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LEUKEMIA

Muhammad Riza
Departement Of Child Health, Faculty Of Medicine,
University Of Sebelas Maret, Moewardi Hospital
Surakarta

Leukemia & NHL ?

MALIGNANCY

What Is Leukemia?
Cancer of the white blood cells
Acute or Chronic
Affects ability to produce normal
blood cells
Bone marrow makes abnormally
large number of immature white
blood cells called blasts

Acute leukemia (97%)


1.Acute lymphocytic leukemia ( ALL: 75% )
2.Acute myeloid leukemia ( AML )/ Acute non
lymphocytic leukemia (ANLL:20%)
3.Acute undifferentiated leukemia (AULL:<0,5%)

Chronic leukemia (3%)


1.CML with Philadelphia chromosome +
2.Juvenile chronic myelogenous leukemia (JCML)

Adult and Pediatric Leukemias


ADULTS

CHILDREN

Acute Lymphocytic

11%

75-80%

Acute Myeloid

32%

20%

Chronic Myeloid

15%

<5%

Chronic Lymphocytic

26%

N/A

Epidemiology
Adults: 85% of acute leukemia is AML
Children: 85% of acute leukemia is
ALL
ALL: 3500 cases/year in the U.S.
Children
Adults

2300 cases
1200 cases

ALL: peak incidence age 3-4, falls off


after age10, second rise after age 40

Causes of acute leukemias

idiopathic (most)
underlying hematologic disorders
chemicals, drugs
ionizing radiation
viruses (HTLV I)
hereditary/genetic conditions

Clinical manifestations
symptoms due to:
marrow failure
tissue infiltration
leukostasis
constitutional symptoms
other (DIC)

usually short duration of symptoms

Marrow failure
- Anemia:

pallor,

fatigue,

tachycardia,

dyspnoe
- Neutropenia: fever, ulceration of buccal
mucosa, infection
- Thrombocytopenia:

petechiae,

bleeding ( mucous, intracranial )

purpura,

Infiltration of tissues/organs
enlargement of liver, spleen, lymph nodes
gum hypertrophy

bone pain
other organs: CNS, skin, testis, any
organ

Leukostasis
accumulation of blasts in
microcirculation with impaired
perfusion
lungs:
hypoxemia, pulmonary
infiltrates
CNS: stroke
only seen with WBC >> 50 x 109/L

Clinical manifestation:
1. Skin: pale, petechiae, mucous
membrane bleeding.
2. Epistaxis, diathesis hemorrhage
,ulceration likes noma, Ludwig angina.
3. General lymphadenopathy.
4. Splenomegaly is common and
hepatomegaly is less common.
5. Bone and joint: polyarthritis, bone
necrotic.
6. Heart :as result of anemia.
7. Pulmonal infiltration.


1.
2.
3.
4.
5.
6.

Diagnosis.
Most patients will have anemia,
thrombocytopenia.
White blood cells counts < 3.000/mm3
and 20% have > 50.000/mm3.
Blast cells on blood smear and BMP
(20%)
Chest X rays : a mediastinal mass T
cell ALL.
Cerebrospinal should be examined for
leukemic cells.
Uric acid level and renal function should
be determined before treatment.

Diagnosis
Darah lengkap

Hb turun: anemia
normositiknormokromik
Jumlah Lekosit :
rendah,normal
atau meningkat
Thrombositopeni
<10x109/l

Distinguishing
ALL from AML

Blast morphology
Cytochemical studies
Immunophenotype
Chromosomal abnormalities

ALL
FAB Classification
Cytologic
Features

L 1:75%

L 2 :20%

L 3:3%

Small cells

Large,heterogene Large &


ous in size
heterogeneous.

Nuclear
chromatin

Homogeneous in
any one case

Variable,hetrogen Finely stippled


eous in any case. and
homogeneous

Nuclear shape

Regular, clefting
or identation

Irregular,
clefting,
identation
common

Regular, oval to
round

Nucleoli

Not visible or
small and
inconspicuous

One or more
present, often
large

Prominent, one
or more vesicular

Amount of
cytoplasm

Scanty

Variable, often
moderately
abundant

Moderately
abundant

Basophilia of
cytoplasm

Slight or
moderate, rarely

Varable, deep in
some

Very deep

Cell size

L1: uniform small blasts


with scanty cytoplasm

L 2: larger blasts with more cytoplasm,


more prominent nucleoli, more heterogeneity

L3: perinuclear and cytoplasmic vacuoles


(very distinctive)

Auer rods in AML

Chronic Myelogenous Leukemia


basofil

segme
n

batang

mielosi
t

ALL vs. AML


Cytochemistry
Cytochemical stain
AML
ALL
myeloperoxidase
+
Sudan black
+
non-specific esterase
+ (M4,5)
PAS
+ (M6) + (c)
acid phosphatase

+ (M6)

+ (T)

Principles of treatment
combination chemotherapy
first goal is complete remission
further Rx to prevent relapse

supportive medical care


transfusions, antibiotics, nutrition

psychosocial support
patient and family

Protokol Kemoterapi :
Thn. 1999

COM-ALL-92

WK-ALL-2000 SR dan HR

Protokol BMF

Protokol ALL VI Belanda


COM-ALL-92
Protokol BM (moskow)

Protokol Belanda
Mahal

Protokol CCG
Murah, Optimal
Indonesia 2008

Chemotherapy for acute


leukemias
Phases of ALL treatment
induction
intensification
CNS prophylaxis
maintenance

post-remission therapy

AML treatment
induction
consolidation (post-remission therapy)

Prognosis, depend on:


1. Age : between 2 6 years : good
prognosis, < 1 year and > 10 years :
bad prognosis.
2. WBC > 50.000 /mm3 : bad prognosis
3. Meningeal leukemia : bad prognosis.
4. cALL >preB-ALL >T-ALL > B-ALL.
5. Mediastinal mass + : bad prognosis.
6. Bleeding, infection/sepsis: bad
prognosis.

EMERGENCIES IN LEUKEMIA

Mauro, M. J. N Engl J Med 2003;349:767

Hyperleukocytosis with
Leukostasis

WBC >100k (or lower)


Myeloid > Lymphoid blasts
Hydroxyurea 2-5 grams po
Hold PRBC transfusions
Leukopheresis
Induction chemotherapy

Acute Tumor Lysis Syndrome

Hyperuricemia
Hyperkalemia
Hyperphosphatemia
Hypocalcemia
Azotemia->ARF