BEST PRACTICES: IMMUNOSUPPRESSIVE AND/OR RADIATION THERAPY

Dental Management of Pediatric Patients Receiving

Immunosuppressive Therapy and /or Head and Neck
Radiation
Latest Revision How to Cite: American Academy of Pediatric Dentistry. Dental man-
2022 agement of pediatric patients receiving immunosuppressive therapy
and/or head and neck radiation. The Reference Manual of Pediatric Den-
tistry. Chicago, Ill.: American Academy of Pediatric Dentistry; 2022:507-16.

Abstract
This best practice provides recommendations for oral health care for children undergoing immunosuppressive therapy and/or head and neck
radiation. These children have unique oral health needs and are at risk of developing multiple associated oral and systemic complications.
Dentists play an essential role in diagnosing, preventing, stabilizing, and treating oral health problems that can compromise a patient’s
quality of life before, during, and following such therapies. All children undergoing immunosuppressive therapy and/or head and neck
radiation should have an oral examination before such treatment commences. Dental interventions must be performed promptly, efficiently,
and with attention to the patient’s unique circumstances and treatment protocol. Preventing new dental problems and treating existing
dental conditions before immunosuppressive therapy and/or head and neck radiation is paramount. Preventive strategies include oral
hygiene, diet, fluoride, and patient education. When completing all dental care prior to therapy is not feasible, priorities should be treatment
of odontogenic and periodontal infections, extractions, periodontal care, and removal of sources of tissue irritation. Recommendations for
management of caries lesions, pulp therapy, orthodontia, periodontal conditions, and extractions are included. Strategies to manage oral
conditions related to immunosuppressive therapies and head and neck radiation are addressed. For children undergoing hematopoietic cell
transplantation, all dental treatment should be completed before the patient becomes immunosuppressed and elective care postponed
until immunological recovery has occurred.
This document was developed through a collaborative effort of the American Academy of Pediatric Dentistry Councils on Clinical Affairs and
Scientific Affairs to offer updated information and guidance regarding dental management of pediatric patients receiving immunosuppressive
therapy and/or head and neck radiation.

KEYWORDS: IMMUNOSUPPRESSION, DENTAL CARE, RADIATION THERAPY, MUCOSITIS, TREATMENT PROTOCOL, PHOTOBIOMODULATION

Purpose and associated oral manifestations and appropriately address

The American Academy of Pediatric Dentistry (AAPD) dental concerns in conjunction with the patient’s medical team.
recognizes that the pediatric dental professional plays an
important role in the diagnosis, prevention, stabilization, and Methods
treatment of oral and dental problems that can compromise Developed by the Clinical Affairs Committee as Management
the child’s quality of life before, during, and after immuno- of Pediatric Dental Patients Receiving Chemotherapy and/or
suppressive therapy and/or head and neck radiation. Immuno- Radiation and adopted in 19861, this best practice was last
suppression may be the intended goal of therapies to prevent revised in 20182. This revision is based upon a review of current
rejection of a donor organ or hematopoietic cell transplantation dental and medical literature related to immunosuppressive
(HCT), or it may be a consequence of anti-neoplastic chemo- therapy, head and neck radiation, and best current practice.
therapy or HCT conditioning. Children undergoing such The revision by the Council on Clinical Affairs included a
therapies will benefit from dental interventions that are ®
new literature search of the PubMed /MEDLINE database
prompt, efficient, and modified according to the patient’s
medical history, cancer treatment protocol, and health status.
ABBREVIATIONS
Immunosuppressive therapy and/or head and neck radiation AAPD: American Academy Pediatric Dentistry. ANC: Absolute neu-
may cause many acute and long-term side effects in the oral trophil count. CBC: Complete blood count. GVHD: Graft versus
cavity. Furthermore, any existing or potential sources of oral/ host disease. HCT: Hematopoietic cell transplantation. MASCC /
dental infections and/or soft tissue trauma can compromise ISOO: The Multinational Association of Supportive Care in Cancer/
medical treatment, leading to greater morbidity and mortality, International Society of Oral Oncology. /mm3: per cubic millimeter.
MRONJ: Medication-related osteonecrosis of the jaw. OM: Oral
as well as higher hospitalization costs. It is imperative that the mucositis. PBM: Photobiomodulation.
pediatric dentist be familiar with the patient’s medical history

THE REFERENCE MANUAL OF PEDIATRIC DENTISTRY 507

BEST PRACTICES: IMMUNOSUPPRESSIVE AND/OR RADIATION THERAPY

using the terms: pediatric cancer, pediatric oncology, hemato- • to educate the patient and parents about the importance
poietic cell transplantation, bone marrow transplantation, im- of optimal oral care to minimize oral problems and dis-
munosuppressive therapy, mucositis, stomatitis, chemotherapy, comfort before, during, and after treatment and to
radiotherapy, acute effects, long-term effects, dental care, oral inform them about the possible acute and long-term
health, pediatric dentistry, practice guideline; field: all; limits: effects of the therapy in the oral cavity and the craniofacial
within the last 10 years, humans, English, birth through age complex.
18. Two thousand sixty-five articles matched these criteria.
Ninety-five papers were chosen for review from this list and Initial evaluation
from the references within selected articles. When data did not Medical history review: should include disease/condition (type,
appear sufficient or were inconclusive, recommendations were stage, prognosis), treatment protocol (conditioning regimen,
based upon expert and/or consensus opinion by experienced surgery, chemotherapy, location and dose of radiation), medica-
researchers and clinicians.   tions (including bisphosphonates and other bone modifying
agents), allergies, surgeries, secondary medical diagnoses,
Background hematological status (e.g. complete blood count [CBC]),
A multidisciplinary approach involving physicians, nurses, immunosuppression status, presence of an indwelling venous
dentists, social workers, dieticians, and other related health access line, and contact of medical team/primary care physi-
professionals is essential to care for the child before, during and cian(s).4 For HCT patients, the type of transplant, HCT source
after immunosuppressive therapy and/or head and neck (i.e., bone marrow, peripheral stem cells, cord blood stem cells),
radiation.3,4 Acute and chronic oral complications that may matching status, donor, conditioning protocol, expected date
occur as sequelae of such therapies include oral mucositis of transplant, and GVHD prophylaxis should be elicited.
(OM) and associated pain, bleeding, taste dysfunction, oppor-
tunistic infections (e.g., candidiasis, herpes simplex virus), Dental history review: includes information such as fluoride
dental caries, dry mouth (e.g., salivary gland dysfunction, exposure, habits, trauma, symptomatic teeth, previous care,
xerostomia), neurotoxicity, mucosal fibrosis, gingival hyper- preventive practices, oral hygiene, and diet.
trophy, osteoradionecrosis, medication-related osteonecrosis,
soft tissue necrosis, trismus, craniofacial and dental develop- Oral/dental assessment: should include a thorough head,
mental anomalies, and oral graft versus host disease (GVHD).4-8 neck, and intraoral examination, oral hygiene assessment, and
All patients undergoing immunosuppressive therapy and/ radiographic evaluation based on history and clinical findings.
or head and neck radiation should have an oral examination
prior to initiation of treatment3,4 to identify any existing or Preventive strategies
potential source of oral disease or infection that may compli- Oral hygiene: Brushing of the teeth and tongue two to three
cate the patient’s medical treatment.9,10 Every patient requires times daily should be performed with a regular soft nylon-
an individualized management approach. Consultations with bristled or electric toothbrush, regardless of hematological
the patient’s physicians and, when appropriate, other dental status.11,12,15.16 Ultrasonic brushes and dental floss should only
specialists, should be sought before dental care is instituted.4 be allowed if the patient is properly trained.12 If capable, the
Additionally, the key to success in maintaining a healthy oral patient should gently floss daily. If pain or excessive bleeding
cavity during therapy is patient compliance. Educating the occurs, the patient should avoid the affected area, but floss
child and the parents regarding the possible acute and long- the other teeth. 4 Patients with poor oral hygiene and/or
term side effects of cancer therapies is essential, as this may periodontal disease may use chlorhexidine rinses until the
improve patient motivation to adhere to oral care protocols tissue health improves or mucositis develops. 10,17 The high
during cancer therapy.8,10-13 alcohol content of commercially-available chlorhexidine
mouthwash may cause discomfort and dehydrate the tissues
Recommendations in patients with mucositis. An alcohol-free chlorhexidine
Dental and oral care before the initiation of immunosup- solution is indicated in this situation.
pressive therapy or head and neck radiation
Objectives13,14 Diet: Dental practitioners should discuss the importance of
The objectives of a dental/oral examination before therapy a healthy diet to maintain nutritional status and emphasize
starts are three-fold: food choices that do not promote caries. Patients and parents
• to identify and stabilize or eliminate existing and poten- should be advised about the high cariogenic potential of
tial sources of infection and local irritants in the oral carbohydrate-rich dietary supplements and sucrose-sweetened
cavity—without needlessly delaying the treatment or medications.18,19 They should also be instructed that sharp,
inducing complications. crunchy, spicy, and highly-acidic foods and alcohol should
• to communicate with the medical team regarding the be avoided during chemotherapy, head and neck radiation,
patient’s oral health status, plan, and timing of treatment. and HCT.4

508 THE REFERENCE MANUAL OF PEDIATRIC DENTISTRY

 BEST PRACTICES: IMMUNOSUPPRESSIVE AND/OR RADIATION THERAPY

Fluoride: Preventive measures include the use of fluoridated — < 1,000/mm3: defer elective dental care.7,22 In dental
toothpaste, fluoride supplements if indicated, neutral fluoride emergencies, discuss management with a course of
gels/rinses, or applications of fluoride varnish for patients at antibiotic therapy versus one dose of antibiotics for
risk for caries and/or dry mouth. A brush-on technique is prophylactic coverage with the medical team before
convenient and may increase the likelihood of patient com- proceeding with treatment.
pliance with topical fluoride therapy.12
Patients undergoing cancer treatments are at risk for thrombo-
Lip care: Lanolin-based creams and ointments are more cytopenia. The following parameters may be used to determine
effective in moisturizing and protecting against damage than need for pre- and postoperative interventions:
petrolatum-based products.20 • Platelet count:
— < 60,000/mm3: Defer elective treatment and avoid
Trismus prevention/treatment: Patients who receive head and invasive procedures when possible. When medically-
neck radiation may develop trismus. Thus, daily oral stretch- necessary dental treatment is required, a hospital set-
ing exercises/physical therapy should start before radiation ting is most appropriate. Discuss supportive measures
is initiated and continue throughout treatment.11,21 (e.g., platelet transfusions pre- and postoperatively,
bleeding control, hospital admission and care) with
Reduction of head and neck radiation to healthy oral tissues: the patient’s physician before proceeding. Localized
The use of lead-lined stents, prostheses, and shields, as well as hemostatic measures to manage prolonged bleeding may
salivary gland sparing techniques (e.g., three-dimensional be utilized (e.g., sutures, hemostatic agents, pressure
conformal or intensity modulated radiotherapy, concomitant packs, microfibrillar collagen, topical thrombin and/or
cytoprotectants, surgical transfer of salivary glands), should be gelatin foams). Systemic measures (e.g., aminocaproic
discussed with the radiation oncologist. acid, tranexamic acid) may be recommended by the
hematologist/oncologist. If platelet transfusions are
Education: Patient and parent education includes the import- administered, the dentist should consult with the
ance of optimal oral care in order to minimize oral problems hematologist regarding the need for a posttransfusion
and discomfort before, during, and after treatment and the platelet count before the commencement of dental
possible acute and long-term effects of the therapy in the treatment. Additional transfusions would ideally be
craniofacial complex.4,17 available in the event of excessive and persistent intra-
operative or postoperative bleeding,23
Dental care • Other coagulation tests may be in order for individual
Dental providers should be aware of the patient’s hematologic patients.
status and related risks of bacteremia and excessive bleeding.
Hematologic management of the patient should be directed Dental procedures:
by the patient’s oncologist, and consultation with the medical • Ideally, all dental care should be completed before im-
team is necessary to determine the need for prophylactic munosuppressive therapy is initiated. When that is not
interventions prior to dental treatment. feasible, temporary restorations may be placed and non-
In particular, patients who are immunosuppressed may not acute dental treatment may be delayed until the patient’s
be able to tolerate a transient bacteremia following invasive hematological status is stable.4,24 The patient’s blood
dental procedures. A decision regarding the need for antibiotic counts typically start falling five to seven days after the
prophylaxis prior to dental treatment should be made in beginning of treatment cycle and stay low for approxi-
consultation with the child’s physician. Unless advised other- mately 14 to 21 days before rising again to normal levels.
wise, the American Heart Association’s standard regimen to Patients who require an organ transplant are best able to
prevent endocarditis is an acceptable option for the immu- tolerate dental care at least three months after transplant
nocompromised patient.4,16 The following parameters may be when overall health improves.3
used to guide decisions regarding need for antibiotic prophylaxis: • Prioritizing procedures: In the event that definitive
• Absolute neutrophil count (ANC): dental care would result in a delay of oncologic treatment
— > 2,000 per cubic millimeter (/mm3): no need for and a resultant poorer medical prognosis, providers
antibiotic prophylaxis;4,21 may prioritize treatment of symptomatic or potentially
— 1,000 to 2,000/mm3: Use clinical judgment based on symptomatic caries lesions (risk of irreversible pulpitis),
the patient’s health status and planned procedures. infections, hopeless teeth (e.g., root tips, nonrestorable
Some authors4 suggest that antibiotic coverage may be teeth) and removal of sources of tissue irritation before the
prescribed when the ANC is in range. If infection is treatment of asymptomatic carious teeth (e.g., incipient,
present at the site of the planned procedure, a more small asymptomatic caries lesions), root canal therapy
aggressive prophylactic antibiotic therapy regimen may for asymptomatic permanent teeth, and replacement of
be discussed with the medical team; and faulty restorations.7,21,24 It is important for the practitioner

THE REFERENCE MANUAL OF PEDIATRIC DENTISTRY 509

BEST PRACTICES: IMMUNOSUPPRESSIVE AND/OR RADIATION THERAPY

to be aware that the signs and symptoms of periodontal • Periodontal considerations: Extraction is the treatment of
disease and infection may be decreased in immunosup- choice for teeth with a poor prognosis (e.g., nonrestorable
pressed patients.11,21 teeth, periodontal pockets greater than five millimeters,
• Pulp therapy in primary teeth: Few studies have eval- significant bone loss, furcation involvement, mobility,
uated the safety of performing pulp therapy in primary infection) that cannot be treated by definitive periodontal
teeth prior to the initiation of chemotherapy and/or therapy. Partially-erupted molars can become a source of
head and neck radiation. Many clinicians choose to extract infection because of pericoronitis. The overlying gingival
pulpally-involved carious teeth because of the potential tissue should be excised if the dentist believes it is a po-
for pulpal/periapical/furcal infections to become life- tential risk and if the hematological status permits.12,21
threatening during periods of immunosuppression.12 • Third molars and other impacted teeth: Some practi-
Asymptomatic teeth that are already pulpally treated tioners prefer to extract all third molars that are not fully
and are clinically and radiographically sound should be erupted, particularly prior to HCT. Others favor a more
monitored periodically for clinical and radiographic signs conservative approach and only recommend extraction of
of failure. third molars at risk for pulpal infection, with significant
• Endodontic treatment in permanent teeth: Symptomatic pathology, infection, periodontal disease, or pericoronitis,
nonvital permanent teeth ideally should receive root or when malposed or nonfunctional.12,25,26
canal treatment in a single visit at least one week before • Primary teeth that are mobile due to natural exfoliation
initiation of immunosuppressive therapy to allow suffi- may be left alone.
cient time to assess treatment success.7,21 If that is not • Extractions: Surgical procedures must be as atraumatic
possible, alternative options include pulpectomy and as possible, with no sharp bony edges remaining and
closure with an antibacterial agent or extraction. The satisfactory closure of the wounds. These extractions
need for antibiotics is determined by the patient’s health ideally are performed three weeks (or at least 10 to 14 days)
status and should be discussed with the patient’s phys- before cancer therapy is initiated to allow for adequate
ician. Endodontic treatment of asymptomatic nonvital healing.12,21 If the patient is immunocompromised and
permanent teeth may be delayed until the immunologic at risk of infection from transient bacteremia, antibiotic
status of the patient is stable.7,21 The etiology of periapical prophylaxis should be discussed with the patient’s
radiolucencies associated with teeth previously treated physicians. Regardless of hematologic status, if there is
endodontically should be determined because they may documented infection associated with the extracted tooth,
represent pulpal infections, inflammatory reactions, apical antibiotics (ideally chosen with the benefit of sensitivity
scars, cysts, or malignancies.12 Periapical lesions that are testing) should be administered for about one week post-
asymptomatic and most likely depict apical scars do not operatively.12,21
need retreatment.24 • Pediatric patients who are on bone modifying agents
• Orthodontic appliances and space maintainers: Poorly- (e.g., bisphosphonates, antiresorptive, agents, anti-
fitting appliances can result in a breach of oral mucosa angiogenic agents) as part of their cancer treatment or
and increased the risk of microbial invasion into deeper who have had head and neck radiation are at an increased
tissues.22 Fixed appliances should be removed if the risk of medication-related osteonecrosis of the jaw
patient has poor oral hygiene or if the treatment pro- (MRONJ) or osteoradionecrosis27-30, although most of
tocol (e.g., HCT conditioning regimen, head and neck the evidence has been described in the adult population28.
radiation) carries a risk for the development of moderate Patients deemed to be at a significant risk of MRONJ
to severe mucositis.7 Simple appliances (e.g., band and or osteoradionecrosis are best managed by a dentist in
loops, fixed lower lingual arches) that are not irritating coordination with the medical team in a hospital setting.
to the soft tissues may be left in place in patients with To minimize the risk of development of osteoradione-
good oral hygiene.7,12 Removable appliances and retainers crosis or MRONJ, patients ideally would have all oral
that fit well may be worn as long as tolerated by the surgical procedures (e.g., extractions, periodontal treat-
patient with good oral care.12 Patients should be instructed ment) completed before those therapies are instituted.27,28
to clean their appliance daily and routinely clean appli- For patients who have been on antiresorptive (e.g.,
ance cases with an antimicrobial solution to prevent bisphosphates, denosumab) or anti-angiogenic agents as
contamination and reduce the risk of appliance-associated part of their cancer treatment or have had radiation to
oral infections. Consider removing orthodontic bands or the jaws and an oral surgical procedure or invasive perio-
adjusting prostheses that approximate gingival tissue if a dontal procedure is necessary, it is important to discuss
patient is expected to receive cyclosporine or other drugs risks with the patient and caregivers prior to the procedure.
known to cause gingival hyperplasia. If band removal is
not possible, vinyl mouth guards or orthodontic wax Communication:
should be used to decrease tissue trauma.12 The dentist’s communication of the comprehensive oral care
plan with the medical team is vital. Information to be shared

510 THE REFERENCE MANUAL OF PEDIATRIC DENTISTRY

 BEST PRACTICES: IMMUNOSUPPRESSIVE AND/OR RADIATION THERAPY

includes the extent of non-elective dental treatment needed, OM.15,31 Currently, data for the pediatric population is limited;
need for supportive care (e.g., hospital admission, blood thus, recommendations are based largely on adult studies. The
product replacement, antibiotic coverage) and the amount of recommended prescriptions for prevention of OM include
time needed for stabilization of oral disease and healing from good oral hygiene, bland mouth rinses (saline or sodium bi-
the dental procedures. Discussions with the medical team can carbonate), benzydamine mouthrinse, cryotherapy, palifermin,
ensure ideal coordination between needed dental services and and photobiomodulation therapy (PBM).31,32 Mucosal coating
planned cancer therapy.4 agents (e.g., hydroxypropylmethylcellulose) and film-forming
agents also have been suggested. 4 The use of sucralfate,
Oral care during immunosupression periods and radiation antimicrobial lozenges, chlorhexidine, pentoxifylline, and
therapy granulocyte-macrophage colony stimulating factor mouthwash
Preventive strategies for OM are not recommended.15,31
Oral hygiene: Maintenance of good oral care in patients Oral cryotherapy, the cooling of intraoral tissue with ice, is
undergoing immunosuppressive therapy and head and neck recommended as OM prophylaxis for patients receiving bolus
radiation is necessary to reduce the microbial load in the oral infusion of chemotherapy drugs with short half-lives.31,33 Oral
cavity. This may decrease the host inflammatory response and cryotherapy reduces the blood flow to the mouth by narrowing
subsequent severity of OM. Furthermore, a clean oral cavity the blood vessels, thus limiting the amount of chemotherapy
reduces the risk of opportunistic infections.4,10-12,15,21,22 Patients drugs delivered to the tissues. Cryotherapy is inexpensive and
should use a soft nylon brush two to three times daily and readily available, but further research is needed to confirm the
replace it every two to three months.12,15 effectiveness of oral cryotherapy in children.32,33
Thrombocytopenia is not the sole determinant of oral hy- Palifermin (keratinocyte growth factor-1) is a drug approved
giene as patients are able to brush without bleeding at widely by the United States (U.S.) Food and Drug Administration
different levels of platelet counts.12 Fluoridated toothpaste is for the prevention of oral mucositis34 in patients undergoing
effective for caries prevention, and a mildly-flavored toothpaste conditioning with high-dose chemotherapy and total body
may be better tolerated during periods of OM. If moderate to irradiation followed by HCT.31 Palifermin exerts its effect by
severe OM develops and the patient cannot tolerate a regular stimulating epithelial cell reproduction, growth, and develop-
soft nylon toothbrush or an end-tufted brush, foam brushes ment so that mucosal cells damaged by chemotherapy and
or super soft brushes soaked in chlorhexidine may be used.13,14 radiation are replaced quickly, accelerating the healing
Otherwise, foam or super soft brushes are discouraged because process.11,35
they do not allow for effective cleaning. The use of a regular The current MASCC/ISOO guidelines support the use of
brush should be resumed as soon as the OM improves. 12,15 PBM therapy to prevent OM in patients undergoing HCT
Brushes should be air-dried between uses.12 Electric or ultra- conditioning with high-dose chemotherapy with or without
sonic brushes are acceptable if the patient can use them total body irradiation as well as patients undergoing radiation
without causing trauma and irritation. If patients are skilled treatment for head and neck cancer.31 PBM can decrease pain
at flossing without traumatizing the tissues, it is reasonable and the duration and severity of chemotherapy-induced OM
to continue flossing throughout treatment. Toothpicks and in children.36-38 PBM may not be available at all cancer treat-
water irrigation devices should not be used when the patient ment centers due to the cost of the equipment and the need
is pancytopenic to avoid tissue trauma.12 for trained personnel. Appropriate protocol must be followed
when using PBM to prevent contamination and occupational
Dental care risks to the child and dental team.
During immunosuppression, elective dental care should be With regard to chlorhexidine, most studies have not dem-
deferred. If a dental emergency arises, the treatment plan onstrated a prophylactic impact or a reduction in the severity
should be discussed with the patient’s physician who will of OM. 11,21,39,40 Chlorhexidine is not recommended for
make recommendations for supportive medical therapies (e.g., prevention of oral mucositis in patients undergoing head and
antibiotics, platelet transfusions, analgesia). The patient’s oral neck radiation.15,31
health should be reevaluated every six months (or in shorter Patient-controlled analgesia is helpful in relieving pain
intervals if there is a risk of dry mouth, caries, trismus, and/or associated with OM, reducing the requirement for oral anal-
chronic oral GVHD) during treatment, in times of stable gesics. The use of topical anesthetics and mixtures containing
hematological status and always after reviewing the medical topical anesthetics (e.g., Philadelphia mouthwash, magic
history. mouthwash) has been suggested for pain management.15,41
However, topical anesthetics only provide short-term pain
Management of oral mucositis and associated pain related to relief. 15 In addition to possible cardiovascular and central
immunosuppressive therapies nervous system effects, their use may obtund or diminish taste
Oral mucositis: The Multinational Association of Supportive and the gag reflex11 and/or result in a burning sensation. Cur-
Care in Cancer/International Society of Oral Oncology rently, the evidence for its benefit is lacking17, and potential
(MASCC/ISOO) has published guidelines for treatment of for toxicity is a concern in young children.

THE REFERENCE MANUAL OF PEDIATRIC DENTISTRY 511

BEST PRACTICES: IMMUNOSUPPRESSIVE AND/OR RADIATION THERAPY

Oral mucosal infections: The signs of oral mucosal inflamma- • malignant disorders treated with allogenic HCT
tion and infection may be diminished during neutropenic – acute lymphocytic leukemia.
periods. Thus, the clinical appearance of infections may dif- – acute myeloid leukemia.
fer significantly from the expected.21 Close monitoring of the – high-risk solid tumors.
oral cavity allows for timely diagnosis and treatment of fungal, – juvenile myelomonocytic leukemia.
viral, and bacterial infections. Oral cultures and/or biopsies of – myelodysplastic syndrome.
all suspicious lesions are appropriate if medical status permits. • nonmalignant disorders treated with allogenic HCT
While waiting for the results, empiric therapy typically is ini- – bone marrow failure syndromes.
tiated until laboratory results dictate more specific medica- – chronic granulomatous disease.
tions.4,12,21 Of note, nystatin is not effective for the prevention – Fanconi anemia.
and/or treatment of fungal infections.11,42 – metabolic storage disorders.
– osteopetrosis.
Oral bleeding: Oral bleeding in patients undergoing immuno- – severe aplastic anemia.
suppressive therapy commonly occurs due to thrombocyto- – sickle cell anemia.
penia and/or damaged vascular integrity. Management consists – thalessemia.
of local (e.g., pressure packs, antifibrinolytic rinses or topical – Wiskott-Aldrich syndrome.
agents, gelatin sponges) and systemic measures (e.g., platelet Specific oral complications can be correlated with phases
transfusions, aminocaproic acid).11,12,21 of HCT.3,4,7,10,15

Dental sensitivity/pain: Tooth sensitivity may be related to Phase I: Preconditioning

dry mouth during chemotherapy or head and neck radiation The oral complications are related to the patient’s current
therapy and the lowered salivary pH.11,12,21 Patients who are systemic and oral health, oral manifestations of the underlying
using plant alkaloid chemotherapeutic agents (e.g., vincristine, condition, and oral complications of recent medical therapy.
vinblastine) may experience neurotoxicity that presents as Oral complications observed include opportunistic infections,
deep, constant jaw pain (affecting the mandibular molars with gingival leukemic infiltrates, bleeding, and ulceration.4 Most
greater frequency) or paresthesia in the absence of odonto- of the principles of dental and oral care before the transplant
genic pathology. The pain usually is transient and generally are similar to those discussed for patients undergoing immu-
subsides shortly after dose reduction and/or cessation of nosuppressive cancer therapy.13 The two major differences in
chemotherapy.11,12,21 HCT are: 1) the patient receives extremely high dose chemo-
therapy and/or total body irradiation immediately prior to (a
Dry mouth: Sugar-free chewing gum or candy, sucking tablets, few days before) the transplant, and 2) there will be prolonged
special dentifrices for oral dryness, saliva substitutes, frequent immunosuppression following the transplant. Elective den-
sipping of water, alcohol-free oral rinses, and/or oral moistur- tistry will need to be postponed until immunological recovery
izers are recommended.5,12,43 Placing a humidifier by the child’s has occurred, at least 100 days following HCT. This may
bedside at night may be useful.21 Fluoride rinses and gels are be longer if chronic GVHD or other complications (e.g.,
highly recommended for caries prevention in these patients. persistent immunodeficiency) are present.12 Therefore, all
dental treatment should be completed before the patient
Trismus: Daily oral stretching exercises/physical therapy should undergoes HCT.
be implemented during head and neck radiation treatment.
Management of trismus may include prosthetic aids to reduce Phase II: Conditioning neutropenic phase
the severity of fibrosis, trigger-point injections, analgesics, In this phase, which encompasses the day the patient is admitted
muscle relaxants, and other pain management strategies.11,22,44 to the hospital to begin the transplant conditioning to 30 days
post-HCT, the majority of oral complications are related to
Hematopoietic cell transplantation the conditioning regimen and supportive medical therapies.12
Hematopoietic cell transplantation is used in children to Mucositis, dry mouth, oral pain, hemorrhage, opportunistic
treat malignancies and hematologic disorders, as well as infections, taste dysfunction, neurotoxicity (including dental
certain metabolic syndromes. Examples include:45 pain, muscle tremors), and temporomandibular dysfunction
• malignant disorders treated with autologous HCT (including jaw pain, headache, joint pain) may be present.4
– brain tumors. Oral mucositis usually begins seven to 10 days after initiation
– Ewing sarcoma. of conditioning, and symptoms continue approximately two
– germ cell tumors. weeks after the end of conditioning.4 Among allogeneic
– Hodgkin lymphoma. transplant patients, acute GVHD can occur, causing more
– leukemia. severe inflammation and severe mucositis symptoms. Acute
– neuroblastoma. GVHD may begin as early as two to three weeks after the
– non-Hodgkin lymphoma. start of HCT and continue up to two months posttransplant.
– Wilms tumor.

512 THE REFERENCE MANUAL OF PEDIATRIC DENTISTRY

 BEST PRACTICES: IMMUNOSUPPRESSIVE AND/OR RADIATION THERAPY

The timing of this presentation may help distinguish acute Dental care
GVHD from chemotherapy-induced OM.4 The patient may Periodic evaluation: The patient should be seen every six
be followed closely to monitor and manage the oral changes months (or more frequently if issues such as chronic oral
and to reinforce the importance of optimal oral care. Elective GVHD, dry mouth, or trismus are present). Patients who
dental procedures are avoided in this phase due to the patient’s have experienced moderate or severe mucositis and/or chronic
severe immunosuppression. If emergency treatment is necessary, oral GVHD should be followed closely for signs of malignant
the dentist should consult and coordinate with the attending transformation of their oral mucosa (e.g., oral squamous cell
transplant team. carcinoma).4,10,46

Phase III: Engraftment to hematopoietic recovery Education: The importance of optimal oral and dental care
The intensity and severity of acute complications observed in for life must be reinforced. It is also important to emphasize
Phase II usually begin to decrease three to four weeks after the need for regular follow-ups with a dental professional,
transplantation. During this phase, acute GVHD can become especially for patients who are at risk for or have developed
a concern for allogeneic graft recipients. Dry mouth, hemor- GVHD and/or dry mouth and those who were younger than
rhage, neurotoxicity, temporomandibular dysfunction, and six years of age during treatment due to potential dental de-
granulomas/papillomas also are observed sometimes.4 With velopmental problems.
regard to opportunistic infections, oral fungal infections and
herpes simplex virus infection are most likely.4 HCT patients Orthodontic treatment: Orthodontic care may start or resume
are particularly sensitive to intraoral thermal stimuli between after completion of all therapy and after at least a two-year
two and four months posttransplant.12 The mechanism is not disease-free survival when the risk of relapse is decreased and
well understood, but the symptoms usually resolve sponta- the patient is no longer using immunosuppressive drugs.7 A
neously within a few months. Topical application of neutral thorough assessment of any dental developmental disturbances
fluoride or desensitizing toothpastes helps reduce the caused by the therapy must be performed before initiating
symptoms.12 A dental/oral examination should be performed orthodontic treatment. The following strategies may be
and invasive dental procedures, including dental cleanings and considered when providing orthodontic care for patients with
soft tissue curettage, should be done only if authorized by the dental sequelae: (1) use appliances that minimize the risk of
HCT team because of the patient’s continued immunosup- root resorption, (2) use lighter forces, (3) terminate treatment
pression.12 Patients should be encouraged to optimize oral earlier than normal, (4) choose the simplest method for the
hygiene and avoid a cariogenic diet. treatment needs, and (5) do not treat the lower jaw.47 How-
ever, specific guidelines for orthodontic management, including
Phase IV: Immune reconstitution/recovery from systemic toxicity optimal force and pace, remain undefined. Patients and their
After day 100 post-HCT, the oral complications are predom- families may be made aware of the potential for a higher risk
inantly related to the chronic toxicity associated with the of orthodontic relapse among cancer survivors.48 Patients who
conditioning regimen, including dry mouth, craniofacial growth were on intravenous antiresorptive or anti-angiogenic agents
abnormalities, late viral infections, chronic oral GVHD, and as part of their cancer treatment, or in those who have had
oral squamous cell carcinoma.4,12 Unless the patient is neutro- head and neck radiation, may present a challenge for ortho-
penic or with severe chronic GVHD, mucosal bacterial infec- dontic care. Although bisphosphonate inhibition of tooth
tions are less frequently seen. Periodic dental examinations with movement has been reported in animals, it has not been
radiographs can be performed, but invasive dental treatment is quantified for any dose or duration of therapy in humans.47,49
to be avoided in patients with persistent profound impairment Consultation with the patient’s caregivers and physician
of immune function.12 Consultation with the patient’s physician regarding the risks (e.g. prolonged treatment time, MRONJ,
and parents regarding the risks and benefits of orthodontic treatment modifications)49 and benefits (e.g., reduced root
care is recommended. resorption, anchorage, less relapse)49 of orthodontic care in
this situation is recommended.
Dental and oral care after immunosuppressive therapy and
head and neck radiation have been completed Oral surgery and invasive periodontal therapy: Patients at
Objectives risk for MRONJ or osteoradionecrosis should be managed
The objectives of a dental/oral examination after immuno- in coordination with the oncology team in the hospital set-
suppressive therapy ends are three-fold: ting.27,28,30 Elective invasive procedures are best avoided in
• to maintain optimal oral health. these patients.27,49
• to reinforce to the patient/parents the importance of
optimal oral and dental care for life. Long-term concerns
• to address any dental issues that may arise as a result of Craniofacial, skeletal, and dental developmental issues are
the long-term effects of immunosuppressive therapy or some of the complications faced by survivors3,7,8,12 and usually
head and neck radiation. develop among children who were less than six years of age

THE REFERENCE MANUAL OF PEDIATRIC DENTISTRY 513

BEST PRACTICES: IMMUNOSUPPRESSIVE AND/OR RADIATION THERAPY

at the time of their cancer therapy.7,12 Long-term effects of 5th ed. Chicago, Ill.: American Academy of Pediatric
immunosuppressive therapy may include tooth agenesis, Dentistry; 2018:361-9.
microdontia, crown disturbances (size, shape, enamel hypo- 8. Gawade PL, Hudson MM, Kaste SC, et al. A systematic
plasia, pulp chamber anomalies), root disturbances (early review of dental late effects in survivors of childhood
apical closure, blunting, changes in shape or length), reduced cancer. Pediatr Blood Cancer 2014;61(3):407-16.
mandibular length, reduced alveolar process height, and 9. Velten DB, Zandonade E, Monteiro de Barros Miotto
reduced vertical growth of the face.5,7,8 The severity of the MH. Prevalence of oral manifestations in children and
dental developmental anomaly will depend on the age and adolescents with cancer submitted to chemotherapy.
stage of development during exposure to cytotoxic agents or BMC Oral Health 2017;17(1):49.
ionizing radiation. Patients may experience permanent salivary 10. Elad S, Raber-Durlacher JE, Brennan MT, et al. Basic oral
gland hypofunction/dysfunction or dry mouth.44 Relapse or care for hematology-oncology patients and hematopoietic
secondary malignancies can develop at this stage.4,46 Routine stem cell transplantation recipients: A position paper from
periodic examinations are necessary to provide comprehensive the joint task force of the Multinational Association of
oral healthcare. Careful examination of extra-oral and intra- Supportive Care in Cancer/International Society of Oral
oral tissues (including clinical, radiographic, and/or additional Oncology (MASCC/ISOO) and the European Society
diagnostic examinations) are integral to diagnosing any for Blood and Marrow Transplantation (EBMT). Support
secondary malignancies in the head and neck region. Dental Care Cancer 2015;23(1):223-36.
treatment may require a multidisciplinary approach, involving 11. Kwok K, Vincent E, Gibson J. Antineoplastic drugs. In:
a variety of dental specialists to address the treatment needs Dowd FJ, Johnson BS, Mariotti AJ, eds. Pharmacology
of each individual. Consultation with the patient’s physician is and Therapeutics for Dentistry. 7th ed. St. Louis, Mo.:
recommended if relapse occurs or the patient’s immunologic Mosby Elsevier, 2017:530-62.
status declines. 12. Schubert MM, Pizzigatti Correa ME, Peterson DE. Oral
complications of hematopoietic cell transplantation. In:
References Antin JH, Appelbaum RF, Forman SJ, Negrin RS, eds.
1. American Academy of Pediatric Dentistry. Management Thomas’ Hematopoietic Cell Transplantation: Stem Cell
of pediatric dental patients receiving chemotherapy and/ Transplantation. 5th ed. Oxford, UK: Wiley-Blackwell;
or radiation. Colorado Springs, Colo.: American Academy 2016:1242-68.
of Pediatric Dentistry; May, 1986. 13. Hong CH, da Fonseca M. Considerations in the pediatric
2. American Academy of Pediatric Dentistry. Best practices population with cancer. Dent Clin North Am 2008;52
for dental management of pediatric patients receiving (1):155-81.
immunosuppressive therapy and/or radiation therapy. 14. Ritwik P, Chrisentery-Singleton TE. Oral and dental
Pediatr Dent 2018;40(6):392-400. considerations in pediatric cancers. Cancer Metastasis
3. National Institute of Dental and Craniofacial Research. Rev 2020;39(1):43-53.
Dental management of the organ or stem cell transplant 15. Peterson DE, Boers-Doets CB, Bensadoun RJ, Herrstedt
patient. Bethesda, Md.: National Institute of Dental and J, Roila F, ESMO Guidelines Working Group. Manage-
Craniofacial Research; Modified July, 2016. Available ment of oral and gastrointestinal mucosal injury: ESMO
at: “https://www.nidcr.nih.gov/sites/default/files/2017- clinical practice guidelines for diagnosis, treatment, and
09/dental-management-organ-stem-cell-transplant.pdf ”. follow-up. Ann Oncol 2015;26(Suppl_5):vi139-v151.
Accessed September 22, 2022. 16. Wilson WR, Gewitz M, Lockhart PB, et al. Prevention
®
4. PDQ Supportive and Palliative Care Editorial Board. of viridans group streptococcal infective endocarditis:
PDQ Oral Complications of Chemotherapy and Head/ A scientific statement from the American Heart Associ-
Neck Radiation. Bethesda, Md.: National Cancer Insti- ation. Circulation 2021;143(20):e963-e978. Erratum in:
tute. Updated July 14, 2021. Available at: “https: Circulation 2021;144(9):e192.
//www.cancer.gov/about-cancer/treatment/side-effects/ 17. Hong CHL, Gueiros LA, Fulton JS, et al. Mucositis Study
mouth-throat/oral-complications-hp-pdq”. Accessed Group of the Multinational Association of Supportive
September 22, 2022. Care in Cancer/International Society for Oral Oncology
5. Chaveli-López B. Oral toxicity produced by chemother- (MASCC/ISOO). Systematic review of basic oral care
apy: A systematic review. J Clin Exp Dent 2014;6(1): for the management of oral mucositis in cancer patients
e81-e90. and clinical practice guidelines. Support Care Cancer
6. Gandhi K, Datta G, Ahuja S, Saxena T, Datta A G. Preval- 2019;27(10):3949-67.
ence of oral complications occurring in a population of 18. Wang Y, Zeng X, Yang X, et al. Oral health, caries risk
pediatric cancer patients receiving chemotherapy. Int J profiles, and oral microbiome of pediatric patients with
Clin Pediatr Dent 2017;10(2):166-71. leukemia submitted to chemotherapy. Biomed Res Int
7. da Fonseca M. Childhood cancer. In: Nowak AJ, Casa- 2021;2021:6637503.
massimo PS, eds. The Handbook of Pediatric Dentistry.

514 THE REFERENCE MANUAL OF PEDIATRIC DENTISTRY

 BEST PRACTICES: IMMUNOSUPPRESSIVE AND/OR RADIATION THERAPY

19. Nirmala SV, Popuri VD, Chilamakuri S, et al. Oral health Oral Oncology (MASCC/ISOO). MASCC/ISOO clini-
concerns with sweetened medicaments: Pediatricians’ cal practice guidelines for the management of mucositis:
acuity. J Int Soc Prev Community Dent 2015;5(1):35-9. Sub-analysis of current interventions for the management
20. Santos PS, Tinôco-Araújo JE, Souza LM, et al. Efficacy of oral mucositis in pediatric cancer patients. Support
®
of HPA Lanolin in treatment of lip alterations related Care Cancer 2021;29(7):3539-62.
to chemotherapy. J Appl Oral Sci 2013;21(2):163-6. 33. Peterson DE, Ohrn K, Bowen J, et al. Systematic review
21. Little JW, Miller CS, Rhodus NL. Cancer and oral care of oral cryotherapy for management of oral mucositis
of patients with cancer. In: Little and Falace’s Dental caused by cancer therapy. Support Care Cancer 2013;21
Management of the Medically Compromised Patient. 9th (1):327-32.
ed. St. Louis, Mo.: Elsevier; 2018:501-13. 34. U.S. Food and Drug Administration. Palifermin (marketed
22. Levi LE, Lalla RV. Dental treatment planning for the as Kepivance). July 16, 2015. Available at: “https://www.
patient with oral cancer. Dent Clin North Am 2018;62 fda.gov/drugs/postmarket-drug-safety-information-patients
(1):121-30. -and-providers/ palifermin-marketed-kepivance”. Accessed
23. Schiffer CA, Bohlke K, Delaney M, et al. Platelet trans- July 12, 2021.
fusion for patients with cancer: American Society of 35. Logan RM, Al-Azri AR, Bossi P, et al. Mucositis Study
Clinical Oncology Clinical Practice Guideline Update. J Group of the Multinational Association of Supportive
Clin Oncol 2018;36(3):283-99. Care in Cancer/International Society of Oral Oncology
24. Hong CHL, Hu S, Haverman T, et al. A systematic review (MASCC/ISOO). Systematic review of growth factors
of dental disease management in cancer patients. Support and cytokines for the management of oral mucositis in
Care Cancer 2018;26(1):155-74. cancer patients and clinical practice guidelines. Support
25. American Academy of Pediatric Dentistry. Management Care Cancer 2020;28(5):2485-98.
considerations for pediatric oral surgery and oral pathol- 36. He M, Zhan B, Shen N, et al. A systematic review and
ogy. The Reference Manual of Pediatric Dentistry. meta-analysis of the effect of low level laser therapy
Chicago, Ill.: American Academy of Pediatric Dentistry; (LLLT) on chemotherapy-induced oral mucositis in
2022:485-94. pediatric and young patients. Eur J Pediatr 2018;177(1):
26. American Association of Oral and Maxillofacial Surgeons. 7-17.
Management of third molar teeth. 2016. White Paper. 37. Amadori F, Bardellini E, Conti G, et al. Low-level laser
Available at: “https://www.aaoms.org/docs/govt_affairs/ therapy for treatment of chemotherapy-induced oral
advocacy_white_papers/management_third_molar_white mucositis in childhood: A randomized double-blind
_paper.pdf ”. Accessed July 12, 2021. controlled study. Lasers Med Sci 2016;31(6):1231-6.
27. Yarom N, Shapiro CL, Peterson DE, et al. Medication- 38. Eduardo Fde P, Bezinelli LM, de Carvalho DL, et al. Oral
related osteonecrosis of the jaw: MASCC/ISOO/ASCO mucositis in pediatric patients undergoing hematopoietic
Clinical Practice Guideline. J Clin Oncol 2019;37(25): stem cell transplantation: Clinical outcomes in a context
2270-90. of specialized oral care using low-level laser therapy.
28. Migliorati CA, Brennan MT, Peterson DE. Medication- Pediatr Transplant 2015;19(3):316-25.
related osteonecrosis of the jaws. J Natl Cancer Inst 39. Worthington HV, Clarkson JE, Bryan G, et al. Interven-
Monogr 2019;2019(53):lgz009. tions for preventing oral mucositis for patients with
29. Ruggiero SL, Dotson TB, Fantasia J, et al. American cancer receiving treatment. Cochrane Database Syst Rev
Association of Oral and Maxillofacial Surgeons position 2011(4):CD000978.
paper on medication-related osteonecrosis of the jaw-- 40. Cardona A, Balouch A, Abdul MM, et al. Efficacy of
2014 update. J Oral Maxillofac Surg 2014;72(10): chlorhexidine for the prevention and treatment of oral
1938-56. mucositis in cancer patients: A systematic review with
30. Kühl S, Walter C, Acham S, Pfeffer R, Lambrecht JT. meta-analysis. J Oral Pathol Med 2017;46(9):680-8.
Bisphosphonate-related osteonecrosis of the jaws--A 41. Saunders DP, Rouleau T, Cheng K, et al. Mucositis Study
review. Oral Oncol 2012;48(10):938-47. Group of the Multinational Association of Supportive
31. Elad S, Cheng KKF, Lalla RV, et al. Mucositis Guidelines Care in Cancer/International Society of Oral Oncology
Leadership Group of the Multinational Association of (MASCC/ISOO). Systematic review of antimicrobials,
Supportive Care in Cancer and International Society of mucosal coating agents, anesthetics, and analgesics for
Oral Oncology (MASCC/ISOO). MASCC/ISOO clinical the management of oral mucositis in cancer patients and
practice guidelines for the management of mucositis clinical practice guidelines. Support Care Cancer 2020;
secondary to cancer therapy. Cancer 2020;126(19): 28(5):2473-84.
4423-31. 42. Gøtzsche PC, Johansen HK. Nystatin prophylaxis and
32. Miranda-Silva W, Gomes-Silva W, Zadik Y, et al. Mucositis treatment in severely immunodepressed patients.
Study Group of the Multinational Association of Cochrane Database Syst Rev 2014;2014(9):CD002033.
Supportive Care in Cancer/International Society for
References continued on the next page.

THE REFERENCE MANUAL OF PEDIATRIC DENTISTRY 515

BEST PRACTICES: IMMUNOSUPPRESSIVE AND/OR RADIATION THERAPY

43. Carvalho CG, Medeiros-Filho JB, Ferreira MC. Guide for 47. Zahrowski JJ. Bisphosphonate treatment: An orthodontic
health professionals addressing oral care for individuals concern for a proactive approach. Am J Orthod Dento-
in oncological treatment based on scientific evidence. facial Orthop 2007;131(3):311-20.
Support Care Cancer 2018;26(8):2651-61. 48. Mitus-Kenig M, Derwich M, Czochrowska E, Pawlowska
44. Jensen SB, Vissink A, Limesand KH, Reyland ME. E. Cancer survivors present significantly lower long-term
Salivary gland hypofunction and xerostomia in head and stability of orthodontic treatment: A prospective case-
neck radiation patients. J Natl Cancer Inst Monogr control study. Eur J Orthod 2021;43(6):631-8. Available
2019;2019(53):lgz016. at: “https://doi.org/10.1093/ejo/cjaa083”. Accessed
45. Majhail NS, Farnia SH, Carpenter PA, et al. Indications March 27, 2022.
for autologous and allogenic hematopoietic cell trans- 49. Bhatt RN, Hibbert SA, Munns CF. The use of bisphos-
plantation: Guidelines from the American Society for phonates in children: Review of the literature and
Blood and Marrow Transplantation. Biol Blood Marrow guidelines for dental management. Aust Dent J 2014;59
Transplant 2015;21(11):1863-96. (1):9-19.
46. Inamoto Y, Shah NN, Savani BN, et al. Secondary solid
cancer screening following hematopoietic cell transplanta-
tion. Bone Marrow Transplant 2015;50(8):1013-23.

516 THE REFERENCE MANUAL OF PEDIATRIC DENTISTRY