异基因造血干细胞移植治疗恶性组织细胞病

目的 探讨异基因造血干细胞移植(Allo-HSCT)治疗恶性组织细胞病(MH)的方法和疗效. 方法 对1例MH患者进行Allo-HSCT,采用改良马利兰/环磷酰胺(Bu/Cy)预处理方案进行亲缘HLA全相合的外周血干细胞移植,移植物抗宿主病(GVHD)的预防采用环孢素A联合短疔程甲氨蝶呤的方案. 结果 患者移植后造血功能恢复顺利,中性粒细胞绝对数＞0.5×109/L时间为+20 d,Pt＞20×109/L时间为+27 d.患者+30 d行骨髓短串联重复序列(STR)-PCR检测显示为完全供者的基因型,移植后2个月发生Ⅱ度急性GVHD,加用泼尼松后病情得到控制,未发生慢性GVHD,随访至移植后8个月,造血功能恢复良好,病情处于持续完全缓解状态,仍在继续随访中. 结论 对符合传统意义上或WHO重新定义的MH患者,Allo-HSCT是一种有效的根治方法.     

造血干细胞移植治疗再生障碍性贫血进展

异基因造血干细胞移植用于治疗重型再生障碍性贫血（severe aplastic anemia）,其患者的预后及生活质量明显提高。总体生存率提高获益于移植供者的选择、预处理方案的改进、支持技术的提高,尤其现今造血干细胞来源多样性、预处理方案的改进等。     

儿童恶性血液病异基因造血干细胞移植指征

造血干细胞移植（hematopoietic stem cell transplant,HSCT）在儿童恶性肿瘤中应用广泛,自体HSCT （autologous hematopoietic stem cell transplant,auto-HSCT）主要应用于化疗敏感的儿童晚期实体肿瘤,而异基因 HSCT（allogene hematopoietic stem cell transplant,allo-HSCT）主要针对儿童难治性白血病.由于对化疗的敏感性差异,儿童恶性血液疾病的HSCT指征与成年人有一定区别,为了便于临床对HSCT指征的把握,笔者拟主要对allo-HSCT治疗各种儿童恶性血液疾病的指征进行阐述如下.     

异基因外周血造血干细胞移植治疗白血病

探讨用 Ｈ Ｌ Ａ 相合的同胞异基因外周血干细胞移植治疗急性髓细胞白血病及 Ａ Ｂ Ｏ 血型不合的 Ｐ Ｂ Ｓ Ｃ Ｔ 的情况,采用 Ｃ Ｔ Ｘ６０ｍｇ／ｋｇ ×２ ＋ Ｔ Ｂ Ｉ７０ ～７５ Ｇｙ 直线加速器照射＋ Ｃ Ｃ Ｎ Ｕ５０ｍｇ／ｋｇ ×１ ± Ｖ Ｐ１６３０ｍｇ／ｋｇ ×１ 对受者作预处理,供者经 Ｇ－ Ｃ Ｓ Ｆ６μｇ／ｋｇ ×５ｄ 动员后,用血细胞分离机（ Ｂａｘｔｅｒ Ｃ Ｓ３０００ｐｌｕｓ） 分离采集干细胞去除红细胞。对 Ａ Ｂ Ｏ 血型不合的 Ｐ Ｂ Ｓ Ｃ,强化移植物抗宿主病（ Ｇ Ｖ Ｈ Ｄ） 预防方案中 Ｍ Ｔ Ｘ 用量及次数;选输合适血制品。结果３ 例病人输注单个核细胞数分别为４０ 、１００ 、５０ ×１０８／ｋｇ , Ｃ Ｄ３４ ＋ 细胞分别为３６ 、１９０ 、２０ ×１０６／ｋｇ ;干细胞悬液中红细胞残存量分别为２３ｍｌ、１４ｍｌ、２６ ｍｌ,红细胞残存率分别为４ ％ 、３ ％ 、５３ ％ 。移植后造血重建迅速。例１ 于＋ ３４ｄ 染色体完全转变为供者型;例２ 于＋ ４０ｄ 血型完全转变为供者型,＋ ４５ｄ 染色体完全转变为供者型,例３ ＋ ５５ｄ 血型完全转变为供者型。没有输血溶血和免疫溶血发生。例２ 为主,次要 Ａ Ｂ Ｏ 均不合,则早期     

异基因造血干细胞移植后闭塞性细支气管炎的诊断及治疗

近年来造血干细胞移植（HSCT）已成为良、恶性血液系统疾病、实体恶性肿瘤、代谢和遗传疾病的重要治疗手段，有40％-60％的HSCT患者会出现感染或非感染性的肺部并发症，导致移植术后患者的病死率明显增加。其中65％的异基因造血干细胞移植（allo-HSCT）患者会出现非感染性的肺部并发症，这与使用免疫抑制剂引起的免疫缺陷、移植物抗宿主病（GVHD）等因素有关，在allo—HSCT后的晚期并发症中闭塞性细支气管炎（BO）最为常见，严重影响患者的长期生存及生活质量，现就BO相关问题进行综述，以提高临床对此疾病的认识，达到早期诊断和治疗的目的。[第一段]     

异基因外周血造血干细胞移植66例护理体会

目的探讨异基因外周血造血干细胞移植并发症的护理策略。方法根据患者移植过程中出现的状况进行一系列的环境准备、心理护理、治疗指导等护理措施。结果 66例患者均移植成功,其中11例出现aGVHD（急性移植物抗宿主病）,8例出现HC（出血性膀胱炎）,2例出现HVOD（肝静脉闭塞病）,发生口腔溃疡29例,肛周感染16例,但经过精心的护理和正确的治疗全部治愈。结论做好移植各阶段的护理,可以减少移植相关并发症的发生,利于移植过程的顺利进行。     

替考拉宁经验性治疗异基因造血干细胞移植并发感染的临床研究

目的评价替考拉宁经验性治疗异基因造血干细胞移植并发感染的有效性及安全性。方法回顾性分析2006年1月-2011年1月,在血液科进行异基因造血干细胞移植的42例患者,并发感染后应用替考拉宁经验性治疗的临床疗效,并对其安全性进行评价。结果在42例患者中,治疗有效35例,有效率为83.3%;不良反应发生率为4.8%,均为轻度、可逆的不良反应,患者耐受性好。结论替考拉宁治疗异基因造血干细胞移植并发感染疗效确切,安全性高,值得在临床上推广应用。     

2例HLA部分不合的异基因造血干细胞移植并发aGVHD的护理报告

急性移植物抗宿主病是异基因造血干细胞移植后的主要并发症。其根本原因是供者与受者的组织相容性抗原的差异。根据急性移植物抗宿主病具有粘膜损害、斑丘疹(手足、掌、面、耳、颈部)、黄疸、肝功异常、腹泻、严重脱水及电解质紊乱等临床特征以及造血干细胞移植的特点,着重阐述造血干细胞移植术后并发移植物抗宿主病时皮肤皮疹的护理、腹泻的护理、饮食的护理以及心理护理体会。     

异基因外周血造血干细胞移植的护理

目的探讨异基因外周血造血干细胞移植的护理要点。方法根据患者的多种状况进行一系列的环境准备、心理护理、自我护理、治疗指导等护理措施。结果66例患者均移植成功,其中21例出现急性移植物抗宿主病,4例出现出血性膀胱炎,2例出现肝静脉闭塞病,但经过精心地护理和正确地治疗全部治愈。结论做好移植各阶段的护理,可以减少移植相关并发症的发生,利于移植过程的顺利进行。     

异基因造血干细胞移植后乙型病毒性肝炎防治新进展

 异基因造血干细胞移植（allo-HSCT）是治愈恶性血液病的有效手段,但移植患者因接受感染乙型肝炎病毒（HBV）的移植物、免疫功能严重受损等原因,术后并发乙型病毒性肝炎的风险增加。恩替卡韦和替诺福韦是目前公认用于预防allo-HSCT后乙型病毒性肝炎的有效药物,显著减少移植后患者的肝损伤。移植后患者的免疫重建时间长且重建规律存在异质性,导致术后监测和预防性抗HBV治疗的最佳持续时间尚未能明确。本文对allo-HSCT后HBV再激活的发生机制、乙型病毒性肝炎的特点及防治的最新研究进展进行综述。     

he impact of Gaucher disease and its treatment on quality of life

To obtain information about how Gaucher disease and its treatment, specifically enzyme replacement therapy, affect patients' health-related quality of life (HRQoL), we interviewed 16 patients with type I Gaucher disease (range 8–67 years). All but three patients had been receiving enzyme replacement therapy for at least 6 months. The quality of life factors examined for these patients included physical health, social life, emotional health, financial burden, future plans and satisfaction with health care. The results indicated that bone pain and chronic fatigue interfered with school, job and social activities and were the most debilitating symptoms of Gaucher disease. Most patients experienced a significant increase in energy level from therapy and reported significant improvements in quality of life. Most patients did not perceive an effect of Gaucher disease on their overall emotional health, but some patients expressed anxieties about the discomfort, inconvenience and high costs of therapy. We conclude that a measure of HRQoL for Gaucher patients should include a generic core of items supplemented by disease-specific items designed to assess the changes in symptoms and in the occupational, recreational, social and emotional aspects of patients' lives that occur as a result of disease progression and/or management.     

Quality of life assessment in adults with type 1 Gaucher disease

The effect of enzyme replacement therapy on health-related quality of life in 25 adults with type 1 Gaucher disease was investigated over a 2-year period. Quality of life was assessed using the SF-36 Health Survey (SF-36). Psychological functioning was assessed using the Symptom Checklist-90R. The results indicated significant improvement in 7 of 8 SF scale scores beginning at 18 months of therapy (P<0.05 to 0.001). The SF scale showing improvement first was Vitality (energy level and fatigue) at 6 months of therapy (P<0.01). The SF-36 scales showing the largest improvements were Role-Physical and Social Functioning (P<0.001). Compared to the general US adult population, the study population's health profile was significantly lower prior to starting therapy but by 24 months of therapy there were no differences between the two. No differences were found in psychological functioning compared to a US adult normative group at the start of therapy. However, within the study population there was significant improvement in mood and global functioning and fewer psychological symptoms reported at 24 months of therapy. The findings indicate that enzyme replacement therapy for type 1 Gaucher disease has a positive impact on health-related quality of life from the patient's perspective.     

异基因造血干细胞移植后巨细胞病毒及多瘤病毒感染相关临床特征

目的探讨异基因造血干细胞移植(allo-HSCT)术后人巨细胞病毒(HCMV)和多瘤病毒(BKV和JCV)感染相关临床特征。方法收集2016年6月—2017年12月共53例行allo-HSCT的恶性血液病患者临床资料。移植当天开始监测患者外周血与尿的HCMV、BKV和JCV核酸载量,每周一次至100 d。分析病毒感染的发生率、发生时间、相关临床表现及危险因素。结果 51例患者发生病毒感染,感染率为96.23%。其中,HCMV感染率为54.72%(29/53)、BKV感染率为77.36%(41/53)、JCV感染率为28.30%(15/53)。肺部感染、急性移植物抗宿主病(aGVHD)和出血性膀胱炎(HC)的发生率分别为54.72%、58.49%和20.75%。危险因素分析显示:发生aGVHD(OR=24.61,95%CI:2.30～46.24)、预处理采用全身照射(OR=33.39,95%CI:1.57～79.13)及使用ATG(OR=24.77,95%CI:1.16～52.58)是影响HCMV血症的独立危险因素,HLA全相合(OR=0.003,95%CI:0.00～0.10)可降低发生HCMV血症的风险;预处理采用全身照射(OR=15.10,95%CI:1.14～39.27)是影响BKV尿症的独立危险因素,供受者血型相合(OR=0.07,95%CI:0.01～0.64)可降低发生BKV尿症的风险。结论移植术后应尽早监测受者血及尿中HCMV及多瘤病毒感染情况,以期及时预防及减少并发症的发生。     

谷氨酰胺双肽对造血干细胞移植后患者血清Th1/Th2类细胞因子水平的影响

目的研究谷氨酰胺双肽对造血干细胞移植患者血清Th1／Th2细胞因子水平的影响，及对移植后急性移植物抗宿主病（GVHD）的预防作用。方法将20例接受异基因造血干细胞移植患者随机分为两组，谷氨酰胺组10例，对照组10例。从移植后当天至第20天，谷氨酰胺组患者除接受标准胃肠外营养支持外，每天给予N（2）-L-丙氨酰-L-谷氨酰胺200ml；对照组采用不含谷氨酰胺的标准化胃肠外营养支持。两组均采用改良白消安加环磷酰胺（BuCy2）预处理方案，采用环孢霉素加霉酚酸酯预防移植物抗宿主病（GVHD），分别干预处理当天，移植后第7、14、21、28和42天收集患者姐清标本，采用酶联免疫吸附实验（ELISA）分别检测肿瘤坏死因子α（TNF-α）、干扰素1（INF-γ）、白介索2（IL-2）、IL-4、IL-10的水平，同时监测两组GVHD发生率及严重程度。结果谷氨酰胺组TNF-α、INF-γ和IL-2水平较对照组低，其中TNF-α、INF-γ与对照组差异有显著意义（P〈0．05）；谷氨酰胺组IL-4和IL-10水平略高于对照组，但仅移植后第42天差异有显著意义（P〈0．05）。GVHD发生两组无明显差异。结论符氨酰胺能使造血干细胞移植患者的Th1／Th2细胞因子向有利于预防GVHD的方向偏移。     

No Effect of Vitamin C Administration on Neutrophil Recovery in Autologous Stem Cell Transplantation for Myeloma or Lymphoma: A Blinded,Randomized Placebo-Controlled Trial

Vitamin C is an important micronutrient for various immune cells. It increases phagocytic cell function and is necessary for T and natural killer (NK) cell development. Patients in need of an autologous hematopoietic stem cell transplantation (HSCT) are often vitamin C-depleted. We therefore hypothesized that vitamin C supplementation could improve immune recovery in autologous HSCT patients. This blinded, placebo-controlled trial included 44 patients randomized to receive vitamin C or a placebo. The following outcome measures used were clinical and immunological parameters, among others: time to neutrophil recovery, serum, and intracellular vitamin C values. Twenty-one patients received vitamin C, and 23 received a placebo. The time to neutrophil recovery did not differ between the two groups at 11.2 days (p = 0.96). There were no differences in hospitalization time (19.7 vs. 19.1 days, p = 0.80), the incidence of neutropenic fever (57% vs. 78%, p = 0.20), or 3-month overall survival (90.5% vs. 100%, p = 0.13). Bacteremia seemed to occur less in the vitamin C group (10% vs. 35%, p = 0.07). Our study shows no benefit from vitamin C supplementation on neutrophil recovery and hospitalization, despite possible lower rates of bacteremia in the vitamin C group. Therefore, we do not advise vitamin C supplementation in this treatment group.     

Malnutrition Prevention after Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT): A Prospective Explorative Interventional Study with an Oral Polymeric Formulation Enriched with Transforming Growth Factor Beta 2 (TGF-β2)

Malnutrition is common after allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT), and interventions directed to correct nutritional status are warranted to improve transplant outcomes. In this prospective study, an oral polymeric formulation enriched with TGF-β2 (TE-OPF) was explored to correct malnutrition according to Patient-Generated Subjective Global Assessment (PG-SGA). TE-OPF was proposed to 51 consecutive patients who received transplants at our institution for hematological malignancies, and sufficient dose intake was established per protocol as at least 50% of the prescribed dose of TE-OPF: group A received adequate nutritional support; group B, inadequate. The study met the primary outcomes in terms of safety (no adverse events reported during TE-OPF intake except for its disgusting taste) and malnutrition (PG-SGA C 28 days after transplant): severely malnourished patients (PG-SGA C) accounted for 13% in group A and 88.9% in group B (p = 0.000). At the end of the study, after a median follow-up of 416 days, the estimated median Overall Survival (OS) was 734 days for well or moderately nourished patients (PG-SGA A/B) in comparison to 424 for malnourished patients (p = 0.03). Inadequate TE-OPF intake was associated with an increase in acute gastrointestinal Graft Versus Host Disease (GVHD) cumulative incidence (38% vs. 0% p = 0.006). A higher incidence of pneumonia was reported in group B (p = 0.006). IGF-1 levels at 14 and 28 days after transplant were significantly higher in group A and were associated with a lower incidence of acute GVHD (aGVHD). Higher subsets of B, T, and NK cells were found in group A, and a higher number of CD16+ NK cells was associated with a lower incidence of acute GVHD (p = 0.005) and increased survival at the end of the study (p = 0.023). Artificial neural network analysis suggested that inadequate TE-OPF intake, pneumonia, and sepsis significantly affected malnutrition 28 days after alloHSCT and survival 365 days after alloHSCT (normalized importance 100%, 82%, and 68%, respectively). In this exploratory and preliminary study, the use of TE-OPF appeared to reduce the incidence of malnutrition after alloHSCT, but larger and controlled studies are required.     

哌拉西林/他唑巴坦治疗异基因造血干细胞移植后肺部感染的临床观察

目的评价经验型应用哌拉西林/他唑巴坦,治疗异基因造血干细胞移植术后,患者并发肺部感染的有效性及安全性。方法 2009年1月-2010年12月完成的60例异基因造血干细胞移植患者,术后并发的肺部感染经验性采用哌拉西林/他唑巴坦初始抗感染治疗,哌拉西林/他唑巴坦静脉滴注,2.5g,1次/8h,疗程10～24d,平均15d。结果经验型应用哌拉西林/他唑巴坦治疗异基因造血干细胞移植术后患者并发肺部感染的总有效率为75.0%,不良反应发生率为3.3%。结论哌拉西林/他唑巴坦治疗异基因造血干细胞移植术后肺部感染效果良好,具有高效、安全、低毒特点。     

自体外周血造血干细胞移植在小儿恶性血液肿瘤的应用研究

目的　对 2 6例自体外周血干细胞移植 (APBSCT)治疗的小儿恶性血液肿瘤患儿有关材料进行总结分析。方法　自1989-0 1～ 2 0 0 3 -0 62 6例恶性血液肿瘤患儿 (急性淋巴细胞白血病 11例、急性髓系白血病 3例、恶性淋巴瘤 7例、神经母细胞瘤 5例 ) ,男 17例 ,女 9例 ,年龄 3 5～ 12 (平均 7 4)岁 ,在其完全缓解 ( 2 4例 ) ,部分缓解 ( 2例 )后进行了APBSCT治疗。移植时病程中位时间 12月 ( 6-64 )。 18例用化疗加rhGM -CSF或rhG -CSF动员 ,8例采用常规化疗方案作为动员剂。预处理方案中 19例基本方案为全身放疗 (TBI)加环磷酰胺 (CTX)。 7例未用TBI ,仅以马法兰为主做为预处理方案 (马法兰 +卡铂 +足叶乙甙 4例 ,白消胺 +马法兰 3例 )。结果　移植后白细胞 >0 5× 10 9/L、>1 0× 10 9/L、血小板 >2 0× 10 9/L的中位时间分别为 12 ( 8～ 2 0 )d、17d( 10～ 2 8)、2 1( 7～ 78)d。中位随访时间 7 3年 ( 1月至 14年 )。至今无病生存 70 %( 18/2 6) ,死亡 3 0 %( 8/2 6) ,其中移植相关死亡 2例 ( 7 7%)。结论　化疗联合G -CSF是一高效、低毒的动员方案 ;APBSCT是治疗小儿血液系统肿瘤 ,改善其预后的重要手段之一。