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。     

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。     

Role of complement in graft rejection after organ transplantation

Activation of the complement system may significantly contribute to the inflammatory reaction after solid organ transplantation. In allotransplantation, the complement system may be activated by ischemia/reperfusion and, possibly, by antibodies directed against the graft. In xenotransplantation from nonprimates to primates, the major activators for complement are preexisting antibodies. Studies in animal models have shown that the use of complement inhibitors may significantly prolong graft survival. This review describes the role of the complement system in organ injury after organ transplantation and the use of complement inhibitors to prevent damage to the graft after allo- or xenotransplantation.     

ABO血型不合外周血造血干细胞移植10例

背景：ABO血型不合供受者之间进行外周血造血干细胞移植,面临受者血型的转变、移植后输血的选择等问题.目的：观察ABO血型不合外周血造血干细胞移植治疗血液病的临床疗效和近远期并发症.方法：回顾性分析了2005/2008武警总医院收治的10例ABO血型不合异基因外周血同胞供者造血干细胞移植患者的资料.总结植入效果,血型转变,移植物抗宿主病以及不良反应.结果与结论：9例患者恢复造血功能,血型转变为完全供者型,1例患者白细胞血小板恢复,但红细胞植入延迟.所有患者在输注移植物时未出现短暂的血红蛋白尿,无严重急性溶血和迟发型溶血的发生,1例出现严重的移植物抗宿主病.可见ABO血型不合外周血造血干细胞移植对移植疗效无明显影响,红细胞植入延迟的预防和处理十分重要.     

输血支持在造血干细胞移植中的应用

背景：接受造血干细胞移植的患者经常需要血液制品输注支持,而患者对红细胞和血小板输注的需求差异非常大,这主要依赖于造血干细胞移植的类型和患者本身的疾病性质。目的：评价中山大学附属中山医院接受造血干细胞移植患者移植期间输血的需求和数量。方法：收集中山大学附属中山医院2004-01/2010-06接受造血干细胞移植患者的资料,包括移植的适应证、移植的类型、CD34＋细胞的数量、红细胞和血小板的输注数量、费用、脱离输注时间以及中性粒细胞和血小板植入时间;红细胞输注的阈值是血红蛋白计数为70g/L,而血小板的输注阈值是计数为20×109L-1。研究分析了患者移植期间红细胞和血小板输注的需求、输注量、输血费用,以及患者的生存情况。结果与结论：自体造血干细胞移植组中有14例（93%）患者,而异基因造血干细胞移植组中有35例（90%）患者显示了造血细胞植入和脱离输注证据。自体造血干细胞移植组取得脱离红细胞输注天数为14.6d,明显短于异基因造血干细胞移植组。与异基因造血干细胞移植组比较,自体造血干细胞移植组红细胞输注单位明显减少;而异基因造血干细胞移植组的红细胞输注费用明显高于自体造血干细胞移植组。输血花费昂贵,但却是造血干细胞移植中必不可少的一部分,异基因造血干细胞移植组需要更多的输血支持。脱离输注时间有望成为评估造血干细胞移植成功的指标。     

输血支持在造血干细胞移植中的应用

背景:接受造血干细胞移植的患者经常需要血液制品输注支持,而患者对红细胞和血小板输注的需求差异非常大,这主要依赖于造血干细胞移植的类型和患者本身的疾病性质。目的:评价中山大学附属中山医院接受造血干细胞移植患者移植期间输血的需求和数量。方法:收集中山大学附属中山医院2004-01/2010-06接受造血干细胞移植患者的资料,包括移植的适应证、移植的类型、CD34+细胞的数量、红细胞和血小板的输注数量、费用、脱离输注时间以及中性粒细胞和血小板植入时间;红细胞输注的阈值是血红蛋白计数为70g/L,而血小板的输注阈值是计数为20×109L-1。研究分析了患者移植期间红细胞和血小板输注的需求、输注量、输血费用,以及患者的生存情况。结果与结论:自体造血干细胞移植组中有14例(93%)患者,而异基因造血干细胞移植组中有35例(90%)患者显示了造血细胞植入和脱离输注证据。自体造血干细胞移植组取得脱离红细胞输注天数为14.6d,明显短于异基因造血干细胞移植组。与异基因造血干细胞移植组比较,自体造血干细胞移植组红细胞输注单位明显减少;而异基因造血干细胞移植组的红细胞输注费用明显高于自体造血干细胞移植组。输血花费昂贵,但却是造血干细胞移植中必不可少的一部分,异基因造血干细胞移植组需要更多的输血支持。脱离输注时间有望成为评估造血干细胞移植成功的指标。     

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。     

Reduced hemoglobin on day of peripheral blood progenitor cell collection is associated with low graft content of vascular progenitors and increased toxicity after autologous hematopoietic stem cell transplantation

BACKGROUND: Tissue damage after hematopoietic stem cell transplantation (HSCT) occurs as a result of high‐dose chemotherapy and radiation. The aim was to determine the importance of pretransplant anemia on toxicity and red blood cell (RBC) transfusion requirements after autologous HSCT. STUDY DESIGN AND METHODS: A total of 350 patients undergoing autologous HSCT were included in the analysis. Patient factors and pretransplant laboratory values of possible relevance were assessed in multivariate regression analysis. RESULTS: Reduced hemoglobin (Hb) on the first day of peripheral blood progenitor cell (PBPC) collection was significantly associated with increased organ toxicity after HSCT, as measured by the Seattle criteria. Lower Hb levels at baseline before transplantation, but not at PBPC collection, were significantly associated with increased RBC transfusion requirements. In a second cohort of 28 patients, higher Hb levels on the day of PBPC collection were significantly associated with increased levels of endothelial‐like vascular progenitor cells in PBPC grafts. CONCLUSION: Our observations suggest that higher Hb levels on the day of PBPC collection may be a marker of reduced toxicity associated with HSCT and increased vascular progenitors in PBPC collections. Further, baseline anemia before transplant may reflect an unfavorable hematopoietic microenvironment that leads to increased RBC transfusion requirements.     

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。     

杀伤细胞免疫球蛋白样受体基因对异基因造血干细胞移植后常见并发症及复发的影响

造血干细胞移植(HSCT)是某些血液肿瘤疾病、免疫缺陷疾病、遗传代谢疾病等的有效治疗手段.伴随着接受H SCT患者的增多,移植后各种并发症日益受到关注,其中以病毒感染、移植物抗宿主病(GVHD)最为常见.移植后疾病复发是导致移植失败的主要原因.自然杀伤(NK)细胞是人体非特异性细胞免疫的重要组成部分,对外来病原菌的入侵起到第一道防线作用.NK细胞的杀伤细胞免疫球蛋白样受体(KIR)基因家族可编码KIR,而部分KIR可与人类白细胞抗原(HLA)-Ⅰ类分子特异性结合.近年来,有关供者KIR与移植后病毒感染,GVHD及复发的研究逐渐增多,某些KIR基因或者单倍体型可能与之密切相关.     

Sirolimus for Refractory Autoimmune Hemolytic Anemia after Allogeneic Hematopoietic Stem Cell Transplantation: A Case Report and Literature Review of the Treatment of Post-Transplant Autoimmune Hemolytic Anemia

Autoimmune hemolytic anemia (AIHA) may occur after any type of allogeneic hematopoietic stem cell transplantation (HCT), even ABO-matched transplantation. It tends to be refractory to standard corticosteroid treatment and requires multiple transfusions. Though, there is no consensus regarding the optimal treatment for post-transplant severe AIHA. We present a pediatric patient with refractory AIHA after umbilical cord blood transplantation. She developed severe AIHA at 3 months after transplantation and was unresponsive to multiple treatment modalities, including corticosteroids, intravenous immunoglobulin, plasma exchange and rituximab, resulting in persistent transfusion dependency. Sirolimus, a mammalian target of rapamycin inhibitor, was started on day 67 after the onset of AIHA, and this patient was successfully rescued without any complications. Sirolimus induces apoptosis in autoreactive lymphocytes, increases regulatory T cells and has been reported to have a positive effect on AIHA following solid organ transplantation (SOT). We reviewed the literature regarding post-transplant AIHA in the PubMed database and evaluated the treatment outcome of sirolimus in AIHA after SOT.     

ABO血型不合外周血造血干细胞移植10例

背景:ABO血型不合供受者之间进行外周血造血干细胞移植,面临受者血型的转变、移植后输血的选择等问题.目的:观察ABO血型不合外周血造血干细胞移植治疗血液病的临床疗效和近远期并发症.方法:回顾性分析了2005/2008武警总医院收治的10例ABO血型不合异基因外周血同胞供者造血干细胞移植患者的资料.总结植入效果,血型转变,移植物抗宿主病以及不良反应.结果与结论:9例患者恢复造血功能,血型转变为完全供者型,1例患者白细胞血小板恢复,但红细胞植入延迟.所有患者在输注移植物时未出现短暂的血红蛋白尿,无严重急性溶血和迟发型溶血的发生,1例出现严重的移植物抗宿主病.可见ABO血型不合外周血造血干细胞移植对移植疗效无明显影响,红细胞植入延迟的预防和处理十分重要.     

Concluding commentary on current trends to enhance the clinical safety of pediatric transfusion,focusing on prevention of untoward complications of HSC transplantation & newer strategies for improving the standards of safety/quality of stem cells expansion for cellular therapy

Clinical practice and related diagnostic, development and research [DDR] strategies in pediatric transfusion and transplantation cover a broad range of multidisciplinary studies, performed by many professionals involved in this most challenging clinical field [1]. This commentary on the current position and future perspectives in pediatric transfusion field is aimed to highlight major unresolved transfusion complications in pediatric patients, namely red blood cell and platelet alloimmunisation, and new ones such as nosocomial infection, thrombosis and multi-organ failure. Some other safety related issues issues in clinical management of neonates/young infants with urgent medical conditions, requiring immediate transfusion or apheresis treatment, especially, those resulting from hematopoietic stem cell transplantation (HSCT), have been addressed. Pediatric HSCT has evolved along with its growth and progress in adult population. New sources of stem cells, and greater donor options including apheresis donation by identical or haploidentical young children, new immunosuppressive drug and cell therapy regimens for prevention and treatment of transplantation related graft versus host disease (GVHD), recent developments in gene and immune cell as well as regenerative therapies, requiring implementation of advanced laboratory methods designed for efficient and safe HSC cell engineering are also discussed. Finally, the use of novel blood components, obtained from allogeneic cord bloods or platelet concentrates in successful treatment of ulcerative lesions in inherited or acquired conditions and in expansion of stem cells, as the growth media clinical grade supplement will be presented. Management of these new and challenging clinical situations in pediatric patients requires an integrated approach involving many specialties with overall goal of improving treatment outcome and quality of life. This only could be accomplished by adhering to existing practice standards in current practices and timely developing guidelines for new clinical applications. It is hoped that this commentary on the pediatric theme, by bridging the gap from bench to bedside and bringing the input from the prospective clinical trials back to laboratories provides a step forward to help in educational aspects of better understanding the specifics of pediatric patient care more fitting for the future interventional treatments.     

Current status and future of clinical kidney transplantation in Japan

Kidney transplantation has been established to be the therapy for an end-stage renal disease. In Japan, living donor kidney transplantation is frequently performed (> 80%) because of a shortage of the deceased donors. The graft survival has been improved to 93.4% (5-year graft survival in living donor kidney transplantation after 2001). ABO-incompatible cases are increasing and more than 20% are ABO-incompatible in Japan (30% in our institution). In our institution, 225 kidney transplantations (182: living donors, 43: deceased donors) have been performed from 2004.4 to 2010.6. Although the graft survival is excellent, posttransplant infections including cytomegalovirus, EB virus and BK virus are problems which should be solved. For the safety of the recipients, we should use kidney grafts from brain-dead donors.     

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。     

Immunological factors in organ transplantation

Several immunological factors affect the outcome of human kidney transplants. HLA-A,-B and-DR matching improves kidney graft survival rate, especially matching for HLA-DR antigens. The beneficial effect of pretransplant blood transfusion has been confirmed although the mechanisms of the beneficial effect are not clear. Donor specific transfusion prior to living related donor kidney transplantation improve graft survival but some 30% of potential recipients become sensitized to the donor during the transfusion process. Major improvements in the results of organ transplantation have been achieved during the past few years with the use of new immunosuppressive agents, namely cyclosporin and monoclonal antibodies reacting with T lymphocytes. Both agents act selectively on T lymphocytes. However, nephrotoxicity of cyclosporin may limit its use.     

Immunological factors in organ transplantation

Several immunological factors affect the outcome of human kidney transplants. HLA-A,-B and-DR matching improves kidney graft survival rate, especially matching for HLA-DR antigens. The beneficial effect of pretransplant blood transfusion has been confirmed although the mechanisms of the beneficial effect are not clear. Donor specific transfusion prior to living related donor kidney transplantation improve graft survival but some 30% of potential recipients become sensitized to the donor during the transfusion process. Major improvements in the results of organ transplantation have been achieved during the past few years with the use of new immunosuppressive agents, namely cyclosporin and monoclonal antibodies reacting with T lymphocytes. Both agents act selectively on T lymphocytes. However, nephrotoxicity of cyclosporin may limit its use.     

造血干细胞移植的研究进展

造血干细胞移植（HSCT）是近年来发展起来的重要的细胞治疗方法,也是根治血液系统恶性疾病及部分自身免疫性疾病的重要方法.现就近年来HSCT领域的移植预处理方案、移植后并发症的处理、移植后免疫重建及移植物抗宿主病等方面的研究进展,综述如下.     

ABO血型不合异基因造血干细胞移植后不同血型混合红细胞的分离鉴定

目的 建立不同血型混合红细胞的分离鉴定方法,应用于ABO血型不合造血干细胞移植患者的混合红细胞分离鉴定及植活红细胞研究.方法 应用红细胞血型抗原与相应抗体反应凝集,800×g和50×g分步离心,分离并收集凝集的和未凝集的红细胞进行计数和鉴定.结果 18例ABO血型不合造血干细胞移植后均成功分离鉴定出植活红细胞和患者自身红细胞.初次分离鉴定出植活红细胞的时间为移植后第11天至第72天.植活红细胞数量随移植后时间改变.本分离方法的灵敏度为1%,准确度为100%,回收率为92.5%,重复性为100%.结论 本方法可广泛用于不同血型混合红细胞的分离鉴定,为进一步研究干细胞移植患者2种不同红细胞变化的临床意义提供可靠的实验方法.     

地中海贫血造血干细胞移植供体及预处理方案选择的研究进展

地中海贫血为常染色体隐性遗传疾病,是由于基因突变导致血红蛋白的a或β珠蛋白链生成障碍引起的血液系统疾病.目前,造血干细胞移植(HSCT)是唯一可以治愈地中海贫血的方法.但是,由于受到HSCT供者与患者人类白细胞抗原(HLA)相合程度的限制,以及HSCT后的移植排斥与移植相关不良反应等并发症与预处理方案相关,因此选择合适的造血干细胞供体与预处理方案,对提高HSCT治疗地中海贫血的疗效至关重要.笔者拟就无关供者HSCT、亲缘供者HSCT、脐血移植(UCBT)及预处理方案的研究现状与研究进展进行综述.