High Serum Level of APRIL Is Related to Increased Risk of Acute Gvhd
Authors: Kim Soo-Jeong , Kim Yundeok , Hyun Shin Young , Jang Ji Eun , Hwang Doh Yu , Kim Yu Ri , Lee Hye Won , Cheong June-Won , Kim Jin Seok , Min Yoo-Hong 
Published: October 2019

Abstract
Abstract 4161

Introduction:
Traditionally T cells were recognized as main effector of acute graft-versus-host disease. Many studies revealed that grafted T cell dose and activity or repertoire development of T cell is related to GVHD. Recently, the role of B-cells in pathogenesis of acute GVHD is actively investigated. BAFF and APRIL is known to be related to increased activity of many autoimmune diseases. APRIL (a proliferation-inducing ligand) is a cytokine of the tumor necrosis factor superfamily secreted by myeloid cells, dendritic cells and T cells. We studied on serum level of APRIL at early transplantation period for investigation of relationship between APRIL concentration and risk of acute GVHD.

Materials and Methods:
Forty-six patients who received HLA-matched sibling allogeneic stem cell transplantation in Severance Hospital From September 2003 to September 2009 with remaining stored blood samples were selected. Blood samples were collected at day 0 and day 14. After clot formation, sera were separated at 1,000 g for 3 minutes then stored at -80°C for analysis. Samples were measured by commercial ELISA kit for APRIL (Bender MedSystems, Vienna, Austria) according to the manufacturer's recommendations. Grading of acute GVHD followed IBMTR severity index.

Result:
Age at transplantation ranged from 16 to 52 years(median 35.5 yrs). Bone marrow was used in 7 patients (15.2%) and PB in 39(84.8%). Myeloablative conditioning regimen was used in 18 patients (39.1%) and total body irradiation in 6 patients (13.0%), 28 patients used reduced intensity conditioning regimens. Disease status at SCT was CR 29 patients (63%), non-CR 14(30.4%). Incidence of all grade of acute GVHD was 56.5% (26 patients) and incidence of aGVHD exceeding grade 1 was 34.8% (16 patients). Serum APRIL concentration ranged from 1.859 to 6.219 (median 3.101 ng/mL) for day0 sera and 1.822 to 15.507 (median 3.683 ng/mL) for day14 sera. Patients with higher level than median concentration showed correlation with increased tendency of acute GVHD by χ2 test in both day 0 (P=0.021) and day 14 (P=0.147). And then, patients were divided into two groups, one group included patients with steady higher level than median in both day 0 and day 14 (group1), while the others constituted group2. By χ2 test, group 1 showed correlation with acute GVHD (P=0.037). In multivariate analysis, conditioning intensity, donor-patient sex mismatch, stem cell dose, CD3+ cell dose, donor parity were included with steady higher APRIL level as variables. Higher APRIL was strongest variable for increased risk of acute GVHD (hazard ratio 64.67, P=0.005).

Conclusion:
Our data suggest that higher level of APRIL at early phase of allogeneic stem cell transplantation with HLA-matched sibling donor can be used as predictor of acute GVHD. Confirm of our hypothesis should be done also in larger patient data including alternative donors.

Disclosures:
No relevant conflicts of interest to declare.