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减低剂量预处理和异基因造血干细胞移植后外周T细胞扩增及低感染率

Peripheral T-cell expansion and low infection rate after reduced-intensity conditioning and allogeneic blood stem cell transplantation.

作者信息

Larosa F, Marmier C, Robinet E, Ferrand C, Saas P, Deconinck E, Bulabois C-E, Rohrlich P-S, Ledu K, Helias P, Tiberghien P, Cahn J-Y

机构信息

Department of Hematology. Centre Hospitalo-Universitaire Jean Minjoz, Besançon Cedex, France.

出版信息

Bone Marrow Transplant. 2005 May;35(9):859-68. doi: 10.1038/sj.bmt.1704889.

DOI:10.1038/sj.bmt.1704889
PMID:15765116
Abstract

Peripheral blood stem cell transplantation after reduced-intensity conditioning (RIC-PBSCT) regimen is an alternative to conventional regimens with less immediate toxicity. Since immune recovery is of crucial importance for the control of infections, we retrospectively studied the recovery of T-, B- and NK cell subsets in 20 consecutive patients undergoing RIC-PBSCT. We also studied the thymic output using T-cell receptor excision circle assay. Engraftment was rapid and few infectious complications were seen: three early (before 2.5 months) cases of asymptomatic cytomegalovirus reactivation, two late Gram-negative bacterial infections and no fungal infection. While CD4+ T-cell reconstitution was slow, CD8+ T-cell counts were close to normal values at 4 months. Median CD19+ B-cell counts reached normal values at 11 months. Rapid CD56+ NK cell reconstitution was noticed as early as 1.5 months. Low T-cell receptor excision circle numbers and preponderance of memory-type subsets among T cells further suggested that CD8+ T-cell reconstitution resulted predominantly from peripheral expansion and that thymic-dependent reconstitution was severely impaired. In conclusion, large peripheral T-cell expansion may compensate for late thymic-dependent lymphopoiesis, and may, with other factors such as NK and B-cell reconstitution and careful antiinfectious prophylaxis, help limit the incidence of severe infections after RIC-PBSCT.

摘要

减低强度预处理后的外周血干细胞移植(RIC-PBSCT)方案是一种具有较低即时毒性的传统方案替代方案。由于免疫恢复对于控制感染至关重要,我们回顾性研究了20例接受RIC-PBSCT的连续患者中T、B和NK细胞亚群的恢复情况。我们还使用T细胞受体切除环检测法研究了胸腺输出。植入迅速,几乎未见感染并发症:3例早期(2.5个月前)无症状巨细胞病毒再激活,2例晚期革兰氏阴性菌感染,无真菌感染。虽然CD4+T细胞重建缓慢,但CD8+T细胞计数在4个月时接近正常值。CD19+B细胞计数中位数在11个月时达到正常值。早在1.5个月时就注意到CD56+NK细胞的快速重建。低T细胞受体切除环数量以及T细胞中记忆型亚群占优势进一步表明,CD8+T细胞重建主要源于外周扩增,且胸腺依赖性重建严重受损。总之,外周T细胞大量扩增可能弥补晚期胸腺依赖性淋巴细胞生成的不足,并可能与NK和B细胞重建以及仔细的抗感染预防等其他因素一起,有助于限制RIC-PBSCT后严重感染的发生率。

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