Acupuncture for treatment-induced leukopenia

Acupuncture typically entails needling specific points of the body surface. According to Traditional Chinese Medicine (TCM) philosophy, illness is caused by imbalances of energies in the body, while acupuncture is a treatment that re-balances energies. Therefore, it is claimed by TCM-practitioners to be helpful in many health-related problems. By contrast, most Western acupuncturists follow the principles of conventional medicine and would employ acupuncture only for specific conditions. Yet both types of practitioners might advocate acupuncture for a wide range of conditions and symptoms. Treatment-induced leukopenia (reduced number of white blood cells) is one condition for which acupuncture treatment has been suggested. 

  • The evidence for the effectiveness of acupuncture for this indication is very limited. Systematic reviews (including 11 trials assessing leukocyte counts) as well as two additional trials are available. Trials are mostly published in Chinese and thus difficult to access; more importantly, they are all of poor methodological quality.
  • Two reviews of moxibustion, one thereof a Cochrane review (n=25 small RCTs), concluded that although some small trials showed some positive effects they were all at high risk of bias.
  • More recent evidence in the form of a systematic review of 17 studies from China of both acupuncture and moxibustion did not provide conclusive evidence of effectiveness.Results from one RCT (n=191) of transcutaneous electrical acupuncture stimulation on bone marrow suppression are not consistent showing higher white blood cell counts compared to control at some selected time points but not others.

Mild adverse effects, e.g. pain or bleeding at the site of acupuncture can be expected in about 10% of all cases, and serious complications, such as pneumothorax and hepatitis, seem to be very rare.

Citation

Pilkington K, Ernst E, CAM Cancer Consortium. Acupuncture for treatment-induced leukopenia [online document], Jun 8, 2021.

Document history

Latest update: June 2021
Next update due: June 2024

Description

Acupuncture refers to the insertion of fine needles at specific points (acupuncture points or acupoints) on the body for the prevention or treatment of disease or the maintenance of health. The term ‘acupuncture’ is derived from Latin and means ‘piercing with a sharp instrument’ from acus, ‘needle’ (noun), and pungere, ‘to prick or puncture’ (verb).

Acupuncture is usually performed with fine, solid needles but many variations exist. ‘Acupoints’ might, for instance, be stimulated by electrical currents with or without needles (electro-acupuncture), by pressure (acupressure involving use of ‘press’ needles, studs or manual pressure), by heat (moxibustion) or laser light (laser-acupuncture). Techniques that do not involve the insertion of needles are not always classed as acupuncture.

Acupuncture is often part of a complex intervention that includes use of herbal mixtures, moxibustion (burning of herbs), and dietary and lifestyle advice.

Background and prevalence

The history of acupuncture can be traced to ancient China and its Taoist philosophy (White 1999). It has been practised in China for more than 2000 years and in other East Asian countries, including Japan, Korea and Vietnam, for between 1000 to 2000 years arriving in Europe several hundred years ago (Birch 1999). In traditional Chinese medicine (TCM), the life energy ‘Qi’ flowing through the body in meridians and the balance of ‘yin’ and ‘yang’ are thought to determine human health. Illness is seen as an imbalance of these energies and acupuncture is perceived to be one method for re-balancing the imbalance. Traditionally, acupuncture was not used primarily for specific problems such as pain control but to treat a wide range of symptoms or problems based on the pattern of diagnosis (Birch 1999). Yet, in recent years, pain-control seems to have become its main purpose in many clinical settings.

Acupuncture became particularly popular outside Asia after the US president Richard Nixon visited China in 1971 (White 1999). Acupuncture treatments were originally provided by traditional acupuncturists but, as interest in the technique extended, health professionals adopted and adapted the techniques, using acupuncture alongside conventional treatment.

In many countries, acupuncture is now one of the most popular forms of CAM. Most modern pain clinics and many oncology centres across the world routinely offer acupuncture as one of several therapeutic options. Exact prevalence figures vary from country to country and from setting to setting. A survey of cancer patients in Europe reported use of acupuncture by between 2 to 4% of patients before and after diagnosis but use varied by cancer type, for example, acupuncture was used by up to 17% of gynaecological cancer patients (Molassiotis 2006, Molassiotis 2005). Acupuncture was the therapy most frequently provided by integrative oncology centres across Europe, being provided by 55% of 47 centres (Rossi 2015).

Application and providers

Acupuncture is applied to the body surface including the ears and scalp. The dosage (number of points stimulated, depth of needle insertion, duration of stimulation and frequency and duration of treatment sessions) depends on the condition treated. Sometimes only one acupoint is stimulated; more commonly several needles are applied. A specific area of the body (for example, ear-acupuncture) may be treated but, more commonly, several areas are needled. Needles are usually removed after a 30 minute treatment session but press needles and studs may be left for several days or, in some cases, weeks. Needles may be stimulated by manual manipulation or left unstimulated. Treatments may be repeated at regular intervals, for example once or twice weekly, or treatment can comprise of a single session.

The placement of needles is determined by the condition being treated and, to some extent, by the type of acupuncture being applied. In traditional Chinese or East Asian forms of acupuncture, acupoints are considered to be located along channels or ‘meridians’ through which a vital force or energy (‘Qi’) flows (BAcC 2019). Diagnosis is carried out using a number of methods including peripheral pulses, the appearance of the tongue, speech, history and overall impressions of the patient. The ‘symptom pattern’ and underlying ‘imbalances’ guide selection of points. In ‘Western medical’ acupuncture, points are selected according to contemporary neurophysiology and are considered to be sites where external stimuli result in a greater sensory stimulus, so-called ‘trigger points’ (Filshie 1999, White 2009).

Alleged indications

According to TCM concepts, acupuncture is a therapy for most symptoms and diseases. Modern Western concepts are centred around conditions likely to be influenced through effects on neurotransmitters, such as musculoskeletal pain and nausea and vomiting (White 2009,  Zhao 2008).

Mechanism of actions

Considerable research effort has been focused on finding physiological or histological evidence of the existence of concepts postulated within TCM acupuncture such as Qi, meridians and specific acupuncture points but conclusive proof has not been obtained (Ahn 2008). Neurophysiological theories to explain acupuncture’s modes of action in pain have been developed, e.g. gate-control mechanism, and effects on neurotransmitters like endorphins (Zhao 2008).

Legal issues

In most countries, acupuncture can be administered by both medically-trained and statutorily-regulated health professionals (e.g. doctors, physiotherapists, nurses, midwives) and by non-medically-trained acupuncturists. The regulation of acupuncture varies from one country to another. Information on the regulation of acupuncture in European countries can be found on websites such as that of the European Traditional Chinese Medicine Association (ETCMA).

The notion that acupuncture might normalise pathologically low leukocyte counts in cancer patients emerged from several Chinese case series (e.g Wei 1998, Huang1993) and poorly-controlled studies (e.g Chen 1991). Subsequently, several controlled clinical trials were published and summarised in one systematic review (Lu 2007).

  • The evidence for the effectiveness of acupuncture for this indication is very limited. Systematic reviews of acupuncture (including 11 trials assessing leukocyte counts) as well as two additional trials are available. Trials are mostly published in Chinese and thus difficult to access; more importantly, they are all of poor methodological quality.
  • Two reviews of moxibustion, one thereof a Cochrane review (n=25), concluded that although some small trials showed some positive effects they were all at high risk of bias.
  • More recent evidence in the form of a systematic review of 17 studies from China of both acupuncture and moxibustion did not provide conclusive evidence of effectiveness.
  • Results from one RCT (n=191) of transcutaneous electrical acupuncture stimulation on bone marrow suppression are not consistent showing higher white blood cell counts compared to control at some selected time points but not others.

Acupuncture

An overview of systematic reviews of acupuncture for palliative care in cancer included two systematic reviews (Wu 2015). The first review included 11 controlled clinical trials published up to 2004, in which patients were randomised to receive either acupuncture or usual care only (Lu 2007). All the studies were from China and were published in non-Medline listed Chinese journals. Their quality was rated by the review authors to be poor. Patients were treated once a day for 21 days on average. Only 7 trials published leukocyte counts; a meta-analysis across these studies showed a significant increase of leukocyte counts of 1,221 WBC/microliter (WMD 1.22; 95%CI 0.64 to 1.81) in the acupuncture compared to the control groups. The authors of the review concluded that the poor quality of the primary studies and publication bias might have generated a false positive overall impression.

The second review included two trials in breast cancer patients published up to 2008 (Chao 2009). Only one study was controlled but both trials involved injection of a drug at acupuncture points, thus confounding any effects of needling. The methodological quality of both studies was rated as poor.

Since the publication of these reviews, two trials have been published in journals indexed in English language databases.

A randomised pilot RCT compared acupuncture with sham-acupuncture in 21 patients with chemotherapy-induced leukopenia (Lu 2009). The authors reported clinically relevant trends towards normalisation of the leukopenia; however, due to the fact that this was merely a small pilot, no conclusions regarding effectiveness can be drawn from this study.

A Chinese team randomised 86 patients with chemotherapy-induced leukopenia into receiving granulocyte colony-stimulating factor with or without acupuncture (Han 2010). After 10, 17 and 24 days, the leukocyte counts were higher in the group receiving acupuncture. Apparently, there were no inter-group differences at the end of the follow-up period at 45 days. The study was published in Chinese, and only an English abstract is available which omits important details; interpretation of its results is therefore problematic.

A systematic review has recently been published on acupuncture-moxibustion therapy (AMT) for leukopenia (Jin 2020). Nine databases (English and Chinese) were searched up to September 2020 for trials of either acupuncture or moxibustion compared with conventional leukocyte-enhancing drugs (e.g., leucogen tablets, berbamine hydrochloride tablets, and rhG-CSF injection) or no treatment. A total of 17 studies (1206 patients) were included.  All the included studies were conducted in China and published from 2010 to 2019 (it is unclear why studies prior to 2010 were not included). The authors reported that 12 of the 17 trials were of acupuncture therapy and 5 of moxibustion but the table of studies indicate that 12 were of moxibustion.  Several of the trials were unpublished dissertations and Chinese herbs were used as control interventions in two trials. Three of the studies were included in the Cochrane review of moxibustion (discussed below). The general quality of all the trials was rated as moderate as relevant information was often missing or incomplete. Based on Cochrane risk of bias assessments it appears that the risk of bias was unclear due to lack of details on allocation concealment and blinding. Heterogeneity of the results was substantial (I2 = 92%) possibly due to the different test and control interventions but this was not adequately investigated. Thus, there are concerns about methods and reporting of this systematic review and the trials on which conclusions were based. Results showing that AMT was more effective than conventional treatment in improving leukocyte counts (MD 1.10; 95% CI, 0.67–1.53; P < 0.00001) and the claim that AMT is a safe and effective alternative for the patients with leukopenia must be viewed with caution.

Moxibustion

Moxibustion (burning of a herb above acupuncture points) which is often considered part of acupuncture therapy has also been assessed. A 2018 Cochrane review of 25 heterogeneous RCTs report small single studies showing various beneficial effects of moxibustion including increasing blood cell counts (Zhang 2018). Poor reporting and high risk of bias affected confidence in this evidence. Similar results were reported in a previous systematic review which included 6 RCTs with a total of 681 patients (Choi 2015). All the studies had a high risk of bias and evidence was judged to be low level on the superiority of moxibustion over drug therapies in the treatment of chemotherapy-induced leukopenia.

A more recent systematic review which included trials of moxibustion is described above (Jin 2020).

Transcutaneous electrical acupuncture stimulation (TEAS)

A Chinese team carried out a 3-arm randomised controlled trial to assess the effects of transcutaneous electrical acupoint stimulation (TEAS) on bone marrow suppression (Hou 2017). A total of 191 chemotherapy naive non-small cell lung cancer patients participated. They were allocated to routine nursing care (control group), oral administration of prophylactic agents (medication group) or TEAS at set acupoints. White blood cell counts were significantly higher in the TEAS group compared with the control group on days 8 and 14. While the authors suggested this was a positive result, no such significant results were seen at other time points (days 11, 21, 28).

Adverse events

In about 8-10% of all patients, acupuncture causes mild, transient adverse effects such as pain, haematoma or bleeding at the site of needling (White 1997, Witt 2009). Most commonly reported problems are local pain (3.3%), bruising (3.2%), minor bleeding (1.4%), and orthostatic problems (0.5%) (Melchart 2004).   In addition, in rare cases complications due to tissue trauma, pneumothorax, cardiac tamponade or infection are on record (White 2004). Risk of cross-infection of blood borne disease, particularly hepatitis B, is minimised by the use of sterile disposable needles, and immunisation of acupuncturists. Rare cases of fatalities after acupuncture treatment have been reported although causality was not confirmed in many of these reports (Ernst 2010).

Safety incidents have been assessed that were linked to acupuncture treatments received in a healthcare setting (UK National Health Service) (Wheway 2012). The 325 incidents over a 3 year period included retained needles (31%), dizziness (30%), loss of consciousness/unresponsive (19%), falls (4%), bruising or soreness at needle site (2%), pneumothorax (1%) and other adverse reactions (12%). The majority (95%) of the incidents were categorised as low or no harm.

Contraindications

Professional bodies for acupuncture vary somewhat in defining contraindications, particularly in relation to pregnancy (BAcC 2021, BMAS 2021). Bleeding abnormalities and anticoagulant treatment, oedema, epilepsy, pregnancy and needle phobia are among those conditions that have been suggested as relative, or in some cases absolute, contra-indications. Some points are considered ‘forbidden’ or not to be used for acupuncture needling.

Interactions

None known, except for electro-acupuncture where the electrical current might interfere with pacemakers and is used with caution in epilepsy (Filshie 1999).

Warnings

Strict asepsis and use of sterile disposable needles are mandatory to avoid infections. Some patients faint during acupuncture and should thus be treated lying down.

Recommendations from the US National Cancer Institute's Conference on Acupuncture for Symptom Management in Oncology in 2017 indicate that “oncology acupuncture” is a specialty area of practice (Zia 2017). Specific concerns include higher risks of infection and bleeding due to neutropenia and thrombocytopenia and possibility for hemodynamic instability due to dehydration and malnutrition. It was proposed that clinical practice guidelines are followed that take into account lab values such as absolute neutrophil and platelet Counts.

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