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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]

Background Lymphomatoid papulosis (LyP) is a rare cutaneous T-cell lymphoproliferative disorder. Comprehensive data on LyP in the paediatric population are scarce. Objectives To characterize the epidemiological, clinical, histopathological and prognostic features of paediatric LyP. Methods This was a retrospective multicentre international cohort study that included 87 children and adolescents with LyP diagnosed between 1998 and 2022. Patients aged ≤ 18 years at disease onset were included. LyP diagnosis was made in each centre, based on clinicopathological correlation. Results Eighty-seven patients from 12 centres were included. Mean age at disease onset was 7.0 years (range 3 months–18 years) with a male to female ratio of 2 : 1. Mean time between the onset of the first cutaneous lesions and diagnosis was 1.3 years (range 0–14). Initial misdiagnosis concerned 26% of patients. LyP was most often misdiagnosed as pityriasis lichenoides et varioliformis acuta, insect bites or mollusca contagiosa. Erythematous papules or papulonodules were the most frequent clinical presentation. Pruritus was specifically mentioned in 21% of patients. The main histological subtype was type A in 55% of cases. When analysed, monoclonal T-cell receptor rearrangement was found in 77% of skin biopsies. The overall survival rate was 100%, with follow-up at 5 years available for 33 patients and at 15 years for 8 patients. Associated haematological malignancy (HM) occurred in 10% of cases (n = 7/73), including four patients with mycosis fungoides, one with primary cutaneous anaplastic large cell lymphoma (ALCL), one with systemic ALCL and one with acute myeloid leukaemia. If we compared incidence rates of cancer with the world population aged 0–19 years from 2001 to 2010, we estimated a significantly higher risk of associated malignancy in general, occurring before the age of 19 years (incidence rate ratio 87.49, 95% confidence interval 86.01–88.99). Conclusions We report epidemiological data from a large international cohort of children and adolescents with LyP. Overall, the disease prognosis is good, with excellent survival rates for all patients. Owing to an increased risk of associated HM, long-term follow-up should be recommended for patients with LyP. [ABSTRACT FROM AUTHOR]

The article in the British Journal of Dermatology discusses primary cutaneous acral CD8+ T-cell lymphoproliferative disorder (TLPD), a rare condition that presents as a benign or malignant process. The disorder is characterized by a diffuse infiltrate of medium-sized CD8+ cytotoxic T cells, resembling an aggressive lymphoma but with a generally indolent clinical course. Recent research by Wobser et al. identified recurrent genetic alterations in patients with acral CD8+ TLPD, including a homozygous deletion of the KIR3DL1 gene, suggesting potential mechanisms underlying the pathogenesis of this condition. [Extracted from the article]

The article discusses the use of pegylated interferon α-2a (PEG-IFN-α) in the treatment of mycosis fungoides (MF) and Sézary syndrome (SS), which are types of cutaneous T-cell lymphoma (CTCL). The immune system plays a role in restraining tumor growth in the early stages of CTCL, but as the disease progresses, there is a shift towards immune evasion and tumor advancement. Recombinant IFN-α has been used effectively in the treatment of CTCL, and PEG-IFN-α has emerged as an alternative therapy. A retrospective study analyzed the response and adverse events associated with PEG-IFN-α and found an overall response rate of 53% and a time to next treatment of 9.2 months. PEG-IFN-α is recommended to be used in combination with skin-directed therapies. Overall, PEG-IFN-α represents an innovative treatment option for patients with early and advanced CTCL. [Extracted from the article]

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]

This article presents the findings of a retrospective multicenter study conducted by the French Study Group of Cutaneous Lymphomas (GFELC) on patients with Sézary syndrome (SS), a type of cutaneous T-cell lymphoma. The study aimed to evaluate the outcomes of patients after discontinuing treatment with mogamulizumab (Moga) for reasons other than disease progression. The study included 52 patients with SS, and the primary endpoint was progression-free survival post-Moga discontinuation (PFSpmd). The results showed that after a median duration of 7 months, 48% of patients experienced relapse or progression. However, a high response level was observed when Moga was resumed. The study suggests that a progressive discontinuation of Moga could be considered to minimize adverse events and treatment costs. Further studies with longer follow-up are needed to confirm these findings. [Extracted from the article]

This article discusses the successful re-treatment of two patients with Mycosis fungoides (MF), a type of cutaneous T-cell lymphoma, using brentuximab vedotin (BV). BV is an antibody-directed systemic treatment that has shown positive responses in previous studies. The two patients in this case study achieved complete response (CR) with BV, and their disease remained in remission for a significant period of time. The article suggests that re-treatment with BV can be effective, durable, and safe in selected patients with CD30+ MF. However, further research is needed to establish specific evidence for re-treatment in MF. [Extracted from the article]

A retrospective cohort study published in the British Journal of Dermatology examines the survival disparities among Black patients with cutaneous lymphoma. The study found that Black patients had significantly worse overall survival compared to other racial/ethnic groups, even when accounting for prognostic factors such as disease stage, age, and sex. The study also identified large-cell transformation (LCT) as a significant determinant of poorer survival in Black patients. The findings highlight the need for increased vigilance in identifying poor prognostic features and early, aggressive treatment for Black patients with cutaneous lymphoma. [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]

Background: The relationship between immune checkpoint status and disease outcome is a major focus of research in cutaneous T‐cell lymphoma (CTCL), a disfiguring neoplastic dermatological disorder. Mycosis fungoides (MF) and Sézary syndrome (SS) are the two most common types of CTCL. Objectives: The aim was to evaluate the immune checkpoint markers programmed death protein 1 (PD1), inducible T‐cell co‐stimulator (ICOS) and programmed death‐ligand 1 (PD‐L1) in skin biopsies from patients with CTCL relative to disease stage and overall survival. Methods: This consecutive case series enrolled 47 patients: 57% had stage IA–IIA disease and 43% had stage IIB–IVA2 disease (including seven with SS). Results: PD1, PD‐L1 and ICOS expression was seen in all biopsies. Notably, PD‐L1 was predominantly expressed on histiocytes/macrophages, but focal expression on CTCL cells was seen. High expression of either ICOS or PD‐L1 was associated with advanced‐stage disease (P = 0·007 for both) and with the appearance of large‐cell transformation (LCT), a histopathological feature associated with a poor prognosis (ICOS: P = 0·02; PD‐L1: P = 0·002). PD1 expression was not significantly associated with disease stage (P = 0·12) or LCT (P = 0·49), but expression was high in SS biopsies. A high combined checkpoint marker score (PD1, PD‐L1 and ICOS) was associated with advanced‐stage disease (P = 0·001), LCT (P = 0·021) and lower overall survival (P = 0·014). Conclusions: These findings demonstrate the existence of a complex immunoregulatory microenvironment in CTCL and support the development of immunotherapies targeting ICOS and PD‐L1 in advanced disease. [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 infiltrate was CD3 SP + sp CD4 SP + sp with CD7 loss, the Ki67 index was 30-40% and a dominant T-cell clone was found in skin. In Sézary syndrome, the immunophenotypic abnormalities of blood tumour CD4 SP + sp T cells may include CD7 loss, and CD3 and/or CD4 downregulation. Four had no detectable blood CD3 SP - sp CD4 SP + sp , but a CD3 SP + sp CD4 SP + sp CD7 SP - sp population. [Extracted from the article]

Summary: Background: Mogamulizumab is a humanized antibody against chemokine receptor type 4. It was recently approved by the US Food and Drug Administration for relapsed or refractory mycosis fungoides (MF) and Sézary syndrome (SS). The most commonly reported adverse event in the phase III licensing trial was drug eruption (28%), now termed mogamulizumab‐associated rash (MAR). Clinical recommendations about MAR and its treatment differ between the current package insert and postapproval insights reported from two single‐centre studies that focused on its characterization, but less so on outcomes and clinicopathological differentiation from cutaneous T‐cell lymphoma (CTCL). Objectives: To describe our experience in the diagnosis of MAR and treatment of patients with CTCL with mogamulizumab. Methods: This is a single‐centre retrospective case series study. Results: We found a higher incidence of MAR in patients with CTCL (17 of 24, 68%) than previously reported. MAR development is associated with complete (11 of 17) or partial (four of 17) responses, with an overall response rate of 88%, compared with 29% (two of seven) in patients without MAR. Diagnosis of MAR may be obscured by its ability to mimic key CTCL features both clinically and histologically, but an absence of T‐cell‐receptor clonality and relatively decreased CD4 : CD8 ratio compared with baseline lesions strongly favour MAR over recurrent disease. Conclusions: MAR has the potential to create a significant management problem for patients on mogamulizumab. Misidentification of MAR as recurrent CTCL may detrimentally result in the premature discontinuation of mogamulizumab in patients whose disease is historically hard to treat. Thorough clinicopathological investigation of new lesions during treatment with mogamulizumab is required to inform ideal treatment decisions and achieve better outcomes. What is already known about this topic? Previous descriptions of mogamulizumab‐associated rash (MAR) include case reports or series and two subgroup analyses of the mogamulizumab‐approving MAVORIC clinical trial.Previous reports lacked clinical outcome data or robust clinicopathological differentiation from recurrent cutaneous T‐cell lymphoma (CTCL).Patients with Sézary syndrome develop MAR more often than those with mycosis fungoides. What does this study add? Outside of clinical trial constraints, we describe a Sézary syndrome‐predominant cohort of patients with CTCL who developed both a higher incidence of MAR and a higher overall response rate to mogamulizumab than previously reported.We describe the diverse manifestations of MAR, including four histopathological and five clinical patterns, in relation to other reports.We confidently differentiate between MAR and recurrent CTCL through molecular testing and provide our diagnostic methodology. Linked Comment: G. Blanchard and E. Guenova. Br J Dermatol 2022; 186:15–16. Plain language summary available online [ABSTRACT FROM AUTHOR]

Considering all skin biopsy samples at diagnosis, CD30 > 10% and Ki67 > 20% was more frequent in LCT+ samples than in LCT- samples (67% vs. 9%; I P i = 0-003 and 100% vs. 22%; I P i = 0-016, respectively). Mean cell surface was significantly higher in LCT+ than in LCT- skin biopsy sample images [27 m SP 2 sp (SD 3-3) vs. 22 m SP 2 sp (SD 2-3); I P i < 0-001]. Dear Editor, Sézary syndrome (SS) is a rare cutaneous T-cell lymphoma (CTCL) grouped with mycosis fungoides (MF) in the international classification and staging criteria of CTCL.1,2 Large-cell transformation (LCT) has been widely described in MF and associated with reduced overall survival, suggesting the importance of early and sequential histological screening of LCT in MF.3 However, LCT has never been studied and characterized in a large cohort of SS. [Extracted from the article]

The TRBC1 evaluation is a useful, simple, and fast flow cytometry tool for the assessment of T-cell clonality in the blood of patients suspicious of mycosis fungoides and Sézary syndrome. TRBC1 expression assessed by flow cytometry as a novel marker of clonality in cutaneous T-cell lymphomas with peripheral blood involvement The recently described monoclonal antibody JOVI-11 is directed against the C1 constant region of the TCR chain (TRBC1), and is an interesting tool for the assessment of clonality in T-cell tumours by flow cytometry (FCM). [Extracted from the article]

Summary: Background: Brentuximab vedotin (BV) was approved as a therapy for mycosis fungoides (MF) based on the ALCANZA trial. Little real‐world data, however, are available. Objectives: To evaluate the efficacy and safety of BV in patients with MF/Sézary Syndrome (SS) with variable CD30 positivity in a real‐world cohort and to explore potential predictors of response. Methods: Data from 72 patients with MF/SS across nine EORTC (European Organization for Research and Treatment of Cancer) centres were included. The primary endpoint was to evaluate the proportion of patients with: overall response (ORR), ORR lasting over 4 months (ORR4), time to response (TTR), response duration (RD), progression‐free survival (PFS) and time to next treatment (TTNT). Secondary aims included a safety evaluation and the association of clinicopathological features with ORR, RD and TTNT. Results: All 72 patients had received at least one systemic treatment. ORR was achieved in 45 of 67; ORR4 in 28 of 67 with a median TTR of 8 weeks [interquartile range (IQR) 5·5–14] and with a median RD of 9 months (IQR 3·4–14). Median PFS was 7 months (IQR 2–12) and median TTNT was 30 days (6–157·5). Patient response, RD, PFS and TTNT were not associated with any clinicopathological characteristics. In the MF group, patients with stage IIB/III vs. IV achieved longer PFS and had a higher percentage of ORR4. There was a statistically significant association between large‐cell transformation and skin ORR (P = 0·03). ORR4 was more frequently achieved in patients without lymph node involvement (P = 0·04). Conclusions: BV is an effective option for patients with MF/SS, including those with variable CD30 positivity, large‐cell transformation, SS, longer disease duration and who have been treated previously with several therapies. What is already known about this topic?Mycosis fungoides (MF) and Sézary syndrome (SS) are rare, heterogeneous and difficult to treat malignancies.A stage‐dependent therapeutic algorithm is used with short‐lived responses in advanced stages.Brentuximab vedotin (BV) has been recently used for the treatment of patients with MF with CD30 positivity based on the ALCANZA study but few data are available from a real‐world setting. Whatdoes this study add?This retrospective multicentric European study evaluated BV efficacy and safety in 72 patients with MF/SS and BV appeared to be an effective therapy independently from CD30 positivity and previous treatments.Patients with stage IIB and III MF achieved longer progression‐free survival and a higher percentage of overall response over 4 months (ORR4) vs. patients with stage IV MF.Patients without lymph node involvement more frequently achieved ORR4 and large‐cell transformation was significantly associated with skin ORR. Plain language summary available online [ABSTRACT FROM AUTHOR]

Summary: Background: Clinical and histological diagnosis of Sézary syndrome (SS) and mycosis fungoides (MF) is challenging in clinical routine. Objectives: We investigated five blood markers previously described for SS (T‐plastin, Twist, KIR3DL2, NKp46 and Tox) in a prospective validation cohort of patients. Methods: We included 447 patients in this study and 107 patients were followed up for prognosis. The markers were analysed by reverse transcriptase quantitative real‐time polymerase chain reaction (RT‐qPCR) on peripheral blood leucocytes and CD4+ T cells in a cohort of consecutive patients with early MF, erythrodermic MF and SS and compared with patients presenting with benign inflammatory dermatoses (BID) and erythrodermic BID. The markers were assessed in parallel to gold standard values such as CD4/CD8 ratio, loss of CD7 and CD26 membrane expression and CD4 absolute values. Sensitivity and specificity were analysed by receiver operator characteristic curves. The prognostic value of selected markers was analysed on a subset of patients. This study was conducted in one centre. Results: We defined cut‐off values for each marker. T‐plastin, Twist and KIR3DL2 had the best validity. SS may be overrepresented. The combination of T‐plastin and Twist was able to differentiate between erythrodermic MF or BID and SS. The additional analysis of KIR3DL2 may be useful to predict the prognosis. Conclusions: We propose T‐plastin, Twist and KIR3DL2 measured by RT‐qPCR as new diagnostic markers for Sézary syndrome. What is already known about this topic? T‐plastin, Twist, KIR3DL2, NKp46 and Tox have been described as blood markers for Sézary syndrome (SS). What does this study add? We defined cut‐off values and tested the validity of these markers.Our study suggests that a combination of these markers could be a useful, noninvasive tool for the early diagnosis of mycosis fungoides and SS. Linked Comment: P.L. Ortiz Romero. Br J Dermatol 2021; 185:250–251. Plain language summary available online [ABSTRACT FROM AUTHOR]

Summary: Mycosis fungoides (MF) and Sézary syndrome (SS) are the best‐studied subtypes of cutaneous T‐cell lymphoma. The level of blood tumour burden in patients is important for diagnosis, disease staging, prognosis and management, as well as assessing treatment response. Until recently, the assessment of blood involvement was made using manual counts of morphologically atypical T cells (Sézary cells), but this approach may be subjective, and is affected by interobserver variability. Objective and consistent approaches to accurately quantifying blood involvement are required to ensure appropriate stage‐related management of patients and to improve our understanding of the prognostic implications of blood tumour burden in these diseases. While assessment of blood involvement is common in SS and advanced‐stage MF, an improved understanding of the implications of blood involvement at early disease stages could help identify patients more likely to progress to late‐stage disease, and hence guide treatment decisions and frequency of follow‐up assessment, ultimately improving patient outcomes. This concise review discusses the development of flow cytometry‐based classifications for assessing blood involvement in MF and SS, and summarizes current recommendations for blood classification and assessment of blood response to treatment. [ABSTRACT FROM AUTHOR]

(b) Sex of black patients diagnosed at age < 40 years (n = 39) and (c) age at diagnosis among black female patients (n = 108). Outcomes and prognostic factors in African American and black patients with mycosis fungoides and Sézary syndrome: retrospective analysis of 157 patients from a referral cancer center. The only dissimilarities by sex within race/age groups were observed in younger black patients (Figure S3), and the only dissimilarities by age within race/sex groups were observed in black female patients (Figure S4). [Extracted from the article]

Dear Editor, Mycosis fungoides (MF) may present at an early stage with patch/plaque disease or at advanced stages with tumours/erythroderma. Eleven patients had advanced MF/SS [IIIB ( I n i = 1), IVA1 (3), IVA2 (6), IVB (1)], one patient had adult T-cell leukaemia/lymphoma and MF lesions (HTLV1 SP + sp ) and another recalcitrant stage IIA MF. Of those with advanced MF/SS, three patients had primary and seven patients had secondary SS. [Extracted from the article]

A transthoracic echocardiogram was performed in all patients before and after doxorubicin treatment (recommended before and after treatment, with additional measurement at 200 mg m SP -2 sp cumulative dose)8 without cardiac AEs, indicating that doxorubicin is also a safe maintenance therapy in terms of cardiotoxicity. Single-centre experience of using pegylated liposomal doxorubicin as maintenance treatment in mycosis fungoides Dear Editor, Primary cutaneous T-cell lymphomas (CTCLs)1 are characterized by the cutaneous clonal accumulation of T cells; mycosis fungoides (MF) is the most common subtype. Prospective international multicenter phase II trial of intravenous pegylated liposomal doxorubicin monochemotherapy in patients with stage IIB, IVA, or IVB advanced mycosis fungoides: final results from EORTC 21012. [Extracted from the article]

Summary: Background: The early diagnosis of Sézary syndrome (SS) is challenging. Loss of CD7 and CD26 expression on CD4+ T cells is the currently used criterion in the initial diagnosis and staging of patients with SS. Objectives: Our aim was to evaluate the respective value of CD26, CD7 and KIR3DL2 expression on CD4+ T cells and total lymphocytes at initial diagnosis of SS. Methods: This prospective study included 254 patients with clinical features consistent with cutaneous T‐cell lymphoma seen at our institution between March 2014 and February 2019. Peripheral blood analysis by flow cytometry was performed for each patient at the time of diagnosis and during follow‐up. The diagnosis of SS was based on ISCL/EORTC criteria. Results: The presence of KIR3DL2+ Sézary cells (SCs) ≥ 200 μL−1 correlated with the diagnosis of SS, with sensitivity of 88·6% and specificity of 96·3%. All 154 patients with either inflammatory skin disease or other haematological disease had KIR3DL2+ cells < 200 μL−1, while eight of them had CD4+CD26− T cells ≥ 1000 μL−1. Of five patients with SS and lymphopenia, four had CD4+CD7− T cells < 1000 μL−1 and three had CD4+CD26− T cells < 1000 μL−1. However, all of them had KIR3DL2+CD4+ T cells ≥ 200 μL−1. Among patients with available samples during evolution, all B1‐staged patients with ≥ 200 μL−1KIR3DL2+SCs at diagnosis evolved to B2 stage within 7 months. Conclusions: KIR3DL2 expression on T cells is highly specific and helps the early diagnosis of SS, especially in those patients with lymphopenia. What's already known about this topic? In the ISCL/EORTC cutaneous T‐cell lymphoma (CTCL) categorization of blood involvement (B0–B2), B2 is defined as a T‐cell receptor clonal rearrangement in blood, associated with high blood‐smear Sézary cell (SC) count.Flow cytometry was developed to circumvent interobserver variability of SC manual counts; however, it mostly relies on detection of cells lacking CD7 and/or CD26 expression.We previously reported the reliability of KIR3DL2 as the first positive SC marker. What does this study add? Based on our analysis of 254 patients, we propose that KIR3DL2 be added to the ISCL/EORTC criteria for initial diagnosis of Sézary syndrome (SS) and B2 staging.This marker improved sensitivity of SS B2‐stage CTCL diagnosis with a specificity > 95%, especially for patients with lymphopenia.We found KIR3DL2 helped early diagnosis of SS and was more reliable than CD26 in assessing blood tumour burden during therapy. What is the translational message? SC quantification is the major means of staging at initial diagnosis and monitoring blood tumour burden in a clinical trials setting.We recommend using a threshold value of KIR3DL2+ SCs ≥ 200 μL−1 or KIR3DL2+ SCs/lymphocytes ≥ 10% in the diagnostic criteria of SS and propose a novel algorithm for CTCL B2 blood staging. Linked Comment:Sun and Wang. Br J Dermatol 2020; 182:1325–1326. [ABSTRACT FROM AUTHOR]

Summary: Background: Mycosis fungoides (MF) and Sézary Syndrome (SS) are the most common cutaneous T‐cell lymphomas. MF/SS is accompanied by considerable morbidity from pain, itching and disfigurement. Aim: To identify factors associated with poorer health‐related quality of life (HRQoL) in patients newly diagnosed with MF/SS. Methods: Patients enrolled into Prospective Cutaneous Lymphoma International Prognostic Index (PROCLIPI; an international observational study in MF/SS) had their HRQoL assessed using the Skindex‐29 questionnaire. Skindex‐29 scores were analysed in relation to patient‐ and disease‐specific characteristics. Results: The study population consisted of 237 patients [60·3% male; median age 60 years, (interquartile range 49–70)], of whom 179 had early MF and 58 had advanced MF/SS. In univariate analysis, HRQoL, as measured by Skindex‐29, was worse in women, SS, late‐stage MF, those with elevated lactate dehydrogenase, alopecia, high modified Severity Weighted Assessment Tool and confluent erythema. Linear regression models only identified female gender (β = 8·61; P = 0·003) and alopecia (β = 9·71, P = 0·02) as independent predictors of worse global HRQoL. Item‐level analysis showed that the severe impairment in symptoms [odds ratio (OR) 2·14, 95% confidence interval (CI) 1·19–3·89] and emotions (OR 1·88, 95% CI 1·09–3·27) subscale scores seen in women was caused by more burning/stinging, pruritus, irritation and greater feelings of depression, shame, embarrassment and annoyance with their diagnosis of MF/SS. Conclusions: HRQoL is significantly more impaired in newly diagnosed women with MF/SS and in those with alopecia. As Skindex‐29 does not include existential questions on cancer, which may cause additional worry and distress, a comprehensive validated cutaneous T‐cell lymphoma‐specific questionnaire is urgently needed to more accurately assess disease‐specific HRQoL in these patients. What's already known about this topic? Cross‐sectional studies of mixed populations of known and newly diagnosed patients with mycosis fungoides (MF)/Sézary syndrome (SS) have shown significant impairment in health‐related quality of life (HRQoL).Previous studies on assessing gender‐specific differences in HRQoL in MF/SS are conflicting.More advanced‐stage disease and pruritus is associated with poorer HRQoL in patients with MF/SS. What does this study add? This is the first prospective study to investigate HRQoL in a homogenous group of newly diagnosed patients with MF/SS.In patients newly diagnosed with MF/SS, HRQoL is worse in women and in those with alopecia and confluent erythema.MF/SS diagnosis has a multidimensional impact on patient HRQoL, including a large burden of cutaneous symptoms, as well as a negative impact on emotional well‐being. Linked Comment:Talpur. Br J Dermatol 2020; 182:541–542. Plain language summary available online [ABSTRACT FROM AUTHOR]

At diagnosis of ECTL, only one patient displayed an enlarged node > 1-5 cm (not biopsied), and the median number of Sézary cells was 1440 per mm SP 3 sp (range 396-4930). Dear Editor, The prognosis of erythrodermic cutaneous T-cell lymphomas (ECTL) depends on lymph node (N) and visceral (M) involvement, and blood stage (B). Pathological data at progression were reviewed for eight patients: skin biopsy (four patients), node biopsy (five patients) and cerebrospinal fluid (one patient). [Extracted from the article]

Dear Editor, CD30, also known as tumour necrosis factor receptor 8 (TNF-R 8), was initially called Ki-1 and is a cell-surface molecule that was first described by a group of pathologists from Kiel in 1982.1 CD30 can be targeted with the drug brentuximab vedotin (BV), which is approved for relapsed or refractory CD30 SP + sp cutaneous T-cell lymphoma (CTCL) including primary cutaneous anaplastic large-cell lymphoma and CD30 SP + sp mycosis fungoides and Sézary syndrome. The question of how much CD30 expression is needed for a valuable clinical response to a CD30-targeted therapy is still not finally resolved. [Extracted from the article]

Evaluation of haematopoietic stem cell transplantation in patients diagnosed with cutaneous T-cell lymphoma at a tertiary care centre: should we avoid chemotherapy in conditioning regimes? Dear Editor, Advanced-stage mycosis fungoides (MF) and Sézary syndrome (SS) account for ~30% of patients with cutaneous T-cell lymphomas (CTCL). Stages at transplant ranged from stages IIB to IVB within the MF/SS cohort, with IVA2 being the most common and both patients with ALCL had nodal disease (T3N2M0, T2cN2M0). [Extracted from the article]

Cutaneous T-cell lymphoma (CTCL) is a non-Hodgkin lymphoma of skin-homing T lymphocytes that is difficult to diagnose and treat due to a high degree of clinical and genomic heterogeneity. Mutations in PLCG1 /PLCγ1 occur in 10% of CTCL tumours. Meanwhile, signal transducer and activator of transcription 3 (STAT3) – a common driver of lymphomagenesis – is frequently activated (pY705-STAT3) in CTCL in the absence of mutation. Activation of STAT3 may also be mediated by serine phosphorylation (pS727-STAT3), and there is a lack of data on the role of this modification in CTCL. We aimed to identify if gain-of-function PLCG1 mutations in CTCL activate STAT3, either directly or indirectly, via downstream mitogen-activated protein kinase (MAPK) signalling. Flow cytometry was used to study STAT3 phosphorylation and subcellular localization in ex vivo CD4+-enriched tumour cell populations from patients with CTCL and healthy donors. STAT3 phosphorylation was also studied in the J.gamma1 T-cell line (PLCγ1-null) and primary ex vivo CD4+ cells upon lentiviral overexpression of wild-type (WT) and mutant (p.R48W, p.S345F) PLCγ1 constructs. To investigate the role of MAPK signalling, the CTCL-derived Hut78 and SeAx cell lines were treated with MAPK inhibitors (trametinib), and STAT3 phosphorylation assessed by Western blotting. Significantly increased basal levels of pS727-STAT3 (P < 0.05) and pY705-STAT3 (P < 0.001) were observed in CD4+-enriched populations from patients with Sézary syndrome compared with healthy donors. Mitochondrial translocation of STAT3 was also increased in CD4+-enriched populations from patients with Sézary syndrome (P < 0.05). In transduced J.gamma1 cells, p.S345F-PLCγ1 overexpression activated pS727-STAT3 (P < 0.05), while overexpression of both WT and mutant PLCγ1 constructs activated pS727-STAT3 in primary ex vivo CD4+ cells (P < 0.05 and P < 0.01, respectively). Inhibition of MAPK kinase (MEK)–extracellular signal regulated kinase (ERK) signalling did not significantly modulate STAT3 phosphorylation or subcellular localization in CTCL cell lines, suggesting that pS727-STAT3 phosphorylation is not mediated via ERK in CTCL. This work extends our understanding of PLCγ1 signalling and identifies pS727-STAT3 as a potential target of interest for further study in CTCL. [ABSTRACT FROM AUTHOR]

The article discusses a case of Chanarin-Dorfman syndrome with rare renal involvement in a 17-year-old male patient with nonconsanguineous parents referred by a nephrologist for erythroderma.

Epidemiology of primary cutaneous T-cell lymphoma and subcutaneous panniculitis-like T-cell lymphoma in the U.S.A. from 2006 to 2015: a Surveillance, Epidemiology, and End Results-18 analysis Dear Editor, Primary cutaneous gamma/delta T-cell lymphoma (pcGDTCL) is a rare, aggressive T-cell lymphoma that presents with ulcerated nodules, extranodal dissemination, constitutional symptoms and often, haemophagocytic lymphohistiocytosis.[1] pcGDTCL is so named because of the gamma/delta ( ) phenotype of the T-cell receptor (TCR). pcGDTCL is a histological mimic of subcutaneous panniculitis-like T-cell lymphoma (SPTCL), a lymphoma with an / TCR phenotype. GLO:F03/01oct19:bjd17985-fig-0001.jpg PHOTO (COLOR): (a) Kaplan-Meier plot describing the survival distribution function for 37 cases of primary cutaneous gamma/delta T-cell lymphoma (pcGDTCL) and 132 cases of subcutaneous panniculitis-like T-cell lymphoma (SPTCL). [Extracted from the article]

Dear Editor, The early diagnosis of cutaneous T-cell lymphoma (CTCL) may be challenging and based on a combination of clinical, biological, histological and molecular criteria.1 High-throughput sequencing (HTS) of the T-cell receptor genes allows identification and quantification of each T-cell clone through the recognition of CDR3 (complementarity-determining region 3) sequences in tissue samples.2 It can be used for the sensitive monitoring of CTCL minimal residual disease.3,4 It has also been shown that tumour clone frequency (TCF, defined as the frequency of the top T-cell clone as the percentage of all T cells in a skin sample) > 25% was an independent prognostic factor of progression-free and overall survival in early-stage mycosis fungoides (MF),5 and that it correlated with the degree of skin involvement in CTCL.6 Some studies suggested that HTS was more sensitive than standard polymerase chain reaction (PCR) for the identification of a dominant T-cell clone in early MF,2,7 whereas others found a similar sensitivity.8 However, the interpretation of HTS clonality data remains subjective, as internationally validated thresholds for the definition of a dominant T-cell clone by HTS have not been published. Diagnostic performance of high-throughput sequencing of the T-cell receptor beta gene for the diagnosis of cutaneous T-cell lymphoma Both techniques identified an identical T-cell clone in all blood-skin couples of samples, except in one blood sample in which a dominant T-cell clone was identified by HTS I TRB i , identical to the skin, but no dominant T-cell clone was identified by PCR. [Extracted from the article]

Background Patients with erythrodermic disease are a diagnostic challenge regarding the clinical and histological differential diagnosis. Objectives To evaluate histopathological and immunohistochemical diagnostic markers for Sézary syndrome. Methods Ninety-seven erythrodermic cases [Sézary syndrome ( SS), n = 57; erythrodermic inflammatory dermatoses ( EIDs), n = 40] were collected by the EORTC Cutaneous Lymphoma Task Force histopathology group. Evaluation criteria were (i) epidermal and dermal changes; (ii) morphology of the infiltrate; (iii) immunohistochemical analysis of marker loss ( CD2, CD3, CD4, CD5 and CD7); (iv) bystander infiltrate by staining for CD8, FOXP3 and CD25; and (v) expression of Ki-67, CD30, PD-1 and MUM-1. Results The workshop panel made a correct diagnosis of SS in 51% of cases ( cutaneous T-cell lymphoma 81%) and of EID in 80% without clinical or laboratory data. Histology revealed a significantly increased degree of epidermotropism ( P < 0·001) and more intraepidermal atypical lymphocytes ( P = 0·0014) in SS biopsies compared with EID. Pautrier microabscesses were seen only in SS (23%) and not in EID ( P = 0·0012). SS showed significantly more dermal cerebriform and blastic lymphocytes than EID. Immunohistochemistry revealed a significant loss of CD7 expression (< 50%) in 33 of 51 (65%) cases of SS compared with two of 35 (6%) EID ( P < 0·001). The lymphocytic infiltrate in SS skin samples was found significantly to express PD-1 ( P = 0·0053), MUM-1 ( P = 0·0017) and Ki-67 ( P < 0·001), and showed less infiltration of CD8+ lymphocytes ( P < 0·001). A multivariate analysis identified CD7 loss, increased numbers of small cerebriform lymphocytes, low numbers of CD8+ lymphocytes and increased proliferation (Ki-67+ lymphocytes) as the strongest indicators for the diagnosis of SS. Conclusions A number of different histological and immunophenotypical criteria are required to differentiate between SS and EIDs. [ABSTRACT FROM AUTHOR]

Linked Article: Calvani et al. Br J Dermatol 2021; 185:419–427. [ABSTRACT FROM AUTHOR]

Linked Article: Dobos et al. Br J Dermatol 2021; 185:405–411. [ABSTRACT FROM AUTHOR]

Dear Editor, Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of non-Hodgkin lymphomas that differ greatly in clinical presentation and prognosis. Between January 2000 and December 2019, 1044 patients with MF, including 238 patients with folliculotropic MF (FMF), and 93 patients with SS were included in the DCLR (Figure 1). In summary, a significant increase of patients with classical MF, FMF and SS included in the DCLR was seen over the past 20 years. [Extracted from the article]

Linked Article: Roelens et al. Br J Dermatol 2022; 186:1010–1025. Sézary syndrome (SS) is a rare form of skin cancer (T‐cell lymphoma) arising in the skin from white blood cells. Management involves many successive treatments, as disease relapse and lack of response to treatment often occur. Also, patients with SS experience immunodeficiency as their disease progresses, this means their immune system is less able, or completely unable, to fight infectious diseases and cancer. Mogamulizumab therapy has been shown to increase progression‐free survival in patients with SS. It is a monoclonal antibody treatment. This study from France included 26 patients with hard‐to‐treat SS that had not responded to at least one systemic treatment (given by mouth or injection). The authors wanted to find out more about how mogamulizumab might improve patients' long‐term clinical response. They undertook various investigations including using a process called multicolour flow cytometry. Both malignant and non‐malignant T‐cells were monitored. They found that mogamulizumab not only eradicates malignant cells but also potentially contributes to the restoration of efficient immunity. In conclusion, this study provides new insights that will help with the management of this condition. Linked Article: Roelens et al. Br J Dermatol 2022; 186:1010–1025. [ABSTRACT FROM AUTHOR]

Background Histological differentiation between Sézary syndrome ( SS) and erythrodermic inflammatory dermatoses ( EID) can be very difficult. Recent studies show that programmed death-1 ( PD-1) is strongly expressed by the neoplastic cells in skin biopsies of SS, while similar studies in EID are lacking. Objectives To determine whether the number and distribution of PD-1+ T cells could be used as an adjunct in the differentiation between SS and EID. Methods Expression of PD-1 and a panel of T-cell markers was investigated in skin biopsies from 30 patients with various types of EID (12 idiopathic, 10 atopic, six psoriatic and two paraneoplastic) and 25 patients with SS. Results Expression of PD-1 by > 50% of the infiltrating T cells was observed in 23 of 25 (92%) SS cases and in only four of 30 (13%) EID cases. PD-1 is expressed by neoplastic CD4+ T cells in SS, while in contrast, PD-1 was predominantly expressed by dermal and epidermal CD8+ T cells in EID. Expression of CD7 by ≤ 20% of the infiltrating T cells was observed only in SS (13 of 24; 54%), and not in any of the 30 cases of EID. Conclusions While PD-1 is expressed by CD4+ neoplastic T cells in SS, our results suggest that PD-1 is expressed mainly by activated dermal and epidermal CD8+ T cells in EID. Expression of PD-1 by > 50% of CD4+ T cells and expression of CD7 by ≤ 20% of the infiltrating T cells strongly support a diagnosis of SS in skin biopsies of patients with erythroderma. [ABSTRACT FROM AUTHOR]

Mycosis fungoides is the most prevalent form of primary cutaneous T-cell lymphoma. Patients frequently present with early-stage disease typically associated with a favourable prognosis and survival of 10-35 years, but over 25% may progress to advanced disease with a median survival < 4 years, and just 13 months in those with nodal involvement. Sézary syndrome presents in advanced disease with erythroderma, blood involvement and lymphadenopathy. The Bunn and Lamberg staging system (1979) includes stages IA- IIA (early-stage disease) and IIB- IVB (advanced-stage disease) and provides prognostic information, but some patients with tumour-stage disease ( IIB) have a worse prognosis than those with erythrodermic-stage ( III). Conversely, patients with plaque-stage ( IB) folliculotropic mycosis fungoides may have a worse outcome than those with tumour-stage ( IIB). The more recent staging system of the European Organisation for the Research and Treatment of Cancer/ International Society for Cutaneous Lymphoma has been designed to reflect tumour burden at different sites. However, this staging system has not been validated prospectively for prognosis. Furthermore, this staging system does not include a detailed measurement of skin tumour burden, as indicated by the modified skin weighted severity assessment tool. This assessment measures body surface area of disease and is weighted to record patch, plaque and tumour to produce a numerical value from 0·5 to 400 and is an established endpoint for clinical studies. Nor does this staging include clinicopathological features associated with a poor prognosis such as folliculotropism. Here we review the clinical, haematological, pathological and genotypic parameters outside the staging system, which may affect survival in mycosis fungoides and Sézary syndrome. Most studies are retrospective and single centre. The identification of poor prognostic factors may be used to develop a prognostic index to use alongside staging, which may be of benefit in mycosis fungoides/Sézary syndrome to identify patients with a potentially poor prognosis. [ABSTRACT FROM AUTHOR]

Disparities in outcomes of CD8+ cutaneous T-cell lymphoma by race and presenting lesion location Dear Editor, While cutaneous T-cell lymphoma (CTCL) presents most commonly with a CD4 SP + sp phenotype, CD8 SP + sp and CD30 SP + sp variants have also been described. Primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphomas: reappraisal of a provisional entity in the 2016 WHO classification of cutaneous lymphomas. [Extracted from the article]

Background Primary cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group with Sézary syndrome (SS) as one of the most aggressive variants. Recently, we identified a loss of E2A as a recurrent event in SS, which enhanced proliferation via upregulation of the proto-oncogene MYC. MYC-induced transformation usually requires deleterious alterations of key apoptotic genes including p53; however, p53 functionality and mutation status in SS are unclear. Objectives We investigated functionality of p53 signalling by pharmacological treatment with the MDM2 antagonist nutlin-3, which might result in p53 activation. Furthermore, we analysed the TP53 mutation status in CTCL cell lines and highly purified tumour cells from patients with SS by mRNA and DNA sequencing. Methods We analysed the apoptosis induction due to nutlin-3 treatment in various SS cell lines and primary patient samples by annexin V/propidium iodide staining. Induction of p53 target genes was analysed by immunoblotting, and TP53 was sequenced at the mRNA and DNA level. Results We identified various TP53 mutations and an impaired p53 signalling in the vast majority of the investigated cell lines and primary SS cells. Conclusions In accordance with the importance of MYC deregulation in SS, p53 signalling is frequently nonfunctional in SS. However, although most likely ineffective as exclusive treatment in SS, it remains possible that pharmacological p53 activation could be beneficial in combination with other approaches including classical chemotherapeutics. [ABSTRACT FROM AUTHOR]

Summary [ABSTRACT FROM AUTHOR]

Microarray hybridization studies in Sézary syndrome (SS) have compared T lymphocytes from patients with cutaneous T-cell lymphoma with those of normal controls; a major limitation of this design is that significant inherent genetic variability of lymphocyte populations between individuals may produce differences in gene expression unrelated to disease state. The objective of this study was to minimize the heterogeneity of information derived from whole-genome expression analysis and to identify specific genetic differences between highly purified malignant and nonmalignant (control) T cells from the same patient with SS. Peripheral blood mononuclear cells were obtained from a patient with SS, stained with anti-T-cell receptor Vβ (TCR-Vβ) antibodies, and sorted by multiparameter flow cytometry. Malignant cells expressed the dominant TCR-Vβ; control T cells lacked the dominant TCR-Vβ but were otherwise phenotypically identical (CD3+CD4+CD45RO+). These cell populations were compared using the Illumina Inc. Sentrix Human-6 expression BeadChip system. Transcriptome analysis using the J5 test, which was selected for data analysis based on an efficiency analysis of competing statistical methods, showed differential expression of 44 genes between the malignant and nonmalignant cell subsets. Promyelocytic leukaemia zinc finger protein ( ZBTB16) was the most profoundly upregulated gene in the malignant cell population, while interferon regulatory factor 3 ( IRF3) and interferon-induced protein 35 ( IFI35), which are important elements of the cellular response to viral infection, were significantly downregulated. The results of this study suggest the feasibility of this novel comparative approach to genomic profiling in SS. Using this method, we identified several differentially expressed genes and pathways not previously described in SS. While these findings require validation in larger studies, they may be important in SS pathogenesis. [ABSTRACT FROM AUTHOR]

A letter to the editor discussing T-plastin (PLS3) gene expression as a valuable marker to differentiate mycosis fungoides (MF) from SÉzary syndrome (SS) is presented.

Background CD158k/KIR3DL2 is a specific marker for Sézary cells which can be used to diagnose Sézary syndrome (SS) in erythrodermic patients with abnormal circulating T cells. Objectives To evaluate the suitability of CD158k/KIR3DL2 for detecting and evaluating blood tumour load during the follow up of patients with SS. Methods The absolute CD3+ CD158k+ lymphocyte count was compared with the absolute count of cytomorphological Sézary cells and was correlated with clinical flares in a cohort of patients with SS. Twenty-five patients were included in the study and 48 blood samples were analysed. Results The absolute count of CD3+ CD158k+ cells strongly correlated with the absolute count of atypical circulating cells ( r = 0·97, P < 10−15). The CD3+ CD158k+ lymphocyte cell count was in eight cases more sensitive than cytomorphology for detecting atypical circulating cells especially for small-sized tumour cells. The tumour burden evaluated by CD3+ CD158k+ immunostaining was significantly associated with clinical flare ( P < 10−4). Conclusions CD3+ CD158k+ phenotyping is a reliable and objective test to monitor the blood tumour burden in patients with SS under systemic therapy. [ABSTRACT FROM AUTHOR]

Background Bexarotene (Targretin®) is a synthetic retinoid which is licensed for the treatment of advanced refractory cutaneous T-cell lymphoma (CTCL). Objectives To summarize our experience with bexarotene for patients with CTCL with the aim of assessing efficacy and safety. Methods A retrospective study of 66 patients (44 male, 22 female) with mycosis fungoides (40 patients) or Sézary syndrome (26 patients) who were commenced on bexarotene prior to August 2007 was carried out. Nineteen patients had early-stage (IB–IIA) refractory mycosis fungoides and 47 patients had advanced-stage CTCL (IIB–IVB). Results Fifty-two out of 66 (79%) patients completed over 1 month of therapy with an intention-to-treat response rate of 44% (29/66). Of the patients, six (9%) had a complete response, 23 (35%) had a partial response, 15 (23%) had stable disease and eight (12%) had progressive disease. Median time to maximal response was 3 months (1–9 months). Median response duration was 8 months (1 to > 48 months). Median time to progression was 9 months (3–44 months). Fourteen patients (21%) did not complete a month of bexarotene therapy. Adverse effects of the whole group included central hypothyroidism in 100% (all grade II and managed with thyroid replacement) and hyperlipidaemia in 100% (all managed with lipid-lowering therapy ± dose reduction). Responses were seen in all stages and were higher in advanced stages: 26% (five of 19) with early-stage and 51% (24/47) of advanced-stage disease. Responses were seen in skin, blood and lymph nodes. Twenty-eight out of 66 patients were treated with bexarotene monotherapy and the remainder were on one or more additional anti-CTCL therapies. Conclusions Our data demonstrate that bexarotene is well tolerated in most patients and responses are seen in almost half of patients with all disease stages. However partial responses were not graded and would include any improvement seen in the skin, blood and lymph node. [ABSTRACT FROM AUTHOR]