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异基因外周血干细胞移植后淋巴细胞和粒细胞嵌合体的动态改变 预览 被引量:8

Serial and quantitative analysis of lymphoid and myeloid chimerism after allogeneic peripheral blood stem cell transplantation
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摘要 目的:探讨异基因外周血干细胞移植(allo-PBSCT)后T细胞、粒细胞嵌合体的动态改变及临床价值.方法:将多重PCR扩增短串联重复序列(STR-PCR)的法医试剂进行条件优化,间隔短时间抽取9例恶性血液病患者(5例清髓性PBSCT,4例非清髓性PBSCT)的外周血样,STR-PCR定量分析T细胞和粒细胞的嵌合体,并观察其对移植后应用免疫抑制剂的指导作用.结果:STR-PCR定量分析嵌合体的敏感性为5%,并具高度可重复性.清髓性PBSCT后10 d(+10 d),5/5例患者的粒细胞迅速演变为完全供者嵌合体(CDC),+14 d,4/5例患者的T细胞获得CDC.非清髓性PBSCT,+7~+14 d,供者T细胞信号的植入速度快于粒细胞;随后,供者粒细胞的比例突然增加,并迅速获得CDC,T细胞的植入却渐缓慢,最后,T细胞取得CDC的时间迟于粒细胞.依据供者T细胞信号的植入程度,及时调整非清髓性PBSCT后环孢素A(CsA)的用量,移植早期T细胞即获CDC,随访2~16个月,T细胞和粒细胞均呈稳定的供者植入状态.结论:供者T细胞的完全植入迟于粒细胞,动态监测T细胞嵌合体,可能有助于免疫抑制剂的调整. Objective:To explore the sequential change of chimerism in lymphoid and myeloid lineages after allogeneic peripheral blood stem cell transplantation (PBSCT).Method:A commercial multiplex short tandem repeat (STR) assay with fluorescence-based detection for forensic purposes was optimized. All blood samples were taken from 9 patients with hematologic malignancies at very short time intervals following ablative or nonablative PBSCT. The quantitative determination of chimerism in pure populations of T cells and neutrophils was performed using STR-PCR. The role of lineage-specific chimerism in directing immunosuppressive agents was also studied.Result:A sensitivity threshold was set at 5%, and reproducible results were obtained using optimized STR-PCR. By 10 days after ablative allo- PBSCT(day+10), the proportion of donor signals within myeloid cells attained complete donor chimerism (CDC) promptly in all five patients. By day +14, T-cells also gained CDC in 4/5 cases. By day 7 or 14 days after nonablative PBSCT, the proportion of donor STR signals within T cells was higher than that of myeloid cells. Thereafter, the proportion of donor signals within myeloid cells increased sharply to attain CDC, T cell engraftment became relatively slow. Ultimately, CDC in T cells lagged behind CDC in myeloid cells. Depending on the degree of donor signals in T cells, the dose of cyclosporine(CsA) was adjusted after nonablative PBSCT. CDC in T cells was gained in the early post-transplant period. Furthermore, stable T cell and myeloid cell engraftment was achieved following up 2 to 16 months.Conclusion:Complete donor T cell engraftment may lag behind donor myeloid engraftment. Sequential monitoring of T cell chimerism may be used to design individual patient immunosuppressive protocols.
作者 李大启 王椿 秦尤文 张帆 谢匡成 颜式可 金力 赵寿元 LI Daqi1 WANG Chun1 QIN Youwen1 ZHANG Fan2 XIE Kuangcheng1YAN Shike1 JIN Li2 ZHAO Shouyuan2(1Department of Hematology, First Hospital of Shanghai, Shanghai, 200080, China;2Genetic Research Institute of Fudan University)
出处 《临床血液学杂志》 2005年第2期 67-70,共4页 Journal of Clinical Hematology
基金 中国博士后科学基金
关键词 造血干细胞移植 异基因 嵌合体 T细胞 短串联重复序列 Hematopoietic stem cell transplantation, allogeneic Chimerism, T cell Short tandem repeat
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参考文献11

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共引文献35

同被引文献85

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