儿童异基因造血干细胞移植后细胞免疫重建的临床研究
收稿日期: 2021-09-29
网络出版日期: 2022-05-13
基金资助
武汉市卫建委2020年度科研项目(WX20D20)
Clinical research on cellular immune reconstitution after allogeneic hematopoietic stem cell transplantation in children
Received date: 2021-09-29
Online published: 2022-05-13
目的 探讨儿童异基因造血干细胞移植(allo-HSCT)后免疫重建的临床特性。方法 选取2019年7月至2020年10月接受allo-HSCT且临床资料完整的患儿为研究对象。动态监测患儿移植后第0、14、21、28、60及100 d外周血淋巴细胞亚群(CD3+ T细胞、CD4+ T细胞、CD8+ T细胞、CD16+ CD56+ NK细胞、CD19+ B细胞、CD4+ CD25+ Treg细胞)绝对计数;将患儿按有无急性移植物抗宿主病(aGVHD)分为non-aGVHD组和aGVHD组,比较两组间淋巴细胞亚群的差异。结果 共75例患儿接受allo-HSCT,其中移植后满100 d、临床资料完整的42例患儿纳入本研究,男20例、女22例,中位年龄5.4(2.8~9.3)岁。移植前后不同时间点之间患儿CD3+ T细胞、CD4+ T细胞、CD8+ T细胞、CD16+ CD56+ NK细胞、CD19+ B细胞、CD4+CD25+ Treg细胞水平以及CD4+/CD8+比值差异均有统计学意义(P<0.05)。其中CD16+ CD56+ NK细胞恢复最快,在移植后21 d基本可达到移植前水平;CD3+ T细胞在移植后60 d基本可以达到移植前水平,CD8+ T 细胞到移植后60 d已超过移植前水平。42例患儿中发生aGVHD 16例,aGVHD 发生的中位时间为20.0(6.0~36.0)d。移植后28 d和60 d,aGVHD 组CD16+ CD56+ NK细胞绝对计数均低于non-aGVHD 组,差异有统计学意义(P<0.05)。结论 儿童allo-HSCT后淋巴细胞亚群中重建最早的为CD16+ CD56+ NK细胞。NK细胞重建与aGVHD 的发生密切相关,或有助于早期识别aGVHD 患儿。
宋娜 , 孙鸣 , 祁闪闪 , 王卓 , 杨李 , 卢文婕 , 吴旻 , 夏维 , 陈燕 , 熊昊 . 儿童异基因造血干细胞移植后细胞免疫重建的临床研究[J]. 临床儿科杂志, 2022 , 40(5) : 388 -394 . DOI: 10.12372/jcp.2022.21e1384
Objective To investigate the clinical characteristics of immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children. Methods Children with complete clinical data who received allo-HSCT in the department of hematology and oncology from July 2019 to October 2020 were selected as the study subjects. The absolute count of peripheral blood lymphocyte subsets (CD3+ T cells, CD4+ T cells, CD8+ T cells, CD16+ CD56+ NK cells, CD19+ B cells, CD4+ CD25+ Treg cells) was dynamically monitored on day 0, 14, 21, 28, 60 and 100 after transplantation. The children were divided into non-aGVHD group and aGVHD group according to the presence or absence of acute graft-versus-host disease (aGVHD), and the differences of lymphocyte subsets between the two groups were compared. Results A total of 75 children received allo-HSCT, and 42 of them with complete clinical data after 100 days of transplantation were included in this study. There were 20 boys and 22 girls with a median age of 5.4 (2.8~9.3) years. There were statistically significant differences in the levels of CD3+ T cells, CD4+ T cells, CD8+ T cells, CD16+ CD56+ NK cells, CD19+B cells, CD4+CD25+ Treg cells and CD4+/CD8+ ratio at different time points before and after transplantation (P<0.05). CD16+CD56+ NK cells recovered the earliest and reached the level of pre-transplantation at 21 days post-transplantation. CD3+ T cells almost reached the pre-transplantation level at 60 days after transplantation, while CD8+ T cells exceeded the pre-transplantation level at 60 days after transplantation. The aGVHD occurred in 16 of 42 children, and the median time of aGVHD occurrence was 20.0 (6.0-36.0) days. At 28d and 60d after transplantation, the absolute count of CD16+ CD56+ NK cells in aGVHD group was lower than that in non-aGVHD group, the difference was statistically significant (P<0.05). Conclusions CD16+ CD56+ NK cells were the earliest lymphocyte subsets reconstructed after allo-HSCT in children. NK cell reconstitution is closely related to the occurrence of aGVHD after allo-PBSCT, which may be used as an effective predictor of prognosis in patients with aGVHD.
[1] | Elfeky R, Lazareva A, Qasim W, et al. Immune reconstitution following hematopoietic stem cell transplantation using different stem cell sources[J]. Expert Rev Clin Immunol, 2019, 15(7): 735-751. |
[2] | Kim HO, Oh HJ, Lee JW, et al. Immune reconstitution after allogeneic hematopoietic stem cell transplantation in children: a single institution study of 59 patients[J]. Korean J Pediatr, 2013, 56(1): 26-31. |
[3] | 中华医学会血液学分会干细胞应用学组. 中国异基因造血干细胞移植治疗血液系统疾病专家共识(Ⅰ)-适应证、预处理方案及供者选择(2014年版)[J]. 中华血液学杂志, 2014, 35(8): 775-780. |
[4] | 中华医学会血液学分会干细胞应用学组. 中国异基因造血干细胞移植治疗血液系统疾病专家共识(Ⅲ)-急性移植物抗宿主病(2020年版)[J]. 中华血液学杂志, 2020, 41(7): 529-536. |
[5] | Pei XY, Zhao XY, Xu LP, et al. Immune reconstitution in patients with acquired severe aplastic anemia after haploidentical stem cell transplantation[J]. Bone Marrow Transplant, 2017, 52(11): 1556-1562. |
[6] | Park BG, Park CJ, Jang S, et al. Reconstitution of lymphocyte subpopulations after hematopoietic stem cell transplantation: comparison of hematologic malignancies and donor types in event-free patients[J]. Leuk Res, 2015, 39(12): 1334-1341. |
[7] | de Koning C, Plantinga M, Besseling P, et al. Immune reconstitution after allogeneic hematopoietic cell transplantation in children[J]. Biol Blood Marrow Transplant, 2016, 22(2):195-206. |
[8] | Ullah MA, Hill GR, Tey SK. Functional reconstitution of natural killer cells in allogeneic hematopoietic stem cell transplantation[J]. Front Immunol, 2016, 7: 144. |
[9] | Gao F, Ye Y, Gao Y, et al. Influence of KIR and NK cell reconstitution in the outcomes of hematopoietic stem cell transplantation[J]. Front Immunol, 2020, 11: 2022. |
[10] | Huttunen P, Taskinen M, Siitonen S, et al. Impact of very early CD4+ /CD8+ T cell counts on the occurrence of acute graft-versus-host disease and NK cell counts on outcome after pediatric allogeneic hematopoietic stem cell transplantation[J]. Pediatr Blood Cancer, 2015, 62(3): 522-528. |
[11] | Stern L, McGuire H, Avdic S, et al. Mass cytometry for the assessment of immune reconstitution after hematopoietic stem cell transplantation[J]. Front Immunol, 2018, 9: 1672. |
[12] | Chaudhry MS, Velardi E, Malard F, et al. Immune reconstitution after allogeneic hematopoietic stem cell transplantation: time to T up the thymus[J]. J Immunol, 2017, 198(1):40-46. |
[13] | 霍莹莹, 庞爱明, 程涛达. 异基因造血干细胞移植后造血及免疫重建研究进展[J]. 中华血液学杂志, 2020, 41(11): 958-963. |
[14] | Ritacco C, Ehx G, Grégoire C, et al. High proportion of terminally differentiated regulatory T cells after allogeneic hematopoietic stem cell transplantation[J]. Bone Marrow Transplant, 2021, 56(8):1828-1841. |
[15] | Bosch M, Khan FM, Storek J. Immune reconstitution after hematopoietic cell transplantation[J]. Curr Opin Hematol, 2012, 19(4): 324-335. |
[16] | Giaccone L, Faraci DG, Butera S, et al. Biomarkers for acute and chronic graft versus host disease: state of the art[J]. Expert Rev Hematol, 2021, 14(1): 79-96. |
[17] | Bunting MD, Varelias A, Souza-Fonseca-Guimaraes F, et al. GVHD prevents NK-cell-dependent leukemia and virus-specific innate immunity[J]. Blood, 2017, 129(5): 630-642. |
[18] | Zhang X, Peng Y, Fan Z, et al. Mesenchymal stem cells may ameliorate nephrotic syndrome post-allogeneic hematopoietic stem cell transplantation-case report[J]. Front Immunol, 2017, 8: 962. |
[19] | Shokouhi S, Bray S, Bakhtiyari S, et al. Effects of aGVHD and cGVHD on survival rate in patients with acute myeloid leukemia after allogeneic stem cell transplantation[J]. Int J Hematol Oncol Stem Cell Res, 2015, 9(3): 112-121. |
[20] | Sheng L, Mu Q, Wu X, et al. Cytotoxicity of donor natural killer cells to allo-reactive T cells are related with acute graft-vs.-host-disease following allogeneic stem cell transplantation[J]. Front Immunol, 2020, 11: 1534 |
/
〈 |
|
〉 |