pediatric leukemia

1.  m/c childhood malignancy
 31 % of all cancer in children <15 Yr of age
 Incidence 4.5 cases per 100,000 children
Dr Chandan Barnwal MD
(Pediatrics)

2.  Define and classify leukemia
 Understand the etio-pathogenesis and it`s
Clinical manifestations
 Able to list down the laboratory
investigations required for diagnosis
 Understand the basic management of
leukemia
Dr Chandan Barnwal MD
(Pediatrics)

3. Group of malignant disease
in which
genetic abnormalities in a hematopoietic cell
give rise to an
unregulated & clonal proliferations of cells.
Dr Chandan Barnwal MD
(Pediatrics)

4. Dr Chandan Barnwal MD
(Pediatrics)

5. Dr Chandan Barnwal MD
(Pediatrics)

6. 1. ALL:- m/c i.e. 77% of all childhood leukemia
:- 2 types:- B-ALL & T-ALL
2. AML:- 11%
3. CML:- 2-3%
4. JMML:-1-2%
Sales
ALL
AML
CML
JMML
Dr Chandan Barnwal MD
(Pediatrics)

7.  Etiology remains unclear in majority of cases
 Most cases are d/t post conceptional somatic
mutations
 Pathogenesis:-
Genetic aberrations (mostly acquired)
Translocation / Inversion
Disrupt genes encoding for factors needed
for
Normal differentiation of Hematopoietic
cell
Dr Chandan Barnwal MD
(Pediatrics)

8. Continue…
e.g.
t(8;21) or and i(6)
Chimeric gene
New protein
Block in differentiation
Proliferation of undifferentiated
blast
BUT
Replication rate is slower than
normal blast
Dr Chandan Barnwal MD
(Pediatrics)

9. Dr Chandan Barnwal MD
(Pediatrics)

10. 1. Genetic:-
Down syndrome,
Bloom syndrome,
Klinefelter syndrome,
kostman syndrome,
Fancony anemia,
Ataxia-telangiectasia,
Neurofibromatosis
Dr Chandan Barnwal MD
(Pediatrics)

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2. Environmental:-
a> Radiation,
b> Benzene,
c> Alkylating agents:- cyclophosphamide,
carboplatin, procarbazine,
d> Epipodophyllotoxins- etoposide,
tenoposide
e> Nitrosourea
Dr Chandan Barnwal MD
(Pediatrics)

12.  1st disseminated cancer shown to be curable
 epidemiology:-
 Incidence:- 2400 per year in children <15
years
 peak age b/w 2-3 YOL
 Male > female
Dr Chandan Barnwal MD
(Pediatrics)

13. 1. FAB classification
2. WHO classification:-
based on immuno-phenotype
now most acceptable classification
Dr Chandan Barnwal MD
(Pediatrics)

14. ALL- L1, ALL-L2, ALL-L3
ALL-L1:-
1. m/c i.e. 80-85%
2. Small cell with scanty cytoplasm
3. Small and inconspicous nucleoi
4. Variable cytoplasmic vacuolation
5. Variable basophilic cytoplasm
Dr Chandan Barnwal MD
(Pediatrics)

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 ALL-L2:-
1. Large cell with variable cytoplasm
2. One or more nucleoli
3. Variable basophilic cytoplasm
4. Variable cytoplasmic vacoulation
Dr Chandan Barnwal MD
(Pediatrics)

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 ALL-L3:-
1. Large cell with moderately abundant
cytoplasm
2. One or more and often prominent nucleoli
3. Prominent cytoplasmic vacuolation
4. Intense basophilic cytoplasm
Dr Chandan Barnwal MD
(Pediatrics)

17.  Precursor B-cell, T-cell, Mature B-cell
Precursor B- cell:-
1. m/c i.e. 80-85 %
2. CD10, CD19, CD20, CD18, CD79a, HLA-DR
are positive
3. CD10 is k/a common ALL antigen
4. if CD10 positive:-favourable prognosis
Dr Chandan Barnwal MD
(Pediatrics)

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T cell ALL:-
1. 15 %
2. CD3, CD7, CD2 or CD5 are positive
3. mainly in older age children
4. a/w mediastinal mass, CNS involvement
Dr Chandan Barnwal MD
(Pediatrics)

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 Mature B cell- ALL
1. 1-2%
2. CD19, CD20, CD21 & sIg are positive
3. Correlates with L3 leukemia
4. needs intensified regimens
Dr Chandan Barnwal MD
(Pediatrics)

20.  Initially non-specific:-
Anorexia
Fatigue
Malaise
Irritability
Low grade fever
Dr Chandan Barnwal MD
(Pediatrics)

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 As disease progresses
1. Signs & symptoms of B/M failure:-
Pallor
Fatigue
Exercise intolerance
Bruising, Epistaxis
Fever- may be caused by secondary infection
Bone pain but tenderness may not be elicited
Dr Chandan Barnwal MD
(Pediatrics)

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2. Signs of organ infiltration:-
a> Hepato-splenomegaly
b> Lymphadenopathy
c> CNS involvement-
Cranial neuropathies,
Headache,
Seizure,
Papilloedema
Retinal hemorrhage
,
Dr Chandan Barnwal MD
(Pediatrics)

23. d> Respiratory distress:-
d/t anemia or airway compression
by
ant mediastinal mass e.g.
Thymus
Mediastinal LN
Dr Chandan Barnwal MD
(Pediatrics)

24.  11 % of all childhood leukemia
 More in adolescence
 36 % in 15-19 years old
 Incidence of all types of AML are uniform
except
Acute Pro-Myelocytic leukemia is more
common in some regions
Dr Chandan Barnwal MD
(Pediatrics)

25. Cellular classification:-
 > 25 % blast cell in B/M
with
Early differentiation states of the
myeloid-monocyte-megakaryocyte series of
blood cells
 WHO classification:-
Recent classification system
Consider morphology,
chromosome
abnormalities,
gene mutations
Dr Chandan Barnwal MD
(Pediatrics)

26.  WHO classification:-
1. AML with recurrent genetic abnormalities:-
a> Good prognosis:- t(2;21), t(15;17), i(10)
b> Bad prognosis:- t(6;9), d(11q23)
2. AML with myelodysplasia related changes:-
Bad prognosis
3. AML not otherwise specified:-
Dr Chandan Barnwal MD
(Pediatrics)

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4. Therapy related myeloid neoplasm:-
Bad prognosis
5. Myeloid sarcoma:-
Bad prognosis
6. Myeloid proliferations related to Down
syndrome:-
Good prognosis
7. Blastic plasmacytoid dendritic cell
neoplasm:-
Dr Chandan Barnwal MD
(Pediatrics)

28.  FAB classification:-
 M0:- Undifferentiated AML
 M1:- AML with minimal differentiation
 M2:- AML with maturation
m/c
t(8;21)
good prognosis
 M3:- Acute Promyelocytic Leukemia
t(15;17)
good prognosis
Faggets- bundle of Aeur rod
Dr Chandan Barnwal MD
(Pediatrics)

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 M4:- Acute Myelomonocytic Leukemia
2nd m/c
inversion of chromosome 16
good prognosis
 M5:- Acute Monoblastic Leukemia
t(9;11)
 M6:- Acute Erythroblastic Leukemia
 M7:- Acute Megakaryoblastic Leukemia
a/w Down syndrome
Dr Chandan Barnwal MD
(Pediatrics)

30.  C/F of AML:-
Signs & symptoms of B/M failure similar to ALL
+
1. Blueberry muffin:-
 Bluish-Purplish subcutaneous nodule
 specially AML-M4, M5
Dr Chandan Barnwal MD
(Pediatrics)

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2. DIC:-
 Specially Acute Promyelocytic leukemia
3. Chloroma:-
 Extramedullary manifestations of AML
 Diagnosed by Tissue biopsy
 k/a Granulocytic sarcoma
Dr Chandan Barnwal MD
(Pediatrics)

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4. Higher incidence of infection
5. Lymphadenopathy & Hepatosplenomegaly is
not common
6. More CNS infiltration:-
mostly in M4 & M5
Dr Chandan Barnwal MD
(Pediatrics)

33.  2-3 % of childhood leukemia
 Philadelphia chromosome is charasteristic
 C/F:-
 Non-specific:-
fever,
fatigue,
weight loss,
Anorexia
spleenomegaly:- pain abdomen
Dr Chandan Barnwal MD
(Pediatrics)

34. Cotinue…
 Initial Chronic phase (Blast<10%) of 3-4 years
 Followed by Accelerated phase (Blast 10-19%)
 Followed by Blast crisis phase (Blast >20%)
 C/F of Blast phase = AML,
 rapidly involves CNS in Blast phase
Dr Chandan Barnwal MD
(Pediatrics)

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 Investigations:-
 Leucocytosis with Myeloid cell
at
all stage of differentiation
 Mild anemia
 Thrombocytosis
 Diagnosis confirmed by Philadelphia
chromosome
Dr Chandan Barnwal MD
(Pediatrics)

36.  Treatment:-
 Imatinib:-
Inhibits BCR-ABL tyrosine kinase
Respone in >70% patient of adult
Safety and efficacy = adults
 Dasatinib:-
2nd gen of Imatinib
Better response
 Hydroxyurea:-
If life threatening C/F
Make leucocyte count normal
 HSCT
Dr Chandan Barnwal MD
(Pediatrics)

37.  Formerly k/a Juvenile CML
 Philadelphia chromosome is absent
 Child <2 years of age
 Mutation in RAS oncogene pathway
 Risk factors:-
NF-1,
Noonan syndrome
Dr Chandan Barnwal MD
(Pediatrics)

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 C/F:-
 Rashes
 Lymphadenopathy
 Spleenomegaly
 Hemorrhagic manifestations
Dr Chandan Barnwal MD
(Pediatrics)

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 Investigations:-
 Leucocytosis with Monocytosis
 Anemia
 Thrombocytopenia
 Erythroblast on PBS
 Blast <20% on B/M
Dr Chandan Barnwal MD
(Pediatrics)

40.  2% of childhood leukemia
 ALL>AML (2:1 Ratio)
 Leukemic clones:- +nt in cord blood at birth
 MLL gene rearrangement- t(4;11)
Dr Chandan Barnwal MD
(Pediatrics)

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Features:-
Hyper-leucocytosis
Extensive tissue infiltration:-
Hepato-spleenomegaly,
Leukemia cutis,
CNS Involvement
CD10 (-ve) --------cf------ ALL
Dr Chandan Barnwal MD
(Pediatrics)

42. Management:-
Very intensive chemotherapy
HSCT
Dr Chandan Barnwal MD
(Pediatrics)

43.  15-20 times increased risk
 Risk of ALL & AML = General population BUT
for first 3 years of life- AML > ALL
 Prognosis:-
ALL:- inferior to general population
AML:- better than general population
 Methotrexate is very effective
Dr Chandan Barnwal MD
(Pediatrics)

44.  Transient leukemia
 Usually resolve within 1st 3 month of life
 10% of newborn with Down syndrome
 Features:-
 Leucocytosis
 Anemia & Thrombocytopenia
 Blast cell at PBS
 Hepato-Spleenomegaly
Dr Chandan Barnwal MD
(Pediatrics)

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 Management:-
 Temporary Blood Transfusion
 No chemotherapy unless life threatening
events
 Close follow up
 20-30% develop acute leukemia by 3 years
of life
Dr Chandan Barnwal MD
(Pediatrics)