自体外周血造血干细胞移植后淋巴细胞亚群的恢复

目的探讨自体外周血造血干细胞移植(auto-PBSCT)后免疫重建的规律。方法测定血液肿瘤患者auto-PBSCT前后淋巴细胞各亚群的绝对值。结果部分亚群在移植前低于正常。移植后各细胞亚群恢复时间不同,其中NK细胞在6个月恢复;B细胞在9个月恢复正常。T细胞总数在9个月恢复正常,其中主要为CD3 CD8 细胞。CD3 CD4 细胞在18个月恢复,而CD4 CD28 细胞在2年内仍未恢复。CD3 CD8 细胞在移植后早期有所下降,在3个月时恢复并高于正常,至9个月时逐渐下降至正常。CD3 CD8 细胞的主要部分是免疫表型呈活化的T细胞,即CD8 HLA-DR 细胞和CD8 CD38 细胞。两者分别在1个月和3个月时高于正常,在9个月时恢复正常。结论血液肿瘤患者移植前即存在淋巴细胞亚群异常的前提下,移植后NK细胞最先恢复,其次为B细胞,T细胞各亚群中CD3 CD8 细胞恢复较早,其中主要为活化T细胞。     

超抗原对NK细胞CD226分子表达与功能的调节

目的研究超抗原对NK细胞CD226分子表达与功能的调节。方法以超抗原金黄色葡萄球菌肠毒素A/B(SEA/B)活化PBMC为模型,应用双重免疫荧光染色和流式细胞术分析,观察CD226分子在NK细胞上的变化;采用51Cr释放实验,观察NK细胞在超抗原作用下杀伤功能的改变;利用激光共聚焦显微镜,观察CD226分子在NK细胞杀伤相的分布。结果在静止PBMC中,CD56 NK细胞的百分率为12.3%,CD56 CD226 细胞仅为1.4%。当效靶比为5∶1时,NK细胞对K562细胞的杀伤率为(3.2±0.2)%。当0.1mg/LSEA或SEB刺激PBMC1d后,CD56 NK细胞的百分率分别为13.5%和14.1%,CD226在NK细胞上的表达水平明显升高,且主要表达在CD56dim细胞上。在刺激第2天,SEA组CD56 CD226 占CD56 细胞69.1%,SEB组CD56 CD226 占CD56 细胞64.3%。刺激第3天,CD226在NK细胞上的表达水平均较第2天明显下降。在超抗原0.1mg/L作用3d中,SEA组和SEB组NK细胞杀伤率均明显高于同期未刺激组NK细胞的杀伤率及新鲜分离NK细胞的杀伤率(P<0.05),在作用的第2天,SEA组和SEB组杀伤率均达到峰值分别为(82.3±6.9)%和(80.6±7.5)%。激光共聚焦结果显示,CD226分子与LFA-1分子共定位于NK细胞与K562细胞的接触部位。结论超抗原SEA和SEB可提高NK细胞杀伤活性,可能与其促进CD226分子在NK细胞上的表达相关,CD226分子可能参与NK细胞免疫突触的形成。     

异基因造血干细胞移植后NK细胞免疫重建的研究进展

异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation, allo-HSCT)是治疗血液系统恶性肿瘤有效且唯一的治愈方法,移植成功与否主要取决于移植后受者造血系统和免疫系统的恢复程度。HSCT后免疫系统的恢复,也被称为免疫重建,其中NK细胞的免疫重建最为重要,它在个体的早期防御和allo-HSCT的成败中发挥重要的作用。文章即对allo-HSCT中NK细胞免疫重建规律、促进NK细胞免疫重建的相关免疫治疗方法及疗效的进展作一综述。     

CD226在NK细胞亚群上表达规律与功能关系的研究

目的：观察CD226分子在NK细胞亚群上的分布和其他NK细胞活化性受体和抑制性受体的共存规律，及与NK细胞功能的关系。方法：分别以IL-2或IL-15刺激PBMC和MLC细胞为模型，采用双重免疫荧光染色和流式细胞术分析，观察CD226分子在CD56^bright和CD56^dim NK细胞亚群上的表达，及与NK细胞活化性受体CD16和抑制性受体NKG2A的共存关系，同时用ELISA方法检测培养上清中IFN-γ的水平。用4小时^51Cr释放试实验检测NK细胞杀伤水平。结果：在PBMC中，CD226主要分布于CD56^dim亚群，在IL-2作用下，CD226主要分布于CD56^bright,亚群，而在IL-15作用下，NKG2A^ CD226^ 双阳性细胞明显增加。在MLC活化的NK细胞中，CD226主要分布于CD56^dim亚群，在IL-15作用下，CD226主要分布于CD56^bright亚群，IL-2和IL-15都能促进CD16^ CD226^ 和NKG2A^ CD226^ 双阳性细胞的增殖。IL-2和IL-15能明显提高PBMC培养上清中IFN-γ的水平，并能促进PBMC和MLC中NK细胞的杀伤活性。结论：CD226主要分布于活化NK细胞CD56^bright群上，其表达水平及与CD16及NKG2A共存关系可能受不同细胞因子调节并与NK细胞功能相关。     

自体外周造血干细胞移植的护理

通过8例自体外周干细胞移植病人的护理,认为针对移植的不同阶段,采取心理护理、预防感染及出血等护理措施,并在层流病房进行全环境护理,能提高移植成功率。加强消毒隔离,预防感染和出血,是自体外周干细跑移植的关键。     

杀伤细胞KIR与造血干细胞移植

NK细胞的杀伤细胞免疫球蛋白样受体(killercellimmunoglobulin-likereceptor,KIR)是属于免疫球蛋白样超家族的一系列分子,表达于自然杀伤(naturekiller,NK)细胞和部分T细胞的表面,能识别HLAI类分子。它们可通过与靶细胞表面的HLAI类分子结合,传导激活或抑制信号,从而调节NK细胞和T细胞的活性。造血干细胞移植(hematopoieticstemcelltransplantation,HSCT)过程中,当供者KIR与受者HLAI类分子不匹配时,供者NK细胞功能不被抑制,从而对受者抗原提呈细胞(antigen-presentingcell,APC)和残留肿瘤细胞产生较强的异源反应。研究也已证实供者NK细胞的异源反应活性可提高移植物植入率、促进移植物抗白血病细胞(graft-versus-leukemia,GvL)作用并降低移植物抗宿主病(graft-versus-hostdisease,GvHD)。     

造血干细胞移植后免疫重建

造血干细胞移植（HSCT）已广泛应用于临床,是治疗血液系统疾患、实体瘤、基因缺陷及自身免疫性疾病的重要手段干细胞移植伴随着严重的免疫缺陷,这一时期,患者有合并严重感染的风险固有免疫恢复迅速．NK细胞、树突状细胞移植后数周内即可恢复。而适应性免疫系统恢复缓慢,T细胞和B细胞移植后数月才可恢复正常,而T细胞功能恢复需要数年的时间：研究造血系统各细胞存移植后数量、功能上的恢复规律,对如何加快免疫重建,降低移植死亡率有重要意义.     

自体外周血干细胞移植治疗下肢缺血性疾病

目的 观察自体干细胞移植治疗下肢缺血性疾病的临床疗效及部分影响因素.方法 下肢缺血性疾病病人15例,其中男性8例,女性7例;年龄44～77岁,平均年龄67.3岁.病人移植前均内科常规治疗半年以上,临床症状、体征未改善.应用自体干细胞移植治疗,按照操作规范和病人实际情况采集外周血干细胞(PBSC),全部病人均给予重组人粒细胞集落刺激因子300～600μg/d,皮下注射,行自体PBSC动员3～5d,然后用费森尤斯血细胞分离机采集PBSc,将干细胞悬液按3×3cm距离进行肢体移植术.术后第1天至3个月定期观察各项指标综合评估.结果 PBSC移植后3个月进行评价,全部病例下肢疼痛明显缓解,皮温升高,下肢冷感消失,14例感染得到控制,溃疡或足趾坏疽明显好转或愈合,足趾颜色由青紫色转为正常,肿胀消失,无1例病人行截肢术;有2例病人趾头已坏死在移植同时行截趾术;移植后所有病人均未出现并发症和明显不良反应.结论 自体PBSC移植治疗糖尿病下肢缺血性疾病是一种安全、有效的手段,可使一部分病人免除截肢,改善生活质量.     

自体外周血造血干细胞移植后序贯CIK细胞治疗急性髓系白血病

背景：细胞因子诱导的杀伤细胞作为一种有效的过继免疫治疗方法,成为治疗急性髓系白血病的一种新的手段,目前关于急性髓系白血病自体移植后序贯细胞因子诱导的杀伤细胞治疗的报道尚少,值得进一步研究。 目的：观察急性髓系白血病M2患者自体外周血造血干细胞移植后序贯细胞因子诱导的杀伤细胞治疗的临床疗效和不良反应。 方法：入选45例低、中危急性髓系白血病M2患者,其中19例在自体外周血造血干细胞移植后序贯了细胞因子诱导的杀伤细胞治疗,另26例未序贯细胞因子诱导的杀伤细胞治疗,比较两组患者的复发率、无病生存率、总生存率,观察细胞因子诱导的杀伤细胞治疗的安全性。 结果与结论：①序贯细胞因子诱导的杀伤细胞治疗组的复发率低于未序贯细胞因子诱导的杀伤细胞治疗组(21.05%,38.46%,P < 0.05);序贯细胞因子诱导的杀伤细胞治疗组患者的2年无病生存率和2年总生存率均高于未序贯细胞因子诱导的杀伤细胞治疗组,差异均有显著性意义(P < 0.05)。②19例接受细胞因子诱导的杀伤细胞治疗的患者均顺利完成治疗方案,治疗过程中除4例出现寒战、发热外,无其他不良反应。结果显示低、中危急性髓系白血病M2患者自体外周血造血干细胞移植后序贯细胞因子诱导的杀伤细胞治疗可降低原发病的复发率,提高患者的无病生存率及总生存率,且无明显不良反应,是一种安全、有效、可行的治疗方法。中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程全文链接：     

人参皂甙Rg3促进自体外周血干细胞移植后免疫重建的临床观察

大剂量放化疗联合自体造血干细胞移植（AHCT）系治疗恶性血液肿瘤及部分实体瘤的新疗法之一。然而，移植后仍有部分病人出现复发和转移。移植后免疫功能的状态及免疫治疗对清除体内残留肿瘤细胞和移植后的抗感染作用都至关重要池。。因此移植后的免疫重建及免疫治疗已成为当今造血干细胞移植领域研究的热点之一。人参皂甙Rg3是从中药人参中提取的一种四环三萜皂甙，能显著促进淋巴细胞的增殖，提高体液免疫的功能、NK细胞和T淋巴细胞亚群的活性水平。本研究利用“扶正祛邪”理论，通过对人参皂甙Rg3（参一胶囊）用于干细胞移植后免疫功能重建的研究，以期找到一种促进免疫重建的新方法，从而提高AHSCT的生存率，降低移植后的复发和感染。     

Immune Reconstitution after Haploidentical Hematopoietic Stem Cell Transplantation

Haploidentical hematopoietic stem cell transplantation (HSCT) offers the benefits of rapid and nearly universal donor availability and has been accepted worldwide as an alternative treatment for patients with hematologic malignancies who do not have a completely HLA-matched sibling or who require urgent transplantation. Unfortunately, serious infections and leukemia relapse resulting from slow immune reconstitution remain the 2 most frequent causes of mortality in patients undergoing haploidentical HSCT, particularly in those receiving extensively T cell–depleted megadose CD34⁺ allografts. This review summarizes advances in immune recovery after haploidentical HSCT, focusing on the immune subsets likely to have the greatest impact on clinical outcomes. The progress made in accelerating immune reconstitution using different strategies after haploidentical HSCT is also discussed. It is our belief that a predictive immune subset–guided strategy to improve immune recovery might represent a future clinical direction.     

Cerebral Toxoplasmosis After Autologous Peripheral Blood Stem Cell Transplantation

Toxoplasmosis appears to be a rare opportunistic protozoal infection following haematopoietic stem cell transplantation (HSCT). Most cases have been reported in allogeneic HSCT recipients, with only anecdotal reports of infection occurring after autologous transplantation. Reported here is the case of a patient who developed cerebral toxoplasmosis following autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma.     

Long-Term Immune Reconstitution and Infection Burden after Mismatched Hematopoietic Stem Cell Transplantation

Mismatched unrelated donor (MMUD) or umbilical cord blood (UCB) can be chosen as alternative donors for allogeneic stem cell transplantation but might be associated with long-lasting immune deficiency. Sixty-six patients who underwent a first transplantation from either UCB (n = 30) or 9/10 MMUD (n = 36) and who survived beyond 3 months were evaluated. Immune reconstitution was prospectively assessed at sequential time points after transplantation. NK, B, CD4⁺, and CD8⁺ T cells and their naïve and memory subsets, as well as regulatory T cells (Treg), were studied. Detailed analyses on infections occurring after 3 months were also assessed. The 18-month cumulative incidences of infection-related death were 8% and 3%, and of infections were 72% and 57% after MMUD and UCB transplantation, respectively. Rates of infection per 12 patient-month were roughly 2 overall (1 for bacterial, .9 for viral, and .3 for fungal infections). Memory, naïve CD4⁺ and CD8⁺T cells, naïve B cells, and Treg cells reconstitution between the 2 sources were roughly similar. Absolute CD4⁺T cells hardly reached 500 per μL by 1 year after transplantation and most B cells were of naïve phenotype. Correlations between immune reconstitution and infection were then performed by multivariate analyses. Low CD4⁺ and high CD8⁺T cells absolute counts at 3 months were linked to increased risks of overall and viral (but not bacterial) infections. When assessing for the naïve/memory phenotypes at 3 months among the CD4⁺ T cell compartment, higher percentages of memory subsets were protective against late infections. Central memory CD4⁺T cells protected against overall and bacterial infections; late effector memory CD4⁺T cells protected against overall, bacterial, and viral infections. To the contrary, high percentage of effector- and late effector-memory subsets at 3 months among the CD8⁺ T cell compartment predicted higher risks for viral infections. Patients who underwent transplantation from alternative donors represent a population with very high risk of infection. Detailed phenotypic analysis of immune reconstitution may help to evaluate infection risk and to adjust infection prophylaxis.     

Impact of a Low CD34+ Cell Dose on Allogeneic Peripheral Blood Stem Cell Transplantation

Although the CD34⁺ cell dose in allogeneic peripheral blood stem cell transplantation (PBSCT) is considered to be associated with transplantation outcomes, a lower acceptable threshold has not been defined. We retrospectively analyzed 2919 adult patients with hematologic malignancies who underwent related PBSCT in Japan between 2001 and 2014. According to the number of CD34⁺ cells in the graft, we categorized 2494 patients in the standard group (2 to 5 × 10⁶ cells/kg), 377 patient in the low group (1 to 2?×?10⁶ cells/kg), and 48 patients in the very low group (<1?×?10⁶ cells/kg). Compared with the standard group, the low and very low groups showed delayed neutrophil recovery (93.8%, 89.5%, and 78.3%, respectively at day +28; P?<?.001) and platelet recovery (69.3%, 53.0%, and 45.5%, respectively at day +28; P?<?.001). The 2-year overall survival (OS) in the 3 groups was 45.5%, 45.3%, and 29.8%, respectively, with inferior survival in the very low group. However, a higher percentage of high-risk patients may account for the inferior survival in the very low group, and no significant difference in OS was found in a multivariate analysis. There were no differences in relapse, nonrelapse mortality, or the development of graft-versus-host disease among the 3 groups. In conclusion, allogeneic PBSCT with low CD34⁺ cell doses of 1 to 2?×?10⁶ cells/kg gives acceptable results, whereas further investigations are needed to evaluate the effects of lower doses of <1?×?10⁶ cells/kg owing to the smaller number and the higher percentage of patients with adverse prognostic factors in this cohort.     

Incidence of Supraventricular Arrhythmias during Autologous Peripheral Blood Stem Cell Transplantation

Arrhythmias, especially supraventricular arrhythmias, often complicate the clinical course during autologous hematopoietic cell transplantation (AHCT). We wanted to determine the incidence and risk factors for cardiac arrhythmias during AHCT. The study included 983 patients (median age, 58 years [range, 19 to 77]; 61% male) who underwent AHCT between August 2006 and December 2010 at a single institution and for whom all relevant medical records were available for review. AHCT was done for plasma cell disorders in 58% patients and for lymphoma or leukemia in the remaining. Overall, 92 patients (9.4%) developed a supraventricular tachyarrhythmia at a median of 9 days posttransplantation (range, 0 to 18) and with a median duration of less than 1 day (range, <1 to 17 days). Atrial fibrillation was the most common and seen in 71 patients (7%), followed by atrial flutter and supraventricular tachycardia in 12 (1%) and 8 (1%) patients, respectively. In multivariate analysis, age older than 63 years, presence of premature supraventricular complexes or atrioventricular conduction delay on pretransplantation electrocardiogram, and history of any prior arrhythmia increased the risk of arrhythmia. Development of arrhythmia resulted in longer outpatient follow-up after AHCT, with the median follow-up for those developing an arrhythmia of 22 days compared with 19 days for the rest; P < .001. In conclusion, 9% of patients undergoing ASCT developed supraventricular arrhythmias posttransplantation, and this risk was elevated among older patients, those with a prior history of arrhythmias, and those with pretransplantation electrocardiographic abnormalities.