Juric Mateja Kralj, Ghimire Sakhila, Ogonek Justyna, Weissinger Eva M, Holler Ernst, van Rood Jon J, Oudshoorn Machteld, Dickinson Anne, Greinix Hildegard T
BMT, Department of Internal Medicine I, Medical University of Vienna , Vienna , Austria.
Department of Internal Medicine III, University Hospital of Regensburg , Regensburg , Germany.
Front Immunol. 2016 Nov 9;7:470. doi: 10.3389/fimmu.2016.00470. eCollection 2016.
Since the early beginnings, in the 1950s, hematopoietic stem cell transplantation (HSCT) has become an established curative treatment for an increasing number of patients with life-threatening hematological, oncological, hereditary, and immunological diseases. This has become possible due to worldwide efforts of preclinical and clinical research focusing on issues of transplant immunology, reduction of transplant-associated morbidity, and mortality and efficient malignant disease eradication. The latter has been accomplished by potent graft-versus-leukemia (GvL) effector cells contained in the stem cell graft. Exciting insights into the genetics of the human leukocyte antigen (HLA) system allowed improved donor selection, including HLA-identical related and unrelated donors. Besides bone marrow, other stem cell sources like granulocyte-colony stimulating-mobilized peripheral blood stem cells and cord blood stem cells have been established in clinical routine. Use of reduced-intensity or non-myeloablative conditioning regimens has been associated with a marked reduction of non-hematological toxicities and eventually, non-relapse mortality allowing older patients and individuals with comorbidities to undergo allogeneic HSCT and to benefit from GvL or antitumor effects. Whereas in the early years, malignant disease eradication by high-dose chemotherapy or radiotherapy was the ultimate goal; nowadays, allogeneic HSCT has been recognized as cellular immunotherapy relying prominently on immune mechanisms and to a lesser extent on non-specific direct cellular toxicity. This chapter will summarize the key milestones of HSCT and introduce current developments.
自20世纪50年代早期开始，造血干细胞移植（HSCT）已成为越来越多患有危及生命的血液学、肿瘤学、遗传性和免疫性疾病患者的既定治愈性治疗方法。这之所以成为可能，得益于全球范围内临床前和临床研究的努力，这些研究聚焦于移植免疫学问题、降低移植相关的发病率和死亡率以及有效根除恶性疾病。后者是通过干细胞移植物中含有的强大的移植物抗白血病（GvL）效应细胞实现的。对人类白细胞抗原（HLA）系统遗传学的令人兴奋的见解使得供体选择得到改善，包括HLA匹配的亲属和非亲属供体。除了骨髓，其他干细胞来源，如粒细胞集落刺激因子动员的外周血干细胞和脐带血干细胞，也已纳入临床常规应用。使用低强度或非清髓性预处理方案与非血液学毒性的显著降低相关，最终还降低了非复发死亡率，使老年患者和患有合并症的个体能够接受异基因HSCT，并从GvL或抗肿瘤效应中获益。在早期，通过高剂量化疗或放疗根除恶性疾病是最终目标；如今，异基因HSCT已被视为一种细胞免疫疗法，主要依赖免疫机制，在较小程度上依赖非特异性直接细胞毒性。本章将总结HSCT的关键里程碑，并介绍当前的发展情况。
