FACT SHEET: Leukemia (The main types include “acute lymphoblastic leukemia” [“ALL”; also known as “acute lymphocytic leukemia” and “acute lymphoid leukemia”]; “chronic lymphocytic leukemia” [“CLL”; also known as “chronic myeloid leukemia”]1; “acute myeloid leukemia” [“AML”; also known as “acute myelogenous leukemia”, “acute non-lymphoblastic leukemia”, and “acute non-lymphocytic leukemia”]; and “chronic myeloid leukemia” [“CML”; also known as “chronic myelogenous leukemia”].)
Date of Publication: February 22, 2018
Note: The therapeutic modalities of chemotherapy, radiation therapy, and hematopoietic cell transplantation are addressed in detail in separate fact sheets.
Is the initiation of non-invasive dental hygiene procedures* contra-indicated?
- Unlikely, but depends on severity and type of leukemia (e.g., acute versus chronic), severity of complications arising from treatment (e.g., medication-related osteonecrosis of the jaw [MRONJ]), and procedure being contemplated.
Is medical consult advised?
- Yes, if the patient/client is undergoing chemotherapy and has, or is suspected to have, certain oral conditions or systemic manifestations.
- Yes, if the patient/client is about to undergo, or is undergoing, radiation therapy.
- Yes, if the patient/client is taking a bisphosphonate (orally, by injection, or intravenously) or other bone antiresorptive agent (e.g., denosumab).
- Yes, if the patient/client appears debilitated.
- Yes, if undiagnosed leukemia is suspected.
Is the initiation of invasive dental hygiene procedures contra-indicated?**
- Yes. This is a blood disorder as per Ontario Regulation 501/07 pursuant to the Dental Hygiene Act, 1991. Leukemia may affect appropriateness or safety, and scaling and root planing, including curetting of surrounding tissue, are contraindicated until the patient/client is medically cleared. Other possible contra-indications include active chemotherapy and/or radiation therapy, as well as significant immunosuppression and/or bleeding disorder (e.g., thrombocytopenia) resulting from the disease itself and/or its treatment.
Is medical consult advised?
- See above. Additionally, pre- and post-radiotherapy/chemotherapy medical and/or dental consultation is often warranted.
Is medical clearance required?
- Yes, if leukemia has been diagnosed or is suspected.
- Yes, if the patient/client is undergoing radiotherapy and/or chemotherapy.
- Yes, if MRONJ exists or is suspected2.
- Yes, if patient/client is being treated with medications (such as corticosteroids) associated with immunosuppression +/- increased risk of infection (e.g., prednisone is often given concurrently with induction chemotherapeutic agents in the treatment of ALL and CLL).
- Yes, if thrombocytopenia or severe anemia exists or is suspected (whether from the disease itself and/or its treatment, particularly in acute leukemias).
Is antibiotic prophylaxis required?
- Possibly, for some patients/clients according to [1] blood indices (e.g., low neutrophil count) that indicate immunosuppression resulting from the disease itself and/or from chemotherapy and/or radiotherapy3 and/or [2] according to delivery mechanism (e.g., in-dwelling central venous catheters or ports4).
Is postponing treatment advised?
- Possibly, depending on blood indices (which indicate degree of immunosuppression and/or thrombocytopenia and/or anemia) in patients/clients undergoing chemotherapy or radiotherapy. Elective invasive procedures should be deferred until after chemo- or radiation-induced immunosuppression ceases.
- Potentially, if MRONJ exists, informed by medical/dental consultation. Ideally, all necessary invasive dental and dental hygiene treatments should be performed before administration of injectable/intravenous bisphosphonate drugs or other bone antiresorptive agents.
- In the case of hematopoietic cell transplantation, 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 to 12 months post-transplantation.
Oral management implications
- Refer to Chemotherapy, Radiation Therapy, Hematopoietic Cell Transplantation, Xerostomia, and MRONJ Fact Sheets, as applicable.
- The dental hygienist should be cognizant of oral manifestations of leukemia, because in some patients/clients these may herald onset of the disease.
- For paediatric patients/clients with leukemia, involvement of parents in oral hygiene education is important. Meticulous oral care can reduce the incidence and severity of oral sequelae of the treatment protocol. Leukemic children who present with poor oral hygiene or periodontal disease may benefit from chlorhexidine rinses.
- The leukemic child may be at elevated risk of dental caries. This is due to the prescription of daily nutritional supplements rich in carbohydrates to gain weight as well as oral paediatric medications that contain high amounts of sucrose (e.g., nystatin for oral candidiasis). Fluoride supplements and/or fluoride rinses or gels may be indicated. Teeth with poor prognosis should be ideally removed 3 weeks before cancer therapy starts to allow adequate healing.
- Because fixed orthodontic appliances can harbour food debris, compromise oral hygiene, and act as mechanical irritants, risk of secondary infection is increased. Therefore, removable appliances and retainers are preferred when tolerated by the leukemic patient/client. Furthermore, orthodontic care may involve deliberately not treating the lower jaw or deferral of orthodontic intervention until after a sufficient disease-free period.
Oral manifestations
- Refer also to Chemotherapy, Radiation Therapy, Hematopoietic Cell Transplantation, Xerostomia, and MRONJ Fact Sheets for details regarding cancer treatment-related dry mouth, caries, mucositis, gingival bleeding, dysgeusia (unpleasant taste), infections, periodontitis, and osteonecrosis.
- Oral involvement is common and may occur in any type of leukemia, although oral manifestations are more frequent in acute5 rather than chronic forms. Defects in white blood cells (WBCs) can manifest as infection, mucosal ulceration, and delayed healing.
- Gingivitis is the first sign of disease in about 25% of children with leukemia.
- In acute leukemias, gingival enlargement (caused by infiltration of leukemic cells) can be severe. This enlargement is often generalized or affects multiple tooth sites, and the gums are dark red, boggy, and edematous. Persistent and severe inflammation in the oral cavity exhibits a red or deep purple colour, shiny surface, and spongy texture. Other oral manifestations include infections (most commonly candidiasis and herpes simplex) and necrotizing ulcerative gingivitis (due to non-functioning white blood cells); oral ulcerations (especially on the gingiva and palate); sore throat; bleeding gums, petechiae, and ecchymoses (due to reduced platelet count); and toothache (due to invasion of pulp by leukemic cells). Loosening of teeth can occur as a result of necrosis of the periodontal ligament.
- Cervical lymphadenopathy is particularly common early in the course of ALL.
- Chloroma is a localized collection of leukemia cells that sometimes occurs in acute leukemia. Typical oral locations for masses are the gingiva, maxilla, and palate. Chloromas may also occur under the skin or in other parts of the body.
- In chronic leukemias, pallor of the lips and gingiva may occur. Other manifestations are gingival enlargement; petechiae and ecchymoses; bleeding gums; and atypical periodontal disease. Generalized gingival hypertrophy is a relatively common complication of CML, particularly the myelomonocytic and monocytic forms.
- Cervical lymphadenopathy may be an early sign of chronic leukemia.
- Neurologic manifestations of leukemia include dysphagia; difficulty in protruding the tongue; paresthesia of the lips and tongue; difficulty in biting food; numbness of the chin (i.e., neuropathy of the mental nerve); and, occasionally, trismus.
- Radiographically, leukemic infiltrates may cause destructive radiolucencies with loss of the lamina dura and erosion of crestal alveolar bone.
- Because bisphosphonates or other bone antiresorptive agents may be used to treat osteopenia resulting from treatment of leukemia (e.g., corticosteroids), medication-related osteonecrosis of the jaw can occur.
- The treatment of leukemia in children alters odontogenesis, and the severity depends on the age of the child. The younger the child, the greater the oral complications, for both dentitions — deciduous and permanent — can be affected. The most common changes resulting from chemotherapy and/or radiation therapy are agenesis of teeth, microdontia, alteration in crown or root shape, defective mineralization of the dental structure, and delayed tooth eruption.
- Cranial irradiation in children alters tooth size and shape as well as affects growth of facial bones leading to facial asymmetry and malocclusion.
Related signs and symptoms
- Leukemia comprises a broad range of blood cancers characterized by the overproduction of atypical white blood cells6. They are primarily disorders of stem cells, in which abnormal WBCs proliferate in the bone marrow and then move into circulating blood and other tissues.7 Leukemic cell multiplication occurs at the expense of normal hematopoietic (blood forming) cell lines, which can lead to bone marrow failure, depressed blood cell count, and death as a result of infection, bleeding, or both.
- Leukemia (predominately ALL) is the most common type of cancer in children (age < 15 years). However, most leukemias (predominately chronic forms), occur in adults, with men being affected more than women.
- Annually, about 6,700 persons in Canada (2,800 in Ontario) are diagnosed with leukemia (representing 27% of hematologic cancers) and 3,100 (1,150) die from the disease. The 5-year survival rate for all types of leukemia is about 61%.8
- Signs/symptoms of acute leukemia include weakness, lethargy, fever, lymphadenopathy, pain in joints/bones/muscles, trouble breathing, pallor, easy bruising, and mucosal bleeding (e.g., frequent or severe nose bleeds). Fatigue results from anemia, fever from infection, and bleeding from thrombocytopenia (decreased platelets). In advanced disease, splenomegaly (enlargement of spleen) and hepatomegaly (enlargement of liver) result from infiltration of leukemic cells.
- Acute leukemias are characterized by the presence of immature cells and a rapidly fatal course if not treated. In its initial stages, acute leukemia may cause signs/symptoms similar to viral conditions such as influenza, with onset typically occurring suddenly and dramatically in days or weeks.
- Symptoms of chronic leukemia may be similar to flu-like illness with bone pain, joint pain, or both, caused by malignant expansion of bone marrow. Non-specific signs/symptoms include easy fatigability, night sweats, weakness, loss of appetite, and weight loss. Generalized lymphadenopathy may be present. Many patients/clients, though, are asymptomatic (particularly with CML), although as disease progresses (particularly with CLL) splenomegaly and hepatomegaly may occur.
- Chronic leukemias are characterized by the presence of differentiated, mature cells and a slow clinical course. Chronic leukemia’s signs/symptoms usually develop gradually, with affected persons often complaining that they do not feel well. The disease is often detected during “routine” blood tests.
- Neurologic manifestations of leukemia include trigeminal neuralgia, facial paralysis, and paresthesia of the face.
- Leukemia cutis — caused by infiltration of leukemic cells in the skin — manifests as plaques, papules, or nodules of any size that are often tan or pink in colour.
- Acute febrile neutrophilic dermatosis9 involves fever and painful sores that may occur anywhere on the body (particularly the arms, neck, head, or trunk). While in most cases the cause isn’t known, it is sometimes associated with cancer, most often leukemia.
- Environmental agents (such as oncogenic viruses10, benzene, and ionizing radiation) may cause some leukemias, whereas others are associated with chromosomal abnormalities11.
- Leukemia-related emergencies include:
- tumour lysis syndrome, which can occur when chemotherapy is given to treat acute leukemia, resulting in a rapid die-off of cancer cells that exceeds the kidneys’ ability to remove cellular contents quickly enough from the blood12;
- superior vena cava syndrome, which may occur in ALL when too many leukemia cells develop in the thymus, resulting in obstruction of the superior vena cava13; and
- disseminated intravascular coagulation (DIC), which may occur in AML when blood clots develop in the blood circulation and bleeding ensues14.
- The main treatment options for leukemia are chemotherapy, stem cell transplantation and targeted therapy using specialized drugs. In certain circumstances, radiation therapy, surgery, leukapheresis15, treatment with monoclonal antibodies, or immunotherapy may be indicated.
- High-dose induction chemotherapy to achieve remission is often followed by low-dose maintenance chemotherapy. Relapse may occur after chemotherapy-induced remission, particularly for acute leukemias.
- In children with ALL, the central nervous system (CNS) can act as a sanctuary site for leukemic infiltrates, because systemically administered chemotherapeutic drugs are unable to cross the blood-brain barrier. Therefore, cranial irradiation and/or weekly intrathecal injection of a chemotherapeutic agent16 (e.g., methotrexate) are used for “CNS preventive therapy/prophylaxis”.
References and sources of more detailed information
- College of Dental Hygienists of Ontario
https://cdho.org/advisories/leukemia/ - Aguilar Quispe R, Marques Aguiar E, de Oliveira CT, Xavier Neves AC, da Silva Santos PS. Oral manifestations of leukemia as part of early diagnosis. Hematology, Transfusion and Cell Therapy. November 22 2021; on-line.
https://doi.org/10.1016/j.htct.2021.08.006 - Byrne H, Zhang H, Baig K, McCarthy C, Brady P. Acute myeloid leukemia: an update for dentists. Journal of the Irish Dental Association. 2021; 67(2):98-101.
https://jida.ie/acute-myeloid-leukaemia-an-update-for-dentists/ - Deliverska EG, Krasteva A. Oral Signs of Leukemia and Dental Management – literature data and case report. J of IMAB. 2013;19(4):388-391.
https://www.journal-imab-bg.org/issue-2013/issue4/JofIMAB2013vol19b4p388-391.pdf - Dawar G. Leukemia: The Oral Perspective. Int J Oral Health Med Res. 2015;2(2):113-114.
http://www.ijohmr.com/upload/Leukemia(1).pdf - Padmini C, Bai KY. Oral and Dental Considerations in Pediatric Leukemic Patient. ISRN Hematology. 2014;2014:895721. doi:10.1155/2014/895721.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3960739/ - Kos M. Incidence and risk predictors for osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates. Archives of Medical Science : AMS. 2015;11(2):319-324. doi:10.5114/aoms.2015.50964.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4424249/ - Leukemia and Lymphoma Society of Canada
https://www.bloodcancers.ca/i-have-blood-cancer/leukemia
https://www.bloodcancers.ca/sites/default/files/2021-11/Chronic%20Myeloid%20Leukemia.pdf
https://www.bloodcancers.ca/sites/default/files/2021-08/LLS1084-F-FS-CLL-E04.pdf
https://www.bloodcancers.ca/sites/default/files/2021-08/LLS1083-F-FS-AML-8P-E05.pdf
https://www.bloodcancers.ca/sites/default/files/2021-07/2020%20LLSC%20Fact%20Sheet-Disease-ALL_Final_EN.pdf - Canadian Cancer Society
https://cancer.ca/en/cancer-information/cancer-types/leukemia/what-is-leukemia
https://cancer.ca/en/cancer-information/cancer-types/leukemia/signs-and-symptoms
https://cdn.cancer.ca/-/media/files/cancer-information/resources/publications/2021-canadian-cancer-statistics-special-report/0835-2976-2021-canadian-cancer-statistics-en.pdf?rev=8e016fe8c5ea4c23b05ea08bf1018ca6&hash=C5BAEC543E496EDD8460CBBF6D44A010&_ga=2.54645736.259579282.1644967259-2070306902.1644967259 - Council for Continuing Pharmaceutical Education
https://mcc.ca/objectives/normal-values/ - Leukemia and Lymphoma Society (USA)
https://www.lls.org/managing-your-cancer/food-and-nutrition/dental-health
https://www.lls.org/sites/default/files/National/USA/Pdf/Publications/FS29_Dental_and_Oral_Fact_Sheet_FINAL_9.2016.pdf - American Cancer Society
https://www.cancer.org/cancer/acute-lymphocytic-leukemia/about/key-statistics.html - Medscape
https://www.medscape.com/viewarticle/883371?spon=34&uac=224173AR&impID=1401612&sso=true&faf=1&nlid=117072_430&src=WNL_mdplsfeat_170801_mscpedit_fmed (Clearing the Patient on Bisphosphonates for Dental Procedures: When Should You Do It?)
https://emedicine.medscape.com/article/1097702-overview (Leukemia Cutis) - Mayo Clinic
https://www.mayoclinic.org/diseases-conditions/sweets-syndrome/symptoms-causes/syc-20351117 - Cancer Research Institute
https://www.cancerresearch.org/en-us/immunotherapy/cancer-types/leukemia - Merck Manual (Consumer Version)
https://www.merckmanuals.com/home/mouth-and-dental-disorders/periodontal-diseases/gingivitis#sec08-ch115-ch115b-246 - Bowen DM (ed.) and Pieren JA (ed.). Darby and Walsh Dental Hygiene: Theory and Practice (5th edition). St. Louis: Elsevier; 2020.
- Ibsen OAC and Peters SM. Oral Pathology For The Dental Hygienist (8th edition). St. Louis: Elsevier; 2023.
- Regezi JA, Sciubba JJ, and Jordan RCK. Oral Pathology: Clinical Pathologic Correlations (7th edition). St. Louis: Elsevier; 2017.
- Little JW, Falace DA, Miller CS and Rhodus NL. Dental Management of the Medically Compromised Patient (9th edition). St. Louis: Elsevier; 2018.
Date: August 15, 2017
Revised: March 25, 2022
FOOTNOTES
1 “Hairy cell leukemia” (HCL) is a rare type of chronic lymphocytic leukemia in which abnormal B-lymphocytes look hairy under a microscope.
2 While MRONJ is a relatively rare occurrence in patients/clients treated with oral bisphosphonates, cancer patients/clients treated with intravenous bisphosphonates have a much higher risk (with risk in this population estimated to range from 1.6% to 14.8%).
3 particularly total body irradiation for bone marrow/stem cell transplantation purposes
4 Most leukemic patients/clients with acute lymphoblastic leukemia have an in-dwelling central venous line.
5 In AML in particular, oral manifestations may be the first clinical signs of leukemia.
6 Normal white blood cell count ranges from 3.5 to 10.5 X 109/L in adults (higher in children, particularly under the age of 2 years), whereas the WBC count in leukemia can increase to 500 X 109/L. Three groups of WBCs are found in the peripheral circulation: granulocytes (normally 90% neutrophils, with the remainder comprised of basophils and eosinophils); lymphocytes (T-lymphocytes, B-lymphocytes, and natural killer cells); and monocytes.
7 Diagnosis of leukemia is established by examination of the peripheral blood count and white blood cell differential (percentage of each type of WBC) and by bone marrow biopsy.=
8 Five-year net survival rate is for ages 15–99 years.
9 also known as Sweet’s syndrome
10 Suspected oncogenic viruses for leukemia include human T-cell lymphotropic virus (HTLV).
11 The Philadelphia chromosome has been implicated in CML, and persons with Down syndrome have a higher tendency to develop leukemia (particularly ALL and AML).
12 High blood levels of uric acid can lead to deposits in the joints (causing a painful gout-like condition) and/or build-up in the kidneys (potentially causing kidney damage and stones). High phosphate levels can also damage the kidneys and lead to kidney failure. Abnormal levels of calcium and potassium can affect heart rhythm and lead to neurological manifestations such as irritability, weakness, and confusion.
13 Symptoms of SVCS may develop gradually or suddenly, depending on how quickly the superior vena cava is squeezed or blocked. Signs/symptoms include shortness of breath; difficulty breathing; swelling of face, neck, upper body, and arms; chest pain; difficulty swallowing; paralyzed vocal cord; and Horner’s syndrome (which is characterized by small pupil, drooping eyelid, and reduced sweating on one side of face).
14 Other signs/symptoms of DIC include shortness of breath; pain or swelling in arms and legs; jaundice; low blood pressure; hypoxia; fever; and multiple organ failure.
15 Leukapheresis involves the removal of while bloods cells from the blood.
16 In intrathecal chemotherapy, anticancer drugs are injected into the fluid-filled space between the thin layers of tissue (theca) that cover the brain and spinal cord.
2 While MRONJ is a relatively rare occurrence in patients/clients treated with oral bisphosphonates, cancer patients/clients treated with intravenous bisphosphonates have a much higher risk (with risk in this population estimated to range from 1.6% to 14.8%).
3 particularly total body irradiation for bone marrow/stem cell transplantation purposes
4 Most leukemic patients/clients with acute lymphoblastic leukemia have an in-dwelling central venous line.
5 In AML in particular, oral manifestations may be the first clinical signs of leukemia.
6 Normal white blood cell count ranges from 3.5 to 10.5 X 109/L in adults (higher in children, particularly under the age of 2 years), whereas the WBC count in leukemia can increase to 500 X 109/L. Three groups of WBCs are found in the peripheral circulation: granulocytes (normally 90% neutrophils, with the remainder comprised of basophils and eosinophils); lymphocytes (T-lymphocytes, B-lymphocytes, and natural killer cells); and monocytes.
7 Diagnosis of leukemia is established by examination of the peripheral blood count and white blood cell differential (percentage of each type of WBC) and by bone marrow biopsy.=
8 Five-year net survival rate is for ages 15–99 years.
9 also known as Sweet’s syndrome
10 Suspected oncogenic viruses for leukemia include human T-cell lymphotropic virus (HTLV).
11 The Philadelphia chromosome has been implicated in CML, and persons with Down syndrome have a higher tendency to develop leukemia (particularly ALL and AML).
12 High blood levels of uric acid can lead to deposits in the joints (causing a painful gout-like condition) and/or build-up in the kidneys (potentially causing kidney damage and stones). High phosphate levels can also damage the kidneys and lead to kidney failure. Abnormal levels of calcium and potassium can affect heart rhythm and lead to neurological manifestations such as irritability, weakness, and confusion.
13 Symptoms of SVCS may develop gradually or suddenly, depending on how quickly the superior vena cava is squeezed or blocked. Signs/symptoms include shortness of breath; difficulty breathing; swelling of face, neck, upper body, and arms; chest pain; difficulty swallowing; paralyzed vocal cord; and Horner’s syndrome (which is characterized by small pupil, drooping eyelid, and reduced sweating on one side of face).
14 Other signs/symptoms of DIC include shortness of breath; pain or swelling in arms and legs; jaundice; low blood pressure; hypoxia; fever; and multiple organ failure.
15 Leukapheresis involves the removal of while bloods cells from the blood.
16 In intrathecal chemotherapy, anticancer drugs are injected into the fluid-filled space between the thin layers of tissue (theca) that cover the brain and spinal cord.
* 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.