Pediatric Hematology and Oncology, 29:285–292, 2012

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C Informa Healthcare USA, Inc.

ISSN: 0888-0018 print / 1521-0669 online
DOI: 10.3109/08880018.2012.669026

INFECTIONS AND SUPPORTIVE THERAPY

Honey and a Mixture of Honey, Beeswax, and Olive

Oil–Propolis Extract in Treatment of
Chemotherapy-Induced Oral Mucositis:
A Randomized Controlled Pilot Study

Mamdouh Abdulrhman, Nancy Samir El Barbary, Dina Ahmed Amin,

and Rania Saeid Ebrahim

Department of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt

In spite of being one of the most investigated subjects among supportive care in cancer, no ther-
apy has been found effective in treatment of chemotherapy-induced oral mucositis. Based on the
observations that honey bees products have anti-inflammatory and wound healing effects, the
present study tried to evaluate the effect of topical application of honey and a mixture of honey,
olive oil–propolis extract, and beeswax (HOPE) in treatment of oral mucositis. This was a random-
ized controlled clinical trial conducted on 90 patients with acute lymphoblastic leukemia and oral
mucositis grades 2 and 3. The mean age of enrolled patients was 6.9 years. The patients were as-
signed into 3 equal treatment groups: Honey, HOPE, and control groups. Topical treatment for
each patient consists of honey, HOPE, and benzocaine gel for honey, HOPE, and control groups,
respectively. Recovery time in grade 2 mucositis was significantly reduced in the honey group as
compared with either HOPE or controls (P < .05). In grade 3 mucositis, recovery time did not differ
significantly between honey and HOPE (P = 0.61) but compared with controls, healing was faster
with either honey or HOPE (P < .01). Generally, in both grades of mucositis, honey produced faster
healing than either HOPE or controls (P < .05). Based on our results that showed that honey pro-
duced faster healing in patients with grade 2/3 chemotherapy-induced mucositis, we recommend
using honey and possibly other bee products and olive oil in future therapeutic trials targeting
chemotherapy-induced mucositis
Keywords honey, mucositis, propolis

Mucositis is an inflammatory response of mucosal epithelial cells to the cyto-

toxic effects of chemotherapy and radiation therapy. All mucous membrane–covered
surfaces from the mouth to the rectum may be affected [1]. The main symptom of
oral mucositis is severe debilitating oral pain [2], which may greatly complicate the

Received 13 December 2011; accepted 20 February 2012.

The authors thank the participating children and their families and the physicians who enrolled
their patients into the study. The authors thank all members of the nursing staff of Hematology
Oncology unit of Children’s Hospital of Ain Shams University, who helped applying topical
treatment to patients, for their cooperation and care. The authors thank the laboratory staff for
doing the laboratory testing. The authors thank the dental team of their hospital for their
cooperation. The authors also thank Dr Ahmed Kamal, Dr Hazem Elhariri, and Dr Waleed Salah
for performing the statistical analysis.

Address correspondence to Mamdouh Abdulrhman, Professor of Pediatrics, Department of

Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt. E-mail:
mamdouh565@hotmail.com


 M. Abdulrhman et al.

management of cancer and compromise cure rates [3]. Furthermore, severe oral mu-
cositis may lead to malnutrition and local and systemic infections [4].
Honey is a natural substance made when the nectar and sweet deposits from plants
are gathered, modified, and stored in the honeycomb by honey bees. Its main compo-
nents are the sugars glucose and fructose; its third greatest component is water. Honey
also contains acids, proteins, and minerals [5, 6]. Honey has anti-inflammatory [7], an-
tioxidant [8, 9], and antimicrobial effects [10–13]. The antioxidant power of honey is
mainly attributed to its content of polyphenols.
In cancers, honey may be used for radiation-induced mucositis [14]. Honey also
has potential for treatment of periodontal disease, mouth ulcers, and other problems
of oral health [15].
Propolis is a natural product derived from plant resins collected by honeybees.
Propolis has antimicrobial, antioxidative, antiulcer, and antitumor activities [16]. Ra-
diation therapists have used propolis successfully for treatment of stomatitis and mu-
cositis [17].
Olive oil is made from the olive (Olea europaea), a species from the Oleaceae fam-
ily, a native plant, growing widely in the east Mediterranean region. Animal studies
showed that topical use of olive oil has a radioprotective effect [18, 19].
The aim of the present study was to evaluate the effect of topical application of
honey and a mixture of honey, olive oil–propolis extract, and beeswax, as natural prod-
ucts, in treatment of chemotherapy-related oral mucositis.

METHODS
This was a randomized controlled clinical phase II trial conducted on 90 children
(33 females and 57 males) suffering from acute lymphoblastic leukemia (ALL) and
chemotherapy-related oral mucositis. Their age ranged from 2 to 18 years (mean: 6.9
± 3.8 years). They were recruited from Hematology-Oncology of Children’s Hospital of
Ain Shams University; one of the referral centers in Egypt, in the period from June 2010
to June 2011. Before enrollment, all patients were subjected to (1) history taking with
special emphasis on any treatment given for mucositis and the date of onset of mu-
cositis; (2) physical examination including grading of oral mucositis according to the
National Cancer Institute Common Toxicity Criteria (NCI-CTC) [20] and orodental as-
sessment by our dental team; and (3) laboratory investigations in the form of complete
blood analysis (using Gen. S system 2 coulter, xx, xx), fasting, and 2-hour postprandial
blood glucose (using Synchroncx9, xx, xx).

Inclusion Criteria
All patients

• with ALL during the consolidation phase of treatment, and

• with chemotherapy-related oral mucositis grades 2 and 3.

Exclusion Criteria
Exclusion criteria included the presence of any of the following: (1) coexisting diabetes
mellitus; (2) administration of antiviral or antifungal therapy and/or any other treat-
ment for oral mucositis before enrollment in the study; (3) presence of neutropenia
(absolute neutrophilic count ≤1500/mm3 ); (4) presence of advanced or severe peri-
odontitis (patients with periodontal pockets of 6 mm or more) [21, 22].
The same patients in whom mucositis recurred during the consolidation phase, and
fulfilled the inclusion/exclusion criteria were re-included in the study.

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 Honeybees Products in Oral Mucositis 

Study Design
An informed consent was obtained from at least 1 parent or guardian of each patient
before the trial. The study was approved by the Research Ethics Committee of Faculty
of Medicine of Ain Shams University.
Enrolled patients were admitted to the hospital during the study period in order to
ensure compliance to topical treatment and not to lose follow up. All enrolled patients
were in the standard risk group following the arm using induction protocol I, consoli-
dation/extra compartmental protocol M, reinduction (delayed intensification) proto-
col II, and maintenance.
All patients were recruited during the consolidation phase of treatment and those
who fulfilled the inclusion/exclusion criteria were randomly assigned into 1 of the 3
groups, 30 patients each. We followed a simple method of randomization so that the
first 2 patients were allocated to group 1, the second 2 patients to group 2, the third 2
patients to group 3, the fourth 2 patients to group 1, and so on. Group 1 received 0.5 g
honey/kg (maximum 15 g) applied topically to the affected oral mucosa 3 times daily
until healing or for 10 days, which ever comes first. Group 2 received 0.25 g/kg (max-
imum 5 g) of a 4:2:1 mixture of honey, olive oil–propolis extract and beeswax (HOPE)
applied topically to the oral mucosa 3 times daily until healing or for 10 days, which
ever comes first. Group 3 served as controls and received benzocaine 7.5% gel applied
topically to the affected oral mucosa 3 times daily.
Routine oral care was done for all patients in all groups. It consisted of tooth brush-
ing using a soft toothbrush followed by oral normal saline rinse 3 times daily. Tooth
brushing followed by oral rinse was done just before each topical treatment.
Application of the topical treatment in each group was done by the resident and/or
the nursing staff under supervision of the researchers. Each patient was followed up
daily for signs of healing or progression to more severe grade 4 mucositis.
The primary outcome measure was the recovery time, defined as the number of
days from initiation of treatment to when complete healing of all ulcers occurred.

Chemotherapy
Enrolled patients with acute lymphoblastic leukemia were treated according to Berlin-
Frankfurt-Münster (BFM 90) protocol [23]. All were on standard risk therapy and
they were followed up during consolidation phase. The day before methotrexate
(MTX) infusion, the patient was admitted to receive intravenous [IV] fluids (3000
mL/m2 /day) containing NaHCO3 to achieve a urinary pH of ≥7 and a urine output of
≥100 mL/m2 /h before, during, and 48 hours after MTX infusion.
During consolidation, MTX was given 4 times: 1 dose every 2 weeks at days 8, 22,
36,and 50. MTX infusion was administered in a dose of 2 g/m2 over 24 hours.
During consolidation, MTX was combined with a late leucovorin (folinic acid) res-
cue: calcium folinate 10 mg/mL injection (Hospira UK, Warwickshire, UK). The first
dose of intravenous leucovorin (30 mg/m2 ) was scheduled for hour 42 after the start
of MTX administration; the subsequent 2 doses (15 mg/m2 each) were given at hours
48 and 54. Additional leucovorin was given only if the MTX level exceeded 1.0 µmol/L
at hour 42 or 0.4 µmol/L at hour 48. If toxicity was acceptable after the first exposure
to systemic MTX, the leucovorin dose at hour 42 was decreased to 15 mg/m2 in sub-
sequent courses. MTX levels were measured 48 hours after start of MTX infusion and
daily for 3 days until levels reach 0.1 µmol/L.

Honey
The main flower involved in the collection of nectar was that of the clover plant Tri-
folium alexandrinum. The origin of honey was El Mahala, Gharbia Governorate, Egypt.
It was supplied directly from a beekeeper without heating or irradiation and stored in

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 M. Abdulrhman et al.

dark containers at room temperature for use in the study. The honey was subjected
to analysis of physical characters and chemical composition in the Chemical Analy-
sis Laboratory of Honey Bee Products, Beekeeping Research Center, Plant Protection
Research Institute, Agriculture Research Center, Giza, Egypt. The honey used in this
study had a pH of 3.7, a moisture content of 18.8%, and a carbohydrate content of
78.4 g/100 g.

The Mixture of Honey, Olive Oil–Propolis Extract, and Bees Wax (HOPE)
Ten grams of grinded propolis was mixed with olive oil. This mixture was kept in a
well-sealed glass container away from light for 3 months. Thereafter the mixture was
gently heated in a water bath, having a maximum temperature of 40◦ C, with continued
mixing for 30 minutes, followed by filtration to separate the fine granules of propolis
and to obtain olive oil propolis extract. One hundred milliliters of this extract was then
mixed with 50 mL bees wax in a liquid state and 200 mL honey. The mixture was then
heated in a water bath with continued mixing to obtain a 4:2:1 homogenous mixture
of honey, olive oil propolis extract and bees wax, respectively. The mixture prepared
was then kept in dark well-sealed containers until use. Stirring of the mixture was done
before each application.
The origin of beeswax was El Mahala, Gharbia Governorate, Egypt. The olive oil used
in the mixture was an extra virgin olive oil from Marsa Matrouh, Egypt. The propolis
used was Brazilian fresh ultragreen propolis. The honey used in the mixture was the
same honey mentioned before.

Statistical Analysis
The collected data were revised, coded, tabulated, and introduced to a personal com-
puter using Statistical package for Social Science (SPSS 15.0.1 for windows; SPSS,
Chicago, IL, 2001). Data were presented and suitable analysis was done according to
the type of data obtained for each parameter. All numeric variables were expressed as
mean ± standard deviation (SD). Student t test was used to assess the statistical signifi-
cance of the difference between 2 study group means. For statistical power calculation
STATA version 11 program (StataCorp, College Station, TX) was used.

RESULTS
Before starting treatment there was no significant difference between groups as re-
gards the age, the sex ratio, and anthropometric measures (weight, height, and body
mass index [BMI]). The mean total leukocytic count in the honey, HOPE, and control
groups was 6.1, 6.4, and 5.8 × 103 /UL, respectively, with no statistically significant dif-
ference between groups (P > .05). The mean hemoglobin concentration did not also
differ significantly between groups. It was 9.0, 8.6, and 8.9 g/dL in the honey, HOPE,
and control groups, respectively (P > .05). The mean platelet count in the honey,
HOPE, and control groups was 145.50, 144.57, and 146.52 × 103 /UL, respectively, with
no statistically significant difference between groups (P > .05). The mean onset of mu-
cositis was 6.13, 6.06, and 6.43 days after methotrexate infusion in the honey, HOPE,
and control groups, respectively, with no statistically significant difference (P > .05).
The mean duration of mucositis before starting treatment was 3.35, 3.60, and 3.80 days
in the honey, HOPE, and control groups, respectively, with no statistically significant
difference between groups (P > .05). Also the severity (grade) of mucositis did not
differ significantly between groups (Table 1). None of enrolled patients experienced
delayed methotrexate (MTX) excretion. All patients had MTX levels below 2 µmol/L
starting 48 to 120 hours after MTX infusion.

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 Honeybees Products in Oral Mucositis 

TABLE 1 Grade of Mucositis Among Studied Groups

P
Grade of Group 1 Group 2 Group 3 Honey vs Honey vs HOPE vs
mucositis (honey) n (HOPE) n (control) n HOPE control control
2 17 15 17 .60 .99 .60
3 13 15 13
Note. P > .05 is not significant.

Complete healing occurred in all patients in all groups but there was difference
in recovery time between groups. All topical treatments were tolerated. However, 8
(26.7%) patients in the HOPE group reported transient burning sensation immediately
after application. This burning sensation, which disappeared spontaneously, is due to
the spicy taste of the Brazilian propolis included in the mixture. On the other hand,
honey was well accepted by all patients in group 1 without any complaint. On clin-
ical grounds, none of the studied patients developed gastrointestinal adverse effects
as a result of swallowing of topical treatment. Also, hypersensitivity reaction to topical
treatment was not observed in any patient.
In grade 2 mucositis, the recovery time was significantly reduced in the honey group
as compared with either HOPE or control group (P < .05). In grade 3 mucositis, the re-
covery time did not differ significantly between honey and HOPE (P = .6108) but com-
pared to the controls, both honey and HOPE produced a significantly faster healing
(P < .01). Combining both grades, honey produced faster healing as compared with
either control (P = .0005; with a statistical power of 96.2%) or HOPE group (P = .0056;
with a statistical power of 81.9%) (Table 2).
We observed that after application, HOPE was mixed with saliva and its particles
clumped together so that the distribution of the mixture in the oral cavity was not ho-
mogenous as honey. It was also noticed that the aggregated particles of HOPE appar-
ently remained in contact with tissues inside ulcers and folds of the oral cavity, mouth
vestibule (space between lips/cheeks and teeth), and under the tongue, for a relatively
longer time before being swallowed. On the other hand, the time of contact of HOPE
with nonulcerative tissues other than mouth folds was apparently less. The clumping
of HOPE particles was due to the fact that it contains propolis, olive oil, and beeswax
that are not soluble in water. On the other hand, the distribution of honey inside the
oral cavity was homogenous because honey is soluble in water.

DISCUSSION
Chemotherapy-related mucositis results from direct toxicity and myelosuppression
that result from therapy [24]. Chemotherapy not only alters mucosal integrity, but also

TABLE 2 Recovery Time Among Studied Patients

Recovery time (days) Mean ± SD P
Grade of Group 1 Group 2 Group 3 Honey vs Honey vs HOPE vs
mucositis (honey) (HOPE) (control) HOPE control control
2 3.6 ± 0.8 4.2 ± 0.7 4.6 ± 0.9 .0324 .0017 .1750
3 5.4 ± 1.1 5.8 ± 2.6 8.6 ± 1.0 .6108 .0001 .0012
2 and 3 4.25 ± 1.25 5.75 ± 2.57 6.10 ± 2.47 .0056 .0005 .5928
Note. P < .05 is significant; P < .01 is highly significant.

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 M. Abdulrhman et al.

changes the microbial flora in the mouth; it also alters the quantity and composition
of saliva and epithelial maturation [25]. In spite of being one of the most investigated
subjects among supportive care in cancer [26], no strategy or standard therapy has
proven effective in prevention and/or treatment of mucositis [27, 28].
To our knowledge, the present study may be the first study using honey bees prod-
ucts and olive oil in treatment of chemotherapy-induced oral mucositis, and since
there was no previously reported significant toxicity to the topical application of these
natural products, we used empirical doses of honey and HOPE, which we found suffi-
cient to cover the oral mucosa. For oral mucositis, basic oral care (tooth brushing and
oral rinses) is the only intervention for which effectiveness has been demonstrated
by strong evidence from rigorously designed studies, meta-analyses, or systematic re-
views [20]. The effectiveness of other interventions has not been established. There-
fore, in our study, and from the ethical point of view, we followed the oral care protocol
for all patients in the 3 groups. Based on our experience, the duration of grade 2 and
3 mucositis under treatment usually does not exceed 10 days. Therefore, we thought
that a 10-day course of treatment might be enough to evaluate the effectiveness of a
treatment, provided that there were no complications (eg, progression to more severe
grade 4 mucositis).
In our study, we tried using honey as a topical treatment for mucositis because
honey was previously shown to induce rapid epithelialization of tissue injuries [29]. In
addition to its antimicrobial properties [30–34], honey can also stimulate monocytes
to release cytokines and interleukins, thus stimulating the healing process [30]. Fur-
thermore, honey has been found to be effective for radiation-induced oral mucositis,
stomatitis, and periodontal gum disease in pediatric oncology patients [35–40]. Biswal
et al [37] also showed the efficacy of honey in reducing the severity and duration of
mucositis occurring as a consequence of radiotherapy.
In the present study, we also tried to evaluate the effect of topical application of
a mixture of honey, olive oil–propolis extract, and beeswax in treatment of oral mu-
cositis. The rational of using propolis was based on the observations that propolis has
antimicrobial, antioxidative, antiulcer, and antitumor activities [16] and that propolis
was proved effective in reducing the severity of oral mucositis induced by head-and-
neck irradiation in rats [41]. The rationale of using olive oil was based on the finding
that topical olive oil has a radioprotective effect in animals [18, 19]. The basis of using
beeswax in the mixture was derived from the observation that beeswax has antibacte-
rial properties and is considered safe for human consumption [42].
The superiority of the topical honey alone may be related to the amount of honey
used and/or the better distribution in oral cavity. The question: Was the beneficial
effect of HOPE in grade 3 mucositis related only to the honey it contains? Or would
the HOPE components other than honey have a role? The positive effect of HOPE in
grade 3 mucositis, which was comparable to honey, seems to be related to the com-
bined effects of all its components and not to honey alone. This is because in grade
2 mucositis HOPE did not produce a significant effect, whereas the recovery time in
grade 3 mucositis did not differ significantly between HOPE and honey, although the
amount of honey in HOPE was much less than the amount of honey used in group 1.
The lack of a significantly positive effect for HOPE in grade 2 mucositis may be due
to the observation that the distribution of HOPE mixture inside the oral cavity was not
homogenous as honey because HOPE made aggregates when it was mixed with saliva,
thus leaving areas inside the oral cavity not in proper contact with the mixture’s con-
tents. Therefore, we suggest, in future studies, improving the quality of this mixture
for better cellular acceptance at the mucosal level by decreasing the concentration of
bees wax and propolis, removing the bees waxes from the mixture, using a less spicy
propolis such as Egyptian one, or using a water propolis extract. However, it was also

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 Honeybees Products in Oral Mucositis 

observed that HOPE aggregates remained for a relatively longer time in contact with
the tissues inside ulcers. This may be the possible reason why HOPE had a significant
positive effect in grade 3 mucositis where the ulcers were larger in size and more in
number, compared to grade 2 mucositis where the ulcers were smaller in size and less
in number.
A drawback to this study was that it was not blinded to both the researcher and
patient. This is because we were not able to make forms similar in shape, consistency,
and taste of HOPE and honey.

CONCLUSION
Based on our results that showed that honey produced faster healing in patients
with grade 2/3 chemotherapy-induced mucositis, we recommend using honey and
possibly other bee products and olive oil in future therapeutic trials targeting
chemotherapy-induced mucositis, particularly in developing countries where the
availability and cost of dressings might be a problem.
Competing interest: Pending patent application for the mixture of honey,
beeswax, and olive oil–propolis extract (Abdulrhman MA. Honey, beeswax and
olive oil–propolis extract ointment mixture (HOPE ointment mixture). Egypt patent
2011030336. 2011 March 1).
Trial registration number: ClinicalTrials.gov identifier: NCT01431729.

Declaration of Interest
The authors report no conflicts of interest. The authors alone are responsible for the
content and writing of the paper.

REFERENCES
[1] Wojtaszek C. Management of chemotherapy-induced stomatitis. Clin J Oncol Nurs. 2000;4:263–270.
[2] Epstein JB, Schubert MM. Oropharyngeal mucositis in cancer therapy. Oncology. 2003;17:1767–1776.
[3] Rose-Ped AM, Bellm LA, Epstein JB, et al. Complications of radiation therapy for head and neck can-
cers: the patient’s perspective. Cancer Nurs. 2002;25:461– 467.
[4] Eilers J. Nursing interventions and supportive care for the prevention and treatment of oral mucositis
associated with cancer treatment. Oncol Nurs Forum. 2004;31(4 Suppl):13–23.
[5] White JW Jr. Composition of American Honeys. Washington, DC: Agricultural, Research Service,
USDA; 1962. Technical Bulletin. 1261.
[6] White JW Jr. Detection of honey adulteration by carbohydrate analysis. J AOAC. 1980;63:11–18.
[7] Al Waili NS, Boni NS. Natural honey lowers plasma prostaglandin concentrations in normal individ-
uals. J Med Food. 2003;6:129–33.
[8] Frankel S, Robinson GE, Berenbaum MR. Antioxidant capacity and correlated characteristics of 14
unifloral honeys. J Apic Res. 1998;37:27–31.
[9] Gheldof N, Engeseth NJ. Antioxidant capacity of honeys from various floral sources based on the
determination of oxygen radical absorbance capacity and inhibition of in vitro lipoprotein oxidation
in human serum samples. J Agric Food Chem. 2002;50:3050–3055.
[10] Molan PC. The antibacterial activity of honey. 1. The nature of the antibacterial activity. Bee World.
1992;73:5–28. [Author]. xxx. 2. Variation in the potency of the antibacterial activity. Bee World.
1992;73:59–76.
[11] Steinberg D, Kaine G, Gedalia I. Antibacterial effect of propolis and honey on oral bacteria. Am J
Dent. 1996;9:236–239.
[12] Molan PC. Honey as an antimicrobial agent. In: Mizrahi A, Lensky Y, eds. Bee Products: Properties,
Applications and Apitherapy. London: Plenum; 1997:27–37.
[13] Theunissen F, Grobler S, Gedalia I. The antifungal action of three South, African honeys on Candida
albicans. Apidologie. 2001;32:371–379.
[14] Bardy J, Slevin NJ, Mais KL, Molassiotis A. A systematic review of honey uses and its potential value
within oncology care. J Clin Nurs. 2008;17:2604–2623.
[15] Molan PC. The potential of honey to promote oral wellness. Gen Dent. 2001;49:584–589.

Copyright

C Informa Healthcare USA, Inc.
 M. Abdulrhman et al.

[16] Khalil ML. Biological activity of bee propolis in health and disease. Asian, Pac J Cancer Prev.
2006;7:22–31.
[17] Golder W. [Propolis. The bee glue as presented by the Graeco-Roman literature]. Wurzbg Medizinhist
Mitt. 2004;23:133–145. [in German]
[18] Ichihashi M, Ahmed NU, Budiyanto A, et al. Preventive effect of antioxidant on ultraviolet-induced
skin cancer in mice. J Dermatol Sci. 2000;23(Suppl 1):S45–S50.
[19] Smith PP, Leith JT. Effects of topically-applied olive oil on the response of hamster skin to single or
multiple doses of 230kV X-rays. Int J Radiat, Biol Relat Stud Phys Chem Med. 1977;31:467–475.
[20] Harris DJ, Eilers J, Harriman A, et al. Putting evidence into practice: evidence-based interventions
for the management of oral mucositis. Clin J Oncol Nurs. 2008;12:141–152.
[21] Elter JR, Champagne CME, Offenbacher S, Beck JD. Relationship of periodontal disease and tooth
loss to prevalence of coronary heart disease. J Periodontol. 2004;75:782–790.
[22] Hujoel PP, Drangsholt MT, Spiekerman C, Derouen TA. Periodontitis-systemic disease associations
in the presence of smoking: causal or coincidental? J Periodontol. 2002;30:51–60.
[23] Schrappe M, Reiter A, Ludwig WD, et al. Improved outcome in childhood acute lymphoblastic
leukemia despite reduced use of anthracyclines and cranial radiotherapy: results of trial ALL-BFM
90. German-Austrian-Swiss ALL-BFM Study Group. Blood. 2000;95:3310–3322.
[24] Volpato LE, Silva TC, Oliveira TM, et al. Radiation therapy and chemotherapy-induced oral mucosi-
tis. Braz J Otorhinolaryngol. 2007;73:562–568.
[25] Turhal NS, Erdal S, Karacay S. Efficacy of treatment to relieve mucositis- induced discomfort. Support
Care Cancer. 2000;8:55–58.
[26] Migliorati CA, Oberle-Edwards L, Schubert M. The role of alternative natural agents, cryotherapy,
and/or laser for management of alimentary mucositis. Support Care Cancer. 2006;14:533–540.
[27] Arora H, Pai KM, Maiya A, et al. Efficacy of He-12. Ne Laser in the prevention and treatment of
radiotherapy-induced oral mucositis in oral cancer patients. Oral Surg Oral Med Oral Pathol Oral
Radiol Endod. 2008;105:180–186.
[28] Jaguar GC, Prado JD, Nishimoto IN, et al. Low-energy laser therapy for prevention of oral mucositis
in hematopoietic stem cell transplantation. Oral Dis. 2007;13:538–543.
[29] Bergman A, Yanai J, Weiss J, et al. Acceleration of wound healing by topical application of honey. Am
J Surg. 1983;145:374–376.
[30] Molan PC. Honey as a topical antibacterial agent for the treatment of infected wounds. World Wide
Wounds. 2001. Available at: http://www.worldwidewounds.com/2001/november/molan/honey-
as-topical-agent.html. Accessed xxx.
[31] Stephen-Haynes J. Evaluation of a honey-impregnated tulle dressing in primary care. Br J Community
Nurs Suppl. 2004;9:S21–S27.
[32] Lusby PE, Coombes A, Wilkinson JM. Honey: a potent agent for wound healing? J Wound Ostomy
Continence Nurs. 2002;29:295–300.
[33] Anderson I. Honey dressings in wound care. Nurs Times. 2006;102:40–42.
[34] Hyslop PA, Hinshaw DB, Scraufstatter IU, et al. Hydrogen peroxide as a potent bacteriostatic antibi-
otic: implications for host defense. Free Radic Biol Med. 1995;19:31–37.
[35] Chiba M, Idobata K, Kobayashi N, et al. [Use of honey to ease the pain of stomatitis during radiother-
apy]. Kangogaku Zasshi. 1985;49:171– 176.
[36] Smirnova II, Filatova EI, Suvorov AN, Bylinskaia EN. [The use of therapeutic/prophylactic dragee
‘honey laminolact’ in radiotherapy of uterine tumors]. Voprosy Onkologii. 2000;46:748–750.
[37] Biswal BM, Zakaria A, Ahmad NM. Topical application of honey in the management of radiation
mucositis: a preliminary study. Support Care Cancer. 2003;11:242– 248.
[38] English HK, Pack AR, Molan PC. The effects of manuka honey on plaque and gingivitis: a pilot study.
J Int Acad Periodontol. 2004;6:63–67.
[39] Moolenaar M, Poorter RL, Van, Der Toorn PP, et al. The effect of honey compared to conventional
treatment on healing of radiotherapy-induced skin toxicity in breast cancer patients. Acta Oncol.
2006;45:623–624.
[40] Simon A, Sofka K, Wiszniewsky G, et al. Wound care with antibacterial honey (Medihoney) in pedi-
atric hematology-oncology. Support Care Cancer. 2006;14:91–97.
[41] Benderli Cihan Y, Deniz K. [Effect of propolis against radiation-induced oral mucositis in rats]. Kulak
Burun Bogaz Ihtis Derg. 2011;21:32–41. [in Turkish]
[42] Bogdanov S. Beeswax: uses and trade. In: Bogdanov S, ed. The Beeswax Book. xx: Bee, Product Sci-
ence; 2009:11–12. Available at: www.bee-hexagon.net. Accessed xxx.

Pediatric Hematology and Oncology

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