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Background: Epidemiologic evidence suggests an inverse association between sun exposure and follicular lymphoma risk., Methods: We conducted an Australian population-based family case-control study based on 666 cases and 459 controls (288 related, 171 unrelated). Participants completed a lifetime residence and work calendar and recalled outdoor hours on weekdays, weekends, and holidays in the warmer and cooler months at ages 10, 20, 30, and 40 years, and clothing types worn in the warmer months. We used a group-based trajectory modeling approach to identify outdoor hour trajectories over time and examined associations with follicular lymphoma risk using logistic regression., Results: We observed an inverse association between follicular lymphoma risk and several measures of high lifetime sun exposure, particularly intermittent exposure (weekends, holidays). Associations included reduced risk with increasing time outdoors on holidays in the warmer months [highest category OR = 0.56; 95% confidence interval (CI), 0.42-0.76; Ptrend < 0.01], high outdoor hours on weekends in the warmer months (highest category OR = 0.71; 95% CI, 0.52-0.96), and increasing time outdoors in the warmer and cooler months combined (highest category OR = 0.66; 95% CI, 0.50-0.91; Ptrend 0.01). Risk was reduced for high outdoor hour maintainers in the warmer months across the decade years (OR = 0.71; 95% CI, 0.53-0.96)., Conclusions: High total and intermittent sun exposure, particularly in the warmer months, may be protective against the development of follicular lymphoma., Impact: Although sun exposure is not recommended as a cancer control policy, confirming this association may provide insights regarding the future control of this intractable malignancy., (©2023 The Authors; Published by the American Association for Cancer Research.)

Despite increasing availability of therapies, patients with Sezary syndrome (SS) commonly endure multi-line treatment journeys, mostly with partial responses of short duration. Measuring clinical benefit is challenging; time-to-next-treatment (TTNT) provides a robust, objective measurement of efficacy. This international observational study examines patterns of clinical care and therapeutic benefit as measured by TTNT. TTNT was calculated for monotherapies and combination therapies, with consideration to treatment line. 178 patients with SS (73% de novo, 27% secondary) were included, receiving 721 lines of systemic therapy, with median follow-up of 56.9 months. Across all lines, 58 different therapeutic regimens were prescribed (54 were systemic therapies) and classified into 17 treatment groups. The most common first-line treatments were extracorporeal photopheresis (ECP)-containing combination therapy (20%) and retinoid monotherapy (19%). Median TTNT for all first-line therapies was short (5.4 months). First-line, combination therapies had longer median TTNT than monotherapies, 10.0 vs 5.0 months (P = .004), respectively. Later delivery of combination therapies was associated with shorter clinical benefit, with median TTNT reduced to 6.2 and 2.2 months for mid-line (2nd-4th line) and late-line (≥5th line), respectively (P < .001). First-line ECP-containing treatments were associated with longer median TTNT than non-ECP-containing treatments, 9.0 vs 4.9 months (P = .007). For both ECP-monotherapy and ECP-containing combination therapy, significant reductions in TTNT were seen in later lines. These data suggest therapeutic benefit from first-line delivery of combination therapy for SS and favor early inclusion of ECP in the treatment algorithm for those who can access it., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

The CD30-postive lymphoproliferative disorders, including lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma, account for up to 30% of all cutaneous T-cell lymphomas (CTCLs) and are the second most common form of CTCLs after mycosis fungoides. Both conditions differ in their clinical presentations; however, they share the expression of the CD30 antigen as a common immunophenotypic hallmark. There is a wide spectrum of management options depending on factors such as extent of disease, staging and treatment tolerability. This Clinical Practice Statement is reflective of the current clinical practice in Australia., (© 2023 Australasian College of Dermatologists.)

CD30 is overexpressed in several lymphoma types, including classic Hodgkin lymphoma (cHL), some peripheral T-cell lymphomas (PTCL), and some cutaneous T-cell lymphomas. The antibody-drug conjugate brentuximab vedotin targets CD30-positive cells and has been evaluated for the treatment of various lymphoma entities. This narrative review summarizes 10 years of experience with brentuximab vedotin for the treatment of CD30-positive lymphomas, discusses novel therapies targeting CD30 in development, and highlights remaining controversies relating to CD30-targeted therapy across lymphoma types. The collective body of evidence for brentuximab vedotin demonstrates that exploitation of CD30 can provide sustained benefits across a range of different CD30-positive lymphomas, in both clinical trials and real-world settings. Preliminary experience with brentuximab vedotin in combination with immune checkpoint inhibitors for relapsed/refractory cHL is encouraging, but further exploration is required. The optimal use of brentuximab vedotin for first-line therapy of PTCL remains to be determined. Further research is required on brentuximab vedotin treatment in high-risk patient populations, and in rare lymphoma subtypes, for which no standard of care exists. Novel therapies targeting CD30 include chimeric antigen receptor therapies and bispecific antibody T-cell engagers, which may be expected to further improve outcomes for patients with CD30-positive lymphomas in the coming years., (© 2022. The Author(s).)

The number of patients with primary cutaneous lymphoma (PCL) relative to other non-Hodgkin lymphomas (NHLs) is small and the number of subtypes large. Although clinical trial guidelines have been published for mycosis fungoides/Sézary syndrome, the most common type of PCL, none exist for the other PCLs. In addition, staging of the PCLs has been evolving based on new data on potential prognostic factors, diagnosis, and assessment methods of both skin and extracutaneous disease and a desire to align the latter with the Lugano guidelines for all NHLs. The International Society for Cutaneous Lymphomas (ISCL), the United States Cutaneous LymphomaConsortium (USCLC), and the Cutaneous Lymphoma Task Force of the European Organization for the Research and Treatment of Cancer (EORTC) now propose updated staging and guidelines for the study design, assessment, endpoints, and response criteria in clinical trials for all the PCLs in alignment with that of the Lugano guidelines. These recommendations provide standardized methodology that should facilitate planning and regulatory approval of new treatments for these lymphomas worldwide, encourage cooperative investigator-initiated trials, and help to assess the comparative efficacy of therapeutic agents tested across sites and studies., (© 2022 by The American Society of Hematology.)

Objectives: Cutaneous T-cell lymphoma (CTCL) is a rare and incurable disease, and patients currently experience a lack of treatment options in Australia. This analysis evaluated the cost-effectiveness of extracorporeal photopheresis (ECP) compared with standard of care therapy for the treatment of patients with erythrodermic (stage T 4 , M 0 ) CTCL, who are refractory to previous systemic treatment., Methods: A Markov model was developed from the perspective of the Australian government. Health states were treatment specific and transition probabilities were modeled from time-to-next-treatment data from a published Australian observational study of ECP and comparator treatments. Quality of life utility values were based on psoriasis as a proxy for CTCL, which was validated by consultation with local clinicians. The time horizon for the model was 5 years. The ECP treatment regimen was compared with a weighted treatment comparator based on results of a treatment survey and Australian prescribing data., Results: ECP as a second-line treatment option for CTCL was less costly and more effective than other treatment strategies. ECP had an average cost saving of $37 592 and incremental quality-adjusted life-year gained of 0.20 to 0.21, attributed to patients being able to better tolerate ECP thus avoiding subsequent treatment with high-cost alternatives., Conclusions: This is the first published cost-utility analysis of ECP for CTCL. This analysis demonstrates that ECP is a cost-effective option for the treatment of patients with erythrodermic CTCL in Australia., (Copyright © 2021 International Society for Pharmacoeconomics and Outcomes Research, Inc. Published by Elsevier Inc. All rights reserved.)

The primary analysis of the phase 3 ALCANZA trial showed significantly improved objective responses lasting ≥4 months (ORR4; primary endpoint) and progression-free survival (PFS) with brentuximab vedotin vs physician's choice (methotrexate or bexarotene) in CD30-expressing mycosis fungoides (MF) or primary cutaneous anaplastic large-cell lymphoma (C-ALCL). Cutaneous T-cell lymphomas often cause pruritus and pain; brentuximab vedotin improved skin symptom burden with no negative effects on quality of life. We report final data from ALCANZA (median follow-up, 45.9 months). Adults with previously treated CD30-expressing MF/C-ALCL were randomly assigned to brentuximab vedotin (n = 64) or physician's choice (n = 64). Final data demonstrated improved responses per independent review facility with brentuximab vedotin vs physician's choice: ORR4; 54.7% vs 12.5% (P < .001); complete response, 17.2% vs 1.6% (P = .002). Median PFS with brentuximab vedotin vs physician's choice was 16.7 months vs 3.5 months (P < .001). Median time to the next treatment was significantly longer with brentuximab vedotin than with physician's choice (14.2 vs 5.6 months; hazard ratio, 0.27; 95% confidence interval, 0.17-0.42; P < .001). Of 44 patients in the brentuximab vedotin arm who experienced any-grade peripheral neuropathy, (grade 3, n = 6; grade 4, n = 0), 86% (38 of 44) had complete resolution (26 of 44) or improvement to grades 1 and 2 (12 of 44). Peripheral neuropathy was ongoing in 18 patients (all grades 1-2). These final analyses confirm improved, clinically meaningful, durable responses and longer PFS with brentuximab vedotin vs physician's choice in CD30-expressing MF or C-ALCL. This trial was registered at https://www.clinicaltrials.gov as #NCT01578499., (© 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: The PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study is a prospective analysis of an international database. Here we examine front-line treatments and quality of life (QoL) in patients with newly diagnosed mycosis fungoides (MF)., Objectives: To identify (i) differences in first-line approaches according to tumour-nodes-metastasis-blood (TNMB) staging; (ii) parameters related to a first-line systemic approach and (iii) response rates and QoL measures., Methods: In total, 395 newly diagnosed patients with early-stage MF (stage IA-IIA) were recruited from 41 centres in 17 countries between 1 January 2015 and 31 December 2018 following central clinicopathological review., Results: The most common first-line therapy was skin-directed therapy (SDT) (322 cases, 81·5%), while a smaller percentage (44 cases, 11·1%) received systemic therapy. Expectant observation was used in 7·3%. In univariate analysis, the use of systemic therapy was significantly associated with higher clinical stage (IA, 6%; IB, 14%; IIA, 20%; IA-IB vs. IIA, P < 0·001), presence of plaques (T1a/T2a, 5%; T1b/T2b, 17%; P < 0·001), higher modified Severity Weighted Assessment Tool (> 10, 15%; ≤ 10, 7%; P = 0·01) and folliculotropic MF (FMF) (24% vs. 12%, P = 0·001). Multivariate analysis demonstrated significant associations with the presence of plaques (T1b/T2b vs. T1a/T2a, odds ratio 3·07) and FMF (odds ratio 2·83). The overall response rate (ORR) to first-line SDT was 73%, while the ORR to first-line systemic treatments was lower (57%) (P = 0·027). Health-related QoL improved significantly both in patients with responsive disease and in those with stable disease., Conclusions: Disease characteristics such as presence of plaques and FMF influence physician treatment choices, and SDT was superior to systemic therapy even in patients with such disease characteristics. Consequently, future treatment guidelines for early-stage MF need to address these issues., (© 2020 British Association of Dermatologists.)

Background: Early-stage mycosis fungoides (MF) includes involvement of dermatopathic lymph nodes (LNs) or early lymphomatous LNs. There is a lack of unanimity among current guidelines regarding the indications for initial staging imaging in early-stage presentation of MF in the absence of enlarged palpable LNs., Objectives: To investigate how often imaging is performed in patients with early-stage presentation of MF, to assess the yield of LN imaging, and to determine what disease characteristics promoted imaging., Methods: A review of clinicopathologically confirmed newly diagnosed patients with cutaneous patch/plaque (T1/T2) MF from PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) data., Results: PROCLIPI enrolled 375 patients with stage T1/T2 MF: 304 with classical MF and 71 with folliculotropic MF. Imaging was performed in 169 patients (45%): 83 with computed tomography, 18 with positron emission tomography-computed tomography and 68 with ultrasound. Only nine of these (5%) had palpable enlarged (≥ 15 mm) LNs, with an over-representation of plaques, irrespectively of the 10% body surface area cutoff that distinguishes T1 from T2. Folliculotropic MF was not more frequently imaged than classical MF. Radiologically enlarged LNs (≥ 15 mm) were detected in 30 patients (18%); only seven had clinical lymphadenopathy. On multivariate analysis, plaque presentation was the sole parameter significantly associated with radiologically enlarged LNs. Imaging of only clinically enlarged LNs upstaged 4% of patients (seven of 169) to at least IIA, whereas nonselective imaging upstaged another 14% (24 of 169). LN biopsy, performed in eight of 30 patients, identified N3 (extensive lymphomatous involvement) in two and N1 (dermatopathic changes) in six., Conclusions: Physical examination was a poor determinant of LN enlargement or involvement. Presence of plaques was associated with a significant increase in identification of enlarged or involved LNs in patients with early-stage presentation of MF, which may be important when deciding who to image. Imaging increases the detection rate of stage IIA MF, and identifies rare cases of extensive lymphomatous nodes, upstaging them to advanced-stage IVA2., (© 2020 British Association of Dermatologists.)

Primary cutaneous lymphomas represent a heterogeneous group of T- and B-cell lymphomas with distinct clinical presentations, histopathologic features, treatment approaches and outcomes. The cutaneous T-cell lymphomas, which include mycosis fungoides and Sézary syndrome, account for the majority of the cutaneous lymphomas. This Clinical Practice Statement is reflective of the current clinical practice in Australia. An expanded form of the Clinical Practice Statement (and updates), along with helpful patient resources and access to support groups, can be found at the following (http://www.australasianlymphomaalliance.org.au)., (© 2020 The Australasian College of Dermatologists.)

Background: Brentuximab vedotin was approved for adult patients with CD30-expressing cutaneous T-cell lymphoma treated with prior systemic therapy based on improved response rates and progression-free survival with brentuximab vedotin (1.8 mg/kg once every 3 weeks; ≤16 cycles) versus physician's choice (methotrexate/bexarotene; ≤48 weeks) in the phase III ALCANZA study. Quality of life (QoL) in ALCANZA patients was also examined., Methods: QoL measures in ALCANZA were based on the Skindex-29, Functional Assessment of Cancer Therapy-General (FACT-G) and European QoL 5-dimension (EQ-5D) questionnaires., Results: Mean maximum reduction from the baseline Skindex-29 symptom domain score (key secondary end-point) was greater with brentuximab vedotin than physician's choice (-27.96 versus -8.62); the difference, -18.9 (95% confidence interval -26.6, -11.2; adjusted p < 0.001), exceeded the study-defined minimally important difference (9.0-12.3). Mean changes from baseline to end-of-treatment visit total FACT-G scores were similar with brentuximab vedotin and physician's choice (0.15 versus -2.29). EQ-5D changes were also comparable between arms. Among brentuximab vedotin-treated patients with peripheral neuropathy (PN), mean maximum reduction in Skindex-29 symptom domain was -35.54 versus -11.11 in patients without PN. PN had no meaningful effect on FACT-G and EQ-5D QoL scores., Conclusions: In summary, brentuximab vedotin produced superior reductions in symptom burden compared with physician's choice, without adversely impacting QoL. QoL was unaffected by the presence of PN in brentuximab vedotin-treated patients., Clinical Trial Registration: NCT01578499., Competing Interests: Conflict of interest statement S.W., P.W., J.A.S. and L.G. declare no conflicts of interest. R.D. reports intermittent, project-focused consulting and/or advisory relationships with Novartis, MSD, Bristol-Myers Squibb, Roche, Amgen, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Pierre Fabre, Sun Pharma and Sanofi. H.M.P. reports consultancy, advisory roles or honoraria from Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Celgene and Eisai, and research funding from Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. S.M.H. reports consultancy or advisory roles from Affimed, Aileron Therapeutics, Merck Sharp and Dome, Kyowa Hakko Kirin Pharma, Corvus Pharmaceuticals, Inc., Celgene, Portola Pharmaceuticals, Takeda Millennium, Innate Pharma, Verastem, Miragen Therapeutics, Inc. and Seattle Genetics, and research funding from ADCT Therapeutics, Aileron, Forty-Seven, Infinity/Verastem, Kyowa Hakko Kirin Pharma, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Seattle Genetics, Inc., Celgene and Trillium. M.D. reports research funding and consultancy from Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, and Seattle Genetics, Inc. J.S. reports consultancy or advisory roles from Helsinn, Kyowa Hakko Kirin, Millennium Pharmaceuticals, Inc., Innate Pharma, 4SC and Mallinckrodt. P.Q. reports advisory roles from 4SC, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Therakos, Innate Pharma and Kyowa Hakko Kirin. P.L.Z. reports consultancy, advisory and/or speakers bureau roles from Verastem, Celltrion, Gilead, Janssen-Cilag, Bristol-Myers Squibb, Servier, Sandoz, Merck Sharp & Dhome, Immune Design, Celgene, Portola, Roche, EUSA Pharma, Kyowa Hakko Kirin and Sanofi. H.E. reports consultancy or advisory roles from Genentech, Roche, AbbVie and Pharmacyclics, honoraria from Genentech, Roche, AbbVie, Pharmacyclics and Millennium Pharmaceuticals, Inc., and research funding from Genentech, Roche, AbbVie, Pharmacyclics, ATARA and Celgene. L.P.B. reports consultancy fees and honoraria from Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. P.L.O.R. reports travel support from Janssen and Almirall, research support from MEDA, advisory roles from Takeda, Kyowa Hakko Kirin, Actelion, 4SC, Innate Pharma and MiRagen, and a patent on the clinical use of PLCG1 mutation detection. O.E.A. reports consultancy or advisory roles from Trillium Therapeutics and Bioniz, and research funding from Trillium Therapeutics and Pfizer. A.H. reports advisory board participation from Precision Oncology. J.W. reports an advisory role for Roche, Celgene, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Janssen-Cilag, Servier, Amgen, Bristol-Myers Squibb, Incyte and Abbvie, research funding from Roche, GSK/Novartis, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited and Janssen-Cilag, honoraria from Roche, Celgene, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Janssen-Cilag and Servier, and conference travel support from Roche. Y.W., J.L., A.R. and J.F. report employment and stock ownership from Seattle Genetics, Inc. Y.Z., V.B., M.L., E.Z. and M.R.D. report employment from Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. Y.H.K. reports honoraria from Eisai, Kyowa Hakko Kirin, Millennium Pharmaceuticals, Inc., Seattle Genetics, Inc., Medivir, Innate Pharma, Portola and Corvus, and research funding from Eisai, Kyowa Hakko Kirin, Merck Sharp & Dhome, Horizon, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Seattle Genetics, Inc., Soligenix, MiRagen, Forty-Seven, Neumedicine, Innate Pharma, Portola, Trillium, Galderma and Elorac., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Extracorporeal photopheresis (ECP) has demonstrated therapeutic benefit in patients with Sézary syndrome (SS) and erythrodermic mycosis fungoides (e-MF). To examine the efficacy of ECP in the modern era of novel therapies, we conducted a retrospective analysis of 65 patients with a diagnosis of SS or e-MF with blood involvement who were treated with ECP at our institute. Overall survival (OS), time to next treatment (TTNT), and skin response rate (RR) were used as the study end points to determine patient outcome. The median follow-up from diagnosis was 48 months (range 1-225 months), with a median predicted OS of 120 months. The majority (88%) of patients commenced ECP at treatment lines 1 to 3, either as a monotherapy or in conjunction with other systemic agents. The use of ECP monotherapy resulted in a significantly longer median TTNT when compared with interferon-α (P = .0067), histone deacetylase inhibitors (P = .0003), novel immunotherapy agents (P = .028), low-dose methotrexate (P < .0001), and chemotherapy (P < .0001). In particular, early commencement of ECP at treatment lines 1 to 3 yielded a TTNT of 47 months. The results of our study support the utilization of ECP for SS/e-MF, and we recommend that ECP should be considered as early as possible in the treatment paradigm for these patients., (© 2019 by The American Society of Hematology.)

Background: Survival in mycosis fungoides (MF) is varied and may be poor. The PROCLIPI (PROspective Cutaneous Lymphoma International Prognostic Index) study is a web-based data collection system for early-stage MF with legal data-sharing agreements permitting international collaboration in a rare cancer with complex pathology. Clinicopathological data must be 100% complete and in-built intelligence in the database system ensures accurate staging., Objectives: To develop a prognostic index for MF., Methods: Predefined datasets for clinical, haematological, radiological, immunohistochemical, genotypic, treatment and quality of life are collected at first diagnosis of MF and annually to test against survival. Biobanked tissue samples are recorded within a Federated Biobank for translational studies., Results: In total, 430 patients were enrolled from 29 centres in 15 countries spanning five continents. Altogether, 348 were confirmed as having early-stage MF at central review. The majority had classical MF (81·6%) with a CD4 phenotype (88·2%). Folliculotropic MF was diagnosed in 17·8%. Most presented with stage I (IA: 49·4%; IB: 42·8%), but 7·8% presented with enlarged lymph nodes (stage IIA). A diagnostic delay between first symptom development and initial diagnosis was frequent [85·6%; median delay 36 months (interquartile range 12-90)]. This highlights the difficulties in accurate diagnosis, which includes lack of a singular diagnostic test for MF., Conclusions: This confirmed early-stage MF cohort is being followed-up to identify prognostic factors, which may allow better management and improve survival by identifying patients at risk of disease progression. This study design is a useful model for collaboration in other rare diseases, especially where pathological diagnosis can be complex., (© 2018 British Association of Dermatologists.)

There are a number of rare T-cell lymphoma subtypes that may be encountered in clinical practice. In recent years, improved immunohistochemical techniques and molecular tumor profiling have permitted refinement of some of the diagnostic categories in this group, as well as the recognition of distinct conditions not previously well elucidated. In this chapter, we cover the diagnostic and clinical features of some of the more common of these conditions, including subcutaneous panniculitis-like T-cell lymphoma, cutaneous gamma-delta T-cell lymphoma, enteropathy-associated T-cell lymphoma, monomorphic epitheliotropic intestinal T-cell lymphoma, primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma, CD4-positive small/medium T-cell lymphoproliferative disorder, and acral CD8-positive T-cell lymphoma. Given the rarity of these conditions, optimal treatments approaches are not always well established, not least as data from large-scale clinical trials are lacking. In this chapter, we aim to provide a summation of current thinking around best treatment, as well as highlighting some controversies in the management of these diagnoses.

A 64-year-old man presented with a 2 week history of progressive phimosis and painful ulcer on his penile meatus. He underwent penile preserving excision, and subsequent pathological examination confirmed T-cell non-Hodgkin lymphoma with immunohistochemical features of large cell transformation of mycosis fungoides. The penis was further treated with local external beam radiotherapy consisting of 27 Gy in 15 fractions and systemic mini-CHOP chemotherapy. An organ-preserving tissue response has since been achieved. This case is the first of its kind in the literature and firmly highlights the role of multidisciplinary management for this rare malignancy.

Objective: To study the effects of alemtuzumab on HIV persistence in an HIV-infected individual on antiretroviral therapy (ART) with Sezary syndrome, a rare malignancy of CD4 T cells., Design: Case report., Methods: Blood was collected 30 and 18 months prior to presentation with Sezary syndrome, at the time of presentation and during alemtuzumab. T-cell subsets in malignant (CD7-CD26-TCR-VBeta2+) and nonmalignant cells were quantified by flow cytometry. HIV-DNA in total CD4 T cells, in sorted malignant and nonmalignant CD4 T cells, was quantified by PCR and clonal expansion of HIV-DNA assessed by full-length next-generation sequencing., Results: HIV-hepatitis B virus coinfection was diagnosed and antiretroviral therapy initiated 4 years prior to presentation with Sezary syndrome and primary cutaneous anaplastic large cell lymphoma. The patient received alemtuzumab 10 mg three times per week for 4 weeks but died 6 weeks post alemtuzumab. HIV-DNA was detected in nonmalignant but not in malignant CD4 T cells, consistent with expansion of a noninfected CD4 T-cell clone. Full-length HIV-DNA sequencing demonstrated multiple defective viruses but no identical or expanded sequences. Alemtuzumab extensively depleted T cells, including more than 1 log reduction in total T cells and more than 3 log reduction in CD4 T cells. Finally, alemtuzumab decreased HIV-DNA in CD4 T cells by 57% but HIV-DNA remained detectable at low levels even after depletion of nearly all CD4 T cells., Conclusion: Alemtuzumab extensively depleted multiple T-cell subsets and decreased the frequency of but did not eliminate HIV-infected CD4 T cells. Studying the effects on HIV persistence following immune recovery in HIV-infected individuals who require alemtuzumab for malignancy or in animal studies may provide further insights into novel cure strategies.

Mycosis fungoides and Sézary syndrome are the most common variants of the cutaneous T-cell lymphomas. Assessment of a patient with a suspected diagnosis requires thorough history taking and physical examination, in combination with skin biopsy. In some cases flow cytometry, molecular studies and imaging are also required in order to diagnose and stage the disease. Staging is derived from the tumour-node-metastasis-blood classification and is currently our best attempt to stratify prognosis and hence guide management in this complex disease. Many other clinical, biological and pathological factors may help to distinguish groups at risk and predict prognosis more accurately. Management remains heavily guided by staging, such that patients with early-stage disease generally begin treatment with skin-directed or local therapies and those with advanced-stage disease have many treatment options, including chemotherapy, the use of biological agents, local and total body radiotherapy, as well as haematopoietic stem cell transplantation. Besides staging, many other patient-related factors influence the treatment strategy, particularly where symptom relief is paramount. There are many challenges remaining in the study of Mycosis fungoides and Sézary syndrome and, given the rarity of the disease, concerted worldwide efforts are required to conduct efficient and effective research., (© 2015 The Australasian College of Dermatologists.)

Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma variant and is closely related to a rare leukemic variant, Sézary syndrome (SS). MF patients at risk of disease progression can now be identified and an international consortium has been established to address the prognostic relevance of specific biologic factors and define a prognostic index. There are a lack of randomized clinical trial data in MF/SS and evidence is based on a traditional "stage-based" approach; treatment of early-stage disease (IA-IIA) involves skin directed therapies which include topical corticosteroids, phototherapy (psoralen with UVA or UVB), topical chemotherapy, topical bexarotene, and radiotherapy including total skin electron beam therapy. Systemic approaches are used for refractory early-stage and advanced-stage disease (IIB-IV) and include bexarotene, interferon α, extracorporeal photopheresis, histone deacetylase inhibitors, and antibody therapies such as alemtuzumab, systemic chemotherapy, and allogeneic transplantation. However, despite the number of biologic agents available, the treatment of advanced-stage disease still represents an unmet medical need with short duration of responses. Encouragingly, randomized phase 3 trials are assessing novel agents, including brentuximab vedotin and the anti-CCR4 antibody, mogamulizumab. A broader understanding of the biology of MF/SS will hopefully identify more effective targeted therapies., (© 2016 by The American Society of Hematology.)

A 72-year-man presented with a 7-month history of progressive patches and plaques over the trunk and limbs. A skin biopsy confirmed mycosis fungoides (MF). After staging investigations, he was considered to have T2N0M0B0 (stage Ib) disease and began ultraviolet (UV) B phototherapy. Despite initial response, his disease progressed after 4 months, with enlarging patches and plaques but without nodal involvement. As second-line therapy, he received interferon alfa-2b (IFN--2b) 2.7 MU daily, which he tolerated well. He again experienced initial partial response (PR), but by 18 months, he had experienced tumor progression, with patches, plaques, and multiple tumors over the body (up to 3 cm; Fig 1). Biopsy of a neck tumor demonstrated tumor-stage MF,with no evidence of large-cell transformation. Approximately 30% of lymphocytes strongly expressed CD30. CD25 was negative. He began treatment with oral methotrexate 20mg per week, which he tolerated well, and achieved a PR lasting 7 months before multiple plaque and tumor lesions recurred, along with the development of inguinal lymphadenopthy. Biopsy of the skin lesions confirmed the same disease, and [18F]fluorodeoxyglucose–positron emission tomography demonstrated avidity in inguinal and internal iliac nodes, with lymphadenopathy measuring up to 3.5 cm. He has been referred for consideration of further systemic therapy.

Purpose: Advanced-stage mycosis fungoides (MF; stage IIB to IV) and Sézary syndrome (SS) are aggressive lymphomas with a median survival of 1 to 5 years. Clinical management is stage based; however, there is wide range of outcome within stages. Published prognostic studies in MF/SS have been single-center trials. Because of the rarity of MF/SS, only a large collaboration would power a study to identify independent prognostic markers., Patients and Methods: Literature review identified the following 10 candidate markers: stage, age, sex, cutaneous histologic features of folliculotropism, CD30 positivity, proliferation index, large-cell transformation, WBC/lymphocyte count, serum lactate dehydrogenase, and identical T-cell clone in blood and skin. Data were collected at specialist centers on patients diagnosed with advanced-stage MF/SS from 2007. Each parameter recorded at diagnosis was tested against overall survival (OS)., Results: Staging data on 1,275 patients with advanced MF/SS from 29 international sites were included for survival analysis. The median OS was 63 months, with 2- and 5-year survival rates of 77% and 52%, respectively. The median OS for patients with stage IIB disease was 68 months, but patients diagnosed with stage III disease had slightly improved survival compared with patients with stage IIB, although patients diagnosed with stage IV disease had significantly worse survival (48 months for stage IVA and 33 months for stage IVB). Of the 10 variables tested, four (stage IV, age > 60 years, large-cell transformation, and increased lactate dehydrogenase) were independent prognostic markers for a worse survival. Combining these four factors in a prognostic index model identified the following three risk groups across stages with significantly different 5-year survival rates: low risk (68%), intermediate risk (44%), and high risk (28%)., Conclusion: To our knowledge, this study includes the largest cohort of patients with advanced-stage MF/SS and identifies markers with independent prognostic value, which, used together in a prognostic index, may be useful to stratify advanced-stage patients., (© 2015 by American Society of Clinical Oncology.)

Primary cutaneous large cell anaplastic lymphoma (C-ALCL) and lymphomatoid papulosis (LyP) are cutaneous CD30+ lymphoproliferative disorders (CD30+ LPD). An association with CD30+ LPD and pseudoepitheliomatous hyperplasia has been recognized. Additionally, rare reports of epithelial neoplasms such as keratoacanthomas and squamous cell carcinomas (SCC) occurring in association with both C-ALCL and LyP have been reported. We report two cases of CD30+ LPD with associated epithelial neoplasms; one patient with a primary cutaneous CD30+ LPD and SCC identified within the same lesion, and the other with a keratoacanthoma arising in a lesion of LyP. The pathogenesis of this association is poorly understood although various hypotheses exist. Awareness of the coexistence of these entities will avoid misdiagnosis and incorrect treatment., (© 2014 The Australasian College of Dermatologists.)

Romidepsin is an epigenetic agent approved for the treatment of patients with cutaneous or peripheral T-cell lymphoma (CTCL and PTCL). Here we report data in all patients treated on the National Cancer Institute 1312 trial, demonstrating long-term disease control and the ability to retreat patients relapsing off-therapy. In all, 84 patients with CTCL and 47 with PTCL were enrolled. Responses occurred early, were clinically meaningful and of very long duration in some cases. Notably, patients with PTCL receiving romidepsin as third-line therapy or later had a comparable response rate (32%) of similar duration as the total population (38%). Eight patients had treatment breaks of 3.5 months to 10 years; in four of six patients, re-initiation of treatment led to clear benefit. Safety data show slightly greater haematological and constitutional toxicity in PTCL. cDNA microarray studies show unique individual gene expression profiles, minimal overlap between patients, and both induction and repression of gene expression that reversed within 24 h. These data argue against cell death occurring as a result of an epigenetics-mediated gene induction programme. Together this work supports the safety and activity of romidepsin in T-cell lymphoma, but suggests a complex mechanism of action., (© 2015 John Wiley & Sons Ltd.)

Numerous systemic treatment options exist for patients with mycosis fungoides (MF) and Sézary syndrome (SS), but no large comparative studies are published. To study the efficacy of treatments, a retrospective analysis of our cutaneous lymphoma database was undertaken, with 198 MF/SS patients undergoing systemic therapies. The primary end point was time to next treatment (TTNT). Patients with advanced-stage disease made up 53%. The median follow-up time from diagnosis for all alive patients was 4.9 years (range 0.3-39.6), with a median survival of 11.4 years. Patients received a median of 3 lines of therapy (range 1-13), resulting in 709 treatment episodes. Twenty-eight treatment modalities were analyzed. The median TTNT for single- or multiagent chemotherapy was only 3.9 months (95% confidence interval [CI] 3.2-5.1), with few durable remissions. α-interferon gave a median TTNT of 8.7 months (95% CI 6.0-18.0), and histone deacetylase inhibitors (HDACi) gave a median TTNT of 4.5 months (95% CI 4.0-6.1). When compared directly with chemotherapy, interferon and HDACi both had greater TTNT (P < .00001 and P = .01, respectively). This study confirms that all chemotherapy regimens assessed have very modest efficacy; we recommend their use be restricted until other options are exhausted., (© 2015 by The American Society of Hematology.)

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., (© 2014 British Association of Dermatologists.)

Background: We aimed to determine duration of response in patients with CTCL treated using DD who experienced partial response, complete clinical response, or complete response., Patients and Methods: Data from 3 phase III studies were pooled. Patients received up to 8 courses of 9 or 18 μg/kg intravenous DD daily for 5 days every 21 days, or placebo. Data on DD-treated patients were analyzed by dose and CD25 status. Kaplan-Meier product limit estimates and 95% confidence intervals were calculated for duration of response and time to response., Results: The pooled population comprised 263 DD-treated and 44 placebo-treated patients, and 100 and 7, respectively, had at least a partial response. Median duration of response using DD was 277 days vs. 81 days using placebo. Overall response vs. placebo (n = 7; 16%) as (n = 25; 31%) for DD 9 μg/kg (P = .05), (n = 56; 47%) for DD 18 μg/kg (P = .004), (n = 8; 28%) for re-treated patients (DD 18 μg/kg; P = .21), and (n = 11; 31%) for CD25 low-expression patients (DD 18 μg/kg; P = .14). Overall response rates were similar between patients who did (n = 95; 36%) and did not (n = 105; 40%) develop capillary leak syndrome (CLS); median duration of response was longer in patients who developed CLS, but was not significant (619 vs. 267 days, respectively; P = .28). Adverse events occurred in 98% of DD-treated patients; most frequent were nausea, pyrexia, fatigue, CLS, and rigors., Conclusion: These data indicate a durable response with DD in CTCL, even in heavily pretreated patients and those with CD25 low-expression disease., (Copyright © 2013 Elsevier Inc. All rights reserved.)

This open-label phase III trial, a companion to an earlier placebo-controlled trial, evaluated safety and efficacy of denileukin diftitox (DD) in patients with cutaneous T-cell lymphoma (CTCL) who relapsed after responding to DD primary treatment in the earlier trial. Twenty relapsed patients (stages IA-III) received DD 18 μg/kg/day intravenously on days 1-5 of a 21-day cycle, for ≤ 8 cycles. Efficacy was assessed monthly during the first year then every 3 months. The overall response rate was 40%, mostly partial responses. Nine patients (all baseline stages ≤ IIA) experienced progression. Intent-to-treat median progression-free survival was 205 days, and median duration of response was 274 days. The most common adverse events were nausea, upper respiratory tract infections, fatigue and rigors. Three patients withdrew because of toxicity. This study showed that DD may provide clinically meaningful benefit in patients with CTCL who relapsed after initial response to DD.

Background: Panobinostat is a potent, oral pan-deacetylase inhibitor (pan-DACi) that increases the acetylation of proteins involved in multiple oncogenic pathways. Here, panobinostat is studied in bexarotene-exposed and -naïve patients with refractory cutaneous T-cell lymphoma (CTCL)., Patients and Methods: Patients with CTCL subtypes mycosis fungoides and Sézary syndrome who received ⩾2 prior systemic therapy regimens received panobinostat (20mg) three times every week. The primary objective was overall response rate (ORR) as determined by a combined evaluation of skin disease and involvement of lymph node and viscera. Disease progression was defined as an unconfirmed, ⩾25% increase in modified Severity Weighted Assessment Tool (mSWAT) compared with nadir., Results: Seventy-nine bexarotene-exposed and 60 bexarotene-naïve patients were enrolled. Reductions in baseline mSWAT scores were observed in 103 patients (74.1%). The ORR was 17.3% in all patients in the primary analysis (15.2% and 20.0% in the bexarotene-exposed and -naïve groups, respectively). The median progression-free survival was 4.2 and 3.7 months in the bexarotene-exposed and -naïve groups, respectively. The median duration of response was 5.6 months in the bexarotene-exposed patients and was not reached at data cutoff in the bexarotene-naïve patients. Additional responses were observed when less-stringent progression criteria were used. The most common adverse events were thrombocytopenia, diarrhoea, fatigue and nausea. Thrombocytopenia and neutropenia were the only grade 3/4 adverse events in >5% of patients and were manageable., Conclusion: Despite a very conservative definition of disease progression, panobinostat demonstrated activity with a manageable safety profile in bexarotene-exposed and -naïve CTCL patients. ClinicalTrials.gov Identifier: NCT00425555., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Mycosis fungoides (MF) and Sézary syndrome (SS), the major forms of cutaneous T-cell lymphoma, have unique characteristics that distinguish them from other types of non-Hodgkin's lymphomas. Clinical trials in MF/SS have suffered from a lack of standardization in evaluation, staging, assessment, end points, and response criteria. Recently defined criteria for the diagnosis of early MF, guidelines for initial evaluation, and revised staging and classification criteria for MF and SS now offer the potential for uniform staging of patients enrolled in clinical trials for MF/SS. This article presents consensus recommendations for the general conduct of clinical trials of patients with MF/SS as well as methods for standardized assessment of potential disease manifestations in skin, lymph nodes, blood, and visceral organs, and definition of end points and response criteria. These guidelines should facilitate collaboration among investigators and collation of data from sponsor-generated or investigator-initiated clinical trials involving patients with MF or SS.

PURPOSE This phase III, placebo-controlled, randomized trial was designed to investigate efficacy and safety of two doses of denileukin diftitox (DD; DAB(389)-interleukin-2 [IL-2]), a recombinant fusion protein targeting IL-2 receptor-expressing malignant T lymphocytes, in patients with stage IA to III, CD25 assay-positive cutaneous T-cell lymphoma (CTCL), including the mycosis fungoides and Sézary syndrome forms of the disease, who had received up to three prior therapies. The primary end point was overall response rate (ORR). PATIENTS AND METHODS Patients (N = 144) with biopsy-confirmed, CD25 assay-positive CTCL were randomly assigned to DD 9 microg/kg/d (n = 45), DD 18 microg/kg/d (n = 55), or placebo infusions (n = 44), administered for 5 consecutive days every 3 weeks for up to eight cycles. Patients were monitored for drug efficacy, clinical benefit, and safety of DD. RESULTS ORR was 44% for all participants treated with DD (n = 100; 10% complete response [CR] and 34% partial response [PR]) compared with 15.9% for placebo-treated patients (2% CR and 13.6% PR). ORR was higher in the 18 microg/kg/d group versus the 9 microg/kg/d group (49.1% v 37.8%, respectively), and both doses were significantly superior to placebo. Progression-free survival (PFS) was significantly longer (median, > 2 years) for both DD doses compared with placebo (median, 124 days; P < .001). Rates of moderately severe and severe adverse events (AEs) were slightly higher in the DD groups, whereas moderate and mild AEs were similar to placebo. No statistical differences were observed for drug-related serious AEs. CONCLUSION DD had a significant and durable effect on ORR and PFS with an acceptable safety profile in patients with early- and late-stage CTCL.

The most common subtypes of primary cutaneous T-cell lymphomas are mycosis fungoides (MF) and Sézary syndrome (SS). The majority of patients have indolent disease; and given the incurable nature of MF/SS, management should focus on improving symptoms and cosmesis while limiting toxicity. Management of MF/SS should use a "stage-based" approach; treatment of early-stage disease (IA-IIA) typically involves skin directed therapies that include topical corticosteroids, phototherapy (psoralen plus ultraviolet A radiation or ultraviolet B radiation), topical chemotherapy, topical or systemic bexarotene, and radiotherapy. Systemic approaches are used for recalcitrant early-stage disease, advanced-stage disease (IIB-IV), and transformed disease and include retinoids, such as bexarotene, interferon-alpha, histone deacetylase inhibitors, the fusion toxin denileukin diftitox, systemic chemotherapy including transplantation, and extracorporeal photopheresis. Examples of drugs under active investigation include new histone deacetylase inhibitors, forodesine, monoclonal antibodies, proteasome inhibitors, and immunomodulatory agents, such as lenalidomide. It is appropriate to consider patients for novel agents within clinical trials if they have failed front-line therapy and before chemotherapy is used.

A 40-year-old woman presented with a prolonged history of recurrent crops of erythematous papules and nodules on her abdomen, arms and legs. Histological examination of a cutaneous biopsy revealed Type A lymphomatoid papulosis. Over a 3-year period, some of the patient's lesions had proven to be resistant to treatment with topical and intralesional corticosteroids and systemic agents including methotrexate, tetracycline and nicotinamide. These resistant lesions were treated with two sessions of methyl aminolevulinate photodynamic therapy given 1 week apart. Review 11 months post-photodynamic therapy demonstrated complete clinical clearance at the treatment site. While photodynamic therapy is considered a standard non-surgical treatment option for non-melanoma skin cancers and has been described in a number of non-oncological indications, this is the first report of its use in lymphomatoid papulosis.

Although mycosis fungoides (MF) is typically an indolent disease, patients with advanced-stage disease (stages IIB-IVB), including Sézary syndrome (SS), often have a poor outcome. A 31-year, retrospective analysis of our cutaneous lymphoma database, of 297 patients with MF and SS, was undertaken to study long-term outcomes and identify clinical predictors of outcome in patients with advanced-stage disease (ASD, n = 92) and large cell transformation (LCT, n = 22). Two-thirds of patients with ASD presented with de novo ASD. The median overall survival (OS) for ASD was 5 years with a 10-year predicted OS of 32%. Age at initial diagnosis (P = .01), tumor stage (P = .01), and clinical stage (P = .001) were found to be significant predictors of outcome. Patients who presented with de novo ASD demonstrated better outcomes that were not statistically significant than those with a prior diagnosis of early-stage MF (P = .25). Transformation developed in 22 of the 297 MF/SS patients (7.4%), with a transformation rate of only 1.4% in patients with early-stage disease, compared with stage IIB (27%) and stage IV (56%-67%) disease. The median OS from diagnosis of LCT was 2 years. We confirm that the incidence of LCT is strongly dependent on tumor stage at diagnosis, and we demonstrate a much lower overall risk of LCT than previously reported.

Various studies have reported that extracorporeal photopheresis is effective in producing meaningful responses in patients with Sézary syndrome. A single-center, 5-year retrospective analysis was performed on our patients with Sézary syndrome who received extracorporeal photopheresis using a novel protocol. Thirteen patients were treated with extracorporeal photopheresis consistently for a minimum of 2 months. All patients received a modified protocol of one treatment per week for 6 sessions, one session every 2 weeks for 6 sessions, and then one session per month. The overall response rate was 62%: two patients achieved a complete response and 6 patients achieved a partial response. The median time to response was 10 months. The 2- and 4-year predicted overall survivals were 82%. This study was limited by its retrospective nature and small sample size. Response and survival compare favorably with those of previous studies. Our modified treatment protocol appears to produce outcomes similar to the two-day protocol.

Purpose: Histone deacetylase inhibitors can alter gene expression and mediate diverse antitumor activities. Herein, we report the safety and activity of the histone deacetylase inhibitor panobinostat (LBH589) in cutaneous T-cell lymphoma (CTCL) and identify genes commonly regulated by panobinostat., Experimental Design: Panobinostat was administered orally to patients with CTCL on Monday, Wednesday, and Friday of each week on a 28-day cycle. A dose of 30 mg was considered excessively toxic, and subsequent patients were treated at the expanded maximum tolerated dose of 20 mg. Biopsies from six patients taken 0, 4, 8, and 24 h after administration were subjected to microarray gene expression profiling and real-time quantitative PCR of selected genes., Results: Patients attained a complete response (n = 2), attained a partial response (n = 4), achieved stable disease with ongoing improvement (n = 1), and progressed on treatment (n = 2). Microarray data showed distinct gene expression response profiles over time following panobinostat treatment, with the majority of genes being repressed. Twenty-three genes were commonly regulated by panobinostat in all patients tested., Conclusions: Panobinostat is well tolerated and induces clinical responses in CTCL patients. Microarray analyses of tumor samples indicate that panobinostat induces rapid changes in gene expression, and surprisingly more genes are repressed than are activated. A unique set of genes that can mediate biological responses such as apoptosis, immune regulation, and angiogenesis were commonly regulated in response to panobinostat. These genes are potential molecular biomarkers for panobinostat activity and are strong candidates for the future assessment of their functional role(s) in mediating the antitumor responses of panobinostat.

In order to investigate the effectiveness of the 308-nm xenon chloride laser in the treatment of patch-stage mycosis fungoides that is refractory to topical steroids, we conducted a prospective, histologically controlled, open-label pilot study. Eight patients with stage 1A or 1B cutaneous T-cell lymphoma that was unresponsive to application of potent topical steroids received 20 treatments with the laser over 10 weeks and were then followed up for a minimum of 30 months. Three patients had a complete clinical and histological response and remained free of disease after 30 months A further three patients had complete clinical and histological clearance of disease, but experienced relapse within the 30 months follow-up period. One patient withdrew from the study and one had a partial response. Further research to establish the role of the 308-nm laser in the treatment of MF appears justified.

Background: Apoptosis of malignant cells has been suggested as an important mechanism of the action of bexarotene in the treatment of cutaneous T-cell lymphoma (CTCL)., Objectives: Our purpose was to examine the in vivo and in vitro responses of patients with Sézary syndrome treated with oral bexarotene and assess them for apoptosis of the Sézary cells., Methods: Six patients with CTCL with circulating Sézary cells, participating in a clinical trial of oral bexarotene (300 mg m(-2) daily) were included in the study. Peripheral blood from the patients was analysed for in vivo and in vitro apoptosis., Results: None of the six patients demonstrated in vivo apoptosis. In vitro apoptosis of Sézary cells was demonstrated in one patient following exogenous bexarotene., Conclusions: Apoptosis is not detectable in the circulation of patients with Sézary syndrome treated with bexarotene.

Rituximab (anti-CD20 chimeric monoclonal antibody) has been demonstrated to have significant activity in nodal B-cell lymphomas, with very few associated adverse effects. Although primary cutaneous B-cell lymphomas (PCBCL) also express the CD20 antigen, relatively few reports of rituximab use in PCBCL have been published to date. We present two cases of primary cutaneous follicular centre lymphoma treated with rituximab (375 mg/m(2)/week intravenously for 4 weeks). Both cases responded to rituximab, with one partial response and one complete response seen. No adverse effects were observed. To date, disease progression has occurred in one case during overall follow up at 6 and 17 months. The potential role of rituximab in the treatment of these lymphomas is discussed.