高致敏单倍体造血干细胞移植患者采用蛋白A免疫吸附联合利妥昔单抗行脱敏治疗的疗效及安全性

The efficacy and safety of protein A immunoadsorption combined with rituximab treatment for highly sensitized patients undergoing haplo-hematopoietic stem cell transplantation

目的探究高致敏单倍体造血干细胞移植(haplo-HSCT)患者移植前行蛋白A免疫吸附(PAIA)联合利妥昔单抗(RTX)脱敏治疗的疗效及安全性。方法回顾性分析2021年3月至2023年6月苏州大学附属第一医院和苏州弘慈血液病医院收治的高致敏haplo-HSCT患者56例, 移植前行PAIA联合RTX脱敏治疗, 吸附前后监测HLA抗体种类数量和平均荧光强度(MFI)、体液免疫和吸附过程的不良反应及100 d内的生存情况。结果仅含HLA Ⅰ类抗体的患者接受PAIA治疗后中位MFI由7 859(3 209~12 444)降至3 719(0~8 275)(P<0.001), HLA Ⅰ+Ⅱ类抗体的中位MFI由5 476(1 977~12 382)降至3 714(0~11 074)(P=0.035), 其中抗供者特异性抗体阳性患者的中位MFI由8 779(2 697~18 659)降至4 524(0~15 989)(P<0.001)。所有患者HLA-A、B、C、DR、DQ抗体种类数量在PAIA治疗后均下降, 差异均有统计学意义(A、B、C、DR:P<0.001, DQ:P<0.01)。PAIA治疗前后体液免疫监测显示IgG和补体C3数量显著下降(P值分别为<0.001和0.002)。44例患者接受了移植后HLA抗体监测, 总体MFI和抗体种类数量均下降, 但有5例患者出现低MFI的新生抗体, 有9例持续高MFI, 移植后100 d总生存率是83.8%, 100 d内无病生存率为80.2%, 100 d内非复发死亡率为16.1%, 移植后100 d复发的累积发生率为4.5%。结论 PAIA联合RTX对haplo-HSCT前高敏患者的脱敏治疗有一定的疗效, 安全性良好。

Objective To investigate the efficacy and safety of protein A immunoadsorption(PAIA)combined with rituximab(RTX)in highly sensitized patients who underwent haplo-hematopoietic stem cell transplantation(haplo-HSCT).Methods The clinical data of 56 highly sensitized patients treated with PAIA and RTX before haplo-HSCT at the First Affiliated Hospital of Soochow University and Soochow Hopes Hematonosis Hospital between March 2021 and June 2023 were retrospectively analyzed.The number of human leukocyte antigen(HLA)antibody types and the mean fluorescence intensity(MFI),humoral immunity,adverse reactions during adsorption,and survival within 100 days before and after adsorption were measured.Results After receiving the PAIA treatment,the median MFI of patients containing only HLAⅠantibodies decreased from 7859(3209-12444)to 3719(0-8275)(P<0.001),and the median MFI of HLAⅠ+Ⅱantibodies decreased from 5476(1977-12382)to 3714(0-11074)(P=0.035).The median MFI of patients with positive anti-donor-specific antibodies decreased from 8779(2697-18659)to 4524(0–15989)(P<0.001).The number of HLA-A,B,C,DR,and DQ antibodies in all patients decreased after the PAIA treatment,and the differences were statistically significant(A,B,C,DR:P<0.001,DQ:P<0.01).The humoral immune monitoring before and after the PAIA treatment showed a significant decrease in the number of IgG and complement C3(P<0.001 and P=0.002,respectively).Forty-four patients underwent HLA antibody monitoring after transplantation,and the overall MFI and number of antibody types decreased.However,five patients developed new antibodies with low MFI,and nine patients continued to have high MFI.The overall survival,disease-free survival,non-recurrent mortality,and cumulative recurrence rates at 100 days post-transplantation were 83.8%,80.2%,16.1%,and 4.5%,respectively.Conclusions The combination of PAIA and RTX has a certain therapeutic effect and good safety in the desensitization treatment of highly sensitive patients before haplo-HSCT.