The Impact of Anti-HLA Antibodies on the Prognosis of Allogeneic Hematopoietic Stem Cell Transplantation in Myelodysplastic Syndrome
Authors: Xie Tiantian , Lu Runqing , Cao Weijie , Zhilei Bian , Li Wei , Jiang Zhongxing , Song Yongping , Li Dengju , Guo Rong 
Published: December 2024

Objective To investigate the risk factors of positive anti-HLA antibodies in myelodysplastic syndrome (MDS) patients and gain insights into the impact of anti-HLA antibodies in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for MDS patients. The goal is to identify high-risk patients with anti-HLA antibodies and implement timely interventions, providing a basis for personalized treatment and improving prognosis.

Methods A total of 94 MDS patients who received anti-HLA antibody screening and allo-HSCT at our center from December 1, 2016 to September 1, 2023 were retrospectively collected. The general clinical data was compared between 50 patients with positive anti-HLA antibodies and 44 patients without, to identify factors influencing anti-HLA antibody positivity in MDS. Furthermore, based on pre-transplant clinical characteristics of patients and post-transplant survival, as well as the occurrence of related complications, the study analyzed the impact of anti-HLA antibodies on complications such as acute graft-versus-host disease (aGVHD) and chronic graft-versus-host disease (cGVHD), graft failure (GF)/poor graft function (PGF), transplant-associated thrombotic microangiopathy (TA-TMA) and long-term survival in MDS patients following HSCT.

Results A total of 94 patients were included in this study, comprising 57 males and 37 females. The positive rate of anti-HLA antibody in patients with pregnancy history was higher than those without pregnancy history and male patients, and the difference was statistically significant (74.1% vs. 44.8%, P=0.022). Female sex was identified as an independent risk factor for positive anti-HLA antibodies (OR=3.741, 95%CI:1.254-11.166, P=0.018). There was a significant difference in mortality between the positive and negative anti-HLA antibody groups (46.0% vs 22.7%, P=0.018). Significant differences in mortality were observed among the three groups based on anti-HLA antibody status: continuous positive, positive to negative, and continuous negative(81.8% vs. 30.0% vs. 37.5%, P=0.043). CD34+ cell count &lt; 4.0×106/kg was an independent risk factor for GF/PGF (OR=5.682, 95%CI: 1.258-25.667, P=0.024). Haploidentical transplantation (OR=2.239, 95%CI: 1.079-4.544, P=0.030) and IPSS-R prognosis stratified very low risk/low risk (OR=6.033, 95%CI: 1.704-21.359, P=0.005) were independent risk factors for aGVHD in MDS patients. Being stratified as high-risk according to IPSS-M classification (HR=2.745, 95%CI: 1.269-5.939, P=0.010) is an independent risk factor for overall survival (OS) in MDS transplant patients. The median OS of the positive group was 380 days, while the median OS of the negative group was not reached, with a statistically significant difference (P=0.017). The 1-year, 2-year and 3-year OS rates of anti-HLA antibody positive and negative groups were 51.7% vs. 77.2%, 47.7% vs. 70.7% and 40.9% vs. 70.7%, respectively. The median disease-free survival (DFS) of the positive group was 380 days, but the median DFS of the negative group was not reached, with a statistically significant difference (P=0.017). There were also statistically significant differences in OS(P=0.041) and DFS(P=0.033) between female and male patients in the positive group. Survival analysis showed significant differences in OS (P=0.022) and DFS (P=0.025) among the continuous positive, positive to negative, and continuous negative anti-HLA antibody groups. The risk of GVHD accumulation in anti-HLA positive group was higher than that in negative group, and there was a statistically significant difference (P=0.037).

Conclusion Female patients with MDS demonstrate increased susceptibility to positive anti-HLA antibodies. In MDS patients undergoing transplantation, long-term survival rates were notably lower among female patients and those with persistent positive anti-HLA antibodies post-transplantation. The cumulative incidence of GVHD (both aGVHD and cGVHD) was significantly higher in the anti-HLA antibody-positive cohort. Additionally, MDS patients undergoing haploidentical transplantation or stratified based on IPSS-R prognosis face an elevated risk of aGVHD.

Key words Myelodysplastic Syndrome; Allogeneic Hematopoietic Stem Cell Transplantation; Anti-HLA antibody; Graft-versus-host disease；Transplant-associated thrombotic microangiopathy