Ando Toshihiko, Yujiri Toshiaki, Nomiyama Jun, Mitani Noriyuki, Seguchi Masato, Matsubara Atsushi, Tanizawa Yukio
Third Department of Internal Medicine, Yamaguchi University School of Medicine, Ube, Japan.
Tohoku J Exp Med. 2008 Feb;214(2):159-63. doi: 10.1620/tjem.214.159.
In allogeneic stem cell transplantation, immune reactions can occur in 2 directions. The recipient's lymphocytes can recognize the donor's cells as "foreign" and attempt to kill them, which results in the host-versus-graft (HVG) reaction that is commonly termed graft rejection. The other direction is the graft-versus-host (GVH) reaction. When the recipient is homozygous at a mismatched human leukocyte antigen (HLA) locus, HLA disparity is present only in the former direction and not in the latter direction. If transplants harvested from such an HVG-mismatched donor can be used to achieve stable engraftment with minimal toxicity, then these donors can potentially be a useful alternative donor source. Here, we report 2 patients (1 with acute myeloblastic leukemia and another with lymphoblastic lymphoma) who were transplanted with peripheral blood stem cells (PBSCs) obtained from related donors mismatched at 2 HLA loci in the HVG direction but completely matched in the GVH direction. Our conditioning regimen, consisting of busulfan, cyclophosphamide, low-dose total body irradiation (TBI) (4 Gy), and fludarabine, achieved successful engraftment with an acceptable level of regimen-related toxicity. Our experience suggests that PBSC transplantation with an HVG-mismatched related donor and an appropriate conditioning regimen may be a therapeutic option for patients in whom early transplantation is desirable.
在异基因干细胞移植中，免疫反应可在两个方向发生。受者的淋巴细胞可将供者细胞识别为“外来的”并试图杀死它们，这会导致宿主抗移植物（HVG）反应，通常称为移植物排斥。另一个方向是移植物抗宿主（GVH）反应。当受者在不匹配的人类白细胞抗原（HLA）位点为纯合子时，HLA差异仅存在于前一个方向，而后一个方向不存在。如果从这种HVG不匹配的供者采集的移植物能够以最小的毒性实现稳定植入，那么这些供者可能是一种有用的替代供者来源。在此，我们报告2例患者（1例急性髓细胞白血病，另1例淋巴细胞淋巴瘤），他们接受了从相关供者获取的外周血干细胞（PBSC）移植，这些供者在HVG方向上有2个HLA位点不匹配，但在GVH方向上完全匹配。我们的预处理方案包括白消安、环磷酰胺、低剂量全身照射（TBI）（4 Gy）和氟达拉滨，实现了成功植入，且预处理方案相关毒性处于可接受水平。我们的经验表明，采用HVG不匹配的相关供者进行PBSC移植并结合适当的预处理方案，对于希望尽早进行移植的患者可能是一种治疗选择。
