减低预处理强度的异基因造血干细胞移植治疗老年急性髓系白血病的研究进展

急性髓系白血病(AML)是一种恶性血液病,发病高峰年龄超过60岁,采用传统化疗的患者2年总存活率仅为10%～15%[1].异基因造血干细胞移植(allo-HSCT)是治疗AML较有效的手段,但因老年患者的并发疾病多,若行标准预处理强度的allo-HSCT,受者移植相关死亡率较高.     

供体NK细胞对非清髓异基因造血干细胞移植受体异基因反应的抑制作用

<正>异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,allo-HSCT)可以彻底治愈恶性血液病,且复发危险小。但allo-HSCT存在发生移植物抗宿主病及移植排斥反应的风险,临床上主要采用清髓照射及非特异性免疫抑制剂来应对,但部分患     

非清髓性异基因外周血造血干细胞移植治疗恶性血液病七例

非清髓性异基因造血干细胞移植(allo-HSCT)应用剂量相对较低的骨髓非清除性预处理，移植后形成混合嵌合体，减少了移植相关并发症和相关死亡，特别是年龄较大或器官功能异常的患者也可耐受。我们对7例恶性血液病患者采用以氟达拉滨(Flu)为基础的预处理，然后行异基因外周血造血干细胞移植，现报道如下。     

非清髓性异基因造血干细胞移植后CD45RA+细胞的监测及其意义

异基因造血干细胞移植(allo-HSCT)已成为治疗恶性血液病的有效手段,但移植后仍有些患者出现疾病的复发。allo-HSCT后外周血中T淋巴细胞表型和功能的恢复在免疫监视中起着重要作用。我们监测了20例非清髓性异基因造血干细胞移植(NST)患者移植后外周血中CD45RA 细胞的变化,现报告如下。对象与方法一、研究对象20例均为2000年10月至2003年7月在本院接受HLA相合的同胞间外周血异基因造血干细胞移植的患者,其中男性12例,女性8例,年龄18~56岁,中位数35岁。20例的原发病,7例为急性粒细胞白血病(AML),2例为急性淋巴细胞白血病(ALL),11例为…     

移植物抗肿瘤效应及其应用于大肠癌治疗的研究进展

从实验动物模型和临床经验的最新数据表明,异基因干细胞移植(allo-HSCT)可产生类似于移植物抗白血病效应(GVLR)的移植物抗肿瘤效应(GVT),并对实体瘤如大肠癌有治疗作用.笔者就allo-HSCT中产生GVT及其GVT的免疫机制和近几年本allo-HSCT在大肠癌治疗中的研究进展进行综述.     

自体及非清髓性异基因造血干细胞移植治疗多发性骨髓瘤二例

多发性骨髓瘤(multiple myeloma,MM)是浆细胞的恶性肿瘤,大剂量化疗及自体造血干细胞移植(auto-HSCT)使MM的完全缓解率及长期生存有了明显提高,但二者均不能治愈MM.只有接受异基因造血干细胞移植(allo-HSCT)的患者才能够长期无病生存,清髓性allo-HSCT由于其较高的移植相关死亡率,临床应用明显受限.近期我们采用auto-HSCT后序贯给予非清髓性allo-HSCT(NST)治疗2例MM患者,获得较好治疗效果,报道如下.     

自体骨髓间充质干细胞与造血干细胞共移植治疗恶性血液病患者的护理

目的 探讨自体骨髓间充质干细胞(MSCs)与造血干细胞共移植治疗恶性血液病患者的护理.方法 从无骨髓浸润的恶性血液病患者本人骨髓中分离、培养间充质干细胞.经放化疗等预处理后,与造血干细胞共移植治疗恶性血液病患者5例,并对其进行全程共移植护理.结果 在移植过程中5例患者均未出现感染,无移植并发症.自体骨髓间充质干细胞和造血干细胞输注过程中未见明显不良反应.移植后造血功能恢复,中性粒细胞≥0.5×109/L的中位时间为9.4(8～11)d,血小板≥20×109/L的中位时间为12.2(10～14)d.结论 自体骨髓闻充质干细胞与适血干细胞共移植治疗恶性血液病安全性好,不良反应小;做好移植护理是减少感染和并发症的重要措施.     

异基因造血干细胞移植联合利妥昔单抗治疗B淋巴细胞非霍奇金淋巴瘤二例

异基因造血干细胞移植(allo-HSCT)已成为近年来治疗难治、复发的非霍奇金淋巴瘤(NHL)的重要方法之一,而allo-HSCT后的移植物抗肿瘤(GVT)作用有限,且起效时间多在移植3个月以后[1],所以NHL的早期复发是影响allo-HSCT疗效的重要因素之一.     

异基因造血干细胞移植治疗慢性淋巴细胞白血病的研究进展

大多数慢性淋巴细胞白血病(CLL)患者发病时年龄较大,因CLL呈惰性病程,临床上通常不将高强度治疗方案作为治疗CLL的一线应用,但少数患者的CLL恶性程度高,病情进展较快,必要时需考虑行异基因造血干细胞移植(allo-HSCT).鉴于allo-HSCT的风险较高,故明确适应证和选择移植时机至关重要.本文就异基因造血干细胞移植治疗慢性淋巴细胞白血病的进展作如下综述.     

异基因造血干细胞移植后带状疱疹的临床分析

目的 探讨异体基因造血干细胞移植(allo-HSCT)后带状疱疹的发病情况、临床特点、诊治及预后.方法 对河南省肿瘤医院血液科allo-HSCT受者带状疱疹的发生时间、临床表现、治疗及预后进行回顾性分析.结果 可评估的191例接受allo-HSCT患者中有18例并发带状疱疹,发病率为9.42%,其中14例发生在干细胞移植治疗后3～12个月内.10例合并慢性移植物抗宿主病(GVHD),1例合并急性GVHD.临床表现主要为区域性皮肤疱疹.3例出现严重疱疹后神经痛,需强效止痛.无泛发性疱疹及内脏受累病例.所有患者接受抗病毒药物阿昔洛韦和阿糖腺苷静脉输注治疗,全部治愈,无疱疹相关死亡患者,平均治疗时间为15.5 d.结论 带状疱疹是allo-HSCT后常见的病毒感染性疾病,主要发生在干细胞移植治疗后3～12个月,GVHD是其发生的高危因素.阿昔洛韦和阿糖腺苷的疗效较好.     

儿童眼移植物抗宿主病诊治进展

眼移植物抗宿主病是造血干细胞移植术后的常见并发症之一,主要临床表现为干眼,病情进展可出现角膜溃疡穿孔、眼表衰竭等严重并发症,影响患者视力和生活质量.目前,国际上已有较多关于成人眼移植物抗宿主病的研究及临床规范,但关于儿童眼移植物抗宿主病的研究尚未受到足够关注,缺乏相关的基础数据和诊断标准.儿童对眼部症状表述能力有限、临...     

氟达拉滨联合阿糖胞苷化疗治疗异基因造血干细胞移植后急性白血病复发

目的 观察氟达拉滨联合阿糖胞苷(FA方案)大剂量化疗对异基因造血干细胞移植(allo-HSCT)后急性白血病复发的治疗效果.方法 急性白血病患者10例,7例接受亲缘供者造血干细胞移植,3例接受非亲缘供者造血干细胞移植,所有患者移植后均获得造血重建,为完全供者型.10例于首次移植后38～213 d(中位数为126 d)急性白血病复发,其中完全供者型复发1例,完全受者型复发4例,混合嵌合体型复发5例.原发病复发后均采用FA方案化疗,氟达拉滨用量为25 mg/m2,阿糖胞苷用量为1.5 g/m2,用5 d,其中6例于化疗结束后第2天还接受原供者外周造血干细胞(PBSC)移植,未使用预防移植物抗宿主病(GVHD)的药物.结果 除1例早期(8 d)死亡外,其余9例再次获得造血重建,经外周血DNA序列分析证实为完全供者型.获得造血重建的9例,4例由于复发、感染、多脏器功能衰竭等原因死亡,5例无病存活至随访结束,存活时间分别为585、442、405、213和243 d.治疗后,3例未发生GVHD,其余7例发生急性或慢性GVHD;7例并发肺部真菌感染,3例并发出血性膀胱炎,4例并发巨细胞病毒血症.10例的6个月实际无病存活率为60%,2年预期无病存活率为53%.结论 对于allo-HSCT后的急性白血病复发,采用FA方案化疗,如条件允许联合原供者造血干细胞输注,可能是目前可采取的一种有效治疗方案.     

供者NK细胞及其嵌合状态在异基因造血干细胞移植中的研究进展

目前,异基因造血干细胞移植(allo-HSCT)已广泛应用于造血系统疾病的治疗,但移植术后也存在一系列并发症。NK细胞的运用为改善allo-HSCT受者预后带来希望,供者来源NK细胞通过其细胞膜上的杀伤细胞免疫球蛋白样受体与其配体错配发挥同种异体反应,该过程具有保留移植物抗白血病和减少移植物抗宿主病双重效应。NK细胞是allo-HSCT后受者体内最早重建的免疫细胞群,因此移植后供、受者NK细胞嵌合状态评估对预测疾病预后及指导干预治疗具有重要意义。基于NK细胞嵌合状态的供者NK细胞输注免疫干预疗法可改善疾病预后,在血液系统疾病治疗中表现出良好的应用前景。本文就近年来供者NK细胞及其嵌合状态在allo-HSCT中的研究进展作一综述。     

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.     

Highlighting the interaction between immunomodulatory properties of mesenchymal stem cells and signaling pathways contribute to Graft Versus Host Disease management

BackgroundAllogeneic hematopoietic stem cell transplantation (Allo-HSCT) has been increasingly used as a therapeutic approach for hematological malignancies. Several potential strategies have been developed for treating or preventing allo-HSCT complications, specifically graft-versus-host disease (GVHD). GVHD could significantly affect the morbidity and mortality of patients after allo-HSCT. Curative treatment and prophylaxis regimens for GVHD could reduce GVHD incidence and improve survival rate. Among these therapeutic strategies, mesenchymal stem cell (MSCs) mediated immunomodulation has been explored widely in clinical trials. MSCs immunomodulation ability in GVHD correlates with the interactions of MSCs with innate and adaptive immune cells. However, signaling pathways responsible for MSCs' impact on GVHD regulation, like JAK/STAT, NOTCH, MAPK/ERK, and NFκβ signaling pathways, have not been clearly described yet. This review aims to illuminate the effect of MSCs-mediated immunomodulation in GVHD management after allo-HSCT representing the role of MSCs therapy on signaling pathways in GVHD.ConclusionMSCs could potentially modulate immune responses, prevent GVHD, and improve survival after allo-HSCT. Previous studies have investigated different signaling pathways' contributions to MSCs immunoregulatory ability. Accordingly, targeting signaling pathways components involved in MSCs related GVHD regulation is proven to be beneficial.     

伊马替尼治疗慢性移植物抗宿主病2例临床分析

目的探讨伊马替尼治疗异基因造血干细胞移植(allo-HSCT)后慢性移植物抗宿主病(GVHD)伴嗜酸性粒细胞增多的疗效及嗜酸性粒细胞增多与慢性GVHD的关系。方法回顾性分析2例白血病患者allo-HSCT术后慢性GVHD的诊治经过并结合文献复习讨论。结果 2例患者分别于移植后5个月和76d出现口腔溃疡、皮肤瘙痒、皮疹、胆红素水平增高和转氨酶水平增高,伴有嗜酸性粒细胞增多,诊断为局限型慢性GVHD,激素治疗不佳,加用伊马替尼后症状缓解,嗜酸性粒细胞数降至正常,无不良反应。结论伊马替尼治疗慢性移植物抗宿主病安全、有效,嗜酸性粒细胞增多可能与GVHD有一定的关系。     

组织工程角膜上皮联合羊膜移植治疗眼表化学伤效果观察

目的：探讨组织工程角膜上皮联合羊膜移植治疗眼表化学烧伤的临床效果.方法：34例（41只眼）跟表化学烧伤患者按来院先后顺序编号,随机分为两组.观察组18例（22只眼）行组织工程角膜上皮联合新鲜羊膜移植,对照组16例（19只眼）行结膜囊冲洗、前房冲洗和促角膜上皮生长药物点眼等治疗,观察两组临床疗效.术后随访观察角膜上皮化情况和视力恢复情况.结果：全部患者保存了眼球,观察组患者在术后1周内角膜植片水肿明显减轻,术后2～3周角膜缘植片基本透明,未见感染或排斥反应;术后4～6周内,眼表上皮重新上皮化,无瘢痕增生和新生血管化,角膜上皮修复好;术后视力较术前视力明显提高,差异有统计学意义（P〈0.05）;术后随访2～10个月,无假性胬肉及睑球粘连并发症发生.对照组3周内6例眼部炎症基本控制,3例眼部炎症持续超过21 d,4例角膜血管化,3例角膜持续性上皮缺损;治疗后视力较入院时视力变化差异无统计学意义（P〉0.05）.结论：组织工程角膜上皮联合羊膜移植是一种有效的治疗眼表化学烧伤的方法.     

Functional bioengineered corneal epithelial sheet grafts from corneal stem cells expanded ex vivo on a temperature-responsive cell culture surface

BACKGROUND: Limbal stem-cell deficiency by ocular trauma or diseases causes corneal opacification and visual loss. Recent attempts have been made to fabricate corneal epithelial graft constructs, but the technology is still evolving. We have developed a novel cell-sheet manipulation technology using temperature-responsive culture surfaces to generate functional, cultivated corneal epithelial cell sheet grafts. METHODS: Human or rabbit limbal stem cells were cocultured with mitomycin C-treated 3T3 feeder layers on temperature-responsive culture dishes at 37 degrees C. Cell sheets were harvested from the dishes after 2 weeks by reducing temperature to 20 degrees C. Histologic analyses, immunoblotting, and colony-forming assay were performed to characterize the cell sheets. Autologous transplantation was undertaken to reconstruct the corneal surfaces of rabbits with experimentally induced limbal stem cell deficiencies. RESULTS: Multilayered corneal epithelial sheets were harvested intact simply by reducing the temperature, without the use of proteases. Cell-cell junctions and extracellular matrix on the basal side of the sheet, critical to sheet integrity and function, remained intact. A viable population of corneal progenitor cells, close in number to that originally seeded, was found in the sheets. Harvested sheets were easily manipulated, transplantable without any carriers, and readily adhesive to corneal stroma so that suturing was not required. Corneal surface reconstruction in rabbits was highly successful. CONCLUSIONS: Cell sheet engineering technology allows us to create intact, transplantable corneal epithelial cell sheets that retain stem cells from limbal stem cells expanded ex vivo. Our research indicates highly promising clinical capabilities for our bioengineered corneal epithelial sheet.     

异基因造血干细胞移植治疗阵发性睡眠性血红蛋白尿合并再生障碍性贫血

目的探讨异基因造血干细胞移植（allogeneic hematopoietic stem cell transplantation,allo—HSCT）治疗阵发性睡眠性血红蛋白尿（ paroxysmal nocturnal hemoglobinuria, PNH）合并再生障碍性贫血的疗效。方法回顾性分析1例女性PNH合并再生障碍性贫血成功进行allo—HSCT病例的临床资料,患者经药物治疗无效后行allo—HSCT。患者签署知情同意书,符合医学伦理学规定。术前采用清髓性预处理方案。供者为其胞弟,分两次采得单个核细胞数7．8×10^8／kg、6．9×10^8／kg并输入患者体内。观察术后疗效,及复习相关文献。结果allo—HSCT术后30d,骨髓象示增生活跃。术后36d,血常规示血红蛋白110g／L,白细胞5．54×10^9／L,血小板171×10^9／L。术后40d,蔗糖溶血试验、酸溶血试验均阴性;采用流式细胞术检测的红细胞、中性粒细胞的细胞膜上CD55、CD59表达均在正常范围。术后30d,受者原女性染色体变为46,XY[11];术后132d,受者ABO血型由B型转为O型（供者型）,表明移植成功。受者未出现急性移植物抗宿主病（aGVHD）。术后60d出现眼干、分泌物增多等症状,加用甲泼尼龙治疗后好转。随访10个月,血常规、骨髓象、CD55及CD59测定均正常,肝、肾功能正常,受者健康生存。结论难治性PNH可考虑行allo—HSCT治疗予以根治。     

Corneal stem cells in review

The cornea provides the eye with protection and the refractive properties essential for visual acuity. The transparent epithelium is highly specialized with basal and stratified squamous cells that are renewed throughout life from a stem cell population. The stem cells are thought to reside at the corneal limbus and may be maintained by a variety of intrinsic and extrinsic factors such as the local environment, survival factors, and cytokines. A number of markers have been localized to the limbus in an attempt to identify stem cells; however, definite stem cell identification remains elusive. During homeostasis and following injury to the corneal epithelium, the limbal stem cells divide to produce daughter transient amplifying cells that proliferate, migrate, and differentiate to replace lost cells. However, this cannot occur if the stem cell population is depleted. Limbal stem cell deficiency then results in corneal re-epithelialization by the neighboring conjunctiva, causing pain, poor vision, and even blindness. This review will focus on corneal epithelial stem cells in ocular surface repair and regeneration. The current knowledge of stem cell biology in the corneal epithelium, clinical consequences of stem cell deficiency, and therapeutic strategies aimed at reversing stem cell deficiency will be discussed.