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Position Paper Periodontal Considerations in the Management of the Cancer Patient*

THIS POSITION PAPER ON PERIODONTAL considerations in the management of the cancer patient was prepared by the Research, Science and Therapy Committee of The American Academy of Periodontology. It is intended to provide information regarding the effects of head and neck radiation, total body radiation, chemotherapy, and bone marrow transplantation on the oral tissues. In addition, the paper offers suggestions for the prevention and treatment of periodontal and oral side effects of cancer therapy. Reliance on this position paper for patient management will not guarantee a successful outcome. Cancer therapy may be associated with complex problems. Ultimately, decisions regarding the diagnosis and treatment of oral disease in an individual patient must be made by the treating practitioner in light of the specific facts presented by that patient and in consultation with the patient's physician. J Periodontol 1997;68: 791-801.

INTRODUCTION In the past decade, tremendous strides have been made in understanding the cellular changes associated with the development of cancer in humans.1 This has resulted in improved techniques for diagnosis and treatment of malignancies, including oral cancers. Health professionals have been alerted to the importance of the relationship between complete examination of the head and neck area, early cancer detection, and survival of afflicted individuals. Additionally, major emphasis has been placed on the prevention of malignancies by identification and control of factors such as tobacco use and alcohol consumption, which are known to be associated with carcinogenic tissue changes.2-5 Chemopreventive agents such as synthetic retinoids have been used successfully in reversing oral leukoplakic lesions before malignant transformation.4 Early diagnosis, coupled with the aging of the American population, has resulted in an increase in the number of malignancies treated each year. This is especially true of oral cancer, which is classically a disease of older individuals with median age at time of diagnosis of 63 years.6 Some malignancies, such as Hodgkin's lymphoma and certain types of leukemias, are highly curable.7,8 Others, such as metastatic breast cancer, are more difficult to cure, although treatment may prolong survival and allow an improved quality of life for several years.9,10
*This paper was developed under the direction of the Committee on Research,Science, and Therapy and approved by the Board of Trustees of The AmericanAcademy of Periodontology in April 1997.

The periodontist is likely to encounter patients with acute or chronic leukemia since these malignancies sometimes present with oral signs and symptoms. Acute leukemias are usually classified according to morphogenic type (lymphoblastic, myeloid, or hybrid) and diagnosis is usually made by bone marrow biopsy,11,12 Chronic leukemias feature uncontrolled proliferation of mature, differentiated cells of the hematopoietic system.13 Either type may induce mucosal pallor, ulceration, and petechiae, while gingival bleeding, necrosis, and/or enlargement is relatively common in acute leukemia.12,14,15 Gingival enlargement may occur as a result of infiltration of leukemic cells, gingival hemorrhage, or in response to infectious complications in patients with poor oral hygiene.14,16,17 Oral tissues are often further compromised as a result of chemotherapy or bone marrow transplantation used in treatment of this malignancy.18-21 GENERAL CONSIDERATIONS Dental consultation prior to chemotherapy, radiation therapy, or bone marrow transplantation is now considered to be very important in the management of most cancer patients.22-27 This is true in all head and neck cancer patients regardless of treatment method. If surgical excision is anticipated within the oral cavity, attention should be directed toward control of dental disease during the recovery phase and toward preparation for suitable prosthetic reconstruction to correct postsurgical dysfunction. If radiation therapy, chemotherapy, or bone marrow transplantation is planned, the periodontist should be aware

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that oral complications may be quite painful, may have significant impact on the patient's quality of life, and may affect compliance and even continuance of cancer treatment.28-30 These complications may begin during cancer therapy and may be the result of the malignancy or the treatment. For example, chemotherapeutic complications result from myelosuppression, immunosuppression, or direct cytotoxic effects of chemical agent(s) on oral tissues. These effects manifest as mucositis, infection, or hemorrhage. Radiation therapy may directly damage oral mucosa, salivary glands, bone, or oral musculature, which may lead to xerostomia, loss of taste sensation, infection, osteoradionecrosis, trismus, and extensive dental caries.23,31,32 Patients receiving bone marrow transplantation are subject to complications associated with radiation or chemotherapy and may also suffer from graft-versushost disease (GVHD), as well as from side effects related to the immunosuppressive drugs used to prevent marrow graft rejection.33 Pre-existing oral disease may increase the risk of severe oral complications, and dental examination prior to therapy is essential.23,29,34,35 Ideally, in the initial evaluation of the cancer patient, the periodontist should perform a thorough clinical and radiographic examination, and should gather information about the patient's medical and dental history, present illnesses, current level of oral hygiene and oral health, and the anticipated cancer treatment plan. It is important to be aware of the diagnosis and staging of the lesion, the goals and prognosis of proposed therapy, the type and dose of therapy to be administered, and the timing of the treatment. If radiation therapy is to be used in the head and neck area, one should know the size and location of radiation fields, the fractionation pattern, the radiation source (implanted versus external), the type of radiation to be rendered (photon, neutron, or electron), the patient's sensitivity to radiation, and the total dose to be administered.22,24,36-39 The patient's dental awareness should be assessed, as well as his or her motivation and ability to perform oral hygiene procedures.40,41 When evaluating patients with oral cancer, it should be borne in mind that use of known carcinogens such as tobacco and alcohol may have predisposed the patient to development of the malignancy.42 Efforts should be initiated immediately to discourage further use of these and other potentially contributing agents. Dental and periodontal charting should be performed to establish a baseline for subsequent examinations and to identify pathoses requiring immediate, pre-therapeutic management. The nutritional status of the patient should be assessed and counseling should be provided, if needed, to enable the patient to avoid debilitation, delayed wound healing, and increased susceptibility to dental caries.31,32,43-45 Xerostomia is a possible complicating side effect of cancer therapy, and evaluation of salivary function prior to therapy may sometimes be appropriate.46

Oral disease which may complicate cancer therapy should be identified and corrected whenever possible before commencement of therapy.47-50 Periodontal prophylactic procedures and scaling and root planing may be necessary to reduce the oral bacterial load. Daily plaque removal procedures should be emphasized, including tooth brushing and flossing and use of a fluoride toothpaste. Oral hygiene procedures may require modification during some phases of cancer therapy, but they should be reinitiated as soon as feasible. Topically applied fluorides and daily use of mouth rinses such as chlorhexidine may be beneficial.51 Customized soft trays for fluorides should be constructed and fluoride treatment initiated prior to radiation when feasible. Restoration overhangs, rough or sharp edges on teeth, and any other defects likely to cause soft tissue irritation should be corrected.52 Patients should be instructed to avoid potentially abrasive foods likely to traumatize soft tissues. IIU-fitting dental prostheses should not be worn if adjustments cannot be accomplished readily. If dental implants are present, their overall status should be carefully assessed and removal considered if maintenance of periimplant health cannot be reasonably anticipated.53-55 Any potential source of oral infection should be identified and eliminated. Periodontally questionable teeth, or teeth with advanced caries, usually should be extracted. Endodontic therapy has been demonstrated to be suitable for pulpally involved teeth if properly performed. 27 Extractions should be accomplished one to three weeks prior to initiation of cancer therapy to ensure adequate wound healing.28,56,57 Extractions should be performed as atraumatically as possible, sharp bony ledges eliminated, and maximal soft tissue closure achieved in order to promote rapid healing.27,58 It is important to note, however, that osteoradionecrosis has been reported in areas in which teeth were extracted before, during, or after radiation therapy.59 In general, periodontal surgical procedures should be avoided because of the requirement for prolonged healing and meticulous oral hygiene to achieve desired results. In the past, many patients receiving myelosuppressive or immunosuppressive therapy have suffered extensively from post-treatment oral or systemic infections such as herpes simplex virus (HSV) or other viruses, candidiasis, or infections with Gram-positive or Gram-negative microorganisms, believed to have originated from the oral cavity. As a result, the protocol for some oncology centers includes pretreatment testing of patients for HSV antibody titers, and the prophylactic use of the antiviral agent, acyclovir, in the presence of a positive titer.60-62 Pretreatment cultures may be indicated to evaluate for the presence of oral candidiasis or unusually high oral titers of streptococci or enteric Gram-negative microorganisms.

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RADIATION THERAPY Treatment of malignancies with radiation is based on the principle that radiation is cytotoxic to malignant cell populations. This cytotoxicity is most effective during cell mitosis; it is random in nature in tissue exposed to radiation and cell damage is enhanced by the presence of molecular oxygen. As a consequence, non-malignant tissue cells in areas exposed to radiation are subject to damage, a factor which limits radiation dosage. Radiation dosage is often administered at intervals (fractionation) in order to maximize tumor cell death and minimize mucositis and dermatitis in exposed tissues. Overall cell death is related to total dose of radiation, size of the fractions, tissue volume irradiated, and location of the tumor.63,64 Some tumors are more responsive to radiation than others. For example, lymphomas and Kaposi's sarcoma are very radiosensitive and require only small radiation doses, while squamous cell carcinoma is only moderately radiosensitive.31 Relatively low-dose total body irradiation is used in conjunction with chemotherapy to achieve complete myelosuppression in patients receiving bone marrow transplantation. This form of radiation exposure is associated with less severe or even transient radiationinduced complications.65 In contrast, head and neck radiotherapy is usually administered locally, either by means of an intense external beam or by implantation of radioactive substances such as iridium, gold, cesium, or palladium.66-69 Combination cancer therapy may be provided in a variety of ways with radiation performed before or after surgery and with or without adjunctive chemotherapy.5,7074 Often, radiation is fractionated at the rate of 100 to 1,000 centiGrays (cGy) per week, and total radiation dose for head and neck tumors often ranges between 5,000 to 8,000 cGy (1 cGy = 1 rad), a dosage which usually results in oral complications.5,63,75 The cytotoxic effects induced by head and neck radiation therapy may induce both acute and chronic complications and severe pain.76 Often these complications can be minimized or even prevented but to do so, patient compliance with dental recommendations is imperative.40,77,78 Patients are susceptible to dermatitis and mucositis in the area of irradiation, which is often accompanied by xerostomia, dysgeusia (altered taste), hypovascularity of soft and hard tissues, and muscle fibrosis and trismus.79 Widespread oral melanotic hyperpigmentation has been reported80 and developmental abnormalities of the teeth and jaws may occur in irradiated children.81-85 The altered tissues are highly susceptible to infection, especially with fungal organisms such as Candida albicans or other Candida subspecies. Bacterial and viral infections may also occur. Mucositis generally occurs 5 to 7 days after initiation of radiation therapy. The affected tissues will appear erythematous and dry and may subsequently ulcerate, es-

pecially if secondary infection occurs. Severity of mucositis can be partially controlled by having the patient eliminate all secondary sources of irritation such as alcohol, smoking, and ingestion of spicy foods.27 If possible, secondary infection should be prevented, but generally only palliative pain reduction therapy can be provided until after the radiation series has been completed. Several palliative substances have been advocated for topical use, including benzydamine hydrochloride, beta carotene, allopurinol, sucralfate suspension, kamillosan, povidoneiodine, antacids, sodium bicarbonate, local anesthetic agents such as lidocaine hydrochloride, or oral suspension of prostaglandin E2. Unfortunately, very few clinical trials using these substances have been conducted and results have been unimpressive.5,22,29,74,84 Chlorhexidine digluconate shows promise and has been used in several trials but to date results are mixed.51,85-91 This may be due in part to the relatively high alcohol content of commercially available chlorhexidine in the United States. It is generally best to avoid mouth rinses containing alcohol, phenolics, or astringents because they may further dehydrate the mucosa and increase oral discomfort.58,84 Gingiva is sensitive to irradiation, and increased gingival recession may occur even without signs and symptoms of periodontal inflammation, perhaps due to the hypovascularity induced by the radiation.92 There is some evidence that a limited amount of gingival revascularization may occur over time when total radiation dosage is relatively low.39 Good oral hygiene is essential to improve patient comfort and to reduce the risk of infection by oral microorganisms. Bacterial, fungal, and viral infections can occur in the presence of mucositis but are less likely to induce toxemia in the irradiated patient than in the patient receiving chemotherapy. Oral candidiasis, however, can occasionally be invasive, refractory to treatment, and potentially lethal.84 Candidiasis can manifest as pseudomembranous, hyperplastic, or atrophic (erythematous) oral lesions, and as angular cheilitis.29 The tongue, mucosa, and commissures of the lip are most frequently affected. Diagnosis is based on clinical evaluation, fungal cultures, or visualization of organisms using potassium hydroxide or Gram-staining.48,93 Treatment typically consists of topical antifungal agents such as nystatin oral suspension or clotrimazole.3l,57,94,95 Unresponsive patients or those with disseminated infection may require systemic therapy with agents such as ketoconazole, fluconazole, itraconazole, or amphotericin B.31,94 Infections of dental or periodontal origin can represent a severe risk to head and neck radiation patients.96,97 The obliterative endarteritis induced by the radiation characteristically leads to soft tissue ischemia and fibrosis and may severely compromise wound healing. At the same time, irradiated bone becomes hypovascular and hypoxic, and infection can lead to severe progressive osseous de-

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struction (osteoradionecrosis), which is difficult and sometimes impossible to control.98-l00 Susceptibility to osteoradionecrosis (ORN) may continue throughout the lifetime of the patient, and performance of invasive periodontal or other surgical procedures in irradiated areas should be avoided whenever possible.97,l0l For the reasons stated, optimal oral health must be maintained, yet every effort must be made to avoid soft tissue injury during the post-radiation mucositis stage. To do so, some authorities have recommended curtailing all but the most basic oral hygiene procedures. The threat of plaque-related oral infections, however, may outweigh that concern and some suggest that conventional oral physiotherapy can be performed during and after radiation treatment. 29,48 These issues should be discussed with the patient's oncologist. After initial recovery from the radiation effects, non-surgical periodontal therapy is appropriate for teeth retained in the radiation field, usually with prophylactic antibiotic coverage. It is important to detect and treat dental caries or traumatic dental injury which could lead to pulpitis or periapical lesions, although ORN can occur spontaneously in the absence of known injury or infection.96 On occasion, extractions are necessary in an area at risk for ORN. In this event, tissues should be managed gently, yet extensive surgical debridement may be indicated.97,102 Antibiotic coverage is required and local anesthetics containing epinephrine should be avoided, when possible, to prevent further vascular constriction.27 Microbial culture and sensitivity testing may be indicated when antibiotics are used. ORN often requires aggressive treatment and multiple courses of hyperbaric oxygen therapy to facilitate healing.58,103-106 The successful placement of root form implants has been reported in areas at risk of ORN using hyperbaric oxygen as a pretreatment.107,108 Trismus of the muscles of mastication is a relative common occurrence after head and neck radiation, due to induced hypovascularity and soft tissue fibrosis and scarring.32 Once present, the trismus may prove irreversible. Therefore, patients should be encouraged to perform mouth stretching exercises before, during, and after radiation therapy 22,48,109 Permanent impairment of salivary gland production can occur whenever the glands are located within the portals of radiation. Persistent loss of salivary flow has been reported to be more common when total radiation exceeds 6,000 cGy, while glands not fully irradiated may partially rebound with time. Even low-dose total body radiation, however, may induce partial xerostomia.39,110 Dryness of the mucosa may increase susceptibility to oral infections and lead to difficulty in chewing, swallowing, and speech. Dental caries is often a consequence of radiationinduced xerostomia. Oral dryness leads to increased plaque accumulation and lowered salivary pH, while the buffering capacity of saliva is eliminated. This creates a cari-

ogenic oral environment, particularly in patients ingesting a high carbohydrate diet. Caries susceptibility is not limited to teeth within the radiation field. The harmful impact of post-radiation caries is obvious, and extensive effort should be made to minimize this complication. Effective oral hygiene, frequent dental evaluations, and appropriate prophylactic treatment procedures are important to caries prevention. Fluoride applications are essential. Stannous or sodium fluoride can be brushed on or applied in custom-made trays.48,111 Tray application may be more effective than brushing, and sodium fluoride is preferred by some because of its potential to neutralize the acidic environment associated with radiation xerostomia and to prevent dental hypersensitivity.34,111 At present, no totally effective salivary substitute has been developed, but xerostomic patients should be encouraged to use those available, to ingest copious amounts of water, and to control ingestion of cariogenic foods.57 Some reports recommend the use of sodium bicarbonate rinses to neutralize oral acidity, but to date there is no strong evidence that this is beneficial. Stimulation of residual salivary gland function can sometimes be achieved using sugarless gum, sugarless hard candies, or other sialogogues.57,112 Some successful salivary gland stimulation has been reported using pilocarpine hydrochloride (5 to 10 mg, 2 to 5 times daily). Research is underway to determine if this therapy, rendered prior to radiation, will serve to preserve more residual salivary gland function in irradiated patients.22,58,113,114 Attenuation or loss of the sense of taste and smell is commonly associated with radiation therapy. These symptoms are usually transient, but may be permanent and can lead to food aversion, nausea, and vomiting. Dietary counseling and other coping strategies should be provided 31,45,48 CHEMOTHERAPY Drugs are used in cancer treatment, either locally or systemically, to destroy, suppress, or prevent the spread of malignant cells. Some tumors can be controlled with chemotherapy alone, or in combination with radiation and/or surgery, while drug therapy is often used to prolong life and to extend periods of tumor remission.27,1l5 Chemotherapeutic drugs can adversely affect normal tissue cells which are mitotically active, just as they affect multiplying tumor cells. For this reason, chemotherapy often induces adverse effects in the hematopoietic cells, skin, and the gastrointestinal tract (including the oral cavity)116,117 Affected oral soft tissues are also exposed to physical, chemical, thermal, and microbial injury. Therefore, the oral cavity may become the focus of chemotherapeutic complications, especially if bone marrow suppression has also occurred.27,77,118,119 Many of the resultant side effects are similar to those induced by radiation, although sometimes more transient in nature.46

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Xerostomia, dysphagia, and dysgeusia are common, and susceptibility to mucositis, soft tissue ulceration, and infection may increase. Mucositis may be quite severe, with onset occurring within 7 days of initiation of chemotherapy and duration varying from several days to weeks. Combination drug therapy or chemoradiation therapy is more likely to induce longer-lasting lesions.25,120,121 Gingivitis is also common, and gingival bleeding is found during maximal myelosuppression due to induced thrombocytopenia.22,29,115,118 Drugs most frequently associated with mucositis and myelosuppression include etoposide, cyclophosphamide, doxorubicin, dactinomycin, daunorubicin, 5 fluorouracil, bleomycin, melphalan, and meth otrexate.22,29,36,84,115,117,121-124 As previously discussed, periodontal health should be maintained throughout chemotherapy. It is best provided before the cancer treatment is initiated and during intervals between treatments. Chemotherapeutic management is usually episodic over a 3 to 5-day period, with recovery intervals of 21 to 28 days, provided between therapeutic sessions.125 Drug-induced myelosuppression renders patients susceptible to hemorrhage and infections.124 Most authorities recommend that routine hygiene measures be somewhat curtailed when platelet counts decrease to <40,000 to 50,000 per mm,126 although thrombocytopenic hemorrhage in response to trauma is more likely to occur when the platelet count is <20,000/ mm.84,115,126 Carefully monitored oral hygiene measures can be continued at least to that point.127 Gingival hemorrhage can usually be controlled by local measures such as pressure; periodontal dressings; or application of topical thrombin, gelatin sponges, oxidized cellulose, or prefabricated stents lined with a hemostatic agent.128 Persistent hemorrhage may require platelet supplementation 22,27,127 In general, periodontal therapy should be avoided when the white blood cell (WBC) count is reduced to <2,000 cells/mm, 126 and/or the absolute granulocyte count is <1,500/mm.126 Any emergent periodontal treatment under these circumstances usually requires prophylactic antibiotic coverage, and all patients with in-dwelling centralvenous catheters require prophylactic antibiotic coverage for procedures likely to induce bacteremia.129 Selection of the most appropriate antibiotic should be made in consultation with the patient's oncologist. If chemotherapy is ongoing, most invasive procedures are contraindicated and should be postponed until the patient is in remission or until there will be long intervals (several months) between chemotherapeutic treatments.127 Vigorous oral hygiene procedures should also be discontinued when the WBC drops <2,000/mm126 because of increased risk of septicemia.127 Some authorities suggest that gentle oral hygiene measures should be continued, however, because the risk of septicemia induced by gross plaque accumulation may exceed the risk induced

by mechanical cleansing of periodontal tissues.48,130 Many cancer therapy protocols, however, call for limiting oral hygiene measures in high-risk patients to gentle wiping of the teeth using gauze squares, cotton swabs or sponges, and using brushing sticks dipped in chlorhexidine or sodium bicarbonate.29,126,130,131 Patients with mucositis should be encouraged to rinse with lukewarm saline or sodium bicarbonate solution (5%) to dilute mucous secretions, lubricate oral mucosa, and elevate the pH of oral fluids.127 Rinsing with chlorhexidine digluconate or 0.5% povidone iodine solution may be beneficial in preventing infection of ulcerated tissues, while various soothing mouth rinses containing agents such as kaolin and diphenhydramine have been recommended for mucositis if xerostomia is not present.27,117,132 Nutritional deficiencies may ensue as a result of oral discomfort associated with chemotherapy and complicated by any associated nausea, vomiting, or anorexia induced by the malignancy or its treatment.27 Fluoride tray carriers may be considered for patients suffering from protracted vomiting or esophageal reflux to protect the dentition from decalcification by regurgitated gastric acids.22 Bland, semisoft foods that are not acidic or cariogenic in nature are recommended and foods can be thinned with sauces, milk, or gravy to facilitate swallowing until the chemotherapeutic regimen has been completed. Viral infections are common in myelosuppressed chemotherapy patients.30,133 This is not surprising, since 30% or more of adults in the general population have been found to have circulating serum antibodies to HSV. Viral reactivity may lead to severe oral or disseminated infections during periods of immunosuppression, and HSV infections are often associated with severe, painful, and prolonged ulcerations, which are not typical of those found in the immunocompetent host.19,30,134,135 Suspected HSV lesions should be managed as described for the irradiated patient, with diagnosis being established using viral cultures, direct immunofluorescence, or other rapid diagnostic tests, and the lesions treated with antiviral agents such as acyclovir administered orally or intravenously.115,134-136 Bacterial infections following chemotherapy can cause localized mucosal lesions, sialoadenitis, periodontal abscesses, pericoronitis, or acute necrotizing ulcerative gingivitis.117 Because systemic infection is of grave concern in neutropenic patients, constant vigilance must be maintained to control, prevent, or manage oral infections of any type.115 This risk may be higher in leukemic patients than in those with solid tumors, because antileukemic therapy is designed to deliberately achieve myelosuppression.115 Professional removal of plaque and calculus, optimal oral hygiene, and use of antimicrobial mouth rinses such as chlorhexidine are important in preventing septicemia.

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Treatment of oral infections with selected antibiotic combinations is important and should include an agent effective against anaerobic Gram-negative bacilli such as Pseudomonas, Klebsiella, or enterobacteria, which may be found in the oral cavity of immunocompromised individuals.18,21,117,122 Oral and blood microbial culture and sensitivity testing may be used for antibiotic selection, but the tests do not always identify the causative organisms. Gram-negative bacteria are often resistant to penicillin and cephalosporins, and agents such as trimethiprim and sulfamethoxazole may be recommended by the attending oncologist.127 Chemotherapeutic agents may have a toxic effect on peripheral and autonomic nerves and, on occasion, cranial nerves are affected, including the glossopharyngeal and trigeminal. Plant alkaloids such as vincristine sulfate are most commonly associated with neurotoxic effects. These drug-induced neurologic disorders may induce oral pain which mimics that of dental or periodontal origin. In the event this occurs and no obvious etiologic factors are evident in the oral cavity, the patient should be reassured and pain-control treatment administered to minimize the discomfort. These neurological effects will usually subside when the course of chemotherapy has been completed.117 An exact formula for management of chemotherapy patients is beyond the scope of this paper. Proper oral care is imperative, whenever possible, to prevent complications. If complications cannot be prevented, the periodontist must coordinate periodontal therapy with the oncologist to select appropriate times for periodontal treatment and to ensure that the potential for hemorrhage, infections, and other adverse effects is properly controlled.115 BONE MARROW TRANSPLANTATION Bone marrow transplantation (BMT) is an important cancer treatment procedure in which bone marrow from a donor is infused into a patient suffering from a hematologic malignancy or other condition not responsive to chemotherapy alone. Transplantation is currently used for leukemia, lymphoma, multiple myeloma, neuroblastoma, some solid tumors, and various forms of anemia.137-139 BMT grafts may be allogeneic from a histocompatible donor, syngeneic from an identical twin, or autologous from the patient's own marrow. Many allogeneic BMT grafts are used today and an exact histocompatibility match is difficult to achieve. The lack of complete histocompatibility may actually enhance successful treatment of leukemia, however, through a graft-versus-leukemia effect. Allogenically engrafted patients may develop graft-versus-host disease (GVHD), however, in which the donated marrow cells recognize the new host as foreign and attempt rejection.50,138 Chemotherapy and total body irradiation (TBI) are used to remove the malignant marrow cells prior to engraft-

ment. Depending on the type of graft to be implanted, various drugs such as carboplatin, cyclophosphamide, cytosine arabinoside, etoposide, or nitrosurea are used with or without TBI. TBI is generally administered at a dose of 150 to 1,500 cGy and chemoradiation therapy is typically performed 1 to 2 weeks prior to BMT.50,140 Following infusion of 500 to 1,000 ml of donor marrow, the patient is isolated for 30 to 60 days to minimize the risk of opportunistic infections, until adequate engraftment has occurred and host defenses have been reestablished.139,141 This pancytopenic phase is said to exist until the absolute neutrophil count exceeds 500 cells/mm.126 Even mild infections can be life-threatening to the BMT patient early in treatment, and potential oral sources of infection should be controlled.142 The BMT patient is also subject to side effects of chemotherapy and radiation. Generally, induced pancytopenia will last for 3 to 4 weeks after engraftment, predisposing the patient to severe ulcerative oral mucositis and xerostomia 128,141,143-146 Additional chemotherapeutic agents such as methotrexate and cyclosporin are often required to prevent severe GVHD following transplantation.147 BMT patients are at high risk for development of candidiasis, viral infections (most commonly herpes simplex, varicella zoster, and cytomegalovirus),133,148-153 and bacterial infections, including those associated with microorganisms of periodontal origin.154-156 Hairy leukoplakia has been reported in human immunodeficiency virus-negative bone marrow transplantation patients due to the EpsteinBarr virus.157 Atypical, potentially life-threatening pathogenic organisms have been cultured from sites of preexisting periodontitis in myelosuppressed individuals, which emphasizes the importance of establishing periodontal health prior to cancer therapy.158 Leukemia patients and those receiving myeloablative or myelosuppressive therapy may be especially susceptible to necrotizing ulcerative gingivitis or necrotizing stomatitis.159 If such lesions occur, they are best treated with debridement; use of an antibiotic such as metronidazole or chlorhexidine mouth rinses; and frequent recall. Necrotizing stomatitis may require removal of necrotic bone and soft tissue and use of topical and systemic antibiotics administered in consultation with the oncologist.127 GVHD is a potentially life-threatening immunological phenomenon in which the immunocompetent engrafted marrow reacts against the tissues of the host.160 The condition may affect up to 45% of BMT patients with most acute lesions occurring within the first post-engraftment month.144,161 Target organs include the liver, lungs, gastrointestinal tract, exocrine glands, skin, and mucosa. The oral cavity may be involved up to 80% of the time.161 Oral signs and symptoms are similar to those encountered in lupus erythematosus, lichen planus, scleroderma, or Sjogren's syndrome.46,141,162 GVHD is classified as chronic

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if the signs and symptoms persist for several months, but chronic GVHD may appear de novo several months to years after engraftment.163,164 Diagnosis of GVHD is based on the appearance of skin and mucosal lesions, on abnormal liver function tests, and on biopsy which may reveal lichenoid or scleroderma-like changes to skin and mucosa. Oral signs may range from mild mucosal erythema to severe mucositis, ulcerations, gingivitis, desquamation of oral tissues, xerostomia, and infections.50,165 Clinically, the xerostomia may predispose the patient to dental caries as well as to exacerbations of mucositis and oral infections.161 Unusual oral side effects of GVHD include development of salivary retention phenomena which manifest as saliva-filled vesicles, presence of verrucous xanthomas, and occurrence of atypical pyogenic granulomas in response to trauma.50,166-168 Cyclosporin is frequently prescribed for the prevention and treatment of GVHD. This medication is associated with gingival overgrowth in a significant percentage of patients. It is important to note that oral squamous cell carcinoma, lymphoma, and Kaposi's sarcoma have been reported to occur in sites of cyclosporin-induced gingival enlargement, perhaps as a result of over-immunosuppression.169-173 Periodontal management prior to BMT has been described above. Brushing and flossing is usually discontinued when WBC and platelets reach the minimal acceptable level. Oral cleaning is then accomplished using cotton swabs, gauze sponges, soft sponge sticks, and chlorhexidine rinses. During isolation following BMT engraftment, oral hygiene is maintained in the same fashion in concert with prophylactic use of systemic antifungals and antiviral drugs.152,174 After partial recovery, patients are managed as described for other individuals receiving chemoradiation therapy. Oral GVHD can be controlled using coordinated therapy, including maintenance of meticulous oral hygiene, frequent dental visits, and topical and systemic administration of corticosteroids, antifungals, and antivirals.50,165 CONCLUSIONS Increasing skills in cancer detection and treatment have expanded the role of the periodontist in the management of cancer patients. This role begins prior to treatment and continues to a more limited degree during therapy. The cancer survivor presents with special periodontal management considerations which may extend throughout the lifetime of the patient. Periodontists should closely coordinate delivery of periodontal therapy with oncologists and other health care providers to ensure optimal patient treatment results. Acknowledgments The primary author for this paper is Dr. Terry D. Rees. Members of the 1996-97 Research, Science and Therapy

Committee include Drs. David L. Cochran, Chair; Timothy Blieden; Robert E. Cohen; Gary Greenstein; William W. Hallmon; Vincent Iacono; Martha J. Somerman; Thomas E. Van Dyke; Robert J. Genco, Consultant; Roy C. Page, Consultant; Terry D. Rees, Consultant; and W. Lee Young, Jr., Consultant. REFERENCES
1. Chambers MS, Jacob RF. How carcinogens cause cancer. Tex Dent J 1994;June:13-19. 2. Gritz ER. Cigarette smoking: The need for action by health professionals. CA Cancer J Clin 1988;38:194-212. 3. Holmstrup P, Pindborg JJ. Oral mucosal lesions in smokeless tobacco users. CA Cancer J Clin 1988;38:230-235. 4. Lamey PJ. Management options in potentially malignant and malignant oral epithelial lesions. Community Dent Health 1993;10(S): 5362. 5. Peterson DE, D'Ambrosio JA. Nonsurgical management of head and neck cancer patients. Dent Clin North Am 1994;38:425-445. 6. Silverman S Jr. Epidemiologic and demographic update in oral cancer: California and national data-1973 to 1985. J Am Dent Assoc 1990;120:495-499. 7. Menck HR, Garfinkel L, Dodd GD. Preliminary report of the National Cancer Data Base. CA Cancer J Clin 1991;41:7-18. 8. Weinshel EL, Peterson BA. Hodgkin's disease. CA Cancer J Clin 1993;43:325-346. 9. Dahl EC. Breast carcinoma metastatic to the mandible. Compendium Cont Educ Dent 1993;14:1536, 1538-1540. 10. Greenberg EJ. The treatment of metastatic breast cancer. CA Cancer J Clin 1991;41:242-256. 11. Devine SM, Larson RA. Acute leukemia in adults: Recent developments in diagnosis and treatment. CA Cancer J Clin 1994;44:326 352. 12. Williams MC, Lee GT Childhood leukemia and dental considerations. J Clin Pediatr Dent 1991;15:160-164. 13. Morrison VA. Chronic leukemias. CA Cancer J Clin 1994;44:353377. 14. Barrett AP. Gingival lesions in leukemia. A classification. J Periodontol 1984;55:585-588. 15. Bressman E, Decter JA, Chasens AI, Sackler RS. Acute myeloblastic leukemia with oral manifestations. Report of a case. Oral Surg Oral Med Oral Pathol 1982;54:401-403. 16. Dreizen S, McCredie KB, Keating MJ, Luna MA. Malignant gingival and skin "infiltrates" in adult leukemia. Oral Surg Oral Med Oral Pathol 1983;55:572-579. 17. Ellegaard B, Bergmann OJ, Ellegaard J. Effect of plaque removal on patients with acute leukemia. J Oral Pathol Med 1989;18:5458. 18. Cheatham BD, Henry RJ. A dental complication involving Pseudomonas during chemotherapy for acute Iymphoblastic leukemia. J Clin Pediatr Dent 1994;18:215-217. 19. Epstein JB, Sherlock CH, Page JL, Spinelli J, Phillips G. Clinical study of herpes simplex virus infection in leukemia. Oral Surg Oral Med Oral Pathol 1990;70:38-43. 20. Maeda H, Kameyama Y, Nakane S, Takehana S, Sato E. Epithelial dysplasia produced by carcinogen pretreatment and subsequent wounding. Oral Surg Oral Med Oral Pathol 1989;68:50-56. 21. O'Sullivan EA, Duggal MS, Bailey CC, Curzon MEJ, Hart P. Changes in the oral microflora during cytotoxic chemotherapy in children being treated for acute leukemia. Oral Surg Oral Med Oral Pathol 1993;76:161-168. 22. Hurst PS. Dental considerations in management of head and neck cancer. Otolaryngol Clin North Am 1985;18:573-603. 23. Lockhart PB, Clark J. Pretherapy dental status of patients with

798

POSITION PAPER

J Periodontol August 1997

malignant conditions of the head and neck. Oral Surg Oral Med Oral Pathol 1994;77:236-241. 24. Marciani RD, Ownby HE. Treating patients before and after irradiation. J Am Dent Assoc 1992;123:108-112. 25. Niehaus CS, Meiller TF Peterson DE, Overholser CD. Oral complications in children dunng cancer therapy. Cancer Nurs 1987;10: 15-20. 26. Peters E, Monopoli M, Woo SB, Sonis S. Assessment of the need for treatment of postendodontic asymptomatic periapical radiolucencies in bone marrow transplant recipients. Oral Surg Oral Med Oral Pathol 1993;76:45-48. 27. Wescott WB. Dental management of patients being treated for oral cancer. CDA J 1985;13:42-47. 28. Morton ME, Simpson W. The management of osteoradionecrosis of the jaws. Br J Oral Maxillofac Surg 1986;24:332-341. 29. National Institutes of Health. National Institutes of Health consensus development conference statement: Oral complications of cancer therapies: Diagnosis, prevention, and treatment. J Am Dent Assoc. 1989;119:179-183. 30. Poland J. Prevention and treatment of oral complications in the cancer patient. Oncol 1991;5:45-50,52,57,61-62. 31. American Dental Association. Head and neck cancer patients receiving radiation therapy. Chicago: American Dental Association; 1989. 32. Semba SE, Mealey BL, Hallmon WW. The head and neck radiotherapy patient. Part 1. Oral manifestations of radiation therapy. Compendium Cont Educ Dent 1994;15:250, 252-261. 33. Kolbinson DA, Schubert MM, Flournoy N, Truelove EL. Early oral changes following bone marrow transplantation. Oral Surg Oral Med Oral Pathol 1988;66:130-138. 34. Ghalichebaf M, DeBiase CB, Stookey GK. A new technique for the fabrication of fluoride carriers in patients receiving radiotherapy to the head and neck. Compendium Cont Educ Dent 1994;15:470, 473474,476. 35. Shrout MK. Managing patients undergoing radiation. J Am Dent Assoc 1991;122:69-70,72. 36. Allard WF, el-Akkad S, Chatmas JC. Obtaining pre-radiation therapy dental clearance. J Am Dent Assoc 1993;124:88-91. 37. Kluth EV, Jain PR, Stuchell RN, Frich JC. A study of factors contributing to the development of osteoradionecrosis of the jaws. J Prosthet Dent 1988;59:194-201. 38. Lowe O. Pretreatment dental assessment and management of patients undergoing head and neck irradiation. Clin Prev Dent 1986;8:24-30. 39. Markitziu A, Zafiropoulos G, Tsalikis L, Cohen L. Gingival health and salivary function in head and neck-irradiated patients. A five year follow up. Oral Surg Oral Med Oral Pathol 1992;73:427433. 40. Cacchillo D, Barker GJ, Barker BE Late effects of head and neck radiation therapy and patient/dentist compliance with recommended dental care. Spec Care Dentist 1993;13:159-162. 41. Morton M, Roberts H. Oral cancer and precancer: After-care and terminal care. Br Dent J 1990;168:283-287. 42. Hays GL, Lippman SM, Flaitz CM, et al. Co-carcinogenesis and field cancerization: Oral lesions offer first signs. J Am Dent Assoc 1995;126:47-51. 43. Dwyer JT, Efstathion A, Palmer C, Papas A. Nutritional support in treatment of oral carcinomas. Nutr Rev 1991;49:332-337. 44. Guo CB, Ma DQ, Zhang KH. Applicability of the general nutritional status score to patients with oral and maxillofacial malignancies. Int J Oral Maxillofac Surg 1994;23:167-169. 45. McAndrew PG. Oral cancer and precancer: Treatment. Br Dent J 1990;168:191-198. 46. Schubert MM, Izutsu KT. Iatrogenic causes of salivary gland dysfunction. J Dent Res 1987;66(S):680-688. 47. Epstein JB, Rea Giuseppe, Wong FLW, Spinelli J, Stevenson-

Moore P. Osteonecrosis: Study of the relationship of dental extractions in patients receiving radiotherapy. Head Neck Surg 1987;10:48-54. 48. Mealey BL, Semba SE, Hallmon WW. The head and neck radiotherapy patient. Part 2. Management of oral complications. Compendium Cont Educ Dent 1994;15:442, 444, 446-458. 49. Reed JR. Head and neck radiation patients in a small town: Coordinating dental treatment with radiation therapy. Gen Dent 1991 ;39:258-260. 50. Rhodus NL, Little JW. Dental management of the bone marrow transplant patient. Compendium Cont Educ Dent 1992;13:10421050. 51. Ciancio S. Expanded and future uses of mouthrinses. J Am Dent Assoc 1994;125:29S-32S. 52. Engelmeier RL. A dental protocol for patients receiving radiation therapy for cancer of the head and neck. Spec Care Dentist 1987;7: 54-58. 53. Karr RA, Kramer DC, Toth BB. Dental implants and chemotherapy complications. J Prosthet Dent 1992;67:683-687. 54. Sager RD, Theis RM. Dental implants placed in a patient with multiple myeloma: Report of a case. J Am Dent Assoc 1990; 121: 699701. 55. Vassos DM. Dental implant treatment in a severely compromised (irradiated) patient. J Oral Implantol 1992;18:142-147. 56. Makkonen TA, Kiminki A, Makkonen TK, Nordman E. Dental extractions in relation to radiation therapy of 224 patients. Int J Oral Maxillofac Surg 1987;16:56-64. 57. Peterson DE. Dental care for the cancer patient. Compendium Cont Educ Dent 1983;4:115-120. 58. Fleming TJ. Oral tissue changes of radiation-oncology and their management. Dent Clin North Am 1990;34:223-237. 59. McDermott IG, Rosenberg SW. Overdentures for the irradiated patient. J Prosthet Dent 1984;51:314-317. 60. Dreizen S, McCredie KB, Bodey GP, Keating MJ. Mucocutaneous herpetic infections during cancer chemotherapy. Postgrad Med 1988;84:181-188. 61. Wade JC, Newton B, McLaren C, Flournoy N, Keeney RE, Meyers JD. Intravenous acyclovir to treat mucocutaneous herpes simplex virus infection after marrow transplantation: A double blind study. Ann Intern Med 1982;96:265-269. 62. Whitley RJ, Blum MR, Barton N, de Miranda P. Pharmacokinetics of acyclovir in humans following intravenous administration. A model for the development of parenteral antivirals. Am J Med 1982;73(S#IA):165-171. 63. Fletcher GH. The role of irradiation in the management of squamous-cell carcinomas of the mouth and throat. Head Neck Surg 1979; 1:441-457. 64. Klokkevold P, Lew D. Head and neck cancer patients. J Calif Dent Assoc 1989;Jan:44-49. 65. Jones LR, Toth BB, Keene HJ. Effects of total body irradiation on salivary gland function and caries-associated oral microflora in bone marrow transplant patients. Oral Surg Oral Med Oral Pathol 1992;73:670-676. 66. Fujita M, Hirokawa Y, Tomamoto M, et al. Dose-reducing effect of Lipowitz metal-embedded spacers in interstitial brachytherapy for carcinoma of the mobile tongue. Oral Surg Oral Med Oral Pathol 1994;77:589-593. 67. Salisbury PL III, Stump TE, Randall ME. Interstitial radioactive implants for oral and oropharyngeal cancer: Dentistry's role. Spec Care Dentist 1991;11:63-67. 68. Ampil FL, Buechter KJ, Bairnsfather LE, Shockley WW. Timing and dosage of postoperative radiotherapy for squamous cell carcinoma of the upper aerodigestive tract. J Oral Maxillofac Surg 1993;51:11941197. 69. Hansen O, Srensen JA, Siemssen SJ, Poulsen H. Importance of the

Volume 68 Number 8

POSITION PAPER

799

time interval between radiotherapy and surgery in oral cancer. Eur J Cancer B Oral Oncol 1993;29B:35-38. 70. Prosnitz LR. What's new in radiation oncology. BUMC Proceedings 1992;5:55-57. 71. Shingaki S, Ohtake K, Nomura T, Nakajima T. The role of radiotherapy in the management of salivary gland carcinomas. J Cranio Maxillofac Surg 1992;20:220-224. 72. Valente G, Vercellino V, Corradi L, et al. Histopathological findings after preoperative chem-radiotherapy in oral and oropharyngeal carcinoma. A study of 28 resected specimens. Eur J Cancer B Oral Oncol 1993;29B:113-117. 73. Mohr C, Bohndorf W, Carstens J, et al. Preoperative radiochemotherapy and radical surgery in comparison with radical surgery alone. A prospective, multicentric, randomized DOSAK study of advanced squamous cell carcinoma of the oral cavity and the oropharynx (a three-year follow-up). Int J Oral Maxillofac Impl 1994;23: 140-148. 74. Barasch A, Safford MM. Management of oral pain in patients with malignant diseases. Compendium Cont Educ Dent 1993;14:13761383. 75. Jansma J, Vissink A, Spijkervot FK, et al. Protocol for the prevention and treatment of oral sequelae resulting from head and neck radiation therapy. Cancer 1992;70:2171-2180. 76. Rothwell BR. Prevention and treatment of the orofacial complications of radiotherapy. J Am Dent Assoc 1987;114:316-322. 77. Carl W. Local radiation and systemic chemotherapy: Preventing and managing the oral complications. J Am Dent Assoc 1993;124:119123. 78. Barrett AW, Porter SR, Scully C, Eveson JW, Griffiths MJ. Oral melanotic macules that develop after radiation therapy. Oral Surg Oral Med Oral Pathol 1994;77:431-434. 79. Dahllo G, Barr M, Bolme P, et al. Disturbances in dental developf ment after total body irradiation in bone marrow transplant recipients. Oral Surg Oral Med Oral Pathol 1988;65:41-44. 80. Dahllo G, Forsberg CM, Ringden O, et al. Facial growth and morf phology in long-term survivors after bone marrow transplantation. Eur J Orthod 1989;11:332-340. 81. Dahllo G, Krekmanova L, Kopp S, Borgstrom B, Forsberg CM, f Ringden O. Craniomandibular dysfunction in children treated with total-body irradiation and bone marrow transplantation. Acta Odontol Scand 1994;52:99-105. 82. Dahllo G, Rozell B, Forsberg CM, Borgstrom B. Histologic changes f in dental morphology induced by high dose chemotherapy and total body irradiation. Oral Surg Oral Med Oral Pathol 1994;77:56-60. 83. Dury DC, Roberts NW, Miser JS, Folio J. Dental root agenesis secondary to irradiation therapy in a case of rhabdomyosarcoma of the middle ear. Oral Surg Oral Med Oral Pathol 1984;57:595-599. 84. Fleming P. Dental management of the pediatric oncology patient. Curr Opin Dent 1991;1:577-582. 85. Brown AT, Sims RE, Raybould TP, Lillich TT, Henslee PJ, Feretti GA. Oral Gram-negative bacilli in bone marrow transplant patients given chlorhexidine rinses. J Dent Res 1989;68: 1199-1204. 86. Epstein JB, Vickars L, Spinelli J, Reece D. Efficacy of chlorhexidine and nystatin rinses in prevention of oral complications in leukemia and bone marrow transplantation. Oral Surg Oral Med Oral Pathol 1992;73:682-689. 87. Feretti GA, Ash RC, Brown AT, Largent BM, Kaplan A, Lillich TT. Chlorhexidine for prophylaxis against oral infections and associated complications in patients receiving bone marrow transplants. J Am Dent Assoc 1987;114:461-467. 88. Ferretti GA, Hansen IA, Whittenburg K, Brown AT, Lillich TT, Ash RC. Therapeutic use of chlorhexidine in bone marrow transplant patients: Case studies. Oral Surg Oral Med Oral Pathol 1987;63:683687. 89. Raether D, Walker PO, Bostrum B, Weisdorf D. Effectiveness of oral

chlorhexidine for reducing stomatitis in a pediatric bone marrow transplant population. Pediatr Dent 1989;11 :37-42. 90. Rutkauskas JS, Davis JW. Effects of chlorhexidine during immunosuppressive chemotherapy. A preliminary report. Oral Surg Oral Med Oral Pathol 1993;76:441-448. 91. Thurmond JM, Brown AT, Sims RE, Feretti GA, Raybould TP, Lillich TT, Henslee PJ. Oral Candida albicans in bone marrow transplant patients given chlorhexidine rinses: Occurrence and susceptibilities to the agent. Oral Surg Oral Med Oral Pathol 1991;72: 291-295. 92. Toljanic JA, Saunders VW Jr. Radiation therapy and management of the irradiated patient. J Prosthet Dent 1984;52:852-858. 93. Samaranayake LP, MacFarlane TW, Lamey PJ, Ferguson MM. A comparison of oral rinse and imprint sampling techniques for the detection of yeast, coliform and Staphylococcus aureus carriage in the oral cavity. J Oral Pathol 1986;15:386-388. 94. Muzyka BC, Glick M. A review of oral fungal infections and appropriate therapy. J Am Dent Assoc 1995;126:63-72. 95. Ruskin JD, Wood RP, Bailey MR, Whitmore CK, Shaw BW. Comparative trial of oral clotrimazole and nystatin for oropharyngeal candidiasis prophylaxis in orthotopic liver transplant patients. Oral Surg Oral Med Oral Pathol 1992;74:567-571. 96. Fattore LD, Strauss R, Bruno J. The management of periodontal disease in patients who have received radiation therapy for head and neck cancer. Spec Care Dentist 1987;7:120-123. 97. Marciani RD, Ownby HE. Osteoradionecrosis of the jaws. J Oral Maxillofac Surg 1986;44:218-223. 98. Fujita M, Tanimoto K, Wada T. Early radiographic changes in radiation bone injury. Oral Surg Oral Med Oral Pathol 1986;61: 641-644. 99. McClure D, Barker G, Barker B, Feil P. Oral management of the cancer patient. Part II. Oral complications of radiation therapy. Compendium Cont Educ Dent 1987;8:88-92. 100. Pappas GC. Oral roentgenology. Bone changes in osteoradionecrosis: A review. Oral Surg Oral Med Oral Pathol 1969;27:622-630 101. Epstein JB, Wong FLW, Stevenson-Moore P. Osteoradionecrosis: Clinical experience and a proposal for classification. J Oral Maxillofac Surg 1987;45:104-110. 102. Rodu B, Filler SJ, Woodfin GK. Tooth extraction by orthodontic force after radiation therapy: Report of case. J Am Dent Assoc 1985; 111:955-957. 103. Fattore LD, Strauss RA. Hyperbaric oxygen in the treatment of osteoradionecrosis: A review of its use and efficacy. Oral Surg Oral Med Oral Pathol 1987;63:280-286. 104. Kraut RA. Prophylactic hyperbaric oxygen to avoid osteoradionecrosis when extractions follow radiation therapy. Clin Prevent Dent 1985;7:17-20. 105. Marx RE, Johnson RP, Kline SN. Prevention of osteoradionecrosis: A randomized prospective clinical trial of hyperbaric oxygen versus penicillin. J Am Dent Assoc 1985;111:49-54. 106. Stofka S, Liang TS. The use of hyperbaric oxygen therapy before dental treatment in post-irradiated patients. Compendium Cont Educ Dent 1994;15:200-207. 107. Bundgaard T, Tandrup O, Elbrond O. A functional evaluation of patients treated for oral cancer. A prospective study. Int J Oral Maxillofac Surg 1993;22:28-34. 108. Granstrom G, Jacobsson M, Tjellstrom A. Titanium implants in irradiated tissues: Benefits from hyperbaric oxygen. Int J Oral Maxillofac Implants 1992;7:15-25. 109. Ritchie JR, Brown JR, Guerra LR, Mason G. Dental care for the irradiated dental patient. Quintessence Int 1985;12:837-842. 110. Liu RP, Fleming TJ, Toth BB Keene HJ. Salivary flow rates in patients with head and neck cancer 0.5 to 25 years after radiotherapy. Oral Surg Oral Med Oral Pathol 1990;70:724-729. 111. Keene HJ, Fleming TJ, Toth BB. Cariogenic microflora in patients

800

POSITION PAPER

J Periodontol August 1997

with Hodgkin's disease before and after mantle field radiotherapy. Oral Surg Oral Med Oral Pathol 1994;78:577-588. 112. Bemhoft CH, Skaug N. Oral findings in irradiated edentulous patients. Int J Oral Surg 1985;14:416 427. 113. Johnson JT, Feretti GA, Nethery WJ, et al. Oral pilocarpine for postirradiation xerostomia in patients with head and neck cancer N Engl J Med 1993;329:390-395. 114. LeVeque FG, Montgomery M, Potter D, et al. A multicenter, randomized, double-blind, placebo-controlled, dose-titration study of oral pilocarpine for treatment of radiation-induced xerostomia in head and neck cancer patients. J Clin Oncol 1993;11:1124-1131. 115. Mealey BL, Semba SE, Hallmon WW. Dentistry and the cancer patient. Part I. Oral manifestations and complications of chemotherapy. Compendium Cont Educ Dent 1994;15:1252-1256. 116. Krakoff IH. Cancer chemotherapeutic and biologic agents. CA Cancer J Clin 1991;41:264-278. 117. Rosenberg SW. Oral care of chemotherapy patients. Dent Clin North Am 1990;34:239-250. 118. Childers NK, Stinnett EA, Wheeler P, Wright JT, Castleberry RP, Dasanayake AP. Oral complications in children with cancer. Oral Surg Oral Med Oral Pathol 1993;75:41-47. 119. Nikoskelainen J. Oral infections related to radiation and immunosuppressive therapy. J Clin Periodontol 1990;17:504-507. 120. Mattsson T, Arvidson K, Heimdahl A, Ljungman P, Dahllof G, Ringden O. Alterations in test acuity associated with allogeneic bone marrow transplantation. J Oral Pathol Med 1992;21:33-37. 121. Barrett AP, Buckley DJ. Oral complications of high-dose melphalan in multiple myeloma. Oral Surg Oral Med Oral Pathol 1987;64: 264267. 122. Carl W. Managing the oral manifestations of cancer therapy. Part II. Chemotherapy. Compendium Cont Educ Dent 1988;9:376 386. 123. McCarthy GM, Skillings JR. Orofacial complications of chemotherapy for breast cancer Oral Surg Oral Med Oral Pathol 1992;74: 172178. 124. Drugs of choice for cancer chemotherapy. The Medical Letter 1995;37:25-32. 125. Karr RA, Kramer DC. You can treat the chemotherapy patient. Tex Dent J 1992;109:15-20. 126. American Dental Association. Patients receiving cancer chemotherapy. Chicago: American Dental Association; 1989. 127. Semba SE, Mealey BL, Hallmon WW. Dentistry and the cancer patient. Part 2. Oral health management of the chemotherapy patient. Compendium Cont Educ Dent 1994;15:1378-1388. 128. Okamoto GU, Duperon DF Bleeding control after extractions in a patient with aplastic anemia during bone marrow transplantation: Report of case. J Dent Child 1989;Jan-Feb:50-55. 129. Ramos L. Oral aspects of chemotherapy: Patient information. Tex Dent J 1994;111:42-45. 130. Borowski B, Benhamou E, Pico JL, Laplanche A, Margainaud JP, Hayat M. Prevention of oral mucositis in patients treated with highdose chemotherapy and bone marrow transplantation: A randomized controlled trial comparing two protocols of dental care. Eur J Cancer B Oral Oncol 1994;30B:93-97. 131. Lefkoff MA, Beck FM, Horton JE. The effectiveness of a disposable tooth cleansing device on plaque. J Periodontol 1995;66: 218-221. 132. Fay JT, O'Neal R. Dental responsibility for the medically compromised patient. 3. J Oral Med 1984;39:148-156. 133. Vose JM, Kennedy BC, Bierman PJ, Kessinger A, Armitage JO. Long-term sequelae of autologous bone marrow or peripheral stem cell transplantation for Iymphoid malignancies. Cancer 1992;69: 784789. 134. MacPhail LA, Hilton JF, Heinic GS, Greenspan D. Direct immunofluorescence vs. culture for detecting HSV in oral ulcers: A comparison. J Am Dent Assoc 1995;126:74-78. 135. Montgomery MT, Redding SW, LeMaistre CE The incidence of oral

herpes simplex virus infection in patients undergoing cancer chemotherapy. Oral Surg Oral Med Oral Pathol 1986;61:238-242. 136. Flaitz CM, Hammond HL. The immunoperoxidase method for the rapid diagnosis of intraoral herpes simplex virus infection in patients receiving bone marrow transplants. Spec Care Dentist 1988;8:82-85. 137. Berkowitz RJ, Strandjord S, Jones P, et al. Stomatologic complications of bone marrow transplantation in a pediatric population. Pediatr Dent 1987;9:105-110. 138. Cooper B. New concepts in management of acute leukemia. BUMC Proceedings 1990;3:31-33. 139. Maxymiw WG, Wood RE. The role of dentistry in patients undergoing bone marrow transplantation. Br Dent J 1989;167:229-234. 140. Collins RH, Miller GW, Fay JW. Autologous bone marrow transplantation: A review. BUMC Proceedings 1991 ;4:3-12. 141. Dahllof G, Heimdahl A, Modeer T, Twetman S, Bolme P, Ringden O. Oral mucous membrane lesions in children treated with bone marrow transplantation. Scand J Dent Res 1989;97:268-277. 142. Barasch A, Mosier KM, D'Ambrosio JA, Giniger MS, Ascensao J, Peterson DE. Postextraction osteomyelitis in a bone marrow transplant recipient. Oral Surg Oral Med Oral Pathol 1993;75: 391-396. 143. Cutler LS. Evaluation and management of the dental patient with cancer. I. Complications associated with chemotherapy or bone marrow transplantation. J Conn State Dent Assoc 1987;61:236238. 144. Heimdahl A, Mattsson T, Dahllof G, Lonnquist B, Ringden O. The oral cavity as a port of entry for early infections in patients treated with bone marrow transplantation. Oral Surg Oral Med Oral Pathol 1989;68:711-716. 145. Seto BG, Kim M, Wolinsky L, Mito RS, Champlin R. Oral mucositis in patients undergoing bone marrow transplantation. Oral Surg Oral Med Oral Pathol 1985;60:493-507. 146. Shearer BH, Hay KD. Hard and soft tissue oral changes following bone marrow transplantation. N Z Dent J 1987;83: 103-104. 147. LeVeque FG, Ratanatharathorn V, Danielsson KH, Orville B, Coleman DN, Turner S. Oral cytomegalovirus infection in an unrelated bone marrow transplantation with possible mediation by graftversus-host disease and the use of cyclosporin-A. Oral Surg Oral Med Oral Pathol 1994;77:248-253. 148. Birek C, Patterson B, Maxymiw WG, Minden MD. EBV and HSV infections in a patient who had undergone bone marrow transplantation: Oral manifestations and diagnosis by in situ nucleic acid hybridization. Oral Surg Oral Med Oral Pathol 1989;68:612-617. 149. Brown AT, Shupe JA, Sims RE, et al. In vitro effect of chlorhexidine and amikacin on oral Gram-negative bacilli from bone marrow transplant recipients. Oral Surg Oral Med Oral Pathol 1990;70:715-719. 150. LeVeque FG, Ratanatharathom V, Dan ME, Orville B, Coleman DN, Turner S. Oral cytomegalovirus infection in an unrelated bone marrow transplantation with possible mediation by graft-versushost disease and the use of cyclosporin-A. Oral Surg Oral Med Oral Pathol 1994;77:248-253. 151. Schubert MM, Epstein JB, Llyod ME, Cooney E. Oral infections due to cytomegalovirus in immunocompromised patients. J Oral Pathol Med 1993;22:268-273. 152. Schubert MM, Peterson DE, Flournoy N, Meyers JD, Truelove EL. Oral and pharyngeal herpes simplex virus infection after allogeneic bone marrow transplantation: Analysis of factors associated with infection. Oral Surg Oral Med Oral Pathol 1990;70:286-293. 153. Schuchter LM, Wingard JR, Piantadosi S, Burns WH, Santos GW, Saral R. Herpes zoster infection after autologous bone marrow transplantation. Blood 1989;74:1424-1427. 154. Barrett AP, Schifter M. Antibiotic strategy in orofacial/head and neck infections in severe neutropenia. Oral Surg Oral Med Oral Pathol 1994;77:350-355.

Volume 68 Number 8 155. Mattsson T, Heimdahl A, Dahllof G, Ma DQ, Ringden O. Oral and nutritional status in allogenic marrow recipients treated with T-cell depletion or cyclosponne combined with methotrexate to prevent graft-versus-host disease. Oral Surg Oral Med Oral Pathol 1992;74:34-40. 156. Peterson DE, Minah GE, Overholser CD, et al. Microbiology of acute periodontal infection in myelosuppressed cancer patients. J Clin Oncol 1987;5:1461-1468. 157. Epstein JB, Sherlock CH, Wolber RA. Hairy leukoplakia after bone marrow transplantation. Oral Surg Oral Med Oral Pathol 1993;75: 690-695. 158. Peterson DE. Pretreatment strategies for infection prevention in chemotherapy patients. NCI Monogr 1990;9:61-71. 159. Barrett AP. Facial cellulitis responsive to flucloxacillin in acute leukemia. Ann Dent 1989;48:28-29. 160. Dahllof G, Modeer T, Bolme P, Ringden O, Heimdahl A. Oral health in children treated with bone marrow transplantation: A oneyear follow-up. J Dent Child 1988;55:196-200. 161. Curtis JW Jr, Caughman GB. An apparent unusual relationship between rampant caries and graft-versus-host disease. Oral Surg Oral Med Oral Pathol 1994;78:267-272. 162. Hiroki A, Nakamura S, Shinohara M, Oka M. Significance of oral examination in chronic graft-versus-host disease. J Oral Pathol Med 1994;23:209-215. 163. Heimdahl A, Johnson G, Danielsson KH, Lonnquist B, Sundelin P, Ringden O. Oral condition of patients with leukemia and severe aplastic anemia. Follow up one year after bone marrow transplantation. Oral Surg Oral Med Oral Pathol 1985;60:498-504. 164. LeVeque FG. An unusual presentation of chronic graft-versus-host disease in an unrelated bone marrow transplantation. Oral Surg Oral Med Oral Pathol 1990;69:581-584. 165. Wingard JR, Niehaus CS, Peterson DE, et al. Oral mucositis after

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bone marrow transplantation. A marker of treatment toxicity and pre dictor of hepatic veno-occlusive disease. Oral Surg Oral Med Oral Pathol 1991;72:419-424. 166. Allen CM, Kapoor N. Verruciform xanthoma in a bone marrow transplant recipient. Oral Surg Oral Med Oral Pathol 1993;75: 591-594. 167. Barrett AP. Graft-versus-host disease. A clinicopathologic review. Ann Dent 1987;46:7-11. 168. Wandera A, Walker PO. Bilateral pyogenic granuloma of the tongue in graft-versus-host disease: Report of a case. J Dent Child 1994;61:401-403. 169. Little JW, Rhodus NL. Dental treatment of the liver transplant patient. Oral Surg Oral Med Oral Pathol 1992;73:419-426. 170. Maxymiw WG, Wood RE, Lee L. Primary, multi-focal, nonHodgkin's Iymphoma of the jaws presenting as periodontal disease in a renal transplant patient. Int J Oral Maxillofac Surg 1991;20:6970. 171. Regev E, Zeltser R, Lustmann J. Lip carcinoma in renal allograft recipient with long-term immunosuppressive therapy. Oral Surg Oral Med Oral Pathol 1992;73:412-414. 172. Thomas DW, Seddon SV, Shepherd JP. Systemic immunosuppression and oral malignancy: A report of a case and review of the literature. Br J Oral Maxillofac Surg 1993;31:391-393. 173. Varga E, Tyldesley WR. Carcinoma arising in cyclosporin-induced gingival hyperplasia. Br Dent J 1991;171:26 27. 174. Redding SW, Montgomery MT. Acyclovir prophylaxis for oral herpes simplex virus infection in patients with bone marrow transplants. Oral Surg Oral Med Oral Pathol 1989;67:680-683. Send reprint requests to: Marketing Department, The American Academy of Periodontology, Suite 800, 737 North Michigan Avenue, Chicago, IL 60611-2690; fax: 312/787-3670; voice: 312/573-3253; e-mail: Myrna@perio.org