Gurion Ronit, Belnik-Plitman Yulia, Gafter-Gvili Anat, Paul Mical, Vidal Liat, Ben-Bassat Isaac, Shpilberg Ofer, Raanani Pia
Institute of Hematology, Davidoff Center, Beilinson Hospital, Rabin Medical Center, Petah Tikva, Israel.
Cochrane Database Syst Rev. 2012 Jun 13;2012(6):CD008238. doi: 10.1002/14651858.CD008238.pub3.
Acute myelogenous leukemia (AML) is a fatal bone marrow cancer. Colony-stimulating factors (CSFs) are frequently administered during and after chemotherapy to reduce complications. However, their safety with regard to disease-related outcomes and survival in AML is unclear. Therefore, we performed a systematic review and meta-analysis to evaluate the impact of CSFs on patient outcomes, including survival.
To assess the safety/efficacy of CSFs with regard to disease-related outcomes and survival in patients with AML.
We conducted a comprehensive search strategy. We identified relevant randomized clinical trials by searching the Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 7), MEDLINE (January 1966 to July 2010), LILACS (up to December 2009), databases of ongoing trials and relevant conference proceedings.
Randomized controlled trials that compared the addition of CSFs during and following chemotherapy to chemotherapy alone in patients with AML. We excluded trials evaluating the role of CSFs administered for the purpose of stem cell collection and/or priming (e.g. before and/or only for the duration of chemotherapy).
Two review authors appraised the quality of trials and extracted data. For each trial, we expressed results as relative risk (RR) with 95% confidence intervals (CI) for dichotomous data. We analyzed time-to-event outcomes as hazard ratios (HRs).
The search yielded 19 trials including 5256 patients. The addition of CSFs to chemotherapy yielded no difference in all-cause mortality at 30 days and at the end of follow up (RR 0.97; 95% CI 0.80 to 1.18 and RR 1.01; 95% CI 0.98 to 1.05, respectively) or in overall survival (HR 1.00; 95% 0.93 to 1.08). There was no difference in complete remission rates (RR 1.03; 95% CI 0.99 to 1.07), relapse rates (RR 0.97; 95% CI 0.89 to 1.05) and disease-free survival (HR 1.00; 95% CI 0.90 to 1.13). CSFs did not decrease the occurrence of bacteremias (RR 0.96; 95% CI 0.82 to 1.12), nor the occurrence of invasive fungal infections (RR 1.40; 95% CI 0.90 to 2.19). CSFs marginally increased adverse events requiring discontinuation of CSFs as compared to the control arm (RR 1.33; 95% CI 1.00 to 1.56).
AUTHORS' CONCLUSIONS: In summary, colony-stimulating factors should not be given routinely to acute myelogenous leukemia patients post-chemotherapy since they do not affect overall survival or infectious parameters including the rate of bacteremias and invasive fungal infections.
急性髓系白血病（AML）是一种致命的骨髓癌。集落刺激因子（CSF）常在化疗期间及化疗后使用，以减少并发症。然而，其对AML患者疾病相关结局和生存的安全性尚不清楚。因此，我们进行了一项系统评价和荟萃分析，以评估CSF对患者结局（包括生存）的影响。
评估CSF对AML患者疾病相关结局和生存的安全性/有效性。
我们采用了全面的检索策略。通过检索Cochrane对照试验中心注册库（Cochrane图书馆2010年第7期）、MEDLINE（1966年1月至2010年7月）、LILACS（截至2009年12月）、正在进行的试验数据库和相关会议论文集，确定了相关的随机临床试验。
比较在AML患者化疗期间及化疗后加用CSF与单纯化疗的随机对照试验。我们排除了评估用于干细胞采集和/或动员（例如化疗前和/或仅在化疗期间）目的的CSF作用的试验。
两位综述作者评估试验质量并提取数据。对于每项试验，我们将二分数据的结果表示为相对风险（RR）及95%置信区间（CI）。我们将事件发生时间结局分析为风险比（HR）。
检索得到19项试验，共5256例患者。化疗加用CSF在30天及随访结束时的全因死亡率（RR分别为0.97；95%CI 0.80至1.18和RR 1.01；95%CI 0.98至1.05）或总生存方面（HR 1.00；95%CI 0.93至1.08）无差异。完全缓解率（RR 1.03；95%CI 0.99至1.07）、复发率（RR 0.97；95%CI 0.89至1.05）和无病生存（HR 1.00；95%CI 0.90至1.13）也无差异。CSF并未降低菌血症的发生率（RR 0.96；95%CI 0.82至1.12），也未降低侵袭性真菌感染的发生率（RR 1.40；95%CI 0.90至2.19）。与对照组相比，CSF略微增加了需要停用CSF的不良事件（RR为1.33；95%CI 1.00至1.56）。
总之，急性髓系白血病患者化疗后不应常规给予集落刺激因子，因为它们不影响总生存或感染参数，包括菌血症和侵袭性真菌感染的发生率。
