Functions of the endothelium and its role in hematopoietic cell transplantation

The endothelium is a single-layered structure that responds to physical and chemical signals with various factors it synthesizes. In the early days of its discovery, as the inner wall of the vessels, the endothelium was thought to be a simple barrier that lays on the surface. Over time it is discovered that endothelium maintains body homeostasis with the molecules it synthesizes, despite its simple single-layer structure. It has been accepted as an important organ that contributes to the maintenance of vascular tone, cell adhesion, inflammation, vascular permeability and coagulation. Any imbalance in these physiological and pathological events causes endothelial dysfunction. This can cause many diseases such as atherosclerosis, hypertension, diabetes, or it can occur because of these. Endothelial related disorders may also complicate hematopoietic stem cell transplantation (HSCT), which is used to treat various hematologic and neoplastic diseases. These life-threatening complications include graft-versus-host disease, hepatic veno-occlussive disease, transplant-associated thrombotic microangiopathy and diffuse alveolar hemorrhage. They share a similar pathophysiology involving endothelial cells with different clinical presentations. Therefore, current researche on the issue is putting the endothelium under the spotlight for novel markers and treatment options that should be used to monitor or treat at least some of these complications following HSCT.     

Mortality,length of stay and costs associated with acute graft-versus-host disease during hospitalization for allogeneic hematopoietic stem cell transplantation

Objective: Acute graft-versus-host disease (aGVHD) is a common and life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The extent to which aGVHD increases inpatient costs associated with allo-HSCT has not been thoroughly evaluated. In this analysis, mortality, hospital length of stay (LOS) and costs associated with aGVHD during allo-HSCT admissions are evaluated.

Methods: This is a retrospective analysis of discharge records from the National Inpatient Sample database for patients receiving allo-HSCT between 1 January 2009 and 31 December 2013. Allo-HSCT discharges with an aGVHD diagnosis were included in the aGVHD group and those without any graft-versus-host disease (GVHD) diagnosis comprised the non-GVHD group. Mortality, LOS and costs were compared between the two groups, as well as within subgroups, including age (<18 vs. ≥18 years) and survival status (alive vs. deceased) at discharge.

Results: Overall, mortality (16.2% vs. 5.3%; p?<?.01), median hospital LOS (42.0 vs. 26.0 days; p?<?.01) and median total costs ($173,144 vs. $98,982; p?<?.01) were significantly increased in patients with aGVHD versus those without GVHD during hospitalizations for allo-HSCT, irrespective of age group. Patients with aGVHD who were <18 years of age had a lower mortality rate but greater hospital LOS and total costs versus patients aged ≥18 years. Patients who died during allo-HSCT hospitalization had longer LOS and incurred greater costs than those who survived in both the aGVHD and non-GVHD groups.

Conclusion: Occurrence of aGVHD during allo-HSCT admissions resulted in a tripling of the mortality rate and a near doubling of hospital LOS and total costs. In addition, death during allo-HSCT hospitalizations was associated with greater healthcare utilization and costs. Effectively mitigating aGVHD may improve survival and substantially reduce hospital LOS and costs for allo-HSCT.     

非体外循环冠状动脉旁路移植术后造血干细胞动员的临床研究

目的研究非体外循环冠状动脉旁路移植术(OPCAB)后造血干细胞动员的规律及影响因素。方法对55例择期行OPCAB、近期无急性心肌梗死患者,分别于术前30m in、术后6、12、24、48、72和120h采外周静脉血4m l,CD 34和CD 45双抗标记、流式细胞仪检测造血干细胞计数,同时检测心肌酶谱及肌钙蛋白T的变化。结果冠心病患者术前造血干细胞计数占外周血有核细胞数计数的0.13%±0.12%,OPCAB后明显升高,24h达到峰值(0.34%±0.20%),术后120h回到术前基线水平;吸烟、高血脂、糖尿病对造血干细胞动员无明显影响,但合并高血压病患者外周血造血干细胞动员明显低于无高血压病患者;术后24h造血干细胞动员与肌酸激酶及肌酸激酶同工酶、乳酸脱氢酶、肌钙蛋白T呈正相关(r=0.692,P=0.000;r=0.558,P=0.000;r=0.447,P=0.000;r=0.401,P=0.004)。结论OPCAB术后造血干细胞快速、短暂动员,心肌损伤程度、冠心病危险因素参与了造血干细胞动员的调节。     

ABO血型不合的异基因造血干细胞移植--2例报告附文献复习

探讨ABO血型不合的异基因造血干细胞移植 (Allo -HSCT)的造血问题。方法 :对 2例患者分别进行异基因外周血造血干细胞移植 (Allo -PBSCT)及脐血造血干细胞移植 (CBSCT) ,用血细胞分离机或 6 %羟乙基淀粉去除移植物中的红细胞 ,定期检测受者血型 ,根据情况输注血细胞。结果 :2例患者全部获得造血重建 ,未出现溶血反应。结论 :ABO血型不合可以进行Allo -HSCT ,去除供者移植物中的红细胞能有效地防止急性溶血反应的发生 ,定期检测受者血型 ,及时调整输血方案有重要的临床意义。     

造血干细胞移植后慢性移植物抗宿主病相关的膜性肾病一例

目的 总结造血干细胞移植后慢性移植物抗宿主病（cGVHD）相关的膜性肾病的诊疗体会。方法 为1例急性淋巴细胞白血病患者施行HLA全相合的无关供者外周血造血干细胞移植，术后应用甲氨喋呤和他克莫司（FK506）预防GVHD。术后第19d发生急性GVHD，经甲泼尼龙治疗逆转。分别于术后182d、235d停用FK506和泼尼松，5d后患者出现cGVHD表现，肝功能异常，并伴肾病综合征的相关表现，病理诊断为膜性肾病Ⅱ期，遂给予FK506和泼尼松治疗，同时辅以利尿、降脂等措施。结果发生膜性肾病时，患者的尿蛋白＋＋＋＋，白细胞75个／μl，上皮细胞359．5个／pl，病理性管型＋，管型计数为167个／μl，24h尿蛋白定量为4．28g；肾组织活检，无肾小球硬化，肾小球体积稍大，部分血管袢受压，开放欠佳，肾小球基底膜轻微增厚，外观呈僵硬感，系膜基质轻、中度增殖；间质区部分肾小管扩张，肿胀、变性，未见明显间质纤维化和炎症细胞浸润；Masson染色可见基底膜上皮侧嗜复红物沉积；免疫荧光检查，IgG＋＋＋，C3＋＋＋，IgA＋＋，沿毛细血管袢呈颗粒状节段性分布，系膜区呈团块状分布；IgM、Clq、CA均阴性。电镜下可见肾小球基底膜上皮下沉积物，并有基膜增厚，毛细血管系膜基质轻度增生。经泼尼松和FK506治疗，2个月后尿蛋白转阴。结论 造血干细胞移植后出现肾病综合征或蛋白尿，应考虑GVHD相关膜性肾病的可能，肾穿刺活检有助于诊断，糖皮质激素和FK506治疗有效。     

供者表达活化性杀伤细胞免疫球蛋白样受体对造血干细胞移植预后的影响

目的 观察供者表达活化性杀伤细胞免疫球蛋白样受体（aKIR）对受者造血干细胞移植（HSCT）预后的影响。方法 1996年至2001年共行亲缘性人类白细胞抗原（HLA）全相合骨髓移植59例，以序列特异性引物多聚酶链反应法（SSP-PCR）检测供者aKIR的表型。分析供者表达aKIR对受者移植后病毒、细菌和真菌感染及出血、复发、存活情况的影响。结果 供者表达aKIR与受者移植后出血、病毒及细菌感染发生的概率无明显相关性；当供者表达KIR3DS1表型时，发生真菌感染概率增高（X^4．804，P=0．028）。供者表达aKIR对受者HSCT后存活率和白血病复发率均无明显影响。结论 亲缘性HLA全相合HSCT中，供者表达aKIR并不能改善受者的移植效果。     

Hematopoietic turnover index in reactive and neoplastic bone marrow lesions: quantification by apoptosis and PCNA labeling

 In order to determine the dynamics of hematopoietic cell turnover, proliferative activity and incidence of apoptosis (programmed cell death) were evaluated in bone marrow trephine biopsies. Selection of patients (20 in each group) included in addition to a control group, idiopathic thrombocytopenia (ITP), reactive thrombocytosis (TH), secondary polycythemia-smokers' polyglobuly (PG), primary (essential-hemorrhagic) thrombocythemia (PTH), polycythemia vera (PV), and finally acute myeloid leukemia (AML). Apoptosis was demonstrated by the in situ end-labeling technique (ISEL) and proliferative activity by applying the monoclonal antibody PC10 raised against proliferating cell nuclear antigen (PCNA). To assess dynamic features of hematopoiesis, an index was calculated consisting of the ratio between PCNA-positive nuclei and the apoptotic cell fraction. This factor was termed the hematopoietic turnover index (HTI). Morphometric analysis revealed that the HTI was significantly increased in AML and PV. According to cell culture studies both disorders are characterized by either a prevalent proliferation of the myeloid or erythroid cell mass. On the other hand, PG, PTH, and TH showed no relevant enhancement of this index in comparison to the control specimen. In vitro experiment results are in keeping with the finding that PG and PTH are not associated with a significant expansion of the erythroid lineage (CFU-E). Similar to ITP and TH, in PTH megakaryocyte proliferation (CFU-MEG) is the predominant feature of cell turnover. Differences between PTH and TH are in line with the reduced in vitro formation of CFU-MEG in the latter disorder. In conclusion, our in situ study on turnover rates of the bone marrow in various neoplastic and reactive lesions extends previous experimental data on hematopoietic cell kinetics. Received: 10 March 1997 / Accepted: 18 May 1997     

血浆巨细胞病毒多聚酶链反应检测用于指导干预性治疗

目的：分析用血浆巨细胞病毒（cytomegalovirus,CMV)多聚酶链反应（plymerase chain reaction,PCR)检测结果指导抗CMV干预性治疗的临床意义。方法：1999年8月至2001年7月行异基因造血干细胞移植（hematopoietic stem cell transplantation,HSCT)的所有患者自预处理开始，常规用PCR法检测血浆的CMV－DNA（采用华美公司生产的巨细胞病毒4℃ PCR检测试剂盒），每周1次。其中尚无CMV病的临床表现而检测到血浆CMV阳性的患者89例。随机选取52例阳性患者给予干预性治疗。将上述89例患者分为3组（分别为停止治疗时血浆CMV－PCR转阴组、停止治疗时未转阴组、血浆CMV阳性未治疗组）比较各组CMV病的发生率。CMV病的发生率采用Kaplan-Meier曲线表示，曲线间的比较用Log-Rank（曲线无交叉）或Breslow（曲线交叉）检验，某时点率的比较采用RXC列联表或χ^2检验。结果：100d内CMV病的发生率，在治疗后血浆CMV－PCR由阳性转为阴性组为10．26％，治疗结束时血浆CMV－PCR仍为阳性组为66.67%，血浆CMV－PCR阳性未治疗组为36．24％（P＝0.0000)。上述3组中任两组移植后100d CMV病的发生率差异均有显著性。移植后1年时上述3例CMV病累积发生率分别为30.65%、75.00%、42.95%(P=0.0009)，治疗未转阴组与治疗转阴组和阳性未治疗组相比，CMV病的发生率明显升高。结论：血浆CMV－PCR检测结果用来指导干预性治疗有一定临床意义。干预性治疗后血浆CMV－DNA仍未转阴者，应考虑换药或联合用药治疗。     

慢性移植物抗宿主病相关性肌炎一例

目的总结1例异基因造血干细胞移植后并发与慢性移植物抗宿主病(cGVHD)相关的多发性肌炎的诊治体会。方法1例急性淋巴细胞白血病患者在处于完全缓解状态下接受同胞间供髓异基因造血干细胞移植,移植后采用环孢素A和甲氨蝶呤预防移植物抗宿主病(GVHD)。结果移植后11 d,WBC＞0．5×10~9/L,移植后13 d,血小板＞20×10~9/L；27 d时,骨髓细胞染色体分析显示99%为供者型。移植后17 d,发生Ⅰ度急性皮肤型GVHD,经静脉注射地塞米松及甲氨蝶呤后,GVHD被完全控制。移植后8个月,患者发生轻度肝脏cGVHD,经他克莫司及硫唑嘌呤治疗,效果不佳,血清肝酶升高,后改为他克莫司和西罗莫司治疗,血清肝酶逐渐下降,但肌酸激酶从9 U/L上升至272 U/L,随后患者出现全身乏力,并逐渐加重,上下肢近端处活动出现障碍,肌酸激酶升至3010 U/L,股四头肌、肱二头肌的肌电图表现为肌源性损害,双侧大腿磁共振成像符合多发性肌炎表现,给予甲泼尼龙、血浆置换治疗,但无显著效果,患者突发阵发性呼吸困难,经抢救无效,患者死亡,死亡时肌酸激酶为21 010 U/L。结论多发性肌炎为cGVHD的一种较少见形式,累及重要肌组织者预后较差。