Acute leukemia

Acute myeloblastic
leukemia
Malignant tu of hematopoietic
precursor cell of non lymphoid
lineage. It is arising from the bone
marrow
Incidence : commonest acute
leukemia in adults that is 3/100.000

AML
Aetiology: unclear association with
pre existing myelodiplasia or
privious chemotherapy
radiation therapy
Benzene exposure
Down sy

AML

Diagnosis:
Analysis of peripheral blood film
Bone marrow=>20% blasts
Cytochemical stain
Immunological marker
Cytogenetic analysis
Molecular markers
All these are necessary to differentiate
AML from ALL

AML
Morphological classification
French-American-British system is based on
the degree of differentiation is a
morphological classification
Cytochemistry is based on
Sudan black stain
Myeloperoxidase stain
These stains are positive in AML and negative ALL
Non specific esterase is positive monocytic
subtype

AML
WHO classification correlates
morphological genetic and clinical
feature
In this classification the blast
threshold for the diagnosis AML is
>/=20% blasts

AML

The WHO classification of myloid keukemia

AML with recurrent genetic abnormalities
AML with multilineage displasia
AML with myelodysplasic sy therapy
related after alkylating agent and
topoiasomerase inhibitor
AML not otherwise categorized=FAB
classification M0 to M7, acute basophilic
leukemia

AML
Immunophenotyping monoclonal antibody to
cell surface antigen differentiate AML from ALL
Lineage infidelity: in some situation the
expression of markers of more than one cellular
lineage
Biphenotypic leukemia
Cytogenetic analysis should be always
performed, there are 3 groups
Favourable reisk
Intermediate risk
Poor risk

AML
Molecular analysis fluorescence in
situ hybridisation FISH and reverse
transcriptase chain reaction RT
PCR , add sensitivity and precision
the detection of translocation
deletions and aneoplodity in case
when cytogeenetics fails or gives
normal results

AML
Clinical features
Acute presentation is usual often
critically ill due to bone marrow
failure
Symptoms of anemia: weakness ,
letargy, breathlessness
lightheadedness and palpitation
Infections: chest, mouth, perianal,
skin staphylococcus, Pseudomonas,
Candida

AML
Clinical features 2 :
Hemorrhage: purpura, menorrhagia, epistaxis,
bleeding gums rectal retina
Gum hipertrophy and skin infiltration
Signs of leukostasis: hypoxia, retinal
hemorrhage, confusion , pulmonary shadowing
Hepatomegaly 20%, splenomegaly 24% of the
cases If splenomegaly is present then is can be
a transformed chronic myeloid leukemia
Limphadenomegaly
CNS involvement is rare

AML

Investigation and diagnosis

FISH and blood film
Bone marrow aspirate and biopsy
Bone marrow cytogenetics
Immunophenotyping of bone marrow
blasts or blood blasts
Total WBC usually increased with blasts
on blood film but WBC may be low
HB, neurophils and platelets low

AML
Emergency treatment seek expert help
immediately
Intensive cardiovascular and respiratory
resuscitation may be needed if septic shock or
hemorrhage is present
Immediate empiric broad spectrum antibiotic
treatment for neuropenic sepsis
Leucopheresis if peripheral blast count is high or
signs of leucostasis as retinal hemorrhage or
reduces conscious level or hypoxia, or pulmonary
shadowing is present
Intensive hydratrion with alkalinisation of the urine
to prevent tumor lysis syndrome

AML
Supportive treatment
Good communication with patient
and family
Transfusion platelet and RBC
Neutropenic treatment
Hydration Allopurinol for preventing
hypercalcemia
Central venous catheter

AML
Specific treatment
Initial aim of treatment is to eliminate the
leukemic cells and achieve haematological
complete remission defined as normal BM
cells with blast cells < 5% and normal
representation triline haematopoesis,
normalisation of peripheral blood count ,
neurophils >= 1.5 109/L and platelets
>=1oo/109/L Bh.=10g/L

AML
Leukemia is not detected by
conventional morphological methods
but may be demonstrated by more
sensitive molecular technique
CR is not synonymous with cure

AML
Treatment has 3 phases
Remission induction-usually 1-2 courses of
combination CT
Consolidation therapy- to reduce leukemia
burden further and reduce the risk of
relapse
Optimum no of cycles 2-4 with autologus or
allogenic sstem cell transplantation
Maintenance therapy only when intensive
consolidation can not be tolerated

AML
Prognosis
70-80% of pts aged < 60 will achieve
CR
Relapse risk of pts , 60 with
favourable risk cytogentics is 2942%, with intermmediate risk group
39-60%, poor risk group 68-90%
If age group is >60 CR is achieved in
30-60% but relapse occur 80-90%

AML
Prognosis
Age group <60
Leucocytic count at the presentation
<25x109/L is favourablre but when
>100x109/L is unfavourable
History od previous mielodisplasia
some FAB subtype has favourable
prognosis