Occlusal Palliation of a Hematopoietic Stem Cell Transplant Patient

In North America and worldwide, the number of patients undergoing hematopoietic stem cell transplantation (HSCT) is increasing. Long-term survival rates are also increasing.^1-3 Dental providers are integral to preparation for HSCT and survivorship care.⁴ Whether or not a patient with a hematologic malignancy will undergo HSCT depends on the type of tumor, presence of bone marrow involvement, whether or not the disease is chemo-sensitive, the patient's age, and availability of a suitable donor.^1,2

Patients requiring HSCT experience myelosuppresion and immunosuppression due to the disease and/or treatment of the disease as well as long-term side effects from the cancer therapy. Oral complications may include an increased risk of oral infections, oral bleeding, and other oral signs and symptoms. Cytotoxic systemic treatment often results in xerostomia, dysgeusia (altered taste), and mucositis. Eighty percent of HSCT patients report oral complications with a resultant impact on their ability to eat, drink, or speak.⁵

Many patients report the pain associated with mucositis (Figure 1) as one of the most distressing side effects of their cancer treatment.⁶ The dentist's role is to prevent oral complications, ease discomfort, and minimize late consequences in this growing population of cancer survivors. The case presented involves dental treatment on a patient on intravenous (IV) bisphosphonate post-HSCT who had symptomatic malocclusion and obstructive sleep apnea. Therapeutic considerations, including dental care pre-transplant, active treatment, and survivorship, are discussed.

In October 2015 a 56-year-old woman presented to her physician with central chest discomfort, a tender raised area overlying her sternum, and rib discomfort especially when coughing or sneezing. A computed tomography (CT) scan revealed multiple osteolytic lesions. After a subsequent bone marrow biopsy in January 2016 she was given a diagnosis of ASA III, multiple myeloma (MM) (International Staging System [ISS] stage I and Durie-Salmon stage IIIA). She was given an estimated 2- to 4-year survival prognosis. CyBorD (cyclophosphamide-bortezomib-dexamethasone) chemotherapy and autologous bone marrow transplant was completed in July 2016 followed by IV pamidronate treatments monthly.

Prior to the onset of her symptoms, the patient had used a continuous positive airway pressure (CPAP) unit for treatment of sleep apnea. Pressure from the CPAP strap on her skull lesions had become uncomfortable (Figure 2), and her ribs became increasingly sore when sleeping on her side. She perceived a change in her bite with CPAP use, and, in addition to poor sleep and physical discomfort, she experienced pain in her facial muscles. She was experiencing "chipping" of her upper front teeth and day and nighttime "clenching," and wanted a solution to optimize comfort in her remaining years. Her general dentist had referred her for orthodontic treatment that would require 3 years to complete, which was unacceptable to her. She presented to the dental department at BC Cancer Kelowna (Kelowna, British Columbia) asking for advice regarding her dental condition.

Periodontal: Patients with neutropenia and cytopenia should not be probed without antibiotic prophylaxis.^4,5 Given the patient's medical condition and timeline, an approximate periodontal diagnosis was derived from her radiographic and clinical presentation. Minor gingival recession was noted on teeth Nos. 22 and 28 that was due to facial anatomical position of those teeth. The patient's oral hygiene was very good prior to and throughout her HSCT. The diagnosis was AAP type II (Figure 3).

Risk: Low

Prognosis: Good

Biomechanical:The patient had large intracoronal restorations on upper and lower premolars and molars, teeth Nos. 2, 3, 12 through 15, 19, 20, and 31, and full-coverage restorations with open margins on teeth Nos. 18 and 30 (Figure 4 and Figure 5). No caries was detected.

Risk: Moderate

Prognosis: Fair

Functional: The patient reported "chipping" of her front teeth and "clenching." Clinical evidence of lingual attrition of linguoverted central incisors, Nos. 8 and 9; facial attrition and chipping of supererupted lower anteriors; and congenitally missing teeth Nos. 4 and 27 were noted (Figure 6). She further complained of myofascial tension related to inability to relax her jaw in a comfortable position both while awake and while sleeping.

Risk: Moderate due to constricted chewing pattern

Prognosis: Poor

Dentofacial:Maximum tooth display and maximum tissue display were noted in the patient's smile. The maxillary midline was displaced 4 mm to the patient's right with gingival asymmetry on teeth Nos. 7 through 10. Tooth No. 9 was lingually positioned, No. 10 was facially positioned, and No. 21 was facially and mesially misaligned (Figure 7 through Figure 9).

Risk:High

Prognosis: Fair

The treatment goals were to create a relaxed, comfortable bite position for the patient in a timely manner and prevent further chipping of the front teeth, which were hurting the soft tissues of her lips and tongue. Furthermore, the treatment goals would need to work within windows of adequate health and optimize her dental/medical health for her survival prognosis of 2 to 4 years.

The treatment would include increasing occlusal vertical dimension (OVD) by adding to the lower posterior teeth, referencing the incisal height of tooth No. 23 for the occlusal plane.⁷ The lower anterior teeth would be leveled, and teeth Nos. 8 and 9 would be shortened 1.5 mm and inclined facially.

The rationale for increasing the OVD in the lower arch was to level the lower occlusal plane, provide interarch clearance, and reduce frictional load of the anterior teeth in function. Specifically related to the patient's cancer care and status, her oncologist approved dental treatments that might involve disturbing the gingiva at 2 months post-HSCT with the caveat that she would receive antibiotic prophylaxis for all appointments involving the gingiva while neutropenic.

Phase 1: The initial phase involved deprogramming and mounting. A standard Kois deprogrammer was fabricated, and standard protocol was followed to record a centric relation (CR) reference position (Figure 10).⁸ Casts were mounted, and the laboratory fabricated provisionals at the new OVD (Figure 11). To keep the deprogrammer height to a minimum, it was necessary to enameloplasty the lingual surfaces of teeth Nos. 8 and 9 to create clearance for the patient's lower anterior teeth, which came forward as her mandible settled into a relaxed orthopedic joint position. The reduction of the lingual surfaces and desired addition to the facial surfaces of Nos. 8 and 9 indicated full-coverage restorations for these teeth in Phase 3.

Phase 2: Next, the polymethyl methacrylate (PMMA) onlays were delivered to lower posterior teeth to facilitate the newly desired OVD (Figure 12).⁹ Bonded composite restorations were placed to level the lower anterior teeth.

Phase 3:The patient chose to proceed with cohesively retained all-ceramic restorations (IPS e.max^®, Ivoclar Vivadent, ivoclarvivadent.com) cemented with self-adhesive resin cement (RelyX^™ Unicem 2, 3M ESPE, 3mespe.com) on teeth Nos. 18 through 21 and 28 through 31 (Figure 13 through Figure 16), leaving No. 22 unrestored. Teeth Nos. 8 and 9 were also prepared for all-ceramic restorations and gingival recontouring without bone removal on tooth No. 9 for improved esthetics.

Dental Needs Specific to the HSCT Candidate

Dental care goals for patients who may require HSCT⁵ are to improve oral health to minimize oral pain and loss of function and eliminate dental conditions that would be predisposing factors for infection or hemorrhage. Patients being considered for HSCT need a thorough dental assessment as soon as possible. Depending on the cancer agency protocols where the patient receives treatment, this is likely to be the responsibility of a trained dentist at the treating hospital. A pre-HSCT dental consultation includes relevant diagnostic radiographs, a head and neck examination, and a detailed examination of the intraoral soft and hard tissues.

In addition to caries control, treatment by the dental professional typically includes^1,4,5,10 extraction of periodontally involved teeth, extensively decayed teeth, at-risk impacted teeth, and teeth with periapical pathology. Ideally, there should be 2 weeks healing time after extractions or dental hygiene procedures prior to high-dose chemotherapy in preparation for HSCT. Dental treatment may also include elimination of potential sources of trauma such as ill-fitting dentures and rough or sharp teeth or restorations, removal of all orthodontic appliances or space maintainers until the risk of mucositis is minimized, treatment of any dental conditions that cannot wait 6 to 12 more months,¹¹ and optimization of periodontal status via thorough dental hygiene and instruction for patients to use "safe oral hygiene."⁵ Safe oral hygiene includes rinsing with sterile water^5,10 or a bland oral rinse of 5 mL salt and 5 mL baking soda mixed with 1 L of water, which can be stored at room temperature and shaken before rinsing; the patient gargles 15 mL of the solution two to three times every 2 hours while awake.¹² Dental professionals also can ensure that patients are comfortable and skilled with an oral care routine prior to the pre-engraftment phase to minimize traumatic injury from inexperience with oral aids or techniques.

Meanwhile, patient self-care includes^1,4,5,10 following "safe oral hygiene" as described above. In addition, it is recommended that the patient brush two to three times per day with an ultra-soft or soft toothbrush with bristles softened in hot water, the toothbrush be air-dried and replaced after each neutropenic cycle, and non-minty toothpaste without surfactants be used.¹ Also, the patient should floss or use interproximal hygiene aids daily. Finally, diligent hygiene care is needed for removable appliances, which should be worn only if necessary.

There are two types of HSCT: autologous (self) and allogeneic (non-self) transplant.^4,6 With the autologous type there is no chronic graft versus host disease (cGVHD) side effect, and a transplant match is guaranteed. However, there is no early graft versus tumor effect to fight tumor cells, and there is a risk that tumor cells may be re-infused. With allogeneic-type transplants there is an early graft versus tumor effect that fights tumor cells. Also, success increases with match similarity, and tumor-free cells are used. On the downside, however, cGVHD is likely and rates of morbidity and mortality are higher.

In both types, stem cells are collected and cryopreserved. The patient undergoes "conditioning," where myeloablative therapy destroys the circulating immune system and any malignant cells. Once all cytotoxic agents are cleared from the circulation, stem cells are returned to their body via an indwelling venous catheter. Reconstitution of the new immune system is called "engraftment."^1,4,8,9

Infection is one of the leading causes of death post-HSCT.^1,2,4,5 A complete blood count is recommended prior to invasive dental treatments and considerations should be given for antibiotic prophylaxis and/or blood product support, depending on the dental procedures being undertaken. The dental care team must achieve the best possible periodontal status for at least 1 year after stem cell transplant to reduce the risk of oral infections and to facilitate the resolution of oral mucositis.^5,9 Caution must be taken when caring for patients on IV bisphosphonates regarding invasive procedures that involve bone, such as dental extractions.¹³

Other important issues for the general dentist to consider include the following:

Infections: fungal and viral. Patients on treatment with broad-spectrum antibiotics and/or steroids are at increased risk for opportunistic fungal infections. Oral aids must be frequently replaced or decontaminated after each use, and dentures or oral appliances must be decontaminated to avoid oral re-infection. The use of instruments that create aerosols (eg, ultrasonic scaler) should be avoided if the patient is immunocompromised.⁵

Decreased elasticity of oral tissues with cGVHD⁵ can make dental impressions, removable prostheses, and/or appliance wear and basic oral care more difficult.

Persistent xerostomiamay be managed with the use of sialagogue medications and an emphasis on low-acid, unsweetened food and beverage choices. Patients need to be aware of increased risk for dental decay. Routine daily use of fluoride gel (1.1% neutral sodium fluoride) is recommended for xerostomia patients either through the use of brush-on pastes or gel tray carriers.⁵

Oral squamous cell carcinomas are more frequent in patients with cGVHD.^1,14 Careful screening for head and neck cancers is indicated (head and neck and intraoral soft-tissue examinations). Consultation with a medical colleague or oral medicine specialist is recommended regarding biopsy for suspicious persistent areas of active cGVHD.

Phases 1 and 2 were completed in 6 weeks after starting 2 months post-HSCT. After placement of the PMMA onlays, the patient developed a rash and became concerned about an allergic reaction. Though an allergy was never substantiated, she elected to proceed with definitive porcelain restorations as described in phase 3. Phase 3 restoration was completed by 8 months post-HSCT. Removal of the PMMA restorations and replacement with all-ceramic crowns did not resolve her rash, which was diagnosed as shingles. The condition improved with dexamethasone therapy.

Several limiting factors and challenges for the care of this patient presented themselves. Her desire to complete her travel "bucket list" competed for the same windows of opportunity of health needed for dental appointments. Also, use of dexamethasone, chemotherapies, cytopenias, headaches, increasing vertigo, and gag reflex all made it difficult to provide oral care. At the time of this writing, there are indicators of relapse via blood tests.

Fortunately, prior to these indicators of relapse, the original treatment goals were achieved. The patient stated that she now had a smile she liked and that she was relaxed and comfortable. She reported an increased frequency of restful sleep.

It is important to note that this article does not address the clinical question regarding whether or not a patient on IV bisphosphonates should be advised to have orthodontic movement of teeth. That discussion is beyond the scope of this article. The literature to date regarding that topic is inconclusive.^15-18

Following successful medical treatment, HSCT patients eventually return to the care of a general dentist. It is, therefore, crucial for the dentist and team to understand the importance of assessing and managing these individuals in collaboration with medical colleagues.¹⁹ Immune-mediated outcomes related to survivorship predispose this population to oral complications such as mucositis, xerostomia,^20,21 cGVHD, and immunosuppression.⁵ IV bisphosphonate therapy is a common management strategy for MM patients and needs to be considered in light of invasive dental procedures involving bone.¹³ Patients on long-term chemotherapy may be at risk for oral complications. Therapies meant to further control lymphoid tumors may leave patients susceptible to neutropenia, thrombocytopenia, anemia, neuropathy, and shingles. Dental care should be delivered with consideration of immune-mediated outcomes in cancer survivors.²²

The author thanks Schell Dental (schelldental.ca) and Drs. Norm Ickert, Angelyn Salaberry, Allan Hovan, John Kois, and Michele Williams (in memoriam) for their support and excellent work over the years. This article is dedicated to the memory of Michelle Twigg and many other cancer patients who have touched Dr. Pada's life.

Hilary Pada, DMD

Dental Consultant, BC Cancer, Kelowna, British Columbia, Canada; Private Practice, Kelowna, British Columbia, Canada; Mentor, Kois Center, Seattle, Washington