Allogeneic transplantation of CD34+selected hematopoietic cells -: Clinical problems and current challenges

Allogeneic transplantation of CD34+selected hematopoietic cells -: Clinical problems and current challenges
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DOI:
10.1080/10428190310001615684
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发表时间:
2004-03-01
影响因子:
2.6
通讯作者:
Bornhäuser, M
Bornhäuser, M
中科院分区:
医学4区
文献类型:
--
作者:
Platzbecker, U;Ehninger, G;Bornhäuser, M

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由于G-CSF动员的外周血已成为恶性血液病患者异基因移植的主要造血细胞来源,新的T细胞去除技术被开发出来以降低移植物抗宿主病的风险。免疫磁分离CD34+选择已被证明是最有效的方法,以实现3-4对数耗竭的T细胞,同时保留移植物中大量的造血祖细胞。阳性部分中包含大量CD34+细胞,这使得只有一种单倍型匹配的同胞捐赠者的植入变得容易。此外,对儿童受者的研究表明,大量输注造血祖细胞可以在移植后第一年及时恢复T细胞和B细胞。在慢性粒细胞白血病患者中,也有报道称,他们接受了来自相合的兄弟姐妹捐赠者的CD34+选择的PBSC,并随后输注捐赠者的T细胞,以建立移植物抗白血病效果。另一方面,在晚期白血病患者中进行的研究表明,接受来自半相合或无关捐赠者的CD34+选择的PBSC的移植排斥反应、复发和晚期机会性感染的风险增加。未来的努力将不得不集中在通过适应性地转移抗原特异性效应细胞或通过研究白细胞介素7等细胞因子的使用来恢复细胞免疫。尽管这些问题尚未得到解决,但高纯度CD34+PBSC异基因移植已成为重度GvHD高危患者的一种治疗选择。
Since G-CSF mobilized peripheral blood has become the major source of hematopoietic cells (PBSC) for allogeneic transplantation of patients with hematological malignancies, new technologies of T-cell depletion were developed to reduce the risk of graft-versus-host disease. CD34+ selection by immunomagnetic separation has been shown to be the most effective method to achieve a 3 - 4 log depletion of T-cells while preserving the high number of hematopoietic progenitors in the graft. The high number of CD34+ cells contained in the positive fraction have allowed to facilitate engraftment from sibling donors matched for only one haplotype. In addition, studies in pediatric recipients have shown that high numbers of hematopoiteic progenitors infused can lead to timely recovery of T- and B-cells in the first year after transplantation. Positive results have also been reported in patients with chronic myelogenous leukemia who had received CD34+ selected PBSC from HLA-identical sibling donors and subsequent infusions of donor T- cells to establish graft-versus-leukemia effects. On the other hand, studies performed in adults with advanced leukemia receiving CD34+ selected PBSC from haploidentical or unrelated donors demonstrated an increased risk for graft-rejection, relapse and late opportunistic infections. Future efforts will have to concentrate on the restoration of cellular immunity by either adaptively transferring antigen specific effector cells or by studying the use of cytokines like interleukin-7. Although these question have not been resolved yet, allogeneic transplantation of highly purified CD34+ PBSC has become an therapeutic option for patients who are at high-risk for severe GvHD.