造血干细胞移植的临床进展

 异基因造血干细胞移植（allo-HSCT）是治愈恶性血液病、重型再生障碍性贫血和遗传性血液病的重要方法,近年造血干细胞移植（HSCT）在诸多方面都取得了重要及深刻的发展,就al-lo-HSCT在血液病治疗体系中的地位、单体型HSCT、非血缘供体HSCT、非清髓性HSCT和脐血HSCT的策略以及临床移植免疫研究领域的相关进展进行了阐述。     

脐血干细胞移植的研究现状与应用前景

造血干细胞移植在多种血液病和某些恶性实体肿瘤的治疗中有肯定的疗效,是某些白血病和恶性淋巴瘤的唯一根治手段。但无论是自体或异基因造血干细胞移植,都存在着某些不足,限制了这一疗法的广泛应用。而脐带/胎盘血则可以弥补自体或异基因移植的某些不足,且来源广泛,因而近年来受到越来越多的重视。自从1989年世界上首例脐血干细胞移植成功后,近年来进行了广泛的研究,本文就此作一综述。 1 脐血干细胞的特点 脐带/胎盘血是在足月胎儿娩出之后,经结扎脐带断脐,通过脐静脉穿刺或切开引流收集到的残存在胎盘和脐带中的血液。在胚胎发生的过程中,造血干细胞起源于卵黄囊,逐渐经血液循环迁移至胎儿肝脏及骨髓,32周胎龄前的胎儿循环中含丰富的造血干祖细胞,至34周龄时大部分造血干细胞已完成迁移,但在出生前胎儿的血循环中仍含有较多的造血干细胞成分,至出生后数月才降至成人外周血水平。1974年Knudtzon报告,在半固体琼脂培养中发现人脐血粒单系集落形成单位(CFU—GM)的产率(17～385/2×10~5)明显高于成人外周血(0～11/2×10~5)。随后的研究发现,脐血中含有各系造血干祖细胞,包括红系集落形成单位(CFU—E)、爆式红系集落形成单位(BFU—E)、巨核系集落形成单位(CFU—Meg)、粒、红、巨核、巨嗜集落形成单位     

异基因造血干细胞移植治疗晚期胸部肿瘤

异基因外周血造血干细胞移植（allogeneic hematopoietic stem cell transplantation,allo-HSCT）已成为治疗恶性疾病的有效手段之一。但既往干细胞移植多用于血液系统疾病的治疗。晚期胸部恶性肿瘤常规治疗效果极差,为了寻找新的有效的治疗方法对3例晚期胸部恶性肿瘤患者成功进行了非清髓异基因外周血造血干细胞移植（allo—NST）治疗，其中1例患者移植后生存19个月。     

大力开展异体外周血造血干细胞移植的研究

大力开展异体外周血造血干细胞移植的研究曹履先造血干细胞移植是近３０年来血液病治疗上的一个重要进展，它可以使许多恶性血液病（如白血病）、非恶性血液病（如再障贫血）得到根治。近５年来自体外周血造血干细胞的移植已广泛用于恶性血液病及实体瘤的治疗上。由于造血...     

自体造血干细胞移植后血液重建影响因素研究进展

自体造血干细胞移植是血液系统恶性肿瘤治疗策略之一,成功的自体造血干细胞移植需要具有快速血液重建能力和造血能力持久恢复,若能合理改善影响造血重建因素,将会加速移植后造血重建,从而避免潜在的移植相关并发症出现和减少治疗所需费用。本文综述了影响自体造血干细胞移植后血液重建的最新进展,以期对临床工作及相关研究有所帮助。     

自体造血干细胞移植在恶性淋巴瘤中的应用进展

 近年来,自体造血干细胞移植（ASCT）在多种恶性血液病中被成功应用,使之成为治疗恶性淋巴瘤的又一有效手段。就ASCT治疗恶性淋巴瘤的疗效、预处理方案、干细胞采集净化、移植后治疗等方面作简要综述。     

亲缘间单倍体造血干细胞移植治疗心,3E性血液病六例

目的 探讨亲缘间单倍体造血干细胞移植在恶性血液病治疗上的安全性和可行性.方法 对采用亲缘间单倍体造血干细胞移植治疗的6例恶性血液病患者进行病例分析和文献复习.结果 6例患者均达到造血功能重建,Ⅱ～Ⅳ度急性移植物抗宿主病(aGVHD)发生率为33.33%,Ⅲ度以上慢性移植物抗宿主病(cGVHD)发生率16.67%,移植相关死亡一例,复发一例.结论亲缘间单倍体造血干细胞移植经改良预处理方案后为恶性血液病的治疗探索了又一安全、有效的新途径.值得临床推广和应用.     

无血缘关系脐血移植治疗儿童恶性淋巴瘤(附1例报告)

近年来 ,骨髓移植及外周血干细胞移植越来越多地被用于化疗敏感恶性肿瘤的治疗 ,但由于人类白细胞抗原 (ＨＬＡ )配型不合及自愿献骨髓的人数较少 ,应用受到限制 ,尤其是独生子女因无同胞供体 ,开展例数更少。近年来的研究表明 ,人脐血中富含ＣＤ34+细胞 ,而且脐血具有独特的免疫特性 ,移植物抗宿主病发生率低 ,反应轻 ,移植成功率高 ,是可替代骨髓的造血干细胞资源。目前国内外均在逐步开展脐血移植的临床研究。我们对 1例恶性淋巴瘤患儿进行了无血缘关系ＨＬＡ不全相合、ＡＢＯ血型不合的脐血移植成功 ,已随访 1 5年 ,目前状况良好 ,现报…     

自体造血干细胞移植后的免疫重建研究进展

大剂量放化疗联合造血干细胞移植是治疗恶性血液肿瘤及部分实体瘤的新疗法之一。在世界范围内,每年大约有1万例自体造血干细胞移植用来治疗恶性肿瘤。近年来的各项随机实验证实,大剂量化疗联合自体造血干细胞输注可明显延长血液系统恶性疾病包括复发的非霍奇金淋巴瘤犤1犦,急性髓性白血病犤2犦和多发性骨髓瘤犤3犦患者的无病生存期(DFS)。在实体瘤的治疗上也已取得了较好的效果犤4犦。然而,移植后仍有部分病人出现复发和转移,移植后免疫功能的长期抑制是造成移植后恶性肿瘤复发的重要原因之一,移植后免疫功能的状态及免疫治疗对清除体内残…     

大剂量化疗联合自体造血干细胞移植治疗淋巴瘤的疗效

目的:观察大剂量化疗联合自体造血干细胞移植治疗恶性淋巴瘤的疗效。方法:选择2009年12月－2015年12月于我科住院治疗的恶性淋巴瘤病例30例,均接受大剂量化疗联合自体造血干细胞移植治疗。结果:1例患者造血干细胞回输后因严重肺部感染死亡,其余均成功植入并快速重建造血;随访至2016年3月1日,有22例存活,无病生存19例,9例复发,中位复发时间为4.5(1~15)个月,其中6例复发后3年内死亡,2例治疗后重新评估为CR随访至今未再复发,1例为单一椎体复发至今仍存活。移植相关死亡率为6.7%。结论:大剂量化疗联合自体造血干细胞移植能很快重建造血,是治疗恶性淋巴瘤安全有效的方法。     

Cord blood transplantation

Unrelated cord blood transplantation (CBT) has now become more common. In the last decade, CBT has increasingly been utilized not only for children, but also for adults. As a source of hematopoietic stem cells (HSCs), umbilical cord blood has the advantages of speed of availability, tolerance of 1-2 antigen HLA mismatch, and a low incidence of severe graft-versus-host disease (GVHD). Thus, UCB represents a highly convenient HSC source that may significantly extend the HSC donor pool. As graft cell dose is the major factor determining hematopoietic recovery and survival in CBT, methods to increase cell dose such as multiple-unit transplant and ex vivo expansion, or to increase stem cell homing such as intra-bone transplantation are being pursued. We could also speculate the existence of unique pathophysiology of acute GVHD after CBT compared with after bone marrow transplantation due to our clinical analysis. It might be very important to establish new standard management including immunosuppressive procedure after CBT to consistently keep better clinical results. Umbilical cord blood is promising alternative to bone marrow-derived stem cells. More prospective studies are needed to establish the role of CBT during various allogeneic HSC transplantations.     

Umbilical cord blood transplantation

Over the past decade umbilical cord blood has been established as a viable source of hematopoietic stem cells for allogeneic transplantation. Early experience with umbilical cord blood transplantation (CBT) demonstrated a lower incidence of graft-versus-host disease even though the procedure was performed with HLA-disparate grafts. The overall outcome of CBT appears similar to that of allogeneic bone marrow transplantation. The expansion of the donor selection is particularly beneficial to ethnic minorities, whose representation in the marrow registries is relatively small. The major drawbacks of CBT are slow hematopoietic recovery and a high incidence of graft failure, as a result of a lower number of progenitors infused. This paper reviews the current results of CBT and ongoing investigations to increase its availability to a larger number of recipients.     

Umbilical cord blood transplantation

Over the past decade umbilical cord blood has been established as a viable source of hematopoietic stem cells for allogeneic transplantation. Early experience with umbilical cord blood transplantation (CBT) demonstrated a lower incidence of graft-versus-host disease even though the procedure was performed with HLA-disparate grafts. The overall outcome of CBT appears similar to that of allogeneic bone marrow transplantation. The expansion of the donor selection is particularly beneficial to ethnic minorities, whose representation in the marrow registries is relatively small. The major drawbacks of CBT are slow hematopoietic recovery and a high incidence of graft failure, as a result of a lower number of progenitors infused. This paper reviews the current results of CBT and ongoing investigations to increase its availability to a larger number of recipients.     

Umbilical cord blood transplantation

Over the past decade umbilical cord blood has been established as a viable source of hematopoietic stem cell for allogeneic transplantation. Early experience with umbilical cord blood transplantation (CBT) demonstrated a lower incidence of graftversus-host disease even though the procedure was performed with HLA-disparate grafts. The overall outcome of CBT appears similar to that of allogeneic bone marrow transplant. The expansion of the donor selection is particularly beneficial to ethnic minorities, whose representation in the marrow registries is relatively small. The major drawbacks of CBT are slow hematopoietic recovery and a high incidence of graft failure, as a result of a lower number of progenitors infused. This paper reviews the current results of CBT and ongoing investigations to increase its availability to a larger number of recipients.     

Cord stem-cell transplantation in Ontario: do we need a public bank?

It has been 21 years since the first successful use of umbilical cord blood as a source of donor cells for hematopoietic stem cell transplantation (HSCT). Over those years, cord blood transplantation (CBT) has shown marked success as an effective modality in the treatment of children and adults with hematologic malignancies, marrow failure, immunodeficiency, hemoglobinopathy, and inherited metabolic diseases. Furthermore, transplantation without full human leukocyte antigen (HLA) matching is possible and, despite a lower incidence of graft-versus-host disease, graft-versus-leukemia effect is preserved. More than 20,000 cbts have been performed worldwide. Ontario is the most populated province in Canada, and its cbt numbers have increased dramatically in recent years, but most of the umbilical cord blood units are purchased from unrelated international registries. There is no public cord bank in Ontario, but there is a private cord banking option, and notably, Ontario has the largest number of live births in Canada [approximately 40% of all Canadian live births per year occur in Ontario (Statistics Canada, 2007)]. In this brief review, the pros and cons of private and public cord banking and the feasibility of starting an Ontario public cord bank are discussed.     

Umbilical cord blood transplantation: current state of the art

Human leukocyte antigen-matched sibling donor umbilical cord blood transplantation, or 0-2 human leukocyte antigen mismatched unrelated donor umbilical cord blood, is now considered an acceptable alternative to the use of bone marrow as a source for hematopoietic stem cells for pediatric hematopoietic stem cell transplantation, and is being investigated in adults. Major advantages of umbilical cord blood include the speed of availability compared with unrelated donor bone marrow, and tolerance of 1-2 human leukocyte antigen mismatch, which offers the opportunity to extend the donor pool. Umbilical cord blood transplantation is associated with durable engraftment and low incidence of severe graft-versus-host disease, even in the 1-2 human leukocyte antigen mismatched setting. Clinical experience has established the importance of graft cell dose in determining engraftment and survival in unrelated donor umbilical cord blood transplantation. More recently, the influence of human leukocyte antigen on outcome has become apparent. This review outlines the state of the art of umbilical cord blood transplantation, with emphasis on practical considerations in umbilical cord blood selection, and describes current research directions for this hematopoietic stem cell source.     

Ex Vivo Expansion or Manipulation of Stem Cells to Improve Outcome of Umbilical Cord Blood Transplantation

The outcome of umbilical cord blood transplantation for adult patients with hematologic malignancies now rivals that of matched unrelated donor transplantation. However, delayed hematopoietic and immunologic recovery remains a source of significant morbidity and mortality. Multiple strategies are now being studied to overcome these limitations. One strategy involves ex vivo expansion of the umbilical cord blood unit prior to transplantation. A second strategy involves exposure of the umbilical cord blood graft to compounds aimed at improving homing and engraftment following transplantation. Such a strategy may also address the problem of slow hematopoietic recovery as well as the increased risk of graft failure. Many of these strategies are now being tested in late phase multi-center clinical trials. If proven cost-effective and efficacious, they may alter the landscape of donor options for allogeneic stem cell transplantation.     

脐带血血清体外培养的人骨髓间充质干细胞对干细胞移植病人造血重建的影响

目的：观察脐带血血清体外培养体系培养的人骨髓间充质干细胞对干细胞移植病人造血重建的影响及不良反应。方法：用10%脐带血血清体外培养体系培养的人骨髓间充质干细胞联合自体外周血干细胞移植治疗3例恶性淋巴瘤患者,计数BM-MSC的数目,观察其造血重建时间、不良反应。结果：采用10%脐带血血清培养体系培养BM-MSC,回输时达到2.82-3.96×106/kg,3例患者中性粒细胞〉0.1×109/L的时间为移植后第9-12天,血小板〉20×109/L的时间为移植后第9-15天,无明显不良反应。结论：10%脐带血血清培养体系是一种基于临床移植需要的分离、培养人BM-MSC的方法,此法培养的BM-MSC联合APBSC移植治疗恶性淋巴瘤患者,加速了造血重建,未见明显不良反应,具有临床应用价值。     

脐血联合单倍型造血干细胞共移植治疗恶性血液病的研究进展

单倍型造血干细胞移植（haploidentical hematopoietic stem cell transplantation,haplo-HSCT）近年来被广泛应用,减轻移植物抗宿主病（graft-versus-host disease,GVHD）发生率,减少移植后并发症、提高患者生存质量为目前临床亟待解决的问题。脐血联合haplo-HSCT已逐渐在国内外部分中心开展,其可以克服haplo-HSCT和脐血干细胞移植的局限性,并保留单倍型移植物抗白血病的作用,在加速造血重建、降低GVHD发生率等方面显示出一定的疗效和应用前景,并且可取得与人类白细胞组织相容性抗原（human leukocyte antigen,HLA）全相合移植类似的疗效。本文就该移植方案的疗效及影响因素,并对移植后病毒感染、免疫重建、造血嵌合状态等进行综述,旨在为临床应用提供参考。      

Allogreffe de sang placentaire chez l’adulte : actualités et perspectives

Hematopoietic stem cell transplantation is the choice treatment of many hematopoietic disorders. However, there is still no related or HLA-matched unrelated donor for one-third of the patients. Cord blood, which contains a lot of hematopoietic progenitors immunologicaly naive, represents not only an interesting alternative as hematopoietic stem cell source but also allows more HLA incompatibilities than the other sources. Promising results in children lead to develop cord blood transplantation in adults first of all in hematopoietic malignancies (acute leukemias and lymphoid diseases) and in a second time, in non-malignant diseases such as aplastic anaemia. The main problems for the development of this new strategy in adults are the poor number of cells per unit, the delay for hematopoietic recovery in comparison with other hematopoietic stem cell sources and, consequently higher transplant related mortality. In order to improve the results in adults, new strategies emerged. Double cord blood transplantation, expansion methods and intrabone injection of the graft will be reviewed here, as well as alternative transplantation strategies such as non-myeloablative conditioning.