Proteolytic enzyme levels are increased during granulocyte colony-stimulating factor-induced hematopoietic stem cell mobilization in human donors but do not predict the number of mobilized stem cells

Previous studies from our laboratory indicate that functional, mature neutrophils are essential for interleukin-8 (IL-8)-induced stem cell mobilization. To study a possible role of neutrophils in granulocyte colony-stimulating factor (G-CSF) induced hematopoietic mobilization, we assessed the number of circulating CD34+ cells in healthy allogeneic stem cell donors on days 3, 4, and 5 of mobilization for comparison with the number of peripheral blood neutrophils and the plasma levels of IL-8, Flt3 ligand (FL), matrix metalloproteinase-9 (MMP-9), and human neutrophil elastase (HNE). Thirty-seven of 45 donors required 1 day of apheresis to obtain 5 x 10(6) CD34+/kg recipient body weight (high responders), the remaining 8 donors required 1 extra day of apheresis on day 6 (low responders). On day 5, CD34+ numbers in the blood were significantly highe in high responders (116 x 10(3) +/- 10.4/ml) than in low responders (54.1 x 10(3) +/- 10.3, p < 0.001). In all donors, MMP-9 and HNE levels were increased compared to nonmobilized individuals, but in high responders, plasma MMP-9 levels on days 3-5 of mobilization were substantially higher than in low responders (p < or = 0.02 for MMP-9 and p = 0.89, p = 0.05 and p = 0.52 for HNE on days 3, 4, and 5, respectively). These results are in accordance with the hypothesis that neutrophils play a role in G-CSF-induced mobilization through the release of proteases such as MMP-9 and elastase. No change in plasma levels of IL-8 or Flt3 ligand was observed, suggesting that these cytokines do not play a role in stem cell mobilization. However, because stem cell numbers could not be predicted by proteolytic enzyme levels and/or neutrophil numbers, other undefined factors may be more important.     

Circulating endothelial adhesion molecules (sE-selectin, sVCAM-1 and sICAM-1) during rHuG-CSF-stimulated stem cell mobilization

The role of leukocyte-endothelial cell interactions during granulocyte colony-stimulating factor (G-CSF)-induced stem cell mobilization is unclear. To examine endothelial activation during this process, we determined levels of circulating endothelial adhesion molecules in healthy donors undergoing G-CSF-mobilized stem cell collection. Plasma levels of soluble (s) E-selectin, soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) were serially determined by enzyme-linked immunosorbent assays in 10 healthy donors during G-CSF-stimulated stem cell mobilization. There was a significant increase in plasma levels of all three endothelial adhesion molecules (sE-selectin, p = 0.01; sICAM-1, p = 0.003; sVCAM-1, p = 0.0002) between day 1 and day 5 of G-CSF stimulation, but only sVCAM-1 concentrations exceeded the range obtained from unstimulated controls in all stem cell donors. Increases of sCAM were accompanied by increased numbers of white blood cells and CD34(+) progenitors in peripheral blood. G-CSF-stimulated peripheral blood progenitor cells (PBPC) mobilization results in increased levels of circulating endothelial adhesion molecules that were most evident for VCAM-1 molecules. Because soluble VCAM-1 remains active in binding to the VLA-4 receptor on CD34(+) cells, it may reduce stem cell adhesiveness to endothelial cells and to bone marrow microenvironment.     

Prognostic value of matrix metalloproteinases (MMP-2 and MMP-9) in Hodgkin's and non-Hodgkin's lymphoma

Matrix metalloproteinases (MMPs) are responsible for the degradation of extracellular matrix and have an important role in tumour metastases. We investigated the role of MMP-2 and MMP-9 in Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). The serum samples of patients with HD (n = 12), NHL (n = 30) and healthy control (n = 22) were analysed for MMP-2 and MMP-9. An immunoassay method was used for the determination of MMP-2 and MMP-9 levels. No statistical significance was found between HD and NHL groups for levels of MMP-2. There were no relation between MMP-2, MMP-9 levels and clinical characteristics of patients. The mean MMP-9 levels were found to be 555.6 +/- 140 ng/ml, 446.6 +/- 53.6 ng/ml and 111.2 +/- 10.3 ng/ml in HD, NHL and control groups, respectively. Our results suggest that MMP-9 levels are substantially increased in HD and NHL when compared with controls and may probably be used for distinguishing the benign diseases from malign lymphomas.     

Predictive parameters for granulocyte colony-stimulating factor-induced peripheral blood stem cell mobilization

To improve the selection of donors for allogeneic stem cell transplantation, it is important to identify reliable parameters that predict CD34+-cell yields after granulocyte-colony stimulating factor (G-CSF)-induced peripheral blood stem cell (PBSC) mobilization. We retrospectively investigated the peripheral blood (PB) kinetics of white blood cells (WBCs), CD34+ cells, matrix metalloproteinases (MMP)-9 and -2, and tissue inhibitors of metalloproteinases (TIMP)-1 and -2 in 15 healthy donors during their treatment with G-CSF. All donors received 10 microg/kg of recombinant human G-CSF once a day subcutaneously. Leukapheresis was initiated after 4 days of G-CSF treatment, and G-CSF treatment continued until the last day of leukapheresis. WBC and CD34+ cell numbers in the PB rose after 2 and 3 or 4 days of G-CSF treatment, respectively. The PB CD34+ cell numbers on day 4 correlated weakly with the increase in WBC counts from day 1 to day 2 (R(2) = 0.254, P = 0.056). There were also positive correlations between the CD34+ cell numbers in the PBSC products on day 4 and the CD34+ cells in the PB on days 1 and 4 (R(2) = 0.768, P < 0.0001 and R(2) = 0.816, P < 0.0005, respectively). The MMP-9 plasma levels on days 1 and 4 also correlated positively with the day 4 circulating CD34+ cell numbers (R(2) = 0.393, P < 0.05 and R(2) = 0.406, P = 0.01, respectively). In conclusion, the CD34+ cell numbers in the PB steady state may be a useful parameter selecting allogeneic PBSC donors.     

粒细胞集落刺激因子治疗失代偿期肝硬化的机制及疗效研究

目的 探讨应用粒细胞集落刺激因子(G-CSF)动员治疗失代偿期肝硬化的疗效及其机制.方法 采用流式细胞术和酶联免疫吸附法,对不同类型慢性HBV感染者外周血中造血干细胞及其受体的表达和干细胞迁移相关细胞因子的水平进行检测;对应用G-CSF动员治疗前后患者造血干细胞受体的表达以及肝功能变化进行动态观察.结果 与正常对照组比较,乙型肝炎肝硬化患者的CD34+细胞比例明显升高,差异有统计学意义[(0.21±0.09)% vs.(0.30±0.13)%;F=5.45,P=0.006];慢性乙型肝炎患者和乙型肝炎肝硬化患者基质细胞衍生因子1α(SDF-1α)、干细胞因子(SCF)、基质金属蛋白质酶-9(MMP-9)的表达水平明显升高(F＝13.65,P=0.001;F=23.28,P=0.000;F=18.98,P=0.000).与治疗前比较,G-CSF动员治疗后患者的CD34+干细胞比例明显增加[(0.31±0.14)% vs.(0.95±0.46)%,(0.81±0.37)%;F=20.33,P=0.000];治疗后患者外周血中SCF及MMP-9的表达水平明显升高(F=4.52,P=0.015;F=3.85,P=0.027).治疗组与对照组比较,治疗前后TBil、ALB以及PT的变化水平差异均无统计学意义,两组患者的治愈好转率也无明显差异.结论 乙型肝炎肝硬化患者存在基础水平的造血干细胞动员,可能与肝脏损伤的修复有关;G-CSF可通过调控干细胞动员相关因子的表达水平,促进肝硬化患者的造血干细胞动员;G-CSF动员治疗对改善乙型肝炎肝硬化患者的生化指标及短期预后无明显效果.     

化疗加G-CSF和GM-CSF联合动员自体外周血干细胞

目的　探讨化疗加粒细胞集落刺激因子 (G CSF)和粒 巨噬细胞集落刺激因子 (GM CSF)联合动员自体外周血干细胞 (APBSC)的效果。方法　卡铂 (CBP) 35 0mg m2 ,第 1天静滴 ;足叶乙甙(Vp16 ) 35 0mg m2 ,第 1～第 3天静滴 ;白细胞降至最低点又回升到 (2 .4～ 6 .4)× 10 9 L时 ,皮下注射G CSF 5 μg·kg- 1 ·d- 1 (早 6∶0 0 ) GM CSF 5 μg·kg- 1 ·d- 1 (晚 6∶0 0 ) 地塞米松 5mg d(采集日 10mg d)直到采集结束前 1天 ;白细胞上升到 (2 9.80± 5 .98)× 10 9 L ,开始用CS30 0 0plus血细胞分离机连续 2d采集APBSC。结果　 2 0例患者连续采集APBSC 2次 ,共采集到MNC(5 .93± 1.6 2 )× 10 8 kg ,CD34 细胞 (2 3.10± 11.5 3)× 10 6 kg ,CFU GM(3.44± 2 .85 )× 10 5 kg。无严重不良反应。 9例 10次自体外周血干细胞移植(APBSCT)造血功能均获满意重建。结论　以化疗联合G CSF和GM CSF能高效、安全地动员APBSC ,1次动员采集 2次可满足 1～ 2次的APBSCT。     

Matrix metalloproteinase-9 (gelatinase B) is elevated during mobilization of peripheral blood progenitor cells by G-CSF

BACKGROUND: Matrix metalloproteinase-9 (MMP-9 or gelatinase B) has recently been implicated in the IL-8-induced mobilization of HPCs in rhesus monkeys and mice. It is not known whether administration of G-CSF causes expression of MMP-9 during HPC mobilization. STUDY DESIGN AND METHODS: Blood samples from 15 allogeneic progenitor cell donors were collected before and during G-CSF-induced HPC mobilization. The expression of the gelatinases MMP-2 and MMP-9 in the plasma of the donors was analyzed by ELISA and zymographic analysis. Gelatinolytic activity was measured with a fluorometric assay that was specific for gelatinases. Expression of IL-6, IL-8, and soluble vascular cell adhesion molecule (VCAM) was measured by ELISA. RESULTS: Highly elevated latent gelatinolytic activity was found on Days 4 and 5 of G-CSF treatment in comparison to pretreatment activity. ELISA and zymographic analyses revealed pro-MMP-9 as the major source of the latent gelatinolytic plasma activity during mobilization. Pro-MMP-2 was not elevated compared with pretreatment levels. As IL-8 has been implicated in the expression of MMP-9, IL-8 concentrations were measured in plasma samples from donors and patients immediately before the start of HPC apheresis, but no significantly elevated IL-8 concentrations were noted. In contrast, pro-MMP-9 and latent gelatinolytic activity was highly correlated with IL-6, which was strongly elevated during mobilization therapy. Finally, soluble VCAM was equally significantly elevated on the days of apheresis. CONCLUSIONS: G-CSF mobilization treatment induces MMP-9, IL-6, and soluble VCAM. Expression of MMP-9 might be involved in the mobilization of human HPCs and might be a final common pathway of different mobilization therapies. Our data do not support a role of IL-8 in G-CSF-induced mobilization. In contrast, IL-6 might be involved in the G-CSF-induced expression of MMP-9.     

Increased serum flt3-ligand in healthy donors undergoing granulocyte colony-stimulating factor-induced peripheral stem cell mobilization

The effect of granulocyte colony-stimulating factor (G-CSF) induced mobilization of peripheral blood progenitor cells (PBPC) on the endogenous serum levels of cytokines stem cell factor (SCF) and flt3-ligand (flt3-L) was studied in 18 healthy subjects undergoing allogeneic PBPC donation. Donors received a standardized mobilization regime consisting of a 4-day course of G-CSF, with leukapheresis on day 5. Endogenous serum flt3-L and SCF were determined prior to G-CSF administration, on the day of leukapheresis, and followed up until day +100 after cessation of G-CSF administration. The administration of G-CSF resulted in a transient elevation of endogenous flt3-L serum levels. At the day of leukapheresis serum flt3-L showed a median increase of 75% compared to serum flt3-L levels obtained before G-CSF treatment. The increase in serum flt3-L levels showed no correlation with the total number of progenitor cells mobilized. Cessation of G-CSF treatment led to normalization of serum flt3-L within 7 days post G-CSF administration. In contrast, serum CSF levels remained unchanged in response to G-CSF administration. Our results demonstrate a transient surge in serum flt3-L in relation to G-CSF-induced PBPC mobilization, although the assessment of endogenous flt3-L give no information regarding the ability for G-CSF-induced PBPC recruitment in healthy individuals.     

Matrix metalloproteinase-9 and cell kinetics during the collection of peripheral blood stem cells by leukapheresis.

The plasma levels of matrix metalloproteinase-9 (MMP-9) were determined during 41 collections of peripheral blood stem cells (PBSC) by standard volume (two blood volumes) leukaphereses (SVL) in 29 donors (7 allogeneic and 22 autologous) mobilized with the granulocyte-colony stimulating factor (G-CSF). The association between MMP-9 levels and cell counts in donor's blood was explored. During the processing of the first blood volume (BV), MMP-9 levels declined on average by 31% and persisted at the same level during the processing of the second BV. During the collection, a slight decline of white blood cells (WBC), polymorphonuclear neutrophils (PMN) and platelets (PLT) in donor's blood was accompanied by a significant drop of CD34+ cells by 37% after 1 BV and by 44% after 2 BV had been processed (p=0.001). The drop of MMP-9 plasma levels showed a loose correlation with the decrease of WBC (r=0.68, p=0.002) and PMN counts (r=0.67, p=0.001). We conclude that the levels of MMP-9 that have been elevated by the mobilization of donors with G-CSF, decrease during the collection of PBSC by 4h SVL. The observed decrease was indirectly related to the drop of WBC and PMN counts, suggesting that certain other factors have an influence on MMP-9 kinetics during PBSC collection.     

Seasonal variation of human physiology does not influence the harvest of peripheral blood CD34+ cells from unrelated hematopoietic stem cell donors

There are many reports on factors predicting the outcome of PBSC (peripheral blood stem cell) mobilization, such as the donor’s gender, age, weight, white blood cell count, platelets pre apheresis, LDH and iron status. Although there are reports of seasonal variation in the physiology of the human immune system and hematopoiesis there are no data that such differences play a role in the response to G-CSF in healthy hematopoietic stem cell donors. The response to G-CSF could also impact the collection results during different seasons. To assess the possible impact of seasonal variation we performed a retrospective, single-center analysis of mobilization and harvest of PBSC in 330 healthy unrelated donors. We found no significant differences in the number of CD34+ cells in peripheral blood after G-CSF mobilization and in collection results when all donors were analyzed. In the subgroup of male donors the number of CD34+ stem cells after G-CSF mobilization was higher than average in summer and autumn (p = 0.036), however, it did not translate into clinically relevant differences in stem cell harvest.We conclude that although there is possible seasonal variation in the response to G-CSF in male donors there is no impact on PBSC harvest in healthy unrelated donors.     

Rapid separation of serum does not avoid artificially higher matrix metalloproteinase (MMP)-9 levels in serum versus plasma

OBJECTIVES: To examine whether the time between blood drawing and centrifugation (TBDC) affects the levels of matrix metalloproteinase (MMP)-9 and MMP-2 levels in serum and in plasma samples, and to assess whether there is correlation between MMP-9 and MMP-2 levels in serum and plasma samples. DESIGN AND METHODS: Serum and plasma samples (N=8) were separated from venous blood collected into citrate, heparin, and EDTA tubes, which were either centrifuged immediately or after 5, 10, 20, or 30 min after blood drawing. We assessed the correlation between MMP-9/MMP-2 in serum and citrate, heparin, and plasma samples (N=20), which were assayed for gelatine zymography of MMP-2 and MMP-9. RESULTS: MMPs are released by platelets or leukocytes during platelet activation or sampling process, thus leading to artificially higher MMP-9 levels in serum compared with citrate, heparin, or EDTA plasma samples, independently of TBDC. Citrate and heparin plasma samples had the lowest Pro-MMP-9 and MMP-9 levels, which correlated with each other. Pro-MMP-9 levels in serum correlated with Pro-MMP-9 levels in EDTA or citrate plasma, but not with heparin plasma. While no significant correlations were found between MMP-9 levels in serum and those found in plasma samples, the total MMP-9 levels (Pro-MMP-9+MMP-9) in serum and in plasma samples correlated with each other. No significant differences were found in pro-MMP-2 levels. CONCLUSIONS: These results suggest that the circulating levels of MMP-9 should be assessed in citrate or heparin plasma samples, but not in serum samples because of artificially higher MMP-9 levels in serum, independently of TBDC, and because they do not correlate with the MMP-9 levels in plasma samples.     

类风湿关节炎和系统性红斑狼疮患者血清基质金属蛋白酶2、9检测的意义

目的探讨基质金属蛋白酶（MMPs）在类风湿关节炎（RA）和系统性红斑狼疮（SLE）中的重要作用。方法采用酶联免疫吸附试验和酶谱分析了48例RA和27例SLE患者及186例健康对照者血清中MMP-2和MMP-9的浓度和活性。结果酶谱分析结果显示RA和SLE患者血清MMP-2和MMP-9的活性显著高于对照组（P〈0.01）。ELISA检测结果也表明RA、SLE组的MMP-2和MMP-9浓度明显高于对照组（P〈0.05）。结论MMP-2和MMP-9在RA和SLE患者血清中的水平及活性明显升高,表明MMPs在这些自身免疫疾病起一定的作用,可作为临床辅助诊断指标。     

多发性硬化患者外周血S100A8/A9、TLR4和MMP-2表达水平的变化

目的:探讨多发性硬化(multiple sclerosis,MS)患者外周静脉血血清钙结合蛋白复合物(S100A_8/A_9)、Toll-样受体4(Toll-like receptor 4,TLR4)和基质金属酶蛋白2(matrix metalloproteinase-2,MMP-2)表达水平的变化。方法:选取MS患者16例作为MS组,健康体检者16例作为对照组。采用蛋白芯片检测法对血清样本进行检测,定量分析血清S100A_8/A_9、TLR4和MMP-2表达水平的变化。结果:MS组血清S100A_8/A_9、TLR4和MMP-2水平均高于对照组(P0.01);MS组患者血清中上述3个指标具有明显相关性(P0.05)。结论:MS患者血清S100A_8/A_9、TLR4和MMP-2表达上调,联合检测三者可能有助于临床MS疾病活动状态的判断。     

Predictive factors that affect the mobilization of CD34(+) cells in healthy donors treated with recombinant granulocyte colony-stimulating factor (G-CSF)

No specific characteristics have been identified as predictors of peripheral blood stem cells (PBSC) mobilization in healthy donors. In this study, clinical characteristics and laboratory data for 122 healthy donors who underwent apheresis on day 5 of treatment with recombinant granulocyte colony-stimulating factor (G-CSF) were retrospectively analyzed for correlations with CD34(+) cell mobilization. The variables that were analyzed included age, sex, body weight, basal complete blood count, and maximum white blood count (WBC) before apheresis, G-CSF type, and dosage. Median age and body weight were 42.5 years (range 16-65) and 72.5 kg (range 47-121), respectively. By univariate analysis, male sex (P = 0.007), body weight (< or = 70 vs. >70 kg, P = 0.04), and donor's age (< or = 50 vs. > 50 years; P = 0.015) were correlated with the number of CD34(+) cells mobilized. By multivariate analysis, donor's age and male sex were the only two variables that significantly predicted a high CD34(+) cell level. In conclusion, our data suggest that male sex and younger age are the only factors that significantly affect CD34(+) mobilization in healthy donors.     

血液病患者/健康供者外周血造血干细胞动员及采集效果分析

目的探讨外周血造血干细胞(PBSC)动员采集的方法及其效果。方法对恶性血液病(多发性骨髓瘤、急性白血病和淋巴瘤)患者及健康供者经单一粒细胞集落刺激因子(G-CSF)和化疗联合粒细胞集落刺激因子方案动员后,使用血细胞分离机采集外周血造血干细胞,分析不同动员方案、疾病、年龄、性别及供者的动员采集。结果所有患者和健康供者均成功动员和采集到了PBSC(MNC>5×108/kg,CD34+>2×106/kg);健康供者的动员效果为MNC(8.25±3.07)×109/L;恶性血液病患者中,急性髓细胞白血病患者采集所获得的MNC最多,为(7.48±2.62)×108/kg,多发性骨髓瘤患者最差,为(5.06±1.50)×108/kg;急性淋巴细胞白血病患者采集所获得的CD34+最多,为(5.36±2.64)×106/kg,多发性骨髓瘤患者最少,为(3.45±0.76)×106/kg。化疗联合G-CSF和IL-11为最好的动员方案;18—60岁患者采集效果最好,60—65岁患者最差;男性较女性好。结论健康供者较恶性血液病患者动员效果好,健康供者中性别对采集效果无影响;无论是健康供者还是恶性血液病患者,动员、采集过程副作用小。     

降脂灵胶囊联合非诺贝特治疗高脂血症的疗效及对血清MMP-9、MFG-E8、Klotho水平的影响

目的探讨降脂灵胶囊联合非诺贝特治疗高脂血症的疗效,以及治疗对颈动脉粥样硬化斑块和血清基质金属蛋白酶-9(MMP-9)、乳脂肪球表皮生长因子8(MFG-E8)、Klotho水平的影响。方法选取重庆市第五人民医院2019年4月至2020年7月收治的高脂血症患者92例作为研究对象,按照随机数字表法将患者分为研究组和对照组,每组46例。对照组给予非诺贝特治疗,研究组在对照组基础上联合降脂灵胶囊治疗。对比2组的临床疗效、血脂水平、颈总动脉粥样硬化斑块横切面的最大面积、外周动脉内膜中层厚度(IMT)、血清MMP-9、MFG-E8、Klotho水平及不良反应发生情况。结果研究组总有效率为95.65%,高于对照组的78.26%(P<0.05)。2组治疗后总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、MMP-9水平及斑块面积、IMT均低于治疗前,高密度脂蛋白胆固醇(HDL-C)、MFG-E8、Klotho水平均高于治疗前(P<0.05);研究组治疗后TC、TG、LDL-C、MMP-9水平及斑块面积、IMT均低于对照组,HDL-C、MFG-E8、Klotho水平均高于对照组(P<0.05)。2组患者不良反应比较,差异无统计学意义(P>0.05)。结论降脂灵胶囊与非诺贝特联合治疗高脂血症患者疗效明显,可改善血脂水平,缩小颈动脉粥样硬化斑块面积以及IMT,降低血清MMP-9水平,提升血清MFG-E8、Klotho水平,且不良反应少。     

单中心191例健康供者应用G-CSF动员造血干细胞的影响因素分析

本研究旨在探讨粒细胞集落刺激因子（G-CSF）动员外周血造血干细胞的影响因素及对健康供者的影响。181例志愿健康供者应用G-CSF5-10μg/（kg·d）动员,10例应用G-CSF3．3-4．9μg/（kg·d）动员,12h1次,连续动员4-5d;采集、检测外周血中单个核细胞（MNC）数与CD34＋细胞数,并观察供者动员及采集过程中的不良反应。结果表明,与动员前相比,动员后（采集前）供者外周血白细胞数平均升高7倍（P〈0．01）;血小板数明显下降（P〈0．01）;血红蛋白含量无明显差异性。动员第4或5天采集效果无差异。男性供者采集的MNC、CD34＋细胞数高于女性（P〈0．01）,高体重供者采集的MNC、CD34＋数高于低体重供者,年龄对采集效果无明显影响。G-CSF剂量与采集效果无线性关系。供者不良反应轻微。结论：G-CSF可以有效动员外周血造血干细胞,供者无明显的不良反应。     

The effect of cholesterol levels on hematopoietic stem cell mobilization

Data regarding effects of cholesterol levels on hematopoietic stem cell mobilization are limited. We retrospectively reviewed the relationship between serum total cholesterol levels and peripheral blood CD34 (PBCD34) cell counts in 52 granulocyte colony stimulating factor (G-CSF) induced mobilization cycles with or without chemotherapy. The cholesterol levels between the poor and good mobilization groups (median 172mg/dl vs. 183.5mg/dl, respectively, p=0.18) were not different. No significant correlation was obtained between the cholesterol levels and PBCD34 counts (r=0.02, p=0.85). No significant correlation was obtained between cholesterol levels and PBCD34 counts in patients neither mobilized with G-CSF alone (r=-0.02, p=0.9) nor G-CSF plus chemotherapy (r=0.04, p=0.8). The results of the study indicate that there was no effect of cholesterol on hematopoietic stem cell mobilization. Prospective cohort studies are needed to demonstrate the effect of cholesterol on mobilization and its extent in humans.     

地塞米松对G-CSF动员供体外周血干细胞及其移植受体造血功能恢复的影响

本研究旨在观察不同动员方法对健康供者外周血造血干细胞的动员效果、采集过程中的不良反应及移植后受者造血功能恢复的影响.2008年1月-2013年5月期间本院43例异基因造血干细胞移植供者分为单纯动员和联合动员两组.单纯动员组采用粒细胞集落刺激因子5-10 μg/（kg·d）皮下注射,动员4-6天开始采集;联合动员组在单纯动员基础上于采集前2-4h给予静脉滴注地塞米松10 mg.观察不同组采集的MNC、CD34＋细胞数及其与采集前外周血MNC数的关系,观察采集过程中的不良反应和回输不同组供者造血干细胞后受者造血重建情况.结果表明：两组供者采集造血干细胞数均满足移植需要,单纯动员组采集的MNC及CD34＋细胞数均高于联合动员组.两组采集物中MNC与采集前外周血MNC计数均呈正相关;联合动员组采集后血红蛋白及血小板下降幅度较单纯动员组明显.单纯动员组采集过程中不良反应轻微,可以耐受及逆转,联合动员组未出现不良反应.在两组患者预处理方案无统计学差异的情况下,联合动员组相应的受者造血重建时间较单纯动员组明显缩短.结论：在G-CSF动员供体外周血干细胞时加用地塞米松,可以减少外周血造血干细胞采集的不良反应,可采集到足够的造血干细胞数,采集前外周血中MNC计数仍可以作为评估采集物中MNC高低的一项参考指标,特别是联合地塞米松动员干细胞对于受者造血重建有积极意义.     

Peripheral Blood Allogeneic Stem Cell Mobilization: Can We Predict a Suboptimal Mobilization?

Allogeneic peripheral blood stem cells mobilization is now the basis of most stem cell transplants. In a very limited number of cases, mobilization is suboptimal leading to further collection procedures, to suboptimal cell doses infusion with delayed engraftment time, increased risks of transplant procedure and of related costs. To date we have no recognized and shared criteria for early estimating the probability of poor mobilization in healthy donors. We then analyzed allogeneic peripheral blood stem cell donations performed at the Fondazione Policlinico Universitario A.Gemelli IRCCS Hospital from January 2013 to December 2021 in order to identify premobilization factors associated with successful mobilization. The following data were collected: age, gender, weight, complete blood cell count at baseline, G-CSF dose, number of collection procedures, CD34+ cell count in peripheral blood on the first day of collection, CD34+ cell dose per kg body weight of recipient. Mobilization efficacy was defined according to the number of CD34+ cells in peripheral blood on day +5 of G-CSF administration. We classified donors as sub-optimal mobilizers or good mobilizers according to the achievement of the 50 CD34+ cell/μL threshold. We observed 30 suboptimal mobilizations in 158 allogeneic peripheral blood stem cell donations. Age and baseline white blood cell count were factors significantly associated with negative or positive impact on mobilization, respectively. We did not find significant differences in mobilization based on gender or G-CSF dose. Using cut-off values of 43 years and 5.5×10⁹/L WBC count, we built a suboptimal mobilization score: donors who reach 2, 1 or 0 points have a 46%, 16% or 4% probability of suboptimal mobilization, respectively. Our model explains 26% of the variability of mobilization confirming that most of the mobilization magnitude depends on genetically determined factors; however, suboptimal mobilization score is a simple tool providing an early assessment of mobilization efficacy before G-CSF administration begins in order to support allogeneic stem cells selection, mobilization and collection. Through a systematic review, we looked for confirmation of our findings. According to the published articles, all the variables we included in our model are confirmed to be strongly related to the success of mobilization. We believe that score system approach could be applied in clinical practice to assess the risk of mobilization failure at baseline allowing for a priori intervention.