Posttransplant de novo DSA and NDSA affect GvHD, OS, and DFS after haplo-HSCT in patients without pre-existing HLA antibodies of hematological malignancies

Abstract

To examine the production time, type, and MFI of post-transplantation de novo HLA antibodies, and their effects on haplo-HSCT outcomes, we retrospectively included 116 patients who were negative for pre-existing HLA antibodies. In total, 322 serum samples from pre-transplantation to post-transplantation were dynamically tested by Luminex and single-antigen bead reagents. Patients were divided into: HLA antibody persistently negative group (group 1), the de novo HLA antibody transiently positive group (group 2), the de novo HLA antibody non-persistently positive group (group 3), and the de novo HLA antibody persistently positive group (group 4). Group 4 included DSA+non-DSA (NDSA) (group 4a) and NDSA (group 4b) groups. The detection rate of de novo HLA antibodies was 75.9% (88/116). The median MFI for de novo HLA antibodies was 2439 (1033-20162). The incidence of II-IV aGvHD was higher in group 2 than in group 1 (52.6% vs 17.9%, P < 0.01); in group 4a than in group 1 (87.5% vs 17.9%, P < 0.001); and in group 4a than in group 4b (87.5% vs 40.0%, P = 0.001). The DFS (37.5% vs 85.7%, P < 0.01) and OS (37.5% vs 85.7%, P < 0.01) of group 4a were lower than those of group 1. The DFS (48.0% vs 85.7%, P < 0.01) and OS (56.0% vs 85.7%, P = 0.03) of group 4b were lower than those of group 1. Multivariate analysis showed that de novo HLA antibody being transiently positive (HR: 5.30; 95% CI: 1.71-16.42, P = 0.01) and persistently positive (HR: 5.67; 95% CI: 2.00-16.08, P < 0.01) were both associated with a higher incidence of II-IV aGvHD. Persistently positive de novo HLA antibodies were a risk factor for reduced DFS (HR: 6.57; 95% CI: 2.08-20.70, P < 0.01) and OS (HR: 5.51; 95% CI: 1.73-17.53, P < 0.01). DSA and NDSA can be detected since 15 days after haplo-HSCT in patients without pre-existing HLA antibodies, and affect aGvHD, DFS, and OS. Haplo-HSCT patients must be monitored for HLA antibodies changes for appropriate preventive clinical management, and we recommend that 1-month post-transplantation is the best test time point.

Keywords: acute graft-versus-host disease (aGvHD); de novo human leukocyte antigen antibody (de novo HLA antibody); donor-specific anti-HLA antibody (DSA); haploidentical hematopoietic stem cell transplantation (haplo-HSCT); outcomes.

Figure 1

Production time, type, and MFI level of de novo HLA antibodies. (A) Type of de novo HLA antibodies detected at different times after haplo-HSCT. The Y-axis represents the quantity of de novo HLA antibodies. The bars correspond to the left Y-axis; the lines correspond to the right Y-axis and represent the cumulated quantity of antibodies; cum, reprensents accumulation. (B) Specificity of de novo antibodies detected 1 month after transplantation. (C) MFI level distribution of de novo antibodies in 88 patients.

Figure 2

Type of HLA-DR, DQ, and DP specific antibodies. (A) DR antibody specificity type. (B) DQ antibody specificity type. (C) DR antibody specificity type. The numbers on the bars represent the number of patients positive for the specific antibodies.

Figure 3

Effects of de novo antibodies on grade II–IV aGvHD. (A) De novo HLA antibodies in four groups. (B) Persistent de novo antibodies. (C) Different de novo HLA antibody types. (D) De novo HLA-DR+DQ+DP antibodies.

Figure 4

Effects of de novo HLA antibody, persistent de novo HLA antibody, and changes in MFI on DFS and OS. (A) Effects of de novo HLA antibodies in four groups on DFS. (B) Effects of de novo HLA antibodies in four groups on OS. (C) Effects of persistent de novo antibodies on DFS. (D) Effects of persistent de novo antibodies on OS. (E) Effects of MFI level changes of de novo antibodies on DFS. (F) Effects of MFI level changes of de novo antibodies on OS. Tables.