Extracorporeal photopheresis (ECP) has been in clinical use for over three decades after receiving FDA approval for the palliative treatment of the Sézary Syndrome variant of cutaneous T-cell ...lymphoma (CTCL) in 1988. After the first positive experiences with CTCL, additional indications have been successfully explored including areas such as graft-vs.-host disease (GVHD), scleroderma, and solid organ transplantation. The mechanism of action is still not fully resolved, but important steps in understanding ECP in recent years have been very informative. Originally, the primary hypothesis stated that psoralen and ultraviolet A (UVA) in combination induce apoptosis in the treated immune cells. This view shifted in favor of dendritic cell initiation, modification of the cytokine profile and stimulation of several T-cell lineages, in particular regulatory T-cells. A number of ECP guidelines have been produced to optimize treatment regimens in the clinical context. In CTCL, enough evidence is available for the use of ECP as a first line treatment for Sézary Syndrome (SS), but also as a second line or rescue treatment in therapy-refractory forms of mycosis fungoides (MF). ECP in the treatment of acute and chronic GVHD has shown promising results as second line therapy in steroid-refractory presentations. In solid organ transplantation, ECP has been used to increase tissue tolerance and decrease infections with opportunistic pathogens, attributed to the use of high doses of immunosuppressive medication. Infection with cytomegalovirus (CMV) remains a limiting factor affecting survival in solid organ transplantation and the role of ECP will be discussed in this review. A trend toward prophylactic use of ECP can be observed and may further contribute to improve the outcome in many patients. To further deepen our knowledge of ECP and thus facilitate its use in patients that potentially benefit most from it, future prospective randomized trials are urgently needed in this rapidly growing field. The aim of this review is to (1) introduce the method, (2) give an overview where ECP has shown promising effects and has become an essential part of treatment protocols, and (3) to give recommendations on how to proceed in numerous indications.
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.
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.
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.
The Revised Illness Perception Questionnaire (IPQ-R) has been shown to assess illness perception reproducibly in primary cutaneous T-cell lymphomas (CTCL). Illness perception reflects patients' ...individual concepts of understanding and interpretation of the disease, influencing illness behaviour and health-related quality of life (HRQOL). This study investigated the clinical relevance of the relationships between illness perception, illness behaviour, and HRQOL in CTCL and cutaneous B-cell lymphomas (CBCL). A total of 92 patients completed the IPQ-R, the Scale for the Assessment of Illness Behavior (SAIB), and a skin-specific HRQOL tool (Skindex-29). Data on illness behaviour were not evidently related to illness perception, whereas illness perception was significantly associated with HRQOL. Both, IPQ-R and HRQOL results correlated with disease entity, stage, and socio-demographics. Only IPQ-R results provided practical information on patients' needs to train personal coping strategies. IPQ-R assessment in CTCL and CBCL might be a useful instrument to improve individual disease management.
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.
Mycosis 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.
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/m2 on days 1 and 15, every 28 days (one cycle). The primary end point was response rate (RR).
Nine centers recruited 49 eligible patients. The median number of chemotherapy cycles received was five. There were no grade 3 to 4 hematologic toxicities. Grade 3 or 4 nonhematologic/nonbiochemical toxicities included cardiac symptom (2%), allergy/hypersensitivity (2%), constitutional symptom (4%), hand and foot reaction (2%), other dermatologic toxicity (6%), other GI toxicity (4%), infection (4%), pulmonary embolism (2%), and cardiac ischemia (2%). Of 49 patients, 20 (40.8%) were responders (complete clinical response CCR or partial response PR as overall response): 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.
PLD has an acceptable safety profile in patients with advanced MF. The efficacy of PLD seems promising.
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.
Cutaneous T-cell lymphomas (CTCLs) comprise a heterogeneous group of extranodal non-Hodgkin lymphomas involving primarily the skin and mycosis fungoides is its most frequent entity. Whereas most ...patients show an indolent course in early disease (clinical stages IA to IIA), some patients progress to advanced disease (stage IIB or higher), and the 5-year survival rate is unfavorable: only 47% (stage IIB) to 18% (stage IVB). Except for allogeneic stem cell transplantation, there is currently no cure for CTCL and thus treatment approaches are palliative, focusing on patients' health-related quality of life. Our aims were to review the current understanding of the pathogenesis of CTCL, such as the shift in overall immune skewing with progressive disease and the challenges of making a timely diagnosis in early-stage disease because of the lack of reliable positive markers for routine diagnostics, and to discuss established and potential treatment modalities such as immunotherapy and novel targeted therapeutics.
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.
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