浆样树突状细胞重建与单倍体相合造血干细胞移植的慢性移植物抗宿主病和复发关系研究

Investigation of Plasmacytoid Dendritic Cell Reconstitution and Its Relationship with cGVHD and Relapse after Haploidentical Hematopoietic Stem Cell Transplantation

为了探讨浆样树突状细胞(PDC)在单倍体相合造血干细胞移植术后重建的特点及其与慢性移植物抗宿主病(cGVHD)和患者复发的关系,采用流式细胞术对19例白血病患者移植后外周血树突状细胞(DC)亚群晚期重建进行动态监测,并将其与患者cGVHD和复发的关系进行分析。结果显示:白血病患者髓样树突状细胞(MDC)、MDC1和DC百分比和绝对细胞数以及MDC/PDC比率均低于正常对照(P<0.05),而髓样树突状细胞2(MDC2)、PDC百分数与对照组相比无统计学差异。患者移植后PDC比例于12月时达到正常(P=0.494),而PDC绝对值和其余各亚群比例及数量均于移植后9月时恢复到正常水平,与对照组相比无统计学差异(P>0.05);MDC/PDC于移植后120天时已达到正常对照组水平(P=0.602)。发生cGVHD患者移植后120天PDC比例高于未发生组;患者复发后MDC1比例及数值下降,而MDC2和PDC比例及数值略回升。结论:白血病患者单倍体相合造血干细胞移植前外周血DC比例、绝对数及MDC/PDC比率均减少;移植后MDC/PDC比率恢复较快;各亚群比例和数量在移植后9月后基本恢复正常;且恢复情况与慢性移植物抗宿主病发生和患者复发相关。

To investigate the characteristics and significance of reconstitution of peripheral blood plasmacytoid dendritic cell （PDC） precursors after allogeneic human leukocyte antigen mismatched/ haploidentical hematopoietic stem cell transplantation, and its relationship with chronic graft versus host disease（cGVHD） and relapse, 19 patients with leukemia were enrolled for this study. Peripheral blood dendritic cell （DC） subsets of patients and healthy controls were detected by flow cytometry, and the correlations between reconstitution of DC and cGVHD, relapse were analyzed. The results showed that compared with healthy subjects, patients with leukemia had a significantly decreased proportion and absolute number of myeloid dendritic cell （MDC） , MDC1 , DC and the ratio of MDC/PDC （ P 〈 0.05 ）. There were not statistically different in MDC2 and PDC between patients and healthy subjects. After transplant, all the proportion of WBC and absolute numbers of DC reached to healthy controls levels at 9 months （ P 〉 0.05 ）, besides the proportion of PDC which reached to healthy controls levels at 1 year（P =0.494）. Compared with levels before relapse, the proportions of MDC1, MDC, DC and the ratio of MDC/PDC were lower, but proportions of MDC2 and PDC were slightly higher after relapse. Patients with a high＇PDC recovery profile had an improved cumulative incidence of cGVHD in contrast to patients with a tow PDC recovery profile on day 120 after transplantation （P = 0.007 ）. It is concluded that compared with healthy subjects, de novo leukemia patients have a significantly decreased proportion and absolute number of DC and the ratio of MDC/PDC before haploidentical hematopoietic stem cell transplantation; while ratio of MDC/PDC can be normalized with relative rapidity, the proportions of all DC subsets reached to normal levels on the whole at 9 months after transplantation, and also recovery level of DCs is correlated with occurrence of cGVHD and relapse.