血浆置换联合抗B细胞治疗药物应用于造血干细胞移植DSA阳性患者中的效果观察*

doi:10.3969/j.issn.1671-2587.2025.02.002

临床输血与检验 ›› 2025, Vol. 27 ›› Issue (2): 156-162.DOI: 10.3969/j.issn.1671-2587.2025.02.002

血浆置换联合抗B细胞治疗药物应用于造血干细胞移植DSA阳性患者中的效果观察^*

张媛媛¹, 王慧茹¹, 应美爱¹, 潘健¹, 刘磊¹, 刘会兰^1,2

¹中国科学技术大学附属第一医院（安徽省立医院）输血科;
²中国科学技术大学附属第一医院（安徽省立医院）血液内科,安徽合肥 230001

收稿日期:2024-08-29 出版日期:2025-04-20 发布日期:2025-04-17
通讯作者: 刘会兰,主要从事造血干细胞移植研究,（E-mail）huilanl@ustc.edu.cn。共同通信作者：刘磊,主要从事输血医学研究,（E-mail）360919918@qq.com。
作者简介:张媛媛,主要从事输血医学研究,（E-mail）zyuan224@126.com。
基金资助:
*本课题受科大新医学培育项目（No. YD9110002033）资助

Clinical Application of Plasma Exchange in Desensitization Therapy for DSA Positive Patients Undergoing Hematopoietic Stem Cell Transplantation

ZHANG Yuanyuan¹, WANG Huiru¹, YING Meiai¹, PAN Jian¹, LIU Lei¹, LIU Huilan^1,2

¹Department of Blood Transfusion, First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital);
²Department of Hematology, First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, Anhui 230001

Received:2024-08-29 Online:2025-04-20 Published:2025-04-17

摘要/Abstract

摘要： 目的观察血浆置换在造血干细胞移植供者特异性HLA抗体（DSA）阳性患者脱敏治疗中的临床应用效果。方法回顾分析2021年7月—2023年7月本院30例行血浆置换联合抗B细胞治疗方案脱敏的DSA阳性患者,观察血浆置换治疗前后DSA平均荧光强度值的变化对移植过程中细胞植入和移植后GVHD发生率的影响,分析血浆置换治疗过程中不良反应发生情况。结果 30名患者共行64次血浆置换,血浆置换治疗前后DSA平均荧光强度值为7 182.9±5 535.3 vs 2 311.8±2 835.9（P<0.001）。25/30例异基因造血干细胞移植（allo-HSCT）,其中非亲缘脐血移植（UCBT）19例,单倍体造血干细胞移植（haplo-HSCT）6例,23例患者（23/25,92%）实现了造血重建,中性粒细胞和血小板中位植入时间分别为14（9~60）天和31（10~64）天。两例患者植入失败行二次移植。5例患者未移植或数据删失。23例患者移植后30天内Ⅱ~Ⅳ aGVHD的累积发生率为41%。血浆置换过程中共发生24次轻度低钙和过敏不良反应,经处理后缓解,不影响执行。结论血浆置换联合抗B细胞治疗是造血干细胞移植DSA阳性患者脱敏治疗的有效方法,增加了HLA抗体阳性患者的移植机会。

关键词: 造血干细胞移植, 供者特异性HLA抗体, 血浆置换

Abstract: Objective To observe the clinical efficacy of plasma exchange in desensitization treatment of DSA (donor-specific antibody) positive patients undergoing hematopoietic stem cell transplantation (HSCT). Methods A retrospective analysis was carried out of 30 DSA positive patients desensitized with plasma exchange and combined with anti-B cell therapy in our hospital from July 2021 to July 2023. We primarily investigated the changes in the average fluorescence intensity of DSA before and after plasma exchange therapy, its impact on the incidence of cell implantation during transplantation and GVHD (graft-versus-host disease) after transplantation, and the adverse reactions during plasma exchange therapy. Results Totally 64 plasma exchanges were performed on 30 patients, with 24 mild adverse reactions including hypocalcemia and allergies. These reactions were relieved after treatment and did not didrupt the plasma exchange process. The average fluorescence intensity of DSA before and after plasma exchange was 7 182.9±5 535.3 and 2 311.8±2 835.9, respectively (P<0.001). Among the 30 patients, 25 underwent allo-HSCT (umbilical cord blood transplantation in 19 and Haplo HSCT in 6), with 23 (92%) achieving hematopoietic reconstruction. The median engraftment times were 14 (9~60) days for neutrophils and and 31 (10~64) days for platelets. Two patients underwent secondary transplantation due to failed engraftment. Five patients were not transplanted or their data was deleted. The cumulative incidence of Ⅱ~Ⅳ aGVHD within 30 days after transplantation in 23 patients was 41%. Conclusion Plasma exchange combined with anti B cell therapy is an effective desensitization therapy for DSA positive patients subjected to hematopoietic stem cell transplantation.

Key words: Hematopoietic stem cell transplantation, Donor-specific antibody, Plasma exchange

张媛媛, 王慧茹, 应美爱, 潘健, 刘磊, 刘会兰. 血浆置换联合抗B细胞治疗药物应用于造血干细胞移植DSA阳性患者中的效果观察^*[J]. 临床输血与检验, 2025, 27(2): 156-162.

ZHANG Yuanyuan, WANG Huiru, YING Meiai, PAN Jian, LIU Lei, LIU Huilan. Clinical Application of Plasma Exchange in Desensitization Therapy for DSA Positive Patients Undergoing Hematopoietic Stem Cell Transplantation[J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2025, 27(2): 156-162.

参考文献

[1] WIEDUWILT M J,METHENY L,ZHANG M J, et al.Haploidentical vs sibling,unrelated,or cord blood hematopoietic cell transplantation for acute lymphoblastic leukemia[J].Blood Adv,2022,6(1):339-357.
[2] NAGLER A,LABOPIN M,HOUHOU M,et al.Outcome of haploidentical versus matched sibling donors in hematopoietic stem cell transplantation for adult patients with acute lymphoblastic leukemia:a study from the acute leukemia working party of the European society for blood and marrow transplantation[J].J Hematol Oncol, 2021,14(1):53.
[3] XU Z L,XU L P,WU D P,et al.Comparable long-term outcomes between upfront haploidentical and identical sibling donor transplant in aplastic Anemia:a national registry-based study[J].Haematologica,2022, 107(12):2918-2927.
[4] TAKANASHI M,ATSUTA Y,FUJIWARA K,et al.The impact of anti-HLA antibodies on unrelated cord blood transplantations[J].Blood,2010,116(15):2839-2846.
[5] GLADSTONE D E,BETTINOTTI M P.HLA donor-specific antibodies in allogeneic hematopoietic stem cell transplantation:challenges and opportunities[J].Hematology Am Soc Hematol Educ Program,2017, 2017(1):645-650.
[6] XIE Y Y,PAREKH J,TANG Z X,et al.Donor-specific antibodies and primary graft failure in allogeneic hematopoietic stem cell transplantation:a systematic review and meta-analysis[J].Transplant Cell Ther,2021, 27(8):687.e1-687687.e7.
[7] HUANG Y R,LUO C X,WU G X,et al.Effects of donor-specific antibodies on engraftment and long-term survival after allogeneic hematopoietic stem cell transplantation-a systematic review and meta-analysis[J].Bone Marrow Transplant, 2023,58(5):544-551.
[8] SPELLMAN S,BRAY R,ROSEN-BRONSON S, et al.The detection of donor-directed,HLA-specific alloantibodies in recipients of unrelated hematopoietic cell transplantation is predictive of graft failure[J].Blood, 2010,115(13):2704-2708.
[9] CIUREA S O,CAO K,FERNANDEZ-VINA M, et al.The European society for blood and marrow transplantation(EBMT)consensus guidelines for the detection and treatment of donor-specific anti-HLA antibodies(DSA)in haploidentical hematopoietic cell transplantation[J]. Bone Marrow Transplant,2018, 53(5):521-534.
[10] 王志东,孙于谦,闫晨华,等.单倍型相合造血干细胞移植前血液病患者体内供者特异性抗人类白细胞抗原抗体水平对利妥昔单抗去敏治疗后造血重建不良的影响分析[J].中华内科杂志,2021,60(7):644-649.
[11] 杨昊,董树岭,杨乾坤,等.双重滤过血浆置换和血浆置换对ABO血型不容肾移植受者术前血型抗体去除效果单中心对比研究*[J].临床输血与检验,2024,26(3):325-331.
[12] 胡艳,朱帮强,闻慧琴,等.淋巴血浆置换术在ABO血型不相容亲属活体肾移植中的应用[J]. 临床输血与检验,2021,23(5):608-611.
[13] 张媛媛,应美爱,潘健,等.血浆置换在ABO血型不相容的亲属活体肾移植中应用效果评价*[J].临床输血与检验,2021,23(2):167-172.
[14] 常英军,赵翔宇.供者特异性HLA抗体在配型不合Allo-SCT植入失败中的作用: 现状与挑战[J].现代免疫学, 2020,40(2):89-92.
[15] KONGTIM P,CAO K,CIUREA S O.Donor specific anti-HLA antibody and risk of graft failure in haploidentical stem cell transplantation[J].Adv Hematol,2016,2016: 4025073.
[16] CIUREA S O,THALL P F,MILTON D R,et al.Complement-binding donor-specific anti-HLA antibodies and risk of primary graft failure in hematopoietic stem cell transplantation[J].Biol Blood Marrow Transplant, 2015,21(8):1392-1398.
[17] CHANG Y J,ZHAO X Y,XU L P,et al.Donor-specific anti-human leukocyte antigen antibodies were associated with primary graft failure after unmanipulated haploidentical blood and marrow transplantation:a prospective study with randomly assigned training and validation sets[J].J Hematol Oncol,2015,8:84.
[18] VO A A,LUKOVSKY M,TOYODA M,et al.Rituximab and intravenous immune globulin for desensitization during renal transplantation[J].N Engl J Med,2008, 359(3): 242-251.
[19] PHILOGENE M C,SIKORSKI P,MONTGOMERY R A, et al.Differential effect of bortezomib on HLA classⅠ and classⅡ antibody[J].Transplantation,2014,98(6):660-665.
[20] CHOE H,GERGIS U,HSU J,et al.Bortezomib and immune globulin have limited effects on donor-specific HLA antibodies in haploidentical cord blood stem cell transplantation:detrimental effect of persistent haploidentical donor-specific HLA antibodies[J].Biol Blood Marrow Transplant,2019,25(2):e60-e64.
[21] LIU L Z,JI X Y,ZHU P P,et al.Double filtration plasmapheresis combined with rituximab for donor-specific antibody desensitization in haploidentical haematopoietic stem cell transplantation[J].Br J Haematol, 2023,203(5):829-839.
[22] 王增胜,聂玉玲,郎涛,等.双重膜滤过式血浆置换联合脱敏治疗单倍体相合造血干细胞移植供者特异性抗体的临床研究[J].中国血液净化,2024,23(1):22-25.
[23] PEREIRA J,CRETNEY C,ASTER R H.Variation of classⅠ HLA antigen expression among platelet density cohorts:a possible index of platelet age?[J].Blood,1988,71(2):516-519.
[24] ZHANG R L,HE Y,YANG D L,et al.Combination treatment of rituximab and donor platelets infusion to reduce donor-specific anti-HLA antibodies for stem cells engraftment in haploidentical transplantation[J].J Clin Lab Anal,2020,34(7):e23261.
[25] CIUREA S O,AL MALKI M M,KONGTIM P,et al. Treatment of allosensitized patients receiving allogeneic transplantation[J].Blood Adv,2021,5(20):4031-4043.

血浆置换联合抗B细胞治疗药物应用于造血干细胞移植DSA阳性患者中的效果观察^*

Clinical Application of Plasma Exchange in Desensitization Therapy for DSA Positive Patients Undergoing Hematopoietic Stem Cell Transplantation

RichHTML

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

关于本刊

作者中心

在线期刊

访问统计

联系我们

[1]	付丽辉, 马春娅, 罗圆圆, 沈伟, 向东, 于洋. 一例意外抗体阳性患者造血干细胞移植后抗体监测结果分析[J]. 临床输血与检验, 2025, 27(2): 169-174.
[2]	徐慧, 张全诚, 许倩文, 薛磊, 王兴兵. 贝林妥欧单抗与CD19 CAR-T细胞治疗急性B淋巴细胞白血病的安全性和短期疗效比较分析^*[J]. 临床输血与检验, 2025, 27(2): 224-233.
[3]	庄远, 于洋. 输血（医学）科基于离心分离技术建立单采/血液净化治疗体系的探索[J]. 临床输血与检验, 2024, 26(6): 721-725.
[4]	明静, 丁凯阳, 胡茂贵, 王馨辰. 阿伐曲泊帕联合rhTPO在恶性血液病自体造血干细胞移植中的临床疗效分析^*[J]. 临床输血与检验, 2024, 26(6): 812-817.
[5]	杨昊, 董树岭, 杨乾坤, 韩月, 王书亚, 靳慧芳, 郑露, 唐悦. 双重滤过血浆置换和血浆置换对ABO血型不容肾移植受者术前血型抗体去除效果单中心对比研究^*[J]. 临床输血与检验, 2024, 26(3): 325-331.
[6]	李佩华, 苏焕正, 沙夏珺, 罗文英. 慢加急性肝衰竭血浆置换治疗期间死亡的危险因素探讨：基于PSM法[J]. 临床输血与检验, 2024, 26(3): 345-352.
[7]	童欣欣, 钟明璐, 黄慧瑛, 邓晖, 黄建云, 魏亚明. 血液病患者异基因造血干细胞移植后Rh血型转变研究^*[J]. 临床输血与检验, 2024, 26(2): 230-235.
[8]	异基因造血干细胞移植临床输血专家共识起草专家组. 异基因造血干细胞移植临床输血专家共识[J]. 临床输血与检验, 2023, 25(5): 586-593.
[9]	卓海龙, 邵春燕, 骆群. 体外模拟A型/O型不同比例混合红细胞对血型抗原鉴定的影响^*[J]. 临床输血与检验, 2023, 25(4): 475-479.
[10]	孙秋爽, 梁卉. 行异基因造血干细胞移植治疗的伴严重血小板减少的儿童MYH9相关疾病1例并文献复习[J]. 临床输血与检验, 2023, 25(4): 544-548.
[11]	徐丽娟, 秦京京, 谭亦超, 骆群. 血浆置换联合血液灌流救治重度汞中毒1例[J]. 临床输血与检验, 2023, 25(4): 552-554.
[12]	樊凤艳, 马越云. RhD血型不匹配异基因造血干细胞移植输血RhD血型选择[J]. 临床输血与检验, 2023, 25(2): 189-192.
[13]	朱灿, 陈立, 杨振兴, 张根玲, 苗莹莹, 李忠俊. 思维导图在外周血造血干细胞供者单采术前宣教中的应用探讨^*[J]. 临床输血与检验, 2022, 24(6): 803-806.
[14]	刘奇, 张彬. 血浆置换在自身免疫性疾病肾脏损伤中的治疗作用[J]. 临床输血与检验, 2022, 24(2): 264-267.
[15]	葛东梅, 张少强, 杨元铭, 刘姣, 鞠强, 王海燕. TPE联合药物治疗低体重儿童慢性难治性自身免疫性溶血性贫血1例[J]. 临床输血与检验, 2022, 24(1): 46-48.