Two Decades of Extracorporeal Photopheresis for the Treatment of Steroid-Refractory Acute Graft-Versus-Host-Disease: A Meta-Analysis

Document Type

Conference Proceeding

Publication Date

2-1-2025

Publication Title

Transplant Cell Ther

Keywords

steroid, acute graft versus host disease, adult, conference abstract, drug combination, drug therapy, first-line treatment, hematopoietic stem cell transplantation, human, meta analysis, mortality, overall response rate, overall survival, photopheresis, Preferred Reporting Items for Systematic Reviews and Meta-Analyses, quality of life, quantitative analysis, relapse, side effect, steroid therapy, survival rate, systematic review, therapy, treatment outcome

Abstract

Introduction: Steroid-refractory acute graft-versus-host-disease (SR-aGVHD) remains a significant challenge following hematopoietic stem cell transplantation (HSCT), negatively impacting patient outcomes and quality of life. Despite the decades-long use of extracorporeal photopheresis (ECP) for steroid-refractory acute graft-versus-host disease (SR-aGVHD), only two meta-analyses of its efficacy exist, both published at the same time nearly a decade ago. This study aims to address this gap by presenting an updated meta-analysis incorporating historical and recent data on ECP's impact on SR-aGVHD. Methods: A systematic search was conducted per PRISMA guidelines using PubMed, Scopus, and the Cochrane Library, covering all records up to September 2024. Studies using ECP as prophylaxis or first-line treatment were excluded. A meta-analysis assessed efficacy-related outcomes including overall survival rate (OS) stratified by time points, overall response rate (ORR), and organ-specific response. Additional outcomes include the percentage of patients tapering or discontinuing steroid treatment and non-relapse mortality (NRM). Pooled hazard ratios were also calculated comparing the effect of grade 3 and 4 aGVHD vs grade 2 aGVHD and ECP vs other treatments on OS. A multivariate meta-regression model investigated the effect of the publication year, grading system, age, and combination of ECP with other therapies on ORR, NRM, and steroid-sparing rate. Results: Our search identified 954 unique studies, 38 were of interest and 29 were included in the quantitative analysis. A total of 1285 patients were included, most studies were conducted on adult patients (n=23), with most utilizing a retrospective single-group study design (n=30). There was high variability in the regimens, with differences in duration and frequency. I2 values ranged from 11% to 85%, with most analyses exhibiting considerable heterogeneity. In the meta-analysis, the pooled ORR was 72% (95% CI: 68% - 77%; Figure 1), with a 1-year OS rate of 52% (95% CI: 38% - 66%; Figure 2). The skin response was 89% (95% CI: 80% - 95%), gut 54% (95% CI: 42%- 67%), and liver 36% (95% CI: 24% - 48%). The pooled steroid-sparing rate was 66% (95% CI: 58% - 74%). The pooled HR showed significantly worse OS in patients with grade 3 and grade 4 aGVHD vs grade 2 aGVHD (HR: 2.35, 95% CI: 1.67 – 3.29; Figure 3). ECP insignificantly demonstrated longer OS than other treatments (HR: 0.64, 95% CI: 0.29 - 1.42). The meta-regression showed no significant effect of any of the groups on the variables analyzed. Conclusion: This systematic review shows that ECP is an effective treatment for (SR-aGVHD), with a positive but insignificant effect on OS compared to other treatments. However, due to the heterogeneity of the studies, further studies are needed to explore synergistic interactions between ECP and other therapies and how ECP fares against other treatments.

Volume

31

Issue

2

First Page

S301

Last Page

S302

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