异基因干细胞移植ABO血型主侧不合的造血干细胞分离及其应用

在ＨＬＡ相合的异基因造血干细胞移植中，供、受者ＡＢＯ血型不合的发生率为１０％～１５％［１］。将供者异型红细胞含量控制在一定水平，避免受者输注ＡＢＯ血型主侧不合的骨髓或外周血发生输血反应及溶血，是ＡＢＯ血型不合异体干细胞移植中一个非常重要的环节。用单个...     

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。     

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血型主要不合的异基因外周血干细胞移植后纯红细胞再生障碍

报告 5例异基因外周血干细胞移植 (ａｌｌｏ ＰＢＳＣＴ)后纯红细胞再生障碍 (ＰＲＣＡ) ,并对临床特点 ,发病机制及治疗方法作一探讨。病例和方法1　病例　 1997年 6月～ 1999年 5月 ,我院施行ＨＬＡ相合的ａｌｌｏ ＰＢＳＣＴ 40例中 ,ＡＢＯ血型相合 2 0例 ,男 11例 ,女 9例 ,年龄 2 4～ 45岁 ,急性髓系白血病 (ＡＭＬ) 9例 ,慢性髓系白血病(ＣＭＬ) 7例 ,急性淋巴细胞白血病 (ＡＬＬ) 4例 ;ＡＢＯ血型主要不合 12例 (含主次不合 ) ,男 8例 ,女 4例 ,年龄 2 3～ 46岁 ,ＡＭＬ 3例 ,ＣＭＬ 9例 ;ＡＢＯ血型次要不合 8例 ,男 5例 ,女 3例 ,…     

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血型不合异基因外周血干细胞移植对红系造血重建的影响

在ABO血型不合的异基因造血干细胞移植(allo—HSCT)中，红系造血延缓甚至纯红细胞再生障碍(纯红再障)时有发生。为进一步观察ABO血型不合对红系造血重建的影响并探讨其发生原因，我们将我院近年来进行的ABO血型不合allo—HSCT 30例与同期进行的ABO血型相合移植30例患者进行对比分析。     

异基因骨髓移植后纯红细胞再障

主要ＡＢＯ血型不合的异基因骨髓移植（Ａｌｌｏ－ＢＭＴ）后纯红细胞再障（ＰＲＣＡ）是ＢＭＴ的少见并发症，本文就此病的发生机理，发病情况及治疗方法进行了简要综述。     

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。     

异基因外周血干细胞移植治疗急性白血病三例

对３例急性髓系白血病（ＡＭＬ）患者进行了异基因外周血干细胞移植（ａｌｌｏＰＢＳＣＴ）治疗，报道如下。病例和方法１供、受者情况例１男性，２５岁，Ｏ型血，为急性早幼粒细胞白血病首次缓解（ＡＭＬＭ３ａＣＲ１），供者为其大姐，４２岁，已分娩１胎，Ｏ型血；例２男性，９岁，Ｂ型血，急性单核细胞白血病首次缓解（ＡＭＬＭ５ＣＲ１），供者为其姐，１５岁，Ａ型血；例３男性，２５岁，Ｂ型血，为急性粒细胞白血病部分分化型首次缓解（ＡＭＬＭ２ａＣＲ１），供者为其兄，３７岁，Ｏ型血。３例供、受者间ＨＬＡＡ，Ｂ，Ｄ…     

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。     

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

目的 研究主要ABO血型不合异基因造血干细胞移植（allo-HSCT）后患者纯红细胞再生障碍（PRCA）的发病情况及危险因素。方法 分析移植后患者PRCA的发病危险因素，比较抗A凝集素与抗B凝集素对红系造血恢复的影响。结果 100例ABO血型主要及主次要均不合allo-HSCT患者中，12例发生PRCA。A供O者9例，A供B者1例，B供O者2例。有抗A凝集素的患者（10例）较有抗B凝集素的患者（2例）易发生PRCA（P〈0．05）。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。发生PRCA时血型转换的中位时问为150．5d，显著长于无PRCA发生患者（60．0d）（P〈0．05）；红系恢复的中位时间为203．5d，显著长于无PRCA发生患者（76．0d）（P〈0．05）。有抗A凝集素的患者血型转换中位时间为90．0d，显著长于有抗B凝集素的患者（55．0d）（P〈0．05）；红系恢复中位时间为98．0d，长于有抗B凝集素者（80．0d）（P〉0．05），但差异无统计学意义。结论 PRCA是ABO血型不合移植的合并症之一。A供O是主要ABO血型小合allo-HSCT后PRCA发病的危险因素。     

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.     

Regeneration of erythropoiesis after related- and unrelated-donor BMT or peripheral blood HPC transplantation: a major ABO mismatch means problems

BACKGROUND: Blood group incompatibility in allogeneic BMT is common but does not appear to affect the outcome in terms of incidence of graft rejection or delayed engraftment. However, major ABO incompatibility may be associated with prolonged erythroid aplasia. STUDY DESIGN AND METHODS: In a retrospective analysis of 286 allogeneic transplant recipients, the prevalence of prolonged erythroid aplasia, including pure RBC aplasia, was determined. RESULTS: Patients receiving major ABO-incompatible grafts showed a significant delay in reticulocyte engraftment (median, 32 days; range, 12-347) from that in patients receiving ABO-identical (20; 10-152) or minor ABO-incompatible (21; 12-47) grafts. Pure RBC aplasia occurred in 7 (3%) of 240 evaluable recipients and was observed only in the major ABO-incompatible group (7/43, 16%). Treatment of pure RBC aplasia consisted of either plasma exchange, which resulted in a response within 16 to 68 days, or immunoadsorption, in which the response occurred between Days 119 and 204 after initiation of treatment. CONCLUSION: Major ABO incompatibility may lead to delayed reticulocyte engraftment, resulting in prolonged transfusion dependency and increased risks of transmission of infection and iron overload. Therefore, therapeutic strategies should be taken into consideration to allow erythroid reconstitution in these patients.     

ABO血型不合异基因造血干细胞移植治疗恶性血液病

背景:由于移植技术的提高,供受者ABO血型不合已不再是异基因造血干细胞移植的障碍,但是由于宿主血凝素抗体的持续存在,ABO血型不合异基因造血干细胞移植后常出现红细胞系统恢复的延迟.目的:观察ABO血型不合异基因造血干细胞移植患者红细胞系统恢复情况,评价血型不合、人类白细胞抗原配型不相合对造血功能重建的影响.设计:回顾性分析.单位:南京大学医学院附属鼓楼医院血液科.对象:选择2002-05/2007-09在南京大学医学院附属鼓楼医院血液科行ABO血型不合异基因造血干细胞移植的恶性血液患者(受者)14例,男11例,女3例;年龄15～60岁.14例患者中7例供受者人类白细胞抗原配型完全相合.7例供受者人类白细胞抗原配型半相合.纳入同期ABO血型相合的造血干细胞移植患者11例为对照.受者在接受异基凶造血干细胞移植前签署移植同意书,供者为同胞姊妹、胞弟、儿子、母亲,均同意提供用于移植的骨髓.实验经医院伦理委员会批准.方法:①预处理方案:人类白细胞抗原配型全相合组采取马利兰和环磷酰胺为主的方案.人类白细胞抗原配型半不合组采用北京人民医院的GlAC方案.②造血干细胞输注:沉降供者骨髓.取上层有核细胞输给受者.主要观察指标:观察ABO血型不合异基因造血干细胞移植的副反应、并发症及造血重建情况.结果:14例ABO血型不合患者仅1例发生单纯红细胞再生障碍性贫血未进入结果分析.①造血功能重建情况:与对照组比较,ABO血型不合组血红蛋白恢复时间明显延迟(t=2.352,P＜0.05),ABO血型相同与ABO血型不合组中性粒细胞和血小板恢复情况差异无显著性意义(P＞0.05).ABO血型不合的人类白细胞抗原配型半不合造血干细胞组血红蛋白恢复和血型转换时间迟于全相合,但其差异无显著性意义(P＞0.05).②并发症:14例ABO血型不合患者移植后成分输血过程未出现溶血反应,移植后也均未发生迟发性溶血反应.结论:ABO血型不合不影响造血干细胞移植的效果,且较为安全.     

ABO-incompatible bone marrow transplantation: prevention of hemolysis by alkaline hydration with mannitol diuresis in conjunction with red cell reduced buffy coat bone marrow.

Bone marrow transplantation (BMT) in the presence of major ABO incompatibility presents the risk of a potentially fatal hemolytic transfusion reaction at the time of marrow infusion. We describe the use of a forced alkaline hydration/mannitol diuresis regimen in combination with red blood cell (RBC) reduced bone marrow given as buffy coat in 5 patients undergoing allogeneic BMT from ABO incompatible donors. Three patients had ABO antibody titers of 1:32 and were not subjected to antibody removal procedures. Two patients with respective antibody titers of 1:512 and 1:128 underwent plasmapheresis to reduce the antibody titers to below 1:64. The forced diuresis/mannitol regimen was well tolerated. Although the RBC content was still high in the buffy coat preparation a significant hemolytic transfusion reaction was successfully prevented. No patient had back pain, hyperbilirubinemia or renal impairment despite clinical and laboratory evidence of hemoglobinuria. These data indicate that patients with antibody titers below 1:64 might be spared the risks and cost associated with plasmapheresis or complete RBC depletion of the bone marrow transplant.     

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。     

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.