leukemia

1. ACUTE LYMPHOBLASTIC LEUKEMIA

2. INTRODUCTION
 Leukaemia are the neoplastic proliferation of
hemopoietic cells
 Divided into 2 broad categories depending
upon cell lineage-
MYELOID
LEUKAEMIA
LYMPHOID
LEUKAEMIA

3. Nuclear chromatin Coarse Fine
Nucleoli 1-2 3-5
N:C ratio
Auer rod
High
-ve
High
+ve
Accompanying
cells
Lymphocytes Myeloid precursor
Myelo peroxidase -ve +ve
Sudan Black B -ve +ve
PAS stain Block positivity -ve in blast

4. AML: the myeloblast is
a large blast with a
moderate amount of
granular cytoplasm, fine
lacy chromatin &
prominent nucleoli. Auer
rods may be seen
ALL: the
lymphoblast is a
small blast with scant
cytoplasm, dense
chromatin, indistinct
nucleoli, and no Auer
rods or granules.

5.  ALL are neoplasm composed of immature B
(pre-B) or T (pre-T) cells
 ALL is primarily a disease of children, 75% of
cases occurunder 6 yr.
 B Cell (75-80%) orT Cell (15-20%)
 B-ALL peak at 3yr while T-ALL
adolescence
 Slight Male predominance is seen
peak at

6.  Byconvention, the minimum numberof bone marrow
lymphoblasts required fordiagnosis is setat 20 %
 In children - ALL the mostcommon malignant
disease.

7. ETIOLOGY
 Geneticabnormality
 Down syndrome
 Radiation exposure
 Industrial exposure tochemicals(benzene)

8. PATHOGENESIS
 Apprx 90% of ALLs have numerical or structural
chromosomal changes
 Most Common is hyperploidy, but hypoploidy & variety
of balanced translocation also seen
 These chromosomal aberrations dysregulate the expression
& function of transcription factors that are required for
normal B & T cell development.
 These mutations disturb the differentiation of lymphoid
precursors & promote maturation arrest.

9. Clinical Presentation
 Abrupt onset
 Nonspecific Symptoms
 Fatigue
 pallor
 Easy bruising
 Bleeding
 fever
 Dyspnoea
 Dizziness
 weight loss
 Joint, extremity
pains
 CNS involvement
 Lymphadenopathy
 Splenomegaly
 Hepatomegaly
 Gonadal mass
 Mediastinal mass

10. INVESTIGATION
1. Peripheral blood smear
2. Bone marrow examination
3. Cytochemistry
4. Immunohistochemistry
5. Other : testicularBx, CSF examination, chestX-ray

11. PBS EXAMINATION
 Normocytic normochromicanaemia
 TLC : usually increased
 Lymphoblasts
 Granulocytopenia
 Thrombocytopenia

12. ALL : PERIPHERAL BLOOD SMEAR

13.  The blast havevaried appearance from a homogenous
population of small cells with a round to slightly
irregular nucleus, condensed chromatin &
inconspicuous nucleoli to large cells with irregular,
clefted or indented nuclei, variably distributed
chromatin & one or more distinct nucleoli.
 Cytoplasm is scant to moderate & slight basophilic to
deeply basophilic as cell size increase
 Compared with B- lymphoblast, T-lymphoblast
show greater nuclear convulation & significant
nuclear hyperchromasia.

14. ALL (BMA) : lymphoblastwith condensed nuclear
chromatin ,small nucleoli & scant agranularcytoplasm

15. MARKER FOR THE Dx OF ALL
LINEAGE ANTIGEN
Precursor-B ALL CD19, CD10, CD79a, TdT, cCD22,
HLA-DR, cCD79a
Precursor-T ALL CD1, CD2, CD3, CD4, CD5, CD7
CD8, TdT, cCD3

16. OTHER INVESTIGATIONS:
 CSF examination for lymphoblast
 Testicular biopsy-to ruleout residual disease
 ChestX-ray

17. CLASSIFICATION
 FAB classification
 Immunologicclassification
 WHO classification

18. FAB CLASSIFICATION
BASED ON MORPHOLOGY
Blasts Morphology
Subtype Occ (%)
L1
Small round blasts, scant cytoplasm,round
nucleus, homogenous chromatin &
indistinct nucleolus
75%
L2
Pleomorphic larger blasts, moderate
amount of cytoplasm,irregular nuclei, fine
chromatin one or more often large distinct
nucleoli.
20%
L3
Large blasts, moderate amount of
basophilic vacuolated cytoplasm, round to
oval nucleus with stippled chromatin & one
or more, distinct nucleoli.
05%
28

19. Fig. 6.2 Bone marrow (BM)
aspirate, F
AB Ll ALL,showing a
uniform population of s1nall and
mediWll-sized blasts with a high
nucleocytoplasmic ratio. May
Griinwald-Giemsa (MGG) XlOO.

20. Fig. 6.3 BM aspirate, F
AB L2ALL,
showing large pleomorphic blasts.
MGG xlOO.

21. Bone marrow aspirate smear showing ALL-L3 blast with large
nucleus, basophilic cytoplasm with prominent vacuolization
(Burkitt type)

22. WHO Classification
 B-Lymphoblastic leukaemia, NOS
 B-Lymphoblastic leukaemiawith recurrentgenetic
abnormalities
 T-Lymphoblastic leukaemia

23. WHO Classification
B-Lymphoblastic
leukaemia, NOS
B-Lymphoblastic
leukaemiawith
recurrentgenetic
abnormalities
T-
Lymphoblastic
leukaemia
B-Lymphoblastic leukaemiawith t(9:22) (q34;q11.2); BCR-ABL 1
B-Lymphoblastic leukaemiawith t(v:11q23);MLL rearranged
B-Lymphoblastic leukaemiawith t(12;21) (p13;q22); TEL-AML1 (ETV6-
RUNX 1)
B-Lymphoblastic leukaemiawith hyperdiploidy
B-Lymphoblastic leukaemiawith hypodiploidy
B-Lymphoblastic leukaemiawith t(5:14) (q31;q32);IL3-IGH
B-Lymphoblastic leukaemiawith t(1:19); E2A-PBX 1 (TCF3-PBX 1)

24. THANK YOU