Extracorporeal Photopheresis—An Overview

Abstract

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.

Extracorporeal Photopheresis: A Case of Immunotherapy Ahead of Its Time

“…Multiple interactions between apoptotic bodies and exposed and nonexposed cells initiate a cascade of immunological changes that cement the core elements of the ECP therapeutic mechanism. As patients benefit from a response with anticlonal and/or immunotolerance characteristics and they do not enter into a generalized immunosuppression state (opportunistic infections are rarely seen in ECP-treated patients and they have a normal response to vaccination) [42, 43], it is reasonable to infer that ECP provides a pool of antigens and immunomodulatory mediators that resettle the immune system. This, however, challenges one of the long-standing assumptions that apoptosis is a silent modality of cell death that prevents the elicitation of autoimmunity [44].…”

Pathogenesis and Therapy of Primary Cutaneous T-Cell Lymphoma: Collegium Internationale Allergologicum (CIA) Update 2020

“…ECP and PUVA Both extracorporeal photopheresis (ECP) and psoralen plus ultraviolet A (PUVA) consist of the systemic or local application of 8-metoxypsolaren and subsequent photoactivation resulting in apoptosis of malignant lymphocytes [89][90][91][92]. However, despite the established use in the management of CTCL, their mechanism of action is still not sufficiently investigated.…”

Elutriate isolation of Sézary cells in extracorporeal photopheresis

“…Both can present with pruritic plaques and patches, however, MF may not have associated erythroderma. Erythrodermic MF and SS are American Society for Apheresis (ASFA) category I indications for ECP, 2 an FDA‐approved leukapheresis‐based form of phototherapy 3 . Approximately 60% of CTCL cases at least partially respond to ECP therapy 3,4 .…”

“…The elutriate is treated with a photoactivating agent, 8‐methoxypsoralen, photoactivated with ultraviolet A light, and returned to the patient. ECP is believed to have an immunomodulatory effect, activating dendritic cells, increasing anti‐inflammatory cytokines, and stimulating T‐regulatory cells 3 …”