Bone marrow transplantation across HLA barriers by increasing the number of transplanted cells.
Bone marrow transplantation across HLA barriers by increasing the number of transplanted cells.
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DOI：
10.1016/0167-5699(95)80021-2
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发表时间：
1995-09
期刊：
影响因子：
--
通讯作者：
Y. Reisner;Massimo F. Martelli
中科院分区：
文献类型：
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作者：
Y. Reisner;Massimo F. Martelli
在整个20世纪70年代，移植物抗宿主病(GVHD)在接受人类白细胞抗原不相合骨髓移植的受者中都是致命的。这一主要障碍在2980年通过在严重联合免疫缺陷患者移植前引入严格的T细胞耗竭而被克服。然而，在白血病患者中，移植物排斥或移植物衰竭抵消了预防移植物抗宿主病的益处。在这篇文章中，Yair Reisner和Massimo Marelli讨论了如何通过加强条件调节方案并大幅增加移植干细胞的剂量来克服这个问题。由于缺乏合适的主要组织相容性复合体(MHC)匹配的供者，异基因骨髓移植(BMT)在治疗恶性血液病和其他疾病方面的应用受到阻碍。在可能受益于骨髓移植的患者中，只有不到30%的患者有HLA相合的兄弟姐妹，只有3%-5%的患者的亲属只有一个HLA基因不匹配。最近建立了大量的人类白细胞抗原分型个人登记，导致来自非血缘关系捐赠者的移植大幅增加。在美国，虽然40%-50%的高加索患者能够成功地找到与人类白细胞抗原A、B、DR相匹配的、无血缘关系的捐献者，但由于显著的多态性，其他种族找到捐赠者的几率要低得多；一般来说，许多患者找不到合适的(有血缘或无血缘关系的)捐赠者。相比之下，几乎所有的患者都有一个可以作为捐赠者的单倍体相合的亲属(父母、孩子、兄弟姐妹)。
Throughout the 1970s graft-versus-host disease (GVHD) was uniformly lethal in recipients of HLA-mismatched bone marrow. This major obstacle was overcome in 2980 by the introduction of rigorous T-cell depletion prior to transplantation into patients with severe combined immunodeficiency. However, in leukemia patients, the benefit of preventing GVHD was offset by graft rejection or graft failure. In this article, Yair Reisner and Massimo Martelli discuss how this problem may be overcome by intensification of the conditioning protocol in conjunction with a major increase in the dose of transplanted stem cells.The application of allogeneic bone marrow transplantation (BMT) for the treatment of patients with hematological malignancies and other diseases is hampered by the lack of availability of suitable major histocompatibility complex (MHC)-matched donors. Less than 30% of patients who might benefit from BMT have HLA-identical siblings, and only 3-5% have a relative with only a single HLA-locus mismatch. The recent establishment of large registries of HLA-typed individuals has led to a substantial increase in transplants from unrelated donors. Although 40-50% of Caucasian patients in the USA are successful in locating an HLA-A, B, DR-matched, unrelated donor, other ethnic groups have a much lower probability of finding donors due to marked polymorphism; in general, many patients fail to find an appropriate (related or unrelated) donor. By contrast, nearly all patients have an HLA-haploidentical relative (parent, child, sibling) who could serve as a donor.