Acute myeloid leukemia or myelodysplastic syndrome following use of granulocyte colony-stimulating factors during breast cancer adjuvant chemotherapy
Acute myeloid leukemia or myelodysplastic syndrome following use of granulocyte colony-stimulating factors during breast cancer adjuvant chemotherapy
复制标题
DOI：
10.1093/jnci/djk028
复制
发表时间：
2007-02-07
影响因子：
10.3
通讯作者：
Grann, Victor R.
中科院分区：
文献类型：
--
作者：
Hershman, Dawn;Neugut, Alfred I.;Grann, Victor R.
背景近年来，越来越多接受乳腺癌辅助化疗的妇女同时接受了粒细胞集落刺激因子(G-CSF)或粒-巨噬细胞集落刺激因子(GM-CSF)治疗。虽然这些生长因子支持化疗，但它们的长期安全性尚未得到评估。方法在1991年1月1日至1999年12月31日期间在监测、流行病学和最终结果-医疗保险数据库中65岁或以上的女性中，我们确定了在化疗的同时接受G-CSF或GM-CSF治疗的I-III期乳腺癌患者。我们使用COX比例风险模型来估计使用G-CSF或GM-CSF治疗和随后(到2003年12月31日)诊断急性髓系白血病(AML)或骨髓增生异常综合征(MDS)相关的风险比。结果5510名接受化疗的女性中，906名(16%)接受了粒细胞集落刺激因子或粒-巨噬细胞集落刺激因子治疗，(1.16%)在肿瘤复发前被诊断为MDS或AML。G-CSF和GM-CSF的使用与较新的诊断、较年轻的年龄、居住在城市、较少的合并症、接受放射治疗、阳性淋巴结和环磷酰胺治疗有关。在接受G-CSF治疗的906例患者中，16例(1.77%)发展为AML或MDS；在4604例未接受G-CSF治疗的患者中，48例(1.04%)发展为AML或MDS。接受G-CSF或GM-CSF治疗的患者与未接受治疗的患者相比，AML或MDS的风险比为2.14(95%可信区间[CI]=1.12至4.08)。在接受G-CSF或GM-CSF治疗的乳腺癌患者中，1.8%的患者在确诊后48个月内发展为AML或MDS，而未接受治疗的患者中仅有0.7%发生AML或MDS(风险比=2.59，95%CI=1.30~5.15)。结论在我们研究的人群中，尽管绝对风险仍然很低，但使用G-CSF与随后发生AML或MDS的风险增加了一倍。即使这种关联得到证实，G-CSF的好处也可能超过风险。然而，与此同时，G-CSF的使用不应被认为是无风险的。
Background Recently, increasing numbers of women receiving adjuvant chemotherapy for breast cancer have also received granulocyte colony-stimulating factors (G-CSFs) or granulocyte-macrophage colony-stimulating factors (GM-CSFs). Although these growth factors support chemotherapy, their long-term safety has not been evaluated. We studied the association between G-CSF use and incidence of leukemia in a population-based sample of breast cancer patients.Methods Among women aged 65 years or older in the Surveillance, Epidemiology, and End Results-Medicare database who were diagnosed with stages I-III breast cancer from January 1, 1991, to December 31, 1999, we identified those who received G-CSF or GM-CSF concurrently with chemotherapy. We used Cox proportional hazards models to estimate hazard ratios for the association of treatment with G-CSF or GM-CSF and subsequent (through December 31, 2003) diagnosis of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). All statistical tests were two-sided.Results Of 5510 women treated with chemotherapy, 906 (16%) received G-CSF or GM-CSF therapy, and 64 (1.16%) were subsequently diagnosed with either MDS or AML before a cancer recurrence. Use of G-CSF and GM-CSF was associated with more recent diagnosis, younger age, urban residence, fewer comorbidities, receipt of radiation therapy, positive lymph nodes, and cyclophosphamide treatment. Of the 906 patients who were treated with G-CSF, 16 (1.77%) developed AML or MDS; of the 4604 patients not treated with G-CSF, 48 (1.04%) developed AML or MDS. The hazard rate ratio for AML or MDS among those treated with G-CSF or GM-CSF compared with those who were not was 2.14 (95% confidence interval [CI] = 1.12 to 4.08). AML or MDS developed within 48 months of breast cancer diagnosis in 1.8% of patients who received G-CSF or GM-CSF but only in 0.7% of patients who did not (hazard ratio = 2.59, 95% CI = 1.30 to 5.15).Conclusions The use of G-CSF was associated with a doubling in the risk of subsequent AML or MDS among the population that we studied, although the absolute risk remained low. Even if this association is confirmed, the benefits of G-CSF may still outweigh the risks. Meanwhile, however, G-CSF use should not be assumed to be risk free.