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Dental Management of Pediatric Patients Receiving

Immunosuppressive Therapy and/or Head and Neck Radiation

Latest Revision
2022

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 treatments 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
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ABBREVIATIONS
AAPD: American Academy Pediatric Dentistry. ANC: Absolute neutrophil count. CBC: Complete blood
count. GVHD: Graft versus host disease. HCT: Hematopoietic stem cell transplantation. MASCC/ISOO:
The Multinational Association of Supportive Care in Cancer/ International Society of Oral Oncology.
/mm3: per cubic millimeter. MRONJ: Medication-related osteonecrosis of the jaw. OM: Oral mucositis.
PBM: Photobiomodulation.

Purpose
The American Academy of Pediatric Dentistry (AAPD) recognizes that the pediatric dental professional
plays an important role in the diagnosis, prevention, stabilization, and treatment of oral and dental problems
that can compromise a child’s quality of life before, during, and after immunosuppressive therapy and/or
head and neck radiation. Immunosuppression may be the intended goal of therapies to prevent rejection of
a donor organ or hematopoietic cell transplantation (HCT) or it may be a consequence of anti-neoplastic
chemotherapy or HCT conditioning. Children undergoing such therapies will benefit from dental
interventions that are prompt, efficient, and modified according to the patient’s medical history, cancer
treatment protocol, and health status.

Immunosuppressive therapy and/or head and neck radiation may cause many acute and long-term side
effects in the oral cavity. Furthermore, any existing or potential sources of oral/dental infections and/or soft
tissue trauma can compromise medical treatment, leading to greater morbidity and mortality, as well as
higher hospitalization costs. It is imperative that the pediatric dentist be familiar with the patient’s medical
history and associated oral manifestations and appropriately address dental concerns in conjunction with
the patient’s medical team.

Methods
Developed by the Clinical Affairs Committee as Management of Pediatric Dental Patients Receiving
Chemotherapy and/or Radiation and adopted in 19861, this best practice was last revised in 20182. This
revision is based upon a review of current dental and medical literature related to immunosuppressive
therapy, head and neck radiation, and best current practice. The revision by the Council on Clinical Affairs
included a new literature search of the PubMed®/ MEDLINE database using the terms: pediatric cancer,
pediatric oncology, hematopoietic cell transplantation, bone marrow transplantation, immunosuppressive
therapy, mucositis, stomatitis, chemotherapy, radiation therapy, acute effects, long-term effects, dental care,
oral health, pediatric dentistry, practice guideline; field: all; limits: within the last 10 years, humans,
English, birth through age 18. Two thousand sixty-five articles matched these criteria. Additional strategies
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such as Google scholar and hand searches were employed. Papers were chosen for review from these
searches and from the references within selected articles. When data did not appear sufficient or were
inconclusive, recommendations were based upon expert and/or consensus opinion by experienced
researchers and clinicians.

Background
A multidisciplinary approach involving physicians, nurses, dentists, social workers, dieticians, and other
related health professionals is essential to care for the child before, during and after immunosuppressive
therapy and/or head and neck radiation.3,4 Acute and chronic oral complications that may occur as sequelae
dysfunction
of such therapies include oral mucositis (OM) and associated pain, bleeding, taste , opportunistic
infections (e.g., candidiasis, herpes simplex virus), dental caries, dry mouth (e.g., salivary gland
dysfunction, xerostomia), neurotoxicity, mucosal fibrosis, gingival hypertrophy, osteoradionecrosis,
medication-related osteonecrosis, soft tissue necrosis, trismus, craniofacial and dental developmental
anomalies, and oral graft versus host disease (GVHD).4-8

All patients undergoing immunosuppressive therapy and/or head and neck radiation should have an oral
examination prior to initiation of treatment3,4 to identify any existing or potential source of oral disease or
infection that may complicate the patient’s medical treatment.9,10 Every patient requires an individualized
management approach. Consultations with the patient’s physicians and, when appropriate, other dental
specialists, should be sought before dental care is instituted.4 Additionally, the key to success in maintaining
a healthy oral cavity during therapy is patient compliance. Educating the child and the parents regarding
the possible acute and long-term side effects of cancer therapies is essential, as this may improve patient
motivation to adhere to oral care protocols during cancer therapy.8,10-13

Recommendations
Dental and oral care before the initiation of immunosuppressive therapy or head and neck radiation
Objectives13,14
The objectives of a dental/oral examination before therapy starts are three-fold:
 to identify and stabilize or eliminate existing and potential sources of infection and local irritants
in the oral cavity—without needlessly delaying the treatment or inducing complications.
 to communicate with the medical team regarding the patient’s oral health status, plan, and timing
of treatment.
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 to educate the patient and parents about the importance of optimal oral care to minimize oral
problems and discomfort before, during, and after treatment and to inform them about the possible
acute and long-term effects of the therapy in the oral cavity and the craniofacial complex.

Initial evaluation
Medical history review: should include disease/condition (type, stage, prognosis), treatment protocol
(conditioning regimen, surgery, chemotherapy, location and dose of radiation), medications (including
bisphosphonates and other bone modifying agents), allergies, surgeries, secondary medical diagnoses,
hematological status (e.g. complete blood count [CBC]), immunosuppression status, presence of an
indwelling venous access line, and contact of medical team/primary care physician(s). 4 For HCT patients,
the type of transplant, HCT source (i.e., bone marrow, peripheral stem cells, cord blood stem cells),
matching status, donor, conditioning protocol, expected date of transplant, and GVHD prophylaxis should
be elicited.

Dental history review: includes information such as fluoride exposure, habits, trauma, symptomatic teeth,
previous care, preventive practices, oral hygiene, and diet.

Oral/dental assessment: should include a thorough head, neck, and intraoral examinations, oral hygiene
assessment, and radiographic evaluation based on history and clinical findings.

Preventive strategies
Oral hygiene: Brushing of the teeth and tongue two to three times daily should be performed with a regular
soft nylon-bristled or electric toothbrush, regardless of hematological status.11,12,15.16 Ultrasonic brushes and
dental floss should only be allowed if the patient is properly trained.12 If capable, the patient’s teeth should
be gently flossed daily. If pain or excessive bleeding occurs, the patient should avoid the affected area, but
floss the other teeth.4 Patients with poor oral hygiene and/or periodontal disease may use chlorhexidine
rinses until the tissue health improves or mucositis develops.10,17 The high alcohol content of commercially-
available chlorhexidine mouthwash may cause discomfort and dehydrate the tissues in patients with
mucositis. An alcohol-free chlorhexidine solution is indicated in this situation.

Diet: Dental practitioners should discuss the importance of a healthy diet to maintain nutritional status and
emphasize food choices that do not promote caries. Patients and parents should be advised about the high
cariogenic potential of carbohydrate-rich dietary supplements and sucrose-sweetened medications.18,19
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They should also be instructed that sharp, crunchy, spicy, and highly acidic foods and alcohol should be
avoided during chemotherapy, head and neck radiation, and HCT.4

Fluoride: Preventive measures include the use of fluoridated toothpaste, fluoride supplements if indicated,
neutral fluoride gels/rinses, or applications of fluoride varnish for patients at risk for caries and/or dry
mouth. A brush-on technique is convenient and may increase the likelihood of patient compliance with
topical fluoride therapy.12

Lip care: Lanolin-based creams and ointments are more effective in moisturizing and protecting against
damage than petrolatum-based products.20

Trismus prevention/treatment: Patients who receive head and neck radiation may develop trismus. Thus,
daily oral stretching exercises/physical therapy should start before radiation is initiated and continue
throughout treatment.11,21

Reduction of head and neck radiation to healthy oral tissues: The use of lead-lined stents, prostheses, and
shields, as well as salivary gland sparing techniques (e.g., three-dimensional conformal or intensity
modulated radiotherapy, concomitant cytoprotectants, surgical transfer of salivary glands), should be
discussed with the radiation oncologist.

Education: Patient and parent education includes the importance of optimal oral care in order to minimize
oral problems and discomfort before, during, and after treatment and the possible acute and long-term
effects of the therapy in the craniofacial complex.4,17

Dental care
Hematological considerations:
Dental providers should be aware of the patient’s hematologic status and related risks of bacteremia and
excessive bleeding. Hematologic management of the patient should be directed by the patient’s oncologist,
and consultation with the medical team is necessary to determine the need for prophylactic interventions
prior to dental treatment.

In particular, patients who are immunosuppressed may not be able to tolerate a transient bacteremia
following invasive dental procedures. A decision regarding the need for antibiotic prophylaxis prior to
dental treatment should be made in consultation with the child’s physician. Unless advised otherwise, the
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American Heart Association’s standard regimen to prevent endocarditis is an acceptable option for the
immunocompromised patient.4,16 The following parameters may be used to guide decisions regarding need
for antibiotic prophylaxis:
• Absolute neutrophil count (ANC):
— >2,000 per cubic millimeter (/mm3): no need for antibiotic prophylaxis;4,21
— 1000 to 2000/mm3: Use clinical judgment based on the patient’s health status and planned
procedures. Some authors4 suggest that antibiotic coverage may be prescribed when the ANC is in
this range. If infection is present at the site of the planned procedure, a more aggressive prophylactic
antibiotic therapy regimen may be discussed with the medical team; and
— <1,000/mm3: defer elective dental care.7,22 In dental emergencies, discuss management with a course
of antibiotic therapy versus one dose of antibiotics for prophylactic coverage. with the medical team
before proceeding with treatment.

Patients undergoing cancer treatments are at risk for thrombocytopenia. The following parameters may be
used to determine need for pre- and post-operative interventions:
• Platelet count:
— <60,000/mm3: Defer elective treatment and avoid invasive procedures when possible. When
medically-necessary dental treatment is required, a hospital setting is most appropriate. Discuss
supportive measures (e.g., platelet transfusions pre- and post-operatively, bleeding control, hospital
admission and care) with the patient’s physician before proceeding. Localized hemostatic measures
to manage prolonged bleeding may be utilized (e.g., sutures, hemostatic agents, pressure packs,
microfibrillar collagen, topical thrombin and/ or gelatin foams). Systemic measures (e.g.,
aminocaproic acid, tranexamic acid) may be recommended by the hematologist/oncologist. If
platelet transfusions are administered, the dentist should consult with the hematologist regarding the
need for a post-transfusion platelet count before the commencement of dental treatment. Additional
transfusions would ideally be available in the event of excessive and persistent intraoperative or
postoperative bleeding,23

• Other coagulation tests (e.g., prothrombin time, partial thromboplastin time, international normalized
ratio, platelet function) may be recommended for certain patients with other coagulopathies.

Dental procedures:
• Ideally, all dental care should be completed before immunosuppressive therapy is initiated. When
that is not feasible, temporary restorations may be placed and non-acute dental treatment may be
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delayed until the patient’s hematological status is stable.4,24 The patient’s blood counts typically
start falling five to seven days after the beginning of treatment cycle and stay low for approximately
14 to 21 days before rising to normal levels. Patients who require an organ transplant are best able
to tolerate dental care at least three months after transplant when overall health improves.3
• Prioritizing procedures: In the event that definitive dental care would result in a delay of oncologic
treatment and a resultant poorer medical prognosis, providers may prioritize treatment of
symptomatic or potentially symptomatic caries lesions (risk of irreversible pulpitis), infections,
hopeless teeth (e.g., root tips, non-restorable teeth) and removal of sources of tissue irritation before
the treatment of asymptomatic carious teeth (e.g., incipient, small asymptomatic caries lesions),
root canal therapy for asymptomatic permanent teeth, and replacement of faulty restorations. 7,21,24
It is important for the practitioner to be aware that the signs and symptoms of periodontal disease
and infection may be decreased in immunosuppressed patients.11.21
• Pulp therapy in primary teeth: Few studies have evaluated the safety of performing pulp therapy in
primary teeth prior to the initiation of chemotherapy and/or head and neck radiation. Many
clinicians choose to extract pulpally-involved carious teeth because of the potential for
pulpal/periapical/furcal infections to become life-threatening during periods of
immunosuppression.12 Asymptomatic teeth that are already pulpally treated and are clinically and
radiographically sound should be monitored periodically for clinical and radiographic signs of
failure.
• Endodontic treatment in permanent teeth: Symptomatic non-vital permanent teeth ideally should
receive root canal treatment in a single visit at least one week before initiation of
immunosuppressive therapy to allow sufficient time to assess treatment success.7,21 If that is not
possible, alternative options include pulpectomy and closure with an antibacterial agent or
extraction. The need for antibiotics is determined by the patient’s health status and should be
discussed with the patient’s physician. Endodontic treatment of asymptomatic non-vital permanent
teeth may be delayed until the immunologic status of the patient is stable.7,21 The etiology of
periapical radiolucencies associated with previously endodontically treated teeth should be
determined because they may represent pulpal infections, inflammatory reactions, apical scars,
cysts, or malignancies.12 Periapical lesions that are asymptomatic and most likely depict apical
scars do not need retreatment.24
• Orthodontic appliances and space maintainers: Poorly-fitting appliances can result in a breach of
oral mucosa and increased the risk of microbial invasion into deeper tissues.22 Fixed appliances
should be removed if the patient has poor oral hygiene and/or if the treatment protocol (e.g., HCT
conditioning regimen, head and neck radiation) carries a risk for the development of moderate to
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severe mucositis.7 Simple appliances (e.g., band and loops, fixed lower lingual arches) that are not
irritating to the soft tissues may be left in place in patients with good oral hygiene. 7,12 Removable
appliances and retainers that fit well may be worn as long as tolerated by the patient with good oral
care.12 Patients should be instructed to clean their appliance daily and routinely clean appliance
cases with an antimicrobial solution to prevent contamination and reduce the risk of appliance-
associated oral infections. Consider removing orthodontic bands or adjusting prostheses that
approximate gingival tissue if a patient is expected to receive cyclosporine or other drugs known
to cause gingival hyperplasia. If band removal is not possible, vinyl mouth guards or orthodontic
wax should be used to decrease tissue trauma.12
• Periodontal considerations: Extraction is the treatment of choice for teeth with a poor prognosis
(e.g., non-restorable teeth, periodontal pockets greater than five millimeters, significant bone loss,
furcation involvement, mobility, infection) that cannot be treated by definitive periodontal therapy.
Partially erupted molars can become a source of infection because of pericoronitis. The overlying
gingival tissue should be excised if the dentist believes it is a potential risk and if the hematological
status permits.12,21
• Third molars and other impacted teeth: Some practitioners prefer to extract all third molars that are
not fully erupted, particularly prior to HCT. Others favor a more conservative approach and only
recommend extraction of third molars at risk for pulpal infection, with significant pathology,
infection, periodontal disease, or pericoronitis, or when malposed or non-functional.12,25,26
• Primary teeth that are mobile due to natural exfoliation may be left alone.
• Extractions: Surgical procedures must be as atraumatic as possible, with no sharp bony edges
remaining and satisfactory closure of the wounds. These extractions ideally are performed three
weeks (or at least 10 to 14 days) before cancer therapy is initiated to allow for adequate healing.12,21
If the patient is immunocompromised and at risk of infection from transient bacteremia, antibiotic
prophylaxis should be discussed with the patient’s physicians. Regardless of hematologic status, if
there is documented infection associated with the extracted tooth, antibiotics (ideally chosen with
the benefit of sensitivity testing) should be administered for about one week post-operatively.12,21

• Pediatric patients who are on bone modifying agents (e.g., bisphosphonates, anti-resorptive, agents,
anti-angiogenic agents) as part of their cancer treatment or who have had head and neck radiation
are at an increased risk of medication-related osteonecrosis of the jaw (MRONJ) or
osteoradionecrosis27-30, although most of the evidence has been described in the adult population28.
Patients deemed to be at a significant risk of MRONJ or osteoradionecrosis are best managed by a
dentist in coordination with the medical team in a hospital setting. To minimize the risk of
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development of osteoradionecrosis or MRONJ, patients ideally would have all oral surgical
procedures (e.g., extractions, periodontal treatment) completed before those therapies are
instituted.27,28 For patients who have been on anti-resorptive (e.g., bisphosphates, denosumab) or
anti-angiogenic agents as part of their cancer treatment or have had radiation to the jaws and an
oral surgical procedure or invasive periodontal procedure is necessary, it is important to discuss
risks with the patient and caregivers prior to the procedure.

Communication:
The dentist’s communication of the comprehensive oral care plan with the medical team is vital.
Information to be shared includes the extent of non-elective dental treatment needed, need for supportive
care (e.g., hospital admission, blood product replacement, antibiotic coverage) and the amount of time
needed for stabilization of oral disease and healing from the dental procedures. Discussions with the
medical team can ensure ideal coordination between needed dental services and planned cancer therapy.4

Oral care during immunosuppression periods and radiation therapy

Preventive strategies
Oral hygiene: Maintenance of good oral care in patients undergoing immunosuppressive therapy and head
and neck radiation is necessary to reduces the microbial load in the oral cavity. This may decrease the host
inflammatory response and subsequent severity of OM. Furthermore, a clean oral cavity reduces the risk of
opportunistic infections.4,10-12,15,21,22 Patients should use a soft nylon brush two to three times daily and
replace it (every two to three months).12,15

Thrombocytopenia is not the sole determinant of oral hygiene as patients are able to brush without bleeding
at widely different levels of platelet counts.12 Fluoridated toothpaste is effective for caries prevention, and
a mildly flavored toothpaste may be better tolerated during periods of OM. If moderate to severe OM
develops and the patient cannot tolerate a regular soft nylon toothbrush or an end-tufted brush, foam brushes
or super soft brushes soaked in chlorhexidine may be used.13,14 Otherwise, foam or super soft brushes are
discouraged because they do not allow for effective cleaning. The use of a regular brush should be resumed
as soon as the OM improves.12,15 Brushes should be air-dried between uses.12 Electric or ultrasonic brushes
are acceptable if the patient can use them without causing trauma and irritation. If patients are skilled at
flossing without traumatizing the tissues, it is reasonable to continue flossing throughout treatment.
Toothpicks and water irrigation devices should not be used when the patient is pancytopenic to avoid tissue
trauma.12
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Dental care
During immunosuppression, elective dental care should be deferred. If a dental emergency arises, the
treatment plan should be discussed with the patient’s physician who will make recommendations for
supportive medical therapies (e.g., antibiotics, platelet transfusions, analgesia). The patient should be
reevaluated every six months (or in shorter intervals if there is a risk of dry mouth, caries, trismus, or chronic
oral GVHD) during treatment, in times of stable hematological status and always after reviewing the
medical history.

Management of oral mucositis and associated pain related to immunosuppressive therapies

Oral mucositis: The Multinational Association of Supportive Care in Cancer/International Society of Oral
Oncology (MASCC/ ISOO) has published guidelines for treatment of OM.15,31 Currently, data for the
pediatric population is limited; thus, recommendations are based largely on adult studies. The recommended
prescriptions for prevention of OM include good oral hygiene, bland mouth rinses (saline or sodium
bicarbonate), benzydamine mouthrinse, cryotherapy, palifermin, and photobiomodulation therapy
(PBM).31,32 Mucosal coating agents (e.g., hydroxypropylmethylcellulose) and film-forming agents also
have been suggested.4 The use of sucralfate, antimicrobial lozenges, chlorhexidine, pentoxifylline, and
granulocyte-macrophage colony stimulating factor mouthwash for OM are not recommended.15,31

Oral cryotherapy, the cooling of intraoral tissue with ice, is recommended as OM prophylaxis for patients
receiving bolus infusion of chemotherapy drugs with short half-lives.31,33 Oral cryotherapy reduces the
blood flow to the mouth by narrowing the blood vessels, thus limiting the amount of chemotherapy drugs
delivered to the tissues. Cryotherapy is inexpensive and readily available, but further research is needed to
confirm the effectiveness of oral cryotherapy in children.32,33

Palifermin (keratinocyte growth factor-1) is a drug approved by the U.S. Food and Drug Administration for
the prevention of oral mucositis34 in patients undergoing conditioning with high-dose chemotherapy and
total body irradiation followed by HCT.31 Palifermin exerts its effect by stimulating epithelial cell
reproduction, growth, and development so that mucosal cells damaged by chemotherapy and radiation are
replaced quickly, accelerating the healing process.11,35

The current MASCC/ISOO guidelines support the use of PBM therapy to prevent OM in patients
undergoing HCT conditioning with high-dose chemotherapy with or without total body irradiation as well
as patients undergoing radiation treatment for head and neck cancer.31 PBM can decrease pain and the
duration and severity of chemotherapy-induced OM in children.36-38 PBM may not be available at all cancer
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treatment centers due to the cost of the equipment and the need for trained personnel. Appropriate protocol
must be followed when using PBM to prevent contamination and occupational risks to the child and dental
team.

With regard to chlorhexidine, most studies have not demonstrated a prophylactic impact or a reduction in
the severity of OM.11,21,39,40 Chlorhexidine is not recommended for prevention of oral mucositis in patients
undergoing head and neck radiation.15,31

Patient-controlled analgesia is helpful in relieving pain associated with OM, reducing the requirement for
oral analgesics. The use of topical anesthetics and mixtures containing topical anesthetics (e.g., Philadelphia
mouthwash, magic mouthwash) has been suggested for pain management.15,41 However, topical anesthetics
only provide short term pain relief.15 In addition to possible cardiovascular and central nervous system
effects, their use may obtund or diminish taste and the gag reflex11 and/or result in a burning sensation.
Currently, the evidence for its benefit is lacking 17, and potential for toxicity is a concern in young children.

Oral mucosal infections: The signs of oral mucosal inflammation and infection may be diminished during
neutropenic periods. Thus, the clinical appearance of infections may differ significantly from the
expected.21 Close monitoring of the oral cavity allows for timely diagnosis and treatment of fungal, viral,
and bacterial infections. Oral cultures and/or biopsies of all suspicious lesions are appropriate if medical
status permits. While waiting for the results, empiric therapy typically is initiated until laboratory results
dictate more specific medications.4,12,21 Of note, nystatin is not effective for the prevention and/or treatment
of fungal infections.11,42

Oral bleeding: Oral bleeding in patients undergoing immunosuppressive therapy commonly occurs due to
thrombocytopenia and/or damaged vascular integrity. Management consists of local (e.g., pressure packs,
antifibrinolytic rinses or topical agents, gelatin sponges) and systemic measures (e.g., platelet trans-fusions,
aminocaproic acid).11,12,21

Dental sensitivity/pain: Tooth sensitivity may be related to dry mouth during chemotherapy or head and
neck radiation therapy and the lowered salivary pH.11,12,21 Patients who are using plant alkaloid
chemotherapeutic agents (e.g., vincristine, vinblastine) may experience neurotoxicity that presents as deep,
constant jaw pain (affecting the mandibular molars with greater frequency) or paresthesia in the absence of
odontogenic pathology. The pain usually is transient and generally subsides shortly after dose reduction
and/or cessation of chemotherapy.11,12,21
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Dry mouth: Sugar-free chewing gum or candy, sucking tablets, special dentifrices for oral dryness, saliva
substitutes, frequent sipping of water, alcohol-free oral rinses, and/or oral moisturizers are
recommended.5,12,43 Placing a humidifier by the child’s bedside at night may be useful.21 Fluoride rinses
and gels are highly recommended for caries prevention in these patients.

Trismus: Daily oral stretching exercises/physical therapy should be implemented during head and neck
radiation treatment. Management of trismus may include prosthetic aids to reduce the severity of fibrosis,
trigger-point injections, analgesics, muscle relaxants, and other pain management strategies.11,22,44

Hematopoietic cell transplantation

Hematopoietic cell transplantation is used in children to treat malignancies and hematologic disorders, as
well as certain metabolic syndromes. Examples include:45
• malignant disorders treated with autologous HCT
– brain tumors.
– Ewing sarcoma.
– germ cell tumors.
– Hodgkin lymphoma.
– leukemia.
– neuroblastoma.
– non-Hodgkin lymphoma.
– Wilms tumor.
• malignant disorders treated with allogenic HCT
– acute lymphocytic leukemia.
– acute myeloid leukemia.
– high-risk solid tumors.
– juvenile myelomonocytic leukemia.
– myelodysplastic syndrome.
• non-malignant disorders treated with allogenic HCT
– bone marrow failure syndromes.
– chronic granulomatous disease.
– Fanconi anemia.
– metabolic storage disorders.
– osteopetrosis.
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– severe aplastic anemia.

– sickle cell anemia.
– thalassemia.
– Wiskott-Aldrich syndrome.

Specific oral complications can be correlated with phases of HCT.3,4,7,10,15

Phase I: Preconditioning
The oral complications are related to the patient’s current systemic and oral health, oral manifestations of
the underlying condition, and oral complications of recent medical therapy. Oral complications observed
include opportunistic infections, gingival leukemic infiltrates, bleeding, and ulceration.4 Most of the
principles of dental and oral care before the transplant are similar to those discussed for patients undergoing
immunosuppressive cancer therapy.13 The two major differences in HCT are: 1) the patient receives
extremely high dose chemotherapy and/or total body irradiation immediately prior to (a few days before)
the transplant, and 2) there will be prolonged immunosuppression following the transplant. Elective
dentistry will need to be postponed until immunological recovery has occurred, at least 100 days following
HCT. This may be longer if chronic GVHD or other complications (e.g., persistent immunodeficiency) are
present.12 Therefore, all dental treatment should be completed before the patient undergoes HCT.

Phase II: Conditioning neutropenic phase

In this phase, which encompasses the day the patient is admitted to the hospital to begin the transplant
conditioning to 30 days post-HCT, the majority of oral complications are related to the conditioning
regimen and supportive medical therapies.12 Mucositis, dry mouth, oral pain, hemorrhage, opportunistic
infections, taste dysfunction, neurotoxicity (including dental pain, muscle tremors), and temporomandibular
dysfunction (including jaw pain, headache, joint pain) may be present.4 Oral mucositis usually begins seven
to 10 days after initiation of conditioning, and symptoms continue approximately two weeks after the end
of conditioning.4 Among allogeneic transplant patients, acute GVHD can occur, causing more severe
inflammation and severe mucositis symptoms. Acute GVHD may begin as early as two to three weeks after
the start of HCT and continue up to two months post-transplant. The timing of this presentation may help
distinguish acute GVHD from chemotherapy-induced OM.4 The patient may be followed closely to monitor
and manage the oral changes and to reinforce the importance of optimal oral care. Avoid elective dental
procedures in this phase due to the patient’s severe immunosuppression. If emergency treatment is
necessary, the dentist should consult and coordinate with the attending transplant team.
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Phase III: Engraftment to hematopoietic recovery

The intensity and severity of acute complications observed in Phase II usually begin to decrease three to
four weeks after transplantation. During this phase, acute GVHD can become a concern for allogeneic graft
recipients. Dry mouth, hemorrhage, neurotoxicity, temporomandibular dysfunction, and
granulomas/papillomas also are observed sometimes.4 With regard to opportunistic infections, oral fungal
infections and herpes simplex virus infection are most likely.4 HCT patients are particularly sensitive to
intraoral thermal stimuli between two and four months post-transplant.12 The mechanism is not well
understood, but the symptoms usually resolve spontaneously within a few months. Topical application of
neutral fluoride or desensitizing toothpastes helps reduce the symptoms.12 A dental/oral examination should
be performed and invasive dental procedures, including dental cleanings and soft tissue curettage, should
be done only if authorized by the HCT team because of the patient’s continued immunosuppression. 12
Patients should be encouraged to optimize oral hygiene and avoid a cariogenic diet.

Phase IV: Immune reconstitution/recovery from systemic toxicity

After day 100 post-HCT, the oral complications are predominantly related to the chronic toxicity associated
with the conditioning regimen, including dry mouth, craniofacial growth abnormalities, late viral infections,
chronic oral GVHD, and oral squamous cell carcinoma.4,12 Unless the patient is neutropenic or with severe
chronic GVHD, mucosal bacterial infections are less frequently seen. Periodic dental examinations with
radiographs can be performed, but invasive dental treatment is to be avoided in patients with persistent
profound impairment of immune function.12 Consultation with the patient’s physician and parents regarding
the risks and benefits of orthodontic care is recommended.

Dental and oral care after the immunosuppressive therapy and head and neck radiation have been
completed:
Objectives
The objectives of a dental/oral examination after immunosuppressive therapy ends are three-fold:
 to maintain optimal oral health.
 to reinforce to the patient/parents the importance of optimal oral and dental care for life.
 to address any dental issues that may arise as a result of the long-term effects of immuno-
suppressive therapy or head and neck radiation.

Dental care
Periodic evaluation: The patient should be seen every six months (or more frequently if issues such as
chronic oral GVHD, dry mouth, or trismus are present). Patients who have experienced moderate or severe
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mucositis and/or chronic oral GVHD should be followed closely for signs of malignant transformation of
their oral mucosa (e.g., oral squamous cell carcinoma).4,10.46

Education: The importance of optimal oral and dental care for life must be reinforced. It is also important
to emphasize the need for regular follow-ups with a dental professional, especially for patients who are at
risk for or have developed GVHD and/or dry mouth and those who were younger than six years of age
during treatment due to potential dental developmental problems.

Orthodontic treatment: Orthodontic care may start or resume after completion of all therapy and after at
least a two-year disease-free survival when the risk of relapse is decreased and the patient is no longer using
immunosuppressive drugs.7 A thorough assessment of any dental developmental disturbances caused by
the therapy must be performed before initiating orthodontic treatment. The following strategies may be
considered when providing orthodontic care for patients with dental sequelae: (1) use appliances that
minimize the risk of root resorption, (2) use lighter forces, (3) terminate treatment earlier than normal, (4)
choose the simplest method for the treatment needs, and (5) do not treat the lower jaw.47 However, specific
guidelines for orthodontic management, including optimal force and pace, remain undefined. Patients and
their families may be made aware of the potential for a higher risk of orthodontic relapse among cancer
survivors.48 Patients who were on intravenous antiresorptive or anti-angiogenic agents as part of their cancer
treatment, or in those who have had head and neck radiation, may present a challenge for orthodontic care.
Although bisphosphonate inhibition of tooth movement has been reported in animals, it has not been
quantified for any dose or duration of therapy in humans.47,49 Consultation with the patient’s caregivers and
physician regarding the risks (e.g. prolonged treatment time, MRONJ, treatment modifications) 49 and
benefits (e.g., reduced root resorption, anchorage, less relapse)49 of orthodontic care in this situation is
recommended.

Oral surgery and invasive periodontal therapy: Patients at risk for MRONJ or osteoradionecrosis should be
managed in coordination with the oncology team in the hospital setting.27,28,30 Elective invasive procedures
are best avoided in these patients.27,49

Long-term concerns
Craniofacial, skeletal, and dental developmental issues are some of the complications faced by
survivors3,7,8,12 and usually develop among children who were less than six years of age at the time of their
cancer therapy.7,12 Long term effects of immunosuppressive therapy may include tooth agenesis,
microdontia, crown disturbances (size, shape, enamel hypoplasia, pulp chamber anomalies), root
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disturbances (early apical closure, blunting, changes in shape or length), reduced mandibular length,
reduced alveolar process height, and reduced vertical growth of the face.5,7,8 The severity of the dental
developmental anomaly will depend on the age and stage of development during exposure to cytotoxic
agents or ionizing radiation . Patients may experience permanent salivary gland hypofunction/dysfunction
or xerostomia.44 Relapse or secondary malignancies can develop at this stage.4,46 Routine periodic
examinations are necessary to provide comprehensive oral healthcare. Careful examination of extra-oral
and intra-oral tissues (including clinical, radiographic, and/or additional diagnostic examinations) are
integral to diagnosing any secondary malignancies in the head and neck region. Dental treatment may
require a multidisciplinary approach, involving a variety of dental specialists to address the treatment needs
of each individual. Consultation with the patient’s physician is recommended if relapse occurs or the
patient’s immunologic status declines.

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