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Acute graft-versus-host disease (aGVHD) is a significant complication of allogeneic hematopoietic stem cell transplant (HSCT) and negatively affects T cell reconstitution. Extracorporeal photopheresis (ECP) reduces aGVHD, but the mechanisms remain incompletely understood. Our objective was to examine the impact of ECP on thymopoiesis in pediatric aGVHD and the mechanisms at a cellular and transcriptional level. Sixteen pediatric HSCT patients were recruited: 6 with ECP-treated aGVHD, 5 without aGVHD, and 5 with aGVHD treated with corticosteroids only. Thymopoiesis was evaluated by measuring naive T cells, TRECs, IL-7, and T cell receptor repertoire diversity. Regulatory T cell (Treg) enumeration and function and dendritic cell (DC) enumeration and phenotype were analyzed using flow cytometry. T cell transcriptome analysis was performed on ECP patients after treatment and responders pre- and post-treatment. Four ECP responders demonstrated thymic-dependent T cell recovery, and superior median naïve T cell numbers at 8 and 12 months post-HSCT compared to the aGVHD corticosteroid group. Increased Tregs and Treg suppressive function, reduced cDC/pDC and DC co-stimulatory marker expression in ECP responders suggest upregulated peripheral tolerance; these findings were not observed in partial responders. Responder post-ECP CD3+ T cell transcriptional profile demonstrated 3333 downregulated and 364 upregulated genes, with significant downregulation of ERRα and GαS pathways, and reduced expression of pro-inflammatory and adhesion proteins. Thymic function improves with successful ECP treatment. ECP reduces T cell activation and impacts peripheral tolerance via DCs and Tregs. Differences in thymic recovery, DC, and Treg cellular patterns and the T cell transcriptome were observed between ECP responders and partial responders and require further validation and investigation in additional patients. [ABSTRACT FROM AUTHOR]

Copyright of Der Hautarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: Rituximab is an anti-CD20 monoclonal antibody that is used to suppress B-cell function in graft-versus-host-disease (GVHD). We sought to determine the effects of rituximab treatment on lung function in those patients with bronchiolitis obliterans syndrome (BOS) as a manifestation of GVHD. Methods: Thirteen patients were treated with rituximab with a diagnosis of BOS and a significant reduction in the forced expiratory volume in 1 s (FEV1) after hematopoietic stem cell transplantation (HSCT). The changes in their pulmonary function for 12 months following treatment with rituximab were followed, along with other intervention performed and daily average dosing of prednisone. Results: Following rituximab administration, there was an improvement in the slope of decline in lung function from −5.12 ml/month prior to rituximab infusion to −0.31 ml/month after 3 months and to +2.27 ml/month 12 months later. Seven of the 13 patients had an increase in their FEV1 after treatment with rituximab. Additionally, the mean daily dose of prednisone decreased from 27 mg prior to rituximab treatment to 11 mg 12 months after treatment. Nine out of 13 patients survived 12 months after rituximab treatment. All of the patients with improvement in FEV1 following rituximab treatment were receiving concomitant extracorporeal photopheresis. Conclusion: Rituximab is safe with the potential to stabilize or improve lung function in patients with BOS after HSCT and should be considered as a treatment option in those patients. [ABSTRACT FROM AUTHOR]

Purpose of Review: Extracorporeal photochemotherapy (photopheresis, ECP) is a cell-based immunomodulatory treatment that separates leukocytes from peripheral blood, exposes them to a photosensitizing agent followed by ultraviolet A light, and then reinfuses them back into the patient. ECP has been found to be effective for graft versus host disease, transplant rejection, and various autoimmune diseases. The mechanism is not well understood but studies have shown clinical benefit in the treatment of systemic sclerosis (SSc). This review examines the ECP technique, advances in our knowledge of its mechanism, and the data supporting its use in SSc-like fibrosing diseases and in SSc itself. Recent Findings: Multiple lines of evidence support ECP use in SSc. ECP generates apoptotic cells and dendritic cells, induces production of anti-inflammatory cytokines, and increases regulatory T cell numbers. Clinical studies have generally demonstrated improvement, especially the skin, in SSc patients receiving ECP. Summary: ECP may be an effective and safe procedure for the treatment of SSc. [ABSTRACT FROM AUTHOR]

Extracorporeal photopheresis (ECP) is an immunomodulatory alternative for treatment of graft versus host disease (GVHD). The blood is then separated into its various components through apheresis; buffy coat cells are thereafter treated with 8-methoxypsoralen before exposure to ultraviolet light and finally reinfused into the patient. There is a general agreement that this treatment has an anti-GVHD effect, but the mechanisms of action behind this effect are only partly understood. However, altered maturation of dendritic cells (DC) and thereby indirect modulation of T-cell reactivity seems to be one important mechanism together with DC-presentation of antigens derived from apoptotic donor T cells and induction of regulatory T cells. The treatment has been best studied in patients with chronic GVHD (both pediatric and adult patients), but most studies are not randomized and it is difficult to know whether the treatment is more effective than the alternatives. The clinical studies of ECP in adults with acute GVHD are few and not randomized; it is not possible to judge whether this treatment should be a preferred second- or third-line treatment. There is no evidence for increased risk of leukemia relapse or suppression of specific graft versus leukemia reactivity by this treatment, so specific antileukemic immunotherapy may still be possible. Thus, even though the treatment seems effective in patients with GVHD, further clinical (especially randomized) as well as biological studies with careful standardization of the treatment are needed before it is possible to conclude how ECP should be used in acute and chronic GVHD. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic cell transplantation (HCT) is a well-established curative treatment option for selected patients with hematologic and oncologic diseases. Acute graft-versus-host disease (GvHD) has remained a serious complication of HCT and is associated with high morbidity and mortality especially in patients not responding to first-line therapy with corticosteroids. So far, no standard for salvage therapy of acute corticosteroid-refractory GvHD has been established worldwide. Use of extracorporeal photopheresis results in high response rates, has a steroid-sparing effect and is associated with improved patients' survival. [ABSTRACT FROM AUTHOR]

Extracorporeal photopheresis (ECP) has been shown to be a promising treatment for chronic graft-versus-host disease; however, only a few case reports are available that examine the effectiveness of ECP for bronchiolitis obliterans (BO) after allo-SCT. Because of the poor response to traditional therapies, ECP has been explored as a possible therapeutic option for severe BO after allo-SCT. Nine patients received ECP between July 2008 and August 2009 after a median follow-up of 23 months (range 9-93 months) post transplant. The primary indication for ECP was the development of BO in patients who had failed prior multidrug regimens. The median number of drugs used for BO management before ECP was 5 (range 2-7); this included immunosuppressive therapy. Six of nine (67%) patients responded to ECP after a median of 25 days (range 20-958 days). No ECP-related complications occurred. ECP seemed to stabilize rapidly declining pulmonary function tests in about two-thirds of patients with severe and heavily pretreated BO that developed after allo-SCT. This finding supports the need for a larger prospective study to confirm the impact of ECP on BO, and to consider earlier intervention with ECP to improve the outcome of BO after allo-SCT. [ABSTRACT FROM AUTHOR]

Copyright of Der Hautarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

One of the ultimate goals in transplantation is to develop novel therapeutic methods for induction of donor-specific tolerance to reduce the side effects caused by the generalized immunosuppression associated to the currently used pharmacologic regimens. Interaction or phagocytosis of cells in early apoptosis exerts potent anti-inflammatory and immunosuppressive effects on antigen (Ag)-presenting cells (APC) like dendritic cells (DC) and macrophages. This observation led to the idea that apoptotic cell-based therapies could be employed to deliver donor-Ag in combination with regulatory signals to recipient’s APC as therapeutic approach to restrain the anti-donor response. This review describes the multiple mechanisms by which apoptotic cells down-modulate the immuno-stimulatory and pro-inflammatory functions of DC and macrophages, and the role of the interaction between apoptotic cells and APC in self-tolerance and in apoptotic cell-based therapies to prevent/treat allograft rejection and graft-versus-host disease in murine experimental systems and in humans. It also explores the role that in vivo-generated apoptotic cells could have in the beneficial effects of extracorporeal photopheresis, donor-specific transfusion, and tolerogenic DC-based therapies in transplantation. [ABSTRACT FROM AUTHOR]

Copyright of Der Hautarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Hautarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Extracorporeal photopheresis (ECP) was given to 23 patients with steroid-refractory acute GVHD (aGVHD, grade II (n=10), III (n=7) or IV (n=6)). The median duration of ECP was 7 months (1–33) and the median number of ECP cycles in each patient was 10. Twelve patients (52%) had complete responses. Eleven patients (48%) survived and 12 died, 10 of GVHD with or without infections and two of leukaemia relapse. The average grade of GVHD was reduced from 2.8 (on the first day of ECP) to 1.4 (on day +90 from ECP) (P=0.08), and the average dose of i.v. methylprednisolone from 2.17 to 0.2 mg/kg/d (P=0.004). Complete responses were obtained in 70, 42 and 0% of patients, respectively, with grades II, III and IV aGVHD; complete responses in the skin, liver and gut were 66, 27 and 40%. Patients treated within 35 days from onset of aGVHD had higher responses (83 vs 47%; P=0.1). A trend for improved survival was seen in grade III–IV aGVHD treated with ECP as compared to matched controls (38 vs 16%; P 0.08). ECP is a treatment option for patients with steroid refractory aGVHD and should be considered early in the course of the disease.Bone Marrow Transplantation (2008) 42, 609–617; doi:10.1038/bmt.2008.221; published online 28 August 2008 [ABSTRACT FROM AUTHOR]

Copyright of Der Hautarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Nervenarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Hautarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Extracorporeal photopheresis (ECP) using UVA irradiation of enriched lymphocytes in the presence of 8-methoxypsoralen as a photoactivatable substrate was originally introduced as a therapeutic regimen for cutaneous T-cell lymphoma (CTCL). Whereas ECP has previously been reported to be useful primarily for erythrodermic lymphoma, our purpose was to obtein data on safety and efficacy of ECP in patients suffering from different stages of CTCL. We report on 17 patients, 3 with erythroderma and 14 with plaque or tumour stages. In contrast to other studies our patients were treated predominantly with ECP alone; only a few patients received concomitant therapy. These data have not been published previously, except for preliminary data on four patients. Of the 17 patients, 12 (70%) responded to ECP. In seven patients at least 50% of skin lesions disappeared (defined as partial response) and in five patients at least 25% of skin lesions disappeared (defined as minor response). In two patients the disease remained stable and in three patients the disease progressed under the ECP treatment. No complete remission was observed. Partial responses were achieved not only in patients with early CTCL (stage I b) but also in those with far progressed tumours (stage IV a). After treatment for 6 months partial responders showed an increase in the number of NK cells in their peripheral blood ( P<0.01). We cannot confirm a relationship between this treatment and CD8 cell counts, as reported by others. Overall, our results indicate that ECP is a safe and effective regimen for the treatment of all stages of CTCL. [ABSTRACT FROM AUTHOR]

Extracorporeal photopheresis using UVA irradiation of enriched lymphocytes in the presence of 8-methoxypsoralen (8-MOP) as a photoactivatable substrate has been employed for the treatment of several immunologically mediated disorders. We report on the first three patients subjected to extracorporeal photopheresis for severe atopic dermatitis. All patients had a lifelong history of atopic skin inflammation, and their disease had finally become resistant to well-established therapeutic regimes. Extracorporeal photopheresis resulted in a marked clinical improvement in the skin lesions of all patients. The decrease in cutaneous inflammatory activity became evident by the end of the second photopheresis cycle. In two patients skin lesions had virtually disappeared after the fifth treatment cycle, while in the third patient a lasting and substantial improvement in pruritus and erythema was achieved. Clinical remission was stable under maintenance therapy with prolonged intervals between photopheresis sessions. Therapeutic efficacy was reflected by a marked reduction in IgE serum levels in all three patients, while serum concentration of IgG, IgM and IgA as well as the profile of circulating lymphocytes remained essentially unchanged. No clinical signs of immunosuppression or other severe adverse events became evident. Collectively, our preliminary results indicate that extracorporeal photopheresis may interfere with the pathomechanisms leading to atopic dermatitis and therefore should be considered as a treatment modality for severe forms of this recalcitrant disorder. [ABSTRACT FROM AUTHOR]

The effect of extracorporeal photopheresis (EP) on various cytogenetic parameters has been investigated. During EP the photoactivatable agent 8-methoxypsoralen (8-MOP) was administered orally. After 2 h a leukocyteenriched blood fraction was collected by haemocentrifugation, irradiated with UVA extracorporeally, and reinfused to the patient. Two patients suffering from cutaneous T-cell lymphoma showed a marked clinical improvement in response to therapy. In order to investigate the cytogenetic effects and mutagenic risks of EP, the mitotic index (MI), the type and number of chromosomal aberrations and the rate of sister chromatid exchanges (SCE) were studied. Following EP treatment the patients' lymphocytes were cultured and stimulated with phytohaemagglutinin (PHA) for 48 or 72 h. The cultured lymphocytes showed a decreased MI after 48 h as an indicator of cytotoxic effects, but not after 72 h. In lymphocyte cultures not stimulated with PHA, the MI was decreased even after 72 h. The number of chromosomal aberrations and SCE were increased upon treatment, but only transiently, returning to basal levels between consecutive treatments. Our data provides no evidence for increased mutagenic risk as a consequence of effective EP treatment. [ABSTRACT FROM AUTHOR]

Copyright of Der Hautarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose of Review: Cutaneous T-cell lymphoma (CTCL) is a rare form of non-Hodgkin lymphoma. Globally, the most common subtypes of CTCL are mycosis fungoides and Sézary syndrome. CTCL can confer significant morbidity and even mortality in advanced disease. Here we review the current and potential future treatments for advanced-stage CTCL.Recent findings: Heterogeneity of treatment choice has been demonstrated both in US and non-US centers. Systemic treatment choice is currently guided by prognostic features, incorporating stage, immunophenotypic and molecular findings, and patient-specific factors such as age and comorbidities. Randomized controlled studies are uncommon, and the literature is composed predominantly of retrospective, cohort, and early-phase studies. International consensus guidelines are available; however, the lack of comparative trials means that there is no clear algorithmic approach to treatment.Summary: This review article reports on the systemic treatment options in current use for advanced CTCL, and on the possible future therapies, acknowledging that an algorithmic approach is not yet forthcoming to guide treatment prioritization. [ABSTRACT FROM AUTHOR]