3. LEUKAEMIA
DEFINITION:
A malignant progressive disease in which the bone
marrow and other blood-forming organs produce increased
numbers of immature or abnormal leucocytes. These
suppress the production of normal blood cells, leading to
anaemia and other symptoms.
3
Leukos
(white)
leukaemia
Haima
(blood)
4. History
Leukemia was first described by anatomist and surgeon Alfred-
Armand in 1827. A more complete description was given by
pathologist Rudolf Virchow in 1845.
Around ten years after Virchow's findings, pathologist Neumann found
that one deceased leukemia patient's bone marrow was colored "dirty
green-yellow" as opposed to the normal red.
By 1947 Boston pathologist Sidney Farber believed from past
experiments that aminopterin, a folic acid mimic, could potentially cure
leukemia in children. The majority of the children with ALL who were
tested showed signs of improvement in their bone marrow, but none of
them were actually cured.
In 1962, researcher Emil Frei used combination chemotherapy attempt to
cure leukemia. The tests were successful with some patients surviving
long after the tests
4
5. In 2012 leukemia developed in 352,000 people globally with 265,000
deaths.
Most common type of cancer in children, with three quarters of leukemia
cases in children being ALL.
90% of all leukaemias are diagnosed in adults, with AML and CLL being
most common in adults.
In US about 2500 new cases of leukaemias are diagnosed each year in
children under the age of 15.
5 in 100,000 children
Peak incidence – 2 to 5 years of age.
5EPIDEMIOLOGY
6. TYPES OF LEUKAEMIA
ACUTE OR CHRONIC LEUKAEMIA
ACUTE LEUKAEMIA - The new or immature cells, called
blasts, remain very immature and cannot perform their
functions. The blasts increase in number rapidly, and the
disease progresses quickly.
CHRONIC LEUKAEMIA - There are some blast cells that
are more mature and are able to perform some of their
functions. The cells grow more slowly, and the number
increases less quickly, so the disease progresses gradually.
6
7. LYMPHOCYTIC OR MYELOGENOUS
LEUKAEMIA
Cancer can occur in either the lymphoid or myeloid
white blood cells.
When the cancer develops in the lymphocytes (lymphoid
cells)- LYMPHOCYTIC LEUKAEMIA.
Cancer develops in the granulocytes or monocytes
(myeloid cells) – MYELOGENOUS LEUKAEMIA.
7
8. LEUKAEMIA
Acute Chronic
Lymphoblastic Myeloid Lymphatic Myeloid
•L1-Childhood
ALL
•L2-Adult ALL
•L3-Burkitt Type
ALL
•Undifferentiate
d
•M1- Undifferentiated
•M2- Differentiated
•M3- Promyelocytic
•M4-
Myelomonocytic
•M5- Monocytic
•M6- Erythrocytic
•M7- Megakaryocytic
•Common B
Cell
•Rare T Cell
Eosinophilic
leukemia
8FRENCH AND BRITISH CLASSIFICATION
9. Etiology
Genetic factors: Associated with syndromes
(Downs, Blooms, Fanconis, Klinefelters)
Environmental factors:
• Ionosing radiation (Japanese survivors)
• Chemical carcinogens (tobacco smoking,
agricultural chemicals, benzene)
• Drugs (alkylating agents)
Infection: viral etiology – T-cell leukaemia and
lymphoma by human retrovirus (HTLV-1)
9
11. Pathogenesis (leukaemogenesis)
Genetic damage to single clone of target cell:
leukaemia arises following malignant transformation
of single clone of cells belonging to myeloid or
lymphoid series followed by proliferation of
transformed clone
Maturation defect: In acute leukaemia single most
prominent characteristic of leukaemic cells is defect
in maturation beyond myeloblast or promyelocyte
level in AML and lymphoblast level in ALL.
Organ infiltration: leukaemic cells proliferate
primarily into bone marrow, circulate in blood and
infiltrate into other tissues such as spleen and CNS.
11
12. Chromosomal translocation: Most consistent
chromosomal abnormality among these is phildelphia
chromosome seen in 70-90% cases with CML
involving reciprocal translocation of parts of long arm
of 22 chromosome
As leukaemic cells accumulate in bone marrow they
suppress normal haemopoietic stem cells partly by
physically replacing normal narrow precursors
12
14. ACUTE LYMPHOCYTIC LEUKAEMIA
Leukemia constitutes approximately 30% of all childhood
cancers and acute lymphoblastic leukaemia (ALL) is the
most common type of malignancy encountered in children
ALL accounts for about 75% of childhood leukemias with its
peak incidence at 4 years of age.
Acute lymphoblastic leukemia (ALL) is a malignant disorder
resulting from the clonal proliferation of lymphoid precursors
with arrested maturation
14
15. The disease can originate in lymphoid cells of
different lineages, thus giving rise to b-cell or
t-cell leukemias or sometimes to mixed
lineage leukemia.
Acute lymphoblastic leukemia was one of the
first malignancies to respond to
chemotherapy.
Among various leukemia categories, it was
the first leukemia that could be cured in a
majority of children.
15
16. EPIDEMIOLOGY
5,000 cases diagnosed annually
Two thirds occuring in children
Only 10-15% adult cases
16
19. DIAGNOSIS
Blood tests and other evaluation procedures
Bone marrow aspiration and biopsy
Spinal tap/lumbar puncture
19
20. 20
(1) Remission Induction: It generally lasts for 28 days and consists of 3 or 4
drugs (examples are vincristine, prednisone, and L-asparaginase), with a
95% success rate.
Achievement of remission is a known prerequisite for prolonged survival.
(2) CNS Preventive Therapy/Prophylaxis: CNS can act as a sanctuary site
for leukemic infiltrates because systemically administered chemotherapeutic
drugs are not able to cross the blood-brain barrier. Cranial irradiation and/or
weekly intrathecal injection of a chemotherapeutic agent, usually methotrexate,
are used. This presymptomatic treatment can be done in each phase as well.
TREATMENT
21. 21
(3) Consolidation or Intensification: It is designed to minimize the
development of drug cross-resistance through intensified treatment, in an
attempt to kill any remaining leukemic cells.
High dose Methotexate
6-mercaptopurine
High dose asparginase c
(4) Maintenance: It is aimed at suppressing leukemic growth through
continuous administration of methotrexate and 6-mercaptopurine. The
optimal length of this phase has not been established yet but usually lasts
from 2.5 to 3 years.
22. ACUTE MYELOGENOUS LEUKAEMIA
Disease of all ages
More in men
Heterogenous clonal disorder of hematopoietic cells (blasts)
Too many granulocytes are produced in the bone marrow.
AML affects the young blood cells (called blasts) that develop
into a type of white blood cell (called granulocytes).
22
23. Blasts-loose ability to differentiate normally
Do not mature & become too numerous,
remain in the bone marrow and blood.
Duration- days to weeks.
Chromosome abnormalities (extra
chromosomes and structural changes in the
chromosome material) are present in the
majority of all patients.
23
24. SIGNS AND SYMPTOMS
General manifestations
Anemia
Bleeding , bruising
Fever , persistent weakness
Fatigue
Aches in bones and joints
Swollen lymph nodes
24
25. ORAL MANIFESTATIONS
Gingival Hyperplasia
Bleeding of Gums
Chloromas: an extramedullary manifestation
of acute myeloid leukemia; in other words, it is a
solid collection of leukemic cells occurring
outside of the bone marrow.
Ecchymosis of Hard palate, Soft palate, Tongue
and Tonsils
Oral Mucositis
25
26. DIAGNOSIS
Diagnosed if marrow contains >30% blasts
Complete medical history and physical examination
Blood tests
Bone marrow aspiration and biopsy
Spinal tap/lumbar puncture
26
27. TREATMENT
Chemotherapy
Rapid induction combination of Anthracycline
(daunorubicin, idarubicin, cytarabine)
6-thioguinine or etoposide
Radiation therapy
Bone marrow transplantation/ HSCT
27
28. ORAL MUCOSITIS
Begins with erythema progressing to ulceration
7-10 days after onset of chemotherapy
Resolves within 2 weeks of cessation of drugs
Mucosal lesions-debilitating pain, compromised
oral function
28
30. Neutropenia
NEUTROPHILS
More susceptible to bacterial infections
Treatment
Alternating rinses of sodium bicarbonate with
saline and 0.12% chlorhexidine and nystatin
Topical anesthetics
30
31. CHRONIC LYMPHOCYTIC LEUKEMIA
>60 years of age
Results from slow accumulation of clonal B lymphocytes
Increased number of lymphocytes
Cells are immature and over abundant
Slowly progressive disease
31
34. DIAGNOSIS
COMPLETE MEDICAL HISTORY
PHYSICAL EXAMINATION
BLOOD TESTS (LYMPHOCYTOSIS >5000/ML)
BONE MARROW BIOPSY
34
35. TREATMENT
Chemotherapy
Radiation therapy
Treatment for complications – infection or anemia
Leukapheresis- a procedure to remove excessive lymphocytes
Bone marrow transplantation
Splenectomy, surgery to remove the spleen
35
36. CHRONIC MYELOGENOUS LEUKAEMIA
Increased number of granulocytes
More in adults (middle aged) , rare in children
Duration- months to years
Distinctive type of CML in children – juvenile chronic
myeloid leukaemia
36
37. Specific chromosome rearrangement
Part of chromosome #9 breaks off and attaches
itself to chromosome #22, so that there is an
exchange of genetic material between these
two chromosomes.
This rearrangement changes the position and
functions of certain genes, which results in
uncontrolled cell growth.
37
38. SIGNS AND SYMPTOMS
Anemia
Bleeding
Bruising
Fever
Persistent weakness
Fatigue
Aches in bones and joints
Swollen lymph nodes
38
39. Oral manifestations:
The most frequently reported oral abnormalities
attributed to the leukaemic process include:
Gingival bleeding
Gingival hypertrophy
Nonspecific ulcerations.
Odontalgia.
Jaw pain.
Loose teeth.
Extruded teeth.
Gangrenous stomatitis.
39
41. TREATMENT
Chemotherapy
Biological therapy - using the body's immune system to fight
cancer
Radiation therapy
Stem cell transplantation
Splenectomy
41
42. Erosive or ulcerative lesions
Common in children with leukemia
Associated with the use of certain drugs
(methotrexate and the anthracycline)
(antibiotics daunomycin and doxorubicin)
After administration of the drug is discontinued,
these lesions usually disappear within a few days.
Treatment is directed toward the relief of discomfort.
42
43. In a patient who is physically debilitated or who is in
relapse, septic, and severely granulocytopenic, ulcerative
lesions require close observation.
Such lesions may serve as a nidus for the proliferation
of microorganisms,which can lead to potentially fatal
viral, fungal, or bacterial infection.
Therefore specimens from these ulcerative lesions should
be cultured and subsequent sensitivity testing performed,
and antibiotic therapy should be initiated or modified
accordingly.
43
44. Hairy cell leukaemia
Unusual and uncommon type of b cell malignancy
characterised by presence of hairy cells in blood
and bone marrow and splenomegaly
Patients are susceptible to infection with M.avium
intercullulare
Hairy cells: Abnormal mononuclear cells with
hairy cytoplasmic projections seen in bone
marrow, peripheral blood and spleen.
Lab diagnosis is made by presence of
pancytopenia due to marrow failure and splenic
sequestration.
Treatment: splenectomy, alpha interferon therapy,
2-cholorodeoxyadenosine.
44
45. ADULT T CELL LEUKAEMIA
45
Neoplasms of CD4 T cells observed in patients infected by HTLV1
Characterised by skin lesions, generalized lymphadenopathy,
hepatosplenomegaly, peripheral blood lymphocytosis and
hypercalcemia.
Tumor cells- multi lobulated nuclei- clover leaf/flower cells ,
contains clonal HTLV1 pro virus compatible with direct pathogenic
involvement of virus in neoplasm.
Patients with rapidly progressive disease- fatal within 1 year.
46. Leukaemoid reactions
Reactive excessive leukocytosis in peripheral
blood resembling that of leukaemia in a subject
who does not have leukaemia
Clinical features such as splenomegaly,
lymphadenopathy and heamorraghes are absent
leukaemoid reactions may be lymphoid or
myeloid.
46
47. 47Myeloid leukaemoid reaction
Causes:
Infections: Staphylococcal pneumonia, disseminated tuberculosis
Meningitis, endocarditis, infected abortions.
Intoxication: Eclampsia, mercury poisoning, severe burns.
Malignant diseases: Multiple myeloma, myelofibrosis, hodgkins
disease.
Severe hemorrhage and severe hemolysis
48. 48
Findings:
Leucocytosis: 1,00,000/ul
Infective cases: Toxic granulation and dohle bodies in
cytoplasm of neutrophils
Proportion of immature cells: Mild to moderate, comprise
of myelocytes, metamyelocytes and blasts
Neutrophil alkaline phosphatase(NAP) : Score is high and
is useful to differentiate in cases of doubt with CML.
49. LYMPHOID LEUKAEMOID REACTION
49
Causes:
Infections : infectious mononeucleosis, CMV infections, pertussis,
chicken pox,tuberculosis.
Malignant diseases may rarely produce lymphoid leukaemoid
reactions
Findings :
Leucocytosis: not exceeding 1,00,000/ul
White cell count reveals mature lymphocytes simulating CLL
50. 50DIAGNOSIS
Confirmed by findings of immature blast cells on either peripheral
blood smear, bone marrow aspiration or both.
Diagnosis of particular type: i.e myeloid or lymphoid- determined by
evaluating blast morphology on peripheral smear
Definitive diagnosis- cell surface markers by flow cytometry and
evaluation of cytochemical staining patterns
Cytogenetic analysis- should be undertaken
Flouroscence in situ hybridization and polymerase chain reaction for
chromosomal abnormalities
Lumbar puncture- performed at the time of diagnosis to evaluate
possibility of CNS involvement
51. Prognosis
Low risk - 1-9 years of age
WBC count- <50,000/mm3
High risk- younger than 1 year of age
WBC- >50,000/mm3
CNS and testicular diseases are seen
Very high risk- Hypodipliod DNA index
or
failed to achieve remission eve after 4 weeks of therapy
Relapse in ALL- Bone marrow and extra medullary sites
51
52. Chemotherapy
Induction chemotherapy:
3-4 agent combination based on risk group assessment
Low or standard risk patients- vincristine, prednisolone,
L.asparginase for 4 weeks
High risk patients- anthracycline
Cranial radiation therapy for existing CNS leukaemia cases is
necessary
During induction chemotherapy intrathecal instillation of
combination of methotrexate, cytarabine, hydrocortisone is
given
52
53. Continuation therapy:
Includes dosage of 2-3 years.
Monthly dose of vincristine.
Short courses of oral corticosteroid therapy
+
6 mercaptopurine (oral, daily doses)
+
methotrexate (weekly doses)
53
54. STEM CELL TRANSPLANT
Goal
Totally eliminate leukemic cells from the body using combinations
of chemotherapy with or without total body irradiation
Eradicates patient’s hematopoietic stem cells
Replaced with those of an HLA-matched (Human Leukocyte
Antigen)
Allogenic- matching donor - may be a sibling, identical twin or
any volunteer
Autogenic: stem cells collected from the patients themselves.
55. Complications 55
As bone marrow transplant is used widely for treatment complications
are commonly seen.
Graft versus host reaction
Results from bone marrow suppression induced by chemotherapy
Bleeding and significant anaemia are noticed
Neutropenia with <500 neutrophils/mm3 predispose to bacterial
infection.
Prophylaxis with oral trimethoprim- preventive treatment is
sulfamethaxazole
Patients not exposed to varicella vaccine are at risk of infection
Non immune patients should receive varicella zoster immunoglobin
56. 56
Throughout the world, there has been a drastic decline in
mortality rate in pediatric leukemic population due to early
diagnosis and improvements in oncology treatment.
The pedodontist plays an important role in the prevention,
stabilization, and treatment of oral and dental problems that
can compromise the child’s health and quality of life during,
and follow up of the cancer treatment.
57. 57
Before any dental treatment is administered to a child
with leukemia, the child's hematologist and
oncologist or primary care physician should be
consulted.
Following information should be ascertained:
1. Primary medical diagnosis
2. Anticipated clinical course and prognosis
3. Present and future therapeutic modalities
4. Present general state of health
5. Present hematologic status
58. 58
Ideally ,all dental care should be completed before cancer
therapy is initiated, and if it is not feasible, priority treatments
should include eradicating acute infectious sources like
extraction of grossly decayed teeth, periodontal diseases, root
canal therapy for permanent teeth, and replacement of faulty
restorations to avoid oral tissue irritation .
The oral mucosa is highly susceptible to the effects of
chemotherapy and radiotherapy due high mitotic activity and is
the most frequently documented source of sepsis in the
immunosuppressed pediatric leukemic patients.
For these reasons, early and definitive dental intervention,
including comprehensive oral hygiene measures, reduces the
risk for oral and associated systemic complications
What to do….?????
59. 59
NR: no restrictions , R: with restrictions, EIHR: elective invasive and high risk
HI: need for evaluation, AP: antibiotic prophylaxis
60. 60
INTERVENTION PRE TRAN POST
NR: no restrictions , R: with restrictions, EIHR: elective invasive and high risk
HI: need for evaluation, AP: antibiotic prophylaxis
61. 61
The goal of treatment is to destroy signs of
leukemia in the body and make symptoms subside.
This is called a remission.
After people go into remission, more therapy may
be given to prevent a relapse i.e recurrence of the
disease.
Remission and relapse
62. First remission has not yet been obtained / relapse –
elective dental procedures deferred.
Preventive, restorative, and surgical treatments - no
complete remission yet and is undergoing chemotherapy.
A patient who has been in complete remission for at
least 2 years and no longer requires chemotherapy- may
be treated in an essentially normal manner..
62
63. Pulp therapy on primary teeth is contraindicated in any
patient with a history of leukemia.
Endodontic treatment for permanent teeth is not
recommended for any patient with leukemia who may
have a chronic, intermittent suppression of granulocytes.
63
64. Clinical significance of WBC count
ANC Significance
>1500 Normal
500-1000 At risk of infection
200-500 Medical care, risk of sepsis,
broad spectrum antibiotics
<200 Significant risk of sepsis
64
65. If the ANC is less than 1000/mm', elective dental treatment
should be deferred.
A leukemic patient with a low ANC may require prophylactic
broad-spectrum antibiotic therapy before certain dental
procedures.
The patient's physician should be consulted regarding the
appropriate drugs and dosages.
65
66. The primary objective of dental treatment in a child
with leukaemia:
Prevention, control, and eradication of Oral
inflammation and hemorrhage
Infection is the primary cause of death in
approximately 80% of children with leukemia. Bleeding
is the second most common cause
The use of a soft nylon toothbrush for the removal
of plaque is recommended even if the patient is
thrombocytopenic.
66
67. It is important that significant local irritants, including
orthodontic appliances, be removed.
Scaling and sub-gingival curettage should not necessarily
be perceived as elective dental treatment in all patients.
Patients with classic leukemic gingivitis experience varying
degrees of discomfort. The use of warm saline rinses several
times each day may assist in the relief of symptoms.
67
68. CONCLUSION
The key to success in maintaining a healthy oral cavity during
cancer therapy is patient compliance.
It is very much vital to educate the caretaker and child about the
importance of oral care to minimize discomfort and increase the
chances for a successful outcome of oncology treatment.
Discussion with caretakers and patient should include dietary
habits, the potential cariogenicity of pediatric medications and
nutritional supplements and late effects of the conditioning
regimen on the craniofacial growth and dental development.
The participation of a pediatric dentist in the
hematology/oncology team during treatment is of importance in
reducing the complications before, during and after leukemic
treatment in children.
68
69. Take away points
Increased leukocytic count
Genetical, environmental and infectious etiology
Most common type of cancer in children
Classified as acute, chronic, lymphoid, mylogenic.
Acute lymphoid leukaemia is most common in children
Gingival lesions like inflammation and bleeding are most
common oral manifestations
Investigations done are Complete blood picture, Bone
marrow aspiration, lumbar puncture.
Prevention, control, and eradication of Oral
inflammation and hemorrhage
Dental treatment should be deferred according to the
condition.
69
70. References:
Robbins & Cotran Pathologic Basis of Disease, 9th
Edition
Burket’s Oral Medicine, 11th Edition
Ralph.E.Mcdonald. Dentistry for child & adolscent,
8thedition.
Cameron & Widmer. Hand book of pediatric
dentistry,
Journal on Leukaemia, Nature Publishing Group,
Muller-Bérat Killmann
70
71. 71
Thank you
World cancer day: February 4th
World leukaemia month: september
People who suffered leukaemia:
Marie curie
B.F.Skinner
Robin bush
Rasika joshi