Porta Matteo Della, Rigolin Gian Matteo, Alessandrino Emilio Paolo, Maiocchi Mariangela, Malcovati Luca, Vanelli Laura, Baratè Claudia, Rumi Elisa, Ciccone Maria, Cuneo Antonio, Lazzarino Mario, Castoldi Gianluigi
Section of Hematology, Department of Biomedical Sciences, University of Ferrara, Italy.
Eur J Haematol. 2004 Jan;72(1):18-25. doi: 10.1046/j.0902-4441.2004.00172.x.
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.
我们分析了19例接受异基因造血干细胞移植(HSCT)的急性白血病患者循环树突状细胞(DC)亚群(髓样DC1和淋巴样DC2)重建的动力学。我们发现,白血病患者移植前的DC1和DC2低于健康受试者(P分别为0.003和0.004),接受外周血干细胞(PBSC)的患者移植时输入的DC2(而非DC1)数量更高(P = 0.03)。患者在+60天内恢复到移植前的DC1和DC2水平;然而,在+365天达到正常DC1数量,而DC2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DC1重建无显著差异,而接受PBSC的患者在+30天(P = 0.008)和+100天(P = 0.047)时DC2水平升高,且在+365天前T淋巴细胞和自然杀伤细胞数量更多。在我们的病例中,移植物抗宿主病(GVHD)的发生不受DC1/DC2移植物组成的影响,但与无急性GVHD的患者相比,急性GVHD患者的DC恢复明显较慢(+30天时DC1 P = 0.03,DC2 P = 0.009;+100天时DC1 P = 0.012,DC2 P = 0.006)。复发时,4例患者的DC1/DC2数量减少,通过荧光原位杂交分析检测到存在两种不同的DC群体,一种核型正常,另一种与恶性克隆具有相同的细胞遗传学异常。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风险增加,并且可能受造血干细胞来源、GVHD的发生和复发的影响。有必要进一步研究以探讨DC重建在移植环境中的意义。