Transfusion policy in allogeneic hematopoietic stem cell transplantation

The incompatibility of ABO blood group between the recipient and the donor is not a barrier to perform allogeneic hematopoietic stem cell transplantation (Allo-HSCT). However, ABO incompatibility may lead to many complications during and after stem cell transplantation at the early or late period. Therefore, the typing of the blood group of the recipient and the donor should be done prior to the transplantation. In addition, the ABO/Rh group of blood products for transfusion should be determined according to the type of ABO-incompatibility. In this review, the subtypes of ABO blood group-incompatibility and transfusion policies will be discussed in detail.     

异基因外周血造血干细胞移植后血型基因型与抗原的转变

目的 探讨异基因外周血造血干细胞移植(Allo—PBSCT)后患者ABO、Rh血型的转变在血液病移植治疗中的意义。方法 选择2例非血源关系的供、受者作为研究对象，采用基因分型与血清学方法检测移植前后ABO、Rh血型的表达，追踪移植后患者血型基因型与抗原的转变。结果 2例患者分别在移植后第7天与第10天检测到供者的A、Rh(c)基因，第7天与第15天不同程度地表达供者的ABO、Rh血型抗原。结论 观察ABO与Rh血型的转变可作为植入证明的检测方法之一，且直观、迅速。     

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;...     

Long-term results of allogeneic peripheral blood hematopoietic stem cell transplantation for severe aplastic anemia

ObjectiveAplastic anemia (AA) is a life-threatening disorder and may be associated with significant morbidity and mortality Currently, the first treatment option is allogeneic hematopoietic stem cell transplant (allo-HSCT) for patients younger than 40 years. Bone marrow is recommended as the stem cell source due to less graft versus host disease (GVHD) risk and better outcomes than peripheral blood (PB)-derived stem cell. The aim of this study is to share the data of AA patients who have underwent PB-derived allo-HSCT in our bone marrow transplantation center.MethodsTwenty-seven patients who underwent PB-derived allo-HSCT from human leukocyte antigen matched sibling donors were analyzed retrospectively.ResultsThe median follow-up time was 95.2 months (range, 4.8–235 months). The 10-year survival was 89 %. The median neutrophil and platelet engraftment time was 11 days (range, 9–16 days) and 13 days (range, 11–29 days), respectively. Primary platelet engraftment failure was observed in 1 patient (3.7 %). Acute and chronic GVHD observed in 2 (7.4 %) and 3 (11.1 %) patients, respectively. Neutropenic fever was observed in 13 (44.8 %) of patients until the engraftment after allo-HSCT. One patient died due to CMV infections, two died due to septic shock secondary to fungal infection.ConclusionAlthough there is no prospective data directly comparing BM with PB as stem cell source in AA, observational studies indicates better OS with BM. PB can be used in certain situations such as higher risk for graft failure and donor preference. This study demonstrated that PB-derived stem cell seems to be a reasonable alternative to BM.     

Effects of ABO incompatibility on the outcome of allogeneic hematopoietic stem cell transplantation

BackgroundABO compatibility between donor and recipient is no necessary in allogeneic hematopoietic stem cell transplantation (AHSCT). Incompatible transplantations can be divided into three groups based on the donor and recipient blood groups. The influence of each kind of incompatibilities on the outcome of patients does not seem to be consistent. This study aimed to investigate the outcome of AHSCT patients focusing on compatibility statues.MethodThis retrospective study was conducted on 186 patients who underwent first AHSCT, includes 108 identical, 38 minor, 32 major and eight bidirectionalABO incompatible recipients. Comparative analysis was performed for common clinical transplantation outcomes.ResultsThere was no statistically significant association betweenABO incompatibility and graft-versus-host disease, WBC or platelet engraftment, and transfusion requirement. WBC engraftment rate was significantly lower in minor-incompatible patients. Furthermore, total and direct bilirubin which (the hemolysis biomarkers) were considerably higher in the bidirectional incompatible group, compared to the other patients.ConclusionOur results indicate that theABO incompatibility might be an effective factor in engraftment time and laboratory hemolysis. Elucidating the impact of ABO incompatibility on the clinical outcome of patients warrants an extended and deep investigation in a large-scale study with comprehensive variables such as survival, relapse, and other complication of transplantation.     

减低剂量预处理方案对血缘与非血缘关系外周血干细胞移植治疗慢性粒细胞白血病疗效的影响

目的 观察和比较血缘与非血缘关系异基因外周血干细胞移植(allo-PBSCT)采用氟达拉滨(Flud)联合白消安(BU)组成的FB减低剂量预处理方案治疗慢性粒细胞白血病(CML)的疗效和移植相关并发症.方法 采用FB(Flud 30 mg·m~(-2)·d~(-1)×5d;BU 4 mg·kg~(-1)·d~(-1)×3 d)方案alloPBSCT治疗CML共44例,接受血缘关系移植29例(血缘组),接受非血缘关系移植15例(非血缘组).急性移植物抗宿主病(aGVHD)预防:血缘组为霉酚酸酯(MMF)+环孢素(CsA)+甲氨蝶呤(MTX),非血缘组在上述基础上另加兔抗人胸腺细胞球蛋白(ATG,5 mg/kg×4 d).结果所有患者移植后均取得造血功能重建,血缘组与非血缘组中性粒细胞＞0.5×10~9/L的中位时间分别为13.7(9～18)d和13.6(12～17)d,血小板＞20×10~9/L的中位时间分别为15.3(9～20)d和14.7(10～26)d.但血缘组与非血缘组分别有2例与1例患者移植后5～8个月发生继发性植入排斥,其中血缘组1例再次行同一供体移植,重获造血功能重建.血缘组累计发生aGVHD共4例(13.8%),均为Ⅱ度;存活6个月以上28例患者中发生慢性GVHD(cGVHD)13例(46.4%),其中局限型和广泛型分别为10例和3例.非血缘组累计发生aGVHD共5例(33.3%),其中Ⅰ～Ⅱ度4例,Ⅲ度1例;存活6个月以上14例患者中发生cGVHD 8例(57.1%),其中局限型和广泛型分别为5例和3例.血缘组有2例患者移植后复发,给予冻存G-CSF动员的供者外周血干细胞输注(DSI)1～2次后再获得CR.本组中位随访时间34.7(2～73)个月,累计移植相关死亡10例(22.7%),主要死因是间质性肺炎、GVHD及继发排斥伴重症感染;34例患者存活,预期5年总生存率(0S)和无病生存率(DFS)分别为77.0%和73.9%;其中,血缘关系移植5年0s和DFS分别为79.0%和74.1%,非血缘关系移植5年OS和DFS均为73.3%.结论 以氟达拉滨联合白消安组成的减低剂量预处理方案allo-PBSCT治疗CML,无论是血缘移植还是非血缘移植均安全有效,重度GVHD发生率和术后复发率均不高,但少数患者需加强植入监测,并及时采用DSI或DLI等干预治疗.     

ABO血型不合供者外周血造血干细胞的采集及移植效果研究

目的探讨应用CS-3000 Plus血细胞分离机采集ABO血型不合供者外周血造血干细胞的效率及不去除红细胞和/或血浆进行异基因外周血造血干细胞移植(PBSCT)的安全性。方法经G-CSF 5μg/(kg.d)动员的异基因外周血干细胞供者33名,应用CS-3000 Plus血细胞分离机的干细胞采集程序于动员后d 5采集,其中ABO血型主要不合12名,次要不合8名以及ABO血型相合13名。根据供者外周血的红细胞压积(Hct)和单个核细胞(MNC)计数,对分离机参数作相应调整。输注前从产品袋中留取干细胞,检测有核细胞数、MNC比例、CD34+细胞数、红细胞、血浆含量。单次处理循环血量(9 986±2 489)ml,抗凝剂用量(971±162)ml。供者采集前注射10%葡萄糖酸钙,以预防低钙反应。观察PBSC输注后受者的生命体征、尿液颜色及是否有溶血相关不良反应等。结果ABO血型主要不合组、次要不合组与ABO血型相合组采集物中的有核细胞数、CD34+细胞数、MNC比例无统计学差异(P>0.05),3组供者每次采集的PBSC产品终体积近60 ml,ABO主要不合组采集物中混入红细胞为(3.67—10.25)×1010/袋,ABO次要不合组采集物中血浆量为22—38 ml,不去除红细胞及血浆,直接回输给受者,均未出现溶血反应,所有患者造血功能均获得重建。结论应用CS-3000 Plus血细胞分离机采集ABO血型不合供者的外周血干细胞,通过调整分离机参数,减少ABO血型不合红细胞的混入,可以获得足够的干细胞数量并安全用于移植。     

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。     

Peripheral blood stem cell collection for allogeneic hematopoietic stem cell transplantation: Practical implications after 200 consequent transplants

Background

Proper stem cell mobilization is one of the most important steps in hematopoietic stem cell transplantation (HSCT). The aim of this paper is to share our 6 years’ experience and provide practical clinical approaches particularly for stem cell mobilization and collection within the series of more than 200 successive allogeneic HSCT at our transplant center.

3种血型鉴定方法监测ABO血型不合造血干细胞移植患者血型嵌合体

目的 探讨盐水介质试管法(试管法),ABO正反定型/RhD定型卡(血型卡)和低离子/抗人球蛋白微柱凝胶卡(LISS/Coombs卡)在ABO血型不合造血干细胞移植(HSCT)患者血型鉴定中的应用价值,指导临床安全输血.方法 以血型卡、试管法和LISS/Coombs卡对24例ABO不合造血干细胞移植患者血型抗原、抗体进行...     

Graft failure after allogeneic hematopoietic stem cell transplantation

Graft failure is a serious complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) defined as either lack of initial engraftment of donor cells (primary graft failure) or loss of donor cells after initial engraftment (secondary graft failure). Successful transplantation depends on the formation of engrafment, in which donor cells are integrated into the recipient’s cell population.In this paper, we distinguish two different entities, graft failure (GF) and poor graft function (PGF), and review the current comprehensions of the interactions between the immune and hematopoietic compartments in these conditions. Factors associated with graft failure include histocompatibility locus antigen (HLA)-mismatched grafts, underlying disease, type of conditioning regimen and stem cell source employed, low stem cell dose, ex vivo T-cell depletion, major ABO incompatibility, female donor grafts for male recipients, disease status at transplantation.Although several approaches have been developed which aimed to prevent graft rejection, establish successful engraftment and treat graft failure, GF remains a major obstacle to the success of allo-HSCT.Allogeneic hematopoietic stem cell transplantation (allo-HSCT) still remains to be the curative treatment option for various non-malignant and malignant hematopoietic diseases. The outcome of allo-HSCT primarily depends on the engraftment of the graft. Graft failure (GF), is a life-threatening complication which needs the preferential therapeutic manipulation. In this paper, we focused on the definitions of graft failure / poor graft function and also we reviewed the current understanding of the pathophysiology, risk factors and treatment approaches for these entities.     

同种异基因造血干细胞移植后基于血细胞嵌合状态的个体化免疫治疗

目的:研究同种异基因造血干细胞移植(allo-HSCT)后血细胞嵌合率变化与复发的关系;观察根据血细胞嵌合率变化给予个体化免疫抑制剂治疗和供者淋巴细胞输注(DLI)的疗效。方法:106例供者细胞顺利植入的allo-HSCT患者,采用聚合酶链反应(PCR)扩增短串联重复序列的方法,动态检测移植后T淋巴细胞、B淋巴细胞、自然杀伤(NK)细胞的嵌合率。根据血细胞嵌合率的变化调整免疫抑制剂剂量和DLI的使用。结果:6例患者在移植后2个月,供者T细胞嵌合状态一直为混合嵌合(MC),将免疫抑制剂减量后均达到完全供者嵌合(FDC)。12例患者在移植后1～5个月,发生供者T细胞嵌合率下降,予免疫抑制剂减量后转为FDC。24例患者血液学复发或髓外复发(进展),有6例在复发前共发生10例次血细胞嵌合率下降,经免疫抑制剂减量或停药后一度回升至FDC,但最终血液学或髓外复发。12例患者在复发或疾病进展后停用免疫抑制剂,共给予DLI23例次,其中8例在DLI前或后给予化疗,最终5例再次达到完全缓解,其余患者最终均因疾病复发死亡。Ⅱ度及Ⅱ度以上急性移植物抗宿主病(GVHD)发生率为28.3%。慢性GVHD发生率为55.7%。中位随访期为17(1.5～90.0)个月,无病生存65例,死亡41例。67例标危患者预期3年生存率为59.0%;39例高危患者预期3年生存率为44.7%。结论:T淋巴细胞、NK细胞和B淋巴细胞的嵌合状态可作为血液恶性肿瘤复发的预测指标;基于血细胞嵌合率的个体化免疫治疗可以推迟甚至避免临床复发,且不增加急性GVHD的发生。     

异基因造血干细胞移植后伴噬血现象分析

目的分析异基因造血干细胞移植(allo-HSCT)后伴噬血现象的特征。方法选取上海市第一人民医院行allo-HSCT后出现噬血细胞性淋巴组织细胞增多症(HLH)的患者2例,讨论其可能的病因。结果患者一入院诊断为免疫缺陷病,行allo-HSCT 13 d后粒系植入,血红蛋白、血小板始终偏低,凝血功能差,消化道出血,巨细胞病毒性肠炎,肺部感染,骨髓细胞形态学检查可见噬血现象。患者二入院诊断为急性单核细胞性白血病,行allo-HSCT 14 d后粒系植入,行allo-HSCT 42 d后三系降低,发热,铁蛋白高,骨髓细胞形态学检查可见噬血现象,嵌合率进行性降低。结论allo-HSCT后伴噬血现象非常罕见,且进展迅速,预后不良,噬血现象常因感染所致。当行allo-HSCT后骨髓出现噬血现象时,应积极排查感染,检测原发病是否复发,同时应检测患者及其父母相关基因,尽早治疗,争取取得更好的预后。     

异基因外周血造血干细胞移植预处理的护理

目的探讨异基因外周血造血干细胞移植（allo-PBSCT）预处理的相关毒性及护理特点，以提高护士时相关病情的观察及护理水平，使患者的移植手术顺利进行。方法对7例行allo-PB-SCT的患者行移植前的各项准备，并均行颈内静脉置管。预处理方案均采用不含全身放疗（TBI）的清髓性联合化疗方案：马利兰（BU）＋环磷酰氨（CY）。结果7例患者均顺利度过预处理期，并成功接受千细胞移植。结论在预处理中加强细致、全面的观察及护理，并及早发现问题，及时处理不良反应是保证患者安全，顺利进行allo-PBSCT的前提，是PBSCT成功很关键的一环。     

Peripheral blood stem cell grafts in allogeneic hematopoietic cell transplantation: It is not all about the CD34+ cell dose

Allogeneic Hematopoietic Cell Transplantation is a curative approach in various malignant and non-malignant disorders. The majority of adult transplants in the current era are performed using mobilized stem cells, harvested from the peripheral blood by leukapheresis. Peripheral blood stem cell (PBSC) collections are designed to target a dose of stem cells that will result in safe engraftment and hematopoietic recovery; however, 99 % of the cells contained in a PBSC graft are not stem cells and a growing number of studies attempt to characterize the associations between graft composition and transplant outcomes. A better understanding of the impact of the quantity and quality of various cell types in PBSC grafts may lead to development of novel collection strategies or improved donor selection algorithms. Here we review relevant findings from recent studies in this area.     

PCR-STR用于异基因造血干细胞移植后的骨髓和外周血嵌合状态的监测及作用

目的用PCR-STR检测观察比较异基因造血干细胞移植术后,骨髓和外周血嵌合状态和植入状态。方法提取17例异基因造血干细胞移植术中的供者外周血及受者移植前后各阶段外周血和骨髓的DNA,PCR PCR-STR检测扩增15个基因位点,和1个性别位点AMEL。用遗传分析仪进行毛细管电泳,确定基因位点,根据基因型的差异选择嵌合率计算公式,分析植入情况和嵌合状态。结果12名患者完全植入,骨髓和外周血的PCR-STR结果一致;1名患者骨髓PCR-STR显示为持续未植入,外周血PCR-STR显示为短期混合植入;4名患者骨髓和外周血PCR-STR显示嵌合状态时间不一致,骨髓PCR-STR显示嵌合状态时间明显早于外周血(P<0.05)。结论PCR-STR是分析异基因造血干细胞移植后供体是否植入的灵敏、准确度高的方法,骨髓嵌合状态的变化的出现早于外周血,混合嵌合状态对白血病复发有预警作用,骨髓嵌合状态的早期变化对实施临床干预治疗尤为重要。     

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。     

The experience of allogeneic hematopoietic stem cell transplantation in a patient with X-linked adrenoleukodystrophy

X-linked adrenoleukodystrophy (X-ALD), a progressive neurometabolic disorder that is caused by a defect in the gene ABCD1 (ATP-binding cassette, subfamily D, member 1), which encodes the peroxisomal ABC half-transporter ALD protein. Recently, allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only therapy known to prevent disease progression. In this study, we would like to present our experience of alloHSCT for X-ALD from a HLA matched related sibling by the use of reduced intensity conditioning regimen composed of fludarabine, busulfan and ATG which allows us to reduce procedure-related toxicity and prevent mortality while achieving a curative effect.