亲缘间单倍体相合造血干细胞移植治疗急性淋巴细胞白血病合并骨髓坏死2例

异基因造血干细胞移植是恶性血液病患者获得治愈的最有效手段,在临床上已广泛开展。急性白血病合并骨髓坏死（bone marrow necrosis,BMN）的病例临床有不少报道,但异基因造血干细胞移植治疗此类病例报道鲜见。我们于2011年收治了2例急性淋巴细胞白血病（acute lymphoblastic leukemia。ALL）合并BMN患者,经化疗诱导BMN逆转后为其实施了亲缘间单倍体相合外周血造血干细胞移植,均成功重建造血功能,现报道如下。     

HLA半相合造血干细胞移植治疗难治性白血病二例

虽然应用HLA半相合造血干细胞移植治疗白血病的病列逐年增加，但用其治疗难治性白血病的病例数仍较少。我完分别于2004年2月和2005年4月对2例难治性白血病施亍了HLA半相合造血干细胞移植，现报告如下。     

系统性红斑狼疮造血干细胞移植治疗进展

系统性红斑狼疮是一种难治性自身免疫病.造血干细胞移植是目前治疗系统性红斑狼疮的较为有效的方法,本文就其移植方面的情况如移植的可能机制、鼠模型及预处理方法的选择、适应症及疗效、如何避免移植排斥反应等做简要阐述.     

慢性移植物抗宿主病的研究进展

异基因造血干细胞移植是目前治疗造血系统恶性肿瘤的重要手段，但移植后的相关并发症严重影响了其治疗效果。目前，在异基因造血干细胞移植后与慢性移植物抗宿主病（cGVHD）相关的死亡率约占非复发性死亡的54％。但对cGVHD发生的机制尚不明确。随着国内外学者研究的不断深入，关于cGVHD的发生机理正逐渐得到揭示，一些新的治疗措施也取得了较理想的效果，这给造血干细胞移植及cGVHD患者带来新的希望。     

造血干细胞移植后并发带状疱疹临床分析

目的 探讨造血干细胞移植后带状疱疹发病情况、临床特点、治疗及转归.方法 回顾分析浙江省中医院血液科可评估的104例接受造血干细胞移植患者预处理方案、移植物抗宿主病预防方案及病毒感染的防治方案等临床资料.结果 104例接受造血干细胞移植患者中有24例(23.08% )并发带状疱疹,其中单倍体相合造血干细胞移植患者带状疱疹发生率为47.6%,非亲缘造血干细胞移植患者带状疱疹发生率为42.1%.应用抗病毒药物,适当减少免疫抑制剂用量及输注人免疫球蛋白,外用干扰素,同时中医中药辅助治疗,平均治疗(20.5±3.8)d后,患者疱疹全部消退,有4 例出现严重疱疹后神经痛,其中2例伴有局部肌肉萎缩.无泛发性疱疹及内脏受累病例,无疱疹相关死亡.结论 造血干细胞移植后发生的带状疱疹起病不典型,综合治疗能够有效地控制,但神经痛持续时间较长.     

用于异基因移植的造血干细胞来源

造血干细胞移植(hcmatopoiedc stem cell transplantation，HSCT)的临床应用已有近50年的历史，目前已成为治疗多种良恶性血液病、实体肿瘤、遗传性疾病和重症自身免疫性疾病等的有效手段。本文试就异基因造血干细胞移植中应用的不同来源造血干细胞(hematopoietic stemcell，HSC)的特点及其对移植效果的影响作一评述。     

造血干细胞移植治疗多发性骨髓瘤(附视频)

自体造血干细胞移植治疗多发性骨髓瘤(MM)始于20世纪80年代。多个历史对照和随机临床研究显示自体造血干细胞移植较传统化疗可提高治疗的反应率、完全缓解率、无事件存活率和/或总存活率,而治疗反应程度与生存相关。由此自体造血干细胞移植在欧美国家已成为年轻、适合移植(年龄≤65岁、肾功能正常和一般状况良好)MM患者的一线标准治疗方法。双次移植有可能进一步提高治疗反应率、无事件存活率和/或总存活率。免疫调节药物沙利度胺及其衍生物来那度胺和蛋白酶体抑制剂硼替佐米等新型抗骨髓瘤药物的发展提高了治疗的反应率和缓解率。目前新药并不能替代自体造血干细胞移植;这些药物运用于移植前后的整体治疗策略进一步提高了移植疗效。尽管如此,MM仍然是难以治愈的疾病。异基因造血干细胞移植有治愈MM的可能,但因清髓性预处理的高死亡率限制了其应用。近年来,联合移植即自体造血干细胞移植后进行减低剂量预处理的异基因造血干细胞移植的研究结果初步显示了其疗效和可行性。     

造血干细胞移植治疗自身免疫性疾病

近十余年来，造血干细胞移植技术(hematopoietic stem cell transplantation，HSCT)治疗难治性自身免疫性疾病(autoinmamedisease，ADs)，业已取得了可喜的成绩。国内外学者把病情进展快，造成明显残疾或早期死亡的ADs，归为“严重自身免疫病”(SADs)，其预期生存期为5～10年；近年随着医学科学的进展，自身造血干细胞移植的治疗相关病死率为1％～5％；对SADs患者，在发展到不可逆脏器损伤前，进行积极的治疗是合理的、必要的。现将HSCT治疗ADs的机制、适应证、方式和过程做简要叙述。     

成人急性淋巴细胞白血病治疗的比较性研究

本文综述了异基因造血干细胞移植与自体造血干细胞移植治疗成人急性淋巴细胞白血病的疗效及研究现状，比较了不同治疗方法的差异，提出了今后研究中需要解决的问题。     

以肾病综合征为主要表现的慢性移植物抗宿主病

移植物抗宿主病是造血干细胞移植后常见的并发症，主要累及皮肤、肝脏及消化道等组织器官，肾脏极少受累及。近年来，临床观察发现以肾病综合征为表现的慢性移植物抗宿主病。本文对异基因造血干细胞移植后以肾病综合征为表现的慢性移植物抗宿主病的病理改变、临床特点、诊断及治疗进行综述。     

非清髓预处理后自体外周血造血干细胞移植治疗难治性重症肌无力远期疗效观察

目的观察体外纯化的自体外周血CD34+细胞移植于经非清髓预处理方案治疗的难治性重症肌无力(MG)患者的远期疗效。方法回顾性分析浙江中医药大学附属第一医院血液科2005年2月至2010年2月期间经纯化的自体外周血CD34+细胞移植治疗5例难治性MG患者资料。采用FAC预处理方案:磷酸氟达拉滨30mg·m-2·d-1,共4d;抗胸腺细胞球蛋白2.5mg·kg-1·d-1或抗淋巴细胞球蛋白30mg·kg-1·d-1,共4d;环磷酰胺50～60mg·kg-1·d-1,共2d。结果 5例患者均获造血、免疫重建,无移植相关死亡。全部患者均随访至2012年2月,中位随访时间44(24～84)个月,其中肌力正常,恢复正常生活、工作,脱离药物治疗4例,另1例移植后12个月因疾病复发而再次应用小剂量泼尼松、溴吡斯的明维持治疗患者目前肌无力症状控制良好,生活自理。结论 FAC预处理方案应用于纯化的自体外周血CD34+细胞移植治疗难治性MG远期疗效较好,患者的耐受性良好,值得进一步临床研究。+     

Immune roles of dendritic cells in stem cell transplantation

Dendritic cells (DCs) are professional antigen‐presenting cells and initial stimulators for immune response. DCs can shape their functions based on their immune states, which are crucial for the balance of immunity and tolerance to preserve homeostasis. In the immune response involved in stem cell transplantation, DCs also play important roles in inducing immune tolerance and antitumor immunity. After the rapid development of stem cell transplantation technology in recent years, the risks of graft rejection, tumor recurrence, and tumorigenicity are still present after stem cell transplantation. It is important to understand the mechanisms of DC‐mediated immune tolerance and stimulation during stem cell transplantation. In this review, we will summarize and analyze the regulatory mechanisms of DCs in stem cell transplantation and their application in clinical settings. It may help to promote the innovation in basic theories and therapeutic approaches of stem cell transplantation.     

调节性T细胞在重症肌无力研究中的进展

重症肌无力(MG)为一种由乙酰胆碱受体的抗体介导的、具有T细胞依赖性的自身免疫性疾病。目前研究发现,调节性T细胞(Treg)功能异常在多种自身免疫性疾病包括重症肌无力的发生、发展起着重要作用。文章重点介绍了Treg细胞的特点及其在重症肌无力作用机制方面的进展,旨在能够发现一种对重症肌无力和其他自身免疫性疾病有效的以异常T细胞为基础的治疗方法。     

Nonmyeloablative stem cell transplantation and cell therapy for malignant and non-malignant diseases

The conditioning prior to allogeneic stem cell transplantation was originally designed as a myeloablative conditioning, designed to eliminate malignant or genetically abnormal cells and then use the transplant procedure for rescue of the patients or to replace missing bone marrow products. However, allografts can induce effective graft vs. malignancy effects and can also eliminate undesirable hematopoietic stem cells in patients with genetic disorders and autoimmune diseases, thus documenting that alloreactive effects mediated by donor lymphocytes post-grafting can play a major role in eliminating hematopoietic cell of host origin, as well as provide effective immunotherapy for the treatment of disease recurrence. The efficacy of donor lymphocyte infusion (DLI) could be improved by activation with rIL-2 or by donor immunization. The cumulative experience over the years suggesting that alloreactive donor lymphocytes were most effective in eliminating tumor cells of host origin resulted in an attempt to reduce the intensity of the conditioning in preparation for the transplant procedure used for the treatment of hematological and other malignancies as well as life-threatening non-malignant disorders for which allogeneic stem cell transplantation may be indicated. Our working hypothesis proposed that the myeloablative conditioning which is hazardous and may be associated with early and late side effects, may not be required for treatment of patients with any indication for allogeneic stem cell transplantation. Instead, nonmyeloablative conditioning based on the use of reduced intensive preparatory regimen, also known as nonmyeloablative stem cell transplantation, may be sufficient for engraftment of donor stem cells while avoiding procedure-related toxicity and mortality, followed by elimination of undesirable cells of host origin by post-transplant effects mediated by alloreactive donor lymphocytes infused along with donor stem cells or administered subsequently as DLI. Improvement of the immediate outcome of stem cell transplantation using NST due to a significant decrease in transplant related mortality has broadened the spectrum of patients eligible for allogeneic stem cell transplantation, including elderly patients and other patients with less than optimal performance status. Likewise, the safer use of stem cell transplantation prompted expanding the scope of potential indications for allogeneic stem cell transplantation, such as metastatic solid tumors and autoimmune disorders, which now are slowly becoming much more acceptable. Current strategies focus on the need to improve the capacity of donor lymphocytes to eliminate undesirable malignant and non-malignant hematopoietic cells of host origin, replacing abnormal or malignant stem cells or their products with normal hematopoietic stem cells of donor origin, while minimizing procedure-related toxicity and mortality and improving the quality of life by reducing the incidence and severity of hazardous acute and chronic GVHD.     

Nonmyeloablative Conditioning Generates Autoantigen‐Encoding Bone Marrow That Prevents and Cures an Experimental Autoimmune Disease

Autoimmune diseases result from chronic targeted immune responses that lead to tissue pathology and disease. The potential of autologous hematopoietic stem cells transplantation as a treatment for autoimmunity is currently being trialled but disease relapse is an issue. We have previously shown in a mouse model of experimental autoimmune encephalomyelitis (EAE) that the transplantation of bone marrow (BM) transduced to encode the autoantigen myelin oligodendrocyte glycoprotein (MOG) can prevent disease induction. However these studies were performed using lethal irradiation to generate BM chimeras and a critical factor for translation to humans would be the ability to utilize low toxic preconditioning regimes. In this study, treosulfan was used as a nonmyeloablative agent to generate BM chimeras encoding MOG and assessed in models of EAE induction and reversal. We find that treosulfan conditioning can promote a low degree of chimerism that is sufficient to promote antigen specific tolerance and protect mice from EAE. When incorporated into a curative protocol for treating mice with established EAE, nonmyeloablative conditioning and low chimerism was equally efficient in maintaining disease resistance. These studies further underpin the potential and feasibility of utilizing a gene therapy approach to treat autoimmune disease.     

From islet of Langerhans transplantation to the bioartificial pancreas

Type 1 diabetes is a disease resulting from autoimmune destruction of the insulin-producing beta cells in the pancreas. When type 1 diabetes develops into severe secondary complications, in particular end-stage nephropathy, or life-threatening severe hypoglycemia, the best therapeutic approach is pancreas transplantation, or more recently transplantation of the pancreatic islets of Langerhans. Islet transplantation is a cell therapy procedure, that is minimally invasive and has a low morbidity, but does not display the same rate of functional success as the more invasive pancreas transplantation because of suboptimal engraftment and survival. Another issue is that pancreas or islet transplantation (collectively known as beta cell replacement therapy) is limited by the shortage of organ donors and by the need for lifelong immunosuppression to prevent immune rejection and recurrence of autoimmunity.A bioartificial pancreas is a construct made of functional, insulin-producing tissue, embedded in an anti-inflammatory, immunomodulatory microenvironment and encapsulated in a perm-selective membrane allowing glucose sensing and insulin release, but isolating from attacks by cells of the immune system. A successful bioartificial pancreas would address the issues of engraftment, survival and rejection. Inclusion of unlimited sources of insulin-producing cells, such as xenogeneic porcine islets or stem cell-derived beta cells would further solve the problem of organ shortage.This article reviews the current status of clinical islet transplantation, the strategies aiming at developing a bioartificial pancreas, the clinical trials conducted in the field and the perspectives for further progress.     

树突细胞在造血干细胞移植相关移植物抗宿主病中的作用及其靶向治疗研究进展

造血干细胞移植（HSCT）是治疗血液系统恶性肿瘤的重要手段,移植物抗宿主病（GVnD）的发生严重影响其整体疗效。树突细胞（DC）是连接固有免疫和适应性免疫的重要桥梁,是GVHD的启动者。对DC功能的研究有助于进一步加深对GVHD的认识,通过靶向治疗实现对DC功能的调节从而提高HSCT整体疗效。     

Use of G‐CSF‐stimulated marrow in allogeneic hematopoietic stem cell transplantation settings: a comprehensive review

Chang Y‐J, Huang X‐J. Use of G‐CSF‐stimulated marrow in allogeneic hematopoietic stem cell transplantation settings: a comprehensive review.
Clin Transplant 2011: 25: 13–23. © 2010 John Wiley & Sons A/S. Abstract: In recent years, several researchers have unraveled the previously unrecognized effects of granulocyte colony‐stimulating factor (G‐CSF) on hematopoiesis and the immune cell functions of bone marrow in healthy donors. In human leukocyte antigen‐matched or haploidentical transplant settings, available data have established the safety of using G‐CSF‐stimulated bone marrow grafts, as well as the ability of this source to produce rapid and sustained engraftment. Interestingly, G‐CSF‐primed bone marrow transplants could capture the advantages of blood stem cell transplants, without the increased risk of chronic graft‐versus‐host disease that is associated with blood stem cell transplants. This review summarizes the growing body of evidence that supports the use of G‐CSF‐stimulated bone marrow grafts as an alternative stem cell source in allogeneic hematopoietic stem cell transplantation.     

Clinical characteristics and prognosis of myasthenia gravis with other autoimmune diseases

Of 277 patients with myasthenia gravis (MG) who underwent thymectomy, including 78 with thymomatous MG, 33 patients had other autoimmune diseases. The clinical characteristics of MG with other autoimmune disease were investigated. Graves's disease and rheumatoid arthritis were the most common autoimmune diseases seen. The association rate of autoimmune disease in patients with thymomatous MG (3.8%) was significantly lower than that in patients with nonthymomatous MG (15.1%). The positive rate for a germinal center in the thymus was significantly higher in patients with other autoimmune disease than in those without such disease. Thymectomy was effective for MG in patients with an associated disease as well as in those without such a complication. The clinical course of the associated autoimmune disease did not seem to be adversely affected by thymectomy. Therefore, thymectomy should be performed in MG patients with other autoimmune disease.     

血浆单核细胞趋化蛋白-2水平不能作为Allo-HSCT术后早期急性移植物抗宿主疾病与感染的鉴别指标

目的 研究检测血浆单核细胞趋化蛋白-2(monocyte chemoattractant protein-2,MCP-2)水平作为区分白血病患者行异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,Allo-HSCT)后出现中性粒细胞缺乏合并感染(...