3. LEUKEMIA
• Leukemia are the neoplastic proliferation of
hemopoietic cells.
• Acute leukemias are defined as neoplsam
• AML - more than 20 % blast
• ALL- more than 25% blast.
4. ACUTE LYMPHOBLASTIC
LEUKEMIA
• Commonest form of malignancy in childhood.
• Peak incidence at 4 – 5 yrs of age.
• Acute onset with short history of duration.
• 85% are B cell , 15% are T cell.
6. MECHANISM OF LEUKAEMOGENESIS
• Activation of a proto-oncogene to an oncogene when it
is translocated to a transcriptionally active site
• Formation of a chimeric transcription factor
• Formation of a fusion protein with enhanced tyrosine
kinase activity
• Activation of FTL3 receptor
• Inactivation of tumour suppressor gene pathway
7. SYMPTOMS
• FEVER
• FATIGUE
• BONE /JOINTS PAIN
• WEIGHT LOSS
• PURPURA AND BLEEDING MANIFESTATION
• LYMPHADENOPATHY
• HEPATOSPLENOMEGALY
• STERNAL TENDERNESS
• MEDIASTENAL MASS
8. FAB CLASSIFICATION
• Based on morphology and cytochemistry.
•
stain AML ALL
MPO + -
SBB + -
NSE
(non-specific esterase)
+ IN M4, M5 AND M7 -
PAS FINE + IN M6 , M7 + , BLOCK
ACID PHOSPHATASE - +, T ALL
9. FAB CLASSIFICATION
ALL L1
ALL L2
ALL L3
In childhood – L1 is the most common type
In adults – L2 is the most common type
10. FAB classification
Morphology L1 L2 L3
1 Size of blast Small Large
heterogeneous
Large
homogenous
2 Cytoplasm Scanty Moderate Moderate,
intensely
basophilic
3 N/C Ratio High Lower Lower
4 Cytoplasmic vacuoles +/- +/- Prominent
5 Nuclear membrane Regular Irregular with clef
ting
Regular
6 Nucleoli Invisible /
indistinct
Prominent 1-2 Prominent 1-2
11. CRITICISM OF FAB CLASSIFICATION
1- It dose not include
• Immunophenotyping
• Cytogentics
• Molecular characteristics
2- immunological subtype of ALL
3-biphenotypic leukemia
4- Limited relevance to therapeutic or
prognostic implications.
12. WHO CLASSIFIACTION OF ALL (2008)
1-B lymphoblastic leukemia
2- B lymphoblastic leukemia
9; 22) , BCR ABL1
• t( v; 11q23) MLL rearangement
• t (12;21) ETV6-RUNX1
• With hypodiploidy
• With hyperdiploidy
• t (5;14) il3 –igh
• t ( 1;19) E2A-PBX1 (tcf3-pbx1)
3-T lymphoblastic leukemia/lymphoma
13. IMMUNOLOGICAL CLLASIFICATION
1- B ALL
•PRO B ALL
•EARLY PRE B ALL
•PRE B ALL
•MATURE B ALL
2- T ALL
3- MIXED LINEAGE ACUTE LEUKEMIA
4-Undifferentiated acute leukemia
15. T ALL
• PAS negative acid phosphatase positive
• CNS involvement and mediastenal mass
• CD3 ,2 and 7 positive
16. Scoring system for biphenotypic leukemia
B lineage T lineage Myeloid
CD 79a
CD 22.
CD 3 MPO
CD 10 CD 1 CD 13
TdT TdT, CD 7 CD 11b
CD 11c
17. Uncommon variants of ALL
• Small cell variant- blast cells are small and
may be mistaken for lymphocytes.
• Hand mirror variants- a subtype with
cytoplasmic protrusion .
• ALL with eosinophilia
• Granular cell ALL- The cells are large and
demonstrate azurophilic granulaes .
20. PERIPHERAL BLOOD EXAMINATION
• Total leucocyte count raised , normal or low.
• Normocytic normochromic anaemia.
• Thrombocytopenia.
21.
22. • Subleukemic leukemia-Total leukocyte count
is normal or low , but blast are seen in the
peripheral blood.
• Aleukemic leukemia- Blast are not seen in the
peripheral blood , but are demonstrable only
in bone marrow.
36. DIFFERENTIAL DIAGNOSIS
• Leukemic phase of Non Hodgkins Lymphoma
• Reactive lymphocytosis due to infections
• Metastatic tumours in bone marrow
• AML
37. ALL Vs AML
ALL AML
Age Mainly children Mainly adults
Lymphadenopathy Usually present Usually absent
Hepatosplenomegaly +ve mild +ve mild
Gum hypertrophy -ve +ve in M4/M5
Skin infiltration -ve +ve in M4/M5
CNS involvement +ve in some +ve in some
Granulocytic sarcoma -ve +ve in few cases
Mediastinal mass +ve in T-ALL -
Associated DIC -ve +ve in M3
Serum muramidase Normal In M4/M5 (monocytic type)
Prognosis Good Bad
38. MorphologyLymphoblast Myeloblast
Nuclear chromatin Coarse Fine
Nucleoli 1-2 3-5
N:C ratio High High
Auer rod -ve +ve
Accompanying
cells
Lymphocytes Myeloid precursor
Myelo peroxidase -ve +ve
Sudan Black B -ve +ve
PAS stain Block positivity -ve in blast
40. PROGNOSTIC FACTORS
Factor Good prognosis Bad prognosis
Race White Black
Age 2-8 yrs <1yr.,adult, >10 yrs
Sex Female Male
Meningeal involvement - +
Lymphadenopathy, liver,
spleen
- Massively enlarged
Mediastinal mass - +
TLC <20x109
/L >50 x109
/L
Type of ALL L1 L2,L3
Cytogenetics Hyperdiploidy >50
chromosomes
Pseudodiploidy, t (4;11),t (9;22), BCR-ABL
fusion m RNA, MLL-AF4 fusion mRNA.
Immuno-phenotype B-ALL,CD 10+, Early pre-B
cell
T-ALL in children
41. Minimal residual disease detection
– ALL – B cell
– Cd20/cd10/cd19/cd45
– Cd9/cd34/cd19/cd45
– Cd58/cd10/cd38/cd19
– Cd20/cd10/cd19/cd34
– ALL –T cell
– TdT/CD5/CD3/CD7