Baron Frédéric, Storb Rainer
Fred Hutchinson Cancer Research Center and the University of Washington, 1100 Fairview Ave N, D1-100, PO Box 19024, Seattle, WA 98109-1024, USA.
Springer Semin Immunopathol. 2004 Nov;26(1-2):71-94. doi: 10.1007/s00281-004-0165-3. Epub 2004 Jul 29.
Allogeneic hematopoietic cell transplantation (HCT) was originally developed as a form of rescue from high-dose chemoradiotherapy, which is given both to eradicate malignancy and provide sufficient immunosuppression for allogeneic engraftment. The first attempts of allogeneic HCT in humans met with little success. However, a better understanding of the complexities of the human leukocyte antigen (HLA) system has allowed selecting compatible sibling donors, and the development of postgrafting immunosuppressive regimens has helped prevent serious graft-versus-host disease, thereby changing the role of allogeneic HCT from a desperate therapeutic maneuver to a curative treatment modality for many patients with malignant hematological diseases. In addition, the establishment of large registries of HLA-typed volunteers has permitted finding suitable unrelated donors for many patients without family donors. Further advances in the immunogenetics of HLA, especially typing by molecular techniques, have improved results after unrelated HCT, which have begun resembling those obtained with HLA-identical sibling grafts, at least in young patients. Important advances have also been made in the prevention and treatment of infectious complications and in other areas of supportive care. Since the late seventies, it has been recognized that allogeneic immunocompetent cells transplanted with the stem cells, or arising from them, mediated therapeutic anti-tumor effects independent of the action of the high-dose therapy, termed graft-versus-tumor (GVT) effects. This has prompted the recent development of non-myeloablative conditioning regimens for allogeneic HCT that have opened the way to include elderly patients and those with comorbid conditions. Remaining challenges include further advances in the prevention and treatment of both severe graft-versus-host disease and infections. Also, progress in adoptive transfer of T cells with relative tumor specificity and disease-targeted therapy with agents such as Imatinib, Rituximab or radiolabeled monoclonal antibodies would make allogeneic HCT even more effective.
异基因造血细胞移植（HCT）最初是作为一种从大剂量放化疗中挽救患者的手段而发展起来的，大剂量放化疗用于根除恶性肿瘤并为异基因植入提供足够的免疫抑制。人类首次进行异基因HCT的尝试收效甚微。然而，对人类白细胞抗原（HLA）系统复杂性的深入了解使得能够选择相匹配的同胞供体，移植后免疫抑制方案的发展有助于预防严重的移植物抗宿主病，从而将异基因HCT的作用从一种孤注一掷的治疗手段转变为许多恶性血液病患者的治愈性治疗方式。此外，建立大型HLA分型志愿者登记库使得许多没有家族供体的患者能够找到合适的非血缘供体。HLA免疫遗传学的进一步进展，尤其是分子技术分型，改善了非血缘HCT后的结果，至少在年轻患者中，这些结果已开始与HLA相同的同胞移植所获得的结果相似。在感染并发症的预防和治疗以及其他支持治疗领域也取得了重要进展。自七十年代末以来，人们认识到与干细胞一起移植或由干细胞产生的异基因免疫活性细胞介导了独立于大剂量治疗作用的治疗性抗肿瘤效应，称为移植物抗肿瘤（GVT）效应。这促使最近开发了用于异基因HCT的非清髓性预处理方案，为纳入老年患者和有合并症的患者开辟了道路。 remaining challenges include further advances in the prevention and treatment of both severe graft-versus-host disease and infections. Also, progress in adoptive transfer of T cells with relative tumor specificity and disease-targeted therapy with agents such as Imatinib, Rituximab or radiolabeled monoclonal antibodies would make allogeneic HCT even more effective.（最后一句原文中“Remaining challenges”表述有误，根据前文推测可能是“Remaining challenges”，翻译为“剩余的挑战”，整体翻译为：剩余的挑战包括在严重移植物抗宿主病和感染的预防和治疗方面取得进一步进展。此外，在具有相对肿瘤特异性的T细胞过继转移以及使用伊马替尼、利妥昔单抗或放射性标记单克隆抗体等药物进行疾病靶向治疗方面取得进展，将使异基因HCT更加有效。） 但由于不清楚是否是原文笔误，所以请根据实际情况判断。如果原文无误，可按以下内容理解：其余挑战包括在严重移植物抗宿主病和感染的预防与治疗方面取得进一步进展。此外，在具有相对肿瘤特异性的T细胞过继转移以及使用伊马替尼、利妥昔单抗或放射性标记单克隆抗体等药物进行疾病靶向治疗方面取得进展，将使异基因HCT更加有效。
