Mobilization characteristics and strategies to improve hematopoietic progenitor cell mobilization and collection in patients with chronic granulomatous disease and severe combined immunodeficiency.
Mobilization characteristics and strategies to improve hematopoietic progenitor cell mobilization and collection in patients with chronic granulomatous disease and severe combined immunodeficiency.
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DOI：
10.1111/trf.12830
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发表时间：
2015-02
期刊：
影响因子：
2.9
通讯作者：
Leitman SF
中科院分区：
文献类型：
--
作者：
Panch SR;Yau YY;Kang EM;De Ravin SS;Malech HL;Leitman SF
G-CSF动员的自体造血祖细胞（HPC）可通过慢性肉芽肿病（CGD）和严重联合免疫缺陷（SCID）患者的单采术收集，用于基因治疗试验。CD 34+细胞动员在这些患者中尚未得到很好的表征。我们回顾性评价了73例连续CGD和SCID患者以及99例年龄、体重和G-CSF剂量匹配的健康同种异体对照的CD 34+细胞动员和收集。在年龄≤20岁的受试者中，CGD和SCID组第5天单采前循环CD 34+计数显著低于对照组;平均峰值CD 34+细胞分别为58、64和87/uL，p=0.01。SCID的CD 34+收集效率低于CGD和对照组;平均效率分别为40%、63%和57%，p=0.003。在>20岁的受试者中，CGD组的CD 34+细胞动员显著低于对照组;平均峰值CD 34+细胞分别为41和113/uL，p<0.0001。在多变量分析中，动员时沉降率（ESR）较低与CD 34+细胞动员较好显著相关，p=0.007。在SCID中，CD 34收集效率与较高的红细胞指数呈正相关（MCV：R2=0.77; MCH：R2=0.94; MCHC：R2=0.7，p<0.007），但与血红蛋白无关。CGD和SCID群体的特征在于与健康对照相比显著较不稳健的CD 34 + HPC动员。ESR升高提示存在活动性炎症/感染可能对动员产生负面影响。在SCID中，CD 34收集效率显著降低与缺铁有关，其中红细胞大小和密度降低可能会损害单采细胞分离机制。
G-CSF mobilized autologous hematopoietic progenitor cells (HPC) may be collected by apheresis of patients with chronic granulomatous disease (CGD) and severe combined immunodeficiency (SCID) for use in gene therapy trials. CD34+ cell mobilization has not been well characterized in such patients. We retrospectively evaluated CD34+ cell mobilization and collection in 73 consecutive CGD and SCID patients and in 99 age, weight and G-CSF dose-matched healthy allogeneic controls. In subjects aged ≤20 years, day 5 pre-apheresis circulating CD34+ counts were significantly lower in CGD and SCID than in controls; mean peak CD34+ cells 58, 64, and 87/uL, respectively, p=0.01. The SCIDs had lower CD34+ collection efficiency than CGDs and controls; mean efficiency 40%, 63% and 57%, respectively, p=0.003. In subjects >20 years, the CGDs had significantly lower CD34+ cell mobilization than controls; mean peak CD34+ cells 41 and 113/uL, respectively, p<0.0001. In a multivariate analysis, lower sedimentation rate (ESR) at mobilization was significantly correlated with better CD34+ cell mobilization, p=0.007. In SCIDs, CD34 collection efficiency was positively correlated with higher red cell indices (MCV: R2=0.77; MCH: R2=0.94; MCHC: R2=0.7, p<0.007) but not hemoglobin. CGD and SCID populations are characterized by significantly less robust CD34+ HPC mobilization than healthy controls. The presence of active inflammation/infection as suggested by an elevated ESR may negatively impact mobilization. Among SCIDs, markedly reduced CD34 collection efficiencies were related to iron deficiency, wherein decreased red cell size and density may impair apheresis cell separation mechanics.
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DOI：
10.1038/nri3062
发表时间：
2011-09-09
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1016/j.bbmt.2009.02.011
发表时间：
2009-06
期刊：
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
影响因子：
--
作者：
Popat U;Saliba R;Thandi R;Hosing C;Qazilbash M;Anderlini P;Shpall E;McMannis J;Körbling M;Alousi A;Andersson B;Nieto Y;Kebriaei P;Khouri I;de Lima M;Weber D;Thomas S;Wang M;Jones R;Champlin R;Giralt S
通讯作者：
Giralt S
影响因子：
2.6
作者：
Uchida, Naoya;Bonifacino, Aylin;Donahue, Robert E.
通讯作者：
Donahue, Robert E.
影响因子：
20.3
作者：
MACIEJEWSKI, J;SELLERI, C;YOUNG, NS
通讯作者：
YOUNG, NS
影响因子：
20.3
作者：
Flomenberg, N;Devine, SM;Calandra, G
通讯作者：
Calandra, G