Engraftment kinetics after nonmyeloablative allogeneic peripheral blood stem cell transplantation: Full donor T-cell chimerism precedes alloimmune responses
Engraftment kinetics after nonmyeloablative allogeneic peripheral blood stem cell transplantation: Full donor T-cell chimerism precedes alloimmune responses
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DOI：
10.1182/blood.v94.9.3234.421k16_3234_3241
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发表时间：
1999-11-01
期刊：
影响因子：
20.3
通讯作者：
Barrett, AJ
中科院分区：
文献类型：
--
作者：
Childs, R;Clave, E;Barrett, AJ
非清髓性异基因干细胞移植最近被认为是传统大剂量移植方案的一种更安全的替代方案。尽管非清髓性手术后混合嵌合体的发生率很高，但供体细胞在特定细胞系中移植的确切动力学尚未确定。我们研究了15名患者在接受了环磷酰胺和氟达拉滨的准备方案后，接受了来自人类白细胞抗原相合(n=14)或5/6抗原相合的同胞供者的异基因外周血干细胞(PBSC)移植后的谱系特异性嵌合体。通过小卫星区域的聚合酶链式反应(PCR)每周评估供者T淋巴细胞和髓系细胞的嵌合体。8名患者在移植后121至409天内存活。存活超过30天的14名患者中，有10名(71.4%)出现了与移植物抗恶性肿瘤(GVM)效应相一致的延迟疾病消退。一名患者排斥移植，随后自体造血功能恢复。血液学恢复迅速(中位数为11天，达到500中性粒细胞/亩L)，最初以受者为主。移植后200天，供者骨髓嵌合体逐渐取代受者造血，成为完全供者。相比之下，T细胞植入更快，在停用环孢素和供者淋巴细胞输注后，30天有7名患者完全嵌合，200天有6名患者进一步嵌合。完全供者T细胞移植先于供者骨髓移植、急性移植物抗宿主病和疾病消退，这与完全表达同种异体反应的100%供者T细胞嵌合的要求是一致的。这些结果强调了谱系特异性嵌合体分析对于成功操纵非清髓性异基因PBSC移植后植入的重要性。
Nonmyeloablative allogeneic stem cell transplantation has recently been explored as a safer alternative to conventional high-dose transplant regimens. Although a high incidence of mixed chimerism after nonmyeloablative procedures has been reported, the exact kinetics of engrafting donor cells in specific cellular lineages has yet to be defined. We investigated lineage-specific chimerism in 15 patients receiving an allogeneic peripheral blood stem cell (PBSC) transplant from an HLA-identical (n = 14) or a 5/6 antigen-matched sibling donor after a preparative regimen of cyclophosphamide and fludarabine. Donor chimerism was assessed weekly in T lymphocytes and myeloid cells by polymerase chain reaction (PCR) of minisatellite regions. Eight patients survived between 121 to 409 days after transplant. Ten of 14 patients surviving more than 30 days (71.4%) had delayed disease regression consistent with a graft-versus-malignancy (GVM) effect. One patient rejected the transplant with subsequent recovery of autologous hematopoiesis. Hematological recovery was rapid (median, 11 days to greater than or equal to 500 neutrophils/mu L) and was initially predominantly recipient In origin. Donor myeloid chimerism gradually supplanted recipient hematopoiesis and became fully donor in all survivors by 200 days after transplantation. In contrast, T-cell engraftment was more rapid, with full chimerism in 7 patients by day 30 and in 6 further patients by day 200 after cyclosporine withdrawal and donor lymphocyte infusion. Full donor T-cell engraftment preceded donor myeloid engraftment, acute graft-versus-host disease, and disease regression, consistent with a requirement for 100% donor T-cell chimerism for full expression of the alloresponse. These results emphasize the importance of lineage-specific chimerism analysis to successfully manipulate engraftment after nonmyeloablative allogeneic PBSC transplantation.