炎症性肠病及其干细胞移植再生修复

炎症性肠病(IBD)在我国发病率逐步升高,其相关病理学研究和再生修复成为研究的热点.炎症性肠病存在易感基因NOD2,发病与感染、饮食、药物、肠道菌群变化及免疫因素有关.肠道干细胞,具有自我更新与增殖能力.肠黏膜被破坏时,陷窝残存的干细胞向外生长并移行,重建绒毛直至肠黏膜恢复正常.肠道干细胞的增殖和分化与多种细胞因子作用有关.造血干细胞移植治疗IBD是最近出现的一种新型治疗方法,自体与异体移植均有较好临床疗效,基础研究已经证实移植的造血干细胞可以定居于肠道上皮,但移植修复损伤肠道黏膜的详细机制则有待于深入研究.     

肾脏疾患的造血干细胞移植

用造血干细胞移植治疗肾细胞癌及非恶性难治性肾脏疾病是近年开展起来的一种新治疗方法。但造血干细胞移植对肾脏的毒副作用也较大，造血干细胞移植相关肾病逐渐引起了人们的重视。本文就造血干细胞移植在肾脏疾病中的应用进展及其移植后的肾性并发症作一综述。     

造血干细胞移植治疗炎症性肠病进展

炎症性肠病(IBD)是胃肠道慢性炎性肉芽肿性疾病,其发病与环境、遗传因素相关,传统治疗包括抗炎和抑制免疫等治疗.新近的研究提示造血干细胞移植(HSCT)治疗IBD有效,此文就HSCT治疗IBD的研究现状和存在的问题进行概述.     

骨髓干细胞移植治疗炎症性肠病的前景可观

炎症性肠病（IBD）在我国的发病率逐年增加，现有的治疗手段和疗效有限，骨髓干细胞移植治疗IBD具有很好的疗效,但有待更大样本的前瞻性、随机、对照研究，并进一步完善其机制，以指导临床实践。本文结合目前国内外干细胞移植治疗IBD的临床和基础研究,对骨髓干细胞移植治疗IBD的可能机制进行述评。     

自体造血干细胞移植对急性髓系白血病的治疗进展

自20世纪80年代至今,自体造血干细胞移植已成为一种治疗急性髓系白血病(AML)的主要疗法。目前自体造血干细胞移植成为因难以找到人类白细胞抗原(HLA)配型相合者而不能行异基因造血干细胞移植的主要治疗手段。该文综述了自体造血干细胞移植在低危、中高危AML及难治性或复发性AML患者中的治疗进展,追踪了降低自体造血干细胞移植治疗AML复发率的策略。     

靶向治疗及免疫治疗时代造血干细胞移植在急性白血病中的应用

目前造血干细胞移植已成为急性白血病治疗中不可或缺的组成部分。虽然过去20年来靶向治疗及免疫治疗迅速发展，提高了急性白血病的疗效，但造血干细胞移植的治疗地位依然不可取代。本文介绍了当前造血干细胞移植在急性白血病治疗中的作用，及靶向治疗与免疫治疗与造血干细胞移植结合对急性白血病患者疗效的改善。     

自体造血干细胞移植治疗老年恶性血液病的疗效和安全性

目的 自体造血干细胞移植是血液系统肿瘤的有效治疗选择，但在老年患者中的应用仍有争议，本文旨在分析自体造血干细胞移植在老年患者中的疗效和安全性。方法 回顾性分析2016年1月—2022年12月在华东医院血液科接受自体造血干细胞移植的患者数据，根据患者年龄分为老年组(≥60岁，n=25)和中青年组(<60岁，n=174),比较2组的外周造血干细胞动员效果、造血重建效果、肿瘤复发率、不良反应发生率和长期预后。结果 与中青年组比较，老年组的造血干细胞动员效果和重建速率差异均无统计学意义(P>0.05),且不加重移植相关的不良反应。长期预后分析显示2组均未达到中位总生存期和中位无进展生存期，2组5年生存率和5年无进展生存率无差异，多因素分析表明年龄不是影响自体造血干细胞移植预后的独立危险因素。结论 自体造血干细胞移植对于体能良好的老年恶性血液病患者是安全有效的治疗选择。     

脐血造血干细胞移植研究进展

脐血已逐渐成为异基因造血干细胞移植治疗中的一个重要的干细胞来源。尽管移植相关病死率稍高,但由于复发率较低、移植后患者的生存质量较高,接受脐血移植患者的存活率与其他类型的造血干细胞移植相当。脐血移植技术的不断改善也给患者带来了更好的移植疗效。双份脐血移植克服了脐血细胞数量不足的缺陷,扩大了脐血移植在高体重的儿童和成人患者中的应用。而减低剂量预处理方案的脐血移植则为一些老年患者提供了新的治疗选择。     

异基因造血干细胞移植治疗骨髓纤维化的若干问题

异基因造血干细胞移植是目前治愈骨髓纤维化的惟一治疗方法。文章通过对哪些患者需要做造血干细胞移 植、芦可替尼时代如何选择造血干细胞移植、芦可替尼在移植中所起作用、造血干细胞移植能否治愈骨髓纤维化、如 何提高移植疗效进行综述,指导临床工作中如何提高造血干细胞移植治疗骨髓纤维化的疗效。     

新药时代造血干细胞移植治疗多发性骨髓瘤若干问题探讨

新药时代,造血干细胞移植在多发性骨髓瘤(MM)综合治疗中的地位受到挑战。一些大规模、多中心、前瞻性的临床研究结果显示,对于年轻,具有遗传学高危因素,且有合适供者的MM患者,应首选异基因造血干细胞移植。对于不能接受异基因造血干细胞移植的患者,自体移植同样可以改善患者预后,延长患者生存期。因此,在新药时代,合理综合地运用新药与造血干细胞移植治疗,将会使患者最大程度获益。     

Haematopoietic stem cell transplantation in the treatment of autoimmune diseases

PURPOSE: During the past ten years, more than 1000 patients suffering from severe autoimmune disease have received an autologous haematopoietic stem cell transplant. These new therapeutic have been used in systemic sclerosis (scleroderma), multiple sclerosis, rheumatoid arthritis, juvenile idiopathic arthritis and systemic lupus erythematosus. CURRENT KNOWLEDGE AND KEY POINTS: Autologous haematopoietic stem cell transplantation has become a curative option for condition with very poor prognosis as severe systemic sclerosis, lupus erythematosus or other systemic diseases. This review summarizes the current experience in the phase I and II clinical trials in Europe and North America. We describe the main results and the limits of stem cell transplantation in systemic diseases. FUTURE PROSPECTS AND PROJECTS: Autologous haematopoietic stem cell transplant in the treatment of autoimmune disease has evolved from a experimental concept to a clinically feasible and powerful therapy for selected patients with severe disease.     

Cord blood transplantation for adults

Allogeneic haematopoietic stem cell transplant has become an import tool for the treatment of high risk and advanced haematological diseases. However, allogeneic transplantation has been limited by the availability of suitable related and unrelated donors. The positive results with umbilical cord blood as an alternative source of haematopoietic stem cells for transplantation in the paediatric setting encouraged studies in adult patients. In adults, however, the progress of cord blood transplantation has been slower, in part limited by the limitation of cell dose. We review here the current state of the art on cord blood transplantation for adults, and discuss some of the newer strategies being pursued in order to improve its safety and efficacy.     

Primary prophylaxis of invasive fungal infections in patients with haematologic malignancies. 2014 update of the recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology

Invasive fungal infections cause substantial morbidity and mortality in immunocompromised patients, particularly in those with haematological malignancies and recipients of allogeneic haematopoietic stem cell transplantation. Difficulties in diagnosing invasive fungal infections and subsequent delays in treatment initiation lead to unfavourable outcomes and emphasise the importance of prophylaxis. Since the recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology in 2009, results of 14 additional clinical studies have been published comprising 2,899 patients and initiating this update. Key recommendations for adult patients are as follows: Posaconazole remains the drug of choice during remission-induction chemotherapy in acute myeloid leukaemia, myelodysplastic syndrome and allogeneic haematopoietic stem cell transplantation with graft versus host disease (AI). In the pre-engraftment period of allogeneic transplantation, several antifungals are appropriate and can be recommended with equal strength: voriconazole (BI), micafungin (BI), fluconazole (BI) and posaconazole (BII). There is poor evidence regarding antifungal prophylaxis in the post-engraftment period of allogeneic haematopoietic stem cell transplantation if no steroids for treatment of graft versus host disease are required. Aerosolised liposomal amphotericin B inhalation in conjunction with fluconazole can be used in patients with prolonged neutropenia (BII).     

Ex vivo expansion of mobilized peripheral blood stem cells.

The scarcity of donors for allogeneic bone marrow transplantation, the limited number of haematopoietic stem cell (HSC)/progenitors in cord blood samples and the sometimes insufficient number of mobilized peripheral blood cells collected from heavily treated cancer patients may benefit from ex vivo expansion of these cells for clinical transplantation. Depending on the clinical application, expansion of different haematopoietic cell subsets is required. HSC transplantation requires expansion of all cellular subsets including precursors, progenitors and HSCs for the short and long-term engraftment of patients. Quiescent HSCs may also be required for gene therapy by retrovirus. Finally, amplification of cells such as dendritic cells (DC) and different subsets of T and natural killer (NK) cells is required for immunotherapy. The different haematopoietic lineages are produced under different experimental conditions and the starting population is a critical parameter for the proposed clinical application. So it is essential to define the aims of haematopoietic cell expansion and to adapt the experimental conditions to obtain the required cell population. Mobilized peripheral blood cells are increasingly used as a source of haematopoietic cells. We review the biological characteristics of mobilized peripheral blood and the expansion of the different components according to the aims of their clinical use in the context of the progress currently achieved.     

Graft-versus-tumour effect in non-small-cell lung cancer after allogeneic peripheral blood stem cell transplantation

Clinical evidence of a graft-vs.-tumour effect in solid tumours after haematopoietic stem cell transplantation is lacking. We report for the first time a complete and durable regression of a stage IB non-small-cell lung carcinoma in a patient who had received an allogeneic peripheral blood haematopoietic stem cell transplant for acute myeloblastic leukaemia in first complete remission. Disappearance of the tumour coincided with development of graft-vs. -host disease. This suggests that simultaneous generation of cytotoxic T lymphocytes against lung carcinoma cells could have been responsible for the regression. This unique clinical observation broadens the possibility of using allogeneic haematopoietic stem cell transplantation in treating neoplasias lacking significant sensitivity to chemotherapy.     

Treatment of inborn errors of immunity patients with inflammatory bowel disease phenotype by allogeneic stem cell transplantation

Patients with inborn errors of immunity (IEI) can suffer from treatment-refractory inflammatory bowel disease (IBD) causing failure to thrive and consequences of long-term multiple immunosuppressive treatments. Allogeneic haematopoietic stem cell transplantation (alloHSCT) can serve as a curative treatment option. In this single-centre retrospective cohort study we report on 11 paediatric and young adult IEI patients with IBD and failure to thrive, who had exhausted symptomatic treatment options and received alloHSCT. The cohort included chronic granulomatous disease (CGD), lipopolysaccharide-responsive and beige-like anchor protein (LRBA) deficiency, STAT3 gain-of-function (GOF), Wiskott–Aldrich syndrome (WAS), dedicator of cytokinesis 8 (DOCK8) deficiency and one patient without genetic diagnosis. All patients achieved stable engraftment and immune reconstitution, and gastrointestinal symptoms were resolved after alloHSCT. The overall survival was 11/11 over a median follow-up of 34.7 months. Graft-versus-host disease (GVHD) was limited to grade I–II acute GVHD (n = 5), one case of grade IV acute GVHD and one case of limited chronic GVHD. Since treatment recommendations are limited, this work provides a centre-specific approach to treatment prior to transplant as well as conditioning in IEI patients with severe IBD.     

Allogeneic haematopoietic stem cell transplantation in children with acute lymphoblastic leukaemia: the BFM/IBFM/EBMT concepts

Children with high risk or relapsed acute lymphoblastic leukaemia (ALL) can benefit from allogeneic haematopoietic stem cell transplantation (SCT). To reduce transplantation-associated complications, the BFM study group, the IBFM study group and the PD-WP-EBMT initiated a prospective cooperative multicentre trail for paediatric ALL patients with an indication for allogeneic stem cell transplantation. Four-digit high-resolution HLA typing for all nonsibling donors, standardised GvHD prophylaxis and therapy, uniform conditioning regimen and minimum standards for supportive care should reduce not only treatment-related mortality but also ameliorate late effects for young patients. Furthermore, the prospective evaluation aims to assess the role of haematopoietic SCT in comparison to chemotherapy to enable valuable treatment recommendations for further decisions.     

Peripheral blood stem cell transplantation.

Haematopoietic stem cells are usually sessile within the bone marrow microenvironment. However, small numbers do circulate in the peripheral blood of normal individuals, and following chemotherapy and/or intravenous growth factors, a substantial transient rise in circulating stem cells occurs. Leukocytes harvested by cytapheresis at this time can be used for autologous reconstitution of the haematopoietic and lymphoid systems following high dosage chemo/radiotherapy for the treatment of malignant disease. Peripheral blood stem cell transplants give rise to similar disease response rates as autologous bone marrow transplants, but have the advantage of more rapid haematopoietic reconstitution, and in addition can be offered to patients in whom marrow harvest is not feasible due to bone marrow damage or infiltration. This article reviews the theoretical and historical background to haematopoietic stem cell research, current clinical practice in peripheral blood stem cell mobilisation and harvesting, addresses the potential advantages and disadvantages compared to bone marrow transplantation, and assesses current experience of comparative efficacy.