Verdonck L F, van Blokland W T, Bosboom-Kalsbeek E K, van Heugten H G, Tilanus M G, de Weger R A
Department of Haematology, University Hospital Utrecht, The Netherlands.
Bone Marrow Transplant. 1996 Aug;18(2):389-95.
T cell depletion of the bone marrow graft, the most effective method to prevent severe graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT), has resulted in approximately three times more relapses of the disease post-transplant than after non-T cell-depleted BMT. It has been hypothesized that this is caused by the development of mixed T cell chimerism, often observed after T cell depleted BMT, whereas non-T cell-depleted BMT generally results in complete donor T cell chimerism. In order to find an approach of T cell depletion which may avoid the high relapse rate but prevent severe GVHD, we gave marrow recipients a partial T cell-depleted marrow graft containing 1 x 10(5) donor T cells/kg recipient's weight. To investigate whether our approach results in complete donor T cell chimerism, we analyzed post-transplant the origin of purified T cells in 56 patients with hematologic malignancies, including 15 patients at the time they relapsed. The T cells were studied for being of host or donor origin by amplification of four loci of variable number of tandem repeats (VNTR) by PCR. From 6 months post-BMT, all 45 patients who could be analyzed in remission (five had died and six had relapsed within 6 months) had T cells that were exclusively of donor origin. Furthermore, the T cells of 15 patients who had relapsed post-BMT were also exclusively of donor origin. Severe GVHD was never observed. Thus, this approach seems to combine the favorable aspects of both T cell-depleted and non-T cell-depleted BMT.
骨髓移植中去除骨髓移植物中的T细胞是预防异基因骨髓移植(BMT)后严重移植物抗宿主病(GVHD)的最有效方法,但与未去除T细胞的BMT相比,移植后疾病复发率高出约三倍。据推测,这是由于去除T细胞的BMT后常出现的混合T细胞嵌合体的形成,而未去除T细胞的BMT通常会导致完全的供体T细胞嵌合体。为了找到一种既能避免高复发率又能预防严重GVHD的T细胞去除方法,我们给骨髓移植受者移植了部分去除T细胞的骨髓移植物,每千克受者体重含1×10⁵个供体T细胞。为了研究我们的方法是否能导致完全的供体T细胞嵌合体,我们分析了56例血液系统恶性肿瘤患者移植后纯化T细胞的来源,其中15例患者处于复发时。通过PCR扩增四个可变数目串联重复序列(VNTR)位点来研究T细胞是宿主来源还是供体来源。自BMT后6个月起,所有45例可分析的处于缓解期的患者(5例在6个月内死亡,6例在6个月内复发)的T细胞均完全来自供体。此外,15例BMT后复发患者的T细胞也完全来自供体。从未观察到严重的GVHD。因此,这种方法似乎结合了去除T细胞和未去除T细胞的BMT的有利方面。