Role of Extracorporeal Photopheresis in Prevention of Graft-Versus-Host Disease in Patients Treated with Allogeneic Hematopoietic Stem Cell Transplantation: A Randomized Controlled Trial

Introduction In many patients diagnosed with a hematological malignancy, the disease cannot be totally eradicated by conventional therapeutic approaches, and for them allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative option. A major complication of allo-HSCT is graft-versus-host disease (GvHD), affecting about 50% of transplant recipients. In addition to increased risk of death and long-lasting debilitating conditions, severe GvHD also impairs health-related quality of life. High-dose systemic steroids is the first line treatment for GvHD, but treatment failure is common, and steroid-refractoriness is a major cause of non-relapse mortality after allo-HSCT. While there is no established second line GvHD-treatment, extracorporeal photophoresis (ECP) has emerged as an attractive and increasingly applied alternative, partly due to its favourable safety profile. However, the use of ECP in preventing GvHD is sparse and data are inconclusive due to lack of randomized controlled trials (RCT). We therefore conducted a RCT to study if ECP given post transplantation could prevent the development of GvHD. Methods Between June 2017 and February 2020, we enrolled 157 patients (> 18 years) diagnosed with a hematological malignancy and treated with an allo-HSCT in first remission into an intention-to-treat open RCT. Ethical and IRB approvals were granted, and the RCT was registered with Clinical Trials (ID NCT03204721). The sample size (76 in intervention group and 81 controls) was calculated based on a reduction of 25% in the total number of patients diagnosed with any form of GvHD within the first year of allo-HCST (primary end-point) as clinically relevant. The patients were stratified according to whether they received myeloablative or reduced intensity conditioning (Table 1), and they were given GvHD prophylaxis as shown in Table 1. ECP (Therakos Cellex ®, Mallinckrodt Pharm., NJ) was initiated when patients had engrafted (i.e. leukocytes > 1 x 10 9/L and platelets > 20 x 10 9/L), and, according to the study protocol, we planned for ECP on two consecutive days/week for two weeks, then weekly for four weeks to a total eight treatments for each patient in the intervention group. Chi-square test was used to test differences between the two study groups. Results Table 1 shows that patient characteristics were well balanced among the two study groups. Four patients did not receive ECP while 39 received all the eight treatments. One year a