Soebandiri

Dept of Medicine, Division of Hematology

Airlangga University School of Medicine
Surabaya

Early Studies
Peripheral Blood : white cells are all nucleated
cells in the peripheral blood
Prevalent disorder of it is the malignant growth
called leukemias
Later on : the RBC and platelet precursors in the
bone marrow are also nucleated those are also
called leukemia with prefix erythrocytic and
megakaryocytic

Lecocyte count : 4-10 x 106 cells/L or 400010000/cmm

Proportion in the blood smear (%) Eo (0-1), Baso
(0-1) stab (5-8) segmented cells (40-80), lympho
(10-30), Mono (5-10)

Initially :
I. Accarding the speed of growth :
Rapid Acute Leukemia
Slow Chronic leukemia
II.

According the cell type growing :

Lymphatic Leukemia
Granulocytic (Myeloid) Leukemia
Monocytic Leukemia, etc

With the progress of Immunology, cytogenetics and

molecular biology, :

Immunologic classification
Cytogenetic Classification
Molecular Classification, etc

Syn. = Chronc Myelocytic Leukemia

= Chronic Granulocytic Leukemia (CGL)
Definition :
CML is malignant growth of hemopoetic stem cell,
which g slowly proggressive (month) which is
caused by
Translocation between gene in the chromosome 9
and gene in the chromosome 22, ma a small
fuzion of chromosomeal parts called Philadelphia
(Ph) cromosome, which consequently forming a
fusion gene called Bcr-abl fusion gene

Complaints
: Infrequent in the early phase.
- after 6-7 month : slight anemia;
mass in the abdomen
Physical exam : + slight anemia (Hb + 6 g%),
splenomegaly +++
Lab exam blood : Hb + 6 g% or increased; thrombo
N/ up to 2 million/cmm. Leuco up to one
million/cmm
Blood smear : many young granulocyte (myelocyte,
metamyelocytes) more mature stab + segmented
cells are also abundant-blast present only slightly
(<5%) in the early chronic phase

CML: Blood Smear (polymorph)

AML: Blood Smear (monotonous)

Early chronic phase (CP)

2. Accelerated phase (AP)
3. Blastic Crisis (BC)
In the AP phase :

Thrombocyte gradually

Blast cells gradually up to 20-30%

Resistance to original therapy

In the BC :
Blast > 30%; thrombopenia with bleeding; fever.
Acute leukemia manifestations
1.

In CP :
Busulfan hydroxyurea interferon imatinib,
etc (molecular targeted therapy)

Preferably by hematologist

Evaluation for remission :

Clinical
Hematological
Cytogenetical
Molecular

CM
L
Essential
Thrombocytopen
ic
(ET)

Myelofibros
is

PV

CML, PV, ET and MF may transform to each other,

therefore they are called Myeloprolioferative group
of disease

Can live long especially in the CP phase >10 year

Cause of death :
BC with sepsis and ICH

Definition : AML is abnormal proliferation and

apoptosis affecting young myeloid (granulocytic)
early progenitors with a rapid course with
thrombopenia bleeding , severe anemia and
monotonous blood picture consisting of blast
forms.
Etiology : similar to other malignancy

There are many classification based on different

aspects :
From the therapeutic point of view
Acute leukemia can be grouped into
1. Acute Lymphoid Leukemia (ALL)
2. Acute non Lymphoid Leukemia (ANLL)
Vincristine + prednisone is active in ALL but not in
ANLL

In 1980 FAB group classified Acute Leukemia into :

I. ALL : L1, L2, L3
II. ANLL (AML) into M0, M1, M2, M3, M4, M5, M6, M7
M0 = undifferentiated AML
M1 = AML without maturation
M2 = AML with some maturation
M3 = AML with hypergranularity (APL)
M4 = Acute Myelomonocytic Leukemia
M5 = Acute Monoblastic (a); Acute Monocytic (b)
M6 = Erythro Leukemia
M7 = Megakaryocytic Leukemia

Late addition FAB classification

M8 = Acute Basophilic Leukemia
M9 = Acute Pammyelosis with Myelofibrosis (acute
Myelofibrosis)

The latest classification (2009) was the WHO

classification :
For ANLL :
A. Groups with specific genetic abnormality
1. M3 = APL with t(15,17) and PML RARA fusion
gene
2. M1, AML with t(8;21) with ETO fusion genes
3. Other less frequent abnormalities
B. Groups preceded by MDS or not
C. Groups preceded by chemotherapy or not
D. AML with NOS (same as FAB)
E. Other less frequent type

There are also Immunologic Classification

based on immunological markers as parameter and
also cytogenetic classification (not discussed
here)
Facilities problem :
Not easy to identify type of leukemic cells: need
ultra structural morphology, cyto chemistry,
immunophenotyping, cytogenetic and molecular
examination)

Complaints/Symptoms :
Anemia symptoms (tiredness, palpitation,
timmates, dyspnea) severe
Bleeding tendency duo to thrombopenia. In M 3
DIC is mostly the presenting symptom
High fever (septic) due to combination of
hypermetabolism, frequent septic infection

Physical Exam : severe anemia, bleeding multiple

sites, highfever, hepatosplenomegaly
Laboratory exam :
Hb often <3 g%; thrombo < 5.000 with bleeding
blood smear : monotonous picture (almost all
nucleated cells are blast)
If facilities permit :
All special technics mentioned above

Vincristine + Prednisone + other for ALL

For ANLL (Vincristine + Prednisone) is not active
we give Ara C + Daunomycin,
e.g regimen 3-7 = 3 day Daunomycin, 7 days AraC
Better by an experienced hematologist
Other options :
Bone marrow transplantation + other advances