What Does the Future Hold for Biomarkers of Response to Extracorporeal Photopheresis for Mycosis Fungoides and Sézary Syndrome?

Extracorporeal photopheresis (ECP) is an FDA-approved immunotherapy for cutaneous T-cell lymphoma, which can provide a complete response in some patients. However, it is still being determined who will respond well, and predictive biomarkers are urgently needed to target patients for timely treatment and to monitor their response over time. The aim of this review is to analyze the current state of the diagnostic, prognostic, and disease state-monitoring biomarkers of ECP, and outline the future direction of the ECP biomarker discovery. Specifically, we focus on biomarkers of response to ECP in mycosis fungoides and Sézary syndrome. The review summarizes the current knowledge of ECP biomarkers, including their limitations and potential applications, and identifies key challenges in ECP biomarker discovery. In addition, we discuss emerging technologies that could revolutionize ECP biomarker discovery and accelerate the translation of biomarker research into clinical practice. This review will interest researchers and clinicians seeking to optimize ECP therapy for cutaneous T-cell lymphoma

Targeting the CD47-SIRPα Axis: Present Therapies and the Future for Cutaneous T-cell Lymphoma

The loss of CD47 on aging cells serves as a signal to macrophages to eliminate the target. Therefore, CD47 is a “do-not-eat-me” sign preventing macrophagal phagocytosis via interaction with its ligand SIRPα. Malignant lymphocytes of mycosis fungoides and Sézary syndrome express CD47 highly, thus, being ideal candidates for targeted anti-CD47 therapies. The classes of current anti-CD47-SIRPα therapeutic molecules present in a large variety and include monoclonal antibodies against CD47 and SIRPα, bioengineered SIRPα proteins, miRNAs, and bispecific antibodies. We provided a detailed analysis of all available investigational drugs in a contest of cutaneous T-cell lymphoma. A combination of blockade of the CD47-SIRPα axis and secondary targets in the tumor microenvironment (TME) may improve the clinical efficacy of current immunotherapeutic approaches. We evaluated the possible combination and outlined the most promising one

Romidepsin Controls Chronic Lymphocytic Leukemia in a Patient with Mycosis Fungoides

Romidepsin belongs to a class of medications called histone deacetylase inhibitors and is currently approved for treatment of cutaneous and peripheral T-cell lymphomas. Romidepsin was previously investigated for the treatment of chronic lymphocytic leukemia (CLL), and demonstrated potential benefit, but interest in its use declined following phase I clinical trials that showed poor tolerance of a significant side effect profile. We presented a patient with a history of stage II CLL, referred to dermatology for treatment of new-onset of mycosis fungoides (MF), who was treated with romidepsin over seven months. The patient achieved a partial response with 50% decrease in body surface area occupied by MF, thinning of remaining plaques, and near complete response in his CLL. His absolute lymphocyte count remained within the normal range for four months following discontinuation of romidepsin. Side effects were well-tolerated and did not limit therapy. Current literature on romidepsin is reviewed and compared to existing treatments for CLL

CD5+ Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type, Presenting as an Asymptomatic Nodule

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT), is a rare and aggressive variant of primary cutaneous lymphoma that typically expresses B cells as well as MUM1/IRF4, BCL2, and FOXP1, whereas BCL6 may be present or undetectable. We present a case of CD5+ PCDLBCL-LT presenting as a 6 mm pink-bluish nodule on the mid-left thigh, which was concerning for basal cell carcinoma. The histological examination reveals the presence of an intradermal proliferation of large, atypical CD5+, CD20+ BCL2+, BCL6+, MUM-1+, and Cyclin-D1+ lymphocytes in a nodular, diffuse interstitial and perivascular distribution. Because the patient presented with a small, single nodule, the systemic treatment of multiagent chemotherapy was avoided and localized electron beam radiation therapy with rituximab was initiated instead, achieving complete response. Early identification of PCDLBCL-LT is key for maximal therapeutic benefit and prognosis; it is important to consider PCDLBCL-LT on the differential when evaluating small, single nodules on the lower extremities of elderly patients

Optimization of Topical Photodynamic Therapy With 3,7-bis(di-n-butylamino)Phenothiazin-5-ium Bromide for Cutaneous Leishmaniasis

Background And Objective: Photodynamic therapy (PDT) has evolved as a promising therapeutic measure for the treatment of cutaneous leishmaniasis (CL). In particular, phenothiazine compounds have demonstrated efficacy for PDT of CL. The objective of our present study is to define the use of a new specific phenothiazine photosensitizer, 3,7-bis(di-n-butylamino)phenothiazin-5-ium bromide (PPA904) applied topically as a cream to treat CL. Materials And Methods: To establish the optimal conditions for this treatment, we compared two different ways to improve current regimens of PDT with PPA904 cream (500 mu M of PPA904 in Unguentum M) by changing the duration of topical application, and by administration of several consecutive PDT procedures. An initial regimen recommended by the manufacturer (Photopharmica Co. Ltd., Leeds, UK) was maintained as a control: the cream was applied topically for 30 minutes at a final concentration of PPA904 at 500 mu M, and the designated treatment area was irradiated with a broad band light source of 665 +/- 15 nm at a fluence of 50 J/cm(2) (50 MW/cm(2)). Results: The best curative PPA904-PDT regimen was achieved under the conditions of a longer duration of topical application time (90 minutes) and several (three) consecutive treatments with 4-day intervals between treatments. The mechanisms responsible for such improvements (kinetics of drug penetration, depth of necrosis of the CL lesions after PDT, and daily changes in the parasitic load after PDT) are discussed in the present study. Conclusion: Topical PPA904-PDT, implemented as described above, is a promising treatment for CL, and clinical studies will be initiated to establish efficacy in humans

Non-random geographic distribution of patients with cutaneous T-cell lymphoma in the Greater Pittsburgh Area

Background: Environmental hazards may play a role in the etiology of cutaneous T-cell lymphoma (CTCL). Some studies have found an increased incidence of CTCL among workers in chemical science, transportation, and manufacturing industries, but other studies have not. This discrepancy may be attributable to population migration, complicating accurate assessment of lifetime exposures. The Pittsburgh population has very low migration rates and most CTCL patients seen at the University of Pittsburgh Medical Center (UPMC) Cutaneous Lymphoma Center are life-long local residents. The Greater Pittsburgh Area used to be an industrial hub. There are residential communities positioned within close proximity to inactive industrial sites that continue to contain pollutants.Objective: To determine whether CTCL patients’ residences cluster within specific Pittsburgh regions, in particular, those with high levels of environmental pollutants.Methods: Our study included patients diagnosed with CTCL at the UPMC Cutaneous Lymphoma Center between 2000 and 2012. We mapped the longitudinal and latitudinal coordinates of patients’ residences at diagnosis, superfund sites, toxic release inventory sites, particular matter levels, and dermatologists’ offices using ArcMap 10.1. We then performed a SaTScan analysis using zip codes to assess for geographic clustering of patients’ residences in the Pittsburgh metropolitan statistical area. We assessed for a correlation between case distribution and both environmental hazards sites and dermatologist density in the area.Results: We identified 274 patients with CTCL in the Greater Pittsburgh area. We identified a statistically significant geographic cluster (p<.001) in zip code 15213, which is the most densely populated neighborhood in Pittsburgh and the site of the region’s only CTCL clinic.  We observed no relationship between the locations of superfund sites, toxic release inventory sites, or particular matter levels and CTCL case distribution.Conclusion: Our findings do not support an association between exposure to environmental toxins and CTCL. CTCL cases clustered in areas with the highest population density, which also happen to include a regional CTCL center. To evaluate a possibility of urban pollutants playing a role in etiology of CTCL, dermatologist density and access to care need to be addressed as potential confounders in the future studies