Original Article
Extracorporeal photopheresis in steroid-refractory chronic graft-versus-host disease: A retrospective multicenter study

https://doi.org/10.1016/j.transci.2021.103243Get rights and content

Abstract

Background and objectives

Extracorporeal photopheresis (ECP) is a treatment strategy in steroid-refractory chronic graft-versus-host disease (cGvHD). In this study, we aimed to share our multicenter experience using ECP in our steroid-refractory cGvHD patients.

Materials and methods

In this multicenter observational retrospective study with the participation of four Turkish transplant centers, 100 patients with the diagnosis of steroid-refractory cGvHD who underwent ECP were analyzed. All ECP procedures were performed with the off-line system.

Results

Severe cGvHD was observed in 77 % of the patients. 50 % of the patients had more than 1 organ involvement. The overall response rate in cGvHD was 58 %, and the complete response (CR) rate was 35 %. The skin was the most involved organ, with a response rate of 61.2 % (CR rate 30.6 %) in cGvHD. At a median 13 months (1−261) follow-up, overall survival (OS) was 41 % (n = 41) and the mortality rate was 59 % (n = 59). Median overall survival (OS) was 2 months for non-responders and 91 months for responders (p < 0.001). Significant OS differences were observed for patients responding to ECP in cGvHD (HR = 4.1, p = 0.001) patients.

Conclusions

ECP is a good therapeutic alternative and could be used earlier in patients with steroid-resistant cGvHD.

Introduction

About 60 % of the allogeneic transplant patients develop chronic graft-versus-host disease (cGvHD), resulting in non-relapse morbidity and 25 % mortality [1,2]. Its incidence has increased over the last two decades due to the increasing patient age and the increased use of unrelated and/or incompatible donors, reduced-intensity conditioning (RIC) regimens, and source of peripheral blood stem cell source (PBSC) [3]. Corticosteroids are the initial systemic therapy of choice for patients with moderate-to-severe cGvHD [4]. However, only 50–60 % of the patients respond to this treatment, and most patients require additional salvage and/or second-line therapy [5].

Extracorporeal photopheresis (ECP) is recommended as second-line therapy in graft-versus-host disease (GvHD) by the American Apheresis Society guidelines and the joint recommendations of the British Standards Committee of Hematology and the British Bone Marrow Transplantation Society [6,7]. ECP consists in the collection of a patient’s peripheral blood lymphocytes that, after incubation with a photosensitive molecule (8-methoxypsoralen), are exposed to ultraviolet-A and then re-infused into the patient [8]. There is a 30 %–70 % overall response rate (ORR) in cGvHD, and better responses are reported in patients with skin involvement [[9], [10], [11], [12]].

Although there are several studies that have been performed to show the effectiveness of ECP in steroid refractory cGvHD worldwide, the number of research studies available in Turkey is limited, sample sizes are relatively small, and, mostly, there are single center data [13,14]. The objective of this study is to report the real-life effectiveness of an off-line ECP system for steroid-refractory cGvHD patients from 4 Turkish transplant centers.

Section snippets

Patients and response definitions

A multicenter observational retrospective study was conducted with the participation of 4 Turkish transplant centers. One hundred patients who underwent ECP for steroid refractory cGvHD between 2011 and 2020 at these centers were included in the study, and no reported patients were excluded.

One hundred patients (62 males/38 females) with steroid-refractory cutaneous and/or visceral cGvHD were treated with ECP on two consecutive days every 2 weeks until the resolution of signs. GvHD was graded

Results

The characteristics of the patients are summarized in Table 1. The median time from cGvHD diagnosis to the beginning of ECP was 55 days. Twenty-three (23 %) patients had mild or moderate cGvHD, while seventy-seven (77 %) had severe cGvHD. While the ORR was 78.1 % in patients with mild-moderate involvement, it was 51.9 % in patients with severe involvement (p = 0.025). The median OS was 91 months for mild-moderate involvement and 12 months for severe involvement (p = 0.032). Fewer patients

Discussion

This multicenter study encompasses the largest number of patients with steroid refractory cGvHD who underwent ECP in Turkey. The main findings of the study are; (i) ORR was 78.1 % in patients with mild-moderate involvement and it was 51.9 % in patients with severe involvement; (ii) significant survival advantage was seen for responders to ECP treatment compared to the non-responders.

The prognosis for steroid-refractory patients with severe cGvHD is poor, and recommendations for second-line and

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    • Guidelines on the Use of Therapeutic Apheresis in Clinical Practice – Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Ninth Special Issue

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