Higher BMI is not a barrier to stem cell mobilization with standard doses of plerixafor and G-CSF.
Higher BMI is not a barrier to stem cell mobilization with standard doses of plerixafor and G-CSF.
复制标题
使用标准剂量的普乐沙福和 G-CSF 时，较高的 BMI 并不是干细胞动员的障碍。
DOI：
10.1038/bmt.2011.199
复制
发表时间：
2012
影响因子：
4.8
通讯作者：
Basak GW
中科院分区：
文献类型：
--
作者：
Basak GW
超重和肥胖是世界范围内日益严重的流行病问题。体重指数（BMI）定义为一个人的体重（以公斤为单位）除以身高（以米为单位）的平方（kg/m2），是一种常用的简单测量方法。1根据世界卫生组织的定义，BMI X25 kg/m2的人超重，BMI X30 kg/m2的人肥胖。BMI升高被认为是心血管疾病、糖尿病和肌肉骨骼疾病的主要风险因素，也是许多癌症的主要风险因素，包括非霍奇金淋巴瘤和多发性骨髓瘤。2最近，已经观察到BMI可能与基于粒细胞集落刺激因子（G-CSF）给药的标准方案的干细胞动员效果相关，并且已经表明这可能是肥胖个体中G-CSF的药代动力学改变的结果。3-5此外，经常伴随BMI增加的高胆固醇血症似乎促进了干细胞动员，这在实验小鼠模型和临床数据的回顾性分析中都有记录。6，7高胆固醇水平可能会通过诱导促炎症状态、激活补体级联反应和血清SDF-1的增加来干扰SDF-1/CXCR 4轴。普乐沙福是一种与G-CSF联合使用的新药，用于既往动员尝试失败的骨髓瘤和淋巴瘤患者。8普乐沙福的作用基于通过特异性抑制CXCR 4受体可逆性破坏CXCR 4/SDF-1轴。我们假设，在超重和肥胖个体中，普乐沙福的干细胞动员可能会受损，这些个体需要动员和收集更多的CD 34+细胞，因为他们的体重较高。我们在来自13个国家的606例患者中进行了研究，这些患者入组了欧洲普乐沙福同情使用项目。普乐沙福和G-CSF给药方案已在其他地方发表，9，10所有患者均签署了知情同意书，以纳入同情使用项目并收集其数据。这项回顾性分析共纳入了356例患者，这些患者的BMI数据充足。患者特征和活动特征总结见表1。该组包括168例骨髓瘤患者，154例非霍奇金淋巴瘤（NHL）和25例霍奇金淋巴瘤（HL）。体重中位数为74 kg（43-132 kg），身高中位数为168 cm（146- 194 cm）。中位BMI为25.7 kg/m2（范围：15.1-47.5）。2例患者（0.6%）的BMI为16。0 kg/m2（体重严重不足），9例患者（2.5%）的BMI> 18。5 kg/m2（体重不足），139例患者（39.0%）BMI为18.5-25.0 kg/m2（正常），134例患者（37.6%）BMI为25-30 kg/m2（超重），51例患者BMI为30- 35 kg/m2（肥胖I级）者18例（5.1%），BMI为35- 40 kg/m2（肥胖II级）者18例（5.1%），BMI> 40 kg/m2（肥胖III级）者3例（0.8%）。与BMI <25 kg/m2的患者（45.6%，P <0.05）相比，BMI> 25 kg/m2的患者（57%）中男性不常见。03）。BMI <25 kg/m2的患者的中位体重和BMI分别为82 kg和28.4，而BMI <25 kg/m2的患者的中位体重和BMI分别为61 kg和22.6。在中位年龄、疾病特征、既往化疗方案数量、既往治疗、既往动员方案数量、动员前WBC和血小板计数以及普乐沙福动员方案方面，两组间无显著差异。统计学分析显示，在BMI X25 kg的患者中，干细胞动员的结果...
Overweight and obesity are growing epidemiologic problems worldwide. Body mass index (BMI) defined as a person’s weight in kilograms divided by the square of his height in meters (kg/m2) is a simple measure in common use. 1 According to the WHO definition, people with a BMI X25 kg/m2 are overweight and those with a BMI X30 kg/m 2 are obese. A raised BMI is recognized as a major risk factor for cardiovascular diseases, diabetes and musculoskeletal disorders, and also for a number of cancers, including non-Hodgkin’s lymphoma and multiple myeloma. 2 Recently, it has been observed that BMI may correlate with the efficacy of stem-cell mobilization with standard regimens based on administration of granulocytecolony stimulating factor (G-CSF), and it has been suggested that this may be a result of the altered pharmacokinetics of G-CSF in obese individuals. 3–5 Moreover, hypercholesterolemia, which frequently accompanies increased BMI, seems to promote stem-cell mobilization, and this was documented in both an experimental murine model, and a retrospective analysis of clinical data. 6, 7 High cholesterol levels may interfere with the SDF-1/CXCR4 axis by induction of a proinflammatory state, activation of complement the cascade and an increase in serum SDF-1. Plerixafor is a new agent used in combination with G-CSF in myeloma and lymphoma patients, who failed a previous mobilization attempt. 8 The action of plerixafor is based on reversible disruption of the CXCR4/SDF-1 axis by specific inhibition of the CXCR4 receptor. We hypothesized that stem-cell mobilization with plerixafor might be impaired in overweight and obese individuals, who need to mobilize and collect more CD34þ cells in total on the basis of their higher body weight. We investigated this in a group of 606 patients from 13 countries who were enrolled in the European plerixafor compassionate use program. The regimen of plerixafor and G-CSF administration was published elsewhere, 9, 10 and all patients signed the informed consent form for inclusion in the compassionate use program and for collection of their data. This retrospective analysis included a total of 356 patients for whom adequate data regarding BMI were available. Patient characteristics and mobilization features are summarized in Table 1. This group included 168 patients with myeloma, 154 with non-Hodgkin lymphoma (NHL) and 25 with Hodgkin lymphoma (HL). The median body weight was 74 kg (43–132 kg), while their median height was 168cm (146–194cm). The median BMI was25.7 kg/m2 (range, 15.1–47.5). Two patients (0.6%) had a BMI o16. 0 kg/m2(severely underweight), 9 patients (2.5%) had a BMI o18. 5 kg/m2 (underweight), 139 patients (39.0%) a BMI of 18.5–25.0 kg/m2 (normal), 134 patients (37.6%) a BMI of 25–30 kg/m2(over weight), 51 patients (14.3%) a BMI of 30–35kg/m2 (obese class I), 18 patients (5.1%) a BMI of 35–40kg/m2 (obese class II) and 3 patients (0.8%) a BMI X40 kg/m 2 (obese class III). Male gender was not frequently represented among patients with BMI X25 kg/m2,(57%) compared with patients with BMI o25 kg/m2 (45.6%, P¼0. 03). The median body weight and BMI in patients with BMI X25 kg/m2 was 82kg and 28.4, compared with 61kg and 22.6 in patients with BMI o25 kg/m2. There were no significant differences between the groups in regard to median age, disease profile, number of prior chemotherapy regimens, prior treatments, number of prior mobilization regimens, pre-mobilization WBC and platelet counts, and the regimen of mobilization with plerixafor. Statistical analysis revealed that the outcomes of stem-cell mobilization in patients with BMI X25 kg …