Low-energy Laser Therapy in Oral Mucositis
César Miglioratia, Celso Massumotob, Fernanda de Paula Eduardoc,Karin Praia Mullerd, Teresa Carrierie, Patrícia Haypekf, Carlos de Paula Eduardog
a Hospital Sírio Libanês, São Paulo, Brazil. b Hospital Sírio Libanês, São Paulo, Brazil. c Sociedade de Odontologia a Laser, São Paulo, Brazil. d Faculdade de Odontologia da Universidade de São Paulo, Brazíl. e Sociedade de Odontologia a Laser, São Paulo, Brazil. f Faculdade de Odontologia da Universidade de São Paulo, Brazil. g Faculdade de Odontologia da Universidade de São Paulo, Brazil. Purpose: The use of high-dose chemotherapy as part of the preparative regimen for stem cell transplantation is associated
with mucosal damage. Laser irradiation of the oral, mucosa may help to decrease the severity of mucositis. This pilot trial
was conducted to evaluate the usefulness of low-energy laser therapy in the control of pain associated with oral mucositis
after stem cell transplantation or high-dose chemotherapy. Materiais and Methods: Eleven patients with the diagnosis of chronic myelogenous leukemia (n=4), non- Hodgkin’s
lymphoma (n=3), acute myelocytic leukemia (n=1), and other malignancies (n=3) were submitted to high-dose chernotherapy
for myeloablation. Seven patients received autologous stem cell transplantation two from allogeneic sources, and two
were given high-dose chemotherapy only. The oral cavity of all patients was examined by an oral medicine specialist during
the pretransplant and prechemotherapy work-up. The patients received irradiation with the mucolaser daily until post-
transplant day 5. The entire oral mucosa was treated with a final energy density of 2J/cm2. Mucositis was clinically evaluated
according to the WHO scale, and pain was measured by a visual analogue scale (VAS). Results: The laser treatment was well tolerated by the patients. Two patients had mucositis grade I-II, 8 patients had grade
III-IV, and 1 patient had none. None of the patients had the maximal pain score. Six patients had grade 0-3 and 5 patients
had grade 5-8 by VAS. The majority of patients associated the daily application of laser with prompt pain relief. Conclusion: The use of low-energy laser therapy may play a role in the control of pain associated with oral mucositis. In
order to evaluate the efficacy of laser therapy in the prevention of mucositis after stem cell transplantation, a randomized
Key words: bone marrow transplantation, laser therapy, oral mucositis, high dose chemotherapy.
J Oral Laser Applications 2001; 1:97-101 Submitted for publication:17.04.01; accepted for publication: 11.06.01
High-dose chemotherapy followed by stem cell
followed by atrophy of the mucosa and ulceration
transplantation is the therapy of choice for a variety
that may be followed by bleeding and intense pain,
of hematological diseases and solid tumors. Unfor-
as discussed by Sonis.16 Oral mucositis appears
tunately, the preparative regimen is associated with
during the second week of chemotherapy and shows
damage of the gastrointestinal epithelium and hema-
its peak between post-transplant days 7 and 11. The
topoietic cells from the bone marrow. Following the
oral mucositis may change the patients’ quality of
epithlelial damage, a high incidence of oral mucositis
life leading to decreased caloric intake and increased
use of narcotic drugs for pain relief.
Oral mucositis presents as an erythematous process
Mester et al18 observed a decreased healing time in
rats after treating the wounds with low-level laser
was maintained 20,000/uL at all times with irradiated
therapy (LLLT). LLLT can increase the protein
(25 Gy single dose) platelet concentrares.
synthesis in cells and the endorphin release by the
Preparative regimen: All patients received busulfan
(BU) 4mg/Kg/dx4 days (from days -5 to -2) followed
This pilot trial was initiated to evaluate the useful-
by cyclophosphamide (120 mg/kg). Dilantin was
ness of LLLT in controlling pain associated with oral
given for seizure prophylaxis during busulfan
mucositis after stem cell transplantation. MATERIALS AND METHODS High Dose Chemotherapy (HDC)
Eleven patients referred to the Hospital Sirio Libanês
Two patients received HDC only. Patient number 8
was treated for NHL with I-phosphamide 1.2g/m2 X
February 2001 were enrolled in the study. The
5 and VP-16 150mg/m2 for 3 days. Patient number
patients’ characteristics and disease status at the
10 was treated for a lymphangiosarcoma with
time of transplant and/or chemotherapy are
doxorubicin 75 mg/rn2 and I-phosphamide 1.8g/m2
Transplant Preparation Oral Examination Colony stimulating factor: All patients received
The oral cavity of all patients was examined by an
granulocyte colony-stimulating factor (G-CSF)
oral medicine specialist before the preparative
beginning the day after PBSC infusion. All patients
regimen; all patients received information regarding
received a combination of teicoplanin and
oral hygiene. They were given a mouthwash, a
ceftazidime whenever the absolute neutrophile count
toothpaste, an extra- soft toothbrush, and a lubricant
(ANC) was lower than 500/ul or when fever
gel (Lacled Laboratories, California, USA) to
developed. All patients were screened weekly for
cornpensate for possible xerostomia. All patients
hematologic CMV antigenemia from day 0 to day
signed a consent form before the inclusion in the
Apheresis was performed using a cell separatorFenwall, with 10 to 12 L of blood processed during
Laser Application: The patient’s entire oral mucosa
each collection procedure at 50 mL/min. Apheresis
was treated with the mucolaser (GaAlAs laser,
started during the CD34+ cells peak. Platelet count
MMOptics São Carlos, Brazil). The parameters used
Fig 1 Oral mucositis of the lateral border of the tongue in a bone
marrow transplant patient. Day 12 post marrow infusion.
were 780 nm wavelength and an output power of
oncological diseases and increased the success of
60 mW, giving a final energy density of 2 J/cm2. The
bone marrow transplantation (BMT). However, most
tip of the laser device roughly touched the oral
of the patients (70% to 80%) develop severe oral
mucosa for a total of 35 min per session. Daily
sessions beginning on day -5 were performed in
ln the present study, we have presented evidence
each patient. Treatrnent was interrupted only if
that GaAlAs laser therapy may play a role in the
patients refused the application or in case of nausea/
control of pain during the process of mucositis in
vomiting episodes. Applications continued through
BMT patients. Previous studies have indicated that
post-transplant day 5. The presence and severity of
laser therapy may have an analgesic effect on
mucositis was clinically evaluated using the WHO
tissues.6,9,10,15 The mechanism involved in pain
scale, and pain was measured by using a visual
control is still not well understood. However, it is
speculated that the modulation of nociception bymodification of nerve conduction rnay be improvedby the local release of endorphins and enkephalins.19
The treatment protocols of the present study popu-lation included high-dose chemotherapy, a known
Patients tolerated the laser irradiation well. Applica-
mucositis inducer. Despite the development of oral
tions were not performed in a few instances because
mucositis, all patients tolerated the treatment well
of nausea or vomiting, but this did not interfere with
and none developed the maximal pain intensity on
the completion of the entire protocol for all patients.
Two patients developed mucositis grade I-II, 7
Several studies have demonstrated evidence that
patients had grade III-IV, and one patient developed
laser therapy may be beneficial in the healing of
tissues.7,8,15.20,22,23 Although this was not the main
None of patients had the maximal pain score (10).
focus of the present study, none of the 11 patients
Six patients had grade 0-3 and five patients had
had to interrupt their treatment because of oral
grade 4-8 (severe) according to the VAS. The
mucositis and no complications of infection or
majority of patients associated the daily application
bleeding were observed. The encouraging results
of laser on the oral mucosa with prompt pain relief.
from this pilot trial led us to initiate a randomizedcontrolled trial to better understand the role of LLLTin the control and severity of rnucositis after stem
DISCUSSION
cell transplantation and high-dose chernotherapy.
The use of high-dose chemotherapy followed bystem cell support has allowed for a better control of
Fig 2 Extensive oral mucositis lesion on the tongue of a patient Fig 3 Same patient six days later. The tongue was treated with
who received allogeneic bone marrow transplant. The patient
low intensity laser daily. Observe the healing process. There is
only mild erythema on the tongue and the patient is free of pain. CONCLUSION
7. Longo L, Evangelista S, Tinacci G, Sesti AG. Effect of diodes-
laser silver arsenide-aluminiurn (Ga-Al-As) 904 nm on healing of
experimental wounds. Lasers Surg Med 1987;7:444-447.
We conclude that LLLT rnay play a role in the control
8. Mester E, Mester AF, Mester A. The biomedical effects of laser
of pain in oral mucositis after stem cell transplantation.
application. Lasers Surg Med 1985;5:31-39.
9. Mezawa S, lwata K, Naito, Kamogawa H. The possible effect of
ACKNOWLEDGMENTS
soft-laser irradiation on heat nociceptors in the cat tongue. Arch
Centro de Oncologia do Hospital Sírio Libanês, São Paulo, Brazil;
10. Pimenta HM. Laser em Medicina e Biologia. São Paulo: ROCA
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soft laser em odontologia. Rev paul Odont 1992;14:30-32.
12. Taube S, Pironen J, Ylipaavalniemi P. Helium-neon laser therapy
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Artur Ramos Street, 178 Apt. 12-A, São Paulo,
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