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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.

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