脐血造血干细胞移植抗白血病作用的研究

HLA匹配同胞供者造血干细胞移植 (HSCT)是治疗血液系统恶性疾病的有效方法之一 ,但由于供者来源的限制 ,约 2 /3的患者找不到匹配的同胞供者而不能进行HSCT ;而采用其他来源如HLA匹配相关供者及无关供者进行HSCT的成功率较低 ,而且配型时间长 ,无关供者HSCT易并发严重移植物抗宿主病 (GVHD)导致早期死亡、移植后生活质量下降和并发严重感染等。脐血干细胞由于来源广泛 ,寻找相合脐血花费时间短 ,故近年来脐血造血干细胞移植 (UCBSCT)逐渐成为外周血或骨髓造血干细胞移植的一种有效替代手段〔1〕。研究认为UCBSCT用于儿童和…     

间充质干细胞在HLA半相合移植中的应用

造血干细胞移植是治愈恶性血液系统疾病的唯一方法,但寻找HLA完全相合的供者越来越难,HLA半相合移植显示出它独特的优势。骨髓间充质干细胞是骨髓微环境中具有自我更新和多向分化的非造血干细胞,在造血干细胞移植中发挥重要的作用,它能够促进造血重建,与造血干细胞共输注能增强造血干细胞的植入。     

异基因外周血干细胞移植治疗骨髓增生异常综合征18例疗效分析

目的：评价同胞供者异基因外周血干细胞移植（allo—PBSCT）治疗骨髓增生异常综合征（MDS）患者的疗效。方法：1998年5月-2007年4月对18例MDS及MDS转急性髓系白血病（AML）患者进行同胞供者allo-PBSCT治疗。其中供受者HLAA、B、DR6个位点相合者16例,5个位点相合者2例。预处理主要采用修改的Bu-Cy方案。结果：所有患者移植后均重建造血,中性粒细胞数〉0．5×10^9／L中位时间为移植后15．5（11～28）d,血小板≥20×10^9／L中位时间为移植后17（10～50）d。移植后3年总生存率（OS）及无病生存率（DFS）均为（43．2±12．0）％,3年复发率（RR）（9．2-±7．0）％,移植相关死亡率（TRM）（42．1±12．0）%,移植后继发肿瘤2例。截止随访日期,存活10例,中位生存时间16．5（2～112）个月。结论：同胞供者allo—PBSCT是治疗MDS的有效方法。     

ABO血型不合异基因造血干细胞移植临床观察

目的：探讨ABO血型不合异基因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：对15例包括恶性血液病5例(多发性骨髓瘤1例、急性白血病3例、慢性粒细胞白血病1例)、再生障碍性贫血一阵发性睡眠性血红蛋白尿2例、重型再生障碍性贫血8例，进行同胞供者外周血干细胞移植、外周血联合骨髓造血干细胞移植和无关供者脐血造血干细胞移植。观察植入效果、血型的转变、以及移植近远期并发症。结果：15例患者均恢复造血功能，13例植入混合性嵌合体(MC)、其中5例由MC转变为供者完全性嵌合体(CC)，8例长期保持MC状态，2例未植入。所有患者在输注移植物时出现轻微短暂的血红蛋白尿，无严重急性溶血和迟发性溶血发生，无急性移植物抗宿主病(aGVHD)，1例局部型慢性移植物抗宿主病(cGVHD)，1例广泛型cGVHD。在造血植入的患者，脐血移植4例保持MC状态、血型未转变，其余干细胞移植血型在1～2个月转变。结论：ABO血型不合异基因造血干细胞移植治疗血液病疗效肯定，对移植物和供受者体内凝集素的处理十分重要。     

人类白细胞抗原不合或单倍体亲属供者造血干细胞移植

异基因造血干细胞移植(allo-HSCT)是重症血液病的主要根治性治疗方法。除人类白细胞抗原(HLA)相合的健康同胞为首选供者外,非血缘、脐带血和亲属HLA不合或单倍体造血干细胞都作为重要的干细胞来源进入了临床。美国的统计资料显示只有不超过40%的患者可以找到HLA相合的同胞供者。白人中找到非血缘HLA相合供者的机会约为75%,但在少数人种中这一几率低于50%。尽管如此,非血缘供者的查询过程耗时长,使得许多急性患者无法在最适宜的时机接受移植。脐带血来源的造血干细胞虽然可以立即得到,对供者不构成任何负担而且运输过程污染机会小,但…     

重型再生障碍性贫血的异基因造血干细胞移植北大核心CSCD

艾曲泊帕等TPO受体激动剂的加入,重型再生障碍性贫血的免疫抑制治疗疗效取得一定提高,因具有长期治愈的优势,造血干细胞移植、尤其是替代供者造血干细胞移植治疗的进展更为迅速。同胞相合供者造血干细胞移植一直是≤50岁再障患者首选的一线治疗,其适应证具有向51~60岁发展趋势;非血缘相合供者造血干细胞移植广泛应用于儿童重型再障之外,一线治疗成人重型再障的研究也显示出良好疗效和较少的移植物抗宿主病;亲缘单倍体供者造血干细胞移植一线治疗重型再障的临床研究不仅显示良好的生存率、无失败生存率,而且长期随访证实其良好的移植后生活质量。而且造血干细胞移植在难以控制活动性感染下重型再障患者的抢救以及非重型再障发展而来的重型再障治疗方面具有较好的可行性和有效性。     

非血缘造血干细胞移植现状与问题

异基因造血干细胞移植(Allo HSCT)是某些血液系统恶性疾病惟一有望治愈的手段,也是某些血液系统非恶性疾病的重要治疗手段。HLA相合同胞供者是Allo HSCT首选的供者来源,但是只有部分患者可以找到相合的同胞供者。因此,寻找合适的非血缘供者就变得十分重要。近年来,随着移植技术方案的成熟和支持治疗的进步,移植现状已获得明显的改善,非血缘供者造血干细胞移植疗效已达到了与同胞供者移植接近的水平。     

异基因造血干细胞移植治疗白血病的临床研究

目的：探讨异基因造血干细胞移植治疗白血病的疗效及主要并发症的处理。方法：30例5～50岁白血病患者，其中25例接受HLA完全相合、2例接受1～2个HLA主要位点不合同胞供者的外周血干细胞移植。2例接受HLA全相合的非血缘供者骨髓移植。1例接受1个HLA主要位点不合的非血缘脐带血移植。采用改良的环磷酰胺联合全身放疗(CYTBI)或白消安环磷酰胺(BUCY2)方案预处理。采用环孢素A(CsA)联合短程甲氨蝶呤(MTX)方案预防移植物抗宿主病(GVHD)，3例非血缘供者及HLA不全相合移植加用抗人胸腺细胞蛋白(ATG)、霉酚酸酯(MMF)及抗CD25人鼠嵌合抗体。结果：30例均获得植入，2例无关供者移植出现继发性植入失败。13％(4／30)出现Ⅰ～Ⅳ度急性GVHD，26．6％(8／30)出现慢性GVHD。并发间质性肺炎2例。重症(Ⅳ度)出血性膀胱炎1例。纯红细胞性再生障碍性贫血1例。随访2～34个月，现存活21例，8例死于白血病复发，1例死于CMV相关的间质性肺炎。结论：异基因造血干细胞移植是治疗白血病的有效方法，但移植前处于高危难治状态的病例复发率仍较高。     

双份HLA不全相合非血缘脐血移植成功治疗成人急性髓细胞白血病1例报告并文献复习

目的：探讨双份HLA不全相合非血缘脐血移植(UCBT)治疗成人急性髓细胞白血病的造血、免疫重建及植人状态。方法：l例急性单核细胞白血病，43岁，体重75kg，采用双份HLA不全相合非血缘脐血移植治疗急性髓细胞白血病患者1例。预处理方案由白消胺(BU)、环磷酰胺(CY)和抗胸腺细胞球蛋白(ATG)组成。应用环孢素A(CsA)和骁悉(MMF)预防移植物抗宿主病(GVHD)。结果：移植后19天造血重建，NK细胞和B细胞分别于术后30天和120天恢复正常，DNA短串联重复序列多态型(STR)和HLA差异分析显示移植后17天、30天、150天基因型表现为完全性双份供者的嵌合型，未发生GVHD。随访150天，血常规、骨髓象检查正常。结论：双份HLA配型不合的脐血用于成人脐血移植是可行的。     

异基因造血干细胞移植治疗MDS临床研究

目的探讨HLA配型相合异基因造血干细胞移植（allo—HSCT）治疗骨髓增生异常综合征（MDS）的可行治疗方案和疗效。方法以HLA配型相合的骨髓移植治疗MDS患者6例，预处理方案为非清髓性预处理方案1例，清髓性预处理方案5例；以霉酚酸酯、环孢菌素A加短疗程的甲氨喋呤预防移植物抗宿主病（GVHD）。结果6例患者均造血重建。5例清髓性预处理方案仍然无病存活，非清髓性预处理方案1例移植后出现MDS，于移植后17个月死亡。移植后最长无病存活时间已达8a。移植期间发生Ⅰ、Ⅱ°急性移植物抗宿主病（aGVHD）4例。结论allo-HSCT治疗MDS可行、有效，清髓性预处理方案可能对于长期稳定植入有利。     

Heart-lung transplantation

Heart-lung transplantation itself is not a particularly difficult operation technically. It is the setting in which this procedure is performed which is difficult. The three issues of importance in a successful outcome are appropriate harvest of the heart-lung bloc from the donor, careful explant of the heart and lungs of the recipient, and finally the implant of the heart-lung bloc into the recipient. None of this requires extraordinary technical skill, but does require careful coordination and planning as well as adhering to some fundamental principles. One of the major pitfalls encountered is bleeding related to the explant procedure. Another is graft failure related to harvest and/or the implant procedure. The third is injury to either the phrenic nerve(s) or the left recurrent laryngeal nerve related to the explant procedure. Heart-lung transplantation is a major investment in resources of all sorts including financial, personnel, as well as the organs themselves. It is absolutely imperative that this procedure be performed only by experienced surgeons in centers with established expertise.     

Kidney transplantation after liver transplantation

Kidney transplantation after liver transplanta-tion (KALT) offers longer survival and a better quality of life to liver transplantation recipients who develop chronic renal failure. This article aimed to discuss the efifcacy and safety of KALT compared with other treatments. The medical records of 5 patients who had undergone KALT were retrospectively studied, together with a literature review of studies. Three of them developed chronic renal failure after liver transplanta-tion because of calcineurin inhibitor (CNI)-induced neph-rotoxicity, while the others had lupus nephritis or non-CNI drug-induced nephrotoxicity. No mortality was observed in the 5 patients. Three KALT cases showed good prognoses, maintaining a normal serum creatinine level during entire follow-up period. Chronic rejection occurred in the other two patients, and a kidney graft was removed from one of them. Our data suggested that KALT is a good alternative to dialysis for liver transplantation recipients. The cases also indicate that KALT can be performed with good long-term survival.     

Heart transplantation

Heart failure remains a major global problem with approximately 6 million individuals suffering from heart failure in the United States alone. The surgical technique of heart transplantation, popularized by Dr. Norman Shumway, has led to its success and currently remains the best treatment options for patients with end-stage. However, with the continued limitation of donor organs and the rapid development of ventricular assist device technology, the number of patients bridged to transplant with mechanical circulatory support has increased significantly. This has created some new technical challenges for heart transplantation. Therefore, it is now important to be familiar with multiple new technical challenges associated with the surgical techniques of heart transplantation with an ultimate goal in reducing donor heart ischemic time, recipient cardiopulmonary bypass time and post-operative complications. In this review, we described our technique of heart transplantation including the timing of the operation, recipient cardiectomy and donor heart implantation.     

Hepatitis B in transplantation

Hepatitis B has been a major challenge within the field of transplantation over the past few decades. Due to aggressive recurrence post‐transplant, patients with hepatitis B have been excluded from the benefits of both solid organ and bone marrow transplants. Progress has been made, however, through an improved understanding of the biology of hepatitis B and the development of new antiviral strategies that can reliably suppress the virus. Patients with hepatitis B are now candidates for transplantation in an increasing number of circumstances. Careful pre‐transplant evaluation is mandatory, together with a tailored antiviral regimen depending on the replicative status of the virus and the organ being transplanted. Minimizing steroid dose following transplantation is an important part of the strategy to reduce the risk of viral reactivation. Lamivudine has been an important development and it has assumed an increasing role in the management of these patients. As additional antivirals are developed, increasingly effective drug combinations will prevent viral recurrence as well as the emergence of drug‐resistant mutants, which plagues the use of single agents. It is a rapidly evolving field and there is every reason for continued optimism.     

胰腺和胰岛移植的现状和展望

成功的胰岛细胞替代（胰腺器官移植或分离胰岛移植）是治疗1型糖尿病的根本途径。目前胰腺移植主要作为肾移植的附属手术，应用于糖尿病合并尿毒症患者。胰岛细胞移植比胰腺移植更简单、安全。胰岛保存、分离技术和免疫抑制剂的发展将胰岛移植从基础研究推向临床应用。Edmonton方案在胰岛移植临床应用中具有里程碑意义。成体胰岛干细胞研究、胰岛异种移植等新技术的发展，将解决胰岛供体来源不足问题，为胰岛移植带来新的曙光。     

Tolerance and chimerism and allogeneic bone marrow/stem cell transplantation in liver transplantation

The liver has particular tolerogenic properties that allow its spontaneous acceptance in some animal species.Liver structure is considered to favor a tolerogenic environment.The peripheral tolerance mechanisms also play a role in spontaneous tolerance to liver graft.In a clinical setting,the main challenge nowadays facing liver transplantation is minimization of immunosuppression with the goal of donor-specific tolerance.Mechanisms involved in tolerance to transplanted organs are complex and partly unknown.A significant mechanism in tolerance induction is chimerism.Chimerism can be induced through transplantation of allogeneic donor bone marrow/stem cells under appropriate host conditioning.This review focuses on the tolerance mechanisms in liver transplantation and highlights the role of chimerism and allogeneic bone marrow/stem cell transplantation in tolerance development.     

Outcomes in partial liver transplantation: deceased donor split-liver vs. live donor liver transplantation

BackgroundOrgan shortage has resulted in greater emphasis on partial liver transplantation (PLT) as an alternative to whole-organ liver transplantation.MethodsThis study was conducted to assess outcomes in PLT and to compare outcomes of deceased donor split-liver transplantation (DD-SLT) and live donor liver transplantation (LDLT) in adults transplanted in the USA using data reported to the United Network for Organ Sharing in the era of Model for End-stage Liver Disease (MELD) scores.ResultsBetween 2002 and 2009, 2272 PLTs were performed in the USA; these represented 5.3% of all liver transplants carried out in the country and included 557 (24.5%) DD-SLT and 1715 LDLT (75.5%) procedures. The most significant differences between the DD-SLT and LDLT groups related to mean MELD scores, which were lower in LDLT recipients (14.5 vs. 20.9; P < 0.001), mean recipient age, which was lower in the LDLT group (50.7 years vs. 52.8 years; P < 0.001), and mean donor age, which was lower in the DD-SLT group (23.0 years vs. 37.3 years; P < 0.001). Allograft survival was comparable between the two groups (P= 0.438), but patient survival after LDLT was better (P= 0.04). In Cox regression analysis, LDLT was associated with better allograft (hazards ratio [HR]= 0.7, 95% confidence interval [CI] 0.630–0.791; P < 0.0001) and patient (HR = 0.6, 95% CI 0.558–0.644; P < 0.0001) survival than DD-SLT.ConclusionsPartial liver transplantation represents a potentially underutilized resource in the USA. Despite the differences in donor and recipient characteristics, LDLT is associated with better allograft and patient survival than DD-SLT. A different allocation system for DD-SLT allografts that takes into consideration cold ischaemia time and recipient MELD score should be considered.     

Stem-cell transplantation in multiple myeloma

In patient with newly diagnosed multiple myeloma (MM), randomized studies have shown that autologous stem-cell transplantation (ASCT) is superior to conventional chemotherapy, and ASCT is now standard care, at least for younger patients. The best conditioning regimen is melphalan 200 mg/m2, and the best stem-cell source is unselected peripheral progenitor cells. Recent results of the IFM94 trial show that double ASCT is superior to single ASCT, at least in patients who do not achieve a 90% response after one transplant. By combining biologic markers (beta2-microglobulin, albumin) and genetic markers (hypodiploidy, chromosome 13 deletion) it is possible to accurately predict prognosis after ASCT. The results of allogeneic SCT remain disappointing due to a high transplant mortality. Strategies combining ASCT and reduced-intensity allogeneic SCT are currently being studied.