摘要
目的探讨三联脱敏疗法对供者特异性抗体(DSA)阳性急性白血病(AL)患者单倍体造血干细胞移植(haplo-HSCT)疗效及安全性的影响。方法选择2022年1月1日至2023年11月30日于上海交通大学医学院附属瑞金医院接受haplo-HSCT的53例AL患者为研究对象。其中位年龄为38.0岁(28.5,47.0岁);男性患者为31例,女性为22例;急性淋巴细胞白血病(ALL)和急性髓细胞白血病(AML)患者分别为43和10例。根据患者接受清髓性预处理(MAC)前的DSA平均荧光强度(MFI)值,将这53例患者分为DSA阳性组(n=14,MFI值≥500)和DSA阴性组(n=39,MFI值<500)。于围MAC期,对DSA阳性组患者采取双重过滤血浆置换(PE)、CD20单克隆抗体(mAb)、静脉注射免疫球蛋白(IVIG)的三联脱敏疗法清除DSA。采用回顾性研究方法收集患者的临床资料,包括临床基线特征,移植前、后外周血DSA水平,移植后造血重建时间,移植物嵌合率、急性移植物抗宿主病(aGVHD),移植后100 d内EB病毒(EBV)及巨细胞病毒(CMV)感染率等。分析比较2组患者的移植疗效及不良反应发生情况。2组患者计数资料的比较,采用χ^(2)检验或Fisher确切概率法;呈偏态分布定量资料比较,采用Wilcoxon秩和检验。本研究遵循的程序符合2013年修订版《世界医学协会赫尔辛基宣言》要求,与所有患者签署临床研究知情同意书。结果①本研究DSA阳性组女性占比高于DSA阴性组,并且差异有统计学意义(11/14比11/39;χ^(2)=10.76,P=0.001)。2组患者的年龄、AL疾病种类构成比、诊断到移植时间、单个核细胞输注量、CD34^(+)细胞输注量分别比较,差异均无统计学意义(均为P>0.05)。②DSA阳性组14例患者脱敏治疗前的DSA MFI中位值为9758(2903,10923),高于脱敏治疗后的2628(425,4771),并且差异有统计学意义(Z=-3.16,P=0.002)。③本研究53例患者均获得粒细胞及血小板,均成功植入,疗效均为完全缓解(CR),微小残留病(MRD)均呈阴性。DSA阳性组与阴性组患者的中性粒细胞植入时间、血小板植入时间、移植后第28天移植物嵌合率分别比较,差异均无统计学意义(均为P>0.05)。④本研究DSA阳性组与DSA阴性组AL患者,移植后100 d内EBV感染率(1/14比1/39)、CMV感染率(5/14比7/39)、aGVHD发生率(3/14比13/39)分别比较,差异均无统计学意义(均为P>0.05)。结论对接受haplo-HSCT的DSA阳性AL患者,采取双重过滤PE、CD20 mAb、IVIG的三联脱敏策略,可有效降低其DSA水平,使患者获得良好的近期移植效果,并且安全性良好。
Objective To investigate the impact of triple desensitization therapy on the efficacy and safety in patients with acute leukemia(AL)with donor-specific antibody(DSA)-positive undergoing haploidentical hematopoietic stem cell transplantation(haplo-HSCT).Methods From January 1,2022 to November 30,2023,a total of 53 patients with AL who underwent haplo-HSCT at Ruijin Hospital,Shanghai Jiao Tong University School of Medicine were selected as research subjects.These patients′median age was 38.0 years(28.5,47.0 years).The patients included 31 males,22 females,43 with acute lymphoblastic leukemia(ALL),and 10 with acute lymphoblastic leukemia(AML).According to the mean fluorescence intensity(MFI)value of DSA before myeloablative conditioning(MAC),the 53 patients were divided into DSA-positive group(n=14,MFI value≥500)and DSA-negative group(n=39,MFI value<500).During the peri-MAC period,triple desensitization therapy consisting of dual-filter plasma exchange(PE),CD20 monoclonal antibodies(mAb),and intravenous immunoglobulin(IVIG)was administered to the patients in DSA-positive group to reduce DSA levels.A retrospective study was conducted to collect clinical data,including baseline characteristics,peripheral blood DSA level of patients before and after haplo-HSCT,hematopoietic reconstruction time,graft chimerism rate,incidence of acute graft-versus-host disease(aGVHD),infection rate of Epstein-Barr virus(EBV)and cytomegalovirus(CMV)within 100 d after transplantation.The transplantation efficacy and adverse reactions of the two groups were analyzed and compared.Chi-square test or Fisher exact probability test was used for categorical data comparisons,while Wilcoxon rank-sum test was applied for skewed distribution measurement data.This study was in line with World Medical Association Declaration of Helsinki revised in 2013 and informed contents for clinical research were obtained from the subjects.Results In this study,the proportion of females in the DSA-positive group was higher than that of DSA-negative group,and the difference was statistically significant(11/14 vs 11/39;χ^(2)=10.76,P=0.001).There were no statistically significant differences in the age,AL disease type composition ratio,time from diagnosis to transplantation,mononuclear cell infusion volume,and CD34^(+)cell infusion volume between the two groups(all P>0.05).②In the DSA-positive group,the median value of DSA MFI before desensitization treatment was 9758(2903,10923),which was higher than that of 2628(425,4771)after desensitization treatment,and the difference was statistically significant(Z=-3.16,P=0.002).③All 53 patients in this study achieved successful engraftment of granulocytes and platelets,with complete remission(CR)and negative minimal residual disease(MRD).There were no significant differences in the neutrophil engraftment time,platelet engraftment time,and graft chimerism rate on 28 d after transplantation between the DSA-positive and DSA-negative groups(all P>0.05).④In this study,the EBV infection rate(1/14 vs 1/39),CMV infection rate(5/14 vs 7/39),and aGVHD incidence rate(3/14 vs 13/39)within 100 d after transplantation between the DSA-positive and DSA-negative groups of AL patients were compared respectively,and there were no significant differences(all P>0.05).Conclusions For DSA-positive AL patients receiving haplo-HSCT,a triple desensitization strategy of double-filtered PE,CD20 mAb,and IVIG could effectively reduce their DSA levels,enabling patients to obtain good short-term transplant outcomes with good safety.
作者
程丽华
金诗炜
潘萌萌
糜坚青
章卫平
许捷
Cheng Lihua;Jin Shiwei;Pan Mengmeng;Mi Jianqing;Zhang Weiping;Xu Jie(Department of Hematology,People′s Hospital of Deyang City,Deyang 618000,Sichuan Province,China;Department of Hematology,Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China)
出处
《国际输血及血液学杂志》
2025年第2期134-141,共8页
International Journal of Blood Transfusion and Hematology
基金
国家自然科学基金项目(82370201)
关键词
造血干细胞移植
白血病
髓样
急性
脱敏法
免疫
血浆置换
抗体
单克隆
抗体
供者特异性
单倍体造血干细胞移植
Hematopoietic stem cell transplantation
Leukemia,myeloid,acute
Desensitization,immunologic
Plasma exchange
Antibodies,monoclonal
Antibodies,donor-specific
Haploidentical hematopoietic stem cell transplantation
