Dendritic cell recovery after allogeneic stem-cell transplantation in acute leukemia:: correlations with clinical and transplant characteristics
Dendritic cell recovery after allogeneic stem-cell transplantation in acute leukemia:: correlations with clinical and transplant characteristics
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DOI：
10.1046/j.0902-4441.2004.00172.x
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发表时间：
2004-01-01
影响因子：
3.1
通讯作者：
Castoldi, G
中科院分区：
文献类型：
--
作者：
Della Porta, M;Rigolin, GM;Castoldi, G
我们分析了19例接受异基因造血干细胞移植（HSCT）的急性白血病患者的循环树突状细胞（DC）亚群（髓样DC 1和淋巴样DC 2）重建的动力学。我们发现，白血病患者移植前DC 1和DC 2低于健康受试者（分别为P = 0.003和P = 0.004），接受外周血干细胞（PBSC）的患者中输注移植物的DC 2（而不是DC 1）数量较高（P = 0.03）。患者在+60天内恢复到移植前的DC 1和DC 2水平;然而，在+365天达到正常的DC 1数量，而DC 2在移植后1年内仍低于对照组。接受骨髓干细胞（BMSC）或PBSC的患者之间的DC 1重建没有显著差异，而接受PBSC的患者在第+30天（P = 0.008）和+100天（P = 0.047）表现出DC 2水平的增加，T淋巴细胞和自然杀伤细胞的数量增加，直到第+365天。在我们的病例中，移植物抗宿主病（GVHD）的发生不受DC 1/DC 2移植物组成的影响，但是与没有急性GVHD的患者相比，患有急性GVHD的患者表现出显著更慢的DC恢复（在+30天时DC 1 P = 0.03，DC 2 P = 0.009，在+100天时DC 1 P = 0.012，DC 2 P = 0.006）。在复发的那一刻，DC 1/DC 2的数量减少，观察到在4例患者和两个不同的DC群体的存在下，一个正常的核型，和其他具有相同的细胞遗传学异常的恶性克隆荧光原位杂交分析检测。总之，这些观察结果表明，在异基因HSCT受者中，DC恢复是一个缓慢的过程，可能导致移植后感染的高风险，并可能受到HSC来源、GVHD发生和复发的影响。需要进一步研究DC重建在移植环境中的意义。
We have analyzed the kinetics of reconstitution of circulating dendritic cell (DC) subsets (myeloid-DC1 and lymphoid-DC2) in 19 patients affected by acute leukemia undergoing allogeneic hematopoietic stem-cell transplantation (HSCT). We have found that pretransplant DC1 and DC2 were lower in leukemic patients than in healthy subjects (P = 0.003 and P = 0.004, respectively) and that the number of DC2 (but not DC1) infused with the graft was higher in patients receiving peripheral blood stem cells (PBSC) (P = 0.03). Patients recovered to the pretransplant DC1 and DC2 levels within day +60; however, a normal DC1 number was reached on day +365, while DC2 remained lower than in controls up to 1 yr after transplant. DC1 reconstitution did not differ significantly between patients receiving bone marrow stem cells (BMSC) or PBSC, while patients receiving PBSC presented increased levels of DC2 on day +30 (P = 0.008) and +100 (P = 0.047) and a higher number of T lymphocytes and natural killer cells until day +365. The occurrence of graft vs. host disease (GVHD) was not influenced in our cases by DC1/DC2 graft composition, but patients with acute GVHD when compared with patients without acute GVHD presented a significantly less rapid DC recovery (DC1 P = 0.03, DC2 P = 0.009 on day +30, and DC1 P = 0.012, DC2 P = 0.006 on day +100). At the moment of relapse, a decrease of DC1/DC2 numbers was observed in four patients and the presence of two different DC populations one with a normal karyotype, and the other with the same cytogenetic abnormality as the malignant clone was detected by fluorescence in situ hybridization analysis. In conclusion, these observations suggest that in allogeneic HSCT recipients, DC recovery is a slow process possibly contributing to the high risk of infections in the post-transplant period and is possibly influenced by the source of HSC, the occurrence of GVHD and relapse. Further studies are warranted to investigate the significance of DC reconstitution in the transplant setting.