Effectiveness of Acupuncture for Relieving Chemotherapy-Induced Bone Marrow Suppression: A Systematic Review with a Meta-analysis and Trial Sequential Analysis

Abstract

Objective:

Bone marrow suppression is the most common side effect of chemotherapy that may lead to discontinuation for treatment pertaining to patients during the therapy course. Acupuncture may relieve bone marrow suppression with regulation hematopoietic function during chemotherapy. The purpose of this study is to evaluate the effectiveness of acupuncture in relieving chemotherapy-induced bone marrow suppression and determine the effects of acupuncture on bone marrow function.

Design:

PubMed, Embase, Cochrane Library, Medline OVID, CINAHL Plus, Web of Science, and Chinese articles in the Airiti Library and China National Knowledge Infrastructure databases were searched up to February 2023. Publications in both English and Chinese were eligible for inclusion without any limitations on the publication date. Only randomized controlled trials investigating the impact of acupuncture on chemotherapy-induced bone marrow suppression were considered. In addition, a trial sequential analysis was performed to assess the adequacy of the current sample size.

Results:

A total of 25 studies met the inclusion criteria. Acupuncture was found to increase the levels of hematopoietic cytokine granulocyte colony-stimulating factor (G-CSF) (Hedges' g = 0.79, p < 0.001), as well as stimulate the production of white blood cells (Hedges' g = 0.69, p < 0.001), red blood cells (Hedges' g = 0.37, p = 0.01), neutrophils (Hedges' g = 0.66, p < 0.001), absolute neutrophil count (Hedges' g = 0.89, p = 0.01), hemoglobin (Hb) (Hedges' g = 0.37, p = 0.02), platelets (Hedges' g = 0.50, p < 0.001), and natural killer (NK) cells (Hedges' g = 1.30, p = 0.02). Further, the levels of platelets and NK cells were observed to increase cumulatively over time.

Conclusions:

Acupuncture may improve chemotherapy-induced bone marrow suppression due to increasing levels of the hematopoietic cytokine, G-CSF and further relieving chemotherapy-induced bone marrow suppression.

PROSPERO Registration:

This review was registered with PROSPERO (International Prospective Register of Systematic Reviews: CRD42020185813).

Background

Bone marrow suppression is extremely prevalent during chemotherapy and may lead to discontinuation or delay when patients are undergoing a treatment course for cancer.¹ The major problem is that chemotherapy-induced myelosuppression is the fatal side effect of chemotherapy, which consequently leads to decreased production of red blood cells (RBCs), resulting in anemia, white blood cells (WBCs), resulting in neutropenia or granulocytopenia, and platelets, resulting in thrombocytopenia, which may delay the treatment or life-threatening to cancer patients.^2,3

Granulocyte colony-stimulating factor (G-CSF) subcutaneous injection is commonly used in clinical settings to prevent or manage chemotherapy-induced leukopenia.⁴ However, that results in nausea, syncope, bones and muscles aching, and flushing.⁵ Further, not all cancer patients can benefit from this treatment as the National Health Insurance in Taiwan only covers those with WBCs <1000/μL or absolute neutrophil count (ANC) <500/μL.⁶

Acupuncture involves the stimulation of specific acupoints on the skin with needles and is a modality of traditional Chinese medicine (TCM) used to relieve various symptoms. It was proven to improve menopausal symptoms,⁷ premenstrual syndrome,⁸ and mood, such as depression and anxiety.⁹ It was also certified to improve side-effects for treatment of cancer, such as postoperative arm lymphedema,¹⁰ chemotherapy-induced leucopenia,^3,11 chemotherapy-related nausea and vomiting,¹² and chemotherapy-induced peripheral neuropathies.^13,14 However, the efficacy of acupuncture for chemotherapy-related myelosuppression remains unclear.

Many studies revealed the impacts of acupuncture on chemotherapy-induced leukopenia.^15

–18 Thus far, only a few kinds of literature focused on the chemotherapy-related myelosuppression,^1,19,20 among which, one of them was systematic review¹⁹; one was a protocol for a systematic review and meta-analysis²⁰; another one study reported only blood values: WBCs, RBCs, hemoglobin (Hb) as an outcome variable.¹

The most recent meta-analysis was published in 2019, which only mentioned that TCM combined therapy may be associated with bone marrow suppression but did not report any specific indicators of blood cell counts.²¹ Nonetheless, the mechanism for acupuncture stimulates anticancer immunity, promoting the protective effects of bone marrow or increasing the activity of serum colony-stimulating factors remain unclear nowadays.

Those reviews mostly focused on chemotherapy-induced leucopenia and are now outdated. In addition, the hematopoietic cytokine, G-CSF, in patients during chemotherapy and using a trial sequential analysis (TSA) to detect whether the sample size is enough has not been assessed in previous reviews.

Therefore, the purpose of this study was to systematically evaluate the effectiveness of acupuncture in relieving chemotherapy-induced bone marrow suppression and determine the mechanism for effects of acupuncture on bone marrow functions.

Methods

The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement guidelines were followed in conducting this systematic review and meta-analysis. The review was registered with PROSPERO-CRD42020185813. For more details on PRISMA, please refer to Supplementary Data S1.

Literature sources and search strategy

The literature search for relevant studies was conducted until February 2023 using electronic databases such as Cochrane Library, Embase, PubMed, Medline OVID, Web of Science, CINAHL Plus, China National Knowledge Infrastructure, and Airiti Library. The search was limited to articles published in English or Chinese, involving human participants.

Further, we also explored pertinent literature in the references, government publications, and recommendations provided in the studies that were included. We also searched several websites, including scholar.google.com,www.baidu.com, www.clinicaltrialsregister.eu, and www.clinicaltrials.gov, for potentially relevant literature.

The search strategy applied a combination or separation of Medical Subject Headings (MeSH) terms and text words associated with several keywords such as G-CSF, granulocyte-macrophage colony-stimulating factor (GM-CSF), GM-CSF, stem cell factor (SCF), SCF, white blood cell, leukocyte, leukopenia, neutropenia, Hb, anemia, platelet, thrombocyte, thrombocytopenia, chemotherapy, and acupuncture. Please refer to Supplementary Table S1 for a detailed search strategy used for PubMed.

Inclusion criteria

We included randomized controlled trials (RCTs) published in English or Chinese languages, without any time restriction, that examined the use of acupuncture in managing chemotherapy-induced bone marrow suppression in cancer patients. Study participants with a cancer diagnosis undergoing chemotherapy, regardless of age, gender, or race, were considered eligible for inclusion.

Studies that assessed any type of invasive acupuncture, with or without electrical stimulation, and involved needle insertion at acupuncture points, were included in the analysis. To meet eligibility criteria, studies had to measure at least one hematopoietic outcome indicator, such as G-CSF, GM-CSF, SCF, WBCs, Hb, or platelets.

Exclusion criteria

Studies that were excluded from our analysis, such as cohort and case-control studies, observational studies, case reports, qualitative studies, non-RCTs, review articles, and laboratory studies involving animals. Moreover, studies that enrolled participants with hematopoietic diseases or those that had overlapping participants with other studies already included in our analysis were also excluded.

Data extraction and quality assessment

The titles and abstracts of the articles obtained through the search strategy were assessed by two researchers (Y.W.S. and M.H.W.) independently, who also extracted the pertinent information about the eligible studies. In the event of any discrepancies between the two investigators, a third researcher (H.T.T.) was consulted to resolve the issue through discussion.

We selected studies for further review based on the following criteria, also known as PICO: Population, Intervention, Comparator, and Outcome. The study population comprised individuals who had been diagnosed with cancer at any stage and were receiving chemotherapy treatment. The intervention included real acupoint stimulation using invasive techniques such as manual acupuncture, electro-acupuncture (EA), acupoint injection, or warm-acupuncture.

The outcome of interest was the investigation of at least one hematopoietic outcome indicator, including changes in G-CSF, GM-CSF, SCF, WBCs, Hb, and platelets, to evaluate the bone marrow function. We only included RCTs with at least one control group that received routine therapy, a placebo, or other appropriate controls. The primary outcomes of this study were hematopoietic relevant cytokines and blood indicators, including G-CSF, WBCs, RBCs, Hb, neutrophils, platelets, ANC, and natural killer (NK) cells. The secondary outcomes were the cumulative time-dependent responses of acupuncture, as well as subgroup analyses for various types of acupuncture.

Two reviewers (Y.W.S and M.H.W.) assessed the methodological quality of each study using the Cochrane Handbook for Systematic Review of Intervention's risk of bias assessment tool, version 5.1.0.²² The reviewers evaluated various aspects of the studies, including random sequence generation, allocation concealment, blinding of participants and staff, blinding of outcome assessments, incomplete outcome data, and selective reporting.

In the event of any disagreements, a third reviewer (H.T.T.) was consulted to resolve the issue through discussion. The data from the studies were extracted independently by the two reviewers (Y.W.S and M.H.W.) and compiled in Table 1. Any discrepancies that arose were resolved through discussion or consultation with the third independent reviewer (H.T.T.).

Table 1.

Characteristics of the Included Studies

No.	Authors	Country	No. of subjects in each arm (E: C)	Cancer (ca) type	Chemotherapy drug	Acupuncture group			Control group intervention	Assessment of relevant outcomes
No.	Authors	Country	No. of subjects in each arm (E: C)	Cancer (ca) type	Chemotherapy drug	Acupoints	Intervention	Intervention dose (min)	Control group intervention	Assessment of relevant outcomes
1	Beith et al. (2012)³⁷	Australia	14: 16	Breast ca	AC FEC	PC6/IL4/ST36	Electro-acupuncture	80	Sham Electro-acupuncture	WBC, neutrophil
2	Bii (2008)³⁵	China	22: 21	Lung ca, colon ca	GP, PC, FLO	ST36, SP6, BL26, CV6, GV20, BL13, BL17, BL20, BL23, BL25	Electro-acupuncture	n/a	Chinese medicine oral	WBCs, platelets, Hb
3	Chen and Huang (1991)²⁹	China	121: 34	Lung ca, gastric ca, lymphoma, breast ca	n/a	ST36, SP6, PC6, SP9, BL26, BL24, SP10	Warm-acupuncture	n/a	Chinese medicine oral	WBCs
4	Chen et al. (2004)³³	China	28: 28	NPC Lung ca	DDP 5-FU CTX	ST36	Electro-acupuncture	n/a	Usual care	WBCs, NK cells T cell
5	Gao and Luo (2019)⁷	China	42: 42	Lung ca	GP	ST36, KI3, LI4, GV14, SP6, BL17, LR14	Acupuncture	210	Usual care	WBCs, platelets, RBCs, Hb
6	Han et al. (2010)³⁶	China	43: 43	Carcinoma of endometrium	AP	TE6, LI11, LI4	Acupuncture	210	GCSF	WBCs
7	Hou et al. (2017)²⁰	China	47: 55	Lung ca	NA	DU14, BL17, ST36, SP6, LI4	Electro-acupuncture	270	Chinese medicine oral	WBCs, platelets, RBCs, Hb
8	Hu et al. (2016)³⁹	China	30:30	Breast ca	TAC	ST36/SP6/SP10/BL23	Acupuncture	150	Western medicine routine	WBC, neutrophil
9	Li et al. (1997)³⁰	China	22: 20	Lung ca, gastric ca, breast ca, malignant lymphoma, rectal ca, esophageal ca, nasopharyngeal carcinoma	n/a	ST36, SP6, LI4, LI11	Acupuncture	540	Usual care	WBCs, platelets, NK cells
10	Liu Meng et al. (2018)⁴²	China	32: 31	Colon ca, rectal ca	Folfox	CV4, CV6, ST36, PC6	Acupuncture	150	Usual care	WBCs, platelets, neutrophils
11	Lu et al. (2009)¹⁶	USA	11: 10	Ovarian ca	Carboplatin/paclitaxel, gemcitabine, topotecan, vinorelbine	LR3, K3, SP6, ST36, SP10, LI4, PC6, LI11, GV20	Acupuncture	300	Sham-acupuncture	WBCs, ANC, G-CSF
12	Meng and Lu (2012)³	China	27: 27	Breast ca	CAF	ST36/ST25/BL21/BL17/CV6/SP6/SP4/HT7	Acupoint catgut-embedding+moxibustion	10080	Western medicine routine	WBCs
13	Ni Weimin et al. (2018)⁴³	China	40: 40	Lung ca, gastric ca, somatic ca, esophageal ca	5-FU, ADM, DDP, paclitaxel	ST36, SP6, GV20, CV12, EX-HN1	Acupoint injection	240	GCSF	WBCs
14	Pais et al. (2014)¹¹	Portugal	9: 9	Colon ca, rectal ca	Folfox, xelox, folfiri, capecitabine	LV3, ST36, SP3, GB39, LI4, PC5, TB5, LU7	Warm-acupuncture	270	Usual care	WBCs, ANC, NK cells
15	Yan (2016)⁴⁰	China	43: 43	Lung ca	GP	GV14, BL17, ST36, SP6, LI4	Electro-acupuncture	270	Usual care	WBCs, platelets, RBCs, Hb
16	Xinying (2019)⁴⁵	China	30: 28	Breast ca	n/a	GV20, CV12, CV4,CV6, CV3, GV4,GV3, GV2	Electro-acupuncture	210	Sham-Electro-acupuncture	WBC/neutrophil
17	Wu Guoliang et al. (2018)⁴⁴	China	120: 120	Lung ca, gastric ca, liver ca, breast ca	n/a	CV4, CV6, ST36, SP6, ST25, HT7, PC6	Acupuncture	n/a	Sham-Electro-acupuncture	WBCs, RBCs, Hb
18	Xie et al. (2003)³²	China	40: 50	lung ca, breast ca, esophageal carcinoma, malignant lymphoma	CAP	ST36	Acupoint injection	n/a	Chinese medicine oral	WBCs
19	Yiyuan (2013)³⁸	China	30: 30	lung ca, breast ca, liver ca, ovary ca	DDP,CTX,VCR,5-FU	PC6, SP4, ST36, SP10, SP6, CV12, CV4, CV6	Electro-acupuncture	210	Usual care	WBCs, platelets, Hb, granulocytes
20	Zhu et al. (2017)⁴¹	China	23: 23	Breast ca	FEC	ST36, BL23	Acupoint catgut-embedding	n/a	Western medicine and Chinese decoction	WBC/neutrophil
21	Yang (2011)¹⁸	China	40: 40	n/a	n/a	ST36, SP6, SP10, GV20, CV6, GB39	Acupuncture	560 min	GCSF	WBCs
22	Ye et al. (2007)³⁴	China	21: 21	Lung ca, gastric ca, breast ca, malignant lymphoma	MVP, CF +5-FU, CMF, CAP, CHOP	ST36, SP6, CV12, PC6	Electro-acupuncture	150 min	n/a	WBCs, NK cells
23	Zhao and Kao (2001)³¹	China	38: 38	Lung ca, breast ca, liver ca, gastric ca, lymphoma	ADM, MMC, DDP, BCN U, 5-FU, C TX, M TX, CMF/CAF-breast ca CBEP-lung ca	ST36, SP6, LI4, DU14, CV12, BL17	Acupuncture	n/a	Chinese medicine oral	WBCs
24	Zhu et al. (2016)⁹	China	40: 38	Breast ca	CAT, CET	ST36, SP10, BL26, SP6, BL23, BL18	Acupuncture	150	Western medicine	WBCs
25	Zhao et al. (2022)⁴⁶	China	76: 78: 70	Lung ca	n/a	PC6, ST36, CV12	Acupuncture	150	Tropisetron hydrochloride	WBCs, G-CSF, GM-CSF, Hb, platelets, neutrophil

ADM, ÿdriamycin; ANC, absolute neutrophil count; AP, ÿdriamycin/cisplatin; BCNU, bis-chloroethylnitrosourea; BEP, bleomycin/etoposide/cisplatin; CAF, cyclophosphamide/ÿdriamycin/5-fluorouracil; CAP, cyclophosphamide/ÿdriamycin/cisplatin; CF, carboplatin; CHOP, cyclophosphamide, doxorubicin/hydroxydaunorubicin, vincristine/oncovin, prednisone/prednisolone; CMF, cyclophosphamide/methotrexate/5-fluorouracil; CTX, cyclophosphamide; DDP, cisplatin; FLO, fluorouracil/leucovorin/oxaliplatin; Folfiri, folinic acid/5-fluorouracil/irinotecan; Folfox, folinic acid/fluorouracil/oxaliplatin; 5-FU, 5-fluorouracil; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; GP, gemcitabine/cisplatin; Hb, hemoglobin; MMC, mitomycin C; MTX, methotrexate; MVP, mitomycin/vindesin/cisplatin; n/a, not applicable; NK, natural killer; NPC, nasopharyngeal carcinoma; PC, cisplatin/cyclophosphamide; RBCs, red blood cells; WBCs, white blood cells.

Statistical analysis

We calculated two-sided p-values, with a level of statistical significance set at p < 0.05. First, we obtained pre- to post-test score changes for both the intervention and control groups from each included study. Subsequently, we calculated the effect size for the difference between the intervention and control groups for each study. The Hedges' g was used to determine the effect size index, and it was calculated using the formula: g = d(1 − (3/(4(n1 + n2) − 9))).²³

We presented the results as the effect size (Hedges' g) with a confidence interval (95% CI). An effect size of Hedges' g ranging from 0.2 to 0.4 indicates a small effect, 0.5 to 0.7 represents a moderate effect, and an effect size of ≥0.8 represents a large effect.²⁴ A random-effects model was chosen due to the variation in the characteristics of the included studies, such as different cancer stages, types of cancer, types of acupuncture used (manual acupuncture or EA ), theoretical principles of acupuncture point selection (fixed or unfixed points), total treatment dose (min), and study quality.

To evaluate heterogeneity among the studies, Cochran's Q test was employed with statistical significance set at p < 0.1. Moreover, we utilized the I ² statistic to determine the proportion of total variance in the pooled effect size that could be attributed to heterogeneity among studies. An I ² value of 0% indicates no heterogeneity, 25% indicates low heterogeneity, 50% indicates moderate heterogeneity, and an I ² value of ≥75% indicates high heterogeneity.²⁴

To identify the potential sources of heterogeneity, moderator analyses were conducted. When heterogeneity was observed, subgroup analyses were conducted for categorical variables, and meta-regression analyses were conducted for continuous variables.²⁵

The moderator analyses were limited to groups reported by at least two studies to ensure that sufficient data were obtained for analysis.²⁴ The sensitivity analyses were conducted to assess the robustness of synthesized results. The asymmetry of the funnel plot was evaluated using Egger's regression intercept test, and a p-value of <0.05 indicated the presence of publication bias.

To further account for possible bias in the overall log odds ratio, the trim-and-fill method was used to estimate the number of missing studies. Funnel plots were only generated if there were >10 studies.^26,27 Moderator analyses and all statistical analyses were performed using Comprehensive Meta-analysis version 3.0.

We employed TSA to calculate the optimal sample size to avoid Type I errors (α). By analyzing the cumulative Z-curve, we determined whether it intersected the trial sequential monitoring boundary or crossed into the futility area, which would indicate whether there was enough evidence to support the anticipated intervention effect, and whether further studies were unnecessary.

To determine the required sample size, we considered the mean difference and variance in changes in blood cell count levels, while setting the Type I error (α) and power (1 − β) at 0.05 and 80%, respectively.²⁸ TSA versus 0.9 beta software was used for the analysis.

Results

Study selection

Initially, a total of 1004 studies were searched, and 136 duplicate articles were eliminated. Subsequently, 601 articles were excluded from the study, as they did not meet the eligibility criteria: conference papers (n = 6), editorial letters/comments (n = 26), animal/cell studies (n = 174), meta-analyses or reviews (n = 87), study protocols (n = 8), and non-relevant outcomes (n = 300).

Thus, 267 studies remained for full manuscript review, of which 242 studies were excluded for various reasons: different target population (n = 174), non-invasive acupuncture approach (n = 53), non-RCT study design (n = 9), and data could not be extracted (n = 6). Ultimately, 25 studies were selected for further qualitative and quantitative analyses.^{3,7,9,11,16,18,20,29

–46} Figure 1 depicts the review process in the form of a PRISMA flow diagram.

FIG. 1.

PRISMA flow diagram of the review process. RCTs, randomized controlled trials.

Characteristics of the included studies

A total of 25 studies were included in the analysis, with a combined sample size of 1974 participants.^{3,7,9,11,16,18,20,29

–46} These studies employed a randomized controlled design and investigated various types of cancer, including lung cancer, gastric cancer, breast cancer, liver cancer, and lymphomas. The chemotherapeutic regimens utilized in the included studies were also diverse.

The publications covered a time period from 1991 to 2022, and among the 25 studies, 1 was conducted in Portugal,¹¹ 1 took place in the United States,¹⁶ 1 in Australia³⁷; and most of them were carried out in China,^{3,7,9,18,20,29

–36,38

–46} in which, some of the included studies were not described articles in English.^{7,9,18,29
–31,33,35,36,38

–45} Various types of acupuncture interventions were utilized, which included eleven trials of manual acupuncture, eight trials of EA, two trials of acupoint injection, two trials of acupoint catgut-embed, and two trials of warm-acupuncture. Table 1 provides details characteristics of the included studies.

Methodological quality assessment

Table 2 presents data on the methodological rigor of the chosen studies. All of the studies analyzed in the review reported random sequence generation. Nonetheless, two studies failed to report allocation concealment or blinding of participants and personnel, leading to a higher risk of bias.^9,46 Most of the included studies had unclear risk for blinding of participants and personnel.

Table 2.

Risk of Methodological Bias of the Included Studies

Study	Random sequence generation	Allocation concealment	Blinding of participants and personnel	Blinding of outcome assessment	Incomplete outcome data addressed	Selective reporting
Beith et al. (2012)³⁷	L	L	U	U	L	L
Bii (2008)³⁵	L	U	U	H	L	L
Chen and Huang (1991)²⁹	L	U	U	U	H	L
Chen et al. (2004)³³	L	U	U	U	L	L
Gao and Luo (2019)⁷	L	L	U	U	L	L
Han et al. (2010)³⁶	L	U	U	U	L	L
Hou et al. (2017)²⁰	L	L	U	U	L	L
Hu et al. (2016)³⁹	L	U	U	U	L	L
Li et al. (1997)³⁰	L	U	U	U	L	L
Liu Meng et al. (2018)⁴²	L	L	U	U	L	L
Lu et al. (2009)¹⁶	L	L	L	U	L	L
Meng and Lu (2012)³	L	L	H	U	L	L
Ni et al. (2018)⁴³	L	L	U	U	L	L
Pais et al. (2014)¹¹	L	U	U	U	L	L
Yan (2016)⁴⁰	L	L	U	U	L	L
Xinying (2019)⁴⁵	L	L	U	H	L	L
Wu et al. (2018)⁴⁴	L	L	U	U	L	L
Xie et al. (2003)³²	L	U	U	U	H	L
Xie (2013)³⁸	L	L	U	H	L	L
Zhu et al. (2017)⁴¹	L	L	U	U	L	L
Yang (2011)¹⁸	L	U	U	H	L	L
Ye et al. (2007)³⁴	L	U	U	U	L	L
Zhao and Kao (2001)³¹	L	U	U	U	H	L
Zhu et al. (2016)⁹	L	H	H	U	L	L
Zhao et al. (2022)⁴⁶	L	H	H	U	L	L

H, high risk; L, low risk; U, unclear risk of bias.

Only four studies were classified as having high risk for blinding of the outcome assessment,^18,35,38,45 whereas the remaining studies were classified as having unclear risk.^{3,7,9,11,16,20,29

–34,36,37,39

–44,46} In terms of addressing incomplete outcome data, three studies were classified as having high risk,^29,31,32 whereas the remaining studies had low risk. Finally, all of the studies had a low risk of selective reporting.

The overall effect of acupuncture on indicators of bone marrow function

The 25 studies demonstrated significant improvements in the counts of G-CSF white blood cells, RBCs, neutrophils, ANC, Hb, platelets, and NK cells through acupuncture during chemotherapy, as evidenced by the overall effect sizes.^{3,7,9,11,16,18,20,29

–32,34

–46} The overall effect size was Hedges' g of 0.69, p < 0.001, I ² = 70% for increased WBCs by acupuncture (Fig. 3).

A sensitivity analysis was performed by removing the study with the largest effect size.⁴⁴ The effect size of the acupuncture intervention remained statistically significant (Hedges' g = 0.61, p < 0.001) (data not shown). Hedges' g indicated statistical significance for outcomes of G-CSF (Hedges' g = 0.79, p < 0.001, I ² = 0%) (Fig. 2), RBCs (Hedges' g = 0.37, p = 0.01, I ² = 57%) (Fig. 4), neutrophil counts (Hedges' g = 0.66, p < 0.001, I ² = 44%) (Fig. 5), the ANC (Hedges' g = 0.89, p = 0.01, I ² = 0%) (Fig. 6), Hb counts (Hedges' g = 0.37, p = 0.02, I ² = 69%) (Fig. 7), platelet counts (Hedges' g = 0.50, p < 0.001, I ² = 56%) (Fig. 8), and NK cell counts (Hedges' g = 1.30, p = 0.02, I ² = 85%) (Fig. 9).

FIG. 2.

Forest plot of the overall effect sizes for studies measuring G-CSF counts and acupuncture. Q = 0.09, p = 0.76, I ² = 0.00. Fixed-effects Hedges' g = 0.79, p < 0.001. Random-effects Hedges' g = 0.79, p < 0.001. G-CSF, granulocyte colony-stimulating factor.

FIG. 3.

Forest plot of the overall effect sizes for studies measuring WBC counts and acupuncture. Q = 82.11, p < 0.001, I ² = 70.77. Fixed-effects Hedges' g = 0.70, p < 0.001. Random-effects Hedges' g = 0.69, p < 0.001. WBC, white blood cell.

FIG. 4.

Forest plot of the overall effect sizes for studies measuring RBC counts and acupuncture. Q = 7.11, p = 0.07, I ² = 57.79. Fixed-effects Hedges' g = 0.43, p < 0.001. Random-effects Hedges' g = 0.37, p = 0.01. RBC, red blood cell.

FIG. 5.

Forest plot of the effective response of neutrophil counts. Q = 7.24, p = 0.12, I ² = 44.74. Fixed-effects Hedges' g = 0.63, p < 0.001. Random-effects Hedges' g = 0.66, p < 0.001.

FIG. 6.

Forest plot of the effective response of ANCs. Q = 0.06, p = 0.81, I ² = 0.00. Fixed-effects Hedges' g = 0.89, p = 0.01. Random-effects Hedges' g = 0.89, p = 0.01. ANCs, absolute neutrophil counts.

FIG. 7.

Forest plot of the effective response of hemoglobin counts. Q = 16.28, p = 0.01, I ² = 69.28. Fixed-effects Hedges' g = 0.47, p < 0.001. Random-effects Hedges' g = 0.37, p = 0.02.

FIG. 8.

Forest plot of the effective response of platelet counts. Q = 13.86, p = 0.03, I ² = 56.70. Fixed-effects Hedges' g = 0.49, p < 0.001. Random-effects Hedges' g = 0.50, p < 0.001.

FIG. 9.

Forest plot of the effective response of NK-cell counts. Q = 14.02, p = 0.001, I ² = 85.74. Fixed-effects Hedges' g = 0.83, p < 0.001. Random-effects Hedges' g = 1.30, p = 0.02. NK, natural killer.

Moderator analyses

I² statistics indicated moderate heterogeneity of WBC values (Q = 82.11, p < 0.001, I ² = 70%), RBC (Q = 7.11, p = 0.07, I ² = 57%), Hb (Q = 16.28, p = 0.01, I² = 69%) and platelet values (Q = 13.86, p = 0.03, I ² = 56%), and neutrophil (Q = 7.23, p = 0.12, I ² = 44%) across the included studies. High heterogeneity of NK-cell values (Q = 14.02, p = 0.001, I ² = 85%) was observed. In addition, the G-CSF and ANC was homogeneous. Therefore, subgroup analyses and a meta-regression were performed on NK cells to further explore factors that might have contributed to the heterogeneity.

Subgroup analyses

Regarding heterogeneity, the subgroup analyses examined different acupuncture types of WBCs, platelets, NK cells, and neutrophils. However, the mixed effects for types of acupuncture groups were not significant (WBC: Q = 5.04, p = 0.28; platelets: Q = 3.19, p = 0.07, NK cells: Q = 3.00, p = 0.08; neutrophils: Q = 4.37, p = 0.11). This suggested that regardless of the type of acupuncture, WBCs, platelets, NK cells, and neutrophils increased overall. Data are not shown.

Meta-regression analyses

For continuous moderators, the meta-regression analyses revealed that cumulative time-dependent responses of acupuncture and NK cells, platelets significantly increased (p = 0.005, and p = 0.001, respectively). This implied that the cumulative time-dependent responses of NK cells and platelets increased over time. The data are shown in Figures 10 and 11. The WBCs showed the trend increased over time but not statistically significantly. Other blood indicators were not significantly increased.

FIG. 10.

Meta-regression analyses performed by different total treatment doses (min) for NK cells. NK, natural killer.

FIG. 11.

Meta-regression analyses performed by different total treatment doses (min) for platelet counts.

Publication bias

No significant publication bias existed for the main blood indicators in WBC. The results of Egger's regression test are displayed in Figure 12, with a t-value of 0.06 and a p-value of 0.95. Publication bias was not evaluated for other blood indicators, because there were fewer than ten studies for the funnel plot.

FIG. 12.

Funnel plot of the meta-analysis of included papers that examined WBC counts. Egger's test showed that the t value was 0.06, p = 0.95. WBC, white blood cell.

Trial sequential analysis

TSA was utilized to investigate the effects of acupuncture on bone marrow suppression across 14 trials^{9,18,20,30,34,36,38

–45} A random-effects model was utilized to generate the cumulative z-curve, with an α value of 5% (two-sided) and β of 20%. The necessary information size was determined to be 263, and the z-curve intersected both the conventional and trial sequential monitoring boundaries, meeting the required information size. As a result, there is enough evidence to reach a conclusion (as depicted in Fig. 13). However, the TSA data only presented the impact of acupuncture on myelosuppression for the main outcome of WBCs, as there were insufficient data available for other indicators.

FIG. 13.

Trial sequential analysis of the effects of bone marrow suppression and acupuncture.

Discussion

The current meta-analysis consists of 25 RCTs indicated, the significant effect of invasive acupuncture for ameliorating myelosuppression when cancer patients are undergoing chemotherapy.^{3,7,9,11,16,18,20,29

–46} Based on previous research, acupuncture may relieve bone marrow suppression and increase G-CSF production, thereby further improving hematopoietic function during chemotherapy.^47,48 The possible mechanism would be the G-CSF-stimulated increased neutrophil proliferation and differentiation, with blood cell counts for the ANC, WBCs, Hb, and platelets subsequently being enhanced.

The G-CSF is a kind of hematopoietic cytokine, and it has a vital role in modulating hematopoiesis.⁴⁹ The G-CSF stimulates hematopoietic stem cells to produce granulocytes and stem cells and release them into the bloodstream. The G-CSF also stimulates the survival, proliferation, differentiation, and function of neutrophil precursors and mature neutrophils via signal transduction pathways.^49,50

The G-CSF is a glycoprotein that has multiple functions in both physiological and pathophysiological conditions.⁵¹ From a biological perspective, an increase in G-CSF levels might be a possible mechanism underlying the effectiveness of acupuncture in patients undergoing chemotherapy, and it would be valuable to hypothesize a causal pathway that might explain this association.⁴⁷

In addition, the primary concern of cancer patient's health status is chemotherapy-induced pancytopenia, which refers to myelosuppression.¹⁰ The findings of the current meta-analysis of RCTs showed that acupuncture was associated with increased bone marrow function during chemotherapy.

Acupuncture has been found to increase granulocyte counts, including neutrophils and WBCs, as well as the ANC, according to a meta-analysis. A study by Pais et al. suggested that acupuncture is effective in boosting the immune system. Their RCT showed that acupuncture led to a statistically significant overall enhancement of WBCs, ANC, and NK cells in the acupuncture group (p = 0.036, p = 0.046, and p < 0.001, respectively).¹¹

In contrast, Lu et al.'s RCT consisted of 21 gynecologic cancer patients undergoing chemotherapy who were included and randomly assigned to either the acupuncture group or the sham acupuncture group. The sham acupuncture group involved inserting needles away from the usual TCM acupuncture points. The study evaluated the impact of treatment on WBCs, ANC, and G-CSF levels.

After six sessions, the WBC values were significantly higher in the acupuncture group (p = 0.04); however, no significant differences were observed between the acupuncture and sham groups for ANC and G-CSF values (p = 0.09 and p = 0.78, respectively). The study's small sample size (n = 21) may have contributed to the lack of significant differences in ANC and G-CSF levels.¹⁶

The findings of this meta-analysis revealed that platelet values were higher than those of the control group due to the effect of acupuncture. This finding is consistent with a meta-analysis of 35 RCT studies by Li et al,⁵² involving 2618 patients. They investigated the effect of acupoint stimulation on chemotherapy for non-small cell lung cancer, and leukocytopenia, thrombocytopenia, and immune function significantly improved overall.

Large effect sizes were exhibited in WBC values (Z = 7.45, 95% CI = 0.46–0.63) (p < 0.001), platelets (Z = 3.40, 95% CI = 0.36–0.76), and NK cells (Z = 4.08, 95% CI = 1.18–3.36), but not in Hb (Z = 1.32, 95% CI = 0.34–1.24, p = 0.19).⁵² However, some scholars had contrary opinions, as an acupoint stimulation RCT study comprised 28 women with gynecological cancer revealed that Hb significantly decreased from (mean ± standard deviation [SD]) 11.6 ± 2.2 to 10.8 ± 1.6 mg/dL (p = 0.03) in the control group, compared with the experimental group (mean ± SD) 11.4 ± 1.0 to 10.9 ± 1.1 mg/dL (p = 0.29).

Those findings suggested that acupoint stimulation may be associated with preventing chemotherapy-induced myelosuppression hypochromia,⁶ the results of which are similar to our findings.

Acupuncture can regulate immune function among cancer patients by two cytokines: interleukin (IL)-2 and interferon (IFN)-α, which then stimulate NK-cell proliferation and differentiation.⁴⁹ Johnston et al.,⁵³ using normal rats with EA applied at the Zu-Sanli point (ST36) for 2 h daily on 3 consecutive days, found enhanced values of NK cells compared with the non-acupuncture control group.⁵³

In addition, a previous in vivo study suggested that acupuncture is useful in anticancer therapy either by actively stimulating immune activity or by preventing chemotherapy suppression of immune activity.³⁴ One study discovered that acupuncture treatment significantly increased NK-cell activity in mice with mammary cancer compared with the control group (p < 0.05) after eight sessions.⁵⁴

In addition, a recent study demonstrated that patients with stage IIb–IIIb cervical squamous cell carcinoma who underwent four cycles of cisplatin combined with EA treatment had increased NK cells in their peripheral blood and reduced tumor volumes.⁵⁵

To investigate further heterogeneity, a subgroup analysis was conducted to examine the effect of different types of acupuncture on the increase in WBCs. The analysis revealed that no matter of the manner for acupuncture used, there was an overall increase in leucocytes (mixed-effects model: Q = 5.04, p = 0.28). The current finding aligns with the outcomes of a prior meta-analysis that suggested that diverse types of acupuncture, such as needle insertion at acupoints, acupoint injection, plaster application, and moxibustion, can boost the immune response of cancer patients undergoing chemotherapy and improve myelosuppression via blood regulation.⁵⁶

In addition, different modalities of acupoint stimulation, such as EA, transcutaneous electrical acupoint stimulation (TEAS), and moxibustion, have been shown to improve myelosuppression and immunosuppression in patients undergoing chemotherapy.¹ There is a randomized control trial comprising 100 lung cancer patients, who were treated with chemotherapy and combined with TEAS for chemotherapy-induced immunosuppression.

The results indicated that the leukocyte and platelet counts were significantly enhanced within 2 weeks by TEAS.²⁰ And another pilot showed that acupuncture was an effective method for boosting leukocyte, neutrophil, and NK cells in patients with colorectal cancer after chemotherapy.¹¹ Thus, it can be concluded that the peripheral leukocyte and immune cell counts can be enhanced by acupoint stimulation, which is also an efficacious method of preventing myelosuppression and ameliorating immunosuppression in chemotherapy-related side effects.

The meta-regression analyses in this study revealed that levels of platelets and NK cells significantly increased in cumulative time-dependent manners, and the WBCs increased over time. A noteworthy discovery from an RCT is that acupoint stimulation had a significant interactive effect with time on SCF elevation. SCF is a cytokine that promotes the growth and differentiation of progenitor cells, and it is responsible for the maturation of granulocytes, lymphocytes, megakaryocytes, and erythrocytes.⁶

They further indicated that the interactive effect was borderline significant after 3 weeks (p = 0.05), whereas the effect of the intervention on the group was significant after 6 weeks (p = 0.02).⁶ This possibly implies that the efficacy of blood cells cumulatively time-dependently increases over time. Importantly, the cumulative time-dependent increased responses of WBCs, platelets, and NK cells were proven by the current meta-analysis results. Therefore, WBC, platelets, and NK cells increased due to acupuncture over time.

Anemia, thrombocytopenia, and pancytopenia are the most common symptoms of bone marrow suppression during chemotherapy.²¹ The findings of the current study indicated that acupuncture improved bone marrow function during chemotherapy and increased values of WBCs, RBCs, neutrophils, the ANC, Hb, platelets, and NK cells. The possible mechanism is that acupuncture can enhance G-CSF.⁵⁷

The G-CSF is a key role in modulating hematopoiesis, and acupoint stimulation by acupuncture may increase the level of G-CSF, boosting the production of blood cells, and stimulate growth and differentiation of the megakaryocyte erythroid progenitor, which benefits the proliferation of erythrocytes, platelets, and the granulocyte-macrophage progenitor, which is associated with the production of mature blood cell components of neutrophils, the ANC, and WBCs.⁵⁷

The earlier mentioned findings summarize our findings that acupuncture is an effective approach to improve the production of the SCF, and further activate the G-CSF that prompts hematopoietic stem/progenitor cell proliferation, enhancing the production of blood cells, and eventually relieves chemotherapy-related myelosuppression^.6,16,57 The mechanism of hematopoietic regulation on acupuncture ameliorates myelosuppressive-related chemotherapy may involve these two cytokines, particularly of G-CSF, which could be demonstrated in our study.

Limitations and recommendations

First, although all included studies used random allocation, only a few reported the specific method, which may introduce selection bias. In addition, many studies had unclear descriptions of double-blinding or blinding during outcome assessments, which could lead to performance and detection bias. However, it may be difficult to implement blinding of participants in clinical trials.

Second, there was poor consistency between the selection of acupoints and the chemotherapy regimens, doses, duration, and center setting among the included studies, resulting in heterogeneity in the meta-analysis. As a result, the validity of this study may be significantly undermined, and caution should be exercised when interpreting the results. Given the unclear risk of bias in the methodology of many included studies, additional high-quality and rigorous trials are needed.

Lastly, the effect was assessed by very few studies in many cases, and many of the studies suffered from methodological bias, which could threaten the validity of the meta-analyses. Therefore, conclusions drawn from these results should be made with caution.

Conclusions

This meta-analysis of acupuncture effects on chemotherapy-induced bone marrow suppression pooled together existing data of 25 relevant studies. Analysis of the pooled data with a random-effects model showed that chemotherapy-induced bone marrow suppression was relieved by acupuncture. The levels of G-CSF, WBC, neutrophil, ANC, Hb, platelet, and NK cell were increased significantly by acupuncture with cancer patients during chemotherapy.

In addition, despite acupuncture modalities, the levels of WBCs, platelets, and NK cells increased in a cumulative-time manner. These findings are actionable and provide for patients suffering from chemotherapy-related immunosuppression.

Footnotes

Authors' Contributions

The authors' roles in this project were as follows: Y.W.S. and H.T.T. contributed to the conceptualization, Y.W.S., M.H.W., and Y.A.R. were responsible for the methodology, including screening papers for eligibility, appraising study quality, extracting data, and seeking additional information. Y.A.R. worked on software, and C.W.C. conducted validation. Y.W.S. performed formal analysis, whereas Y.W.S., C.W.C., K.A.M., and H.T.T. contributed to the writing of the original draft, and Y.W.S., C.W.C., K.A.M., and H.T.T. participated in the writing-review and editing process. H.T.T. provided supervision. All authors have read and approved the manuscript's published version.

Availability of Data and Materials

Upon reasonable request, the corresponding author can grant access to all the data that were collected and analyzed during the study.

Ethics Approval and Consent to Participate

Not applicable.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

This study was supported by grant nos. MOST 109-2314-B-038-110-, MOST 110-2314-B-038-081-MY3 from the Ministry of Science and Technology, Taiwan, and The National Taipei University of Nursing and Health Sciences (111ntunhs-NT-01). The study design, data collection, data analysis, decision to publish, and manuscript preparation were not influenced by the funders.

Supplementary Material

Supplementary Data S1

Supplementary Table S1

References

Huang

, Li

, et al. [Systematic review and Meta-analysis on chemotherapy-induced bone marrow suppression treated with acupuncture]. Zhongguo Zhen Jiu, 2021; 41(5):557–562; doi: 10.13703/j.0255-2930.20200618-k0005

Zia

, Olaku

, Bao

, et al. The National Cancer Institute's Conference on Acupuncture for Symptom Management in Oncology: State of the science, evidence, and research gaps. JNCI Monogr, 2017; 2017(52); doi: 10.1093/jncimonographs/lgx005

Meng

, Lü

. Twenty-seven cases of adverse reaction in postoperative chemotherapy of breast cancer treated with acupoint catgut-embedding therapy. World J Acupunct Moxibustion, 2012; 22(2):64–67; doi: 10.1016/S1003-5257(12)60031-2

Arroyo-Crespo

, Armiñán

, Charbonnier

, et al. Characterization of triple-negative breast cancer preclinical models provides functional evidence of metastatic progression. Int J Cancer, 2019; 145(8):2267–2281; doi: 10.1002/ijc.32270

Aras

, Bayraktar-Ekincioglu

, Kilickap

. Risk assessment of febrile neutropenia and evaluation of G-CSF use in patients with cancer: A real-life study. Support Care Cancer, 2020; 28(2):691–699; doi: 10.1007/s00520-019-04879-x

Shih

, Yang

, Chien

, et al. Significant effect of acupressure in elevating blood stem cell factor during chemotherapy in patients with gynecologic cancer. J Nurs Res, 2018; 26(6):411–419; doi: 10.1097/jnr.0000000000000257

Gao

, Lau

. The effect of percutaneous electrical stimulation on bone marrow suppression and bad mood in patients with lung cancer undergoing chemotherapy. Chin Med Mod Distance Educ China, 2019; 17(7):72–73.

Zoorob

, Sidani

, Williams

, et al. Women's health: Selected topics. Primary Care Clin Off Pract, 2010; 37(2):367–387; doi: 10.1016/j.pop.2010.02.011

Zhu

, Lu

, et al. Clinical observation of Qi-blood-supplementing needling for Leukopenia after chemotherapy for breast cancer. Shanghai J Acupunct Moxibustion [shang hai zhen jiu za zhi], 2016; 35(8):964–966.

10.

, Chung

VCH

, Hui

, et al. Effectiveness of acupuncture and related therapies for palliative care of cancer: Overview of systematic reviews. J Altern Complement Med, 2016; 22(6):A47; doi: 10.1089/acm.2016.29003.abstracts

11.

Pais

, Correia

, Pimentel

, et al. Effects of acupuncture on leucopenia, neutropenia, NK, and B cells in cancer patients: A randomized pilot study. Evid Based Complement Altern Med, 2014; 9; doi:10.1155/2014/217397

12.

, Yu

, Yang

, et al. Effect of acupuncture in prevention and treatment of chemotherapy-induced nausea and vomiting in patients with advanced cancer: Study protocol for a randomized controlled trial. Trials, 2017; 18(1):185; doi: 10.1186/s13063-017-1927-2

13.

Bao

, Seidman

, Piulson

, et al. A phase IIA trial of acupuncture to reduce chemotherapy-induced peripheral neuropathy severity during neoadjuvant or adjuvant weekly paclitaxel chemotherapy in breast cancer patients. Eur J Cancer, 2018; 101:12–19; doi: 10.1016/j.ejca.2018.06.008

14.

Molasiotis

, Cheng

. A randomized assessor-blinded wait-list controlled trial to assess the effectiveness and cost-effectiveness of acupuncture in the management of chemotherapy-induced peripheral neuropathy. Support Care Cancer, 2019; 27(1):S13; doi: 10.1007/s00520-019-04813-1

15.

Shih

, Su

, Kung

, et al. Effectiveness of acupuncture in relieving chemotherapy-induced leukopenia in patients with breast cancer: A systematic review with a meta-analysis and trial sequential analysis. Integr Cancer Ther, 2021; 20:15347354211063884; doi: 10.1177/15347354211063884

16.

, Matulonis

, Doherty-Gilman

, et al. Acupuncture for chemotherapy-induced neutropenia in patients with gynecologic malignancies: A pilot randomized, sham-controlled clinical trial. J Altern Complement Med, 2009; 15(7):745–753; doi: 10.1089/acm.2008.0589

17.

Nian

, Sun

, Zhao

, et al. Efficacy and safety of acupuncture for chemotherapy-induced leukopenia: A systematic review and meta-analysis. Medicine (Baltimore), 2022; 101(42):e30995; doi: 10.1097/md.0000000000030995

18.

Yang

ZQ.

The cure of the deficient blood and Qi type of post-chemotherapy leucopenia by the use of Acupuncture combined with ginger-partitioned moxiibustion. Dissertation for doctor degree of Guangzhou University of Chinese Medicine [guang zhou zhong yi yao da xue shuo shi BI ye lun wen], 2011; 1–45.

19.

, Chen

, Hong

, et al. Acupuncture therapy for the treatment of myelosuppression after chemotherapy: A literature review over the past 10 years. J Acupunct Meridian Stud, 2015; 8(3):122–126; doi: 10.1016/j.jams.2014.09.003

20.

Hou

, Gu

, Gao

, et al. Transcutaneous electrical acupoint stimulation (TEAS) ameliorates chemotherapy-induced bone marrow suppression in lung cancer patients. J Thorac Dis, 2017; 9(3):809–817; doi: 10.21037/jtd.2017.03.12

21.

, Liu

, Fang

, et al. Traditional Chinese medicine preparation combined therapy may improve chemotherapy efficacy: A systematic review and meta-Analysis. Evid Based Complement Altern Med, 2019; 2019:5015824; doi: 10.1155/2019/5015824

22.

Higgins

JPT

, Green S (eds.). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from: www.handbook.cochrane.org

23.

Walker

DA.

JMASM34: Two group program for Cohen's d, Hedges'g, η2, Radj2, ω2, ɛ2, confidence intervals, and power. J Mod Appl Stat Methods, 2015; 14(2):282–292; doi: 10.22237/jmasm/1446351600

24.

Borenstein

, Hedges

, Higgins

et al. Introduction to Meta-Analysis. Wiley: Hoboken; 2009.

25.

Lipsey

, Wilson

Practical Meta Analysis. Sage: Thousand Oaks; 2001.

26.

Egger

, Davey Smith

, Schneider

, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ, 1997; 315(7109):629–634; doi: 10.1136/bmj.315.7109.629

27.

Lau

, Ioannidis

, Terrin

, et al. The case of the misleading funnel plot. BMJ (Clinical research ed), 2006; 333(7568):597–600; doi: 10.1136/bmj.333.7568.597

28.

Wetterslev

, Jakobsen

, Gluud

. Trial Sequential Analysis in systematic reviews with meta-analysis. BMC Med Res Methodol, 2017; 17(1):39; doi: 10.1186/s12874-017-0315-7

29.

Chen

, Huang

. [Treatment of chemotherapy-induced leukocytopenia with acupuncture and moxibustion]. Zhong Xi Yi Jie He Za Zhi, 1991;11(6):350–352, 325.

30.

, Yu

, Dai

. Analysis of pattern recognition of manipulation controlled needling sensation of soreness, distension, numbness. Chin Acuponct Moxibustion, 1997; 6:327–328.

31.

Zhao Xiaoqing

GX.

Treating arrest of bone marrow in tumor patients after chemotherapy with acupuncture therapy. Shandong J Tradit Chinese Med, 2001; 20(5):349–350.

32.

Xie

, Zhao

, Li

. Zusanli point injection for treating leukopenia induced by radio-chemotherapy. J Tradit Chin Med, 2003; 23(1):59–61.

33.

Chen Chuang

ZZ-J

, Li

H-Z

, Tan

Z-Q

, et al. Clinical observation on effect of electroacupuncture at Zusanli point on chemotherapy attenuation. New Tradit Chin Med, 2004; 36(3):46–47; doi: 10.13457/j.cnki.jncm.2004.03.024

34.

, Liu

, Wang

, et al. Effects of electro-acupuncture on T cell subpopulations, NK activity, humoral immunity and leukocyte count in patients undergoing chemotherapy. J Tradit Chin Med, 2007; 27(1):19–21.

35.

Bii

YZ.

The Clinical Study of the Effect of Electro-acupuncture in Preventing and Treating Bone Marrow Inhibition Caused by Chemotherapy. Guangzhou University of Chinese Medicine: China; 2008.

36.

Han

, Gong

, Huang

, et al. [Clinical study on acupuncture for leukopenia induced by chemotherapy]. Zhongguo Zhen Jiu, 2010; 30(10):802–805.

37.

Beith

, Oh

, Chatfield

, et al. Electroacupuncture for nausea, vomiting, and myelosuppression in women receiving adjuvant chemotherapy for early breast cancer: A randomized controlled pilot trial. Med Acupunct, 2012; 24(4):241–248; doi: 10.1089/acu.2012.0876

38.

Xie

. The Study of Acupuncture in the Treatment of Malignant Tumors After Chemotherapy Toxicity. Guangzhou University of Chinese Medicine: 2013.

39.

, Wang

, Zhao

. Effect of acupuncture treatment on the first WBC reduction symptom after breast cancer chemotherapy. Beijing J Tradit Chin Med, 2016; 35(8):777–778.

40.

Yan

CliIlical effect of transcutanclus electrical acupoint stimulation for patients with non-small cell lung cancer during chemotherapy. Nurs Integr Tradit Chin West Med, 2016; 2(8):7–9.

41.

Xie

, Chen

, Li

, et al. Clinical study of acupoint catgut-embedding therapy for prevention and treatment of bone marrow depression in breast cancer patients induced by FEC chemotherapy. J Guangzhou Univ Tradit Chin Med, 2017; 34(4):530–534.

42.

Liu Meng

, Cheng

. Effects of acupuncture on myelosuppression and quality of life in chemotherapy patients with colorectal cancer. Acad J Shanghai Univ Tradit Chin Med, 2018; 32(2):23–26.

43.

, Duan

, Chen

. The efficacy of acupuncture as main intervention in reducing adverse reactions to chemotherapy and improving bodily immunity. Shanghai J Acupunct Moxibustion, 2018; 37(9).

44.

Wu Guoliang

, Li

, Dai

, et al. Lin Fusheng study of acupuncture treatment preventing bone marrow suppression during chemotherapy. Harbin Med J, 2018; 38(1):81–83.

45.

Xinying

Clinical Study on the Side-Effect of “TiaoRen TongDu” Acupuncture Method on Chemotherapeutic Drugs For Breast Cancer. Nanjing University of Chinese Medicine: Nanjing; 2019.

46.

Zhao

, Du

, Liu

, et al. To Explore the effects of acupuncture and medical treatment at different times on the gastrointestinal reaction and white blood cell count of patients with lung cancer chemotherapy. Appl Bionics Biomech, 2022; 2022:5261344; doi: 10.1155/2022/5261344

47.

Lee

, Jang

, Jung

, et al. Clinical effectiveness of acupuncture in the treatment of chemotherapy-induced leukopenia: A systematic review. Eur J Integr Med, 2016; 8(5):802–808; doi: 10.1016/j.eujim.2016.08.165

48.

Fraczek

, Kilian-Kita

, Püsküllüoglu

, et al. Acupuncture as anticancer treatment?. Wspolczesna Onkol, 2016; 20(6):453–457; doi: 10.5114/wo.2016.65604

49.

Sievers

The immunomodulatory effects of acupuncture in healthy aging and chronic disease conditions: A systematic review of the effectiveness of acupuncture in modulating the immune system as measured by immune system serum biomarkers and the implications of acupuncture as a healthy aging strategy for treating chronic degenerative inflammatory diseases and immunosenescence in an aging population. J Altern Complement Med, 2016; 22(6):A44–A45; doi: 10.1089/acm.2016.29003.abstracts

50.

, Chen

, Liu

. Effects of electro-acupuncture on immune function after chemotherapy in 28 cases. J Tradit Chin Med, 2002; 22(1):21–23.

51.

Vieira

, Paulo

, Martinsa

. Advantages of the use of acupuncture in oncology patients: Report of two cases. Rev Int Acupunt, 2016; 10(4):126–130; doi: 10.1016/j.acu.2016.11.001

52.

, Ji

, Zhang

, et al. Kangai injection combined with platinum-based chemotherapy for the treatment of stage III/IV non-small cell lung cancer: A meta-analysis and systematic review of 35 randomized controlled trials. J Cancer, 2019; 10(21):5283–5298; doi: 10.7150/jca.31928

53.

Johnston

, Ortiz Sánchez

, Vujanovic

, et al. Acupuncture may stimulate anticancer immunity via activation of natural killer cells. Evid Based Complement Altern Med, 2011; 2011:481625–481625; doi: 10.1093/ecam/nep236

54.

Liu

, Guo

, Jiao

. [Effect of acupuncture on immunologic function and histopathology of transplanted mammary cancer in mice]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 1995; 15(10):615–617.

55.

Saraswati

, Dahlan

, Saputra

, et al. Effect of electroacupuncture on natural-killer cells and tumor size in patients with cervical squamous-cell carcinoma: A randomized controlled trial. Med Acupunct, 2019; 31(1):29–36; doi: 10.1089/acu.2018.1316

56.

Chen

, Li

, Cho

, et al. The role of acupoint stimulation as an adjunct therapy for lung cancer: A systematic review and meta-analysis. BMC Complement Altern Med, 2013; 13:362; doi: 10.1186/1472-6882-13-362

57.

, Xiao

, Cao

, et al. Effects of acupuncture and moxibustion on serum contents of hematopoietic growth factor in mice with marrow inhibition. Zhongguo Zhen Jiu, 2015; 35(3):264–268.

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