Successful treatment of sclerotic cutaneous graft‐versus‐host disease using extracorporeal photopheresis

Abstract

Extracorporeal photopheresis (ECP) has been increasingly used off label for the treatment of various inflammatory disorders [1–3]. At our center, one of the most common indications for ECP – second only to stem cell transplantation (SCTx) – is graft-versus-host disease (GVHD). Proposed mechanisms of action of ECP in patients with chronic GVHD include a shift in the immune response from Th1 to Th2 dominance, proliferation of regulatory T cells (Tregs) and induction of anti-inflammatory cytokines [4–6]. In particular, chronic sclerotic GVHD (sGVHD) of the skin is a disease variant that is extremely difficult to treat. It is associated with severe physical impairments and reduced quality of life. In addition to restricted overall mobility, patients complain of limited excursion of the thorax and associated dyspnea, as well as stiffening of the abdominal wall with impaired intestinal motility. Severe sclerosis of the extremities may result in irreversible contractures that are associated with further sequelae [7]. Objective assessment of treatment success in patients with sGVHD is often challenging, given that there are hardly any useful tools in everyday clinical practice with which the extent and severity of sclerosis can be measured during treatment. While surveying the standardized photos that had been taken of our patients over the course of their treatment, we realized that objective photographic assessment of clinical improvement (or deterioration) was indeed possible. This observation prompted us to review the entire patient data. Herein, we present a retrospective analysis of a case series of 13 patients with recalcitrant sGVHD who underwent ECP (Cellex®, Therakos® Inc.) at our department between 2005 and 2018 (Table 1). The patients had a median history of sGVHD of 22 months prior to initiation of ECP and had not responded to conventional immunosuppressive treatment prescribed by the treating hematologists. ECP was administered off label following prior approval by the competent health insurance funds. One cycle included two treatment sessions on two consecutive days. All patients received at least 6–8 cycles at 14-day intervals. Subsequently, the intervals were gradually extended based on each patient’s individual response to treatment. The extent of sclerosis was documented on a regular basis using standardized whole-body photography. The defined whole and partial body pictures were taken repetitively using the same settings: Canon EOS 1 Dx Mark II, aperture (f) 11, exposure (t) 1/125 at ISO 100 using two flashlights of 500 W each against a studio-gray background. Patients received a median of 37 ECP cycles (range: 10 to 90 cycles). In one female patient, ECP was discontinued after twelve cycles despite subjective improvement, as her health insurance declined further coverage of the procedure. In one male patient, ECP was terminated after 15 cycles due to disease progression. Patients reported subjective improvement, such as softer skin and improved mobility, after only six ECP cycles (three months of treatment) (Table 1). Objective improvement of sclerosis based on photo documentation was first seen at a median of 25 months after treatment initiation (equivalent to 25 cycles of ECP) (Figures 1–3, Table 1). Objectifiable changes included the regression of the cobblestone texture of the skin as well as sclerosis-related skin depressions; the latter signified regression of deep sclerosis with fascial involvement. Objective anatomical changes were likewise observed, including regression of the “potbelly” appearance with narrowing of the umbilicus caused by sclerosis of the abdominal skin. Lichen sclerosus-like plaques – as a sign of DOI: 10.1111/ddg.13976 Successful treatment of sclerotic cutaneous graft-versus-host disease using extracorporeal photopheresis Clinical Letter