Leukemia is a malignant disease characterized by the replacement of normal bone marrow elements with abnormal blood cells. The document discusses the history, etiology, pathogenesis, classification, clinical features, laboratory findings, treatment and oral manifestations of various types of leukemia including chronic myeloid leukemia (CML), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), and acute lymphoblastic leukemia (ALL). Guidelines for dental treatment and management of patients with leukemia during different phases of disease and therapy are also provided.

1. LEUKEMIA
Dr. NAVEENA
Ⅰ YEAR M.D.S.

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 Leukaemia is a malignant disease of the hemopoietic tissue, characterized by
the replacement of normal bone marrow elements with abnormal blood cells.
INTRODUCTION
DEFINITION

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• Leukemia was first described by anatomist and surgeon Alfred-Armand-Louis-Marie Velpeau in 1827
• John Hughes Bennett a pathologist gave leukemia its first published recognition as a clinical entity and as
a blood-related disease
• Pathologist Rudolf Virchow in 1845 reported a case and for the first time used the name “leukämie”
(leukemia)
• Pathologist Franz Ernst Christian Neumann found that the bone marrow of a deceased person with
leukemia was colored " green-yellow" as opposed to the normal red.
• By 1900, leukemia was viewed as a family of diseases as opposed to a single disease
Thomas X. First contributors in the history of leukemia. World J Hematol 2013; 2(3): 62-70 [DOI:
HISTORY

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Blasts, which are immature
and dysfunctional cells, normally
make up 1% to 5% of marrow cells.

6. ETIOLOGY
• Heredity – Downs syndrome
• Ionizing radiation
• Infections – HTLV 1
• Chemical carcinogens
• Drugs
• Immunodeficiency diseases
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7. PATHOGENESIS
• Genetic damage to a single
clone of target cells
• Chromosomal translocation
• AML = t(15;17)
• CML = t(9;22)
• Maturation defect
• Myelosuppression
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8. MYELOID NEOPLASMS
 MYELOPROLIFERATIVE DISEASES
 MYELODISPLASTIC DISEASES
 MYELODISPLASTIC SYNDROMES
 ACUTE MYELOID LEUKAEMIA
 ACUTE BIPHENOTYPIC LEUKAEMIA
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9. CHRONIC MYELOID LEUKEMIA (CML)
DEFINITION
 CML is a myeloproliferative neoplasm
characterized by the chromosomal translocation
t(9;22) (q34.1;q11.2), resulting in the BCR-ABL1
fusion gene and formation of the Philadelphia
chromosome (Ph*), which causes an increase in
blood granulocytes and bone marrow myeloid
precursors as the major proliferative component.
 ABL protein functions as a tyrosine kinase enzyme
that in turn activates other kinases which inhibit
apoptosis
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Interphase fluorescence in situ hybridization (FISH), chromosome banding analysis, and PCR
should be integrated for the diagnosis and follow-up of CML

10. CLINICAL FEATURES
 20% of all leukemias
 Incidence: 3rd and 4th decade
 Juvenile CML –rare
 MANIFESTATIONS:
 Anemia
 Hypermetabolism
 Splenomegaly
 Bleeding tendencies
 Juvenile CML- skin rashes
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leucocytosis (20000/μl)
↑ myeloblast
Basophilia
BONE MARROW:
Hypercellularity,
↑ myeloid-erythroid ratio
HISTOPATHOLOGY

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TREATMENT:
 Imatinib oral therapy: It competitively
inhibits ATP binding site of the ABL kinase,
which in turn inhibits signal transduction
BCR/ ABL fusion protein. It also induces
apoptosis in BCR/ ABL positive cells
 Allogenic bone marrow transplantation
 Alpha interferon
 Chemotherapy

13. ACUTE MYELOID LEUKEMIA (AML)
 Acute myeloid leukemia (AML) is the most common
leukemia among the adult population and accounts for
about 80% of all cases.
 It is characterized by clonal expansion of immature
“blast cells” in the peripheral blood and bone marrow
resulting in ineffective erythropoiesis and bone
marrow failure
 The most common risk factor for AML is
myelodysplastic syndrome.
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14. CLINICAL FEATURES
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15. LABORATORY FINDINGS  BLOOD PICTURE
 Anemia
 Thrombocytopenia
 ↑ Myeloblast - Auer rods (clumps of azurophilic granules resembling
elongated needles)
 BONE MARROW EXAMINATION
 Hypercellular – dry tap on aspiration
 Leukemic cells > 20% blast cells in bone marrow
 Immunophenotyping – CD13 and CD33 antigen
 CYTOCHEMISTRY
 Romanowsky staining- type of leukemia
 Myeloperoxidase - + in immature myeloid cells
 Periodic acid Schiff - + in immature lymphoid cells
 BIOCHEMICAL INVESTIGATION
 ↑ Serum uric acid
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TREATMENT:
Neutropenia – highly susceptible to infection
prophylaxis against infections
patients should be isolated and placed in laminar air flow rooms
systemic antibiotics and leucocyte concentrate
CYTOTOXIC DRUG THERAPY
AIM: Induce remission and reduce hidden leukemic cell population
COMBINATION DRUG THERAPY: Cytosine arabinoside, anthracyclines and 6-thioguanine
BONE MARROW TRANSPLANTATION
The basic principle is to reconstitute the patient’s hematopoietic system after total body
irradiation and intensive chemotherapy
The remission rate with AML is lower than in ALL. Medial survival with treatment- 12-18

17. LYMPHOID NEOPLASMS
 Hodgkin’s disease
 Precursor (Immature) B-cell malignancies – B cell acute lymphoblastic leukemia
 Peripheral (Mature) B-cell malignancies – chronic lymphocytic leukemia, hairy cell leukemia
 Precursor (Immature) T-cell malignancies - T cell acute lymphoblastic leukemia
 Peripheral (Mature) T-cell malignancies and NK cell malignancies
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PRECURSOR (IMMATURE) B- AND T-CELL LEUKEMIA
ACUTE LYMPHOBLASTIC LEUKEMIA
 Most ALL cases occur in children, with an incidence of 3 to 4/100,000 in patients 0 to 14 years of
age
 In children, ALLs represent 75% of all acute leukemias, with a peak incidence at 2 to 5 years of age
 A variety of genetic and environmental factors have been related to ALL.
 It occurs with increased frequency in patients with
 Down syndrome,
 Bloom syndrome,
 Neurofibromatosis type I
 Ataxia-telangiectasia

19. CLINICAL FEATURES
 Precursor B-cell lymphoblastic leukemia
 Extranodal site involvement is early
 Hepatomegaly, splenomegaly, CNS infiltration,infections
due to cytopenia
 Precursor T-cell lymphoblastic leukemia
 Differentiate in the thymus
 Presents as a mediastinal mass and pleural effusion
progresses rapidly to develop leukemia in the blood and
bone marrow
 It is more aggressive than its B-cell counterpart.
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French-American-British classification for acute lymphoblastic leukemia
FAB
class
Percent
cases
Morphology
L1 Childhood ALL
(B- ALL & T-ALL)
More
common in
children
Homogenous small lymphoblast;
scanty cytoplasm, regular round
nuclei, inconspicuous nucleoli
L2 Adult ALL
Mostly T-ALL
More
frequent in
adults
Heterogenous lymphoblasts;
variable amount of cytoplasm,
irregular cleft nuclei, large
nucleoli
L3 Burkitt type ALL
(B-ALL)
Uncommon Large Homogenous lymphoblast;
cytoplasmic vacuolation ,
prominent round nuclei,

21. LABORATORY FINDINGS
 BLOOD PICTURE
 Anemia
 Thrombocytopenia
 ↑ lymphoblasts
 BONE MARROW EXAMINATION
 Malignant undifferentiated cells of precursor B or T cell origin
 CYTOCHEMISTRY
 Romanowsky staining- type of leukemia
 Acid phosphatase - + leukemic blasts
 Periodic acid Schiff - + in immature lymphoid cells
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Romanowsky staining
Giemsa staining

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TREATMENT:
CHEMOTHERAPY
COMBINATION DRUG THERAPY: vincristine, prednisolone, anthracyclines, cytosine
arabinoside, and methotrexate
patient with T cell ALL and those with meningeal involvement carry a less favorable
prognosis
BONE MARROW TRANSPLANTATION from a suitable allogenic or autologous donor is used in
adults with relapses
Prognosis and disease-free survival of children with ALL is better than in adults
Medial survival children – 60 months, Adults- 12-18
months

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B-CELL LEUKAEMIA
CHRONIC LYMPHOCYTIC LEUKAEMIA/SMALL LYMPHOCYTIC LEUKAEMIA
 Chronic lymphocytic leukemia (CLL) is a disease characterized by the relentless accumulation of
CD5+ B lymphocytes in the peripheral blood, bone marrow, and secondary lymphoid organs (lymph
nodes and spleen)
 CLL is the most common leukemia in adults, in the western countries, representing about 25–30% of
all leukemias
 RISK FACTOR: Genetic and familial predisposition

24. CLINICAL FEATURES  Asymptomatic
 Anemia
 Enlargement of superficial lymph nodes
 Splenomegaly, hepatomegaly and hemorrhagic
manifestations
 Respiratory tract infection
SAMPLE FOOTER TEXT 20XX 24

25. LABORATORY FINDINGS
 BLOOD PICTURE
 Anemia- 20% of cases develop coombs’ positive autoimmune
hemolytic anemia
 Leucocytosis – mature small lymphoblasts
 BONE MARROW EXAMINATION
 Increased lymphocyte count(25-95%)
 Reduced erythroid and myeloid precursors
 LYMPHNODE BIOPSY
 Diffuse proliferation of well differentiated mature, small and
uniform lymphocytes without any cytologic atypia or
significant mitosis.
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TREATMENT:
• Unlike other leukemias, none of the available drugs and radiation therapy are capable of
eradicating CLL and inducing true complete remission
• Treatment is palliative and symptomatic; these approaches include alkylating drugs,
corticosteroids, and radiotherapy. Splenectomy is indicated in cases with autoimmune
hemolytic anemia
The prognosis of CLL is better than CML since blastic transformation seldom occurs

27. ORAL MANIFESTATIONS OF LEUKEMIA
 In acute leukemias, gingival hyperplasia is generally
observed, mainly affecting the interdental papillae
and the marginal gingiva caused by inflammation, or
leukemic infiltration
 The infiltration of leukemic cells may also involve
periapical tissues and simulate, both clinically and
radiographically, periapical inflammatory lesions
 In chronic leukemia, the leukemic infiltrates in
oral tissues is less frequent and can be
observed: pallor of the mucosa, soft tissue
infections, and generalized lymphadenopathy
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28. DENTAL PROCEDURES IN DIFFERENT STAGES OF THE DISEASE AND TREATMENT
 Dental treatment should be planned according to
the antineoplastic therapy
 Considering the risk of bleeding and serious
infections associated with invasive procedures there
are already some protocols that emphasize the
importance of evaluating certain hematological
indices, mainly neutrophils and platelets.
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HIGH-RISK
•Active leukemia
•Pts under treatment
•present bone marrow
suppression
MODERATE RISK
•Completed the induction
phase
•The maintenance phase
LOW- RISK
•present no evidence of
malignancy or
myelosuppression.

29. DENTAL TREATMENT IN THE PRECHEMOTHERAPY PHASE
 Priority should be on eliminating sources of infection
and trauma, as well as extractions and periodontal
care.
 Endodontic treatment of symptomatic nonvital teeth
should be done at least a week before the start of
chemotherapy
 Extractions should be made, preferably three weeks
prior to chemotherapy or radiotherapy and at least 10
to 14 days earlier.
 A neutrophil count of 1,500/mm3 and platelets
of 40,000 cells/mm3 are required for
performing periodontal probing or extractions.
The procedures must be performed under
antibiotic cover.
 when not possible, dental treatment should be
postponed until the haematological indices
increase.
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30. DENTAL TREATMENT IN THE TRANSCHEMOTHERAPY PHASE
 Dental intervention is limited to emergency care
 The myelosuppression peak is most evident, usually after 14 days of drug administration, and at
this time, dental treatment should be avoided;
 Before or 21 days after the start of chemotherapy the treatment can be performed
 platelet count of at least 60,000 cells/mm3 - for oral surgeries.
 When there is spontaneous bleeding resulting from minor trauma, measures Should be taken to
control the bleeding
MANAGEMENT OF BLEEDING
 Epinephrine – vasoconstrictor
 Topical thrombin - to stabilize blood clots
 Topical aminocaproic acid - to improve
coagulation
 Topical use of tranexamic acid is also cited as an
effective hemostatic in reducing postop bleeding 30

31. DENTAL TREATMENT AFTER CHEMOTHERAPY
 Patients who were cured of leukemia are considered to be of low risk and can be met with normal dental
treatment regimens
 Antibiotic prophylaxis during oral procedures should be performed for at least six months after the completion
of chemotherapy
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32. CONCLUSION
 Performing dental procedures can offer a risk to the patient, depending on his state of health and phase of
therapy.
 Noninvasive procedures can be performed at any stage of the disease or treatment.
 Invasive procedures offer higher risk.
 In emergency situations of risk considered, particularly those involving pain (acute cases), the patient should
be assisted, if necessary, in a hospital setting, with the institution of measures to increase the hematological
indices (transfusions) and, if applicable, with antibiotic coverage.
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• Textbook Of Pathology by Harsh Mohan 8th edition
• Thomas X. First contributors in the history of leukemia. World J Hematol 2013; 2(3): 62-70 [DOI:
10.5315/wjh.v2.i3.62]
• Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW. The
2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016
May 19;127(20):2391-405. [PubMed]
• Zimmermann C, Meurer MI, Grando LJ, Gonzaga Del Moral JÂ, da Silva Rath IB, Schaefer Tavares S. Dental treatment
in patients with leukemia. J Oncol. 2015;2015:571739. doi: 10.1155/2015/571739. Epub 2015 Feb 15. PMID:
25784937; PMCID: PMC4345074
• Chennamadhavuni A, Lyengar V, Shimanovsky A. Leukemia. [Updated 2022 May 4]. In: StatPearls [Internet]. Treasure
Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560490/
REFERENCES

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