Allogeneic transplantation in advanced cutaneous T-cell lymphomas (CUTALLO): a propensity score matched controlled prospective study.

BACKGROUND: Advanced-stage cutaneous T-cell lymphomas (CTCLs) are rare, usually refractory, and fatal diseases. Case series have suggested that allogeneic haematopoietic stem cell transplantation (HSCT) might improve the prognosis of advanced-stage CTCLs. The objective of this study was to investigate the effect of allogeneic HSCT compared with non-HSCT therapy on the outcome of individuals with advanced-stage CTCLs. METHODS: In this prospective, multicentre, matched controlled trial, conducted at 30 hospitals, participants with advanced CTCLs were allocated treatment: if they had an available compatible related donor they were assigned to allogeneic HSCT, or if not they were allocated to non-allogeneic HSCT therapy. Key inclusion criteria were participants aged 18-70 years, with advanced stage mycosis fungoides or Sézary syndrome, and at least one poor prognostic criteria. Participants were excluded if they were not in complete or partial remission of the disease. Propensity score 1:1 matching with replacement (ie, that each participant treated with HSCT was matched to the participant with the closest propensity score treated with non-HSCT therapy, even if they had already been matched) was used to handle confounding factors, with the balance of covariate distribution between HSCT and non-HSCT groups assessed using standardised mean differences. The primary endpoint was progression-free survival in the matched intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02520908), and is currently active but not recruiting. FINDINGS: From June 1, 2016, to March 3, 2022, total of 99 participants were enrolled at 17 centres in France. Participants with a sibling or matched unrelated donor were assigned to allogeneic HSCT (HSCT group, n=55 [56%]) and participants without a donor were assigned to non-allogeneic HSCT treatment (non-HSCT group, n=44 [44%]). The median follow-up among survivors was 12·6 months (IQR 11·0-35·2). In the HSCT group, 51 participants (93%) were 1:1 matched to participants from the non-HSCT group. In the intention-to-treat analysis, median progression-free survival was significantly longer in the HSCT group (9·0 months [95% CI 6·6-30·5]) than in the non-HSCT group (3·0 months [2·0-6·3]), with a hazard ratio of 0·38 (95% CI 0·21-0·69; p<0·0001). In the per-protocol population, 40 participants (78%) in the HSCT group had 101 serious events and 29 participants (67%) in the non-HSCT group had 70 serious adverse events. The most common serious adverse event other than graft-versus-host disease in both groups was infections, occurring in 30 participants (59%) in the HSCT group and in 19 participants (44%) in the non-HSCT group. INTERPRETATION: Allogeneic HSCT was associated with significantly longer progression-free survival in participants with advanced-stage CTCLs. These results indicate that allogeneic HSCT treatment should be made available to individuals with high-risk, advanced-stage mycosis fungoides or Sézary syndrome who achieve pre-transplant disease remission. FUNDING: French Ministry of Health, National Cancer Institute, Programme Hospitalier de Recherche Clinique en Cancérologie.

Predictors of adherence to Narrowband ultraviolet B first-month treatment dosage plan.

BACKGROUND: The adherence to a narrowband ultraviolet B (NB-UVB) treatment plan is derived, in large part, from the patient's skin tolerance to the phototherapy dose. At present, the initial and first-month incremental phototherapy doses are determined prior to treatment initiation based on the patient's Fitzpatrick skin phototyping. OBJECTIVES: To identify variables that predict adherence to NB-UVB first-month treatment dosage plan. METHODS: Charts of 1000 consecutive patients receiving NB-UVB at a hospital-based phototherapy unit were retrospectively analyzed. We included patients receiving NB-UVB for atopic dermatitis, psoriasis, vitiligo, and mycosis fungoides. The first-month NB-UVB treatment plan was determined based on the patient's Fitzpatrick phototype. Adherence to treatment was defined as receiving at least 80% of the planned first-month cumulative dose. We compared adherent vs. non-adherent patient groups for age, sex, Fitzpatrick phototype, presence of freckles, nevus count category, and type of dermatological disease. RESULTS: The study included 817 eligible patients, mean age 40 (2-95) years; 54% men; 32% had Fitzpatrick phototype I-II. Distribution by diagnosis was atopic dermatitis (29%), psoriasis (27%), vitiligo (23%), and mycosis fungoides (21%). Adherence to NB-UVB treatment plan was observed in 71% of patients. Adherence decreased with age, with 7% decrease per year (P = 0.03) and was higher among mycosis fungoides patients (77.3%) compared to all other diagnoses (69.8%; P = 0.02). CONCLUSIONS: Adherence to NB-UVB treatment may be related to age and diagnosis. Fitzpatrick phototype-based first-month treatment plans should be modified accordingly.

Efficacy of narrowband UVB phototherapy in early-stage mycosis fungoides in Iranian patients.

Narrowband UVB (NB-UVB) has been shown to be effective for the treatment of early mycosis fungoides (MF) in light-skinned patients, but the effect of NB-UVB on patients with darker skin phototypes needs further investigation. The aim of this study was to evaluate the effect of NB-UVB in the treatment of early-stage MF in Iranian patients. In this retrospective study, 24 patients with the diagnosis of early MF (9 stage AI, 15 stage IB) were enrolled. All patients were treated with NB-UVB phototherapy 2-3 times weekly. After achieving complete response, a maintenance treatment was recommended. The response rate, side effects, and recurrence rate in the follow-up period were assessed. The follow-up period was ranged 6 to 24 months. Ten patients (41.7%) had complete remission after a mean number of 42.9 treatment and mean cumulative dose of 58.11 J/cm2. Twelve patients (50%) had partial response, and 2 patients (8.3%) had no response. After discontinuation of maintenance treatment, 4 of 10 patients (40%) with complete remission relapsed within a mean of 5 months. Side effects were limited to erythema (12.5%) and hyperpigmentation (4%). NB-UVB is a safe and effective method for the treatment of early MF, but it seems that more treatment sessions and higher doses of NB-UVB are required for darker skin phototypes.

Interferon α-induced lupus-like reaction in a mycosis fungoides patient: A case report.

Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphomas and interferon α is one of the treatment modalities for MF patients. So far, various side effects have been reported in connection with interferon use, including lupus-like reaction, which is relatively rare and classified as an injection-site reactions (ISR). We report a 38-year-old female with history of MF for 2 years who developed cutaneous lesions at the sites of interferon α-2b injections. There are few reports of lupus-like reaction due to therapy with interferon in malignant melanoma and multiple sclerosis (MS) patients, but there is no report in the literature about this side effect among patients with MF.

Management of relapsed cutaneous T-Cell lymphoma following allogeneic hematopoietic stem cell transplantation: Review with representative patient case.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment option for patients with refractory cutaneous T-cell lymphoma (CTCL) through replacement of the bone marrow responsible for lymphoma cells and possibly induction of a graft-versus-lymphoma effect. However, allo-HSCT is not always curative; relapse of CTCL occurs in about half of patients post-transplant. Treatment of relapsed CTCL after allo-HSCT is challenging because post-transplant patients are at high risk of graft-versus-host disease, and this condition may be precipitated or exacerbated by standard CTCL therapies. The benefit of each potential therapy must therefore be weighed against its risk of graft versus host disease (GVHD). In this article, we review the management of relapsed CTCL after allo-HSCT. We begin with an exemplative patient whose relapsed Sezary syndrome was successfully treated without development of GVHD. We also report high-throughput T-cell receptor sequencing data obtained during the patient's disease relapse and remission. We then review general guidelines for management of relapsed CTCL and summarize all reported cases and outcomes of relapsed CTCL after transplant. We conclude by reviewing the current CTCL therapies and their risk of GVHD.

How to Sequence Therapies in Mycosis Fungoides.

OPINION STATEMENT: Choice of therapy in mycosis fungoides is based on both patient- and lymphoma-specific factors, such as disease characteristics, comorbidities, symptoms and effect on quality of life, potential associated toxicities of therapy, response and tolerance to prior lines of therapy, and convenience and practicality. Generally, we sequence therapies from least toxic, targeted, nonimmunosuppressive to more toxic, immunosuppressive and from single agent to multiple agents, as necessary. If more toxic, immunosuppressive agents are required to alleviate disease burden or symptoms, we generally use them just long enough to control the disease, then transition to a maintenance regimen with less toxic, less immunosuppressive agents.

Cutaneous T-cell lymphomas: 2021 update on diagnosis, risk-stratification, and management.

DISEASE OVERVIEW: Cutaneous T-cell lymphomas are a heterogenous group of T-cell neoplasms involving the skin, the majority of which may be classified as Mycosis Fungoides (MF) or Sézary Syndrome (SS). DIAGNOSIS: The diagnosis of MF or SS requires the integration of clinical and histopathologic data. RISK-ADAPTED THERAPY: TNMB (tumor, node, metastasis, blood) staging remains the most important prognostic factor in MF/SS and forms the basis for a "risk-adapted," multi-disciplinary approach to treatment. For patients with disease limited to the skin, expectant management or skin-directed therapies is preferred, as both disease-specific and overall survival for these patients is favorable. In contrast, patients with advanced-stage disease with significant nodal, visceral or blood involvement are generally approached with systemic therapies, including biologic-response modifiers, histone deacetylase inhibitors, or antibody-based strategies, in an escalating fashion. In highly-selected patients, allogeneic stem-cell transplantation may be considered, as this may be curative in some patients.

Mycosis Fungoides and Sézary Syndrome: Updates and Review of Current Therapy.

OPINION STATEMENT: While most patients with early-stage mycosis fungoides (MF) follow an indolent course, patients with advanced-stage MF/Sézary syndrome (SS) have a poor prognosis with a median survival of less than 5 years. Although there are a number of treatments currently available, achieving and maintaining a durable response remain challenging, especially in advanced-stage MF/SS. The choice of frontline therapy is dependent on the stage of disease. For early-stage MF, the treatment concept is to control skin lesions mainly by skin-directed therapies, such as topical therapies, phototherapies, and radiotherapies. For advanced-stage MF/SS, systemic treatments by biological or targeted therapies including bexarotene and interferon either alone or in combination are tried first, with more immunosuppressive chemotherapies being reserved for refractory or rapidly progressive disease. Recent improvements in biological or targeted therapies include brentuximab vedotin and mogamulizumab. When biopsy samples have 10% or more CD30-positive malignant cells, brentuximab vedotin, an anti-CD30 antibody conjugated to monomethyl auristin E, can be a desirable treatment option. For cases with blood involvement, mogamulizumab, an antibody binding to C-C chemokine receptor 4, is effective with high response rates. In the refractory setting, alemtuzumab, histone deacetylase inhibitors, pralatrexate, gemcitabine, and doxorubicin are considered as the treatment option. Because only allogeneic hematopoietic stem cell transplantation can offer a chance of cure with durable complete remission, advanced-stage patients with a markedly short life expectancy should be evaluated for eligibility. Given that there are few randomized controlled studies in the literature, it is necessary to investigate which therapy is preferable for each patient with MF/SS by comparative prospective trials.

Mycosis fungoides development after combined immune checkpoint blockade therapy in a patient with malignant melanoma: a case report.

Immune checkpoint blockade therapy can induce immune-related toxicity, but cutaneous lymphoma development has not been reported. A 56-year-old woman presented with two well-demarcated erythematous macules on the right sole and vitiligo on her extremities. Her facial melanoma had been treated with combination therapy (ipilimumab and pembrolizumab), followed by pembrolizumab monotherapy, a year prior. Microscopy revealed small-to-medium-sized lymphocytes permeating along with the basal epidermal layer. These were immuno-positive for CD2, CD3, and CD5, and showed complete CD7 loss; CD30, TCR-beta F1, and PD-1 were also detected. They exclusively expressed CD8, not CD4, and had a Ki-67 labeling index of 30-40%. Epstein-Barr virus in-situ hybridization was negative. Clonal T-cell receptor beta and gamma chain gene rearrangements were detected. Hence, the lesions were diagnosed as mycosis fungoides. This is the first report of mycosis fungoides development after anti-melanoma immunotherapy. The patient is currently on steroid ointments and phototherapy.

Granulomatous slack skin mycosis fungoides developing simultaneously with sarcoid-like lesions in a patient with repeated anabolic injections in the past?

We present a 32-year-old man with successful treatment and remission of mycosis fungoides of both axillae in 2016 after PUVA therapy and systemic and local administration of corticosteroids. Subsequently, in 2017, the patient also achieved remission of a T-cell CD 30 positive, ALK-1 negative large-cell lymphoma of a retroperitoneal and inguinal lymph node after chemotherapy and radiotherapy. One year later, in 2018, the patient presented to our clinic with progression of skin lesions in both axillary areas and the appearance of а tumor in the right gluteal region.Dermatological examination showed livid-to-erythematous, partly sclerotic plaques in the right inguinal area, cutis laxa-like plaque formations in the right axillary region with similar but less-developed changes in the left axillary fold, a solitary subcutaneous tumor formation affecting the entire right gluteal region, and enlarged, palpable lymph nodes in the right para-axillary area. Biopsies were obtained from an axillary lesion and the surgically removed axillary lymph nodes, and histological examination revealed changes of granulomatous slack skin in the axilla and reactive inflammatory changes in the lymph nodes. Histology of gluteal tissue showed a "foreign body" type of reaction with sarcoid-like features, where the patient in the past have been injected with anabolic and steroidal drugs. Herein we describe a patient with simultaneous occurrence of granulomatous slack skin type mycosis fungoides and a sarcoid-like reaction. The question remains open whether this represents the so-called sarcoidosis-lymphoma syndrome or, more likely, granulomatous slack skin MF associated with a sarcoid-like reaction of "foreign body" type. The possibility that disturbance of tissue homeostasis by incorporation of certain adjuvants within injections (for example) in the past might have been an inducer of cutaneous T cell lymphoma and sarcoidosis/sarcoid like lesions seems reasonable but also speculative.

CLINICAL CASE OF CUTANEOUS T-CELL LYMPHOMA IN A PATIENT WHO GOT INJURED AFTER THE DISASTER ON CHORNOBYL NUCLEAR POWER PLANT. / KLINIChNYY̆ VYPADOK T-KLITYNNOÏ LIMFOMY ShKIRY U PATsIIeNTKY, IaKA POSTRAZhDALA VNASLIDOK AVARIÏ NA ChAES.

A clinical case of cutaneous T-cell lymphoma is presented in this paper - Mycosis fungoides, a tumorous stage that developed in a patient who suffered as a result of the Chornobyl accident. The most likely development of this di- sease is due to the influence of the radiation factor, which led to the affection of lymphoid cells. This disease has characteristic staging with a typical morphological pattern only in later stages, therefore, the diagnosis usually occurs in evident clinical and histological changes of the mycotic and tumorous stages, when treatment is ineffec- tive. The features of the disease and treatment are described.

Mycosis fungoides: A great imitator.

Mycosis fungoides (MF), the most common cutaneous T-cell lymphoma, typically presents in its early stage as inflammatory erythematous patches or plaques, with epidermotropism as the histopathologic hallmark of the disease. Over the past 30 years, numerous atypical types of MF, which deviate from the classic Alibert-Bazin presentation of the disease, have been described. These variants can simulate a wide variety of benign inflammatory skin disorders either clinically, both clinically and histopathologically, or mainly histopathologically. We have summarized the many faces of the disease, which set MF as a "great imitator," with special focus on the differential diagnosis and its benign mimickers.

Pityriasis Lichenoid-like Mycosis Fungoides in a 9-year-old Boy: A Case Report.

Dear Editors, Pityriasis lichenoides (PL)-like mycosis fungoides (MF) is a rare variant of MF, presenting clinical findings of PL but histological features of MF. It was first reported by Ko et al. (1) and only a few cases have been reported since (2-5). Herein we report the case of a boy with PL-like MF and review the related literature. A 9-year-old boy presented with a 1-year history of multiple pruritic crusted erythematous papules and scaly pink maculopatches on the face, trunk, and extremities (Figure 1, a and b). Histologic examination of a papule revealed lymphocytic epidermotropism and lymphocytes tagging the dermoepidermal junction. The nuclei of the lymphocytes were hyperchromatic and irregular (Figure 1, c and d). Immunohistochemically, the infiltrating lymphocytes revealed positivity for CD2, CD3, CD5, CD7, and CD8, but were negative for CD4, CD20, CD30, CD68, and CD163 (Figure 1, e-g). T-cell receptor gene rearrangement analysis (TCR-GRA) demonstrated the rearrangement of the gamma chain (Figure 1, h). PL-like MF was diagnosed. The patient was started on narrowband ultraviolet B (NBUVB) phototherapy. The skin lesions markedly improved after 6 months of treatment. There was no recurrence during the 2 years of follow-up. There has long been a controversy regarding whether PL is just an inflammatory dermatosis or a genuine T-cell lymphoproliferative disease. Wang et al. (2) proposed three categories for the relationship between PL and MF: (A) PL with a dominant T-cell clone, (B) PL subsequently progressing into MF, and (C) PL-like MF. In the first category, PL is a monoclonal T-cell-mediated inflammatory disorder, in which T-cell clones were found in about 50% of patients (6,7). The second category involves progression from long-term PL to MF (8,9). The average time-to-progression is about 8 years. It has been speculated that the PL-related immunologic microenvironment is favorable for developing a tumoral clone. Our patient presented with PL-like lesions clinically, while biopsy findings, results of immunohistochemistry, and TCR-GRA all suggested that this case was MF. Due to the short duration (only one year) of his lesions, we established the diagnosis of PL-like MF de novo, rather than evolution from PL to MF. The features of previously reported cases of PL-like MF and those of our patient are summarized in Table 1 (1-5). Men were predominant (18:7) among the total of 25 patients. Most patients were children or young adults (mean age of 23.4 years).The interval between presence of lesions and diagnosis varied from 1 month to 10 years. The cutaneous eruptions were all PL in appearance and almost all involved both the trunk and extremities. Pruritus was reported by approximately half of the patients. Histologically, the scaly papules were usually indistinguishable from classical MF, showing epidermotropism, haloed lymphocytes, lymphocytes aligning along the dermoepidermal junction, and Pautrier's microabscesses. Immunohistochemically, all tested cases demonstrated positivity for CD3 but were negative for CD20 and CD30. Cases with predominantly CD8-positive cells were twice as prevalent as cases with predominantly CD4-positive cells. TCR-GRA was performed in 20 cases, 15 of which revealed monoclonality. Most patients received psoralen combined with ultraviolet A or NBUVB phototherapy, and demonstrated either a complete or partial response. Recurrence was reported in only 2 cases (5). In summary, PL-like MF is a rare variant of MF. It has some features distinct from classic MF, such as a higher incidence in young men and predominantly CD8-positive T-cells infiltration. Phototherapy can be used as the first line of treatment. A good response and a favorable prognosis can be expected.

The impact of environmental ultraviolet exposure on the clinical course of mycosis fungoides.

BACKGROUND: As phototherapy plays an important role in the treatment of early-stage mycosis fungoides (MF), it is possible that environmental ultraviolet (UV) exposure affects the natural history of the disease. OBJECTIVE: To assess the impact of environmental UV exposure on the clinical course of MF. METHODS: The National Solar Radiation Database was used to identify the top and bottom registries for UV exposure from the Surveillance, Epidemiology, and End Results-18 database. Incidence and survival were determined. RESULTS: The high-UV cohort had a 30% lower risk of developing MF than did the low-UV cohort (hazard ratio, 1.3; 95% confidence interval, 1.20-1.41; P < .001). When stratified by stage and race, this difference was appreciable only among those with early-stage disease and white race. There was no difference in survival between the high- and low-UV cohorts (P = .098); however, a small difference was observed among those with early-stage disease and white race, favoring high UV exposure. LIMITATIONS: Retrospective design, use of the National Solar Radiation Database as a surrogate for individual sunlight exposure. CONCLUSION: It is possible that environmental solar UV exposure may play a role in controlling early-stage MF among patients with photosensitive features.

Folliculotropic mycosis fungoides in a pediatric patient mimicking black dot tinea capitis.

Immunosuppression following organ transplantation is a known risk factor for the development of lymphoproliferative disorders. Mycosis fungoides, a rare entity in pediatric patients, has seldom been reported as a post-transplant lymphoproliferative disorder. We report a case of folliculotropic mycosis fungoides in a pediatric patient following liver transplantation that was initially diagnosed as tinea capitis.

Mycosis Fungoides and Sézary Syndrome: An Update.

Cutaneous T-cell lymphomas are a heterogeneous collection of non-Hodgkin lymphomas that arise from skin-tropic memory T lymphocytes. Among them, mycosis fungoides (MF) and Sézary syndrome (SS) are the most common malignancies. Diagnosis requires the combination of clinical, pathologic, and molecular features. Significant advances have been made in understanding the genetic and epigenetic aberrations in SS and to some extent in MF. Several prognostic factors have been identified. The goal of treatment is to minimize morbidity and limit disease progression. However, hematopoietic stem cell transplantation, considered for patients with advanced stages, is the only therapy with curative intent.

Mycosis fungoides - A cutaneous lymphoproliferative disorder in a patient treated with fingolimod for multiple sclerosis.

Fingolimod was the first oral disease-modifying drug approved for the treatment of relapsing-remitting multiple sclerosis (MS). It has previously been associated with rare cases of lymphoma. Here we describe the first case of mycosis fungoides - a cutaneous lymphoproliferative disorder, in an MS patient treated with fingolimod. who developed histologically confirmed mycosis fungoides 3 years after starting fingolimod. The drug was withdrawn and the patient was treated with radiotherapy and surgical excision with remission. This report points to a possible association between fingolimod and skin lymphoproliferative disorder and emphasizes the need for periodic skin examination.