Combined Low-Dose TBI, Ivig, and DEX for Donor-Specific Antibody Desensitization in Haploidentical and Mmud Haematopoietic Stem Cell Transplantation： a Retrospective Multicenter Case-Control Study
Authors: Li Zhen , Gui Ruirui , Wang Juan , Zu Yingling , Yu Fengkuan , Zhang Yanli , Lv Xiaodong , Song Yunfeng , Dong Xiaofeng , Guo Shuli , Wang Xianjing , Wang Huili , Dang Huibing , Lin Xiaoyuan , Zhang Wenli , Li Xudong , Li Wei , Lu Wenyi , Zhou Keshu , Song Yongping , Zhou Jian 
Published: December 2024

Donor-specific HLA antibodies (DSA) are the main cause of graft failure in patients receiving haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) and mismatched unrelated-donor hematopoietic stem cell transplantation（MMUD-HSCT）.

DSA leads to graft failure by destroying donor hematopoietic stem cells mainly through the action of the ADCC effect. To study the effectiveness of a desensitization regimen including low-dose total body radiotherapy (TBI) combined with intravenous immunoglobulin (IVIg) and dexamethasone, a retrospective nested case-control study was conducted in four transplant centers from September 2020 to December 2023.36 patients with DSA mean fluorescence intensity (MFI ) ≥ 5000 were used as the study subjects for the study group. A control group of 72 patients with MFI &lt; 500 was selected and matched 2:1 to the study group for age, sex, diagnosis, disease status, donor sources, HLA-matched grafts, ABO compatibility, mononuclear cells, and CD34+ cells. All of the study groups received a desensitization program; the control group was untreated. In the study group, 12 patients with MFI ≥10,000 as a strong DSA-positive group; and 14 patients with 5000 ≤ MFI &lt;10,000 as a DSA-positive group. The median fluorescence intensity values of HLA class I antibodies in the study group before desensitization and +14d were 11,167.94 (5,091-21,600) vs. 4,680 (0-17,764) (p&lt;0.001), and the median fluorescence intensity values of HLA class II antibodies before desensitization and +14d were 11,012 ( 7,084-23,781) vs. 5,000 (1,100-20,370) (p&lt;0.001).In the study group, 97.2% of patients achieved hematopoietic reconstitution, and median implantation times for neutrophils and platelets were 12 (10-28) and 13 (10-24) days, respectively. In the study group and control group patients ,+14d neutrophil and platelet cumulative implantation rates were 94.4% ± 3.8% vs 87.5% ± 3.9% (p= 0.882) and 68.6% ± 7.8% vs 69.4% ± 5.4% (p= 0.292), respectively;

The incidence of graft malfunction was 8.3% vs 9.7% (p=1.000), respectively. The 2-year OS, DFS, and CIR were comparable in the study and control groups, 76.6% ± 7.6 vs 88.9% ± 4.0% (p=0.467), 76.44% ± 8.7% vs 87.7% ± 4.1% (p=0.501), and 8.2% ± 5.9% vs 7.4% ± 3.2% (p=0.899), respectively. There was a trend of higher NRM in the study group than the control group (16.5% ± 7.8% vs 9.5% ± 3.7% (p=0.324)), but the difference was not statistically significant. The difference in the incidence of aGVHD, cGVHD, and viral infections between the two groups was not statistically significant. In the subgroup analysis, there were no statistically significant differences in the incidence of 2-year OS, DFS, CIR, NRM, aGVHD, cGVHD, and viral infection in the strongly DSA-positive, DSA-positive, and control groups. Low-dose TBI combined with IVIg and dexamethasone can be effectively used to desensitize DSA-positive patients in the PT/CY transplantation mode and to overcome the effect of DSA on implantation failure of HLA-incompatible hematopoietic stem cell transplants.