FACT SHEET: Hematopoietic Cell Transplantation (also known as “HCT” and “hematopoietic stem cell transplantation” [HSCT]; includes “bone marrow transplantation” [BMT] and blood stem cell transplantation [BSCT], the latter including “peripheral blood stem cell transplantation” [PBSCT] and “umbilical cord blood transplantation” [UCBT])
Is the initiation of non-invasive dental hygiene procedures* contra-indicated?
- Possibly (e.g., during period of patient/client confinement in the transplant centre)
Is medical consult advised?
- Yes, the patient/client’s oncologist/transplantation specialist should be consulted before any oral health procedure, including prophylaxis. This includes overall risk assessment and the safest time to schedule an appointment. Consultation should also occur if the patient/client is experiencing oral ulcerations and pain, is suspected of having active infection, or is suspected of having elevated bleeding tendency. Additionally, medical consult should occur if graft-versus-host disease or second malignancy in the oral region is suspected post-transplantation.
Is the initiation of invasive dental hygiene procedures contra-indicated?**
- Yes. Active chemoradiation therapy may affect appropriateness or safety, and scaling and root planing, including curetting of surrounding tissue, are contraindicated until the patient/client is medically cleared. In some cases, immunosuppression that warrants antibiotic prophylaxis and/or a bleeding disorder (thrombocytopenia) may be present.
Is medical consult advised?
- As above. Specifically, the oncologist/transplantation specialist should be consulted regarding the status of blood counts (white and red cells), platelets, and clotting factors. If dental/dental hygiene procedures are absolutely necessary during the period of myelosuppression, consideration should be given to supportive measures such as administration of immunoglobulin G, adjustment of steroid dosing, and/or transfusion of platelets (in addition to antibiotic prophylaxis).
Is medical clearance required?
- Yes. Inappropriately timed dental hygiene (and dental) procedures in an immunosuppressed patient/client can result in bacteremia, potentially leading to sepsis and even death. As well, bleeding risk needs to be assessed. During high dose chemotherapy +/- total body irradiation for HCT, invasive dental hygiene treatment should be undertaken only on an emergency basis (and with appropriate precautions). Blood work should be conducted 24 hours before dental hygiene treatment to determine if the patient/client’s platelet count, clotting factors, and absolute neutrophil count are sufficient to prevent hemorrhage and infection.
Is antibiotic prophylaxis required?
- Possibly, if invasive procedures are needed during the period of chemoradiation-induced myelosuppression. Prophylactic antibiotics may be recommended if the white blood cell (WBC) count is <2 X109/L (<2000/μL), or the neutrophil count is <1 X109/L (<1000/μL; or <0.5 X109/L [500/μL] in some institutions). As well, immunosuppressive drugs are used to manage complications resulting from transplantation, such as graft-versus-host disease (GVHD); antibiotic prophylaxis may be a consideration in these situations.
Is postponing treatment advised?
- Yes. Elective oral procedures, including scaling and polishing, should be delayed until the patient/client’s immune system sufficiently recovers and the graft stabilizes; typically this takes 3–12 months post-transplantation. In patients/clients undergoing high dose chemotherapy +/- total body irradiation that results in:
- immunosuppression, elective invasive procedures should be deferred until after chemoradiation-induced immunosuppression ceases. Specifically, treatment should be postponed until the patient/client’s absolute neutrophil count is >1 X109/L (>1000/μL) and granulocyte1 count is >2 X109/L (>2000/μL) to reduce risk of infection. Patients/clients who are neutropenic should not undergo invasive dental hygiene procedures without special precautions.
- thrombocytopenia, elective invasive procedures should be deferred until a platelet count of at least 50 X109/L (50,000/μL) has been achieved in order to reduce the risk of bleeding.
Oral management implications
- Before transplantation, all dental hygiene (and dental) treatment should be accomplished, because the patient/client will not be allowed to leave the transplant centre until the bone marrow has engrafted and blood counts have returned to a safe range2. Therefore, all patients/clients scheduled for HCT should undergo a pre-treatment oral health examination, which includes looking for infections on the tongue and oral mucosa.
- The dental hygienist should ensure the patient/client follows the prescribed oral hygiene regimen and fluoride gel application schedule. When the patient/client is scheduled for total body irradiation for BMT, custom fluoride gel trays should be fabricated for daily application of fluoride gel to prevent rampant dental caries.
- Oral surgery or other invasive procedures should be performed at least 7–10 days before myelosuppressive therapy begins.
- During HCT, oral devices should be managed as follows:
- brackets, wires and retainers should be removed before high dose chemotherapy begins;
- dentures should only be worn when eating during the first 3–4 weeks after the transplant;
- dentures should be rigorously cleaned;
- mouth cleaning should occur with dentures or other oral devices out of the mouth; and
- removable oral devices should not be used until mouth sores have healed.
- Many oncology/transplant centres adopt the strategy that the benefits of properly performed dental brushing and flossing in reducing risk of gingival infection outweigh the risks, although some centres have patients/clients discontinue brushing and flossing when peripheral blood components decrease below defined thresholds (e.g., platelets <30 X109/L [<30,000/μL] or <40 X109/L [<40,000/μL]).
- In transplant patients/clients receiving high dose chemo that results in thrombocytopenia, vigorous teeth brushing should be avoided, along with water-irrigating appliances, and toothpicks. However, with appropriate monitoring, patients/clients can often brush and floss throughout the thrombocytopenic episode.
- Holding ice chips in the mouth during high dose chemotherapy may help prevent mouth sores.
- Mucositis can be minimized by meticulous oral hygiene and other supportive measures. This is important because this condition can increase the risk of systemic infection, promote oral hemorrhage, compromise the upper airway, and necessitate total parenteral nutrition3.
- Once mucositis has developed, its severity and the patient/client’s hematologic status determine appropriate oral management. Some established guidelines for oral care include oral assessments twice daily for hospitalized patients/clients and frequent oral care (minimum of every 4 hours and at bedtime) that increases in frequency as the severity of mucositis increases.
- Oral care protocols generally include atraumatically cleansing the oral mucosa, maintaining lubrication of the oral tissues, and relieving pain and inflammation. More specific management of chemotherapy-induced mucositis is contained in the Chemotherapy Fact Sheet, and management of dry mouth is covered in the Xerostomia Fact Sheet.
- Preventing dryness of the lips to reduce risk for tissue injury is important in transplant patients. Lanolin-based creams and ointments may be particularly effective in moisturizing/lubricating the lips and thus protecting against trauma.
- After transplantation, the dental hygienist should ensure adequate monitoring and control of plaque, tooth demineralization, caries, and infection.
- Elective invasive oral procedures should be delayed 6 to 12 months.
- The patient/client should be followed carefully for long-term oral complications, which may indicate graft-versus-host disease or malignancies in the oral region. Oral cancer screening should be a routine part of every dental/dental hygiene examination.4
- Treatment of oral graft-versus-host disease (GVHD) includes:
- topical rinses, gels, creams, and powders (including steroids and immunosuppressants such as azathioprine and cyclosporine, as well as anaesthetics such as lidocaine)
- anti-fungal drugs by mouth (e.g., nystatin and clotrimazole) or parenterally (e.g., fluconazole and itraconazole);
- psoralen and ultraviolet A (PUVA) therapy;
- sialagogue drugs (e.g., pilocarpine or cevimeline) that make salivary glands make more saliva;
- systemic therapy (e.g., corticosteroids such as prednisone and budesonide; immunosuppressive agents such as cyclosporine and mycophenolate mofetil [MMF])
- fluoride treatments; and
- remineralization treatments to replace minerals lost from teeth by acids in the mouth (e.g., solutions containing calcium phosphate).
- Submucosal and/or dermal fibrosis associated with chronic GVHD usually improves or resolves with systemic therapy. However, in rare instances, surgical or chemical techniques to disrupt fibrotic bands can be required to improve the ability to open the mouth.
- Oral complications occur in most bone marrow and stem cell transplant recipients, and especially in patient/clients with graft-versus host disease.
- Due to the cytotoxic and immunosuppressive effects of chemoradiation conditioning, patients/clients are prone to oral complications during the first month post-transplant. These manifestations include xerostomia, mucositis, stomatitis, ulcerations, bleeding, and infection. Although these side effects begin to resolve when hematologic status improves (typically decreasing in frequency and severity about 3 to 4 weeks after cessation of chemotherapy), immunosuppression may last for up to a year after transplant, and thus risk of complications continues.
- Mucositis manifests as erythema and/or ulcerations. Often severe, it typically appears 7 to 10 days after initiation of high dose chemotherapy or chemoradiation for HCT. The mucositis is self-limited when uncomplicated by infection, and it typically heals within 2 to 4 weeks after cessation of cytotoxic chemotherapy.
- Bleeding problems due to thrombocytopenia (abnormally low platelet count) can occur in HCT patients/clients undergoing total body irradiation. Thrombocytopenia and coagulopathy can also result from high dose chemotherapy/ immunosuppressive therapy. Gingival bleeding and submucosal hemorrhage can occur as a result of minor trauma (such as tongue biting or toothbrushing) when the platelet count falls below 50 X109/L (50,000/μL), and spontaneous gingival bleeding may occur with a platelet count <20 X109/L (<20,000/μL), especially when there is pre-existing periodontitis or gingivitis. Although usually not serious, oral bleeding can be of great concern to the patient/client and family. The bleeding may be mild (e.g., petechiae or purpura5 located on the lips, soft palate, floor of the mouth, or lateral tongue) or severe (e.g., persistent gingival hemorrhage from herpes simplex virus ulcers in the presence of severe thrombocytopenia).
- Herpes simplex and Candida albicans are common oral infections post-transplantation.
- Dry lips may result from mouth breathing and/or xerostomia (sometimes secondary to anticholinergic medications used for management of nausea).
- Temporomandibular joint dysfunction — manifesting as TMJ pain, headache, and jaw pain — may occur during the various phases of HCT. Neurotoxicity — manifesting as muscle tremor (e.g., jaws, tongue) — may occur during the neutropenic and engraftment phases.
- After the first 100 days post-transplantation, patients/clients with no evidence of graft-versus-host-disease usually do not have oral complaints except varying degrees of xerostomia.
- Dental hypersensitivity may occasionally arise in patients/clients weeks or months after they discontinue high dose chemotherapy. Furthermore, patients/clients being treated with cyclosporine for treatment of graft-versus-host disease may report increased thermal sensitivity, which resolves after discontinuation of therapy (although it can persist for several months).
- Graft-versus-host disease in its acute form infrequently involves oral structures. When it does occur, its features are similar to erythema multiforme6, with mucosal erythema and erosions/ulcerations appearing in the mouth and on the lips as early as 2 to 3 weeks-post-transplant.
- GVHD in its chronic form often involves the oral cavity and salivary glands in allograft7 recipients, and signs/symptoms can manifest as early as day 70 post-transplant. Manifestations include:
- dry mouth due to persistent reduced salivary function, and often with associated severe caries and tooth demineralization;
- dry lips;
- pain from spices, alcohol, or flavouring agents (e.g., mint in toothpaste);
- feeling of tightness in the perioral skin or in the mucosa of the mouth (see “submucosal and/or dermal fibrosis” bullet point below);
- dysphagia (difficulty swallowing) and odynophagia (painful swallowing) due to gastrointestinal involvement;
- taste changes;
- raised white hyperkeratotic plaques and striae with lichen-planus-like changes and associated mouth discomfort and sensitivity; and
- superficial mucoceles characterized by saliva-filled blisters that develop on the palate (caused by inflammation of minor salivary glands).
- Submucosal and/or dermal fibrosis can occur in persistent cases of chronic GVHD. This scleroderma-like complication can manifest as slight mucosal or skin tightness, or it can progress to skin thickening and fibrosis. Intraoral submucosal fibrotic bands can significantly restrict the ability to open the mouth.
- Oral GVHD is linked to oral pre-cancerous and malignant lesions.
- Gingival hyperplasia can result from use of cyclosporine (an important anti-rejection drug for transplant patients/clients, which is also used to treat GVHD).
- Dental/skeletal growth and development alterations may occur in pediatric patients/clients in the immune reconstitution (late post-transplant) and long-term survival phases of BSCT.
- Oral squamous cell cancer (SCC) is the most common secondary oral cancer in transplant patients/clients, with the lips and tongue being most commonly affected. While oral SCC presents with the same clinical features as in the general population, diagnosis may be difficult in the context of active GVHD changes.
- Oral plasmacytoma8 can develop in patients/clients with multiple myeloma who have received a stem cell transplant using their own (autologous) stem cells.
Related signs and symptoms
- Hematopoietic cell transplantation (which encompasses bone marrow transplantation and blood stem cell transplantation) is used to treat certain cancers (e.g., some acute and chronic leukemias, lymphomas, including Hodgkin’s disease; neuroblastoma)9, as well as some non-malignant conditions (e.g., aplastic anemia and some genetic diseases, such as immunodeficiency syndromes, hemoglobinopathies [including sickle cell disease], and Hurler syndrome10). BMT involves transfer of bone marrow into the patient/client11, whereas BSCT involves the transfer of peripheral blood stem cells or umbilical cord stem cells.
- Autologous stem cell transplantation12 is used to treat multiple myeloma13.
- Prior to intravenously infusing a donor’s marrow or stem cells into the recipient’s blood, most recipients14 require immunosuppressive ablation of their own bone marrow so they will not reject the graft. This pre-operative preparation is accomplished by high dose, myelosuppressive chemotherapy +/- total body irradiation. In the treatment of malignancy, chemoradiation is also intended to destroy the cancer cells.
- Before the marrow/stem cell grafting procedure begins, most patients/clients experience a period of no marrow function as a consequence of the immunosuppressive preparation and their underlying disease. After the transplant, 10 to 28 days (the “critical period”) are required before the transplanted marrow/stem cells have sufficiently engrafted to begin to produce new marrow.
- The post-transplantation period has three phases: the pancytopenic/neutropenic phase; the immune recovery phase (3 to 12 months); and the long-term immunocompetent phase (1 to 3 years). The patient/client is at risk of complications (including infection, bleeding, and anemia) during the period of chemoradiation-induced myelosuppression (particularly during the immunosuppressive preparation and the first 28 days post-transplant), as well as afterwards if graft-versus-host disease occurs. Most patients/clients are given anti-rejection drugs (such as cyclosporine, methotrexate, or steroids) after transplantation. Antifungal drugs (e.g., intravenous miconazole) are also often given during immunosuppressive preparation and during the critical period after HCT. Long-term therapy with broad-spectrum antibiotics is often needed to reduce the risk of infection.
- Upon full bone marrow recovery, signs/symptoms associated with acute cytotoxicity, immunosuppression, and thrombocytopenia disappear.
- Hypertension, bleeding problems, and anemia can result from cyclosporine-induced kidney and liver changes. Cyclosporine is also associated with hirsutism, gynecomastia, and cancers of the skin and cervix.
- Diabetes mellitus, hypertension, osteoporosis, impaired healing, increased risk of infection, and depression are side effects of prednisone (steroid) therapy. Adrenal gland suppression may also occur, which reduces the patient/client’s ability to deal with the stress of trauma, infection, or extreme anxiety.
- Graft-versus-host disease (GVHD) occurs when a patient/client’s tissue reacts to bone marrow or stem cells that come from another (non-identical twin) individual. Acute GVDH occurs within the first 100 days after transplant, and is characterized by dermatitis, non-infectious hepatitis, and intestinal inflammation (usually accompanied by diarrhea). Chronic GVHD usually occurs after the first 70 to 100 days, and it has manifestations similar to those of autoimmune disorders15. These include keratoconjunctivitis, skin diseases, esophageal and vaginal strictures, pulmonary insufficiency, intestinal problems, and chronic liver disease. Both types of GVHD can result in fatal infections, and their various oral and gastrointestinal manifestations may lead to weight loss and malnutrition.
- Patients/clients with hematologic malignancies who undergo hematopoietic cell transplantation remain at risk for relapse of primary disease, usually within the first 1 to 2 years after transplantation.
- Second malignancies later in life, including oral cancer, may be sequelae of HCT.
References and sources of more detailed information
- Gurenlian JR, Benchley L. Oral Effects of Hematopoietic Stem Cell Transplant Therapy. Decisions in Dentistry. March 2019;5(3):30–32,35.
- Elad S, Raber-Durlacher JE, Brennan MT, Saunders DP, Mank AP, Zadik Y, Quinn B, Epstein JB, Blijlevens NM, Waltimo T, Passweg JR, Correa ME, Dahllöf G, Garming-Legert KU, Logan RM, Potting CM, Shapira MY, Soga Y, Stringer J, Stokman MA, Vokurka S, Wallhult E, Yarom N, Jensen SB. Basic oral care for hematology-oncology patients and hematopoietic stem cell transplantation recipients: a position paper from the joint task force of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) and the European Society for Blood and Marrow Transplantation (EBMT). Support Care Cancer. 2015 Jan;23(1):223-36. doi: 10.1007/s00520-014-2378-x. Epub 2014 Sep 5. PMID: 25189149; PMCID: PMC4328129.
- Bollero P, Passerelli PC, D’Addona A, Pasquantonio G, Mancini M, Condò R, Cerroni L. Oral management of patients undergoing hematopoietic stem cell transplantation. European Review for Medical and Pharmacologic Sciences. 2018;22:876-887.
- Castellarin P, Stevenson K, Biasotto M, Yuan A, Woo S-B, Treister NS. Extensive Dental Caries in Patients with Oral Chronic Graft-versus-Host Disease. Biology of Blood and Marrow Transplantation. 2012 Oct;18(10):1573-1579.
- Pisano JJ, Coupland R, Chen SY, Miller AS. Plasmacytoma of the oral cavity and jaws: a clinicopathologic study of 13 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1997 Feb;83(2):265-71.
- Haverman TM, Raber-Durlacher JE, Rademacher WMH, Vokurka S, Epstein JB, Huisman C, Hazenberg MD, de Soet JJ, de Lange J, Rozema FR. Oral Complications in Hematopoietic Stem Cell Recipients: The Role of Inflammation. Mediators of Inflammation. 2014. Article ID 378281, 18 pages, 2014.https://doi.org/10.1155/2014/378281.
- Rothstein JP. Chemotherapy and Oral Care. Dentistry Today December 2004.
- D Saunders. Question 2 – What should I know about treating dental patients who are undergoing chemotherapy and when is the best time for dental treatment? Point of Care in JCDA March 2005;71(3):194-195.
- Canadian Cancer Society
- Leukemia and Lymphoma Society of Canada
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- Managing Oral Complications of High-Dose Chemotherapy and/or Stem Cell Transplant
- Oral Complications and Their Causes
- Preventing and Treating Oral Complications Before Chemotherapy or Radiation Therapy Begins
- Managing Oral Complications During and After Chemotherapy or Radiation Therapy
- Oral Complications in Second Cancers
- Oral Complications and Social Problems
- Oral Complications of Chemotherapy and Radiation Therapy in Children
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2 An allogenic transplant recipient is typically hospitalized for 4 to 6 weeks.
3 Total parenteral nutrition (TPN) is exclusive feeding of a person intravenously, bypassing the usual process of eating and digestion.
4 Patients/clients with chronic GVHD face up to a 16-fold increase in the risk of squamous cell carcinoma of the oral cavity compared with the general population.
5 Petechiae and purpura are red or purple spots on the mucosa or skin, which do not blanch to applied pressure, caused by extravasation of blood (i.e., hemorrhages). Petechiae are pinpoint to pinhead in size (i.e., 1 to < 3 mm in diameter), whereas purpura lesions range from 3 to 10 mm in diameter.
6 Erythema multiforme is an immune complex reaction that manifests as eruptions of macules, erosions, and characteristic “target” lesions that are symmetrically distributed on the mucosa or skin.
7 An allograft is the transplant of tissue or an organ from one person to another with a different genotype (i.e., not identical twins
8 A plasmacytoma is a discrete, solitary mass of malignant plasma cells (white blood cells — lymphocytes — that produce antibodies) in either bone or soft tissue. In the oral cavity, it most commonly manifests as localized pain and as a raised lesion on the alveolar ridge (especially in the posterior mandible.) A radiolucency is typically seen on a radiograph when there is bone involvement.
9 With malignancies, much of the benefit of HCT is in the graft-versus-tumour effect, in which engrafted donor cells mount an alloimmune response against residual cancer cells.
10 Hurler syndrome is a genetic disorder in which an enzyme deficiency results in the build-up of sugar molecules called glycosaminoglycans (formerly called mucopolysaccharides).
11 An autologous bone marrow graft involves transplantation of the patient/client’s own marrow, which was harvested prior to intense chemotherapy or total body irradiation used to prepare for transplantation. An allogenic marrow graft involves a donor and a recipient of different genetic origins, who may be related (e.g., sibling or parent) or unrelated.
12 Autologous stem cells are the patient’s own stem cells.
13 Multiple myeloma is a systemic, malignant proliferation of plasma cells that cause destructive bone lesions.
14 The recipient of a syngeneic marrow graft (from an identical twin) requires no immunosuppressive preparation, nor does the patient/client with severe immunologic deficiency (because of the very nature of the disease).
15 GVHD often mimics autoimmune diseases such as Sjögren’s syndrome, scleroderma, pemphigus and erosive lichen planus.
* Includes oral hygiene instruction, fitting a mouth guard, taking an impression, etc.
** Ontario Regulation 501/07 made under the Dental Hygiene Act, 1991. Invasive dental hygiene procedures are scaling teeth and root planing, including curetting surrounding tissue.