ALL by tara

2. ACUTE
LYMPHOBLASTIC
LEUKEMIA

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.

5. PREDISPOSING FACTORS
• HEREDITARY
• ACQUIRED
• Ionizing radiations
• Therapeutic radiations
• Nuclear fallout
• Diagnostic Xrays
• Chemical agents
• Viruses

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

14. IMMUNOLOGICAL CLLASIFICATION
SUBTYPE HLA DR TdT CD 10 cIg smIg
Pro B ALL +_ + - - -
COMMON ALL + + + - -
Pre BALL + - - + -
Mature B ALL - - - - +

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 .

18. Hand mirror variants

19. DIAGNOSIS OF ACUTE LEUKEMIA
• Peripheral Blood smear
• Bone marrow aspiration smear
• Cytochemistry
• Immunophenotyping
• Cytogenetic analysis
• Molecular genetic analysis

20. PERIPHERAL BLOOD EXAMINATION
• Total leucocyte count raised , normal or low.
• Normocytic normochromic anaemia.
• Thrombocytopenia.

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.

23. BONE MARROW EXAMINATION
• Hypercellular
• Normal hematopoietic elements diminished

24. ALL L1
Size – small.
Cytoplasm scanty basophilic.
N/C Ratio – high.
Nuclear membrane – regular.
Nucleoli – invisible or indistinct.

25. BONE MARROW SMEAR
BLAST

26. ALL L2
 Size of blast – large & heterogenous
 Cytoplasm – moderate
 N/C Ratio – lower
 Cytoplasmic vacuoles – variable
 Nuclear membrane – irregular with clefting
 Nucleoli – prominent ,1-2

27. BONE MARROW SMEAR

28. ALL L3
 Size of blast – large & homogenous
 Cytoplasm – moderate & intensely basophilic
 N/C Ratio – lower
 Cytoplasmic vacuoles – prominent
 Nuclear membrane – regular
 Nucleoli – prominent , 1-2

29. BONE MARROW SMEAR
LYMPHOBLAST WITH CYTOPLASMIC VACUOLES &
NUCLEOLI

30. STARRY SKY PATTERN

31. PAS STAIN
LYMPHOBLAST WITH BLOCK & COARSE GRANULAR STAINING

32. STAINS
METHYL GREEN PYRONINE OIL RED
O(VACUOLES)

33. IMMUNOPHENOTYPING
• Diagnosis and classification.
• Assessment of prognosis.
• Monitoring of minimum residual disease.

34. Molecular Genetics-
• Establishment of lineage-DNA analysis.
• Identification of translocation.
• Detection of relapse.
• Detection of minimum residual disease.

35. OTHER INVESTIGATIONS
• Lumbar puncture.
• Testicular biopsy.
• X-Ray chest.

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

39. AML ALL

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

42. • AML
• CD34/CD33/HLA-DR/CD45
• CD34/CD117/CD33/CD45
• CD115/CD117/CD33/CD34
• HLA-DR/CD117/CD33/CD34
• CLL
• CD20/CD79a/CD19/CD5

43. Factors Predisposing to Childhood
Leukemia
• GENETIC CONDITIONS
Down syndrome
• Fanconi syndrome
• Bloom syndrome
• Diamond-Blackfan
anemia
• Schwachman syndrome
• Klinefelter syndrome
• Turner syndrome
• Neurofibromatosis
• Ataxia-telangiectasia
• Severe combined
immune deficiency
• Paroxysmal nocturnal
hemoglobinuria
• Li-Fraumeni syndrome

44. • ENVIRONMENTAL FACTORS
• Ionizing radiation
• Drugs
• Alkylating agents
• Nitrosourea
• Epipodophyllotoxin
• Benzene exposure
• Advanced maternal age