Blood malignancy

Many of the oral and maxillofacial conditions afflicting those suffering from haematological malignancies are not unique to these underlying haematological conditions or their treatment and thus are discussed in various different sections of the website, regarding diagnosis and treatment. There are, however, some specific considerations associated with oral and maxillofacial conditions in the context of haematological malignancies and their treatments.

Therefore, below we give a sketch of conditions and specific considerations and will point the reader to further appropriate sections of the website for more detailed information.

Biopsies and other surgical interventions

The main role for oral and maxillofacial surgery in support of diagnosis of haematological malignancies is to provide a range of biopsies. Most commonly, these are excision biopsies of cervical (neck) lymph nodes, excision of salivary glands, in some cases incisional biopsies or oral mucosal biopsies. Over time, some may have to be repeated.

In support of treatment, rarely facial skin lesions are related to haematological malignancy and are initially excised by a maxillofacial surgeon. Equally, isolated deposits of rare lymphoma (mucosally-associated lymphoma, salivary-associated lymphoma) may be treated by excision of the lump or associated gland. This is always in conjunction with a haematological malignancy specialist and specialist pathology input.

Management of various dental and oral conditions before and during cancer treatment

If time permits, a careful assessment of dental status and management according to status before starting chemo- or radiotherapy treatment is best practice. The main driving force behind this approach ahead of cancer treatment(s) is the attempt to avoid dental and other oral infections and/or the need for invasive dental treatments during and after cancer treatment. Systemic treatment schemes of malignancies increase the risk for infections, with the oral cavity particularly at risk. This is generally true for chemo- or radiotherapy treatment of haematological and other malignancies. The main difference here is the slightly different demographics of patients with haematological malignancies, with a larger sub-group of young children amongst the patients than is typically the case for other malignancies.

Before oncological treatment starts

For adults, the main focus is on identifying and treating periodontal disease and other chronic oral inflammation, identifying and treating (root canal treatment) or extracting teeth that may otherwise cause problems later on, or may require invasive dental treatments. This general optimisation attempt extends to include dentures and other prostheses such as dental implants. The second pillar for optimisation aims to establish best possible oral hygiene; this typically includes help (and guidance) by a professional dental therapist but otherwise relies on informed self-management. Self-management in turn extends from oral hygiene to include an optimised diet (see below).

For children, the overall approach is very similar. The main difference is that problematic primary teeth in poor condition are usually removed, secondary dentition in children at this stage is managed in the same way as for adults. As a rule of thumb, dental decay of teeth not affecting the pulp calls for restoration. Dental decay of a primary tooth affecting the pulp is a reason to extract the tooth. For permanent teeth, dental decay affecting the pulp may call for extraction (if severe) or root canal treatment. Extensive dental work in young children may have to be carried out under general anaesthesia. A detailed protocol of dental and orofacial anatomical development before oncological treatment should be collated for later reference (see below).

For all ages, if possible / if time permits, tooth extractions should be carried out ideally three weeks before the start of oncological treatment such that any defects will have healed by then, or at least one week prior to the start of oncological treatment. An increased risk of serious bleeding after dental extractions in leukaemia patients mandates careful local haemostasis. When platelet counts in recent blood tests are low, platelet transfusions may be necessary. Cover by antibacterial agents is a common precaution in these circumstances. Extremely low platelet counts may make invasive dental treatment, or extractions, impossible.

Also for all ages, brushing teeth should be done with a supersoft toothbrush to avoid soft-tissue damage and bleeding. When platelet counts in blood tests are very low, it may be a good idea to avoid brushing and instead use a sponge or moist gauze for cleaning, alongside regular rinsing with saline mouth washes. Establishing and maintaining optimal oral hygiene is a major, mostly self-help based, contribution toward the best possible ways of coping with systemic oncological treatments (for haematological and other malignancies).

During oncological treatment

The focus is on attempts to maintain the best possible oral condition throughout oncological treatment, to avoid dental decay and infections (see below). Undoubtedly, for some period of time this can be a daily struggle for many, given the common adverse effects of chemo- and/or radiotherapy, in particular oral mucositis (see below).

Maintaining good oral hygiene becomes even more important throughout oncological treatment, for a number of reasons. High dose chemotherapies often are associated with xerostomia (dry mouth). Xerostomia in turn generally increases the risk for dental decay, as the protective action of saliva for teeth and soft oral tissues is reduced or lacking. Another potential cause for damage to teeth can be repeated vomiting caused by chemotherapy drugs (although effective antiemetic (anti-vomiting) agents are commonly used). With the onset of inflammation of the oral mucosa from chemo- and/or radiotherapy, maintaining good oral hygiene can become more challenging, and is even more important in managing mucositis and preventing oral infections (see below). An effective oral hygiene scheme at this stage should include the use of topical fluoride gels to enhance protection against dental decay and frequent use of saline mouthwashes throughout the day. Another important contribution for optimised maintenance of oral conditions rests with the choice of oral foods. A suitable soft or liquid diet (in the absence of irritating, mostly acidic, foods) and avoiding sugar can make all the difference between maintaining oral food intake or the temporary need to rely on a feeding tube. Oral feeding over the period of oncological treatment may be impacted by change or loss of taste, in addition to problems caused by xerostomia and mucositis (see below).

Support for dental care during oncological treatment is usually provided in the settings of restorative or paediatric dentistry departments associated with an oncology centre for the treatment of haematological malignancies. Management of mucosal conditions is one of the supportive roles of oral and maxillofacial surgery.

Follow-up dental care for children after the completion of haematological cancer treatments is equally important as the treatments can have a direct effect on the development of teeth (see below).

Assessment and management of mucositis

Mucositis is a severe inflammation and painful ulceration of the mucosa, mostly affecting the oral mucosa. Mucositis occurs as a response to the cyctotoxic properties of chemo- and/or radiotherapies and is a serious adverse effect of these treatment modalities, with a high incidence. For example, severe oral mucositis occurs essentially in all chemo- and/or radiotherapy treatment schemes for head and neck malignancies. The incidence of acute and severe oral mucositis is also high, around 80 %, during high-dose chemotherapy treatment for different forms of acute leukaemia and non-Hodgkin lymphoma. Incidence and severity of oral mucositis tend to be highest for chemotherapies with agents that affect DNA synthesis, such as methotrexate. Such agents are widely used in radical chemotherapies in preparation for bone marrow stem cell transplants. Methotrexate is partially secreted by saliva, which may contribute to its causing severe oral mucositis.

Oral mucositis from chemotherapy typically starts one to two weeks after oncological treatment starts and may last for several weeks. Oral mucositis from radiotherapy is related to overall radiation dosage, with a threshold for onset of about 15 to 20 Gy accumulated radiation dosage. Experience would suggest that severe mucositis can take three months or even longer to fully settle after the completion of high dose external beam radiotherapy. It can take even longer if that regimen is rendered more toxic by the addition of chemotherapy.

Despite oral mucositis being a common and severe adverse effect of oncological treatment, there are no gold-standard approaches to prevent it, or significantly reduce its incidence or severity. Accordingly, the role of oral and maxillofacial surgery here is to manage the condition by

Oral mucositis may be so severe that it becomes a limiting condition for the oncological treatment. In severe cases, oral food intake is impossible and non-oral feeding methods may be necessary temporarily.

Many different treatments to alleviate the burden caused by oral mucositis have been suggested and tried; for most of these there is no convincing evidence of efficacy. The only exception with potential relevance is treatment with palifermin as a supportive agent. Palifermin is a synthetic growth factor with cytoprotective properties (by stimulating proliferation of mucosal cell lines, but not interfering with haematological cell lines and malignancies) and has been demonstrated to reduce incidence and severity of oral mucositis slightly. However, until very recently there was no evidence about any potential long-term effects with regard to enhanced risks of secondary malignancies developing later on, clearly a highly relevant consideration for young patients and children. Recent studies with a 15 year time horizon of observation showed no difference in safety and outcomes after oncological treatment of haematological malignancies with or without supportive palifermin treatment.

Assessment and treatment of oral infections

Mucositis and associated oral ulcers are ideal breeding grounds for opportunistic oral infections, especially so because of the immuno-compromised condition caused by chemotherapies. Neutropenia (reduction of the concentration of particular white blood cells that form an important part of the immune response to infections) is commonly observed.

The most common viral infection is by herpes simplex. The most common fungal infections are by candida species; with a compromised immune response such infections may become systemic and may even be fatal. A wide range of bacterial infections occurs and is further facilitated by a reduced and incapacitated immune system. Oral infections in these circumstances can be severe, can cause local necrosis and carry an increased risk of becoming systemic or developing sepsis and may be fatal. Common infective bacterial agents include e. coli, pseudomonas aeruginosa, klebsiella and enterobacter species (many of which are normally commensal bacteria on the skin or in the digestive tract).

Clearly, prevention of oral infections is the first aim (see above). Failing that, any oral infections require determined interventions to control and eliminate the infection. This may include the need for microbiological identification of infective species for targeted selection of antibacterial agents in particular. Treatment approaches are very similar to those for serious oral infections in general, with perhaps one notable exception. Chlorhexidine antibacterial mouthwash is generally widely used in the prevention and treatment of oral infections. Its use is not necessarily recommended during oncological treatment periods and for infections developing from mucositis ulcers, mainly because it is painful, particularly if a version containing alcohol is used.

Long-term monitoring and interventions after completion of oncological treatment

After completion of oncological treatment for haematological malignancies, several long-term monitoring and intervention roles for oral and maxillofacial surgery remain on the agenda. These are all in collaboration with oncology and restorative / paediatric dentistry.

Monitoring and diagnostic interventions (such as biopsies) for relapse and/or for occurrence of secondary haematological and solid malignancies is part of the role. For example, the risk to develop a second primary head & neck malignancy after leukaemia treatment is enhanced, with squamous cell carcinoma the most common following treatment with a bone marrow stem cell transplant.

Long-term maintenance and management are often concerned with symptoms of graft versus host disease after bone marrow cell stem transplants. The immune reactions associated with this complication lead to a chronic form of mucositis and an increased risk of oral infections (see above). This requires careful management as well as long-term monitoring of any developing white mucosal patches to detect any malignant transformations early. Graft versus host disease may also give rise to long-standing xerostomia issues, resulting from inflammation and subsequent dysfunction of salivary glands. Such lasting xerostomia is managed in the same way as similar dry mouth problems arising from other causes, such as following radiotherapy applied to the head & neck region.

A special consideration is the long-term monitoring, support and treatment of children after leukaemia. Most children nowadays survive acute lymphoblastic leukaemia (ALL), the most common form of childhood cancers but delayed late toxicities mandate long-term monitoring and interventions in this group. Chemo- and radiotherapies at an age when tooth germs develop (before 5 years of age) stunt the development of permanent teeth and orofacial growth. The degree of dental abnormalities depends on dose and type of chemotherapy drugs and high-energy radiation. Most teeth of children in the age range up to 5 years will be in a variable state of embryonic development during an intense period of chemo – and/or radiotherapy. These theapy-induced defects of the secondary teeth are permanent and can result in a greater need for input from restorative dentists throughout life.

Adverse long-term effects of chemo- and/or radiotherapies on the developing secondary dentition and orofacial growth, usually in need of treatment include

Oral and maxillofacial interventions to address these issues are overlapping with orthodontic and other restorative dentistry treatment schemes.