-
Reinhard Dummer,
Pietro Quaglino,
Jürgen C Becker,
Baktiar Hasan,
Matthias Karrasch,
Sean Whittaker,
Stephen Morris,
Michael Weichenthal,
Rudolf Stadler,
Martine Bagot,
Antonio Cozzio,
Maria G Bernengo, Robert Knobler
[show abstract]
[hide abstract]
ABSTRACT: PURPOSEMycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma. There is a need for multicenter trials involving defined patient populations using rigorous assessment criteria. We have investigated pegylated liposomal doxorubicin (PLD) in a clearly defined patient population with advanced MF. PATIENTS AND METHODS
Eligible patients had stage IIB, IVA, or IVB MF, refractory or recurrent after at least two previous systemic therapies. Patients were registered to receive a maximum of six cycles of PLD 20 mg/m(2) on days 1 and 15, every 28 days (one cycle). The primary end point was response rate (RR). RESULTS: three (6.1%) experienced CCRs, and 17 (34.7%) experienced PRs. A 50% or greater reduction of cutaneous manifestations was observed in 26 (60.5%) of 43 assessable patients. Two early deaths were reported, resulting from related cardiovascular toxicity and disease progression. The lower limit of the one-sided 90% CI for RR was 31.2%. Median time to progression and median duration of response were 7.4 and 6 months, respectively. CONCLUSIONPLD has an acceptable safety profile in patients with advanced MF. The efficacy of PLD seems promising.
Journal of Clinical Oncology 10/2012; · 18.37 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Extracorporeal photopheresis (ECP) is effective for treating cutaneous T-cell lymphoma. In 1987, a pivotal trial showed 81% overall response rate (ORR) using outdated criteria. No long-term follow-up was available for assessing survival. This study applies modern criteria to the 1987 trial to assess the impact of ECP on skin responses and also updates overall survival of the cohort.
Generalized erythroderma (GE, stage T4, n = 31) or extensive patch-plaque (EPP, stage T2, n = 8) patients received ECP (mean 3.9 years' duration). Patients achieving ≥ 50% partial skin response, ≥ 90% near-complete skin response, treatments required, and duration of response (DOR) were determined. Overall survival (OS) from diagnosis and first ECP treatment was determined for all patients and the GE cohort.
Patients showed 74% skin ORR using modern criteria; 33% of patients achieved ≥ 50% partial skin response (after median 7.1 months, mean 23 ECP treatments); 41% achieved ≥ 90% improvement (after median 19.6 months, mean 40 ECP treatments). Mean DOR was 14 months for ≥ 50% improvement and 8.9 months for ≥ 90% improvement. Response rates were comparable for GE and EPP cohorts. Median OS was 9.2 years from diagnosis and 6.6 years from ECP initiation (71.6 months follow-up).
Analysis of long-term follow-up confirmed durable responses and prolonged survival of patients treated with ECP.
Photodermatology Photoimmunology and Photomedicine 10/2012; 28(5):250-7. · 1.30 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The aim of this prospective study was to evaluate the efficacy and safety of extracorporeal photopheresis (ECP) in patients with bronchiolitis obliterans syndrome (BOS) after lung transplantation and to identify factors predicting treatment response.
The study was performed at a single center and consisted of a cohort of 1,012 lung transplant recipients (November 1989-June 2010). A total of 194 patients developed BOS after a mean of 1,293 ± 1,008 days (range, 99-4,949 days) and received established treatment, and 51 patients received additional ECP.
Thirty-one (61%) of the ECP-treated patients responded to the therapy and showed sustained stabilization (forced expiratory volume in 1 second range, -5% to 5% vs baseline at start of ECP) of lung function over 6 months. Responders to ECP showed significantly greater survival and less need for retransplantation (p = 0.001) than non-responders. Factors associated with an inferior treatment response were cystic fibrosis as underlying lung disease and a longer time between transplantation and development of BOS. No side effects were observed after ECP. Compared with BOS patients not treated with ECP, the ECP responders showed an improved graft survival (p = 0.05).
These results confirm and suggest that early use of ECP could be an effective adjunct treatment for patients who develop BOS after lung transplantation.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 09/2012; 31(9):950-7. · 3.54 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Photopheresis is a form of phototherapy where specialized equipment is used to isolate a leukocyte fraction from the peripheral blood which is then exposed to photoactivated 8-methoxypsoralen and reinfused into the patient. At the time of its invention the treatment was conceptually based on the hypothesis of T cell vaccination, i.e. the observation in experimental studies that exposure of the immune system to physically modified T cell clones leads to a specific inhibition of T cell mediated autoimmunity. Consequently, photopheresis has been tried in a variety of conditions where T cells are thought to have a critical role and has shown clinical efficacy mainly in variants of cutaneous T cell lymphomas, graft-versus-host disease, systemic sclerosis, in solid organ transplant rejection and Crohn's disease. Evidence has accumulated that alterations in antigen presentation and the generation of regulatory T cells are induced by photopheresis and might be related to the observed clinical effects. Summarizing what has been published in the 25 years since its introduction into the clinic, photopheresis to date has found its place in the treatment of the above mentioned conditions as a well tolerated treatment option that can safely be combined with other established modalities. It can be expected that further research will help refine its clinical indications and close the gaps that still exist in our knowledge on when, how, and why photopheresis works.
Photochemical and Photobiological Sciences 08/2012; · 2.58 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Extracorporeal photopheresis (ECP) is an established therapy for transplant rejection, graft-versus-host disease (GvHD) after allogeneic stem cell transplantation, cutaneous T-cell lymphoma and systemic autoimmune disorders such as systemic sclerosis. Knowledge regarding the in vivo behaviour of the cells after reinfusion is very limited. The aim of this prospective study was to investigate the path of 8-MOP-/UVA-exposed radiolabelled cells after ECP treatment and reinfusion. In this prospective single-centre study, peripheral blood mononuclear cells (PBMC) and neutrophils of 10 patients undergoing ECP as part of their regular treatment were labelled separately with (111) In-oxine after exposure to 8-MOP/UVA and prior to reinfusion. The fate of the labelled leucocytes was monitored at 10 min, 3.5 and 24 h following reinfusion with whole-body scintigraphy. Comparison of distribution patterns showed that PBMC and neutrophils have different kinetic patterns after intravenous reinjection. The most prominent difference was immediate retention of PBMC but not of neutrophils in the lungs corresponding to a signal three times more intense. After 24 h, more than 80% of both cell populations could be detected in liver and spleen. By means of a novel tool allowing for tracking of 8-MOP-/UVA-exposed leucocytes in ECP, we could show that organ-specific homing of leucocytes after ECP can be visualized in vivo and that migration patterns differ between PBMC and neutrophils. Based on our results, further studies should (i) extend the morphometric studies described here to specific ECP-responsive conditions and (ii) functionally address the interaction of ECP-modified PBMC with pulmonary tissue in experimental models.
Experimental Dermatology 06/2012; 21(6):443-7. · 3.54 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: Extracorporeal photopheresis (ECP) involves ex vivo leukocyte treatment with methoxsalen and UVA light to generate a tolerogenic response. A previous trial demonstrated that ECP permits corticosteroid withdrawal in steroid-dependent Crohn's disease (CD) patients who were in clinical remission. We studied the effect of ECP on steroid withdrawal in steroid-dependent CD. METHODS: Patients with CD for ≥6 months, in remission at baseline while on steroids, but who had failed at ≥1 steroid withdrawal were included. Patients received two ECP treatments every 2 weeks for the 24-week steroid tapering period and underwent steroid-tapering. Patients completing steroid tapering could receive maintenance ECP (two treatments/week) every month for 24 weeks. RESULTS: Thirty-one patients (Crohn's Disease Activity Index [CDAI] score 91; Inflammatory Bowel Disease Questionnaire [IBDQ] 172.5) were enrolled (baseline corticosteroid dose, 20 mg/day); 65% were refractory to/intolerant of anti-tumor necrosis factor (TNF) agents or immunosuppressants. After 24 weeks of ECP, 7 of 31 (22.6%) patients discontinued steroids while maintaining a CDAI of <150. At week 24, the steroid dose for the remaining patients on corticosteroids was 10 mg (P < 0.003 vs. baseline) with a CDAI of 110 and an IBDQ of 179. Following maintenance treatment, three patients remained in steroid-free remission. The 10 patients in the study and receiving ECP at week 48 had a steroid dose of 3.5 mg with a CDAI of 40 and an IBDQ of 188. CONCLUSIONS: ECP permitted discontinuation or reduction of steroids in a population of refractory steroid-dependent CD patients. ECP may be useful in permitting steroid withdrawal in selected steroid-dependent CD patients. Ideally, these results need to be confirmed in a "sham-controlled" clinical trial. (Inflamm Bowel Dis 2012;).
Inflammatory Bowel Diseases 05/2012; · 4.86 Impact Factor
-
Acta Dermato-Venereologica 09/2011; 92(2):166-8.
-
[show abstract]
[hide abstract]
ABSTRACT: Aberrant expression of microRNAs (miRNAs) has been implicated in oncogenesis of various tumors and primary cutaneous T cell lymphomas. Dicer, a ribonuclease III-like enzyme is essential for miRNA processing.
We initiated a retrospective study to characterize the alterations in the expression profile of Dicer in patients with primary cutaneous T cell lymphomas (CTCL).
A total of 50 consecutive patients with primary CTCL were studied, with the majority having mycosis fungoides (n=34). Five patients had primary cutaneous CD 30+ anaplastic large cell lymphoma, four patients each had lymphomatoid papulosis and primary cutaneous CD4-positive small/medium T-cell lymphoma, one primary cutaneous γδ T cell lymphoma, one Sézary syndrome and another subcutaneous panniculitis-like T cell lymphoma of αβ-phenotype. Immunohistochemistry was performed on paraffin sections using a commercially available antibody against Dicer. Intensity of expression was correlated with clinical parameters including disease specific survival (DSS) and time to progression (TTP).
After a median follow-up of 74 months (range: 1-271), 12/50 patients (24%) have died. Univariate and multivariate analysis for disease-specific survival showed Dicer expression and stage as a negative predictive factor in the sole group of MF patients (n=34) as well as in the heterogeneous group of patients (n=50), but not gender, histological subtype, primary localization of disease, age and recurrence of lymphoma (p>0.05).
Our data suggest Dicer expression as a possible molecular marker in patients with MF and apparently indicate that miRNA(s) might be of clinical relevance in CTCL.
Journal of dermatological science 09/2011; 64(3):185-90. · 3.71 Impact Factor
-
Werner Kempf,
Katrin Pfaltz,
Maarten H Vermeer,
Antonio Cozzio,
Pablo L Ortiz-Romero,
Martine Bagot,
Elise Olsen,
Youn H Kim,
Reinhard Dummer,
Nicola Pimpinelli, [......],
Joan Guitart,
Teresa Estrach,
José A Sanches,
Madeleine Duvic,
Annamari Ranki,
Brigitte Dreno,
Sonja Ostheeren-Michaelis, Robert Knobler,
Gary Wood,
Rein Willemze
[show abstract]
[hide abstract]
ABSTRACT: Primary cutaneous CD30(+) lymphoproliferative disorders (CD30(+) LPDs) are the second most common form of cutaneous T-cell lymphomas and include lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma. Despite the anaplastic cytomorphology of tumor cells that suggest an aggressive course, CD30(+) LPDs are characterized by an excellent prognosis. Although a broad spectrum of therapeutic strategies has been reported, these have been limited mostly to small retrospective cohort series or case reports, and only very few prospective controlled or multicenter studies have been performed, which results in a low level of evidence for most therapies. The response rates to treatment, recurrence rates, and outcome have not been analyzed in a systematic review. Moreover, international guidelines for staging and treatment of CD30(+) LPDs have not yet been presented. Based on a literature analysis and discussions, recommendations were elaborated by a multidisciplinary expert panel of the Cutaneous Lymphoma Task Force of the European Organization for Research and Treatment of Cancer, the International Society for Cutaneous Lymphomas, and the United States Cutaneous Lymphoma Consortium. The recommendations represent the state-of-the-art management of CD30(+) LPDs and include definitions for clinical endpoints as well as response criteria for future clinical trials in CD30(+) LPDs.
Blood 08/2011; 118(15):4024-35. · 9.90 Impact Factor
-
Elise A Olsen,
Sean Whittaker,
Youn H Kim,
Madeleine Duvic,
H Miles Prince,
Stuart R Lessin,
Gary S Wood,
Rein Willemze,
Marie-France Demierre,
Nicola Pimpinelli, [......],
Michael Girardi,
Günter Burg,
Annamari Ranki,
Maartan Vermeer,
Steven Horwitz,
Peter Heald,
Steve Rosen,
Lorenzo Cerroni,
Brigette Dreno,
Eric C Vonderheid
[show abstract]
[hide abstract]
ABSTRACT: 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.
Journal of Clinical Oncology 06/2011; 29(18):2598-607. · 18.37 Impact Factor
-
Hildegard T Greinix,
Koen van Besien,
Ahmet H Elmaagacli,
Uwe Hillen,
Andrew Grigg, Robert Knobler,
Dennis Parenti,
Vijay Reddy,
Koen Theunissen,
Mauricette Michallet,
Mary E D Flowers
[show abstract]
[hide abstract]
ABSTRACT: In a prior multicenter randomized controlled trial, we found that a 12-week course of extracorporeal photopheresis (ECP) plus standard immunosuppressive therapy resulted in several beneficial outcomes in patients with corticosteroid-refractory/intolerant/dependent chronic graft-versus-host disease (GVHD). Here, we report the results of an open-label crossover ECP study in 29 eligible participants randomized initially to the standard of care non-ECP (control) arm. Eligible for the crossover ECP study were control arm patients who either (1) had progression of cutaneous chronic GVHD (cGVHD), defined as >25% worsening from baseline as measured by the percent change in the total skin score (TSS) at any time, or (2) had less than 15% improvement in the TSS, or had a ≤25% reduction in corticosteroid dose at week 12 of the initial study. ECP was administered 3 times during week 1, then twice weekly until week 12, followed by 2 treatments monthly until week 24. The median age of the study cohort was 43 (20-67) years and 90% had extensive cGVHD. The median months from onset of cGVHD to start of ECP were 26 (range: 4-79). Twenty-five of 29 patients (86%) completed the 24-week course of ECP. Complete or partial skin response at week 24 was noted in 9 patients (31%). The median percent of decrease in TSS from baseline to weeks 12 and 24 was -7.9 and -25.8, respectively. In 4 (17%) and 8 (33%) patients, a ≥50% reduction in corticosteroid dose at weeks 12 and 24 was observed. Extracutaneous cGVHD response was highest in oral mucosa with 70% complete and partial resolution after week 24. In conclusion, progressive improvement in cutaneous and extracutaneous cGVHD was observed after a 24-week course of ECP in patients who previously had no clinical improvement or exhibited worsening of cGVHD while receiving standard immunosuppressive therapy alone in a randomized study. These results confirm previous findings and support the notion that prolonged ECP appears to be necessary for optimal therapeutic effects in corticosteroid-refractory cGVHD patients.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 05/2011; 17(12):1775-82. · 3.15 Impact Factor
-
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 12/2010; 16(12):1747-8; author reply 1749. · 3.15 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Extracorporeal photopheresis (ECP) is a leukapheresis-based therapy that uses 8-methoxypsoralen and ultraviolet A irradiation. Used alone or in combination with biological agents, ECP is an established and effective therapy for advanced cutaneous T-cell lymphoma. ECP has also shown promising efficacy in a number of other severe and difficult-to-treat conditions, including systemic sclerosis, graft-versus-host disease, prevention and treatment of rejection in solid organ transplantation, and Crohn disease. Furthermore, the use of ECP in some of these conditions may allow a significant reduction in the use of systemic steroids and other immunosuppressants, reducing long-term morbidity and mortality. The accumulated experience shows ECP to be well tolerated, with no clinically significant side effects. Progress is also being made in the search for understanding of the mechanisms of action of ECP, which will ultimately facilitate improvements in the use of this therapy.
Journal of the American Academy of Dermatology 09/2009; 61(4):652-65. · 3.99 Impact Factor
-
Zoya Kuzmina,
Hildegard T Greinix, Robert Knobler,
Nina Worel,
Michal Kouba,
Roman Weigl,
Ulrike Körmöczi,
Arno Rottal,
David Pohlreich,
Christoph Zielinski,
Winfried F Pickl
Blood 08/2009; 114(3):744-6. · 9.90 Impact Factor
-
Maria T Abreu,
Christian von Tirpitz,
Robert Hardi,
Martin Kaatz,
Gert Van Assche,
Paul Rutgeerts,
Emil Bisaccia,
Sergi Goerdt,
Stephen Hanauer, Robert Knobler,
Peter Mannon,
Lloyd Mayer,
Thomas Ochsenkuhn,
William J Sandborn,
Dennis Parenti,
Kevin Lee,
Walter Reinisch
[show abstract]
[hide abstract]
ABSTRACT: Extracorporeal photopheresis (ECP) is effective in immune-mediated disorders. A prospective, uncontrolled pilot study was conducted to evaluate the safety and efficacy of ECP in patients with active Crohn's disease (CD) who were refractory to or intolerant of immunosuppressants and/or anti-TNF therapies.
Patients with moderate-to-severely active CD (Crohn's Disease Activity Index [CDAI] 220-450 points) underwent 12 weeks of ECP treatment (Weeks 1-4: twice weekly, every week; Weeks 5-12: twice weekly, every other week). Clinical response was defined as a decrease in the CDAI of >or=100 points or remission (CDAI <150 points) at Week 12. Patients who responded at Week 12 could receive an additional 12 weeks of ECP treatment (twice weekly, every other week) in an extension study.
Twenty-eight patients were enrolled with a mean baseline CDAI score of 314 (range 207-457). At Week 12, 14 patients (50%) responded; 13 patients responded within 6 weeks. Seven patients (25%) attained remission by Week 12. Three of 5 patients with open fistulae at baseline had fistula closure. Response was similar among patients naïve to anti-TNF agents and patients who had previously been refractory or intolerant to anti-TNF agents. Of the 12 patients who entered the extension study, 9 (75%) maintained their response at Week 24.
In patients with moderate-to-severely active CD who were refractory to or intolerant of immunosuppressants and/or anti-TNF agents, ECP was well tolerated and induced clinical response (50%) and remission (25%) in patients. Most patients were able to maintain a response with continued treatments.
Inflammatory Bowel Diseases 02/2009; 15(6):829-36. · 4.86 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Extracorporeal photoimmunotherapy-photopheresis (ECP) is an immunomodulatory therapy, which basically consists of separating the patient's leucocyte rich plasma from the red blood cell fraction, followed by extracorporeal administration of a photosensitizer and UVA light prior to reinfusion of the treated cells. Successful use of ECP has been reported in patients with cutaneous T cell lymphoma, the Sezary syndrome variant, graft-versus-host disease, cardiac transplant rejection and other T cell mediated/autoimmune and autoimmune diseases. Apoptosis of malignant lymphocytes and presentation of their antigens to anti-tumor CD8+ T cells with induction of an anticlonotypic response by CD8+ effector cells against the CD4+ neoplastic T cells was one of the intial mechanisms of action proposed. The exact mechanism by which ECP exerts its therapeutic effect remains to be further explored and is still uncertain. The better understanding of its mode of action and the clinical benefits of ECP are important findings that provide additional tools to increase the therapeutic armamentarium in a number of acute and chronic T cell mediated diseases.
Frontiers in Bioscience 02/2009; 14:4769-77. · 3.52 Impact Factor
-
Werner Kempf,
Sonja Ostheeren-Michaelis,
Marco Paulli,
Marco Lucioni,
Janine Wechsler,
Heike Audring,
Chalid Assaf,
Thomas Rüdiger,
Rein Willemze,
Chris J L M Meijer, [......],
Dmitry V Kazakov,
Tony Petrella,
Sylvie Fraitag,
Agnes Carlotti,
Philippe Courville,
Hubert Laeng, Robert Knobler,
Philippa Golling,
Reinhard Dummer,
Günter Burg
[show abstract]
[hide abstract]
ABSTRACT: Granulomatous cutaneous T-cell lymphomas (CTCLs) are rare and represent a diagnostic challenge. Only limited data on the clinicopathological and prognostic features of granulomatous CTCLs are available. We studied 19 patients with granulomatous CTCLs to further characterize the clinicopathological, therapeutic, and prognostic features.
The group included 15 patients with granulomatous mycosis fungoides (GMF) and 4 with granulomatous slack skin (GSS) defined according to the World Health Organization-European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas. Patients with GMF and GSS displayed overlapping histologic features and differed only clinically by the development of bulky skin folds in GSS. Histologically, epidermotropism of lymphocytes was not a prominent feature and was absent in 9 of 19 cases (47%). Stable or progressive disease was observed in most patients despite various treatment modalities. Extracutaneous spread occurred in 5 of 19 patients (26%), second lymphoid neoplasms developed in 4 of 19 patients (21%), and 6 of 19 patients (32%) died of their disease. Disease-specific 5-year survival rate in GMF was 66%.
There are clinical differences between GMF and GSS, but they show overlapping histologic findings and therefore cannot be discriminated by histologic examination alone. Development of hanging skin folds is restricted to the intertriginous body regions. Granulomatous CTCLs show a therapy-resistant, slowly progressive course. The prognosis of GMF appears worse than that of classic nongranulomatous mycosis fungoides.
Archives of dermatology 01/2009; 144(12):1609-17. · 4.76 Impact Factor
-
Mary E D Flowers,
Jane F Apperley,
Koen van Besien,
Ahmet Elmaagacli,
Andrew Grigg,
Vijay Reddy,
Andrea Bacigalupo,
Hans-Jochem Kolb,
Luis Bouzas,
Mauricette Michallet,
H Miles Prince, Robert Knobler,
Dennis Parenti,
Jose Gallo,
Hildegard T Greinix
[show abstract]
[hide abstract]
ABSTRACT: Chronic graft-versus-host disease (cGVHD) is a major limitation of successful hematopoietic cell transplantation. The safety and efficacy of extracorporeal photopheresis (ECP) for 12 to 24 weeks together with standard therapy was compared with standard therapy alone in patients with cutaneous manifestations of cGVHD that could not be adequately controlled by corticosteroid treatment. The primary efficacy end point was a blinded quantitative comparison of percent change from baseline in Total Skin Score (TSS) of 10 body regions at week 12. Ninety-five patients were randomized to either ECP and standard therapy (n = 48) or standard therapy alone (n = 47). The median percentage improvement in TSS at week 12 was 14.5% for the ECP arm and 8.5% for the control arm (P = .48). The proportion of patients who had at least a 50% reduction in steroid dose and at least a 25% decrease from baseline in TSS was 8.3% in the ECP arm at week 12 and 0% in the control arm (P = .04). The nonblinded investigator assessment of skin complete or partial responses revealed a significant improvement in favor of ECP (P < .001). ECP was generally well tolerated. These results suggest that ECP may have a steroid-sparing effect in the treatment of cGVHD. Clinical trials registered at www.ClinicalTrials.gov as NCT00054613.
Blood 07/2008; 112(7):2667-74. · 9.90 Impact Factor
-
Dorian Winter,
Julia Moser,
Ernst Kriehuber,
Christoph Wiesner, Robert Knobler,
Franz Trautinger,
Paula Bombosi,
Georg Stingl,
Peter Petzelbauer,
Antal Rot,
Dieter Maurer
[show abstract]
[hide abstract]
ABSTRACT: Viruses can escape destruction by the immune system by exploitation of the chemokine-chemokine receptor system. It is less established whether human cancers can adopt similar strategies to evade immunologic control. In this study, we show that advanced cutaneous T cell lymphoma (CTCL) is associated with selective and efficient inactivation of CXCR3-dependent T cell migration. Our studies demonstrate that this alteration is at least in part due to CXCR3 down-regulation in vivo by elevated serum levels of CXCR3 ligands. The T cell population most affected by this down-regulatory mechanism are CD8+ cytotoxic effector T cells. In CTCL patients, cytotoxic effector T cells have strongly reduced surface CXCR3 expression, accumulate in peripheral blood, but are virtually absent from CTCL tumor lesions, indicating an inability to extravasate into lymphoma tissue. CTCL-associated inactivation of effector cell recruitment may be a paradigmatic example of a new type of immune escape mechanisms shielding the neoplasm from a tumoricidal attack.
The Journal of Immunology 10/2007; 179(6):4272-82. · 5.79 Impact Factor
-
Elise Olsen,
Eric Vonderheid,
Nicola Pimpinelli,
Rein Willemze,
Youn Kim, Robert Knobler,
Herschel Zackheim,
Madeleine Duvic,
Teresa Estrach,
Stanford Lamberg, [......],
Reinhard Dummer,
Annamari Ranki,
Gunter Burg,
Peter Heald,
Mark Pittelkow,
Maria-Grazia Bernengo,
Wolfram Sterry,
Liliane Laroche,
Franz Trautinger,
Sean Whittaker
[show abstract]
[hide abstract]
ABSTRACT: The ISCL/EORTC recommends revisions to the Mycosis Fungoides Cooperative Group classification and staging system for cutaneous T-cell lymphoma (CTCL). These revisions are made to incorporate advances related to tumor cell biology and diagnostic techniques as pertains to mycosis fungoides (MF) and Sézary syndrome (SS) since the 1979 publication of the original guidelines, to clarify certain variables that currently impede effective interinstitution and interinvestigator communication and/or the development of standardized clinical trials in MF and SS, and to provide a platform for tracking other variables of potential prognostic significance. Moreover, given the difference in prognosis and clinical characteristics of the non-MF/non-SS subtypes of cutaneous lymphoma, this revision pertains specifically to MF and SS. The evidence supporting the revisions is discussed as well as recommendations for evaluation and staging procedures based on these revisions.
Blood 10/2007; 110(6):1713-22. · 9.90 Impact Factor
