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在接受非恶性疾病同种异体造血干细胞移植的儿童中,混合嵌合现象增加及移植物丢失风险。

Increasing mixed chimerism and the risk of graft loss in children undergoing allogeneic hematopoietic stem cell transplantation for non-malignant disorders.

作者信息

Ozyurek E, Cowan M J, Koerper M A, Baxter-Lowe L-A, Dvorak C C, Horn B N

机构信息

Department of Pediatrics, University of California-San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143, USA.

出版信息

Bone Marrow Transplant. 2008 Jul;42(2):83-91. doi: 10.1038/bmt.2008.89. Epub 2008 Apr 7.

Abstract

We performed quantitative PCR-based serial chimerism testing of whole blood (WB) and CD3+ cells and retrospectively correlated the results of chimerism tests and the risk of graft loss in children undergoing transplant for non-malignant disorders. Twenty-four children were included in this study. All patients initially engrafted; subsequently, 12% lost the graft, 21% achieved complete donor chimerism and 67% had mixed chimerism (MC). Patients underwent delayed taper of cyclosporine (CsA) if they had MC. Overall survival was 87+/-7% (s.d.) at 5-years post transplant, and it was not affected by chimerism status. Both WB and CD3+ chimerism showed significant fluctuations with a peak in autologous cell signal occurring at a median of 7 months for WB and 2 months for CD3+ cells. Initial post transplant chimerism percentage in either WB or CD3+ lineage was not related to graft loss. Increasing MC to >30% host cells was seen in 33% of patients, and it was related to increased risk of graft loss, as previously published. However, 63% of children with increasing MC did not lose their graft. Additional studies of post transplant chimerism are required to improve our ability to accurately identify children at risk of graft loss following transplant for non-malignant disorders.

摘要

我们对全血(WB)和CD3+细胞进行了基于定量PCR的系列嵌合体检测,并回顾性地分析了非恶性疾病移植儿童的嵌合体检测结果与移植物丢失风险之间的相关性。本研究纳入了24名儿童。所有患者最初均实现了植入;随后,12%的患者移植物丢失,21%的患者实现了完全供体嵌合,67%的患者为混合嵌合(MC)。如果患者为MC,则进行环孢素(CsA)的延迟减量。移植后5年的总生存率为87±7%(标准差),且不受嵌合状态的影响。WB和CD3+嵌合体均显示出显著波动,自体细胞信号峰值出现的中位数,WB为7个月,CD3+细胞为2个月。移植后早期WB或CD3+谱系中的嵌合体百分比与移植物丢失无关。如先前发表的研究所示,33%的患者MC中宿主细胞增加至>30%,这与移植物丢失风险增加相关。然而,63%的MC增加的儿童并未丢失移植物。需要对移植后的嵌合体进行更多研究,以提高我们准确识别非恶性疾病移植后有移植物丢失风险儿童的能力。

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