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早期 CD3 外周血嵌合体预测清髓性双脐血移植后长期植入单位。

Early CD3 peripheral blood chimerism predicts the long-term engrafting unit following myeloablative double-cord blood transplantation.

机构信息

Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N., Seattle, WA 98109, USA.

出版信息

Biol Blood Marrow Transplant. 2012 Aug;18(8):1243-9. doi: 10.1016/j.bbmt.2012.01.014. Epub 2012 Feb 8.

Abstract

After double-cord blood transplantation, long-term hematopoietic dominance of a single-cord blood donor graft is established in the majority of patients; however, the mechanism behind this observation remains largely unknown. Beginning at day 7 posttransplantation, we prospectively measured weekly lineage-specific peripheral blood donor chimerisms in patients undergoing myeloablative double-cord blood transplantation to evaluate whether the degree of early donor contribution to specific lineage(s) would predict the long-term engrafting unit. Our results demonstrate that the donor unit with higher CD3 chimerism at day 7 became the dominant engrafting unit in 26 of 31 evaluable patients (P = .0002) and in 34 of 34 evaluable patients at day 14 (P < .0001). Similarly, higher donor unit CD33 chimerism was associated with dominant engraftment in 8 of 8 (day 7) and in 31 of 32 (day 14) evaluable patients. No statistically significant correlation between the dominant unit and order of infusion, infused total nucleated cells, CD34, or CD3 cell doses, unit viability, or HLA disparity was observed. The correlation of higher early posttransplantation donor CD3 peripheral blood chimerism with the dominant unit suggests a rapid immune-mediated response as a primary mechanism of action for long-term single-donor dominance. This finding may have clinical implications for early selection of the winning unit after double-cord blood transplantation and for novel cord blood manipulation strategies.

摘要

在双份脐带血移植后,大多数患者中都会建立起由单个脐带血供体移植物主导的长期造血功能;然而,这一观察结果背后的机制在很大程度上仍不清楚。从移植后第 7 天开始,我们前瞻性地测量了接受清髓性双份脐带血移植患者每周的谱系特异性外周血供者嵌合体,以评估早期供者对特定谱系的贡献程度是否可以预测长期的植入单位。我们的研究结果表明,在 31 例可评估患者中的 26 例(P =.0002)和在 34 例可评估患者中的 34 例(P <.0001)中,第 7 天具有更高 CD3 嵌合体的供者单位成为了主要植入单位。同样,在 8 例(第 7 天)和 31 例(第 14 天)可评估患者中,更高的供者单位 CD33 嵌合体与主导植入相关。在主导单位与输注顺序、输注的总核细胞数、CD34 或 CD3 细胞剂量、单位活力或 HLA 差异之间未观察到统计学上显著的相关性。早期移植后供者 CD3 外周血嵌合体与主导单位的相关性提示,快速的免疫介导反应是长期单供体主导的主要作用机制。这一发现可能对双份脐带血移植后早期选择获胜单位以及新的脐带血处理策略具有临床意义。

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