 29, 2016, 372 eligible patients were randomly assigned to receive mogamulizumab (n=186) or vorinostat (n=186), comprising the intention-to-treat population. Two patients randomly assigned to mogamulizumab withdrew consent before receiving study treatment; thus, 370 patients were included in the safety population. Mogamulizumab therapy resulted in superior investigator-assessed progression-free survival compared with vorinostat therapy (median 7·7 months [95% CI 5·7-10·3] in the mogamulizumab group vs 3·1 months [2·9-4·1] in the vorinostat group; hazard ratio 0·53, 95% CI 0·41-0·69; stratified log-rank p<0·0001). Grade 3-4 adverse events of any cause were reported in 75 (41%) of 184 patients in the mogamulizumab group and 76 (41%) of 186 patients in the vorinostat group. The most common serious adverse events of any cause were pyrexia in eight (4%) patients and cellulitis in five (3%) patients in the mogamulizumab group; and cellulitis in six (3%) patients, pulmonary embolism in six (3%) patients, and sepsis in five (3%) patients in the vorinostat group. Two (67%) of three on-treatment deaths with mogamulizumab (due to sepsis and polymyositis) and three (33%) of nine on-treatment deaths with vorinostat (two due to pulmonary embolism and one due to bronchopneumonia) were considered treatment-related.Interpretation: Mogamulizumab significantly prolonged progression-free survival compared with vorinostat, and could provide a new, effective treatment for patients with mycosis fungoides and, importantly, for Sézary syndrome, a subtype that represents a major therapeutic challenge in cutaneous T-cell lymphoma.Funding: Kyowa Kirin. [ABSTRACT FROM AUTHOR]

Cutaneous T-cell lymphomas (CTCLs) represent a group of rare and heterogeneous diseases that are very difficult to treat at advanced stages. The development of monoclonal antibodies is a new hope for the treatment of these diseases. Alemtuzumab (Campath) is a humanized IgGl kappa monoclonal antibody specific for CD52, an antigen expressed by most T and B lymphocytes. Alemtuzumab may frequently induce long-term remissions in patients with Sezary syndrome but high-dose treatments lead to severe cytopenia, immune depletion, and opportunistic infections. This treatment is less efficient in mycosis fungoides (MF). Brentuximab vedotin is a chimeric anti-CD30 monoclonal antibody conjugated to monomethyl auristatin E, a cytotoxic antitubulin agent. Brentuximab vedotin is a very interesting new treatment for advanced tumor MF, Sezary syndrome, and primary cutaneous CD30+ lymphoproliferative disorders. The main limiting adverse event is neurosensitive peripheral neuropathy. Mogamulizumab is a humanized anti-C-C chemokine receptor Type 4 monoclonal antibody with a defucosylated Fc region leading to increased antibody-dependent cellular cytotoxicity. Mogamulizumab is very efficient on aggressive peripheral T-cell lymphomas, particularly adult T-cell leukemia/lymphoma and CTCLs, especially on the blood component of tumor cells. The main limiting events are related to the concomitant depletion of regulatory T-cells. IPH4102 is a humanized monoclonal antibody that targets the immune receptor KIR3DL2/CD158k. Preclinical results with this antibody offer proofs of concept for the clinical development of IPH4102 to treat patients with advanced CTCL. [ABSTRACT FROM AUTHOR]

KIR3DL2 is a killer immunoglobulin-like receptor, expressed in >90% of Sézary syndrome (SS) pts and 50% in pts with MF. Lacutamab is a humanized first-in-class monoclonal antibody designed to deplete KIR3DL2-expressing cells via antibody-dependent cell-cytotoxicity and phagocytosis. In a previous phase 1 trial, lacutamab showed adequate safety profile with no dose limiting toxicities and a global response rate of 42.9% in pts with SS, with a median time to response of 4.9 months (m). TELLOMAK is an open-label, multi-cohort, international phase II trial. Up to 148 pts are planned to be enrolled. Pts are allocated to one of three cohorts: Cohort 1: SS, Cohort 2: KIR3DL2 expressing (≥1%) MF and Cohort 3: KIR3DL2 non-expressing MF, based on central KIR3DL2 testing. Eligible pts should have received at least 2 prior systemic therapies with no evidence of large cell transformation. Lacutamab 750 mg is administered as an intravenous (i.v.) infusion weekly × 5 weeks (w), every 2 w × 10 then every 4 w, until progression or unacceptable toxicity. The primary endpoint is global confirmed response, evaluated using the International Consensus Criteria. Secondary endpoints include safety, quality of life, other efficacy endpoints, and biomarker analysis. Evaluable pts should have at least one response assessment 5 w after treatment initiation. In each of the MF cohorts, the study follows a Simon 2-stage design in which 21 and 18 pts were required in stage 1 for Cohorts 2 and 3, respectively with early termination if <3 global confirmed responses per cohort were observed. Here we report early stage 1 data for the two MF cohorts. As of January 20 2021, recruitment in stage 1 for both cohorts 2 and 3 is ongoing, with 12 pts enrolled in each cohort. Median age for all 24 pts is 57 years (range: 19–81). At study entry, 42% (n=5) and 17% (n=2) had stage III/IV in cohorts 2 and 3, respectively. Median number of prior systemic therapies is 3.5 (range: 2–10). At a median follow-up of 2.8 m (range: 0.3–14.1 m), 7 and 6 pts in cohort 2 and 3, respectively, are ongoing treatment. Overall, 19 pts were evaluable for response in Cohort 2 (n=11) and Cohort 3 (n=8). In Cohort 2, 5 skin responses were observed, of whom 3 had global confirmed responses (1 complete response, 2 partial responses). 7 pts had global stable disease. No responses are reported yet in Cohort 3. Adverse events (AEs) of any grade were observed in 17/24 pts (71%), of which 10/24 (42%) were treatment-related [TR]. Grade ≥3 AEs were observed in 2/24 (8%) pts, of which 1/24 (4%) was TR. Most common AEs were asthenia (N=6, 25%; TR: 2), pruritus (N=3, 12%; TR: 0), and peripheral oedema (N=2, 8%; TR: 1). Lacutamab met the predefined threshold of activity in the KIR3DL2 expressing MF cohort required to expand recruitment to 50 pts. Safety profile is reassuring and consistent with previous phase 1 data. Updated results on all stage 1 pts from cohort 2 and 3 will be presented. [ABSTRACT FROM AUTHOR]

Melanoma is an aggressive malignancy with poor prognosis. Eradication of tumor cells requires an effective interaction between melanoma cells and different players of the immune system. As the most potent professional antigen-presenting cells, dendritic cells (DCs) play a pivotal role in mounting a specific immune response where their intratumoral and peritumoral density as well as their functional status are correlated with clinical staging of the disease and with patients’ survival. Under steady-state conditions, internalization of apoptotic cells by immature DCs designates a state of tolerance to self-antigens. Nevertheless, pathogens and necrotic cells interacting with pattern recognition receptors trigger downstream signaling pathways that evoke maturation of DCs, leading to the production of pro-inflammatory cytokines. These mature DCs are essential for T-cell priming and subsequent development of a specific immune response. Altered functions of DCs have an impact on the development of various disorders including autoimmune diseases and cancers. Herein, we focus on the checkpoints created throughout DCs antigen capturing and presentation to T cells, with subsequent development of either tolerance or immune response, with an emphasis on the role played by DCs in melanoma tumorigenesis and their therapeutic potential. [ABSTRACT FROM AUTHOR]

Cutaneous T cell lymphomas are a clonal proliferation of CD4+ T lymphocytes primarily involving the skin. Mycosis fungoides is an epidermotropic CD4+ cutaneous T cell lymphoma, and a more aggressive form, Sezary syndrome, occurs when the malignant cells become nonepidermotropic. The role of neuropeptides in the growth and chemotaxis capacity of cutaneous T cell lymphoma cells remains unknown. In this report, we found that cutaneous T cell lymphoma cells, similarly to normal resting or activated peripheral lymphocytes, were able to bind neurotensin. We used an interleukin-2-dependent cutaneous T cell lymphoma malignant T cell line derived from cutaneous T cell lymphoma lesions in order to study the role of neurotensin in the proliferation and migration of these malignant cells. First, we determined that the malignant cells expressed neurotensin receptors on their cell membrane. Functional results indicated that neurotensin did not stimulate the growth of the cell line. In contrast, this neuropeptide inhibited the proliferation of the tumor cells in response to exogenous interleukin-2. Furthermore, we found that neurotensin enhanced both spontaneous and chemoattractant-induced migration of the malignant cells. This suggests that neurotensin in skin can play a role in the disease by locally limiting the growth of the cutaneous T cell lymphoma tumor cells in response to cytokines and by enhancing their chemotaxis capacity. [ABSTRACT FROM AUTHOR]

Summary Inhibitory receptors on natural killer cells and on a minority of T lymphocytes are major histocompatibility complex class Ia or Ib specific. We have previously reported several tumor-specific cytotoxic T cell clones infiltrating a CD4+ Vβ13+ cutaneous T cell lymphoma. These clones mediated a specific major histocompatibility complex class I-restricted cytotoxic activity toward the uncultured tumor cells and autologous long-term tumor T cell lines. In this study, we cultured with interleukin-2 the peripheral blood lymphocytes of the same patient a few weeks before invasion of the blood by tumor cells. We report the rapid and selective expansion of a CD8+ Vβ13+ lymphoid population. This population was clonal, as it expressed a unique T cell receptor-Vβ junctional region. Vβ13+ tumor cells and Vβ13+ reactive T cells were shown to have different junctional sequences. The CD8+ reactive clone was functional, as it had a specific autologous tumor-specific, human leukocyte antigen-A2 restricted, cytotoxic activity. This clone coexpressed high levels of CD158a, CD158b, p70, and CD94/NKG2A inhibitory receptors. Interestingly, we found that anti-CD158a and anti-CD158b monoclonal antibodies could inhibit anti-CD3 redirected cytotoxicity mediated by the reactive clonal population. Further, an anti-human leukocyte antigen-B/C monoclonal antibody enhanced the specific cytotoxic activity of the clone against autologous tumor cells. These results are the first evidence that inhibitory receptor expression can lead to the inhibition of cutaneous T cell lymphoma-specific T cell responses. [ABSTRACT FROM AUTHOR]

Summary We have previously described two cytotoxic T lymphocyte clones isolated from lymphocytes infiltrating a human major histocompatibility complex class II–/class I+, CD4+ cutaneous T cell lymphoma. These clones displayed a CD4+CD8dim+ (TC5) and CD4+ CD8– (TC7) phenotype and mediated a specific major histocompatibility complex class I-restricted cytotoxic activity toward Cou-LB autologous tumor cell line. Our studies were performed to elucidate the mechanism involved in T-cell-clone-mediated cytotoxicity and to determine the cytokine profile of both the lymphoma cell line and specific cytotoxic T lymphocyte clones. The results indicate that, despite surface expression of Fas receptor on Cou-LB and Fas ligand induction on TC5 and TC7 cell membranes, the CD4+ cytotoxic T lymphocyte clones do not use this cytotoxic mechanism to lyse their specific target. The TC7 clone uses instead a granzyme–perforin-dependent pathway. Furthermore, quantitative analysis of Th1 and Th2 cytokine mRNA expression in the cutaneous T cell lymphoma cell line as well as in TC5 and TC7 clones indicated that, whereas the tumor cells display a Th2-type profile (interleukin-4, interleukin-6, and interleukin-10), the cytotoxic T lymphocyte clones express Th1-type cytokines (interferon-γ, granulocyte macrophage colony stimulating factor, and interleukin-2). In addition, preincubation of the tumor-infiltrating lymphocyte clones with autologous tumor cells induced their activation and subsequent amplification of the Th1-type response. These results indicate a direct contribution of the malignant cells in the Th1/Th2 imbalance observed frequently in cutaneous T cell lymphoma patients and suggest their potential role in depressed cell-mediated immunity. Identification of CD4+ Th1-type cytotoxic T lymphocyte clones, the tumor antigen they recognize, and optimization of their cytokine expression profile should be useful for the design of new immunotherapy protocols in cutaneous T cell lymphoma. [ABSTRACT FROM AUTHOR]

Mycosis fungoides (MF) is the most common type of cutaneous T‐cell lymphoma. However, it is rare in pediatric population. Most of the cases of pediatric MF present with hypopigmented patches and/or various other forms, which may often mimic common childhood dermatoses, thereby causing a delay in the diagnosis. There are no established treatment guidelines for pediatric MF. As the progression of childhood MF is extremely rare and it has an indolent course, it is usually diagnosed at an early stage (IA, IB, IIA), and hence phototherapy with a response rate of >80% is a well‐established effective treatment in children. However, as recurrences are frequently seen on stopping the therapies, a maintenance regimen and long‐term follow‐up is equally important. This article reviews the epidemiological factors, clinical presentations, diagnosis, and various treatment modalities used in pediatric MF. We analyzed and compared the data of almost 616 childhood MF cases from various studies undertaken from 1988 to 2021. [ABSTRACT FROM AUTHOR]

Whole human skin can be reconstructed in vitro, using dermal equivalents made of fibroblasts in a collagen matrix. We recently described a new method of epidermalization of dermal equivalents, based on the insertion of punch biopsies and the migration of epidermal cells (EC) on the reconstructed dermis. In the present study, we show that no MHC class H or T6 positive Langerhans cells (LC) can be detected in this new epidermis. Functional studies with EC of this reconstructed epidermis show that these EC completely fail to induce proliferation of allogeneic lymphocytes in mixed epidermal cell lymphocyte reactions and to raise an allogencie T cell response. In contrast, fresh EC from the same donors induce a strong proliferative and cytotoxic response of the same effector cells. Moreover, the addition of fresh LC-containing EC autologous to effector lymphocytes does not restore an allogeneic proliferative and cytotoxic response directed against class I different EC of the new epidermis. Such a non-immunogenic whole skin model composed of two compartments, dermis and epidermis, completely devoid of class II-bearing antigen presenting cells. is thus a very promising technique for allogeneic skin grafting in the treatment of burns. [ABSTRACT FROM AUTHOR]

A distinct group of cutaneous lymphomas has been described on the basis of CD30 antigen expression by at least 75% of the tumoral cells. When confined to the skin, these CD30 positive cutaneous lymphomas seem to be associated with a better prognosis than CD30 negative counterparts and spontaneous regression may even occur. We observed a spontaneously regressive evolution in 6 out of 9 CD30 positive primary cutaneous large cell-lymphomas diagnosed during a 5-year period. Clinicopathological data of regressive cases were analysed. The mean age of patients was 56.5 years. They were 3 males and 3 females. Skin lesions were solitary nodule or plaque measuring from 1.5 cm to 11 cm in diameter. Histologically, the lesions were classified as pleomorphic, medium and large cell (5 cases) or large cell anaplastic lymphoma (1 case) according to the updated Kiel classification. Delay for spontaneous regression varied from 1 to 6 months. Three of the 6 patients had cutaneous relapses, followed by a spontaneous regression. All patients remained disease-free with an overall median follow-up of 30 months. Histologically, some distinctive signs such as epidermal pseudo-epitheliomatous hyperplasia, epidermotropism, edema, dermal vascular hyperplasia, seemed to be more frequently associated with spontaneously regressive evolution. [ABSTRACT FROM AUTHOR]

Cyclosporin A (CsA) is a strong inhibitor of skin allograft rejection. It has been also reported to act, not only on helper T cells, but also on the antigen-presenting functions of mouse epidermal cells (EC) enriched in Langerhans cells (LC). We tested the effects of CsA on the human allogeneic mixed epidermal cell-lymphocyte reaction (MECLR) using whole EC and freshly isolated LC as stimulator cells. Results were as follows. 1) CsA inhibited the lymphocyte proliferative response in a dose-dependent fashion, by about 80% for a CsA concentration of 10-7 M. To evaluate the effects of the drug on the two cell populations involved in MECLR, stimulator EC and responder PBMC were separately pulsed for 2 h with CsA, washed, and combined to form MECLR. Inhibition by CsA of the alloantigen-dependent lymphocyte proliferation appeared to be multifactorial, because CsA-pulsed EC and CsA-pulsed effector PBMC led to identical reductions of 40% each in proliferation. 2) The nature of EC sensitivity to CsA during MECLR was then analyzed after freshly separating highly purified CD1-positive LC (>95%) and LC-depleted EC (mainly keratinocytes), using an immunomagnetic particle technique. When responder PBMC were cultured with CsA-pulsed LC, a highly significant reduction of lymphocyte proliferation was observed, indicating that GsA has direct effects on LC. 3) Some of the possible mechanisms by which CsA might act on LC were studied. Substantial IL-1 activity and PGE2 amounts were induced during MECLR by LC and keratinocytes, but CsA did not act via these factors. Neither did it significantly modify HLA-DR, DQ, or DP antigen expressions on EC. In conclusion, CsA directly inhibits antigen presentation by human LC. This inhibition may partly explain the beneficial effects of CsA on skin allografts and certain cutaneous immune reactions. [ABSTRACT FROM AUTHOR]

The clinical efficacy of retinoids in benign and malignant skin diseases involving immune mechanisms suggests that they affect the immunologic functions of the epidermis. However, these effects have yet to be demonstrated. The action of vitamin A (retinol) and the synthetic retinoids, isotretinoin, etretinate, acitretin, and arotinoid-free acid have been studied on the lymphocyte proliferation induced by phytohemagglutinin (PHA), by the mixed lymphocyte reaction (MLR), and the mixed epidermal cell-lymphocyte reaction (MECLR). The results for PHA-induced proliferations were highly variable for all the retinoids. However, in MECLR the synthetic retinoids consistently reduced the proliferation by 20% - 30%. This occurred at therapeutic drug concentrations of about 10-7M. In MLR, a minor decrease of 10% -15% was only found for higher concentrations (10-5M). Retinol induced no effect in either reaction. Further analysis of acitretin on MECLR showed that it reduced lymphocyte proliferation in a dose-dependent fashion. This reduction was combined with a decrease in cytotoxic T-lymphocyte induction (CTL). Addition of 10-6 M acitretin at various times also revealed that its presence at cell culture initiation was necessary to inhibit proliferation significantly. Furthermore, cell treatments prior to MECLR showed that exposure of epidermal cells to acitretin was essential to produce this inhibition, suggesting that it acts directly on epidermal cells. Consequently, it is suggested that the specific inhibitory effect of synthetic retinoids on lymphocyte activation in MECLR may partly account for their therapeutic action on the skin. [ABSTRACT FROM AUTHOR]

Mycosis fungoides (MF) and Sézary syndrome (SS) are the best‐studied subtypes of cutaneous T‐cell lymphoma, a rare non‐Hodgkin lymphoma that primarily presents in the skin but can also involve blood, lymph nodes and viscera. The role of blood involvement in the assessment and staging of MF and SS has evolved in recent years from being classed as simply 'present' or 'absent', with no impact on staging, to full analysis of abnormal peripheral blood T cells using flow cytometry (FC) to detect and quantify aberrant T‐cell phenotypes and polymerase chain reaction (PCR) to characterize T‐cell receptor gene rearrangements. These sensitive peripheral blood assessments are replacing manual Sézary cell counts and have become an important part of clinical workup in MF and SS, providing the potential for more accurate prognosis and appropriate management. However, although international recommendations now include guidelines for FC analysis of peripheral blood markers for staging purposes, many clinics only perform these analyses in patients with advanced‐stage lymphoma, if at all, and there is still a need for standardized use of validated markers. Standardization of a single effective multiparameter FC panel would allow for accurate identification and quantification of blood tumour burden for diagnosis, staging, assessment of therapeutic response, and monitoring of disease progression at all stages of disease. Once defined, validation of an MF/SS biomarker FC panel will enable uptake into clinical settings along with associated standardization of protocols and reagents. This review discusses the evolution of the role of FC in evaluating blood involvement in MF and SS, considers recently published international guidelines and identifies evidence gaps for future research that will allow for standardization of FC in MF and SS. [ABSTRACT FROM AUTHOR]

The term 'sclerosing diseases of the skin' comprises specific dermatological entities, which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present consensus provides an update to the 2017 European Dermatology Forum Guidelines, focusing on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, updated strategies for the first‐ and advanced‐line therapy of sclerosing skin diseases are addressed in detail. Part 2 of this consensus provides clinicians with an overview of the diagnosis and treatment of scleromyxoedema and scleroedema (of Buschke). [ABSTRACT FROM AUTHOR]

Kimura disease (KD) is a rare, chronic angiolymphoproliferative inflammatory disease appearing to be mostly restricted to the skin and soft tissue. Cutaneous involvement of KD includes head and/or neck nodules showing suggestive histological features, frequently associated with an atopic dermatitis-like or prurigo-like presentation. KD is challenging to treat, with high rate of recurrence using current therapeutic strategies. Evidence for involvement of a T-helper type 2 (Th2) immune response in KD pathogenesis has been found in previous studies. Consequently, this study aimed to determine the efficacy and safety of dupilumab, a human monoclonal antibody that inhibits signalling of key Th2 cytokines, interleukin (IL)-4 and IL-13, within a single-centre cohort of patients with cutaneous KD. Two adults with a diagnosis of refractory (failure of at least one treatment line) cutaneous-restricted KD based on clinical, biological, histological, molecular and imaging findings received dupilumab for KD, and showed dramatic response with a good safety profile. [ABSTRACT FROM AUTHOR]

The CCR4-directed monoclonal antibody mogamulizumab has been shown to significantly improve progression-free survival and overall response rate compared with vorinostat in adults with relapsed/refractory mycosis fungoides (MF) and Sézary syndrome (SS). One of the most common adverse events seen with mogamulizumab in MF/SS patients is rash. Because of the protean nature of MF/SS and the variable clinical and histopathological features of mogamulizumab-associated rash, healthcare providers may have difficulty distinguishing rash from disease, and may not be aware of appropriate treatment strategies for this generally manageable adverse event. The objective of this report was to combine results from published literature with experiences and recommendations from multiple investigators and institutions into clinical best practice recommendations to assist healthcare providers in identifying and managing mogamulizumab-associated rash. Optimal management, which includes biopsy confirmation and steroid treatment, requires a multidisciplinary approach among oncology, dermatology, and pathology practitioners. Infographic: [ABSTRACT FROM AUTHOR]

Patients with mycosis fungoides (MF) and Sézary syndrome (SS) often require multiple lines of systemic therapy. In the phase 3 MAVORIC study (NCT01728805), mogamulizumab demonstrated superiority to vorinostat in median progression-free survival (PFS) and confirmed overall response rate (ORR) in patients with MF/SS. This post hoc analysis examined the effects of number and type of prior systemic therapies on mogamulizumab response. MAVORIC patients randomized to mogamulizumab (1.0 mg/kg intravenously weekly) or vorinostat (400 mg orally daily) were grouped by number of prior therapies and immunomodulatory activity of immediate prior systemic therapy while also considering time elapsed since treatment. ORR, PFS, and duration of response (DOR) did not vary with number of prior therapies. ORR and DOR remained consistent regardless of immediate prior therapy type. Additionally, immunomodulatory activity of the last prior therapy and time from prior treatment generally did not affect the ORR or PFS observed in response to mogamulizumab. [ABSTRACT FROM AUTHOR]

This article, published in the Journal of the European Academy of Dermatology & Venereology, explores the impact of blood tumor clone frequency on the time to next treatment in mycosis fungoides (MF), the most common cutaneous T-cell lymphoma. The study used high-throughput DNA sequencing to identify T-cell clones in MF patients and determine the tumor clone frequency (TCF) in the total T-cell infiltrate. The findings suggest that an increased frequency of the malignant T-cell clone in the blood is correlated with reduced time to next treatment in MF patients. However, further validation in a larger cohort is needed to confirm these results. [Extracted from the article]

Recombinant interferon beta‐1b is one of the treatment options of multiple sclerosis (MS). Insertional biologics that are used in the treatment of MS may lead to skin adverse effects, for example, morphea. [ABSTRACT FROM AUTHOR]

On behalf of the EORTC Cutaneous Lymphoma Tumours Group (EORTC-CLTG) and following up on earlier versions published in 2006 and 2017 this document provides an updated standard for the treatment of mycosis fungoides and Sézary syndrome (MF/SS). It considers recent relevant publications and treatment options introduced into clinical practice after 2017. Consensus was established among the authors through a series of consecutive consultations in writing and a round of discussion. Treatment options are assigned to each disease stage and, whenever possible and clinically useful, separated into first- and second line options annotated with levels of evidence. Major changes to the previous version include the incorporation of chlormethine, brentuximab vedotin, and mogamulizumab, recommendations on the use of pegylated interferon α (after withdrawal of recombinant unpegylated interferons), and the addition of paragraphs on supportive therapy and on the care of older patients. Still, skin-directed therapies are the most appropriate option for early-stage MF and most patients have a normal life expectancy but may suffer morbidity and impaired quality of life. In advanced disease treatment options have expanded recently. Most patients receive multiple consecutive therapies with treatments often having a relatively short duration of response. For those patients prognosis is still poor and only for a highly selected subset long term remission can be achieved with allogeneic stem cell transplantation. Understanding of the disease, its epidemiology and clinical course, and its most appropriate management are gradually advancing, and there is well-founded hope that this will lead to further improvements in the care of patients with MF/SS. • Mycosis fungoides and Sézary syndrome are variants of cutaneous T cell lymphomas. • Prognosis and choice of treatment depend on disease stage. • Treatment recommendations are provided by the EORTC Cutaneous Lymphoma Tumour Group. • Considerations for supportive care and treatment of elderly patients are included. [ABSTRACT FROM AUTHOR]

Cutaneous T-cell lymphomas are a diverse group of T-cell neoplasms, characterised by initial infiltration of the skin, and sometimes extension to the lymph nodes, blood and internal organs. Sézary syndrome is an erythrodermic form distinguished by the significant presence of circulating peripheral blood tumour cells. Numerous diagnostic and therapeutic advances have been made in this disease in recent years, and we offer here a non-exhaustive review. [ABSTRACT FROM AUTHOR]

Simple Summary: Here, we report real-world treatment patterns and the overall survival of 104 patients with relapsing/refractory (R/R) MF who had received first-line therapy between 1984 and 2016. Our study found that second- and third-line therapies for R/RMF were heterogeneous, including systemic therapies, radiotherapy and topical therapies. More than two-thirds of patients at second- and third-line treatment received chemotherapy, and we observed that the median overall survival was longer with non-chemotherapy (not reached) vs. chemotherapy (6.5 years) treatment, suggesting that non-chemotherapy options may be more beneficial to patients. (1) Background: Most patients with mycosis fungoides (MF), a form of cutaneous T-cell lymphoma (CTCL), develop relapsed/refractory (R/R) disease following front-line systemic therapy. This report describes treatment patterns and outcomes from the subpopulation with R/R MF. (2) Methods: This observational, retrospective, cohort study analyzed patient records (1984–2016) from 27 clinical sites in Europe. Outcomes included treatments received, response to first-, second- and third-line treatment, overall survival (OS) and progression-free survival (PFS). (3) Results: Of 104 patients with MF, 100 received second-line and 61 received third-line therapy. The median (range) times from the start of first-line therapy to the first R/R MF and from the first to the second R/R MF were 11.2 (0.3–166.5) and 13.5 (0.0–174.6) months, respectively. Second-and third-line treatment options varied and comprised systemic therapies (85% and 79% of patients, respectively), radiotherapy (32% and 34%, respectively) and topical therapies (48% and 36%, respectively). The median (95% confidence interval [CI]) OS from the diagnosis of the first R/R MF was 11.5 (6.5–not reached [NR]) years and was higher with non-chemotherapy (NR) versus chemotherapy (6.5 years); the estimated median PFS (95% CI) from the time of the first R/R MF was 1.3 (1.0–2.1) years. (4) Conclusions: High rates of R/R disease were observed after second- and third-line treatments in this real-world cohort, with longer median OS in patients receiving non-chemotherapy treatment versus chemotherapy. Following the standard management of MF and using recently approved targeted therapies can help improve patient outcomes in advanced-stage MF. [ABSTRACT FROM AUTHOR]

The article discusses the challenges and complexities of diagnosing and treating cutaneous T-cell lymphoma (CTCL), a rare group of non-Hodgkin lymphomas that primarily affect the skin. The lack of standardized approaches and specialized training programs for skin lymphoma specialists in Europe has led to divergent approaches in patient care. The HORIZON program, which involved clinical and research rotations across five European centers, aimed to address this gap and foster a collaborative global network. The rotations provided valuable insights into diagnostics, therapeutics, and research methodologies, including the use of advanced techniques and technologies. Consistency was observed in adopting both traditional and newer treatments, aligning with the latest guidelines. The involvement of clinical nurse specialists, particularly in the UK, was noted as an opportunity for holistic and comprehensive patient-centered care. The program has laid the groundwork for a collaborative network and ongoing research projects. A second program is planned for 2025. The article was funded by Kyowa Kirin International PLC, and the authors declare no conflicts of interest. [Extracted from the article]

Basal cell carcinomas (BCCs) are the most common types of skin neoplasm. The finger, toe, and nail unit are uncommon and rare locations of BCC. Only a few patients with foot BCC have been reported, and ungual BCC is even less frequent. We present a patient with a BCC on the left first toe. Clinically, it appeared as a brown‐colored plaque with an irregular border on the nail fold and dorsum of the left thumb. Histopathological findings were consistent with the pigmented type of BCC. Surgical approach with subsequent full thickness mesh graft led to a complete remission. Follow‐up at 10 months revealed a functionally and cosmetically acceptable outcome. The clinical presentation of nail unit BCC is variable, and nonspecific manifestations occur more frequently. Our case stated the necessity of histopathologic examination in ulcerous lesions resistant to topical treatment. [ABSTRACT FROM AUTHOR]

Presents a letter written to the editor of the 'Journal of Investigative Dermatology.' Comments on a study on primary cutaneous Non-T Non-B CD4[sup +]CD56[sup +] Lymphomas tumors. Laurence Boumsell

Our current mycosis fungoides (MF) and Sézary Syndrome (SS) staging system includes blood-classification from B0-B2 for patch/plaque/tumour or erythroderma based on manual Sézary counts but results from our EORTC survey confirm these are rarely performed in patch/plaque/tumour MF, and there is a trend towards using flow cytometry to measure blood-class. Accurately assigning blood-class effects overall stage and the ‘global response’ used to measure treatment responses in MF/SS and hence impacts management. The EORTC Cutaneous Lymphoma Task Force Committee have reviewed the literature and held a Workshop (June 2017) to agree a definition of blood-class according to flow cytometry. No large study comparing blood-class as defined by Sézary count with flow cytometry has been performed in MF/SS. The definition of blood-class by flow cytometry varies between publications. Low-level blood involvement occurs in patch/plaque/tumour much less than erythroderma (p < 0.001). The prognostic relevance of blood involvement (B1 or B2) in patch/plaque/tumour is not known. Studies have not shown a statistically worse difference in prognosis in erythrodermic MF patients with low-level blood involvement (IIIB) versus those without (IIIA), but Sezary patients who by definition have a leukaemic blood picture (staged IVA1 or higher) have a worse prognosis. For consistency flow, definition for blood-class must be an objective measurement. We propose absolute counts of either CD4+CD7-or CD4+CD26-where B0<250/μL, B1 = 250/μl–<1000/μL and B2≥1000/μL plus a T-cell blood clone. Fluctuations between B0 and B1 should not be considered in the treatment response criteria until further prognostic information is known. [ABSTRACT FROM AUTHOR]

This article discusses two cases of patients with cutaneous T-cell lymphoma (CTCL) who experienced severe relapses after receiving ruxolitinib, a JAK1/2 inhibitor, for the treatment of graft-versus-host disease (GVHD) following allogeneic stem cell transplantation (allo-HSCT). The patients initially showed positive responses to ruxolitinib for GVHD, but their CTCL worsened, leading to erythroderma and skin tumors. The authors suggest that ruxolitinib may have a deleterious effect on CTCL after allo-HSCT, possibly impairing the graft versus leukemia (GVL) response. Further investigation is needed to evaluate the use of JAK inhibitors in CTCL treatment after allo-HSCT. [Extracted from the article]

Presents a letter to the editor about inhibitory effect of Cyclosporin A, published in the November 1991 issue of the journal "The journal of Investigative Dermatology."

Introduction: Leprosy reactions (LRs) are inflammatory responses observed in 30%-50% of people with leprosy. First-line treatment is glucocorticoids (GCs), often administered at high doses with prolonged courses, resulting in high morbi-mortality. Methotrexate (MTX) is an immunomodulating agent used to treat inflammatory diseases and has an excellent safety profile and worldwide availability. In this study, we describe the efficacy, GCs-sparing effect and safety of MTX in LRs. Methods: We conducted a retrospective multicentric study in France consisting of leprosy patients receiving MTX for a reversal reaction (RR) and/or erythema nodosum leprosum (ENL) since 2016. The primary endpoint was the rate of good response (GR) defined as the complete disappearance of inflammatory cutaneous or neurological symptoms without recurrence during MTX treatment. The secondary endpoint was the GCs-sparing effect, safety and clinical relapse after MTX discontinuation. Results: Our study included 13 patients with LRs (8 men, 5 women): 6 had ENL and 7 had RR. All patients had had at least one previous course of GCs and 2 previous treatment lines before starting MTX. Overall, 8/13 (61.5%) patients had GR, allowing for GCs-sparing and even GCs withdrawal in 6/11 (54.5%). No severe adverse effects were observed. Relapse after MTX discontinuation was substantial (42%): the median relapse time was 5.5 months (range 3–14) after stopping treatment. Conclusion: MTX seems to be an effective alternative treatment in LRs, allowing for GCs-sparing with a good safety profile. Furthermore, early introduction during LRs may lead to a better therapeutic response. However, its efficacy seems to suggest prolonged therapy to prevent recurrence. Author summary: Leprosy reactions (LRs) are acute inflammatory episodes that complicate 30% to 50% of Mycobacterium leprae infections. Type 1 is known as reversal reaction (RR), and type 2 is known as erythema nodosum leprosum (ENL). The two types have relatively distinct pathogenesis and clinical features; furthermore, they can advance to become severe and progress to irreversible nerve damage and deformities. Beyond leprosy infection, LR can bring about neurological burden, poor quality of life, and risk of further descent into poverty for often young patients. Despite effective standardized treatment of leprosy infection with multidrug therapy (MDT) since 1981, treating LRs prove to be challenging. First-line treatment of LR is based on prolonged systemic glucocorticoids (GCs) therapy. The current challenge in leprosy is now to develop and evaluate new therapeutic alternatives to reduce not only the sequelae and morbidity of LR but also the lasting side effects of GCs. Thalidomide is an effective alternative in moderate to severe ENL, but its use is limited given its numerous adverse effects. Methotrexate (MTX) is an immunomodulating agent used to treat inflammatory diseases and has an excellent safety profile and worldwide availability. Here, we describe the efficacy, GCs-sparing effect, and safety of MTX in LR. [ABSTRACT FROM AUTHOR]

Primary cutaneous diffuse large B-cell lymphoma, leg-type (PCDLBCL-LT) is an aggressive cutaneous lymphoma. Bone involvement is rare and poorly described. We present five cases of PCDLBCL-LT with bone localization. In four cases, the bone involvement was diagnosed during the initial staging with positron emission tomography (PET) or computed tomography (CT) scan, and in the fifth case after tibial fracture during treatment with rituximab (RTX) and polychemotherapy (PCT). PCDLBCL-LT can be asymptomatic and involve bone sites distant from cutaneous lesions. None had other extracutaneous involvement. In our series, all patients received RTX-PCT as first-line chemotherapy and all had early relapses or progression. Second-line treatments had poor efficacy. Our series shows that bone involvement seems to be associated with poor prognosis in PCDLBCL-LT. Bone localization is not diagnosed with initial thoracic–abdominal–pelvic CT when asymptomatic and affecting the limbs only. If there is a suspicion of PCDLBCL-LT, patients should undergo systematic investigation with alternative imaging techniques, including PET, both at baseline and if there is any concern during follow-up. [ABSTRACT FROM AUTHOR]

Atypical tuberous myxedema (ATM) is a rare skin condition first described by Jadassohn and Dössekker in 1916.[1] Belonging to the heterogeneous group of mucinoses, ATM is considered as an atypical presentation of scleromyxedema with diffuse nodular thickening of the skin and without monoclonal gammopathy. A biopsy sample from a nodule revealed diffuse dermal mucin deposits, extensive fibrosis and fibroblastic proliferation. A deep incisional biopsy sample of the neck revealed diffuse deposit of mucin associated with an extensive fibrosis and a fibroblastic proliferation. [Extracted from the article]

Summary: Background: Primary cutaneous peripheral T‐cell lymphomas with a T‐follicular helper phenotype (pcTFH‐PTCL) are poorly characterized, and often compared to, but not corresponding with, mycosis fungoides (MF), Sézary syndrome, primary cutaneous CD4+ lymphoproliferative disorder, and skin manifestations of angioimmunoblastic T‐cell lymphomas (AITL). Objectives: We describe the clinicopathological features of pcTFH‐PTCL in this original series of 23 patients, and also characterize these cases molecularly. Methods: Clinical and histopathological data of the selected patients were reviewed. Patient biopsy samples were also analysed by targeted next‐generation sequencing. Results: All patients (15 men, eight women; median age 66 years) presented with skin lesions, without systemic disease. Most were stage T3b, with nodular (n = 16), papular (n = 6) or plaque (atypical for MF, n = 1) lesions. Three (13%) developed systemic disease and died of lymphoma. Nine (39%) patients received more than one line of chemotherapy. Histologically, the lymphomas were CD4+ T‐cell proliferations, usually dense and located in the deep dermis (n = 14, 61%), with the expression of at least two TFH markers (CD10, CXCL13, PD1, ICOS, BCL6), including three markers in 16 cases (70%). They were associated with a variable proportion of B cells. Eight patients were diagnosed with an associated B‐cell lymphoproliferative disorder (LPD) on biopsy, including Epstein–Barr virus (EBV)‐positive diffuse large B‐cell lymphoma (n = 3), EBV+ LPD (n = 1) and monotypic plasma cell LPD (n = 4). Targeted sequencing showed four patients to have a mutated TET2–RHOAG17V association (as frequently seen in AITL) and another a TET2/DNMT3A/PLCG1/SETD2 mutational profile. The latter patient, one with a TET2–RHOA association, and one with no detected mutations, developed systemic disease and died. Five other patients showed isolated mutations in TET2 (n = 1), PLCG1 (n = 2), SETD2 (n = 1) or STAT5B (n = 1). Conclusions: Patients with pcTFH‐PTCL have pathological and genetic features that overlap with those of systemic lymphoma of TFH derivation. Clinically, most remained confined to the skin, with only three patients showing systemic spread and death. Whether pcTFH‐PTCL should be integrated as a new subgroup of TFH lymphomas in future classifications is still a matter of debate. What is already known about this topic?There is a group of cutaneous lymphomas that express T‐follicular helper (TFH) markers that do not appear to correspond to existing World Health Organization diagnostic entities.These include mycosis fungoides, Sézary syndrome, or primary cutaneous CD4+ small/medium‐sized T‐cell lymphoproliferative disorder or cutaneous extensions of systemic peripheral T‐cell lymphomas (PTCL) with TFH phenotype. What does this study add?This is the first large original series of patients with a diagnosis of primary cutaneous PTCL with a TFH phenotype (pcTFH‐PTCL) to be molecularly characterized.pcTFH‐PTCL may be a standalone group of cutaneous lymphomas with clinicopathological and molecular characteristics that overlap with those of systemic TFH lymphomas, such as angioimmunoblastic T‐cell lymphoma, and does not belong to known diagnostic groups of cutaneous lymphoma.This has an impact on the treatment and follow‐up of patients; the clinical behaviour needs to be better clarified in further studies to tailor patient management. [ABSTRACT FROM AUTHOR]

At best, stable disease (SD) was achieved after 13 of the treatment lines (43%), partial response (PR) after 12 (40%), CR after two (7%) and progressive disease (PD) after three (10%). GSS treatment is challenging and mostly allows patients to achieve SD or PR. At the last visit, one patient (14%) was in ongoing CR 5 years after stopping methotrexate and three patients (43%) had controlled disease, including one without treatment. [Extracted from the article]

• Cutaneous T-cell lymphomas are a diverse group of malignant blood disorders characterized by initial skin infiltration. • These diseases are characterized by the plasticity and heterogeneity of the tumor cells in different tissue compartments. • Recent advancements in understanding the pathophysiology of CTCL have improved diagnostic and therapeutic strategies. Cutaneous T-cell lymphomas (CTCL) are a diverse group of malignant blood disorders characterized by initial skin infiltration, and sometimes, tumor spreading to lymph nodes, blood, and viscera. Mycosis fungoides is the most common form. Sézary syndrome is a distinctive form of CTCL marked by a significant presence of circulating tumor cells in peripheral blood. These diseases are characterized by the plasticity and heterogeneity of the tumor cells in the different tissue compartments, and a difficulty in identifying these tumor cells for diagnostic purposes and therapeutic monitoring. Progress has been made in the understanding of the pathophysiology of these diseases in recent years, and we provide here a review of these advancements. [ABSTRACT FROM AUTHOR]

Presents a response by the authors to a letter to the editor on their article "Cyclosporin A Inhibits the Antigen Presenting Functions of Freshly Isolated Human Langerhans Cells in Vitro," published in the February 1992 issue of the journal "The Society of Investigative Dermatology."

Presents a letter to the editor T-cell receptor genes.