异基因造血干细胞移植研究进展

异基因造血干细胞移植已成为治愈血液系统恶性肿瘤、骨髓衰竭性疾病、某些先天性及代谢性疾病等的重要方法。本文就外周血干细胞移植（PBSCT）、脐血造血干细胞移植（CBSCT）、非清髓性干细胞移植（NST）、移植物抗宿主病（GVHD）与移植物抗白血病（GVL）效应以及间充质干细胞（MSC）在异基因造血干细胞移植中的应用等方面的新进展进行介绍。     

白血病患者异基因造血干细胞移植后髓外复发二例

异基因造血干细胞移植(allo-HSCT)是治愈白血病的有效方法,并通过移植物抗白血病(GVL)效应而清除骨髓残留病灶。急、慢性白血病HSCT后复发常为单纯骨髓复发,少数患者为髓外或伴骨髓复发,而单纯髓外复发更少见、预后较差。欧洲骨髓移植协作组(EBMT)报道3071例患者al- lo-HSCT后髓外复发仅为0.45%。最近我们发现2例白血病患者HSCT后髓外复发,报道并复习文献如下。     

异基因脐血造血干细胞移植

脐血是指胎儿娩出并断脐后保留在脐带和胎盘近胎儿一侧血管内的血液。脐血中富含造血干细胞，脐血造血干细胞则以其独特的生物学特性、资源优势以及临床适应证的广泛性等弥补了骨髓移植(BMT)和外周造血干细胞移植的不足。脐血造血干细胞移植(CBSCT)正日益受到人们的重视，已成为近几年来造血干细胞移植领域的重大进展之一。     

异基因造血干细胞移植后早期深部真菌感染风险因素分析

目的提高对异基因造血干细胞移植后早期深部真菌感染风险的认识。方法分析22例异基因造血干细胞移植患者的移植方式、病程、白细胞植入时间、移植后白细胞计数与早期深部真菌感染的相关性。结果6例患者异基因造血干细胞移植后早期发生深部真菌感染。采用半相合和无关供者的造血干细胞移植的患者深部真菌感染发生率明显高于全相合亲缘供者的造血干细胞移植,使用过兔抗人胸腺淋巴细胞球蛋白(ATG)或猪抗人淋巴细胞球蛋白(ALG)的患者,深部真菌感染发生率明显高于未使用者。在全相合的亲缘供者的造血干细胞移植中,真菌感染与非感染患者移植后0和14d白细胞计数存在显著性差异,而两组患者移植前病程和移植后7、21 d的白细胞计数差异无显著性。结论移植方式、使用ATG或ALG、移植后0和14 d白细胞数是移植后早期深部真菌感染发生的危险因素。     

异基因造血干细胞移植亲缘供者的护理

针对61例捐献造血干细胞供者的特点，进行心理疏导和术前做好身体和皮肤准备；术中保持静脉通路通畅，严格无菌操作，行全程心电监护；术毕防止穿刺点出血和感染等健康指导，结果均顺利完成造血干细胞采集，无1例发生并发症。住院4～10d出院。提示供者捐献造血干细胞是安全的。     

ABO血型不合异基因造血干细胞移植

目的 探讨ABO血型不合异基因造血干细胞移植(Allo-HSCT)的疗效及并发症。方法 6例患者中1例ABO血型主要不合，5例次要不合；2例脐血，1例外周血干细胞，3例骨髓联合外周血干细胞；对主要不合者骨髓用重力沉降法去除红细胞，对次要不合骨髓以离心分离方法去除血浆，外周血造血干细胞及脐血未经处理直接输注。结果 6例均成功植入，仅在输注干细胞时发生短暂轻微溶血，而无延迟性溶血反应及移植后红系造血延迟。结论 ABO血型不合可顺利进行Allo-HSCT，获得干细胞的植入，移植前后防止溶血发生至关重要。     

异基因造血干细胞移植亲缘供者的护理

针对61例捐献造血干细胞供者的特点,进行心理疏导和术前做好身体和皮肤准备;术中保持静脉通路通畅,严格无菌操作,行全程心电监护;术毕防止穿刺点出血和感染等健康指导,结果均顺利完成造血干细胞采集,无1例发生并发症,住院4~10d出院。提示供者捐献造血干细胞是安全的。     

造血干细胞移植

20世纪50年代初期造血干细胞移植兴起,随着医学科技发展,大剂量化疗（预处理）＋造血干细胞移植为各种晚期肿瘤和癌症治疗提供了有力的支持,目前对造血干细胞的来源、种类、采集、活性测定,异基因造血干细胞的配型、动员剂的效果、骨髓中癌细胞污染的处理、移植后并发症的诊治、疾病观察指标、临床适应证和治疗效果的评估等等都逐渐规范化,且有很多治疗成功病例的报告。     

1例肾癌异基因造血干细胞移植病人的护理

造血干细胞移植是利用移植时诱导移植物抗肿瘤 (ＧＶＴ)效应 ,杀伤体内转移癌细胞 ,达到治疗肿瘤的目的[1] 。 2 0 0 1年 4月我科对 1例肾癌病人行造血干细胞移植 ,护理体会报告如下。1　病例简介　　男 ,38岁。于 2 0 0 0年 4月无明显诱因出现肉眼血尿 ,ＣＴ示右肾占位性病变 ,行右肾癌根治性切除术。同年 8月胸片示两肺肿块进行性增大 ,行健择 +氟尿嘧啶 +卡铂及紫杉醇 +氟尿嘧啶 +卡铂各两周期化疗和长期生物治疗 (罗扰素 6 0 0ＩＵ肌内注射 )无效。 2 0 0 1年 4月在我科采用异基因造血干细胞移植治疗 ,供者为其胞妹 ,ＨＬＡ抗原全相合 ,…     

异基因造血干细胞移植后并发慢性移植物抗宿主病患者生活质量变化及其影响因素分析

目的探究异基因造血干细胞移植(allo-HSCT)后并发慢性移植物抗宿主病(cGVHD)患者生活质量及其影响因素。 方法选取2016年6月至2020年6月于浙江大学医学院附属第一医院骨髓移植中心行allo-HSCT并在移植后诊断为cGVHD的患者作为研究对象,研究时间为allo-HSCT后初次诊断cGVHD至确诊后9个月。收集allo-HSCT后并发cGVHD患者确诊cGVHD时以及确诊后3、6和9个月临床资料,并采用第4版癌症治疗功能评价-骨髓移植测评量表(FACT-BMT V4.0)对其进行问卷调查。非正态分布计量资料采用Kruskal-Wallis H检验进行比较。分类变量采用卡方检验进行比较。对allo-HSCT并发cGVHD患者确诊后3个月生活质量影响因素进行单因素分析,选取单因素分析中P<0.05的因素及患者年龄进行多元线性回归分析。P<0.05为差异有统计学意义。 结果最终纳入247例allo-HSCT后并发cGVHD患者,其中111例为轻度cGVHD,104例为中度cGVHD,32例为重度cGVHD,三组患者原发病及移植时间构成比例差异均有统计学意义(χ²＝15.446和44.456,P均<0.05)。轻、中、重度cGVHD组患者躯体状况、社会/家庭状况、情感状况、功能状况、干细胞移植模块得分以及FACT-BMT V4.0总分差异均有统计学意义(H＝41.184、16.277、22.695、27.014、60.112和64.645,P均<0.05)。截至2021年6月,247例allo-HSCT后并发cGVHD患者中位随访时间为948(246,1 867)d,其中68.4%(169/247)患者经系统治疗后获得完全缓解(CR)/部分缓解(PR)。获得CR/PR患者确诊cGVHD时以及确诊后3、6、9个月FACT-BMT V4.0总分分别为152(111,183)、124(95,154)、129(100,157)和152(120,182)分,各时间点差异有统计学意义(H＝344.113,P<0.05)。单因素及多元线性回归分析结果显示,cGVHD严重程度及糖皮质激素耐药是影响allo-HSCT后并发cGVHD患者确诊后3个月生活质量独立危险因素(P均<0.05)。 结论FACT-BMT V4.0在allo-HSCT人群中具有较好的实践价值。cGVHD严重影响allo-HSCT后患者生活质量,且与cGVHD严重程度及糖皮质激素耐药密切相关。经治疗后获得CR/PR者FACT-BMT总分呈动态上升趋势。     

The relationship between body mass index and outcomes in leukemic patients undergoing allogeneic hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation (HSCT) is being used increasingly in an attempt to cure many hematological disorders. Obesity has become a world wide phenomenon and is a known risk factor for numerous medical conditions, but its role in transplant outcomes remained controversial. Total of 192 patients with acute leukemia who underwent sibling HLA matched HSCT were analyzed to find the effect of pre-transplant body mass index (BMI) on transplant outcomes such as time to engraftment, infections, graft vs. host disease (GvHD), and overall survival (OS) for the period of three yr (April 2006-March 2009). There was a significant correlation between higher pre-transplant BMI and shorter engraftment time (p = 0.010); but no relation between BMI and GvHD, infection, and OS was found. The results of this study showed that patients with higher BMI may have a shorter engraftment time; but lower, although not significant, survival rate compared to non-obese patients.     

自体造血干细胞移植后序贯异基因造血干细胞移植治疗浆母细胞淋巴瘤一例

正浆母细胞淋巴瘤(plasmablastic lymphoma,PBL)是一种罕见的非霍奇金淋巴瘤,来源于B细胞,侵袭性高、预后差,具有独特的临床特征。宁波市第一医院血液科采用自体造血干细胞移植(autologous hematopoietic stem cell transplantation,auto-HSCT)后序贯异基因造血干细胞移植(allogeneic     

Myeloablative allogeneic hematopoietic stem cell transplantation in elderly patients

This study aimed to evaluate the outcome following myeloablative allogeneic hematopoietic stem cell transplantation (SCT) among patients older than 50 yr of age. A total of 215 patients with a median age of 57 yr underwent allogeneic hematopoietic SCT for early (41%) or advanced (59%) hematologic malignancies. After a median follow-up of 36 months a 10-yr survival estimate of 56 +/- 6% could be assessed for patients in early disease stages while patients with advanced diseases showed a significantly decreased survival probability of 31 +/- 5% (p < 0.0002). Transplant related mortality (TRM) at day 100 and 365 post-transplant was 13% and 30% for early but increased to 21% and 49% for advanced disease stages. As major determinants of TRM advanced disease stage (p < 0.0001) and occurrence of grades II-IV graft-vs.-host disease (GVHD) (p < 0.0001) were identified. These results show that hematopoietic SCT following myeloablative conditioning is also applicable to elderly patients whereas disease stage and high-grade GVHD represent the essential prognostic factors for outcome.     

实时定量PCR技术检测BCR-ABL水平在异基因造血干细胞移植治疗慢性粒细胞白血病中的应用

目的探讨实时定量PCR（qRT-PCR）技术检测慢性粒细胞白血病（CML）患者异基因造血干细胞移植（allo．HSCT）治疗后BCR．ABL水平对改善患者预后的临床价值。方法研究纳入河北联合大学附属医院血液科2005年5月至2013年5月接受allo-HSCT治疗的CML患者15例,其中慢性期患者8例,加速期患者3例,急变期患者4例。分别在治疗前及治疗后1,2,3,6,12个月留取骨髓血标本,采用基于TaqMan探针的qRT-PCR技术检测BCR-ABL水平。根据BCR-ABL水平的动态变化,评估患者复发程度,对高复发风险的患者给予早期干预性治疗。两组问均数比较采用t检验。结果慢性期及进展期（加速期＋急变期）患者在治疗前平均BCR—ABL水平分别为（10．120±6．035）％及（43．750±14．173）％,差异具有统计学意义（t=-2．289,P〈0．05）。治疗后第1,2,3,6,12个月,慢性期和进展期患者平均BCRABL水平相比,差异均无统计学意义（t=-1．936,-2．003,-0．687,-1．613和-1．171,均P〉0．05）。治疗后第12个月,8例慢性期患者的BCR-ABL水平均为0,7例进展期患者中有5例为0。2例慢性期患者和5例进展期患者接受早期干预性治疗,除1例急变期患者在治疗后12个月复发,行再次移植无效而死亡外,其余6例患者均达完全分子生物学缓解,至随访截止时均无病存活。结论qRT-PCR是评估CML患者治疗后复发情况的良好方法,通过BCR-ABL水平的动态监测,可筛选出高复发风险的患者,配合早期干预性治疗措施可以提高患者无病生存率。     

Second allogeneic hematopoietic stem cell transplantation: a treatment for graft failure

We evaluated the results in 20 recent patients treated with a second hematopoietic stem cell transplantation (HSCT) after graft failure (GF). There were 10 children <18 yr of age. Ten patients had a non-malignant disease, and the other 10 had a malignant disease. In most of the transplantations, fludarabine-based reduced intensity conditioning (RIC) was given. Bone marrow was given to 11 patients, peripheral blood system cell (PBSC) in seven and cord blood to two patients. For the second transplantation (n = 20), a new donor was used in nine cases, while the initial donor was used in 11 transplants. Eight patients (40%) suffered from a second GF. Five of these patients were treated with a third HSCT. The probability of survival was 65% one yr and 60% three yr after the second HSCT. No difference in survival was found between patients transplanted with a new donor (56%) compared to those using the original donor (64%). The three-yr survival was 70% for children compared to 50% for adults (p = ns). Patients with a non-malignant disorder showed a three-yr survival of 90% compared to 20% in patients with a malignant disease (p = 0.005). We concluded that re-transplantation using RIC is a valid option for GF, especially in patients with non-malignant disorders.     

The significance of cytomegalovirus viremia at day 100 or more following allogeneic hematopoietic stem cell transplantation

We conducted a single‐center retrospective review of patients who had received allogeneic hematopoietic stem cell transplantation (HSCT) between January 2003 and December 2007, to assess the incidence and risk factors for late CMV infection and evaluate its effects on outcomes. Twenty of 49 HSCT recipients (41%) developed CMV infection at day ≥100 after transplant. Univariable analysis showed that having a matched unrelated donor, having early CMV infection, having a diagnosis of lymphoma, and receipt of antithymocyte globulin were risks for developing late CMV. On multivariable analysis, the occurrence of CMV prior to day 100 and lymphoma conferred a significant risk for late CMV infection. Of the 20 patients with late CMV infection, two patients manifested CMV disease (10%). Despite the relatively low incidence of CMV disease, patients with late CMV infection had a 4.8‐fold increased risk of death compared to patients without late CMV. Identifying patients at increased risk for developing late CMV infection may be important for prompting more intensive monitoring of infection late after HSCT, particularly because this manifestation of CMV is associated with poorer outcomes.     

异基因造血干细胞移植后早期特发性肺炎综合征的危险因素及发病机制

目的 研究异基凶造血干细胞移植(allo-HSCT)术后早期特发性肺炎综合征(IPS)的独立危险因素及发病机制.方法 同顾件分析192例allo-HSCT受者的临床资料,观察术后急性移植物抗宿主病(aGVHD)和IPS的发牛情况及其临床表现,对患者年龄、性别、原发病、移植时疾病状态(高危组70例,疾病处于难治、未缓解状态;标危组122例,疾病处于缓解状态)、供者类型、HLA相合程度、移植类型、预处理方案、急性移植物抗宿主病(aGVHD)、aGVHD程度、aGVHD累及器官等11项临床因素进行单因素分析,将有统计学意义的因素进行Logistic多因素同归分析,筛选出发生IPS的独立危险因素,并结合文献,探讨其发病机制.结果 192例allo-HSCT受者中,有23例发生IPS,发生时间为术后76 d(32～120 d),其中20例经治疗无效死亡,发病至死亡的时间为9 d(3～92 d),其余3例治愈.23例IPS患者中,有19例发生过aGVHD,其中肠道aGVHD16例.单因素分析显示,高危组、非亲缘供者、HLA不合、发生aGVHD、Ⅲ～Ⅳ度aGVHD及肠道aGVHD等6个因素具有统计学意义;多凶素分析显示,非亲缘供者、Ⅲ～Ⅳ度aGVHD和肠道aGVHD等3个因素是发生IPS的独立危险因素.结论 非亲缘供者、Ⅲ～Ⅳ度aGVHD及肠道aGVHD是发生IPS的独立危险因素;IPS可能是由aGVHD引起的肺部病变.