Type Of Cutaneous T-cell Lymphoma Research Articles

Effectiveness and safety of interferon α-2a combined with phototherapy for patients with early-stage mycosis fungoides - a single-arm prospective study in 13 patients

Background: Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma. Objectives: This study was conducted to evaluate efficacy and safety of interferon (IFN) α-2a combined with phototherapy for early-stage MF. Methods: Thirteen patients with early-stage MF received subcutaneous injections of IFN α-2a at 3 million IU combined with phototherapy three times per week for 6 months. Treatment efficacy was measured by changes in body surface area (BSA) score and modified severity-weighted assessment tool (mSWAT) score at 1, 3, and 6 months after treatment. Histopathologic examinations of skin lesions were performed before and after treatment. Results: After 3 months of treatment, all 13 patients achieved a partial response, and BSA and mSWAT scores were significantly lower than those at baseline (p < 0.001). After 6 months, BSA and mSWAT scores were significantly lower than those at baseline (p < 0.001) and after 3 months (p < 0.05). Eleven patients achieved complete remission and two patients achieved a partial response (overall response rate, 100%). Histopathologic examination showed a significant decrease in the number of atypical lymphocytes in both epidermis and dermis. No severe adverse effects occurred. Conclusion: IFN α-2a in combination with phototherapy may be an effective and safe alternative modality for early-stage MF.

Stage-related increase in PIM2 expression in mycosisfungoides.

The oncogene PIM2 is upregulated in several malignancies but has never been investigated in mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma (CTCL). PIM2 is a well-known oncogene and is regulated by cell signaling pathways like the JAK/STAT- and NF-kB-pathway, key regulators in the pathogenesis of CTCL. The aim of this study was to examine the role of PIM2 in MF. PIM2 gene expression was measured in 81 formalin-fixed paraffin-embedded skin biopsies from patients with MF and 46 control biopsies from healthy skin (HS) and benign inflammatory skin disease (BID). Validation of PIM2 protein expression was performed on selected biopsies with immunohistochemical staining. We found a significant difference in gene expression levels between both early stage MF and HS (p < 0.0001), and BID (p < 0.0001). In addition, the PIM2 gene expression was higher in advanced-stage MF compared to early stage disease (p = 0.0001). No significant difference in gene expression levels was found between patients with and without disease progression. In conclusion, we found PIM2 expression is significantly increased in MF compared to controls, and in advanced-stage MF compared to early stage MF. These findings could potentially have diagnostic value in discriminating early stage MF from BID.

Skin-directed therapy and biologic response modifiers in mycosis fungoides

The most common and widespread type of cutaneous T-cell lymphoma is mycosis fungoides (MF), and it has a multiphasic clinical and biological course, with early stages being indolent for many years and later stages being faster and more aggressive. The clinical stage has a significant impact on the management and course of treatment: in the early stages, skin-directed therapies (SDT) plus/or biologic response modifiers (BRM); in the later stages, radiotherapy and/or systemic therapies. Even though national and international societies and groups periodically update their clinical recommendations, there is still no universally accepted approach. This paper reviews and discusses the various SDT and BRM options, either separately or in combination.

Cutaneous lymphoproliferative disorders: Back to the future.

In the 1980s, immunohistochemistry and clonality analyses became instrumental in the recognition and definition of new types of cutaneous T-cell lymphoma (CTCL) and cutaneous B-cell lymphoma (CBCL) and the development of new classifications. By accepting loss of pan-T-cell antigens and clonal T-cell receptor gene rearrangements as important criteria to differentiate between benign and malignant T-cell proliferations, and monotypic immunoglobulin light-chain expression and clonal immunoglobulin gene rearrangements as crucial criteria to distinguish between benign and malignant B-cell proliferations, many cases, until then diagnosed as cutaneous lymphoid hyperplasia or pseudolymphoma, were reclassified as primary cutaneous CD4+ small/medium T-cell lymphoma (PCSM-TCL) or primary cutaneous marginal zone lymphoma (PCMZL), respectively. However, in recent years there is growing awareness that neither these immunohistochemical criteria nor demonstration of T-cell or B-cell clonality is specific for malignant lymphomas. In addition, many studies have reported that these low-grade malignant CTCL and CBCL have an indolent clinical behavior and an excellent prognosis with disease-specific survival rates of or close to 100%. As a result, recent classifications have downgraded several low-grade malignant cutaneous lymphomas to lymphoproliferative disorder (LPD). Both the 5th edition of the WHO classification (2022) and the 2022 International Consensus Classification (ICC) of mature lymphoid neoplasms reclassified PCSM-TCL as primary cutaneous CD4+ small/medium T-cell LPD and primary cutaneous acral CD8+ T-cell lymphoma as primary cutaneous acral CD8+ T cell LPD. While the 2022 ICC introduced the term "primary cutaneous marginal zone LPD," in the 5th edition of the WHO classification PCMZL is maintained. In this review we describe the background and rationale of the continually changing terminology of these conditions and discuss the clinical consequences of downgrading malignant lymphomas to LPDs.

Skin Cancer: Back to Basics, Mycosis Fungoides

ABSTRACT Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma occurring when T-cell lymphocytes become malignant and proliferate as well as manifest in the skin. Most commonly, the disease affects the elderly population but has been seen in all ages. Presentations of MF include erythematous patches and plaques with fine scale anatomically favoring the buttocks, trunk, and extremities with complaints of significant pruritus. MF can mimic other benign inflammatory diseases such as atopic dermatitis or psoriasis. Skin biopsy of the rash for simple histology and immunophenotyping will aid in the differentiation from other diseases and confirm accurate diagnosis. Repeat biopsy is often required. A wide range of treatment options exist based on the extent of the disease and patient compliance. The prognosis is good with early detection and treatment. No cure currently exists for the disease, but a deeper understanding of triggers can guide prevention techniques and help develop targeted treatment modalities.

Morpho-Immunohistochemical Characteristics of Different Mycosis Fungoides Stages: A Literature Review

Mycosis fungoides (MF) is the most ubiquitous type of cutaneous T-cell lymphoma. MF pathogenesis has not been well studied up to now. Differential diagnosis of the disease, especially at early stages, is complicated and poses a considerable challenge. The present review covers current views on MF pathogenesis and methods of its diagnosis.

Real-World Treatment Patterns and Clinical Outcomes With Brentuximab Vedotin or Other Standard Therapies in Patients With Previously Treated Cutaneous T-Cell Lymphoma in the United States

Introduction/BackgroundPrimary cutaneous anaplastic large-cell lymphomas (pcALCLs) are a type of cutaneous T-cell lymphoma (CTCL) in which CD30 is uniformly expressed. In mycosis fungoides (MF), another CTCL, CD30 is heterogeneously expressed. In ALCANZA, patients with pcALCLs or CD30-positive MF randomized to brentuximab vedotin (BV) vs. physician's choice of methotrexate or bexarotene had significantly improved outcomes, including higher objective response rates (ORR) lasting ≥4 months (ORR4), as well as longer median progression-free survival (PFS) and time to next treatment (TTNT). In this study, we sought to assess the real-world impact of treatment with BV in second or later lines of therapy for CTCL. Materials and MethodsThis retrospective chart review describes patient characteristics, treatment patterns, clinical outcomes, and healthcare resource use (HRU) in patients with pcALCLs or MF previously treated with ≥1 systemic therapy and subsequently treated with BV (n = 139) or other standard therapy (OST; n = 164). ResultsMost patients in the BV cohort (96.4%) received BV as second-line (2L) systemic therapy. The most common OSTs were methotrexate (11.6%), mogamulizumab (9.1%), and bendamustine (9.1%) monotherapies. For 2L BV and OST, median duration of therapy was 8.4 and 5.2 months, real-world ORR was 82.1% and 66.5%, and real-world ORR4 was 42.5% and 25.0%. Real-world 1- and 2-year PFS, TTNT, and OS were significantly longer (all P < .01) and HRU was lower for BV vs. OST. ConclusionThese real-world outcomes are consistent with ALCANZA results, demonstrating favorable outcomes with BV vs. OST in patients with CTCL previously treated with ≥1 systemic therapy.

Mechanism of action of chlormethine gel in mycosis fungoides.

Mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma, is characterized by proliferation of malignant skin-tropic T cells. Progression from early-stage disease (skin patches and/or plaques) to more advanced stages (cutaneous tumours, erythroderma or extracutaneous involvement) occurs slowly and can be discontinuous. Prognosis is poor for the ~25% of patients who progress to advanced disease. Patients at any stage of MF may experience reduced health-related quality of life (QoL) via a spectrum of physically and psychologically debilitating symptoms that can impact many aspects of daily life. Allogeneic stem-cell transplantation is a curative treatment option for some patients with advanced disease, but otherwise there is currently no cure for MF; patients are often refractory to several treatments and require lifelong management. The goals of therapy are symptom control, prevention of disease progression, avoidance of treatment-related toxicity and maintenance/improvement of QoL. Although treatment regimens exist it can be difficult to know how to prioritize them, hence therapies are tailored according to patient needs and drug availabilities, following clinical recommendations. International consensus guidelines recommend skin-directed therapies (SDTs) as first-line treatment for early-stage disease, and SDTs combined with systemic therapy for advanced stages. Chlormethine (CL), also known as mechlorethamine, chlorethazine, mustine, HN2, caryolysine and embichin, is a synthetic deoxyribonucleic acid-alkylating agent that was used as a chemical weapon (mustard gas) during the First World War. Subsequent investigation revealed that survivors of mustard gas exposure had lymphocytopenia, and that CL could inhibit rapidly proliferating malignant T cells. CL has since been developed as a topical treatment for MF and prescribed as such for over 70 years. This review aims to summarize the current knowledge regarding the mechanism of action of CL in the cutaneous micro-environment, in the specific context of MF treatment.

Successful Treatment of Early-Stage Mycosis Fungoides With Topical PUVA in Adult Patient: Case Report

Mycosis fungoides is fairly common type of cutaneous T-cell lymphoma with prolonged indolent course. Early-stage MF patch/plaque stage disease (T1/T2) can be treated safely and effectively by Phototherapy. Systemic PUVA and Narrowband UVB widely used with considerable result in MF. Topical PUVA is rarely considered as a phototherapy line in MF. We represent in our patient complete clearance of MF plaque after topical PUVA phototherapy without relapse.

Examining Transcriptomic Differences Underlying Mycosis Fungoides in Skin of Color and White Patients

Abstract Mycosis Fungoides (MF), the most common type of cutaneous T-cell lymphoma, typically presents with an erythematous or dyspigmented rash that can progress to tumors and ulcerations on the skin. MF is more common in skin of color (SOC) patients, where it presents earlier and at a higher T-stage. This has led to poorer prognosis in SOC patients, with the poorest prognosis in African Americans. The pathogenesis regarding this racial disparity remains poorly understood. We compared MF skin samples from SOC and White patients to determine differentially expressed genes and elucidate transcriptomic differences. An immune panel of 343 genes were hybridized to 8 MF SOC and 8 MF White skin samples. The resulting gene signatures were analyzed to determine significant differentially expressed genes. Analysis revealed that SOC has significant downregulation of critical immune response genes involved in the recruitment of immune cells to sites of inflammation, including CCR1, CCR2, and CCR3. Genes involved in ‘chemokine signaling,’ ‘differentiation and maintenance of myeloid cells,’ and ‘cell migration and adhesion,’ were downregulated in SOC MF biopsies as compared to White skin MF biopsies. Furthermore, SOC MF biopsies have a greater abundance of mast cells, whereas White skin MF biopsies have a greater abundance of neutrophils. These transcriptomic differences suggest that MF may have a unique pathogenesis in SOC that involves significant downregulation of the host’s immune response. This potentially provides insight into the presentation of MF at a more advanced stage and aggressive course in SOC as compared to White skin. This insight may facilitate the development of immunotherapies targeted to SOC to address this racial disparity. SD - recipient of the Dermatology Foundation DRSA; JMR - recipient of the Skin of Color Society Reseach Grant; ASB - recipient of the American Skin Association Milstein Research Scholar Award for Melanoma/Non-Melanoma Skin Cancer

Single-Fraction Radiation Therapy for Localized Cutaneous T-Cell Lymphoma

Mycosis fungoides is the most common type of cutaneous T-cell lymphoma (CTCL). Single-fraction radiation therapy has been used as a skin-targeted therapy to treat localized CTCL lesions. The objective of this study was to investigate the treatment outcomes associated with single-fraction radiation therapy for CTCL. We retrospectively studied the outcomes among patients with CTCL treated with single-fraction radiation therapy at our institution between October 2013 and August 2022. Clinical response (complete response [CR], partial response [PR], or no response [NR]) and retreatment response were evaluated. A total of 242 lesions from 46 patients were analyzed, for an average of 5.3 lesions treated per patient. The majority of lesions presented with a plaque morphology (n=145, 60.0%). All lesions were treated to a dose of 8 Gy in 1 fraction. Median follow-up was 24.6 months (range, 1-88 months). Of the 242 lesions, 36 (14.8%) had an initial PR or NR; all were retreated with the same regimen to the same site at a median interval of 8 weeks. Eighteen of the retreated lesions (50.0%) went on to have a CR. Thus, the overall CR rate for CTCL lesions was 92.6%. No recurrences were noted in the treated areas after achieving CR. Single-fraction radiation therapy to a dose of 8 Gy in 1 fraction to localized areas provided a high rate of complete and durable responses in the affected sites.

Cell adhesion molecule 1 expression in mycosis fungoides versus parapsoriasis versus inflammatory dermatosis: an immunohistochemical comparative study.

Cell adhesion molecule 1 (CADM1) is one of the immunoglobulin super family adhesion molecules, that is proposed to contribute in the pathogenesis of various types of cutaneous T-cell lymphoma, including mycosis fungoides (MF). In this work, we decided to examine the immunohistochemical expression of CADM1 in MF specimens compared to premycotic parapsoriasis, benign inflammatory dermatosis and normal control skin specimens. 125 participants were enrolled (50 MF, 25 parapsoriasis, 25 inflammatory dermatosis, and 25 healthy controls). Patients were selected from the Outpatient Clinic of Dermatology and Venereology Department, Tanta University Hospitals. From all, 4mm punch skin biopsies were taken and examined for CADM1 immunohistochemical expression. The current study revealed statistically significant upregulation of CADM1 expression in MF specimens in comparison to parapsoriasis, inflammatory dermatosis, and normal control specimens. Additionally, there was statistically significant positive correlation between CADM1 expression and progression of TNMB staging of MF disease. Therefore, it is possible to recommend CADM1 as a beneficial diagnostic immunohistochemical marker for differentiation between early stages of MF and both the premycotic parapsoriasis and benign inflammatory dermatosis. Moreover, it may be of value in early detection of neoplastic transformation of parapsoriasis as well as in assessment of MF progression.

Cost-Effectiveness of Brentuximab Vedotin Versus Physician's Choice of Methotrexate or Bexarotene for the Treatment of Cutaneous T-cell Lymphoma in Canada.

Brentuximab vedotin versus physician's choice of methotrexate (MTX) or bexarotene (BEX) significantly improved progression-free survival (PFS) (median PFS, 16.7 vs. 3.5months) and delayed time to subsequent treatment (8.4 vs. 3.7months), with similar overall survival in patients with CD30-expressing mycosis fungoides (MF) or primary cutaneous anaplastic large cell lymphoma (pcALCL), two types of cutaneous T-cell lymphomas. We assessed the cost-effectiveness of brentuximab vedotin versus MTX or BEX from a Canadian healthcare payer perspective in the indicated population. A 5-state partitioned survival model [pre-progression, non-stem cell transplant (SCT) post-progression, SCT, SCT relapse, death] with a weekly cycle length and 45-year lifetime horizon has been developed. Health-state occupancies, utility estimates, and treatment duration were informed by ALCANZA. Other inputs and costs came from the literature or clinician experts. Scenario analyses varied key parameters and tested assumptions. Brentuximab vedotin versus MTX or BEX was cost-effective; the incremental cost-effectiveness ratio was CAN$43,790 per quality-adjusted life year (QALY) gained. Brentuximab vedotin was more effective (incremental life years: 0.15; QALYs: 0.25) and total treatment costs were slightly higher (incremental costs: $11,105) than MTX or BEX. Key model drivers included end-stage care duration, SCT eligibility, and brentuximab vedotin retreatment rates. Brentuximab vedotin compared with MTX or BEX was cost-effective for CD30-expressing MF and pcALCL. Brentuximab vedotin's higher drug costs versus MTX or BEX were offset by decreased post-progression and end-stage management costs, and showed a 0.25 QALY gain versus MTX or BEX, and increased the proportion of patients eligible for potentially curative SCT.

Imbalanced IL-1B and IL-18 Expression in Sézary Syndrome.

Sézary syndrome (SS) is a rare and aggressive type of cutaneous T-cell lymphoma, with an abnormal inflammatory response in affected skin. The cytokines IL-1B and IL-18, as key signaling molecules in the immune system, are produced in an inactive form and cleave to the active form by inflammasomes. In this study, we assessed the skin, serum, peripheral mononuclear blood cell (PBMC) and lymph-node samples of SS patients and control groups (healthy donors (HDs) and idiopathic erythroderma (IE) nodes) to investigate the inflammatory markers IL-1B and IL-18 at the protein and transcript expression levels, as potential markers of inflammasome activation. Our findings showed increased IL-1B and decreased IL-18 protein expression in the epidermis of SS patients; however, in the dermis layer, we detected increased IL-18 protein expression. In the lymph nodes of SS patients at advanced stages of the disease (N2/N3), we also detected an enhancement of IL-18 and a downregulation of IL-1B at the protein level. Moreover, the transcriptomic analysis of the SS and IE nodes confirmed the decreased expression of IL1B and NLRP3, whereas the pathway analysis indicated a further downregulation of IL1B-associated genes. Overall, the present findings showed compartmentalized expressions of IL-1B and IL-18 and provided the first evidence of their imbalance in patients with Sézary syndrome.

Mycosis Fungoides: A Diagnostic Challenge

Background: Mycosis fungoides (MF) is the most frequent type of cutaneous T-cell lymphomas (CTCL), a heterogeneous group of non-Hodgkin lymphoma of T-cell origin. CTCLs accounts for about 4% of all non-Hodgkin lymphoma. MF mainly involves the skin but in advanced cases it may involve the lymph, blood and other organs. It mimics other skin disorders like erythema necroticans, leprosy, psoriasis etc which leads to delayed diagnosis and subsequent treatment. Case report: A 61 year old male patient visited the OPD of a tertiary care hospital in Eastern India with multiple reddish elevated lesions for last 6 months which later became dome shaped and then ulcerated. He did not have any fever or itching. He informed that he had been taking Homeopathic medicine previously, but the identity of the said medicine could not be confirmed. Physical examination ruled out the presence of pallor, jaundice, oedema and cyanosis. Pulse and BP were within normal range. Systemic examination was unremarkable except mild hepatomegaly. Cutaneous examination revealed multiple erythematous indurated plaques, papules and nodules over chest, abdomen, back, limbs and face. Few of the plaques present on the trunk and left arm had developed ulcers having a necrotic floors. Cervical, axillary and inguinal lymph nodes were palpable, being firm in consistency and mobile in nature. Hair, nail and mucosal examination revealed normal results. Complete blood count (CBC), peripheral blood smear(PBS), serum urea and creatinine level did not deviate from normal findings. Ultrasonography of whole abdomen showed a mildly enlarged liver. A prominent lymph node in the aortocaval groove could be appreciated on the computed tomography(CT) scan of whole abdomen. CT scan of chest revealed bilateral axillary lymphadenopathy. Erythema necroticans, sarcoidosis and CTCL were considered as the differential diagnoses. Lesional biopsy revealed irregular epidermal hyperplasia, parakeratosis and epidermotropism in the absence of spongiosis.There was infiltration of atypical lymphocytes in the epidermis, forming well developed Pautrier’s micro abscesses. The lymphocytes were tagging the dermo-epidermal junction and within the epidermis showing surrounding halo, convoluted nuclei and variable nuclear pleomorphism. Band like papillary dermal lymphoid infiltrate, dermal lymphoid fibroplasia and nodular lymphoid aggregates could be appreciated in the deep dermis. Immunohistochemical tests were performed and the immunophenotypic profile revealed positivity for CD2, CD3, CD5, CD7, CD 8 and TIA1 and negative for CD4, CD20, CD30, CD56 and granzyme B. Based on clinical presentation, histopathology and Immunohistochemical tests, a final diagnosis of MF was made. The patient was then started on systemic antibiotic therapy, due to increased risk of bacterial super infection of lesions due to skin barrier disruption. He was then referred to Oncology department for further treatment. Conclusion: In this case, the male patient was suffering from mycosis fungoides. In the background of its clinical features being similar to other skin disorders like erythema necroticans, clinicians may face a diagnostic dilemma to correctly diagnose it. Timely diagnosis and treatment improves the prognosis in most cases. Histopathological evaluation still remains the investigation of choice.

The Value of Immunohistochemical Expression of TOX, ICOS, and GATA-3 in the Diagnosis of Mycosis Fungoides.

Mycosis fungoides (MF) is considered the commonest type of cutaneous T-cell lymphoma representing about 50% of all primary cutaneous lymphomas. Differentiation between MF and another inflammatory dermatitis (BIDs) is important to ensure proper management. We aimed to evaluate the immunohistochemical expression of T OX, ICOS, and GATA binding protein 3 (GATA-3) in early stages MF (stage IA and IB) to establish their diagnostic value and to guide the use of inhibitors in the treatment of cutaneous T-cell lymphomas. A retrospective study of 75 skin paraffin blocks (punch biopsy) 40 cases of MF and 35 cases of eczematous dermatitis as a group representing other inflammatory dermatitis were retrieved from archives of the pathology department of our University, during the period from October 2017 to May 2021. About 98% and 90% of patients in the MF group had positive T OX and ICOS, while 70% of them had positive GATA-3. High expression of T OX, ICOS, and GATA-3 was associated with higher stages. T OX is considered a diagnostic marker for early MF. The importance of identifying novel markers in MF expressed by immunohistochemistry, such as ICOS, has been established. According to our results, GATA-3 could be used as an accessory marker in the diagnosis of MF when combined with T OX and ICOS in a panel.

Rapidly progressive tumor stage mycosis fungoides: A case report from Syria

Mycosis Fungoides, the most common type of cutaneous T-cell lymphomas (CTCLs), has typically an indolent course over years or decades. Patches grow into infiltrated plaques which may turn eventually into tumors. The tumor stage represents advanced lymphoma, but this occurs in a minority (∼10%) of cases. we present a rare case of mycosis fungoides in a 30-year-old woman showing rapid progression to tumor stage, unlike the indolent clinical course seen classically. Mycosis Fungoides (MF) is the most common primary cutaneous T-cell lymphoma, representing less than 1% of the total number of non-Hodgkin lymphoma. Patients with a classical type of MF progress from patch stage to plaque stage and finally to tumor stage disease, and they have a protracted clinical course over years or even decades. Although mycosis fungoides is a rare disease, it requires a high degree of suspicion clinically. The disease can have an excellent prognosis when identified and treated promptly.

474 Increased Expression of Squamous Cell Carcinoma Antigen 1 and 2 in Mycosis Fungoides and Sézary Syndrome

Mycosis fungoides (MF) and Sézary syndrome (SS) are classical types of cutaneous T-cell lymphoma (CTCL). MF is the most common type of CTCL, which is characterized by malignant proliferation of neoplastic CD4+ T cells with epidermotropism in the skin. SS is an aggressive leukemic type of CTCL characterized by a triad of erythroderma, lymphadenopathy and leukemic involvement. Squamous cell carcinoma antigen (SCCA) was originally isolated as tumor-specific antigens. SCCA comprises 2 proteins, SCCA1 and SCCA2, and both are induced by type 2 cytokines.

454 Digital quantitative detection of methylated DNA biomarkers: A helpful tool in the early diagnosis of Sézary syndrome

Sézary syndrome (SS) is an aggressive type of cutaneous T-cell lymphoma. Diagnosing SS can be challenging, especially in early stages of disease. Previously, in a genome-wide study, we showed that promoter hypermethylation of PROM1, G0S2, CMTM2, PAM, GNMT and NEXN is frequently observed in late stages of disease, but is neither found in healthy donors nor in benign erythrodermic inflammatory dermatoses (EID) patients. In this study, we evaluated the diagnostic value of these biomarkers in early stages of disease.

460 Enhancement of antibody-dependent cellular cytotoxicity is associated with treatment response to extracorporeal photopheresis in Sézary syndrome

Sézary syndrome (SS) is a rare, leukemic type of cutaneous T-cell lymphoma (CTCL), for which extracorporeal photopheresis (ECP) is a first-line therapy. Reliable biomarkers to objectively monitor the response to ECP in patients with SS are missing. We examined the quantitative and qualitative impact of ECP on natural killer (NK) cell activity in SS patients, and especially their functional ability for antibody-dependent cell-mediated cytotoxicity (ADCC). Further, we addressed the question whether the magnitude of the effect on ADCC can be associated with the anti-cancer efficacy of ECP in SS patients.