ABO血型不合异基因造血干细胞移植后并发纯红系再生障碍

为了研究ABO血型不合异基因造血干细胞移植（allo—HSCT）后并发纯红细胞再生障碍（pure red cell aplasia，PRCA）的发病情况及危险因素，对本医院以往血型不合异基因造血干细胞移植进行回顾性分析。探讨移植后患者PRCA的发病危险因素。研究结果表明，72例ABO血型不合allo—HSCT患者中，4例发生PRCA，其中A供O3例，A供B1例。PRCA的发生不影响急性移植物抗宿主病（GVHD）或巨细胞病毒（CMV）感染的发生。PRCA患者红系恢复的时间显著长于未PRCA发生患者。结论：PRCA是ABO血型不合移植的主要并发症。A供O可能是ABO血型不合allo—HSCT后并发PRCA的危险因素。     

主要ABO血型不合异基因造血干细胞移植后纯红细胞再生障碍

20例主要ABO血型不合异基因造血干细胞移植（allo-HSCT)患中，6例发生纯红细胞再生障碍（PRCA）。PRCA对中性粒细胞和血小板植入以及Ⅱ-Ⅳ度aGVHD并无影响。6例PRCA患血型均为O型，而供血型5例为A型，1例B型，提示供／受血型A／O是主要ABO血型不合allo-HSCT后PRCA发生的高危因素。4例除给予RBC输注无其它特殊治疗，随着凝集素滴度降至＜8，红系造血自然恢复，而另2例尽管给予重组人红细胞生成素（rhEPO）治疗红系再障仍持续＞300天，经供型血浆置换而红系恢复造血。在本组病例，环孢菌素在PRCA发生中并无作用，而GVHD发生则可促进红系造血恢复。     

ABO血型不合的同胞异基因外周血干细胞移植

目的探讨HLA配型相合、ABO血型不合的同胞异基因外周血干细胞移植(alloPBSCT)的疗效。方法对27名HLA配型相合、ABO血型不合的血液恶性肿瘤患者作同胞alloPBSCT(实验组,供、受者ABO血型主侧不合的有15例,次侧不合的有10例,主次侧均不合的有2例),其中急性髓细胞白血病(AML)6例、急性淋巴细胞白血病(ALL)8例、慢性粒细胞性白血病(CMLLP)10例、骨髓增生异常综合征(MDSRAEBT)2例、非霍奇金氏淋巴瘤(ⅣB)1例;并选用同期的35名ABO血型相合的移植患者作比较(对照组)。移植物抗宿主病(GVHD)的预防采用霉酚酸酯(MMF)、环孢菌素A(CSA)和短程甲氨喋呤(MTX)三联预防方案。结果62例全部造血重建。实验组:27名alloPBSCT患者均未出现急性溶血反应,主侧不合者红系造血明显延迟,供/受者血型为A/O的患者中有3例(3/7)发生纯红细胞再生障碍性贫血(PRCA),27名患者于移植后25～153d血型成功转变为供者型;实验组GVHD发生率、VOD发生率、CMV感染、HC发生率及疾病复发率、死亡率与对照组相比差异无统计学意义(P>0.05)。结论ABO血型不合可以进行alloPBSCT,并且不影响干细胞移植的植活、GVHD及其它移植相关并发症的发生和预后。供/受者血型为A/O是主侧ABO血型不合患者alloPBSCT后PRCA发生的高危因素。     

ABO血型不合异基因造血干细胞移植对红系造血恢复的影响

本研究探讨ABO血型不合异基因造血干细胞移植对红系造血的影响。对16例ABO血型不合的造血干移植患者的ABO血型,IgM和IgG抗体进行监测。结果显示,16例ABO血型不合的造血干细胞移植患者均恢复造血功能,与ABO血型相合组比较,ABO血型不合组在粒细胞植活时间、血小板植活时间无差异,但红系重建时间明显延长;ABO主侧不合与双侧不合受者抗供者凝集素消失时间与红系恢复时间有相关性。结论 :ABO血型不合的异基因造血干细胞移植会导致红系造血迟缓。移植前用供型血浆置换法或输注供者红细胞来中和受者体内抗供者红细胞的凝集素能缩短红细胞植入时间,减少红细胞的输注。     

ABO血型不合造血干细胞移植后血清EPO水平动态检测及其意义

为了评价红细胞生成素 (EPO)在异基因造血干细胞移植后的动态变化及其意义 ,应用ELISA方法测定ABO血型不合患者移植后EPO水平的动态变化。结果表明 :血清EPO水平在 0天和 2周时最高 ,分别为 2 33 73± 81.95mU ml和 2 2 6 .0 7± 113.87mU ml(P >0 .0 5 ) ,以后血清EPO水平显著下降 ,4周时为 12 8.4 9± 10 8.92mU ml(P <0 .0 5 ) ,血型转变后降至 73.0 7± 6 8.85mU ml(P <0 .0 5 )。血清EPO水平始终与红细胞输注量呈显著正相关 (P <0 .0 5 )。血清EPO水平与急性GVHD发生无显著相关性 (P >0 .0 5 )。移植后 0天和第 4周血清EPO水平与Hb水平呈负相关 (P <0 .0 5 ) ;移植后第 6周、8周血清EPO水平与Hb水平无显著相关性 ,与红系恢复时间呈显著正相关 (P <0 .0 5 ) ,与抗a凝集素滴度呈显著正相关 (P <0 .0 5 )。结论 :ABO血型不合移植后受者体内EPO水平持续性升高 ,提示外源性EPO治疗移植后贫血的疗效可能不佳     

母婴ABO血型不合新生儿溶血病与孕妇IgG抗体效价分析

目的探讨母婴ABO血型不合引起新生儿溶血病（HDN）的发病与孕妇免疫球蛋白G（IgG）抗体效价的关系，以及与新生儿出生后天数的关系，为临床提供HDN的诊断和防治依据。方法新生儿ABO血型及Rh血型、直接抗人球蛋白试验、抗体释放试验、游离抗体试验；夫妻ABO血型、Rh血型鉴定；母亲产前IgG抗A（B）抗体效价试验。结果499例不同程度黄疸怀疑HDN通过上述指标检测得以证实者284例（56．9％），其母亲产前IgG抗A（B）抗体效价大于或等于64者256例（90．1％），ABO血型不合HDN的发病率随IgG抗A（B）抗体效价升高而上升。出生后0～2d发病比例最高。结论HDN的发生率与抗体效价呈正比，出生后0～2d发病率最高。孕妇IgG抗A（B）抗体效价大于或等于64需服用药物并定期复查，以预防HDN的发生。     

ABO血型不合的异基因造血干细胞采集及移植效果研究

本研究评价COBE Spectra血细胞分离机按干细胞采集程序采集HLA配型相合、ABO血型不合供者外周血造血干细胞的效能,观察未去除红细胞和(或)血浆进行异基因外周血干细胞移植的效果。应用COBE Spectra血细胞分离机的自动干细胞采集程序采集28例异基因供者外周血干细胞,并选用同期ABO血型相合15例作对照。检测采集物有核细胞(NC)数、单个核细胞(MNC)比例及CD34+细胞计数,观察造血功能重建情况和转变为供者血型所需要的时间。结果表明,ABO血型不合和相合组采集物中的NC、CD34+细胞数、MNC比例无统计学差异(p>0.05)。ABO血型不合组和相合组中性粒细胞和血小板恢复的时间无统计学差异(p>0.05)。14例ABO血型主要不合患者,红系造血明显延迟,ABO血型不合组28名患者于移植后35-193天血型成功转变为供者型,和ABO血型相合组相比均有统计学差异(p<0.01)。结论:ABO血型不合不是异基因造血干细胞移植的障碍,主要不合可能是红系造血明显延迟的主要原因。     

ABO血型不合的异基因造血干细胞移植后红系恢复多因素分析

本研究目的是探讨ABO血型不合的异基因造血干细胞移植后影响红系恢复时间的多种因素。应用Cox回归模型对157例ABo血型不合的allo-HSCT患者的性别、年龄、移植方式、HLA相合／HLA不合、预处理方案、GVHD预防、Ⅰ-Ⅳ度GVHD发生、CMV感染及血型不合的类型进行多因素综合分析。结果表明：经Cox回归多因素综合分析，次要血型不合、输注的有核细胞数、年龄和非血缘关系的骨髓移植，为影响红系恢复时间的4个主要因素。结论：次要血型不合及输注细胞数多的患者红系恢复较快，而年龄大和非血缘骨髓移植的患者红系恢复慢。     

血型不合的异基因造血干细胞移植治疗恶性血液病

目的探讨ABO血型不合异基因造血干细胞移植的疗效及并发症。方法回顾性分析14例ABO血型不合异基因造血干细胞移植患者的红系恢复情况，以评价血型不合、HLA是否相合等对红系恢复、造血重建、并发症等的影响。结果14洌ABO血型不合患者仅1例发生纯红细胞性再生障碍性贫血（简称：纯红再障），13例ABO血型不合的患者（1例发生纯红再障未计算在内）与同期进行11例ABO血型相同的异基因造血干细胞移植患者比较，血红蛋白恢复在血型不合组明显延迟，中性粒细胞和血小板恢复两组无差异；在血红蛋白恢复和血型转换的时间上血型不合的半相合造血干细胞组明显要迟于全相合，但其差异无统计学意义。结论ABO血型不合不影响造血干细胞移植的植活、相关合并症及预后。     

ABO血型不合的异基因造血干细胞移植治疗恶性血液病

目的探讨ABO血型不合异基因造血干细胞移植的疗效及并发症。方法回顾性分析14例ABO血型不合异基因造血干细胞移植患者的红系恢复情况，以评价血型不合、HLA是否相合等对红系恢复、造血重建、并发症等的影响。结果14例ABO血型不合患者仅1例发生纯红再障。13例ABO血型不合的患者（1例发生纯红再障未计算在内）与同期进行11例ABO血型相同的异基因造血干细胞移植患者比较，血红蛋白恢复在血型不合组明显延迟，中性粒细胞和血小板恢复两组无差异。此外，在血红蛋白恢复和血型转换的时间上血型不合的半相合造血干细胞组明显要迟于全相合，但其差异无统计学意义。结论ABO血型不合不影响造血干细胞移植的植活、相关合并症及预后。     

ABO血型不合的异基因骨髓移植

目的 探讨ＨＬＡ 相合,ＡＢＯ 血型不合的异基因骨髓移植（ａｌｌｏＢＭＴ） 中存在的免疫及造血问题。方法 对本所３８ 例ＡＢＯ 血型主要不合,２３ 例次要不合的ＨＬＡ 相合的ａｌｌｏＢＭＴ 受者进行分析,并选用同期ＡＢＯ 血型相合的ａｌｌｏＢＭＴ 患者作配对比较。结果ＡＢＯ 血型不合的ａｌｌｏＢＭＴ患者,输注骨髓后无一例发生急性溶血。经配对ｔ 检验及χ２ 检验,ＡＢＯ 血型不合对骨髓植活、血小板恢复,ＧＶＨＤ 及５ 年无病生存率均无影响; 在ＡＢＯ 血型主要不合组, 红系开始恢复时间明显延迟,使红细胞输用量明显增多;其中５ 例患者发生纯红细胞再生障碍（ 纯红再障） ,持续约７ ～２４ 个月。发生纯红再障者均为“Ｏ”型血受者,红系恢复与血型抗体滴度具有相关性。结论ＡＢＯ 血型不合可以进行ａｌｌｏＢＭＴ,但对发生纯红再障高危的患者宜慎重。     

ABO血型对异基因造血干细胞移植患者植入的影响探讨

目的探讨ABO同型及3种ABO血型不合对异基因造血干细胞移植患者各系植入的影响,为患者优化移植方案提供依据。方法回顾性分析本院2014年1月~2018年6月期间进行异基因造血干细胞移植患者70例,ABO同型18例,ABO血型不合52例,在确保对比组患者年龄;性别;供/受者亲缘关系;疾病诊断;移植前骨髓造血功能状况;HLA相合情况无差异的情况下,对比分析患者粒系、红系、巨核系植入时间,移植后3个月内红细胞及血小板输注量,ABO血型不合的血型开始转化时间、转化完成时间等指标。研究以上指标在ABO同型及3种ABO血型不合移植中有无差异。结果 70例患者中,ABO同型18例,粒系植入时间12.0(11.0~16.3)d,红系植入时间41.5(35.0~49.0)d,巨核系植入时间19.0(16.0~22.5)d。ABO血型不合52例,移植后血型开始转化时间28.0(22.5~44.0)d,转化完成时间105.5(85.0~141.8)d,粒系植入时间14.5(12.0~16.0)d,红系植入时间61.0(39.5~85.0)d,巨核系植入时间23.0(18.0~31.0)d。ABO同型相较ABO血型不合(主要/主次要双向不合)异基因造血干细胞移植红系植入时间缩短(P<0.05),红细胞及血小板输注量减少(P<0.05),粒系、巨核系植入时间无显著性差异(P>0.05)。ABO血型主要不相合、次要不相合、主次要双向不合异基因造血干细胞移植中的血型转化时间,粒系、红系、巨核系植入时间,红细胞、血小板输注量均无差异(P>0.05)。结论异基因造血干细胞移植优先选择ABO同型供者,在缺乏同型供者情况下,优先选择次要不相合,其次主要不相合、主次要双向不合供者。     

Anti-A and/or anti-B is not detectable in some patients who underwent ABO-incompatible bone marrow transplantation

BACKGROUND: Recently, anti-A and/or anti-B produced by B cells from donor marrow could not be detected for more than 20 weeks in some patients who had undergone ABO-incompatible bone marrow transplantation (BMT). STUDY DESIGN AND METHODS: Twelve to 72 weeks after 11 patients underwent ABO-incompatible BMT, titers of anti-A and anti-B were assayed, A and B antigens were identified by routine methods and flow cytometry, direct and indirect antiglobulin tests were performed, and the red cell antibody was eluted. RESULTS: In some patients who underwent ABO-incompatible BMT, anti-A and/or anti-B produced by the B cells from the donor marrow could not be detected after BMT when red cells taken from the patients before BMT carried the corresponding antigen–that is, when hematopoiesis had already changed the cells to the donor's type according to ABO blood typing. Furthermore, some blood samples from those patients gave positive results in direct antiglobulin tests. Blood typing of patients after BMT showed mixed- field agglutination. In one patient, the half-life of red cells assayed with 51Cr was 22.4 days (30.0 +/− 4.0 days for normal controls). CONCLUSION: Although many hypotheses could be considered to explain the present data, the possibility is proposed that anti-A and/or anti-B in the sera must have been consumed in some patients who underwent ABO- incompatible BMT. This may lead to problems such as difficulty of ABO typing, positive direct antiglobulin tests, and a relatively short life span of red cells.     

Impact of ABO incompatibility on allogeneic peripheral blood progenitor cell transplantation after reduced intensity conditioning

BACKGROUND: Most studies indicate that ABO incompatibility has no effect on the clinical outcome after allogeneic peripheral blood progenitor cell (PBPC) transplantation (allo-PBPCT). However, it carries additional risks of hemolytic reactions, delayed red blood cell (RBC) engraftment, and pure red cell aplasia (PRCA). Data on these events after reduced intensity conditioning (RIC) regimens are limited, but recent studies have suggested a higher transplant-related mortality (TRM) and morbidity in this setting. STUDY DESIGN AND METHODS: We investigated the impact of ABO-matching on the outcome of 77 patients included in a prospective RIC allo-PBPCT protocol, focusing on engraftment, transfusion requirements, graft-versus-host disease, TRM, and survival. RESULTS: There were 17 (22%) minor and 8 (10%) major ABO-incompatible transplants. No graft failures were observed. After major ABO-incompatible grafts, RBC engraftment was delayed, longer thrombocytopenia periods were documented, and transfusion requirements increased. A transient mild hemolysis occurred in 10 patients, 7 (41%) minor and 3 (37%) major ABO-mismatched. A PRCA was observed in a O+ patient with a pretransplant anti-Jka, grafted from an A + Jka+ donor. Graft-versus-host disease, disease progression, and TRM were not affected by ABO matching. CONCLUSION: ABO incompatibility was not associated with clinically relevant hemolysis after the RIC protocol used and did not impair the clinical outcome. PRCA was only observed in one patient, with a non-ABO RBC allo-antibody.     

ABO血型不合的非清髓异基因外周血干细胞移植

为了探讨ABO血型不合对HLA相合的非清髓异基因外周血干细胞移植(NAST)的影响,回顾分析了15例ABO血型主要不舍,9例次要不合的HLA相合的NAST的临床特点,并选用同期ABO血型相合的NAST作成组比较。结果显示：24例ABO血型不合的NAST受者在输入供者外周血千细胞悬液时无1例发生急性溶血,但有2例发生迟发性溶血。统计学分析表明,ABO血型不合对NAST骨髓植活、血小板恢复、GVHD、疾病复发及无病生存均无影响。在ABO血型主要不合组,红系开始恢复时间明显延迟,其中1例“0”型血受者发生纯红细胞再生障碍,持续5个月。结论：ABO血型不合不是NAST的障碍,仅在ABO血型主要不合时．红系恢复时间延迟。     

Nondeletional ABO*O alleles frequently cause blood donor typing problems

BACKGROUND: Difficulties in the demonstration of expected isoagglutinins is a common problem in ABO reverse typing. Some nondeletional ABO*O alleles have been shown to encode for the expression of minimal amounts of A antigen, resulting in very weak anti-A activity in some cases. It is unknown whether minor problems with ABO reverse typing are related to specific ABO*O alleles. STUDY DESIGN AND METHODS: Among 2196 blood group O red cell (RBC) donations, the ABO alleles of those donations in which the isoagglutinins were incorrectly identified were analyzed with an autoanalyzer. The presence of nondeletional ABO alleles was determined by sequence-specific priming and sequencing. RESULTS: Fifty (2.3%) of the group O RBC donations tested had to be typed manually because of isoagglutinin detection problems in automated typing: reduced anti-A activity was observed in 45 cases, reduced anti-B activity in 4 cases, and variably reduced isoagglutinin activity in 1 case. The nondeletional ABO*O alleles ABO*O03 and ABO*Aw08 were implicated in 38 of these 50 cases (1.7% of all blood group O donors). The remaining samples, including those with reduced anti-B activities, were homozygous for deletional ABO*O alleles. CONCLUSION: Nondeletional ABO*O alleles are the most frequent cause of isoagglutinin detection problems in blood group O donors.     

通用O型全血的初步研究

目的探讨冰冻干燥红细胞膜的制备技术及通用O型去除血型抗体全血的可行性。方法将A型及B型红细胞膜经过冰冻干燥处理后，加入O型全血中，经反应后测定血浆中血型抗体效价，并检测红细胞结构及功能，检测血浆中凝血因子活性变化。结果经过冰冻干燥处理后，红细胞膜仍具有抗原性，可有效降低血浆中的血型抗体效价，而全血中红细胞的变形指数、ATP含量与反应前差异无显著性，反应前后均在正常参考范围内；全血血浆中各种凝血因子活性在吸附前后比较，差异无显著性。结论尽管红细胞膜在体内是否产生大量抗体及其清除过程等尚需进行动物实验确定，但使用冰冻干燥红细胞膜制备通用型血液过程简便易行，具有进一步的研究价值。     

After major ABO-mismatched allogeneic hematopoietic progenitor cell transplantation, erythroid engraftment occurs later in patients with donor blood group A than donor blood group B

BACKGROUND: Isohemagglutinins directed against the donor blood group frequently delay erythroid engraftment after major ABO-mismatched allogeneic hematopoietic progenitor cell transplantation (HPCT). Graft-versus-host reactions are capable of accelerating the clearance of isohemagglutinins. Whether immunogenicity of the A- and B-antigen is important in this process is unknown. PATIENTS AND METHODS: Data of 807 patients from three centers were screened for patients with major or bidirectionally ABO-mismatched donors. Clinical data and red blood cell (RBC) transfusion support were analyzed retrospectively. RESULTS: A total of 158 patients with major or bidirectionally mismatched donors were identified. After major mismatched HPCT, patients with anti-A directed against the donor blood group required RBC transfusion support for a median of 109 days (range, 0-324 days) compared to 21 days (range, 2-98 days) for patients with anti-B directed against donor blood group (log-rank test, p = 0.0001). Other risk factors associated with prolonged RBC transfusion support in univariate analysis were age (p = 0.024), cytomegalovirus infection (p = 0.016), hemolytic anemia (p = 0.027), and chronic bleeding disorders (p = 0.038). The independent influence of donor blood group and recipient age were confirmed in a multivariate analysis. CONCLUSION: These results indicate that the immunogenicity of the ABO antigen plays an important role for the kinetics of erythroid engraftment after ABO-mismatched HPCT.