KELAINAN DI RONGGA MULUT KARENA GANGGUAN LEUKOSIT (LEUKEMIA)

Nurdiana, drg, Sp.PM

Introduction
Malignancy WBC bone marrow Characterized differentiation & proliferation malignantly transformed hematopoietic stem cell s uppression of normal cells Effect leukemic overproduction white cell ss other cell lines suppre

 Malignant cell replace & turn off normal marrow el ement anemia, thrombocytopenia & deficiency no rmally functioning leukocytes Leukocyte do not function normally ve migration, phagocytosis, or bactericidal defecti action

 Leukemic cell infiltrate other body organ ing normal tissue Etiology unknown

destroy

Several factors risk of disease :

Genetic factors & families with high incidence Genetic disorders : Down, Klinefelters, & Fancon is syndromes 20-fold acute leukemia

 Familial leukemia rare incidence in sibling Radiation > 1 Gy significant risk of leukemia Exposure to chemical & drug benzene, arthritis drug phenylbutazone, antibiotic chloramphenicol, a nticancer drug

 Classification: Acute : acute lymphocytic leukemia (ALL) & acute myelogenous leukemia (AML)

chronic lymphocytic leukemia (CLL) & chronic myelocytic leukemia (CML)

Acute Leukemia
Malignancies of hematopoietic progenitor cell ail to mature & differentiate f ALL : 65% B lymphocyte , 20% T-cell type, & 1 5% null cell leukemia In older patient AML preceded by a preleukemic o r myelodysplastic syndrome generalized bone marrow abnormalities RBC, leukocyte, & platelet respond poorly to therapy

Clinical Manifestations
Occur at any age but ALL common in children usually 3-5 yrs) & AML more frequent in adults (

Symptoms & signs bone marrow suppression or infiltration leukemic cells into organs & tissues
Bone marrow changes anemia, thrombocytopenia, & decrease in normal functioning neutrophils

 Anemia pallor, shortness of breath, & fatigue Thrombocytopenia spontaneous bleeding : petechiae, ecchymoses, epistaxis, melena, menstrual bleeding , & gingival bleeding platelet count < 25,000/mm3

Diagnosis
Lab exam of peripheral blood & bone marrow Peripheral WBC normal or subleukemic o r aleukemic leukemia immature granulocytic, lymphocytic precursor or stem cell + anemia & t hrombocytopenia

Microscopic examof a bone marrow aspirate finaliz es diagnosis

Treatment
1st step obtain complete remission asymptomatic, peripheral blood counts normal, & < 5% cells in marrow are blasts However = cure leukemia return without additional therapy

Combination chemotherapy treatment of choice ac ute leukemia

CHRONIC LEUKEMIA
Characterized large number of well-differentiated c ell in bone marrow, peripheral blood & tissue, & prolonged clinical course even without therapy Slowly progressive Chronic lymphocytic leukemia completely asympt omatic & not even shorten life

Chronic Lymphocytic Leukemia

Slowly progressing malignancy involving lymphocyte > 90% B lymphocytes immunoglobulin synthe sis & antibody response dont carry out normal immunologic function & differentiate into normal immunoglobulin-producing plasma cells when expose d to antigen

 Disease progresses slowly CLL cells dont turn off normal marrow cells until late in course of disease

Clinical Manifestations
Most frequently males > 40 yrs most common age of onset 60 yrs

Slow natural history detected incidentally by r outine hematology before any signs or symptoms app arent Peripheral blood many small well-differentiated lymphocytes; 100.000 - millions cells/mm3

 Asymptomatic phase last for years signs & symptoms infiltration of leukemic cells in bone marrow, lymph nodes, or other tissues appear Bone marrow infiltration causes anemia & hrombocytopenia pallor, weakness, dyspnea, & purpura t

Infiltration other tissues lymphadenopathy, splenomegaly, hepatomegaly, & leukemic infiltrates o f skin or mucosa

 Cervical lymphadenopathy & tonsillar enlargement frequent head & neck signs Hypogammaglobulinemia susceptibility to bacterial infection & varicella-zoster virus Late in disease massive lymphadenopathy intestinal or urethral obstruction & obstructive jaundice

 Leukemic infiltrates skin masses, liver dysfunction, intestinal malabsorption, pulmonary obstruction, or compression of central or peripheral n ervous system Abnormal immunoglobulins hemolytic anemia or t hrombocytopenia

Treatment
Indications for treatment : progressive fatigue, roublesome lymphadenopathy, or development of anemia or thrombocytopenia t

Standard treatment : chlorambucil, but fludarabine response rate

Chronic Myelocytic Leukemia

Most closely related to exposure to ionizing adiation & toxic chemicals Identified by genetic changes chromosomes 90% Philadelphia chromosome acquired genetic defect translocation of genetic material from chromosome 22 to chromosome 9 affects hemato poietic stem cell present in myeloid & some lymphoid cell lines r

 2 phases: chronic & blastic Chronic phase : large numbers of granulocytes present in bone marrow & peripheral blood, but cells r etain normal functions take 5-8 yrs after formati on of 1st CML cell clinical sign & symptom Blastic phase : take 2-4 yrs after diagnosis further malignant transformation to immature cells act similarly to cells in acute leukemia

Clinical Manifestations
Most frequently in ages of 30-50 yrs No symptoms during 1st few yrs Disease discovered during a routine exam splenomegaly or WBC count Early signs & symptoms secondary to anemia or packing of leukocytes into spleen & bone marrow

 Anemia weakness, fatigue, & dyspnea on exertion Bone pain or abdominal pain in upper left quadrant spleen & bone marrow changes

Disease progresses thrombocytopenia petechiae, ecchymoses, & hemorrhage

 Patient survives for years before enters blastic phase Transformation of blastic phase suddenly or develop slowly over months

Symptoms caused by splenomegaly worsen, & other organs (liver, lymph nodes, & skin) involved
Death occur within months after blastic phase begin

Diagnosis
Lab tests WBC count several hundred housand leukocytes/mm3 t

Bone marrow hypercellular

Diagnosis confirmed by presence of Philadelphia chromosome (90%) & absence of leukocyte alkaline phosphatase

Treatment
Control of chronic phase often successful If disease asymptomatic careful monitoring Symptoms busulfan or other alkylating agents Chronic phase chemotherapy & radiation, but truer emissions rare bone marrow transplantation f rom histocompatible donor

 Blastic phase refractory to treatment Life prolonged chemotherapy protocols reatment of acute leukemia t

Oral & Dental Considerations

ACUTE LEUKEMIA
Head & neck signs leukemic infiltrates or marrow f ailure cervical lymphadenopathy, oral bleeding, gi ngival infiltrates/swelling, oral infections, oral ulcers, leukaemic deposits, purpura, & anemia

 Thrombocytopenia & anemia marrow suppressionf rom disease & chemotherapy pallor of mucosa, p etechiae, ecchymoses, & gingival bleeding

Gingival Swelling
Lack healthy, mature WBC t o counter low-grade infection packed & swollen leukaemic cell purplish, necrotic, & ulcerate acute myelogenous leukemia

Gingival Bleeding
Extent of gingival bleeding depends on severity of hrombocytopenia & extent of local irritants t

Spontaneous gingival bleeding platelet count falls below 20,000/mm3

Severe gingival bleeding managed successfully with local treatment reducing need for platelet ransfusions risk : benefit ???

 Risks of platelet transfusion : hepatitis, HIV infection, transfusion reactions, & formation of antipla telet antibodies reduce usefulness Oral hemorrhage DIC hypofibrinogenemia Topical treatment : removal of obvious local irritants& direct pressure

 Absorbable gelatin or collagen sponges, topical t hrombin, or placement of microfibrillar collagen by pa cking or splints Oral rinses antifibrinolytic agents : tranexamic acid or -aminocaproic acid If local measures not successful platelet ransfusions t

Oral Ulcers
Oral mucosal ulcers direct effect of chemotherapeutic drugs Lockhart & Sonis begin 7 days treatment Ulcer combined effect immunodeficiency & cytotoxic drugs (methotrexate)

Bacterial invasion secondary to severe neutropenia oral ulcers early sign of disease

 Ulceration opportunistic microbes + immunodeficiency acute osteomyelitis following ro utine extractions

 Characteristic : large, irregular, foul smelling, surrounded by pale mucosa anemia & lack normal inflammatory response

 oral ulcers in leukemic patients with chemotherapy recurrent HSV infection intraoral mucosa & lip Classic cluster of vesicles quickly spread large ulcer often have raised white border

 Patients receiving immunosuppressive chemotherapy HSV should be ruled out with cytology smear stained with fluorescent antibody to HSV antibody (d irect fluorescent antibody) & viral culture Lesions respond well to parenteral acyclovir admini stered intravenously or by mouth acyclovir-resista nt HSV strains !!!

 Management non-HSV oral ulcers prevent spread of localized infection, minimize bacteremia, promote healing, & reduce pain Ulcers in hospitalized leukemic patients + chemotherapy infected organisms not commonly associated with oral infection gram (-) e nteric bacilli

 Topical antibacterial treatment : povidone-iodine solutions, bacitracin-neomycin ointments, or chlorhe xidine rinses Kaolin & pectin + diphenhydramine oral rinses educe pain Oral preparations containing sucralfate suspensions bind & protect ulcers r

Leukaemic Deposits
Tumour-like masses form in mouth or salivary glands

Purpura
Excessive gingival bleeding, purplish mucosal patch, blood blister, or prolonged bleeding after surgery

Leukaemic infiltration extraction socket delay h ealing

Anemia
Mucosal pallor important sign in children uncommon

Cervical Lymphadenopathy
Common in lymphocytic leukaemia or secondary to o pportunistic infections in mouth

Oral Infections
Serious potentially fatal complication in neutropenic l eukemic patients

Candidiasis common oral fungal infection other fungi : Histoplasma, Aspergillus, or Phycomycetes, Biopsy specimen, fine-needle aspiration or cytology culture not reliable

 Diagnosis periodontal & pericoronal infections difficult absent normal inflammation Early diagnosis imperative oral flora source of p otentially life-threatening infections with gram (+) & gr am (-) bacilli Dentist screening exam & eliminate sources of potential acute infection or bacteremia before chemo

 Platelet transfusions & combinations antibiotics i.v before dental treatment

 Leukemic infiltrates : palate, alveolar bone, & dental p ulp involvement 5th & 7th cranial nerves vincristine (commonly used to treat ALL) Craniofacial deformities & dental anomalies common in children radiotherapy + chemo < 5 yr Most common anomalies : deficient mandibular & arrested root development, dental agenesis, microdontia, & enamel dysplasia

 Oral lesions common complications HSC ransplant

GVHD lesions 80% lichenoid lesions : desquamative gingivitis, keratotic lesions, atrophy, & ulceration) clinically & histol ogically similar to liche n planus or discoid lupus

 GVHD xerostomia biopsy minor salivary glands changes compatible with Sjgrens syndrome

Management
Biopsy gingival swelling unresponsive conventional treatment diagnosis

Leukemia or cytotoxic treatment meticulous OH control bacterial population complications

Mouth rinses (0.2% chlorhexidine or tetracycline & a mphotericin) control severe gingival changes & su perficial infections

 Mucosal ulceration by Gram (-) bacilli or anaerobes specific antibiotic tx systemic spread infection Extractions avoid risks of severe infection, bleeding, or anaemia unavoidable blood ransfusion & antibiotic t

CHRONIC LEUKEMIA
Oral manifestations uncommon or mild : mucosal pallor, gingival or palatal swelling, purpura & oral ulceration (due to infection/cytotoxic drug or both)

Management
Routine dentistry with normal care Significant anaemia, bleeding tendencies, or suscepti bility to infection precautions acute leukemia

DENTAL EVALUATION PATIENT WITH LEUKEMIA

Undiagnosed Leukemia

1. Oral pathose presenting sign of disease acute

a. Oral manifestation of acute leukemia - Neutropenia : recurrent infection - Thrombocytopenia : gingival bleeding, hematoma b. Gingival infiltrate &/or lymphadeopathy

2. Dental evaluation : a. History b. Exam c. Lab evaluation : WBC & platelet count, hemoglobin, & hematocrit d. Medical referral

Diagnosed Leukemia 1. Physician consult, hematologic status 2. Risk categories (infection & bleeding most signific ant) a. High risk : active leukemia b. Moderate risk : remission & receiving chemo c. Low risk : successfully completed tx no evidenc e malignancy or myelosuppression

DENTAL MANAGEMENT PATIENT LEUKEMIA

Prevention

Eliminate source infection or irritation : sharp r estoration, fractured teeth, remove prostheses, or ort hodontic band
Eliminate partially erupted 3rd molar Eliminate pulpal disease Scaling, root planing, oral hygiene instruction, use louride f

Treatment Guidelines By Risk Category High risk : - Control infection hospitalization & use broadspectrum i.v antibiotic - Control bleeding topical agent, platelet

 Moderate risk : - Plan dental treatment around chemo or when WB count > 3500 cells/mm3 & platelet > 100.000 cells/mm3 - Antibiotic prophylaxis - Hospitalization for type V (multiple ext, flap surgery or gingivectomy, etc.) & VI (full arch/full mouth ext of flap surgery, ext multiple bony impaction, etc.) procedure

Low risk : - Use normal protocol