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.     

儿童血液病异基因造血干细胞移植后中枢神经系统感染MRI特征

目的 观察儿童血液病异基因造血干细胞移植(allo-HSCT)后中枢神经系统(CNS)感染的MRI特征.方法 回顾2 240例因血液病接受HSCT患儿,分析其中13例经手术、穿刺活检、实验室检查确诊的不同病原CNS感染的MRI表现.结果 血液病allo-HSCT后CNS感染率为0.58％(13/2 240),死亡率为3...     

Frequency and prognostic value of D alloantibodies after D-mismatched allogeneic hematopoietic stem cell transplantation after reduced-intensity conditioning

BACKGROUND: Due to the fact that the ABO and D system is inherited independently from the HLA system, approximately 40% of allogeneic hematopoietic stem cell transplants (HSCT) are performed across the blood group barrier. Reports on the development of de novo anti‐D in patients undergoing reduced‐intensity conditioning (RIC) followed by D‐mismatched allogeneic HSCT are rare. The objective of this study was to evaluate the frequency of anti‐D alloimmunization after D‐mismatched HSCT following RIC and its prognostic impact on transplant outcome. STUDY DESIGN AND METHODS: Forty patients with hematologic diseases who underwent D‐mismatched HSCT were retrospectively analyzed: 19 D? patients with a D+ donor and 21 D+ patients with a D? donor. Routine serologic testing for blood group typing and antibody screening was performed by a column agglutination method every time when transfusion of red blood cell units was requested and in the posttransplantation course to demonstrate establishment of donor ABO type and to detect alloimmunization. RESULTS: After a median serologic follow‐up of 21 (range, 0 to 73) months after HSCT, anti‐D was identified in 2 of 21 (10%) D+ patients receiving a D? transplant, 23 and 34 months after HSCT. None of the 19 D? patients with a D+ donor developed an anti‐D. CONCLUSION: We observed an infrequent de novo anti‐D formation that is more likely in D+ recipients of D? grafts. However, the development of anti‐D does not normally impair the transplant outcome and is not of clinical relevance in the posttransplant course.     

异基因造血干细胞移植后的长期随访

背景:近20年来中国的造血干细胞移植工作迅速发展,接受异基因造血干细胞移植后得到治愈的患者越来越多,但关于患者移植后长期随访情况的报道少见.目的:总结异基因造血干细胞移植后患者的长期随访情况.方法:对1995/2005在中山大学附属第三医院进行异基因造血干细胞移植的30例患者进行长期随访,总结患者的远期并发症、长期生存率、死亡原因,调查长期生存患者的生活质量.结果与结论:30例患者的慢性移植物抗宿主病发生率为67%,所有患者均出现不育,1例轻度肺纤维化,无其他远期并发症;移植后2年的无病生存率为60%,2年内未复发的患者均长期生存,生存时间最长的1例已超过14年;12例患者死亡,均发生于移植后2年内,其中5例死于复发,7例为移植相关死亡(均死于感染);长期生存的患者移植后1年时的生活质量较差,随着生存时间的延长生活质量逐渐改善,5年时的生活质量明显提高,8年时多已拥有较高的生活质量,影响生活质量的主要因素是慢性移植物抗宿主病.     

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.     

非清髓异基因造血干细胞移植治疗血液病多中心临床报告

目的 研究观察我国多中心非清髓异基因造血干细胞移植(NST)治疗血液病的疗效和相关并发症.方法 我国NST协作组9个中心共243例血缘相关HLA相合的血液病患者接受了NST治疗.在FAC[氟达拉滨(Flud)、抗胸腺细胞球蛋白(ATG)和环磷酰胺(CTX)]非清髓预处理方案的基础上加用阿糖胞苷或白消安等.移植物抗宿主病(GVHD)预防采用环孢素(CsA)联合霉酚酸酯(MMF)方案.结果 移植后4周供体完全植入163例(67.1%),移植失败2例(0.8%),混合植入78例(32.1%),其中56例移植后1～16个月转为完全植入,16例维持混合嵌合(MC)状态,6例移植排斥.83例(34.2%)发生急性GVHD,其中Ⅰ～Ⅱ度26例(28.9%),Ⅲ～Ⅳ度16例(6.6%);慢性GVHD 78例(32.1%).随访3～99个月,243例中仍存活162例(66.7%),其中骨髓增生异常综合征/再生障碍性贫血、慢性白血病、急性白血病首次完全缓解(CR1)和难治复发急性白血病患者的5年预期存活率分别为76.5%、73.9%、70.7%和27.8%.243例中46例(18.9%)移植后疾病复发或移植排斥.58例急性白血病CR1患者中白血病复发率为17.2%,36例难治复发急性白血病复发率为50%.结论 以FAC为基础的非清髓预处理方案有较好的耐受性和造血恢复作用,供体植入可靠,重度GVHD减少,总体生存率较高,为血液病的治疗提供了新途径.     

Nonmyeloablative allogeneic hematopoietic stem cell transplantation

Allogeneic hematopoietic stem cell transplantation (HSCT) is the most effective treatment for selected hematological malignancies. Its curative potential is largely mediated by an immune-mediated destruction of malignant cells by donor lymphocytes termed graft-versus-leukemia (GVL) effect. However, because of its toxicity, conventional allogeneic HSCT is restricted to younger and fitter patients. These observations led several groups to set up new (less toxic) transplant protocols (nonmyeloablative stem cell transplantation or NMSCT) based on a two-step approach: first, the use of immunosuppressive (but nonmyeloablative) preparative regimens providing sufficient immunosuppression to achieve engraftment of allogeneic hematopoietic stem cells and, in a second step, destruction of malignant cells by the GVL effect. Preliminary results showed that NMSCT were feasible with a relatively low transplant-related mortality (TRM), even in patients older than 65 years. In addition, strong antitumor responses were observed in several hematological malignancies as well as in some patients with renal cell carcinoma. After discussing the mechanisms and efficacy of the GVL effect as well as the rationale for NMSCT strategies, this article reviews the first results of ongoing clinical trials. Innovative modalities that may permit amplification of the GVL effect while minimizing the risk of GVHD are discussed. Because the benefits of NMSCT over alternative forms of treatment remain to be demonstrated, this strategy should be restricted to patients included in clinical trials.     

异基因造血干细胞移植后的相关并发症及危险因素

背景：有效预防和治疗异基因造血干细胞移植后并发症是提高患者存活率的重要因素。目的：分析异基因造血干细胞移植后相关并发症的发生和危险因素。
　　方法：应用文献检索的方法获取异基因造血干细胞移植后相关并发症研究的文献,对符合研究标准的文献进行深入的数据分析,文章选取异基因造血干细胞移植后极易发生的并发症进行分析,如肺部并发症、真菌性败血症、巨细胞病毒感染以及中枢神经系统并发症等。
　　结果与结论：异基因造血干细胞移植后易出现肺部并发症,而且死亡率较高,肺部并发症的发病机制可能与移植物抗宿主病和巨细胞病毒抗原血症相关。异基因造血干细胞移植后真菌性败血症病原菌以假丝酵母菌属为主,死亡率较高,应二级预防性和早期经验性抗真菌治疗。更昔洛韦、膦甲酸钠对异基因造血干细胞移植后巨细胞病毒感染的治疗有效。中枢神经系统并发症在异基因造血干细胞移植后发生率较低,但在治疗过程也不容忽视。异基因造血干细胞移植后相关并发症的发生与多种危险因素有关,在临床治疗过程中要对相关因素采取预防措施,减少并发症的发生,提高患者的存活率。     

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。     

Resilience in patients after allogeneic stem cell transplantation

Purpose

After undergoing allogeneic stem cell transplantation (alloSCT), patients adapt in very different ways to their taxing situation. Some patients cope very well; others almost seem to fail. Psychosocial variables are important factors for successful reintegration. Besides quality of life, resilience may help to understand the variance in individual differences in adaptation after alloSCT.

Methods

A pilot study at the University Hospital Muenster, Germany, assessed resilience in patients after alloSCT. The sample included 75 patients (leukemia, lymphoma, myeloma, aplastic anemia) aged 20–76 years. The instruments Resilience Scale RS-25, Hospital Anxiety and Depression Scale, General Self-efficacy Scale, and EORTC QLQ-C30 were used.

Results

Resilience is positively correlated with quality of life (Spearman’s rho 0.587) and social functioning (0.472), negatively with anxiety (?0.491) and depression (?0.577). Dividing the sample at the median resilience score of 144 reveals that high-resilience patients report less anxiety (p?=?0.008) and depression (p?<?0.001); higher physical (p?=?0.041), emotional (p?=?0.030), and social functioning (p?=?0.003); and a better quality of life (p?<?0.001) than low-resilience patients. No effects on resilience were found for age, gender, and primary disease entity. The high correlation of resilience and self-efficacy (r?=?0.698) shows the strong relationship between the two concepts. Our results indicate a potential influence of the time span from alloSCT on patients’ resilience.

Conclusions

Resilience should be considered as a protective psychosocial factor for patients after alloSCT. A high degree of resilience can help patients to adapt to their situation and to resume their everyday life.     

Reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation

Chemotherapy and radiotherapy administered in preparation for allogeneic hematopoietic progenitor cell transplantation serve the dual role of providing antitumor activity as well as immunosuppression to prevent graft rejection. Conditioning regimens were initially designed to provide dose-intense therapy in order to overcome tumor resistance. These forms of transplants, referred to as ablative regimens, often result in significant extramedullary toxicity, limiting its applicability to younger, fitter patients. Reduced-intensity conditioning (RIC) transplants are a direct result of an understanding of the immunotherapeutic potential of the donated hematopoietic stem cells. These forms of transplants administer chemoradiotherapy with the intent of allowing for donor cell engraftment with less of an emphasis on dose intensity. In so doing, treatment-related mortality has been reduced, and older-aged patients and those with co-morbidities are now frequently offered this therapy. In the decade since its creation, RIC transplantation has changed the spectrum of patients with malignancies who may benefit from this therapy. For the first time, transplant patients are becoming more representative of the populations most at risk for diseases requiring this therapy. This article reviews the science behind RIC transplants and provides a concise summary of the current body of evidence for the major indications for which it is most commonly employed. The data presented will demonstrate that age should no longer be the sole deciding factor for referral for allogeneic transplant.     

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.     

异基因造血干细胞移植植入失败的危险因素分析

异基因造血干细胞移植(allo-HSCT)目前已广泛应用于急性白血病(AL)、再生障碍性贫血(AA)等多种血液病的治疗。植入失败是allo-HSCT后的严重并发症。原发性植入失败是指造血未能重建,常需要二次移植;继发性植入失败是指供者细胞成功植入后再次丢失,少数患者可逐步恢复自身造血[1]。恶性血液病中,清髓性预处理(MAC)移植后植入失败的发生率为1%~5%,减低剂量预处理(RIC)移植后植入失败的发生率可达5%~20%[1-2]。目前已报道的植入失败的危险因素包括HLA配型不合、ABO血型不合、RIC、干细胞输注数量较少、供者年龄较大等[3-7]。本研究对298例接受allo-HSCT的血液病患者进行回顾性分析,探讨发生植入失败的危险因素。     

异基因造血干细胞移植后发生巨细胞病毒感染的临床分析

本研究总结巨细胞病毒(CMV)感染的发生及治疗。对北京军区总医院血液科2010年1月至2012年1月140例异基因造血干细胞移植(allo-HSCT)患者的临床资料进行了回顾性分析。结果表明,140例allo-HSCT中48例患者发生移植后CMV感染,发生率为34.3%,首次检出CMV-DNA阳性中位时间为移植后45(33-68)d,CMV定量范围为1.25×103-5.5×106,其中2例为CMV相关性间质性肺炎,5例为CMV相关性出血性膀胱炎。发生移植物抗宿主病(GVHD)患者共65例,其中合并CMV感染32例,占49.2%。应用更昔洛韦、膦甲酸钠抗CMV治疗45(33-68)d后CMV-DNA转阴,有效率为100%。共有12例患者治疗过程中出现一过性的白细胞和血小板减少。结论:allo-HSCT后较易发生CMV感染,发生GVHD的患者CMV感染发生率也较高,更昔洛韦、膦甲酸钠对allo-HSCT后CMV感染的治疗效果可靠,且不良反应少。     

异基因造血干细胞移植患者预处理后并发毛细血管渗漏综合征的护理

该文总结了4例异基因造血干细胞移植预处理后并发毛细血管渗漏综合征患者的护理经验。护理要点：观察患者病情变化、加强出入量的监测与护理、使用高流量湿化呼吸治疗仪、加强基础护理同时给予适当的心理疏导。经过早发现、早治疗并给予个体化的护理,4例患者均顺利转出移植仓。     

异基因造血干细胞移植术后并发肠道移植物抗宿主病的护理

总结10例异基因造血干细胞移植术后并发肠道移植物抗宿主病(GVHD)患者的护理经验。遵医嘱给予甲强龙冲击治疗,调整免疫抑制剂的种类,联合应用免疫球蛋白;护理中对症支持处理,细致进行病情观察、用药指导及基础护理等。8例患者病情缓解出院,2例死亡。     

2例异基因造血干细胞移植术后移植物抗宿主病患者行肺移植术的护理

总结2例异基因造血干细胞移植术后移植物抗宿主病患者行肺移植术的护理经验。护理要点包括排异反应的观察及预防;严格落实防控措施,降低感染风险;通过各种康复训练,促进呼吸功能恢复;进行营养筛查,制订营养支持计划;及时评估心理状态,个体化靶向心理疏导等。经过积极的治疗和护理,2例患者恢复良好,顺利转出监护室。     

白消安在非亲缘异基因造血干细胞移植预处理中的应用

背景：口服白消安剂型胃肠道吸收不稳定,影响异基因造血干细胞疗效且毒性增加。静脉剂型白消安位国内最近几年用于临床,但在非亲缘异基因移植预处理中应用的相关报道甚少。目的：探讨静脉剂型白消安在非亲缘异基因造血干细胞移植预处理中应用的疗效并观察其毒副作用。方法：14例非亲缘异基因干细胞移植采用静脉剂型白消安联合环磷酰胺预处理方案,18例亲缘异基因千细胞移植采用口服白消安联合环磷酰胺预处理方案,观察两组造血重建、植入率等疗效指标及胃肠道反应、口腔黏膜炎、出血性膀胱炎、肝功能损害、移植物抗宿主病等相关毒性指标。结果与结论：两组患者植入率均为100％。静脉剂掣组肝脏毒性、口腔黏膜炎发生率明显低于口服剂型组（14％VS．67％,7％VS．55％）,差异均有显著性意义（P〈0．01）,而胃肠道反应、出血性膀胱炎、造血承建、急性移植物抗宿主病、局限性移植物抗宿主病等方面差异均无显著性意义（P,0．05）。结果可见静脉剂型白消安应用于非亲缘异基因造缸干细胞移植预处理可获得满意疗效,且毒副反应少。