Pneumococcal polysaccharide vaccination in allogeneic hematopoietic stem cell transplantation recipients: a prospective single-center study

Few studies have evaluated the response of allogeneic hematopoietic stem cell transplantation [allo-HSCT] recipients to pneumococcal polysaccharide vaccine-23 [PPSV23] in the modern transplant era when more elderly patients undergo allo-HSCT. We administered a single dose of PPSV23 to 30 allo-HSCT recipients and evaluated serotype-specific antibody responses using IgG measured by enzyme-linked immunosorbent assay and opsonophagocytic assay [OPA] titers in a multiplexed opsonophagocytic killing assay. The median patient age was 54 years [range, 23–68], and the interval from allo-HSCT to vaccination was 756 days [range, 389–1903]. No severe adverse effects were observed. The median positive response rates at 1 month and 1 year post-vaccination for the 7 serotypes measured by IgG were the same at 43% [range, 33–57], while those for 8 serotypes measured by OPA were 72% [range, 55–86] and 55% [range, 52–62], respectively. Peripheral blood stem cell transplantation improved vaccine response based on OPA titers at 1 month post-vaccination. During the median follow-up period of 1135 days post-vaccination, one patient developed pneumococcal bacteremia at 998 days. Our study suggests that PPSV23 vaccination in allo-HSCT recipients is safe and may result in a serological response.     

造血干细胞移植术对肠道菌群结构的影响

目的监测造血干细胞移植术（Hematopoietic stem cell transplantation,HSCT）前后肠道菌群结构的动态变化。方法收集3例造血干细胞移植患者手术前后8个时间点的粪便样品,提取样品总DNA进行16S rRNA基因的V3区的bar coded 454焦磷酸测序,并用MANOVA、聚类分析、Pearson相关等统计方法对菌群结构的变化进行动态分析。结果 HSCT移植前,经过放、化疗及预防性抗生素治疗,患者的肠道菌群结构和组成发生显著的改变,多样性明显减少;移植4周后,菌群多样性有恢复的趋势,但菌群结构和组成与治疗前仍有明显的差异。整个HSCT过程中,Escherichia/Shigella及Enterococcus属变成肠道中最优势的细菌类群。结论肠道菌群结构在HSCT术前已发生显著的改变,机会致病菌Escherichia/Shigella及Enterococcus属成为HSCT患者肠道中最优势的细菌类群。     

单倍体造血干细胞移植对儿童重型再生障碍性贫血治疗的并发症分析

目的分析儿童重型再生障碍性贫血(SAA)单倍体造血干细胞移植和同胞全相合移植并发症发生率。方法回顾性分析2010年1月1日至2018年12月31日于苏州大学附属儿童医院进行治疗的SAA患儿(56例),分为治疗组(单倍体造血干细胞移植,35例),对照组(同胞全相合移植,21例)。其中患儿年龄、诊断距离移植时间、总单个核细胞数、总CD34+细胞数、中位随访时间、粒细胞植入时间、血小板植入时间及等级资料[供受体血型相合程度、急性移植物抗宿主病(aGVHD)分级、广泛性慢性移植物抗宿主病(cGVHD)分级、出血性膀胱炎分级、渗漏综合征分级]采用Mann-Whitney U检验。性别、疾病种类、供体与受体性别、预处理方案、CD20单抗的使用、HLA配型、供体来源、移植物来源、植入综合征、巨细胞病毒(CMV)血症、EB病毒(EBV)血症、死亡人数、植入失败人数和骨髓增殖不良人数使用卡方检验进行组间分析。生存曲线以及累积发生率用Kaplan-Meier法绘制,并使用Log-rank检验分析组间差异。结果与对照组比较,治疗组CD19+B细胞的重建延迟,而CD16+CD56+NK细胞数量移植后6个月开始增加,逐渐达到对照组的水平。与对照组比较,治疗组aGVHD、cGVHD、植入综合征和骨髓增殖不良累积发生率(14.29﹪±7.64﹪比57.14﹪±8.36﹪,11.67﹪±7.75﹪比61.59﹪±9.65﹪,9.53﹪±6.41﹪比74.86﹪±7.43﹪,0.0﹪比14.29﹪±5.91﹪)均升高,差异具有统计学意义(P<0.05),两组CMV与EBV感染,5年总体生存率(OS)、无失败生存率(FFS)、无GVHD失败存活率(GFFS)、Ⅲ-Ⅳ度aGVHD及广泛性cGVHD累积发生率比较差异无统计意义(P>0.05)。结论单倍体移植是治疗儿童SAA的有效治疗方案,但与同胞全合造血干细胞移植比较,其GVHD发生率较高,植入综合征和骨髓增殖不良的发生率较高,优化单倍体移植方案有望降低并发症,提高儿童重型再生障碍性贫血的生活质量。     

Role of HLA in hematopoietic stem cell transplantation

ABO blood group incompatibility is not a contraindication for allogeneic hematopoietic stem cell transplantation (allo-HSCT). An increasing number of ABO-incompatible HSCT (ABOi-HSCT) procedures have been performed along with advances in donor selection over the years. Currently, whether the recipient-donor ABO incompatibility has detrimental effects on post-HSCT outcomes is a matter of debate. Discrepancies across studies referring to various graft sources, donor types, conditioning regimens, and the use of immunomodulators complicate interpretations of the clinical outcomes of ABOi-HSCT, such as transfusion requirements, graft-versus-host disease (GVHD), disease relapse, overall survival (OS), and non-relapse mortality (NRM). Isohemagglutinins (ISO) targeting red blood cell (RBC) antigens are associated with post-HSCT immunohematological complications, including hemolysis, passenger lymphocyte syndrome (PLS), and pure red cell aplasia (PRCA). Immunohematological events occur frequently and are sometimes difficult to handle in clinical practice. Therefore, it is necessary to form a deeper understanding on the mechanism and a comprehensive management scheme for recipients of ABOi-HSCT. In this review, we summarized literature of the impact of ABO incompatibility on post-HSCT outcomes and outlined important immune-mediated hematological events.     

Cytokines and hematopoietic stem cell mobilization

Hematopoietic stem cell transplantation (HSCT) has become the standard of care for the treatment of many hematologic malignancies, chemotherapy sensitive relapsed acute leukemias or lymphomas, multiple myeloma; and for some non-malignant diseases such as aplastic anemia and immunodeficient states. The hematopoietic stem cell (HSC) resides in the bone marrow (BM). A number of chemokines and cytokines have been shown in vivo and in clinical trials to enhance trafficking of HSC into the peripheral blood. This process, termed stem cell mobilization, results in the collection of HSC via apheresis for both autologous and allogeneic transplantation. Enhanced understanding of HSC biology, processes involved in HSC microenvironmental interactions and the critical ligands, receptors and cellular proteases involved in HSC homing and mobilization, with an emphasis on G-CSF induced HSC mobilization, form the basis of this review. We will describe the key features and dynamic processes involved in HSC mobilization and focus on the key ligand-receptor pairs including CXCR4/SDF1, VLA4/VCAM1, CD62L/PSGL, CD44/HA, and Kit/KL. In addition we will describe food and drug administration (FDA) approved and agents currently in clinical development for enhancing HSC mobilization and transplantation outcomes.     

间充质干细胞在新型冠状病毒肺炎治疗中的研究现状

新型冠状病毒肺炎(COVID-19)由新型冠状病毒(SARS-CoV-2)导致,可发生严重肺部损伤甚至死亡,目前为止仍在全球范围内广泛蔓延。SARS-CoV-2感染依赖于血管紧张素转换酶2(ACE2)和Ⅱ型跨膜丝氨酸蛋白酶,可导致机体免疫紊乱,促发炎症风暴从而损伤靶器官。COVID-19目前尚无特效药物,间充质干细胞(MSCs)具有组织修复和免疫调节等功能,而且在流感病毒相关性肺炎及其他肺疾病中有一定疗效,因此可能是治疗COVID-19潜在有效药物。目前部分研究也显示出积极的治疗效果,而具体的疗效仍需进一步的临床研究来验证。     

造血干细胞移植治疗白血病患者负性因素干预措施的护理研究

目的针对造血干细胞移植治疗白血病患者不同阶段存在负性因素的特点进行干预并观察其临床效果。方法对96例白血病患者在造血干细胞移植前期-预处理期-移植期-移植后期的不同阶段负性因素实施心理支持,全环境保护方案,并发症的预防、观察与处理,健康教育等干预措施。结果减轻或消除负性因素对患者的影响,减少了并发症的发生,缩短留住无菌层流室的时间,提高白血病患者移植后的生活质量。结论制定一整套合理的、规范的、系统的护理流程,使患者获得最佳护理方案,有效减轻负性因素对患者的影响。     

Heterogeneous impact of cytomegalovirus reactivation on nonrelapse mortality in hematopoietic stem cell transplantation

This study aims to retrospectively analyze the efficacy of penciclovir in the prevention of viral infection after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Ninety-six patients with allo-HSCT were enrolled, who were treated at the Medical Center of Hematology of Xinqiao Hospital from June 2020 to September 2021. The experimental and control groups were treated with penciclovir and acyclovir, respectively, to prevent viral infection. By February 2022, the infection rates of cytomegalovirus, BK virus, JC virus, and Epstein-Barr virus (EBV) in the experimental group and the control group were 18.8% and 39.06% (P<0.05), 28.1% and 25% (P>0.05), 6.2% and 7.81% (P>0.05), 21.8% and 23.43% (P>0.05), respectively. The infection-related urinary system symptoms of the experimental group and the control group occurred in 4 and 9 patients, respectively, of which 3 and 9 patients died, respectively. Penciclovir can significantly reduce the cytomegalovirus infection rate after allo-HSCT and has better preventive effects than acyclovir without obvious side effects. The effectiveness and safety of penciclovir will be further verified in the future.     

异基因造血干细胞移植后并发自身免疫性溶血性贫血的治疗进展

异基因造血干细胞移植（HSCT）后自身免疫性溶血性贫血（AIHA）是HSCT后并不少见的并发症,其发病率约1﹪~ 6﹪,不同于一般的AIHA,HSCT后AIHA发病机制尚未完全明确,可能与HSCT后受者体内免疫失调相关。危险因素与移植患者年龄小、非恶性疾病、使用无关供者、半相合供者移植、脐血移植、去T细胞移植及移植后并发慢性移植物抗宿主病（GVHD）等有关。皮质激素作为一线治疗,疗效有限,难以持续缓解,需联合使用利妥昔单抗（RTX）、大剂量丙种球蛋白等,甚至需要联合霉酚酸酯、环磷酰胺、西罗莫司、阿伦单抗、依库丽单抗或蛋白酶体抑制剂硼替佐米等免疫抑制剂治疗,部分患者需行血浆置换,偶有行脾切除术者。移植后AIHA总死亡率常高达50﹪,总体预后差于单纯AIHA。该综述旨在总结HSCT后并发AIHA的最新治疗进展,供临床医师参考。     

Tolerance induction between two different strains of parental mice prevents graft-versus-host disease in haploidentical hematopoietic stem cell transplantation to F1 mice

Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) has been employed worldwide in recent years and led to favorable outcome in a group of patients who do not have human leukocyte antigen (HLA)-matched donors. However, the high incidence of severe graft-versus-host disease (GVHD) is a major problem for Haplo-HSCT. In the current study, we performed a proof of concept mouse study to test whether induction of allogeneic tolerance between two different parental strains was able to attenuate GVHD in Haplo-HSCT to the F1 mice. We induced alloantigen tolerance in C3H mice (H-2k) using ultraviolet B (UVB) irradiated immature dendritic cells (iDCs) derived from the cultures of Balb/c bone marrow cells. Then, we performed Haplo-HSCT using tolerant C3H mice as donors to F1 mice (C3H × Balb/c). The results demonstrated that this approach markedly reduced GVHD-associated death and significantly prolonged the survival of recipient mice in contrast to the groups with donors (C3H mice) that received infusion of non-UVB-irradiated DCs. Further studies showed that there were enhanced Tregs in the tolerant mice and alloantigen-specific T cell response was skewed to more IL-10-producing T cells, suggesting that these regulatory T cells might have contributed to the attenuation of GVHD. This study suggests that it is a feasible approach to preventing GVHD in Haplo-HSCT in children by pre-induction of alloantigen tolerance between the two parents. This concept may also lead to more opportunities in cell-based immunotherapy for GVHD post Haplo-HSCT.     

Perspectives on mesenchymal stem/progenitor cells and their derivates as potential therapies for lung damage caused by COVID-19

The new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which emerged in December 2019 in Wuhan, China, has reached worldwide pandemic proportions, causing coronavirus disease 2019 (COVID-19). The clinical manifestations of COVID-19 vary from an asymptomatic disease course to clinical symptoms of acute respiratory distress syndrome and severe pneumonia. The lungs are the primary organ affected by SARS-CoV-2, with a very slow turnover for renewal. SARS-CoV-2 enters the lungs via angiotensin-converting enzyme 2 receptors and induces an immune response with the accumulation of immunocompetent cells, causing a cytokine storm, which leads to target organ injury and subsequent dysfunction. To date, there is no effective antiviral therapy for COVID-19 patients, and therapeutic strategies are based on experience treating previously recognized coronaviruses. In search of new treatment modalities of COVID-19, cell-based therapy with mesenchymal stem cells (MSCs) and/or their secretome, such as soluble bioactive factors and extracellular vesicles, is considered supportive therapy for critically ill patients. Multipotent MSCs are able to differentiate into different types of cells of mesenchymal origin, including alveolar epithelial cells, lung epithelial cells, and vascular endothelial cells, which are severely damaged in the course of COVID-19 disease. Moreover, MSCs secrete a variety of bioactive factors that can be applied for respiratory tract regeneration in COVID-19 patients thanks to their trophic, anti-inflammatory, immunomodulatory, anti-apoptotic, pro-regenerative, and proangiogenic properties.     

The time is now: moving toward virus-specific T cells after allogeneic hematopoietic stem cell transplantation as the standard of care

Adoptive immunotherapy—in particular, T-cell therapy—has recently emerged as a useful strategy with the potential to overcome many of the limitations of antiviral drugs for the treatment of viral complications after hematopietic stem cell transplantation. In this review, we briefly summarize the current methods for virus-specific T-cell isolation or selection and we report results from clinical trials that have used these techniques, focusing specifically on the strategies aimed to broaden the application of this technology.     

Mesenchymal stem/stromal cells as adjuvant therapy in COVID-19-associated acute lung injury and cytokine storm: Importance of cell identification

Theoretically, mesenchymal stem cells (MSCs) are very promising as adjuvant therapy to alleviate coronavirus disease 2019 (COVID-19)-associated acute lung injury and cytokine storm. Several published studies, which used MSCs to alleviate COVID-19-associated acute lung injury and cytokine storm, reported promising results. However, the evidence came from a case report, case series, and clinical trials with a limited number of participants. Therefore, more studies are needed to get robust proof of MSC beneficial effects.     

Off-the-shelf mesenchymal stem cells from human umbilical cord tissue can significantly improve symptoms in COVID-19 patients: An analysis of evidential relations

Coronavirus disease-2019 (COVID-19) has affected more than 200 countries worldwide. This disease has hugely affected healthcare systems as well as the economy to an extent never seen before. To date, COVID-19 infection has led to about 165000 deaths in 150 countries. At present, there is no specific drug or efficient treatment for this disease. In this analysis based on evidential relationships of the biological characteristics of MSCs, especially umbilical cord (UC)-derived MSCs as well as the first clinical trial using MSCs for COVID-19 treatment, we discuss the use of UC-MSCs to improve the symptoms of COVID-19 in patients.     

Recent advances in crayfish hematopoietic stem cell culture: a model for studies of hemocyte differentiation and immunity

Hematopoiesis is the process by which blood cells (hemocytes) mature and subsequently enter the circulation and we have developed a new technique to culture the hematopoietic progenitor cells in vitro. The reason for the successful culture was the isolation of a plasma protein that turned out to be a novel cytokine, astakine 1 (Ast1) containing a domain present in several vertebrates, so-called prokineticins. Now we have detected several astakines from other invertebrate species. Depending on our discovery of the cytokine Ast1 we have an opportunity to study in detail the differentiation of cells in the hematopoietic tissue of a crustacean, a tissue of evolutionary interest for studies of the connection between the vascular system and the nervous system. We have been able to isolate the entire hematopoietic tissue and for the first time detected a link between this tissue and the brain. We have further localized a proliferation center in the tissue and characterized its different parts. We have also used this system to isolate a new hematopoietic factor CHF that is important in the crossroad between apoptosis and hemocyte differentiation. Our technique for culture of crayfish hematopoietic stem cells provides a simple tool for studying the mechanism of hematopoiesis, but also enables detailed studies of immune defense reactions. Further, the culture system has been used for studies of viral defense and the system is suitable for gene silencing which allows functional characterization of different molecules involved in host defense as well as in hemocyte differentiation.     

Spermatogonial stem cell transplantation and testicular function

Spermatogonial stem cells (SSCs) are responsible for the continual production of spermatozoa throughout adult life. Interactions between SSCs and the surrounding cells in the seminiferous tubules regulate the biological activity of these cells. Factors involved in the regulation of SSCs are beginning to be defined by animal models and the culture of SSCs in defined media. A critical development in the characterization of SSCs has been the development of the germ cell transplantation technique, which provides the only assay for the presence of SSCs in a population of cells, and which allows the determination of whether SSCs are proliferating or differentiating in culture. This approach has accelerated SSC-focused research and promises to provide a better understanding of the factors and mechanisms that regulate these cells. The knowledge provided by this work is also critical to an appraisal of the components of the SSC niche in the seminiferous epithelium. Thus, many aspects of testicular function can be defined by the investigation of SSCs and the factors, cells, and environment that regulate SSCs, thereby leading to a more comprehensive understanding of spermatogenesis.     

Stem cell therapies for COVID-19: Strategy and application

In this perspective, the potential application of stem cells for the treatment of COVID-19 related pneumonia and their potential mechanism of action have been overviewed.