|Year : 2013 | Volume
| Issue : 1 | Page : 22-26
The effect of the low-level laser on prevention of chemotherapy-induced oral mucositis in patients with acute leukemia
Mohammad Mehdi Fani1, Mohammad Reza Azar2, Mani Ramzi3, Azita Azad4, Eslam Hajizadeh3, Nariman Iraji Nasrabadi5, Sara Mogharrabi6
1 Department of Oral Medicine; School of Dentistry, Namazi Hospital; Shiraz University of Medical Sciences, Shiraz, Iran
2 Department of Oral Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
3 Department of Oral Medicine, Shiraz University of Medical Sciences; Department of Oral Medicine, Hematology and Oncology Center, Namazi Hospital, Shiraz, Iran
4 Department of Oral Medicine, Shiraz University of Medical Sciences; Kish Dental School, Shiraz, Iran
5 Department of Oral Medicine, School of Dentistry, Namazi Hospital; Shiraz University of Medical Sciences, Shiraz, Iran
6 Department of Oral Medicine, School of Dentistry, Namazi Hospital; Shiraz University of Medical Sciences, Shiraz; Department of Prosthodontics, Jondi-Shapour University of Medical Sciences, Ahvaz, Iran
|Date of Web Publication||19-Sep-2013|
postgraduate student of prosthodontics, Department of Prosthodontics, School of Dentistry, Ghasrodasht Street, Shiraz
Source of Support: None, Conflict of Interest: None
Statement of Problem: Low-level laser has been shown to be beneficial in reducing significantly chemotherapy-induced mucositis. However, the approach has not gained wide acceptance, so far. Purpose: The aim of this study was to evaluate the effect of low-level laser therapy clinically in prevention of chemotherapy-induced oral mucositis in patients suffering acute hematologic cancers. Materials and Methods: 40 patients who aged 12 and older, who had acute myeloid / lymphoid leukemia and were receiving myeloablative chemotherapy regimen were included. Patients were randomly divided into the control and the experiment groups. A diode laser (Aluminum Gallium Indium; Azor-2k-02, Russia, λ = 660 nm, power: 25 mw, spot size: 2 mm, continuous mode, Energy: 1.5 J per point) was applied on 12 points for one month, twice weekly. Results: Based on the WHO scales, In the fourth session, the people suffering from mucositis were increased to 18 people, 12 of which were in the control group. This increasing trend has been also observed in NCI scales, so that in the fourth session, the number of people suffering from mucositis reached to 12 persons and the severity and degree of leisure reached to 3, 4. Conclusion: Low level laser could reduce the severity and the pain of the mucositis.
Keywords: Chemotherapy, low-level laser, oral mucositis
|How to cite this article:|
Fani MM, Azar MR, Ramzi M, Azad A, Hajizadeh E, Nasrabadi NI, Mogharrabi S. The effect of the low-level laser on prevention of chemotherapy-induced oral mucositis in patients with acute leukemia. J Dent Lasers 2013;7:22-6
|How to cite this URL:|
Fani MM, Azar MR, Ramzi M, Azad A, Hajizadeh E, Nasrabadi NI, Mogharrabi S. The effect of the low-level laser on prevention of chemotherapy-induced oral mucositis in patients with acute leukemia. J Dent Lasers [serial online] 2013 [cited 2022 Jul 4];7:22-6. Available from: https://www.jdentlasers.org/text.asp?2013/7/1/22/118439
| Introduction|| |
Oral mucositis is the most common and uncomfortable adverse effect in patients receiving high doses of chemotherapy or radiotherapy.  This condition is defined as inflammation and ulceration of the mouth pseudomembrane formation.  The occurrence of oral mucositis has a significant impact on the quality of life of the patients and on the cost of care; so progresses in this field are highly needed.  Several therapies for prevention and treatment of oral mucositis have shown to be effective. The most recent one was the recombinant human keratinocyte growth factor, palifermin [kepivance® ]. The reduction of both the incidence and duration of severe oral mucositis and improvement of pain was significant with palifermin. ,
For some therapeutic agents such as chlorhexidine, aminofostine, and chamomile, there is insufficient evidence in the literature regarding to preventive and/or treatment of oral mucositis. 
Some studies have reported beneficial effects of low-level laser therapy to promote tissue repair and reduce pain and inflammation. ,, This therapy has been clinically performed to prevent and treat oral mucositis with some good results reported. ,,,, The effect of this method is based on the mechanisms of the lights without heat on the biologic tissues and it is a noninvasive method. 
It has been shown that low-level laser therapy reduced significantly high dose chemotherapy-induced mucositis.  However, in spite of this evidence that low-level laser therapy might be an efficient and safe method in prevention and treatment of oral mucositis, the approach has not gained wide acceptance, so far. 
The aim of this study was to evaluate the effect of low-level laser therapy clinically in prevention of chemotherapy-induced oral mucositis in patients suffering acute hematologic cancers.
| Materials and Methods|| |
Inclusion and exclusion criteria
A total of 40 patients aged 12 and older, who had acute myeloid leukemia or acute lymphoid leukemia and were receiving myeloablative chemotherapy regimen were included. All participants had to have intact oral mucosa on the 1 st day of the experiment. They must also have signed informed consent. Patients who had other types of hematologic cancers or had received nonablative chemotherapy regimen were excluded.
In the first session, demographic data for each person was recorded and photography of the oral cavity was taken.
Patients were evaluated at the end of each week and the lesions were classified according to World Health Organization (WHO) and National Cancer Institute (NCI) grading systems, as follows:
• WHO grading system:
Grade 0: Indicated absence of mucositis
Grade I: Presence of a painless ulcer, erythema, or mild sensitivity
Grade II: Presence of painful erythema or ulcers that do not interfere with the patient's ability to take food
Grade III: Confluent ulceration that interferes with patient's ability to take solid food
Grade IV: Severe symptoms requiring entral or parenteral support.
• NCI grading system:
Grade I: Painless ulcer, erythema, or mild soreness
Grade II: Painful erythema, edema, and ulcer but the patient is able to eat
Grade III: When there is inability to eat
Grade IV: When the patient requires parenteral or enteral support.
Patients were randomly divided into two groups: The control group and the experiment group. A trained technician performed laser irradiation for 1 month, twice weekly. A diode laser [Aluminum Gallium Indium; Azor-2k-02, Russia, ?λ = 660 nm, power: 25 mw, spot size: 2 mm, continuous mode] was used. Energy used was 1.5 J per point and each irradiation last 1 min.
Irradiated regions were three points on the buccal mucosa, three points on the internal mucosa of the superior and inferior lip, two points on the soft palate, two points on the lateral border of the tongue, and two points on the ventral surface of the tongue.
| Results|| |
Preliminary statistical study on two groups, one under prevention with laser (20 persons) and the other, control group (20 persons) have shown that in the study group, the ratio of the incidence of acute leukemia in men to women is 2.4:1. Furthermore, the relative mean age of the patients in the experimental group was 31.24 and in the control group it was 29.7.
Among the total number of samples, 19 patients were suffering from Acute Myeloid Leukemia and 21 patients had Acute Lymphoblastic Leukemia. In general, according to Chi-square test, no significant difference was observed with regard to sex distribution, type of leukemia, and treatment. Also, at the beginning of research, based on t-test there was no significant difference between the two studied groups with regard to age distribution.
Analyzing the frequency of WHO scales in several follow-up sessions indicated the increase of the quantity and severity of mucositis from the first to the fourth session (8 patients from 40 patients had mucositis degree 1 and 2). In the fourth session, the people suffering from mucositis were increased to 18 people, 12 of which were in the control group. Additionally, patients suffering from 3 rd -degree mucositis were in the group control [Table 1].
This increasing trend has been also observed in NCI scales, so that in the fourth session, the number of people suffering from mucositis reached to 12 persons and the severity and degree of leisure reached to 3, 4.
|Table 1: Severity and incidence of mucositis in case and control groups based on WHO scale|
Click here to view
Furthermore, the severity of the mucositis incidence in the patients of the control group especially in the third and fourth sessions has been increased [Table 2].
|Table 2: Severity and incidence of mucositis in case and control groups based on NCI scale|
Click here to view
In order to study statistical value of the laser effect in reducing the incidence of mucositis during the present study period, the multivariate tests was used; therefore, based on WHO scale, P > 0.05 and based on NCI scale, P < 0.05.
Also, in the follow-up period, the mucositis incidence was compared between two groups according to Mann-Whitney U analysis and it has shown similar results.
In the fourth follow-up session, the mucositis clinical manifestation was compared and studied in two groups based on Chi-square and according to WHO, NCI indices, while P value in WHO index was larger than 0.05 and in NCI index it was smaller than 0.05.
| Discussion|| |
Quality of life of patients with cancer has long been in attention and discussed. The side effects of the drugs and antineoplasm agents are inevitable and unpleasant. Oral mucositis is one of the most prevalent and disturbing side effects of chemotherapy in patients with leukemia, which can clinically cause sore, dysphagia, and difficulty in speaking. 
Preventive effects of low-level laser on oral mucositis was evaluated by Bensadoun et al.,  and Lopes et al.,  and the results showed a significant difference between control group and laser therapy group.
Antunes et al.,  and Khouri et al.,  studies were done on patients who were candidates for bone marrow transplantation, while Zanin et al.,  study was on patients with head and neck cancer who were under daily radiotherapy. But subjects in this study were just selected from acute leukemic patients. This way, patients were more similar in type of therapy, chemotherapy drugs and side effects. Also, in the aspect of the nature of the disease and prevalence in a specific gender or age group, in our study were more subjects harmonic. Demographic results of the patients show that there is no statistically significant difference in the type of leukemia, times of treatment, sex distribution, type of treatment, and age distribution between two groups.
The laser used in the primary studies about the use of the laser in prevention and treatment of mucositis was He-Ne with 632.8 nm wavelength.  Today's newer types of laser diode such as InGaAI with 660 and 685 nm wavelength and GaAIAs with 830 nm wavelength are in use. In the current study, InGaAIP laser diode with 660 nm wavelength, 1.5 J/cm 2 energy and 25 mW in each spot was used.
The most important factor among therapeutic parameters is dosis that depends on the power and time. In the device [Azor-2K] power and wavelength were the same, and the only way to alter the ray dosis was to change the time. Thus, in order to get the least which can produce dosis larger than 1 J/cm 2],[ from five predetermined times in the device, 1 min was selected. Other therapeutic parameters are intermittent treatment sessions and the interval which can be various. Lopes et al.,  used daily laser therapy during radiotherapy for patients with cancer but Zanin et al.,  considering that there is no difference between once in 3 days and once a day, used 2 times a week. According to Zanin et al., results we decided to irradiate patients 2 times a week.
Based on NCI grading systems, in each session, the degree and the incidence of the mucositis increased in comparison to the previous session in both groups and this increase was more prominent in the control group. Difference among two groups was significant (P < 0.05).
But based on WHO scale, the difference in mucositis between two groups was not significant (P > 0.05).
Based on NCI scale, the degree of mucositis in the control group from 0.4 got to 1.75, but in the laser group from 0.1 in the 1 st session got to 0.3 in the 3 rd session and from 3 rd to 4 th had a little decrease. This can show positive effects of laser on prevention of mucositis and even reduction of signs and symptoms in the 3 rd session to 4 th . But statistical evaluation of the recent fact based on WHO, despite NCI, was not significant.
These results may be the possible causes of the difference between the results based on WHO and Khouri et al.,  and Antune et al.,  studies:
The laser used in the current had less power and dosis in comparison to the mentioned studies
Toxicity of the conditioning regimen used in both studies was more invasive than chemotherapy in this study; thus, the incidence of mucositis with higher severity is obvious. In Antunes et al., study, 10 people from control group got to degree 4 and in Khouri et al., study, although the most severe degree was 3, but the overall average of the severity of mucositis was 2.45, while in our study the maximum overall average was 1.3.
The results based on the NCI scale is similar to that of Zanin et al.,  and Simυes et al.,  studies. It could be said that low-level laser laser might be as effective as high power radiation in prevention of larger lesions and the amount of bleeding, and it is also effective in controlling the clinical signs of the lesions.
Although the results of evaluation based on WHO scale showed clinically significant decrease in pain, signs, and patient's complaint, this reduction was not statistically significant. Perhaps, the underlying reason would be that the effect of the laser on the specific signs of mucositis like extent of erythema and amount of bleeding is more than its effect on the concomitant signs such as pain, dysphagia, and difficulty in speech.
Taking psychological effects of laser therapy into attention, although some of the patients reached to NCI degree 4, but none of them got higher than WHO degree 3. This situation means that although some of the patients had multiple deep wounds and spontaneous bleedings were seen and even these lesions affected on patients' ability of eating and their diet, but the signs did not necessitate Intravenous support.
Although current study was a double-blinded clinical trial and interfering factors were avoided as much as possible, having more samples could lead us to more specific results and similar to that of Antunes et al., study based on WHO scale. A longer period of surveillance could be effective on the WHO results and its precision. Thus, it is better to have more studies especially in larger populations, in order to reduce the paradox in the results. Also, according to Zanin et al.,  study in order to have more exact outcome, it is better to have clinical trials carried out by a team including dentist, physician, nutritionist, psychologist, and nurse.
| Conclusion|| |
The results of this study about the effect of laser on prevention of mucositis reveal the positive effects of laser on the decrease of the number and prevalence of the oral mucositis, and as a result improving quality of life in a patient with cancer. In addition, low-level laser could reduce the severity and the pain of the mucositis lesions. This advantage makes patients able to continue chemotherapy and radiotherapy to the end which leads to better response to the treatments. It seems that we could use this method as a standard way of prevention and treatment of oral mucositis in chemotherapy in radiotherapy centers.
| Acknowledgment|| |
This study was supported by Shiraz University of Medical Sciences, Shiraz, Iran.
| References|| |
|1.||Scully C, Sonis S, Diz PD. Oral mucositis. Oral Dis 2006;12:229-41. |
|2.||Scardina GA, Pisano T, Messina P. Oral mucositis. Review of literature. N Y State Dent J 2010;76:34-8. |
|3.||Elting LS, Cooksley C, Chambers M, Cantor SB, Manzullo E, Rubenstein EB. The burdens of cancer therapy. Clinical and economic outcomes of chemotherapy-induced mucositis. Cancer 2003;98:1531-9. |
|4.||Spielberger R, Stiff P, Bensinger W, Gentile T, Weisdorf D, Kewalramani T, et al. Palifermin for oral mucositis after intensive therapy for hematologic cancers. N Engl J Med 2004;351:2590-8. |
|5.||Spielberger RT. Kepivance TM : A breakthrough for oral mucositis associated with mieloablative hematopoietic stem cell transplantation. Center Int Blood Marrow Transplant Res 2005;11:1-12. |
|6.||Khouri VY, Stracieri AB, Rodrigues MC, Moraes DA, Pieroni F, Simões BP, et al. Use of therapeutic laser for prevention and treatment of oral mucositis. Braz Dent J 2009;20:215-20. |
|7.||Reddy GK. Comparison of the photostimulatory effects of visible He-Ne and infrared Ga-As lasers on healing impaired diabetic rat wounds. Lasers Surg Med 2003;33:344-51. |
|8.||Medrado AR, Pugliese LS, Reis SR, Andrade ZA. Influence of low level laser therapy on wound healing and its biological action upon myofibroblasts. Lasers Surg Med 2003;32:239-44. |
|9.||Ferreira DM, Zângaro RA, Villaverde AB, Cury Y, Frigo L, Picolo G, et al. Analgesic effect of He-Ne [632.8 nm] low-level laser therapy on acute inflammatory pain. Photomed Laser Surg 2005;23:177-81. |
|10.||França CM, França CM, Núñez SC, Prates RA, Noborikawa E, Faria MR, et al. Low-intensity red laser on the prevention and treatment of induced-oral mucositis in hamsters. J Photochem Photobiol B 2009;94:25-31. |
|11.||Wong SF, Wilder-Smith P. Pilot study of laser effects on oral mucositis in patients receiving chemotherapy. Cancer J 2002;8:247-54. |
|12.||Bensadoun RJ, Franquin JC, Ciais G, Darcourt V, Schubert MM, Viot M, et al. Low-energy He/Ne laser in the prevention of radiation-induced mucositis. A multicenter phase III randomized study in patients with head and neck cancer. Support Care Cancer 1999;7:244-52. |
|13.||Cowen D, Tardieu C, Schubert M, Peterson D, Resbeut M, Faucher C, et al. Low energy Helium-Neon laser in the prevention of oral mucositis in patients undergoing bone marrow transplant: Results of a double blind randomized trial. Int J Radiat Oncol Biol Phys 1997;38:697-703. |
|14.||Jaguar GC, Prado JD, Nishimoto IN, Pinheiro MC, de Castro DO Jr, da Cruz Perez DE, et al. Low-energy laser therapy for prevention of oral mucositis inhematopoietic stem cell transplantation. Oral Dis 2007;13:538-43. |
|15.||Bensadoun RJ, Magné N, Marcy PY, Demard F. Chemotherapy- and radiotherapy-induced mucositis in head and neck cancer patients: New trends in pathophysiology, prevention and treatment. Eur Arch Otorhinolaryngol 2001;258:481-7. |
|16.||Peterson DE, Jones JB, Petit RG 2 nd . Randomized, placebo- controlled trial of Saforis for prevention and treatment of oral mucositis in breast cancer patients receiving anthracycline-based chemotherapy. Cancer 2007;109:322-31. |
|17.||Genot-Klastersky MT, Klastersky J, Awada F, Awada A, Crombez P, Martinez MD, et al. The use of low-energy laser (LEL) for the prevention of chemotherapy- and/or radiotherapy-induced oral mucositis in cancer patients: Results from two prospective studies. Support Care Cancer 2008;16:1381-7. |
|18.||Lopes C, MAS JR, Zangaro RA. Low level laser therapy in the prevention of radiotherapy-induced xerostomia and oral mucositis. Radiol Bras 2006;39:131-6. |
|19.||Antunes HS, de Azevedo AM, da Silva Bouzas LF, Adão CA, Pinheiro CT, Mayhe R, et al. Low-power laser in the prevention of induced oral mucositis in bone marrow transplantation patients: A randomized trial. Blood 2007;109:2250-5. |
|20.||Zanin T, Zanin F, Carvalhosa AA, Castro PH, Pacheco MT, Zanin IC, et al. Use of 660-nm diode laser in the prevention and treatment of human oral mucositis induced by radiotherapy and chemotherapy. Photomed Laser Surg 2010;28:233-7. |
|21.||Bensadoun RJ, Ciais G. Radiation- and chemotherapy-induced mucositis in oncology: Results of multicancer phase III studies. J Oral Lasr App 2002;2:115-20. |
|22.||Simões A, Eduardo FP, Luiz AC, Campos L, Sá PH, Cristófaro M, et al. Laser phototherapy as topical prophylaxis against head and neck cancer radiotherapy-induced oral mucositis: Comparison between low and high/low power lasers. Lasers Surg Med 2009;41:264-70. |
[Table 1], [Table 2]
|This article has been cited by|
||Low-level laser therapy for oral mucositis in children with cancer
| ||Melody Grace Redman, Katherine Harris, Bob S Phillips |
| ||Archives of Disease in Childhood. 2021; : archdischi |
|[Pubmed] | [DOI]|
||Evaluation of the effect of photodynamic therapy on chemotherapy induced oral mucositis Photodynamic therapy on oral mucositis
| ||Fatemeh Lavaee,Ali Amanati,Mani Ramzi,Setareh Naseri,Hajar Shakiba Sefat |
| ||Photodiagnosis and Photodynamic Therapy. 2020; : 101653 |
|[Pubmed] | [DOI]|
||Comparison of the effect of photodynamic therapy and topical corticosteroid on oral lichen planus lesions
| ||Fatemeh Lavaee,Maryam Shadmanpour |
| ||Oral Diseases. 2019; |
|[Pubmed] | [DOI]|
||Efficacy of a traditional Persian medicine preparation for radiation-induced xerostomia: a randomized, open-label, active-controlled trial
| ||Ghazaleh Heydarirad,Hossein Rezaeizadeh,Rasool Choopani,Seyed Hamdollah Mosavat,Ahmad Ameri |
| ||Journal of Integrative Medicine. 2017; 15(3): 201 |
|[Pubmed] | [DOI]|