Bohlius J, Reiser M, Schwarzer G, Engert A
Department I of Internal Medicine, University of Cologne, Kerpener Str. 15, Cologne, Germany.
Cochrane Database Syst Rev. 2004(1):CD003189. doi: 10.1002/14651858.CD003189.pub2.
Granulopoiesis-stimulating factors (G-CSF and GM-CSF) are being used to prevent febrile neutropenia and infections in the treatment of patients with malignant lymphoma. The question whether G-CSF and GM-CSF improve dose-intensity, tumour response and overall survival in this patient population has not been answered yet. Since the results from single studies are inconclusive a systematic review was required.
To undertake a systematic review in patients with malignant lymphoma to determine the effectiveness of G-CSF and GM-CSF to prevent neutropenia, febrile neutropenia, infection, improve quality of life, adherence to the treatment protocol, tumour response, freedom from treatment failure (FFTF), overall survival (OS) and to assess adverse events of G-CSF and GM-CSF.
Medline, Embase, CancerLit, the Cochrane Library and smaller databases, Internet-databases of ongoing trials, conference proceedings of the American Society of Clinical Oncology and the American Society of Hematology were searched. We included full-text and abstract publications as well as unpublished data.
Randomised controlled trials comparing prophylaxis with G-CSF or GM-CSF versus placebo/no prophylaxis in adult patients with malignant lymphoma undergoing chemotherapy were included in this review. Both study arms had to receive identical chemotherapy and supportive care.
Eligibility and quality assessment, data extraction and analysis were done in duplicate. Authors were contacted to obtain missing data.
We included 12 eligible studies with 1.823 randomised patients. Compared with no prophylaxis, G-/GM-CSF significantly reduced the relative risk for severe neutropenia (RR 0.67 [95% CI 0.60-0.73]), febrile neutropenia (RR 0.74 [95% CI 0.62-0.89]) and infection (RR 0.74 [95% CI 0.64-0.85]). There was no evidence for G-/GM-CSF to decrease the number of patients who required iv antibiotics (RR 0.82 [95%CI 0.57-1.18]), to reduce infection related mortality (RR 1.37 [95% CI 0.66-2.82]), or to improve complete tumour response (RR 1.02 [95% CI 0.94-1.11]), FFTF (HR 1.11 [95% CI 0.91-1.35]) and OS (HR 1.00 [95% CI 0.86-1.16]). One study evaluated quality of life parameters and did not find differences between the groups.
REVIEWER'S CONCLUSIONS: G-CSF and GM-CSF, when given prophylactically in patients with malignant lymphoma undergoing conventional chemotherapy, reduce the risk of neutropenia, febrile neutropenia and infection. However, based on the currently available randomised trials in this clinical setting, there is no evidence for G-/GM-CSF to provide a significant advantage in terms of complete tumour response, FFTF and OS.
粒细胞生成刺激因子（G-CSF和GM-CSF）正被用于预防恶性淋巴瘤患者治疗期间的发热性中性粒细胞减少症和感染。G-CSF和GM-CSF是否能提高该患者群体的剂量强度、肿瘤反应和总生存期，这一问题尚未得到解答。由于单项研究结果尚无定论，因此需要进行系统评价。
对恶性淋巴瘤患者进行系统评价，以确定G-CSF和GM-CSF预防中性粒细胞减少症、发热性中性粒细胞减少症、感染、改善生活质量、依从治疗方案、肿瘤反应、无治疗失败生存期（FFTF）、总生存期（OS）的有效性，并评估G-CSF和GM-CSF的不良事件。
检索了Medline、Embase、CancerLit、Cochrane图书馆及其他较小的数据库、正在进行的试验的互联网数据库、美国临床肿瘤学会和美国血液学会的会议论文集。我们纳入了全文和摘要出版物以及未发表的数据。
本评价纳入了比较G-CSF或GM-CSF预防与安慰剂/不预防对接受化疗的成年恶性淋巴瘤患者疗效的随机对照试验。两个研究组均须接受相同的化疗和支持治疗。
资格和质量评估、数据提取和分析均重复进行。与作者联系以获取缺失数据。
我们纳入了12项符合条件的研究，共1823例随机分组患者。与不预防相比，G-/GM-CSF显著降低了严重中性粒细胞减少症（RR 0.67 [95% CI 0.60-0.73]）、发热性中性粒细胞减少症（RR 0.74 [95% CI 0.62-0.89]）和感染（RR 0.74 [,95% CI 0.64-0.85]）的相对风险。没有证据表明G-/GM-CSF能减少需要静脉使用抗生素的患者数量（RR 0.82 [95%CI 0.57-1.18]），降低感染相关死亡率（RR 1.37 [95% CI 0.66-2.82]），或改善完全肿瘤反应（RR 1.02 [95% CI 0.94-1.11]）、FFTF（HR 1.11 [95% CI 0.91-1.35]）和OS（HR 1.00 [95% CI 0.86-1.16]）。一项研究评估了生活质量参数，未发现组间差异。
在接受传统化疗的恶性淋巴瘤患者中预防性使用G-CSF和GM-CSF可降低中性粒细胞减少症、发热性中性粒细胞减少症和感染的风险。然而，基于目前该临床环境下的随机试验，没有证据表明G-/GM-CSF在完全肿瘤反应、FFTF和OS方面具有显著优势。
