Journal of the European Academy of Dermatology and Venereology

<jats:title>Abstract</jats:title><jats:p>This manuscript provides expert recommendations on the role of allogeneic haematopoietic cell transplantation (allo‐HCT) for cutaneous T‐cell lymphoma (CTCL), specifically mycosis fungoides (MF) and Sezary syndrome (SS). Critical aspects such as patient selection, timing, and bridging therapy are addressed, as well as donor source, conditioning regimens and post‐transplant management. These consensus guidelines are based on a thorough literature review and discussions among leading dermatologists and haematologists. These recommendations aim to harmonize clinical practice towards improving patient outcomes in these rare but aggressive lymphomas. It is of critical importance to consider allo‐HCT early in the management of eligible patients with high‐risk disease. Advanced stage, large‐cell transformation, relapsed or refractory disease following systemic treatment, and N3‐stage lymph node involvement are indicators that should trigger consultation with a transplant haematologist in parallel with a donor search. Early interaction between dermatologists and transplant haematologists is vital to avoiding delays, which can significantly impact post‐transplant outcomes and survival.</jats:p>

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Allogeneic hematopoietic cell transplantation in patients with advanced mycosis fungoides and Sézary syndrome: a retrospective analysis including 63 consecutive patients with long‐term median follow‐up

Bone Marrow Transplant

This manuscript provides expert recommendations on the role of allogeneic haematopoietic cell transplantation (allo-HCT) for cutaneous T-cell lymphoma (CTCL), specifically mycosis fungoides (MF) and Sezary syndrome (SS). Critical aspects such as patient selection, timing, and bridging therapy are addressed, as well as donor source, conditioning regimens and post-transplant management. These consensus guidelines are based on a thorough literature review and discussions among leading dermatologists and haematologists. These recommendations aim to harmonize clinical practice towards improving patient outcomes in these rare but aggressive lymphomas. It is of critical importance to consider allo-HCT early in the management of eligible patients with high-risk disease. Advanced stage, large-cell transformation, relapsed or refractory disease following systemic treatment, and N3-stage lymph node involvement are indicators that should trigger consultation with a transplant haematologist in parallel with a donor search. Early interaction between dermatologists and transplant haematologists is vital to avoiding delays, which can significantly impact post-transplant outcomes and survival.

Allogeneic haematopoietic cell transplant in cutaneous T-cell lymphomas: Recommendations from the EBMT PH&G Committee.

Allogeneic haematopoietic cell transplant in cutaneous T‐cell lymphomas: Recommendations from the <scp>EBMT PH</scp>&amp;G Committee

JDDG: Journal der Deutschen Dermatologischen Gesellschaft

<jats:title>Summary</jats:title><jats:sec><jats:title>Background and Objectives</jats:title><jats:p>While brentuximab vedotin (BV) and radiotherapy (RTx) are established treatment options for CD30‐positive cutaneous T‐cell lymphoma (CTCL), data on their simultaneous or sequential use regarding efficacy and tolerability remain scarce. In this retrospective analysis, we evaluated the combination of BV and RTx in patients with CD30‐positive CTCL.</jats:p></jats:sec><jats:sec><jats:title>Patients and Methods</jats:title><jats:p>We included 14 CD30‐positive CTCL patients from six German cancer centers receiving BV; RTx was initiated within a timeframe of 3 months prior/after BV treatment. RTx was mainly applied as a low‐dose scheme.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Adverse events of any grade occurred in 71% of patients, most commonly peripheral neuropathy, neutropenia, and radiodermatitis. Thirteen patients achieved a complete or partial remission as best overall response, however, 50% of all patients showed disease progression. At a median follow‐up of 14.4 months, median progression‐free survival was 12.0 months, with a 1‐year rate of 34.0%.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>The simultaneous or sequential use of RTx during BV treatment was feasible and well tolerated. Future randomized investigations are needed to identify the benefits of this combination treatment regimen as well as adequate dosing of BV and RTx in a prospective manner.</jats:p></jats:sec>

Cutaneous T‐cell lymphomas‐An update 2021

Hematol Oncol

Primary cutaneous lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow‐up

Ann Oncol

Brentuximab vedotin or physician's choice in CD30‐positive cutaneous T‐cell lymphoma (ALCANZA): an international, open‐label, randomised, phase 3, multicentre trial

Lancet

Randomized phase 3 ALCANZA study of brentuximab vedotin vs physician's choice in cutaneous T‐cell lymphoma: final data

Blood Adv

Modern radiation therapy for primary cutaneous lymphomas: field and dose guidelines from the International Lymphoma Radiation Oncology Group

Int J Radiat Oncol Biol Phys

Radiation Therapy for Cutaneous T‐Cell Lymphomas

Dermatol Clin

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

Am J Hematol

Radiotherapy in cutaneous lymphomas: Recommendations from the EORTC cutaneous lymphoma tumour group

Eur J Cancer

Low dose total skin electron beam therapy for the management of T cell cutaneous lymphomas

Dermatol Ther

Phase Ib study of brentuximab vedotin (BV) with low‐dose total skin electron beam (LD‐TSEB) for treatment of mycosis fungoides (MF) and Sezary syndrome (SS)

J Clin Oncol

Brentuximab vedotin in combination with extended field radiotherapy as salvage treatment for primary refractory Hodgkin lymphoma

Brentuximab vedotin and AVD followed by involved‐site radiotherapy in early stage, unfavorable risk Hodgkin lymphoma

Blood

Near Complete Response in a Patient with Classical Hodgkin Lymphoma Treated with Brentuximab Vedotin Concurrent with Radiation Therapy

Case Rep Oncol

Combined Modality Treatment With Brentuximab Vedotin and Radiation Therapy for Primary Cutaneous Anaplastic Large Cell Lymphoma: A Case Report

J Hematol

Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC)

Near complete responses to concurrent brentuximab vedotin and ultra‐hypofractionated low‐dose total skin electron beam radiation in advanced cutaneous T‐cell lymphoma

The British journal of dermatology

Tumor radiosensitization by monomethyl auristatin E: mechanism of action and targeted delivery

Cancer Res

Safety of Concurrent Radiation Therapy With Brentuximab Vedotin in the Treatment of Lymphoma

Adv Radiat Oncol

Brentuximab vedotin in the treatment of cutaneous T‐cell lymphomas: Data from the Spanish Primary Cutaneous Lymphoma Registry

J Eur Acad Dermatol Venereol

Combination of brentuximab‐vedotin with skin‐directed therapies extends the time to the next therapeutic line in patients with cutaneous T‐cell lymphoma

J Dtsch Dermatol Ges

Real‐World Pattern‐of‐Care Analysis of Primary Cutaneous Lymphomas Radiation Therapy Among European Organisation for Research and Treatment of Cancer Members

While brentuximab vedotin (BV) and radiotherapy (RTx) are established treatment options for CD30-positive cutaneous T-cell lymphoma (CTCL), data on their simultaneous or sequential use regarding efficacy and tolerability remain scarce. In this retrospective analysis, we evaluated the combination of BV and RTx in patients with CD30-positive CTCL.
We included 14 CD30-positive CTCL patients from six German cancer centers receiving BV; RTx was initiated within a timeframe of 3 months prior/after BV treatment. RTx was mainly applied as a low-dose scheme.
Adverse events of any grade occurred in 71% of patients, most commonly peripheral neuropathy, neutropenia, and radiodermatitis. Thirteen patients achieved a complete or partial remission as best overall response, however, 50% of all patients showed disease progression. At a median follow-up of 14.4 months, median progression-free survival was 12.0 months, with a 1-year rate of 34.0%.
The simultaneous or sequential use of RTx during BV treatment was feasible and well tolerated. Future randomized investigations are needed to identify the benefits of this combination treatment regimen as well as adequate dosing of BV and RTx in a prospective manner.

Brentuximab vedotin and radiotherapy for CD30-positive cutaneous T-cell lymphoma - a retrospective multicenter analysis.

Brentuximab vedotin and radiotherapy for CD30‐positive cutaneous T‐cell lymphoma – a retrospective multicenter analysis

Journal of Investigative Dermatology

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The potential role of interleukin-37 in infectious diseases

Int Rev Immunol

Medical history, lifestyle, family history, and occupational risk factors for mycosis fungoides and Sezary syndrome: the InterLymph Non-Hodgkin Lymphoma Subtypes Project

J Natl Cancer Inst Monogr

Infections complicating mycosis fungoides and Sezary syndrome

JAMA

Crosstalk between tumor T lymphocytes and reactive T lymphocytes in cutaneous T cell lymphomas

Ann N Y Acad Sci

The importance of understanding the infectious microenvironment

Lancet Infect Dis

Staphylococcus aureus alpha-toxin inhibits CD8+ T cell-mediated killing of cancer cells in cutaneous T-cell lymphoma

Oncoimmunology

Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4+ T cells in cutaneous T-cell lymphoma

Macrophage-derived CXCL9 and CXCL11, T-cell skin homing, and disease control in mogamulizumab-treated CTCL patients

Exploring the role of the skin microenvironment in cutaneous T-cell lymphoma using single cell RNA-sequencing

Epidemiological changes in cutaneous lymphomas: an analysis of 8593 patients from the French cutaneous Lymphoma Registry

Br J Dermatol

Cutaneous T cell lymphoma

Nat Rev Dis Primers

Cutaneous T cell lymphoma: mycosis fungoides, Sezary syndrome, and other variants

J Am Acad Dermatol

Cutaneous T cell lymphoma: the helping hand of dendritic cells

Linker-improved chimeric endolysin selectively kills Staphylococcus aureus in vitro, on reconstituted human epidermis, and in a murine model of skin infection

Antimicrob Agents Chemother

Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen in erythrodermic cutaneous T-cell lymphoma (CTCL) patients

Arch Dermatol Res

Role of dysregulated cytokine signaling and bacterial triggers in the pathogenesis of cutaneous T-cell lymphoma

J Invest Dermatol

Distinct age-matched serum biomarker profiles in patients with cutaneous T-cell lymphoma

Exp Dermatol

Malignant T cells induce skin barrier defects through cytokine-mediated JAK/STAT signalling in cutaneous T-cell lymphoma

MicroRNAs in the pathogenesis, diagnosis, prognosis and targeted treatment of cutaneous T-cell lymphomas

Cancers (Basel)

Superantigens: mechanism of T-cell stimulation and role in immune responses

Annu Rev Immunol

Multimodal single-cell analysis of cutaneous T-cell lymphoma reveals distinct subclonal tissue-dependent signatures

Mycosis fungoides: A great imitator

Clin Dermatol

Association of Erythrodermic cutaneous T-cell lymphoma, superantigen-positive Staphylococcus aureus, and oligoclonal T-cell receptor V beta gene expansion

Evidence linking atopy and staphylococcal superantigens to the pathogenesis of lymphomatoid papulosis, a recurrent CD30+ cutaneous lymphoproliferative disorder

PLoS One

A continuous T-cell line from a patient with Sezary syndrome

Establishment of T and B cell lines from patients with mycosis fungoides

Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): an international, open-label, randomised, controlled phase 3 trial

Lancet Oncol

Malignant inflammation in cutaneous T-cell lymphoma-a hostile takeover

Semin Immunopathol

Elucidating the role of interleukin-17F in cutaneous T-cell lymphoma

Jak3- and JNK-dependent vascular endothelial growth factor expression in cutaneous T-cell lymphoma

Leukemia

The novel endolysin XZ.700 effectively treats MRSA biofilms in two biofilm models without showing toxicity on human bone cells in vitro

Biofouling

The "Duvic regimen" for erythrodermic flares secondary to Staphylococcus aureus in mycosis fungoides and Sezary syndrome

Int J Dermatol

Staphylococcus aureus and antibiotics in cutaneous T-cell Lymphoma

Dermatology

Antibiotics inhibit tumor and disease activity in cutaneous T-cell lymphoma

Normal and cancer fibroblasts differentially regulate TWIST1, TOX and cytokine gene expression in cutaneous T-cell lymphoma

BMC Cancer

Infectious agents in cutaneous T-cell lymphoma

Chromatin accessibility landscape of cutaneous T cell lymphoma and dynamic response to HDAC inhibitors

Cancer Cell

Interferon-inducible protein-10 and the pathogenesis of cutaneous T-cell lymphomas

Leuk Lymphoma

Cytokine loops involving interferon-gamma and IP-10, a cytokine chemotactic for CD4+ lymphocytes: an explanation for the epidermotropism of cutaneous T-cell lymphoma?

Bacteriophage endolysins as novel antimicrobials

Future Microbiol

Bacteriophage endolysins - extending their application to tissues and the bloodstream

Curr Opin Biotechnol

Evolutionarily distinct bacteriophage endolysins featuring conserved peptidoglycan cleavage sites protect mice from MRSA infection

J Antimicrob Chemother

Cellular interactions and inflammation in the pathogenesis of cutaneous T-cell lymphoma

Front Cell Dev Biol

Prevalence and treatment of Staphylococcus aureus colonization in patients with mycosis fungoides and Sezary syndrome

Genetic and epigenetic insights into cutaneous T-cell lymphoma

Epidermal interferon-gamma inducible protein-10 (IP-10) and monokine induced by gamma-interferon (Mig) but not IL-8 mRNA expression is associated with epidermotropism in cutaneous T cell lymphomas

Stimulation of cutaneous T-cell lymphoma cells with superantigenic staphylococcal toxins

Cutaneous colonization with staphylococci influences the disease activity of Sezary syndrome: a potential role for bacterial superantigens

Epigenomic analysis of Sezary syndrome defines patterns of aberrant DNA methylation and identifies diagnostic markers

Benign T cells drive clinical skin inflammation in cutaneous T cell lymphoma

JCI Insight

Staphylococcus aureus enterotoxins induce FOXP3 in neoplastic T cells in Sezary syndrome

Blood Cancer J

Staphylococcus aureus induces signal transducer and activator of transcription 5-dependent miR-155 expression in cutaneous T-cell lymphoma

Bacterial toxins fuel disease progression in cutaneous T-cell lymphoma

Toxins (Basel)

Staphylococcal enterotoxin A (SEA) stimulates STAT3 activation and IL-17 expression in cutaneous T-cell lymphoma

Nonmalignant T cells stimulate growth of T-cell lymphoma cells in the presence of bacterial toxins

A small molecule CCR2 antagonist depletes tumor macrophages and synergizes with anti-PD-1 in a murine model of cutaneous T-cell lymphoma (CTCL)

Cutaneous T-cell lymphoma: roles for chemokines and chemokine receptors

IL-32 supports the survival of malignant T cells in cutaneous T-cell lymphoma

Staphylococcus aureus is suspected to fuel disease activity in cutaneous T-cell lymphomas. In this study, we investigate the effect of a recombinant, antibacterial protein, endolysin (XZ.700), on S. aureus skin colonization and malignant T-cell activation. We show that endolysin strongly inhibits the proliferation of S. aureus isolated from cutaneous T-cell lymphoma skin and significantly decreases S. aureus bacterial cell counts in a dose-dependent manner. Likewise, ex vivo colonization of both healthy and lesional skin by S. aureus is profoundly inhibited by endolysin. Moreover, endolysin inhibits the patient-derived S. aureus induction of IFNγ and the IFNγ-inducible chemokine CXCL10 in healthy skin. Whereas patient-derived S. aureus stimulates activation and proliferation of malignant T cells in vitro through an indirect mechanism involving nonmalignant T cells, endolysin strongly inhibits the effects of S. aureus on activation (reduced CD25 and signal transducer and activator of transcription 5 phosphorylation) and proliferation (reduced Ki-67) of malignant T cells and cell lines in the presence of nonmalignant T cells. Taken together, we provide evidence that endolysin XZ.700 inhibits skin colonization, chemokine expression, and proliferation of pathogenic S. aureus and blocks their potential tumor-promoting effects on malignant T cells.

Endolysin Inhibits Skin Colonization by Patient-Derived Staphylococcus Aureus and Malignant T-Cell Activation in Cutaneous T-Cell Lymphoma.

Endolysin Inhibits Skin Colonization by Patient-Derived Staphylococcus Aureus and Malignant T-Cell Activation in Cutaneous T-Cell Lymphoma

Cutaneous T-Cell Lymphoma in Dermatology Research

Allogeneic haematopoietic cell transplant in cutaneous T‐cell lymphomas: Recommendations from the <scp>EBMT PH</scp>&G Committee

Brentuximab vedotin and radiotherapy for CD30‐positive cutaneous T‐cell lymphoma – a retrospective multicenter analysis

Endolysin Inhibits Skin Colonization by Patient-Derived Staphylococcus Aureus and Malignant T-Cell Activation in Cutaneous T-Cell Lymphoma

Papers