References
Oral and dental management for people with multiple myeloma: clinical guidance for dental care providers
From Volume 45, Issue 5, May 2018 | Pages 383-399
Article
Multiple myeloma
Multiple myeloma (MM) is a cancer of plasma cells in the bone marrow. It is the second most common bone marrow cancer, yet it only accounts for 2% of all cancers.1 Plasma cells are a type of white blood cell (WBC) that produce antibodies to help fight pathogens. Plasma cells in people with MM function abnormally and release only one type of antibody, known as paraprotein, which has no useful function.2 These cancer cells also produce significant amounts of abnormal proteins, called M protein, which can cause kidney damage.3 Multiple myeloma does not usually take the form of a lump or tumour; instead, it fills the bone marrow with abnormal cells and interferes with the production of other cells, thereby causing damage to bones and affecting the production of healthy blood cells. This leads to low normal white blood cell counts (neutropenia) and low platelet counts (thrombocytopenia). In the UK, 5,500 new cases of MM are diagnosed each year.1There are approximately 17,500 people living with myeloma in the UK at any one time.1 It most commonly affects men over the age of 65 years and has a higher prevalence in black populations compared with Asian and white populations.4 It is 1.5 times more common in men than women.5
Causes of multiple myeloma
The cause of MM is unknown. Studies have shown certain risk factors to play a part. It is known that people diagnosed with monoclonal gammopathy of unknown significance (MGUS) can go on to develop MM. Monoclonal gammopathy is a non-cancerous benign condition characterized by the production of an excess number of a single antibody in the blood.6 Most patients with MGUS are asymptomatic, and its cause is unknown. Each year about 1 in 100 patients diagnosed with MGUS will go on to develop MM and will require treatment.5 Other known risk factors for developing MM include being overweight or obese7 and being exposed to radiation or certain chemicals.8 Further research is ongoing into the biology and genetics of myeloma to determine the factors responsible for its onset and progression.
Signs and symptoms
Multiple myeloma may not cause any symptoms in the early stage. It is often diagnosed after a routine blood or urine test (Figure 1). If left untreated, people may present with persistent dull bone pain and bone fracture (Figure 2). They may also experience generalized weakness and shortness of breath as a result of anaemia, recurrent infections, prolonged bleeding resulting from defective platelets, and hyperviscosity of red blood cells (RBCs).9Table 1 summarizes the signs and symptoms of MM.
| Signs and Symptoms | Description |
|---|---|
| Bone Pain | The extent of myeloma bone diseases varies considerably from one patient to another. It often presents in the middle or lower back, hips and ribs. The long bones of the upper arm and leg and the shoulder may also be involved but the bones of the hands and feet are rarely affected, as they do not contain bone marrow. |
| Vertebral bone fractures and spinal cord compression | MM weakens the vertebrae and makes them more prone to fractures (compression fracture). The spine is most often affected leading to kyphosis. Spine fracture can cause compression of the spinal cord leading to the sensation of pins and needles in the legs and feet. |
| Anaemia | Abnormal plasma cells fill up the bone marrow and interfere with the production of other cells, including healthy red blood cells, and therefore anaemia. Patients usually feel tired and breathless. |
| Recurrent infection | Low production of white blood cells affects the immune system and people become more vulnerable to infection. |
| Hypercalcaemia | High amount of calcium is released from affected bones leading to symptoms of hypercalcaemia (thirst, frequent urination, tiredness, constipation, confusion and drowsiness). |
| Bleeding disorders | Low production of platelets affects clotting resulting in nosebleeds, gingival bleeding and a heavy menstrual period. |
| Hyperviscosity of the blood | Hyperviscosity of the blood can cause headaches, dizziness, nosebleeds, and shortness of breath. |
| Kidney disease | Renal failure can occur due to abnormal proteins (myeloma protein). Signs of kidney damage include loss of energy, swollen feet and legs, breathlessness and itchy skin. |
Diagnosis of multiple myeloma
There are various diagnostic tests that aid the diagnosis of MM, but it is difficult to diagnose based on a single laboratory test result. Many factors are considered such as medical history, physical examination, signs, symptoms and diagnostic testing. Blood and urine tests, as well as a bone marrow biopsy, are the main laboratory tests used to investigate any patients with MM.9 Additionally, radiographs, magnetic resonance imaging (MRI), computerized tomography (CT) scans and Positron Emission Tomography (PET) scanning are used to determine the stage of the disease and determine the type of treatment required (Table 2).10 The standards for diagnosing MM are determined by the myeloma diagnostic criteria. This currently requires confirmation of one major and one minor criterion or three minor criteria in people with symptoms of myeloma.9 These criteria enable classification of MM into three types:
| Imaging Techniques | Description |
|---|---|
| Standard X-ray |
|
| MRI |
|
| CT-scan |
|
| PET-scan |
|
Classification is important because immediate disease-directed treatment is only needed for symptomatic myeloma (Table 3). Diagnostic test results determine the extent of the disease, best treatment options, help with assessing response to treatment and estimate overall prognosis. People in some categories do not have to receive treatment immediately, but may receive bisphosphonates if osteoporosis is present.
| Types | Serum M Protein Level | % of Plasma Cells in Bone Marrow | Anaemia | Osteolytic Lesion | Renal Failure | Hypercalcaemia |
|---|---|---|---|---|---|---|
| MGUS | <3 g/dL | <10% | Absent | Absent | Absent | Absent |
| Asymptomatic myeloma | ≥3 g/dL | ≥10% | Absent | Absent | Absent | Absent |
| Symptomatic myeloma | ≥3 g/dL | >30% | Mild/Moderate | Multiple | Present | High Level |
Treatment of multiple myeloma
People diagnosed with MM receive treatment under the care of a multidisciplinary team (MDT), which is usually led by a haematologist who specializes in myeloma.12 The aims in treating MM are to stabilize the condition and prevent and treat any symptoms related to MM, such as bone pain, anaemia, kidney damage and hypercalcaemia.13 Although there is no absolute cure for MM, treating the myeloma-related symptoms will help to improve quality of life and prevent further complications. The choice of initial treatment depends on various factors, such as the features of the myeloma itself, anticipated risk of side-effects, convenience and the familiarity of the treating physician with the given regimen.
Treatment is usually based on age and fitness. In general, the treatment is less intensive for the older (>65 years) or less fit and more intensive for younger (<65 years) and fitter people. Both groups receive a combination of anti-myeloma agents. A stem cell transplant usually follows the intensive course of chemotherapy. Multiple myeloma drug therapies consist of two aspects: one to control the myeloma, the other to alleviate symptoms and manage complications of the disease (such as bone damage) as well as the side-effects of treatment.
There have been advances in treatment options with the development of newer medications and different approaches. Myeloma is a relapsing-remitting cancer; therefore treatment of MM consists of induction, consolidation and maintenance phases. The length of treatment varies, depending on the type of treatment used and the stage at which the treatment is given. Summary of medical management based on the myeloma classification is as follows:
1. Monoclonal gammopathy of unknown significance (MGUS)
As there are no symptoms or serious complications associated with MGUS, it does not require treatment,13 but regular monitoring every 3–4 months for the first year for any signs or symptoms is crucial to investigate the possibility of myeloma development. In the second year, monitoring reduces to every 6–12 months if no symptoms develop. The Serum Free Light Chain Assay (SFLCA) is a very sensitive test that could be used to monitor these patients and has been reported to be effective in detecting early signs of myeloma development. Recently, researchers have tried to understand what factors might lead to the development of MM from MGUS, and whether any treatment may slow down or prevent the progression to MM. It is well known that MGUS is characterized with asymptomatic plasma cell dyscrasias, with a possibility to progress to symptomatic MM. Recently, there have been developments in risk stratification models, such as assessing the molecular markers of MGUS. This has led to a better understanding of the histopathology and possible transformation of MGUS to an active symptomatic form of MM. Developing individualized risk profiles for patients with MGUS is considered an ongoing challenge. These have to be assessed by prospective clinical monitoring, for example, flow cytometry, free-light chain analyses, cytogenetic, gene expression profiling and microRNA, as well as molecular imaging for predicting risk of progression. All these factors may help develop early treatment strategies to delay and/or prevent development of MM.14
2. Asymptomatic multiple myeloma
Patients with asymptomatic MM can live without any complications and therefore without treatment.13 Early treatment does not seem to make a difference to overall survival. Regular monitoring every 3 to 4 months is recommended.15 Bone-modifying agents, such as a bisphosphonate, must be started as soon as there is any evidence of bone involvement. The most frequently prescribed bisphosphonates are Pamidronate (Aredia®) and Zoledronic acid (Zometa®). These bone-modifying agents are administrated intravenously. The usual dose is once a month at first, but reduced frequency later if there is a reduction in bone damage. Treatment with bisphosphonate can cause the serious side-effect of bone necrosis, which is discussed later.16
3. Symptomatic myeloma (active form)
Treatment of the active form of MM is often started with anti-myeloma drug therapies. The drug regimen chosen depends on the patient's health and whether a stem cell transplant is considered. Generally, triplets (three drugs) are preferred, but doublets (two drugs) may be considered, particularly in cases where the side-effects of triplets are a concern. In this active form of MM, infusion with intravenous bisphosphonate (usually Zoledronic acid) is started with chemotherapy. If bone disease persists, low radiation therapy to the affected area is considered. Additionally, people routinely receive supportive treatments, such as intravenous immunoglobulin (IVIG), as they are at increased risk of infection; blood transfusions to treat low blood cell counts and erythropoietin (EPO) for anaemia. Treatment of symptomatic myeloma consists of induction, consolidation and maintenance phases as follows:
Induction phase
Elderly patients >65 years (in general not suitable for stem cell transplant)
Combinations of oral Melphalan and Prednisolone (MP) are considered the standard treatment in elderly people with the active form of MM. Another two options that might be considered are Melphalan/Prednisolone/Thalidomide (MPT),17 or Bortezomib/Melphalan/Prednisolone (VMP),18 which are both approved by the European Medicines Agency (EMA). A double regimen of Bendamustine plus Prednisolone in people diagnosed with neuropathy is routinely used.19 Some haematologists may consider a triple regimen of Melphalan/Prednisolone/Lenalidomide (MPR).20
Cyclophosphamide/Thalidomide/Dexamethasone (CTD) has also been used, showing acceptable results, but not better than the MP regimen.21 Lenalidomide combined with low-dose Dexamethasone is widely used in the US.
Younger patients <65 years (fit patients suitable for stem cell transplant)
Induction therapy has been significantly increased by the use of novel agent-based combinations22,23 (Table 4). There is no current research that compares the combinations and their effectiveness. Three to four courses are recommended before proceeding to stem cell collection. Stem cell transplant consists of an induction chemotherapy phase followed by high-dose chemotherapeutic agent, such as Melphalan, with autologous blood-producing stem cells to replace healthy cells damaged by the chemotherapy agents.22,24,25
| Multiple Myeloma Treatment | Drug Combination |
|---|---|
| Triplet regimen |
|
| Double regimen (elderly and frail patients) |
|
|
|
|
Consolidation phase
This phase consists of regular follow-up without treatment, or a course of chemotherapy with anti-myeloma agents for a specific time frame. This decision is based on the laboratory results, such as paraprotein levels in the blood. Additional cycles of chemotherapy therapy may be considered for patients who are about to undergo a stem cell transplant, followed by regular monitoring with blood samples taken every 3–4 months after the stem cell transplant.
Maintenance phase
There has been evidence to indicate that additional cycles of short-term anti-myeloma agents can increase overall survival rate. However, long-term maintenance therapy with excessive doses of anti-myeloma agents is not recommended13 and further clinical trials are required to assess the benefits of the long-term anti-myeloma therapy and the effect on overall survival. Table 4 shows the different treatment options in the induction, consolidation and maintenance phases.
Bisphosphonates (bone modifying agents)
Bisphosphonates are analogues of pyrophosphate used in the treatment of myeloma bone disease, usually in conjunction with other cancer therapy.26 These bone-modifying agents help reduce hypercalcaemia, slow down the progression of bone disease,27,28 reduce bone pain, reduce bone fracture and help to improve overall survival rate of patients with MM. Bisphosphonates have an anti-tumour effect.29 A randomized clinical trial (RCT) study by Morgan et al demonstrated the anti-tumour effect of zoledronate, leading to a positive impact on survival rate; there is a 12% improvement in the progression-free survival (PFS) during the first year, and a 16% reduction in the risk of mortality and skeletal related events (SREs).30 Bisphosphonates are also used in the treatment of bone metastases in other malignancies (most often breast, prostate and lung).31 Most patients with MM receive a monthly intravenous infusion of bisphosphonates. The national myeloma IX trial shows the effectiveness of intravenous infusion of bisphosphonates over the oral tablets in reducing bone fractures, increasing period of remission, and increasing overall survival rate.31 Bisphosphonates are generally well tolerated and there are mild side-effects such as fever, nausea, vein irritation and reduced kidney function. There is risk of the serious complication medication-related osteonecrosis of the jaw (MRONJ) (Figure 3 a and b). According to the position paper of the American Association of Oral and Maxillofacial Surgeons (AAOMS), patients may be considered to have MRONJ if all of the following three characteristics are present: current or previous treatment with bisphosphonates, exposed necrotic bone in the maxillofacial region that has not healed for more than eight weeks, with no history of radiotherapy to the jaws.32 This is most likely to develop after an invasive dental procedure such as dental extraction, but can also develop spontaneously. Marx first reported bisphosphonate osteonecrosis of the jaw in 2003 and it is a well-recognized condition.33 The incidence of MRONJ varies across the literature depending on the type of study design, patient follow-up, and the type of bisphosphonate used. Intravenous preparations carry a higher risk and a range of incidences have been stated.34,35 A systematic review by Migliorati et al had shown that the prevalence of MRONJ in MM is 11.3% (86/764 cases) in cohorts with documented follow up, 2.8% (69/2479 cases) in epidemiological studies, and 2.7% (19/693 cases) in cohorts with undocumented follow-up. This confirmed the predominance of patients in developing MRONJ had MM, followed by metastatic breast, prostate and lung cancer, respectively.36 Additionally, a retrospective analysis of 11 studies that evaluated 614 cases of MRONJ shows that 45% (245 cases) were in patients with MM.36Table 5 summarizes bisphosphonates used in the treatment of MM and possible long-term side-effects.
| Type | Brand Name | Route of Administration |
|---|---|---|
| Disodium pamidronate | Aredia | Intravenous infusion over 90–120 minutes |
| Zoledronic acid | Zometa | Intravenous infusion over 15–30 minutes |
|
|
||
Denosumab
Denosumab is a humanized monoclonal antibody agent that has been developed in the last decade and reduces osteoclast activity, and so reduces bone breakdown. It is administered as a single subcutaneous injection into the thigh, abdomen or back of the arm with a recommended dosage of 120 mg every four weeks.37
Denosumab provides an alternative treatment option to bisphosphonates for patients with MM.38 It has been shown to produce less renal toxicity than zoledronic acid. Additionally, it has been reported that denosumab produces fewer skeletal-related events in comparison to zoledronic acid and can lead to a greater reduction in the bone turnover markers.38
People undergoing invasive dental procedures still have a risk of developing osteonecrosis of the jaw. Therefore, a dental assessment prior to starting therapy is recommended. There has been some debate on how long denosumab stays in the bone, and whether, following a ‘drug holiday’ for six months, the risk of osteonecrosis of the jaw after extractions is significantly reduced, which would be an advantage over zoledronic acid.39
Surgery
The skeletal site most often affected by MM is the spine.40 Treatment helps control the disease. It does not repair any structural damage that may have already occurred with a fracture or prevent deterioration of the condition. Two surgical procedures, vertebroplasty and kyphoplasty, are used to treat spinal fractures.41 By stabilizing the bone, these procedures address the structural damage seen with spinal fractures, relieve pain, and improve function and quality of life.
Oral and maxillofacial manifestation
Osteolytic jaw lesion
Five to thirty percent of MM patients have bony lesions in the mandible and maxilla.40 Dental care providers may be the first to come across undiagnosed cases from incidental findings. Although it is uncommon, 14% of patients have oral lesions as the first sign of the disease.42 For example, jaws can be affected, and patients may present with pain, bony swelling, epulis formation, or sudden tooth/teeth movement.43,44 Bony lesions are more common in the mandible than in the maxilla, and have a higher prevalence in the posterior regions of the jaws. This could be partly explained by the fact that the greatest haematopoietic activity is in the posterior parts of the mandible when compared to other sites in the jaws. Punched out lesions are the classical radiological appearance, which are unrelated to the teeth apices.45 Multiple lesions in the skull are more common than in the jaws with ill-defined margins and a lack of circumferential definition.46
Amyloidosis
Amyloidosis is a group of rare but serious conditions caused by deposits of abnormal protein, called amyloid, in tissues and organs throughout the body.47 Although oral amyloidosis is rare to appear as a first symptom of MM, dental care providers should be aware of its appearance. It may appear as papules, nodules or plaques, which are most commonly seen on the tongue.48 This can interfere with speech, chewing and swallowing. In rare cases, amyloidosis in the tongue might appear as macroglossia.48 If there is amyloid deposition in the salivary glands, patients may experience a dry mouth.49 Therefore, dental care providers will need to provide comprehensive management plans to help reduce the effects of dry mouth, which include an increased risk of caries and effects on eating, speech and swallowing. The appearance of amyloid lesions in oral soft tissues indicate poor overall survival rate and the median survival time in these patients is approximately four months if it is untreated.50 All patients with suspicious lesions should be referred for urgent attention to a specialist centre to ensure early diagnosis and therefore improve quality of life.51
Dental considerations
Oral and dental assessment prior to starting antiresorptive medications
Patients with MM treated with antiresorptive medications, whether bisphosphonates or denosumab, are at high risk of developing osteonecrosis of the jaw. The overall prevalence of osteonecrosis of the jaw is 5.2% for MM patients.52 The general dental practitioner (GDP) should liaise with the oral surgery/special care dentistry specialist and the patient's haematologist with regards to clinical assessment and treatment planning.53 Extraction of teeth of poor prognosis should be carried out urgently before the patient starting any antiresorptive medication such as zoledronic acid or denosumab. Four weeks is the minimum time recommended for healing before starting therapy. In addition, excellent oral care should be instigated with regular dental reviews to avoid future extractions. A further study showed a reduction in the incidence of osteonecrosis of the jaw to be 1.3% after implementing a preventive dental programme for MM patients.54
Tendency of bleeding
Achieving optimal haemostasis can be a challenge in patients with MM due to thrombocytopenia, platelet dysfunction, and hyperviscosity.55 Liaison with the patient's haematologist is essential to obtain recent pre-operative blood results and arrange platelet transfusions if necessary. Non-invasive dental procedures, such as supra-gingival scaling and simple dental restorations, are usually not problematic, rarely cause a bleeding problem, and can be managed in a primary care centre. While more invasive dental procedures, such as subgingival scaling (root surface debridement), and dental extraction, may be carried out in a primary care centre only after liaison with the patient's specialist.56 No dental extraction should be performed if the platelet count is less than 50 x 109/L. An inferior alveolar nerve block is not recommended if the platelet count is less than 30 x 109/L.56 However, urgent dental treatment for patients with thrombocytopenia (<50 x 109/L) should be carried out in a secondary care centre.56
Susceptibility to infection
People with MM have myelosuppression of the bone marrow with neutropenia and dysfunctional lymphocytes.57 This is related to the disease or secondary to the chemotherapeutic agents, which may have been started urgently. They are at an increased risk to infections. Liaison with the patient's haematologist prior to dental extraction is essential to assess neutrophil counts. It is recommended not to perform dental extraction if the neutrophil level is <1, 000/mm3.58 In such a case, dental extraction should be carried out in a secondary care centre after liaison with a patient's haematologist as further medical interventions, such as antibiotic prophylaxis or Granulocyte Colony Stimulating Factors (G-CSFs) may be required.56
Corticosteroid therapy
Patients with MM often receive high-dose systemic steroidal therapy (ie 20mg of dexamethasone) for a long time (at least 3 months) as part of their chemotherapy regimen.59 This can lead to adrenal insufficiency. Adrenocortical function is likely to be suppressed if the patient is currently on daily systemic corticosteroid at doses of/or above 10 mg Prednisolone, or has been in the last 3 months.56 These patients are unable to adapt to stress physiologically and may need supplemental steroid therapy when having dental procedures to prevent adrenal crisis. Non-invasive dental procedures, such as dental restorations, root canal treatment and scaling and polishing, do not usually require steroid supplementation.60 However, a GDP should assess patients individually and liaise with the patient's haematologist as steroid supplement will vary.
A more invasive dental procedure, such as dental extraction under local anaesthesia, requires steroid supplementation prior to the procedure, and possibly for up to 24 hours afterwards. A suggested double dose of hydrocortisone should be taken one hour prior to surgery, up to a maximum dose of hydrocortisone 20 mg (or equivalent glucocorticoid).60 If the patient requires multiple dental extractions under general anaesthesia, he/she will be managed in a secondary care centre, with intravenous hydrocortisone pre-operatively. Discussion with the patient and liaison with the patient's haematologist in advance of the dental procedure is vital to plan required steroid therapy in relation to the type and timing of the procedure.
Conscious sedation and general anaesthesia
Conscious sedation and general anaesthesia help to reduce anxiety during dental treatment. If conscious sedation or general anaesthesia is to be considered, it is necessary to ensure that the haemoglobin level is adequate. Scully et al recommended no conscious sedation or general anaesthesia should be carried out when the haemoglobin is less than 10g/dl.56 If urgent dental treatment under either conscious sedation or general anaesthesia is planned, liaising with the patient's haematologist is necessary and patients should be referred to a specialist centre. Anaemia can be managed by whole blood transfusion for a young patient or packed red cells for an elderly patient.56
Timing of treatment
Most patients with MM present with anaemia due to either the myeloma-related symptoms or the treatment. Dental care providers need to be mindful of this and arrange appointments at suitable times. Patients may not be able to tolerate long appointments due to fatigue, and may present with painful ulcers.61 Short dental appointments in the morning are suggested to ensure that the patient is not too fatigued. Patients with frequent blood transfusion should receive dental treatment in a secondary care centre.56
Dental chair position
Patients with MM may experience neck and back pain. Careful positioning of the dental chair will therefore be necessary to avoid pressure to the back. It is important to allow time for rest periods during treatment, if required. A head and neck rest or pillow can be used to support the patient's neck and ease pressure on the back during treatment (Table 6).
| Action | Recommendation |
|---|---|
| Dental chair position | Careful positioning in the dental chair with head and neck rest or pillow to avoid any further neck or back pain. Consider short morning appointment. |
| Radiographical examination | Detailed clinical and radiographical examination of all teeth for caries, pathology, furcation involvement. |
| Periodontal examination | Examine periodontal status, as this can be a potential risk factor for osteonecrosis of the jaw. It is important to check platelets level prior to basic periodontal examination measurement (BPE) to assess risk of bleeding (no BPE recommended if platelets count is less than 30 x 109/L, therefore the GDP should liaise with the patient's haematologist). |
| Treatment plan | A suitable treatment plan should be formulated for patients (consider liaison with the oral surgery/special care dentistry specialist). |
| Dental extraction | All teeth of poor prognosis should be extracted prior to starting treatment with antiresorptive medications (ideally four weeks before). Liaison with the haematologist to check recent blood results prior to extractions. (No dental extraction should be performed if the platelet count is less than 50 x 109/L. An inferior alveolar nerve block is not recommended if the platelet count is less than 30 x 109/L). The GDP should liaise with the patient's haematologist. |
| Oral hygiene instructions | Thorough oral hygiene instruction discussing the importance of maintaining good oral hygiene using a high fluoride toothpaste (5000 ppm), and regular dental recalls. |
| Patient education | Patient education about the side-effects of anti-myeloma treatment or any signs of developing MRONJ, such as exposed bone and mandible paraesthesia. |
| Diet, smoking, alcohol | Emphasis on the importance of a healthy diet, stopping smoking, limiting alcohol intake. It is recommended to discuss with the patient about smoking cessation programme and the negative impacts of the smoking to oral cavity and general health. |
| Dental alert card | A dental alert card may be useful and is currently being trialled in a specialist dental centre. The card is to be shown to patient's dentist alerting him/her that the patient has received antiresorptive medication and is at risk of MRONJ. |
| Follow up | It is recommended that patients have a dental review every 3–6 months. |
| Oral lesions | All patients with suspicious lesions should be referred for urgent attention to a specialist centre to ensure early diagnosis and therefore improve quality of life. |
| Liaison | Liaise with specialists in oral surgery; special care dentistry and haematology to provide best care for the patient. |
Dentistry and haematopoietic stem cell transplant (HSCT)
Pre-transplant dental assessment
Approximately 50,000 people undergo haematopoietic stem cell transplantation (HSCT) annually worldwide.62 The cytotoxic medication that is given to the patient prior to HSCT results in transient thrombocytopenia and neutropenia that can increase the risk of infection and prolonged bleeding.63 The cytotoxic drugs or the transplant procedure itself may have a direct effect on the oral environment.64 Any dental treatment intended during this period should be discussed with the patient's haematologist.65
Pre-transplant oral and dental assessment of patients should be carried out by an oral surgeon or special care dentist. The pre-HSCT oral and dental assessment aim to assess the current oral health status and treat teeth with potential sources of infection which might affect the patient during the treatment and post-transplant.66 The oral and dental assessment helps to underline that oral health is stabilized and establish that any extractions have been carried out a minimum of ten days prior to the start of chemotherapy.58
Post-transplant oral healthcare
As people survive longer after transplants, they are at risk of developing late complications involving the oral cavity. These can be related to non-treated pre-transplant dental diseases and post-transplant side-effects. These complications can cause substantial morbidity, impair quality of life, and can contribute to late mortality in HSCT recipients.62
The most important risk factors for oral late complications are oral chronic graft-versus host diseases (cGVHD).67 People often report oral discomfort, oral dryness, pain and difficulty of swallowing that may limit oral intake.62 Squamous cell oral cancer can develop in the buccal mucosa, salivary glands, gingiva, lip or tongue.68,69 All patients with suspicious lesions should be referred for urgent attention to a specialist centre to ensure early diagnosis and therefore improve quality of life.51
The Centre for International Blood and Marrow Transplant Research (CIBMTR), the European Group for Blood and Marrow Transplantation, and the American Society for Blood and Marrow Transplantation convened a group of experts in 2006 and provided consensus recommendations for screening and preventive practices for autologous and allogeneic HSCT survivors (Table 7).69,70
| Action | Recommendations |
|---|---|
| Education | All HSCT recipients should be educated about preventive oral health and routine dental maintenance. |
| Advice | Advice on smoking cessation, reduce alcohol intake, avoiding intra–oral piercing, and reduce sugary food and drinks. |
| Monitoring | Monitoring of oral complications post-transplantation is facilitated by thorough pre-transplant baseline oral assessment by oral surgery/special care dentistry specialist. |
| Clinical Evaluation | Clinical oral evaluations should be performed at 6 months, 1 year, and yearly thereafter. |
| Regular Check-up | More frequent evaluations may be needed in patients at high risk for developing cGVHD (decided by the haematologist and oral surgery/special care dentistry specialist). |
| Oral Cancer | Patients at high risk for squamous cell cancers of the oral cavity (for patients with previous oral cGVHD or Fanconi's anaemia) should undergo clinical oral evaluations every 6 months by oral surgery/special care dentistry specialist and should be educated to maintain good oral hygiene and taught oral self-inspection. |
| cGVHD | More frequent dental consultations may be considered in patients with oral cGVHD or Fanconi's anaemia. At each visit, it is important to check for a history of xerostomia and high-risk habits and to perform a thorough oral, head and neck, and dental exam. |
Discharge to general dental practitioners (GDPs)
It is important to advise patients about the long-term complications of anti-myeloma treatment during the pre-dental assessment. Afterwards, discharge to a general dental practice is appropriate. A discharge letter should recommend a dental review every 3–6 months (including those wearing complete dentures), with the provision of a comprehensive preventive programme. It is important to highlight that any procedures that expose or manipulate bone should be avoided, as this will significantly increase risk of osteonecrosis of the jaw.
Post-discharged patients can receive dental treatment in a primary care centre. However, GDPs are recommended to explore alternative procedures to dental extraction, such as retaining roots in the absence of infection. If a dental extraction is considered necessary, they should consider consulting an oral surgery/special care dentistry specialist with regards to clinical assessment and treatment planning.53 Moreover, GDPs are recommended to discuss the risk of the procedure with the patient to ensure informed consent. It is important to perform the dental extraction as atraumatically as possible, avoid raising flaps and achieve good haemostasis. No antibiotic or antiseptic prophylaxis should be prescribed unless advised by the patient's specialist.53 If the extraction socket is not healed at 8 weeks, it is necessary to refer the patient to an oral surgery/special care dentistry specialist for review.
Novel approaches, such as using orthodontic elastic bands to exfoliate teeth, are being trialled. This results in a slow extraction over a few weeks, which allows the oral mucosa to migrate down the tooth as it exfoliates so that there is no open wound.71 The use of platelets-rich plasma (PRF) derived from the centrifugation of the patient's own blood is also being trialled. It helps tissue regeneration and accelerates healing in dental and oral surgery, thereby promoting repairing tissue mechanisms.
Conclusion
A multidisciplinary approach is required to manage people with MM. The special care dentist is well placed for this, with follow-up in general dental practice. Dental assessment prior to starting antiresorptive medication (bisphosphonate or denosumab) and haematopoietic stem cell transplant (HSCT) is crucial. The general dental practitioner in primary care should review patients with MM every 3–6 months. This group are at risk of osteonecrosis of the jaw, oral cancer, and cGVHD, therefore early and urgent referral to a specialist centre must be made for any suspicious oral lesions.