. 2020 Jul 3;28(11):5085–5097. doi: 10.1007/s00520-020-05603-w

Table 1.

Characteristics of the studies included in meta-analysis

Study	Year	Design	Chemotherapy regimen	The time of blood collected	Group	Simple size	Age (years)	CSF Name and Origin	Drug interventions (dose)	Primary points	Follow-up
Xu [21]	2019	RCT	Epirubicin + docetaxel; epirubicin + cyclophosphamide	On days 1, 3, 5, 7, 8, 9, 10, 11, 13, 15, 17, and 21 during cycle 1 or until an ANC ≥ 2.0 × 109/L was reached	PG-CSF	111 110	48.21 ± 8.55 48.03 ± 9.01	HHPG-19K, Jiangsu Hengrui Medicine Co., Ltd., Lianyungang, Jiangsu, China	100 μg/kg on day 3 6 mg on day 3	Duration of grade ≥ 3 neutropenia	Four cycles
Xu [21]	2019	RCT	Epirubicin + docetaxel; epirubicin + cyclophosphamide		G-CSF	110	47.37 ± 8.6	Kyowa Hakko Kirin China Pharmaceutical Co., Ltd. (Shanghai, China)	5 μg/kg/day since day 3 (≥ 48 h after chemotherapy), continuing until a documented ANC ≥ 5.0 × 109/L twice or ANC ≥ 15 × 109/L once after the expected nadir or for up to 14 days	Duration of grade ≥ 3 neutropenia	Four cycles
Wang [22]	2019	RCT	Epirubicin + docetaxel; epirubicin + cyclophosphamide	Daily from the first day of chemotherapy to next cycle	PG-CSF	60 61	47.58 ± 8.88 48.97 ± 8.59	HHPG-19K, Jiangsu Hengrui Medicine Co., Ltd., Lianyungang, Jiangsu, China	100 μg/kg on day 3 150 μg/kg on day 3	≥ Grade III ANC neutropenia, adverse events	Two cycles
Wang [22]	2019	RCT	Epirubicin + docetaxel; epirubicin + cyclophosphamide	Daily from the first day of chemotherapy to next cycle	G-CSF	60	47.84 ± 8.67	Jiangsu Wuzhong Pharmaceutical Group Co., Ltd., Suzhou, Jiangsu, China	5 μg/kg on day 3, until (1) continuous injection for 14 days; (2) ANC ≥ 5.0 × 109/L in two consecutive examinations after ANC reached the lowest point; (3) ANC ≥ 15 × 109/L.	≥ Grade III ANC neutropenia, adverse events	Two cycles
Ashrafi [23]	2018	RCT	Doxorubicin + cyclophosphamide	1 and 2 weeks after chemotherapy	PG-CSF	12	45.3 ± 10.5	Pegagen, CinnaGen Company, Iran	6 mg, once	Blood cell counts, adverse events	Two cycles
Ashrafi [23]	2018	RCT	Doxorubicin + cyclophosphamide	1 and 2 weeks after chemotherapy	G-CSF	12	45.3 ± 10.5	Zarxio, Sandoz Company	300 μg 6 days	Blood cell counts, adverse events	Two cycles
Huang [24]	2018	RCT	Adriamycin/epirubicin + cyclophosphamide	Days 0, 3, 5, 7, 9, 11, 13, 17, the blood was collected after chemotherapy	PG-CSF	24	46.5	Jin You Li, CSPC Pharmaceutical Group Limited, China	100 μg/kg on day 3	Grade IV ANC neutropenia, adverse events	Two cycles
Huang [24]	2018	RCT	Adriamycin/epirubicin + cyclophosphamide		G-CSF	22	47.5	NA	5 μg/kg/day began on day 3 and continued for 14 days or until the absolute neutrophil count (ANC) became ≥ 10 × 109/l.	Grade IV ANC neutropenia, adverse events	Two cycles
Xie [25]	2018	RCT	Epirubicin + cyclophosphamide; epirubicin + docetaxel; docetaxel + cyclophosphamide	Days 3, 5, 7–11, 13, 15, 17, and 21 of cycle 1, and on days 5, 7, 9, 11, 13, and 21 of subsequent cycles	PG-CSF	187 188	47.12 ± 8.81 49.40 ± 8.84	Shandong New Time Pharmaceutical China	100 μg/kg on day 3 6 mg on day 3	Grade IV ANC neutropenia, adverse events	Four cycles
Xie [25]	2018	RCT			G-CSF	194	49.22 ± 9.24	Shandong New Time Pharmaceutical China	FN and/or ANC < 0.5 × 109/L for longer than 3 days, 5 μg/kg until an ANC ≥ 5.0 × 109/L or for a maximum of 14 days	Grade IV ANC neutropenia, adverse events	Four cycles
Park [19]	2017	RCT	Doxorubicin + cyclophosphamide + docetaxel	NA	PG-CSF	38	47.11 ± 6.37	Tripegfilgrastim; Dong-A ST, Seoul, Korea	6 mg on day 2 approximately 24 h after completion of chemotherapy	Grade IV ANC neutropenia, adverse events	Six cycles
Park [19]	2017	RCT	Doxorubicin + cyclophosphamide + docetaxel	NA	G-CSF	36	45.76 ± 8.12	Filgrastim; NA	100 μg/m2/day beginning 24 h after chemotherapy until ANC was documented to be 5 × 109/L after nadir, or for up to 10 days	Grade IV ANC neutropenia, adverse events	Six cycles
Zhang [26]	2015	RCT	Doxorubicin + cyclophosphamide + docetaxel	Days 3, 5, 7–11, 13, 15, 17, 21 of the chemotherapy cycle 1 for ANC determination, and if an ANC ≤ 1.0 × 109/L, blood samples were collected daily until ANC reached ≥ 2.0 × 109/L	PG-CSF	43 43 42	47.03 48.18 46.71	Pegfilgrastim; NA	60 μg/kg on day 3	≥ Grade III ANC neutropenia, adverse events	One cycle
									100 μg/kg on day 3
									120 μg/kg on day 3
					G-CSF	42	47.35	Filgrastim; NA	5 μg/kg on day 3 for 14 days or until the ANC reached 10 × 109/L, post-nadir
Park [20]	2013	RCT	Doxorubicin + cyclophosphamide + docetaxel	NA	PG-CSF	20 20	42.50 ± 5.62 46.95 ± 9.19	DA-3031; Dong-A Pharmaceuticals, Seoul, Korea	3.6 mg on day 2 approximately 24 h after completion of chemotherapy 6 mg on day 2 approximately 24 h after completion of chemotherapy 100 μg/m²/day beginning approximately 24 h after chemotherapy and continued until ANC was documented to be 5 × 109/L after nadir, or for up to 10 days	Grade IV ANC neutropenia	One cycle
Park [20]	2013	RCT	Doxorubicin + cyclophosphamide + docetaxel	NA	G-CSF	21	45.29 ± 6.13	Leucostim; Dong-A Pharmaceuticals, Seoul, Korea		Grade IV ANC neutropenia	One cycle
Holmes [27]	2002	RCT	Doxorubicin + docetaxel	NA	PG-CSF	149	50.9 ± 11.7	Pegfilgrastim; NA	100 μg/m²/day beginning approximately 24 h after chemotherapy	Grade IV ANC neutropenia	Four cycles
Holmes [27]	2002	RCT	Doxorubicin + docetaxel	NA	G-CSF	147	51.9 ± 11.1	Filgrastim; NA	5 g/kg/day continuing until a documented ANC ≥ 10 × 109/L after the expected nadir or for up to 14 days	Grade IV ANC neutropenia	Four cycles

RCT, randomized control trial; NA, not applicable; G-CSF, granulocyte colony-stimulating factor; PG-CSF, pegylated granulocyte colony-stimulating factor; ANC, absolute neutrophil count