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预防性应用粒细胞集落刺激因子对早期乳腺癌患者化疗后外周血白细胞及中性粒细胞计数水平的影响:一项回顾性队列研究

Effects of Prophylactic Administration of Granulocyte Colony-Stimulating Factor on Peripheral Leukocyte and Neutrophil Counts Levels After Chemotherapy in Patients With Early-Stage Breast Cancer: A Retrospective Cohort Study.

作者信息

Tian Wei, Wang Yali, Zhou Yunxiang, Yao Yihan, Deng Yongchuan

机构信息

Department of Breast Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Institute of Immunology, School of Medicine, Zhejiang University, Hangzhou, China.

出版信息

Front Oncol. 2022 Apr 25;12:777602. doi: 10.3389/fonc.2022.777602. eCollection 2022.

DOI:10.3389/fonc.2022.777602
PMID:35547875
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9084938/
Abstract

BACKGROUND

Both chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN) frequently occur and can lead to dose-limiting toxicity and even fatal chemotherapy side effects. The prophylactic use of recombinant human granulocyte colony-stimulating factor (rhG-CSF), including pegylated rhG-CSF (PEG-rhG-CSF), significantly reduces the risks of CIN and FN during chemotherapy in early-stage breast cancer (ESBC) patients. However, whether the prophylactic use of granulocyte colony-stimulating factor (G-CSF), especially PEG-rhG-CSF, can influence white blood cell (WBC) counts and absolute neutrophil counts (ANCs) after finishing the chemotherapy remains unknown. Therefore, exploring the development and recovery tendency of WBC counts and ANCs during and after chemotherapy is crucial.

OBJECTIVE

We aimed to investigate the variation tendency and recovery of WBC counts and ANCs during and after chemotherapy and evaluate the independent factors influencing leukopenia and neutropenia lasting longer after chemotherapy. We also aimed to provide individualized prophylactically leukocyte elevation therapy for breast cancer patients.

METHODS

This single-center retrospective cohort study evaluated 515 ESBC patients who received rhG-CSF or PEG-G-CSF for prophylaxis after adjuvant or neoadjuvant chemotherapy. Blood test reports were analyzed during chemotherapy, and on a 12-month follow-up period after finishing the chemotherapy. The WBC counts and ANCs were measured to assess their variation tendency characteristics and to identify independent factors that influenced the occurrence of leukopenia and neutropenia lasting longer than 12 months after chemotherapy.

RESULTS

Prophylaxis with rhG-CSF or PEG-rhG-CSF kept the mean values of WBC counts and ANCs within the normal range during chemotherapy, but a significant difference in WBC levels was detected before the end of the last chemotherapy compared to the prechemotherapy period (baseline) ( < 0.001). During the 12-month follow-up after the end of the last chemotherapy, WBC counts and ANCs gradually recovered, but the group that used only PEG-rhG-CSF (long-acting group, = 0.012) or rhG-CSF (short-acting group, = 0.0005) had better leukocyte elevation effects than the mixed treatment group (PEG-rhG-CSF mixed rhG-CSF). Besides, the short-acting group had a better neutrophil elevation effect than the longer-acting ( = 0.019) and mixed ( = 0.002) groups. Leukopenia was still present in 92 (17.9%) patients and neutropenia in 63 (12.2%) 12 months after the end of the last chemotherapy. The duration of leukopenia over 12 months was closely associated with the baseline WBC level ( < 0.001), G-CSF types ( = 0.027), and surgical method ( = 0.041). Moreover, the duration of neutropenia over 12 months was closely related to the baseline ANC ( < 0.001), G-CSF types ( = 0.043), and molecular typing ( = 0.025).

CONCLUSION

The prophylactic application of G-CSF effectively stabilized the WBC counts and ANCs during chemotherapy in ESBC patients. Nevertheless, the recovery of WBC counts and ANCs after chemotherapy varied between different G-CSF treatment groups. The risk of leukopenia and neutropenia persisting for more than 12 months after chemotherapy was associated with G-CSF types, the baseline level of WBC count/ANCs, surgical method, and molecular typing.

摘要

背景

化疗引起的中性粒细胞减少(CIN)和发热性中性粒细胞减少(FN)都很常见,可导致剂量限制性毒性甚至致命的化疗副作用。预防性使用重组人粒细胞集落刺激因子(rhG-CSF),包括聚乙二醇化rhG-CSF(PEG-rhG-CSF),可显著降低早期乳腺癌(ESBC)患者化疗期间CIN和FN的风险。然而,预防性使用粒细胞集落刺激因子(G-CSF),尤其是PEG-rhG-CSF,在化疗结束后是否会影响白细胞(WBC)计数和绝对中性粒细胞计数(ANC)仍不清楚。因此,探索化疗期间及化疗后WBC计数和ANC的变化及恢复趋势至关重要。

目的

我们旨在研究化疗期间及化疗后WBC计数和ANC的变化趋势及恢复情况,并评估影响化疗后白细胞减少和中性粒细胞减少持续时间更长的独立因素。我们还旨在为乳腺癌患者提供个体化的预防性白细胞升高治疗。

方法

这项单中心回顾性队列研究评估了515例接受辅助或新辅助化疗后接受rhG-CSF或PEG-G-CSF预防的ESBC患者。在化疗期间以及化疗结束后的12个月随访期内分析血液检查报告。测量WBC计数和ANC,以评估其变化趋势特征,并确定影响化疗后白细胞减少和中性粒细胞减少持续超过12个月的独立因素。

结果

使用rhG-CSF或PEG-rhG-CSF进行预防可使化疗期间WBC计数和ANC的平均值保持在正常范围内,但与化疗前(基线)相比,在最后一次化疗结束前检测到WBC水平存在显著差异(<0.001)。在最后一次化疗结束后的12个月随访期间,WBC计数和ANC逐渐恢复,但仅使用PEG-rhG-CSF的组(长效组,=0.012)或rhG-CSF的组(短效组,=0.0005)的白细胞升高效果优于混合治疗组(PEG-rhG-CSF混合rhG-CSF)。此外,短效组的中性粒细胞升高效果优于长效组(=0.019)和混合组(=0.002)。在最后一次化疗结束12个月后,92例(17.9%)患者仍存在白细胞减少,63例(12.2%)患者存在中性粒细胞减少。超过12个月的白细胞减少持续时间与基线WBC水平(<0.001)、G-CSF类型(=0.027)和手术方式(=0.041)密切相关。此外,超过12个月的中性粒细胞减少持续时间与基线ANC(<0.001)、G-CSF类型(=0.043)和分子分型(=0.025)密切相关。

结论

G-CSF的预防性应用有效地稳定了ESBC患者化疗期间的WBC计数和ANC。然而,不同G-CSF治疗组化疗后WBC计数和ANC的恢复情况有所不同。化疗后白细胞减少和中性粒细胞减少持续超过12个月的风险与G-CSF类型、WBC计数/ANC的基线水平、手术方式和分子分型有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73c4/9084938/2733c1a0307a/fonc-12-777602-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73c4/9084938/03b1a59ea162/fonc-12-777602-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73c4/9084938/0c2244b8d3f0/fonc-12-777602-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73c4/9084938/7a19646751b4/fonc-12-777602-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73c4/9084938/2733c1a0307a/fonc-12-777602-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73c4/9084938/03b1a59ea162/fonc-12-777602-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73c4/9084938/0c2244b8d3f0/fonc-12-777602-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73c4/9084938/7a19646751b4/fonc-12-777602-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73c4/9084938/2733c1a0307a/fonc-12-777602-g004.jpg

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