ACUTE LEUKEMIAS

Dr.sravani
 What is leukemias?

 What is acute leukemia?

 Acute because cells are immature(blasts)
 component present
 Acute leukemias chronic leukemias
- immature -Mature
haematopoietic cells haematopoietic cells
- progresses rapidly - indolent couse
with out treatment
 ACUTE LEUKEMIAS
 Acute myelogenous leukemias
 Acute lymphoid leukemias
 what is AML?
 neoplastic proliferation of haematopoietic
 precursor cells myeloid series causing
excessive myeloblasts & other immature
 myeloid cells.
 Neoplastic blasts have nml proliferation
rates but less maturation rates
 Malignant cells replace bonemarrow,may
 infiltrate spleeen,lymphnodes& circulate
 in blood.
 AML– 1)80% adult leukemias
 2)20% of childhood leukemias
 3)less nodal involvement than ALL.
 RISK FACTORS:
 most of the pts have no risk factors
 - Downs syndrome
 - Blooms syndrome
 - Fanconis anaemia
 - Neurofibromatosis
 - Benzene exposure
 - Radiation
 - Alkylating agents
 - topoisomerase II inhibitors
 Symptoms:
 1)anaemia – fatigue
 2)neutropenia – fever & infections
 3)thrombocytopenia – bleeding
 4)organ,skin & CNS infiltration- monoblastic
 & myelomonocytic
 leukemias
 Diagnostic approach to leukemias:
1) Initial Diagnosis basede on counts in
peripheral smear.
2)bonemarrow examination to confirm
diagnosis & obtain material for special
studies.
3)cytogenetics to classify AML & provide
prognostic information.
4)immunostains for poorly differentiated
leukemias.
 Peripheral smear:
 RBC : anisopoikilocytosis
 nucleated RBC
 WBC : neutropenia
 hyposegmented neutrophils.
 50% > 10,000 WBC
 20% > 1,00,000 WBC
 PLATELETS : thrombocytopenia
 large atypical blasts
 MYELOBLASTS : > 10% blasts
 Myeloblasts > 10% in peripheral smear
 morphology:-
 - larger than lymphoblasts
 - abudant cytoplasm
 - azurophilic granules & auer rods in
 APL.
 - delicate nuclear chromatin
 - prominent nucleoli(1-4)
 - dysplastic maturing myeloid cells
 Bone marrow examination:
 3 types of myeloblasts are found
 Type I: - no cytoplasmic granules
 - nucleus is large with delicate
 chromatin & prominent
 nucleolus.
 Type II: -15 to 20 cytoplasmic granules
 Type III: > 15 to 20 cytopladmic granules
 but otherwise has features of
 blast cell.
 Cytogenetics: 90% have cr abnormalities
 denovo leukemias- balanced
translocations.
 Therapy related or myelodysplastic
syndrome:
- deletions
-monosomy 5 or 7
- with out translocations
 Favourable cytogenetics:
 - inv (16)(p13,q22)
 - t (8,21)(q22,q22)
 Intermediate:
 - t(15,17)(q22,q12)
 -t(6,9)(p23,q24)
 -t(9,11)(p22,q23)
 Unfavourable:
 -del.5 & 7
 -t(11q,23),inv(3q),t(9,22),post chemo
 & radiotherapy
 Immunocytochemistry:
 positive stains : MPO
 sudan black B
 chloroacetate esterase
 (stains lysosomes in granulocytes)
 - variable for acid phosphatase.
 M4 / M5 : positive for nonspecific esterase
 (alpha naphthyl butyrate esterase)
 M5 / M6 / M7: positive for PAS.
 Alpha naphthyl acetate esterase(ANAE):
 - modified NSE.
 - stains Tcells & monocytic cells but not
 erythroid cells.
 Alpha naphthyl butyrate esterase:
 - NSE
 - stains monocytes & some T cells
 Chloroacetate esterase:
 -Specific esterase
 - naphthol AS – D chloroacetate esterase
 -LEDER STAIN,stains granulocytes & mast
cells but not agranulocytes.

 Immunohistochemistry
 Positive stains:
 Myeloid – CD13,CD14,CD15,CD33
 CD36,CD61&CD64.
 Lymphoid – Tdt

 B cell T cell
-HLA – DR -CD2
-CD10 -CD3
-CD19 -CD5
-CD22 -CD7
 DD:
 1)reactive process – growth factor RX
 causes ↑blasts.
 2)transient myeloproliferative disorder
 of newborn resembles
 AML – M7
 ALL
 Myelodysplastic syndrome
 AML CLASSIFICATION
 FAB – 1976 TO FAB WHO
2001(M0 –M7)
>30% 1)>20% blasts
 WHO – 2001
Blasts in 2)Myelodysplastic
bonemarro Category of
w/blood to refractory anaemia
diagnose With excess blasts
AML
3)AML with
recurrent genetic
abnormalities also
included
 AML with recurrent genetic abnormalities:
 AML with t(8,21)(q22,q22)
 AML with e inv(16)(p13,q22)/t(16,16)
(p13,q22)
 Acute promyelocytic leukemia
 AML with t(15,17)(q22,q12)(PML/RARα)
 AML with 11q 23 abnormalities
 AML with multilineage dysplasia
 AML & myelodysplastic syndrome,therapy
 related
 -alkylating agent related
 -topoisomerase ii inhibitor related
 Acute myeloid leukemia not otherwise
 categorised:
 -minimally differentiated(M0)
 -differentiation with out maturation(M1)
 -with maturation(M2)
 -Acute myelomonocytic leukemia(M4)
 -Acute monoblastic & monocytic (M5a&M5b)
 -Acute erythroid leukemia(M6)
 - Acute megakaryoblastic leukemia(M7)
 - Acute basophilic leukemia
 - Acute panmyelosis with myelofibrosis
 - myeloid sarcoma
 Acute leukemia of ambiguos lineage:
 -undifferentiated acute leukemias
 - bilineal acute leukemias
 -biphenotypic acute leukemias
 WBC with anaemia and thrombocytopenia,
organomegaly, lymphadenopathy and tissue
infiltration.
 Diagnosis:
 Monoblasts and promonocytes > 20% of
non erytroid cells.
 Myeloblasts and granulocytes constitute
<80% of
 If <20% of monocytes lineage cells in bone
morrow ,still M4 if blood monocytes count is
5000/mm3
 Myelocytic differentiation present.
 myelocytic series cells resembles M2 60%
 60% of myeloblasts have auer rods
 >20% of cells – monocytic differentiation
 Abundent pale gray –blue cytoplasm
 Prominent nucleolus
 Delicate folded nucleus
 Enzymes-chloroacetatae esterase stains
&neutrophils blue.
 Non specific esterase stains monocytes
red brown
 CD 68
 Lysozymes and peroxidase positive.
 Positive stains:
CD4,CD11,CD13,CD14,CD33,CD36,CD6
4,CD68,CD71,HCADR,lysozymes,variable
CD56,CD34,CD117.
 Negative stains:
 CD41,CD61,glycophorin A,keratin.
 Molecules :
 D/D-leukamoid reaction M2,M3,M5
&sarcomatoid ca.
 Acute monoblastic and acute monocytic
leukemia:
 High incident of bleeding disorders
including DIC
 Organomegaly lymphadenopthy ,gingival
hyperplasia- monocytes infiltration.
 May present with acute respiratory failure.
 Dignosis:> 80% of nonerythroid cells are
of monocytic series.
 Enzymes- NSE positive both monoblasts
granules & monocytes
 Negative for
 If NSE –ve ; confirm monocyte linage
immunostain.
 Positive
stains :CD11b,CD11c,CD13,CD33,CD64,
CD68,HLA-DR.
 Molecular 11q23 translocation&trisomy8.
 M5a M56
 Acute monoblastic acute monocytic
 Leukaemia leukaemia
 Children & young all ages affected
 Adults
 80% or more of mature monocytes
 Monocyte linase promonocytes
 Cells are blasts predominate in PB.
 <80% of monocyte
 linase cells mostly
 <20% are blasts.
 Monoblsts: large with promonocytes: less
 Abundant cytoplasm basophilc cytoplasm
 Containing numerous & more azurophilic
 Fine azuropilic granules