Cytopenia and leukocyte recovery shape cytokine fluctuations after myeloablative allogeneic hematopoietic stem cell transplantation
Cytopenia and leukocyte recovery shape cytokine fluctuations after myeloablative allogeneic hematopoietic stem cell transplantation
复制标题
DOI：
10.3324/haematol.2011.053363
复制
发表时间：
2012-06-01
期刊：
影响因子：
--
通讯作者：
Barrett, Austin John
中科院分区：
文献类型：
--
作者：
Melenhorst, Jan Joseph;Tian, Xin;Barrett, Austin John
背景异基因造血干细胞移植与多种细胞因子水平的深刻变化有关。重点已经放在调理相关的粘膜损伤和中性粒细胞减少症和相关的细菌易位作为诱发急性移植物抗宿主病的起始条件。然而，移植后时期也与某些稳态细胞因子的增加有关。目前还不清楚在移植前后和移植后即刻，淋巴细胞恢复的稳态驱动和移植供体免疫系统细胞因子的产生在多大程度上决定了细胞因子的波动。本研究的目的是检查预处理方案、供体植入、感染和移植物抗宿主病对参与体内平衡和炎症的细胞因子波动的贡献。设计和方法我们检查了33种细胞因子的水平与移植前后事件的关系，如预处理方案、嵌合体和清髓性、非移植性和非移植性骨髓增生异常综合征中的急性移植物抗宿主病。non-T细胞充满HLA相合同胞供体干细胞移植治疗血液系统恶性肿瘤。第一次发生在调节后，当所有白细胞处于最低浓度时达到峰值水平。第二次细胞因子风暴同时发生造血重建和消退的实现完全供体淋巴细胞chimerization.ConclusionsOur结果表明，两个与免疫相关和供体相关的因素有助于在异基因造血干细胞移植后的受体细胞因子水平的变化。本文报告的研究使用从临床试验入组患者中采集的血浆样本进行。政府注册试验NCT 00467961和NCT 00378534
BackgroundAllogeneic hematopoietic stem cell transplantation is associated with profound changes in levels of various cytokines. Emphasis has been placed on conditioning-associated mucosal damage and neutropenia and associated bacterial translocation as the initiating conditions predisposing to acute graft-versus-host disease. The post-transplant period is, however, also associated with increases in certain homeostatic cytokines. It is unclear how much the homeostatic drive to lymphocyte recovery and the production of cytokines from the engrafting donor immune system determine cytokine fluctuations in the peri-and immediate post-transplant period. The aim of this study was to examine the contributions of the conditioning regimen, donor engraftment, infections, and graft-versus-host disease to fluctuations in cytokines involved in homeostasis and inflammation.Design and MethodsWe examined the levels of 33 cytokines in relation to peri-and post-transplant events such as conditioning regimen, chimerism, and acute graft-versus-host disease in myeloablative, non-T cell-replete HLA-identical sibling donor stem cell transplantation for hematologic malignancies.ResultsWe identified two cytokine storms. The first occurred following conditioning and reached peak levels when all the leukocytes were at their lowest concentrations. The second cytokine storm occurred concurrently with hematopoietic reconstitution and subsided with the achievement of full donor lymphocyte chimerism.ConclusionsOur results indicate that both recipient-related and donor-related factors contribute to the changes in cytokine levels in the recipient following allogeneic hematopoietic stem cell transplantation. The study reported here was performed using plasma samples drawn from patients enrolled in the ClinicalTrials. gov-registered trials NCT00467961 and NCT00378534