Nakao S, Nakatsumi T, Chuhjo T, Ohtaguro M, Tsuchiya H, Niki T, Shiobara S, Mori T, Matsuda T
Third Department of Medicine, Kanazawa University School of Medicine, Japan.
Bone Marrow Transplant. 1992 Feb;9(2):107-11.
In an attempt to gain insight into the etiology of late graft failure, we analysed the origin of bone marrow mononuclear cells (BMMC) and peripheral blood leukocytes in patients with this syndrome by taking advantage of DNA fragment length polymorphisms in variable number of tandem repeats (VNTR) loci. Amplification of the VNTR loci in DNA from BMMC using the polymerase chain reaction revealed the persistence of host cells in two of four patients studied. One of the patients, whose cultured lymphocytes inhibited in vitro growth of donor-derived hemopoietic progenitor cells, responded to immunosuppressive therapy and donor-derived hemopoiesis was restored. In the other patient, host-derived polymorphonuclear leukocytes (PMN) appeared together with donor-derived PMN from the early post-transplant period, and he proceeded to relapse with myelodysplastic syndrome. In the other two patients in whom host cells were not detectable, the marrow hypoplasia was associated with chronic graft-versus-host disease (GVHD). The hypoplasia improved significantly as the chronic GVHD improved in response to immunosuppressive therapy. We conclude that detecting minimal residual host cells by means of amplification of VNTR loci is valuable for understanding the etiology of late graft failure in marrow transplant recipients, and could prove helpful for choosing appropriate therapy for this syndrome.
为深入了解晚期移植失败的病因，我们利用可变串联重复序列（VNTR）位点的DNA片段长度多态性，分析了该综合征患者骨髓单个核细胞（BMMC）和外周血白细胞的来源。使用聚合酶链反应对BMMC中的DNA进行VNTR位点扩增，结果显示，在研究的4例患者中有2例存在宿主细胞残留。其中1例患者，其培养的淋巴细胞抑制供体来源的造血祖细胞的体外生长，经免疫抑制治疗后有反应，供体来源的造血功能得以恢复。另一例患者，移植后早期宿主来源的多形核白细胞（PMN）与供体来源的PMN同时出现，随后发展为骨髓增生异常综合征复发。另外2例未检测到宿主细胞的患者，骨髓发育不全与慢性移植物抗宿主病（GVHD）有关。随着免疫抑制治疗后慢性GVHD的改善，骨髓发育不全也明显改善。我们得出结论，通过VNTR位点扩增检测微量残留宿主细胞，对于理解骨髓移植受者晚期移植失败的病因很有价值，并且可能有助于为该综合征选择合适的治疗方法。
