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Diagnosis and classificationof acute leukaemia
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The acute leukemias are a heterogeneous group ofneoplasms arising from transformation ofuncommitted or partially committedhematopoietic stem cells
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DIAGNOSTIC EVALUATION
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Morphologychromatin (fine in myeloblasts, often clumped in
lymphoblasts),
nucleoli (distinct in myeloblasts, variable in
lymphoblasts),cytoplasm (moderate or abundant, often with
granules in myeloblasts; scant to moderate,granules uncommon in lymphoblasts)
The granules of standard APL are large andreddish violet; in the microgranular variant ofAPL, they are indistinct
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Auer rods,
The appearance of more differentiated myeloidcells in the marrow may provide a clue to myeloid
lineageErythroid and maturing myeloid precursors may
be megaloblastoid in AML, but normal in ALL.
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Cytochemistry
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myeloperoxidase (MPO)
Sudan black B (SBB)
nonspecific esterase (NSE)
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Immunophenotyping
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Panel of monoclonal
antibodies to differentiateAML & ALL
Myeloid Anti-MPO; CD13; CD33; CDw65; CD117B lymphoid CD19; cytoplasmic CD22; CD79a;
CD10
T lym phoid Cytoplasmic CD3; CD2; CD7
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Immunophenotypic patternsin AML subtypes
Undifferentiated (M0) Anti-MPO; CD13;CD33; CD34; CDw65; CD117; negativecytochemistry; lymphoid markers
Myelomon ocytic (M1-M5): anti-MPO; CD13;CD33; CDw65; CD117
Monocytic (M4 & M5) Stronger expression ofCD11b & CD14
Erythroid (M6) Anti-glycophorin AMegakaryocytic (M7) CD41; CD61
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Cytogenetic analysis
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patients with AML can be assigned to three broad
prognostic groups and their treatment can bemodified accordingly;
specific categories of AML requiring very specifictherapeutic strategies can be identified(particularly M3 and M3 variant);
it facilitates the recognition of therapy-relatedacute leukaemia and the distinction betweenalkylating agent-related and topoisomerase II-interactive drug-related leukaemia.
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Favourable r isk
cytogeneticst(8;21)(q22;q22): FAB M2; 58% adults
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Interm ediate r iskcytogeneticsNormal karyotype: any FAB type; 1520% adults.
+ 8: any FAB type; 10% adults.
abnormal 11q23: >50% infant AML cases; 57%
adults; fusion gene MLL.Others: del(9q); del(7q); +6; +21; +22; Y and 3
5 complex abnormalities plus other structural ornumerical defects not included in the good risk or
poor risk groups
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Poor r isk cytogenetics 5/del(5q): any FAB type; >10% adults >45years.
7/del(7q): any FAB type; >10% adults >45years.
Complex karyotypes (>5 abnormalities)Others: t(6;9)(p23;q34); t(3;3)(q21;q96); 20q;
21q; t(9;22); abn 17p.
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Molecular genetic analysis
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PMLRARA fusion in AML
Use of all-trans-retinoic acid and possibly arsenic
trioxide; good prognosis so overtreatment shouldbe avoided
AML1ETO fusion in AML
Good prognosis, overtreatment should be avoided
High hyperdiploidy in ALL
Good prognosis, overtreatment should be avoided
BCRABL fusion in AML, ALL
Poor prognosis in AML and ALL, intensivetreatment may be justified and
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FRENCH/AMERICAN/BRITISH DESCRIPTIONS
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Acute Lym phoblasticLeukemiaL1
L2
L3
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Acute Myeloid Leukem iaM0AML with minimal differentiation
M1AML without maturation
M2 AML with maturation
M3 Acute promyelocytic leukaemiaM4 Acute myelomonocytic leukaemia
M5a M5b Acute monoblastic/monocytic leukaemia
M6 Acute erythroleukaemia
M7 Acute megakaryoblastic leukaemia
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W HO CLASSIFICATION
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WHO criteria for the diagnosis ofacute myeloid leukaemiaBlast cells are 20% or more in either peripheral
blood or bone marrow
Presence of
t(8;21)(q22;q22) or AML1ETO fusion gene inv(16)(p13q22) or t(16;16)(p13;q22) or CBFB
MYH11 fusion gene
t(15;17)(q22;q12) and variants or PMLRARA
fusion gene or variantsTranslocation with an 11q23 breakpoint and MLL
gene rearrangement
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The AML classification includesfour groups:
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ACUTE M YELOID LEUKEM IA WITHRECURRENT CYTOGENETIC
ABNORMALITIESrecurring balanced translocations and
inversions;;
lack multilineage background dysplasia;
tend to respond favorably to cytotoxicchemotherapy;
unrelated pathogenetically to MDS
They comprise approximately 85% of AML in
young patients but only a small percent of cases inthe elderly.
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ACUTE MY ELOID LEUK EMIA WITH MULTILINEAGE DYSPLASIA
cytogenetic abnormalities shared with MDS;
an exponentially increasing incidence withadvancing age (similar to MDS), with median agein the 70s;
tend to have multilineage background dysplasia;
clonal background and remission hematopoiesis;
respond poorly to cytotoxic chemotherapy,
related pathogenetically to MDS
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ACUTE MYELOID LEUKEMIA,THERAPY RELATED
Alkylating agentrelated AML.Peak incidence isapproximately 5 years after exposure. It is oftenpreceded by MDS.
Topoisomerase II inhibitorrelated AML.
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ACUTE MYELOID LEUKEMIA NOTOTHERW ISE CATEGORIZED
Acute basophilic leukemia
Acute panmyelosis with myelofibrosis
Myeloid sarcoma
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Acute Lym phoblasticLeukemiaPRECURSOR B-LYMPHOBLASTIC
PRECURSOR T-LYMPHOBLASTIC
BURKITT LYMPHOMA/LEUKEMIA
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Acute Leukemia of Ambiguous
Lineage
cases with apparent differentiation to more thanone lineage, usually T/myeloid or B/myeloid(biphenotypic acute leukemia),
cases with no discernible further differentiation beyond hematopoietic stem cells using currenttechniques (undifferentiated acute leukemia) .
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Conclusion
The diagnosis and further classification of acuteleukaemia requires:
1. a full assessment of the medical history, familyhistory and physical findings,
2. assessment of cytological features in blood andbone marrow
3. cytochemistry is selective
4. Application of immunophenotyping can be
selective but is tending to become universal5. cytogenetic analysis should be universally
applied, with molecular analysis being usedselectively.