LEUCEMIA

PATHOPHYSIOLOGY
AND
THERAPY STRATEGY

TJOKORDA GDE DHARMAYUDA

HEMATOLOGY AND MEDICAL ONCOLOGY DEVISION
INTERNAL MEDICINE DEPARTEMENT
SANGLAH GENERAL HOSPITAL
MEDICAL FACULTY UDAYANA UNIVERSITY
2017
 What is Leukaemia

• An neoplastic proliferation of haematological cells

• Commonly affecting a single cell line
• Clonal in nature
• May occur as de novo event or secondary to other
stimulus
• May involve mature or immature cells
 PATHOPHYSIOLOGY OF
LEUCEMIA
PENCETUS
SEMBUH
ETIOLOGI

DIAGNOSIS
BERHASIL
FACTOR RESIKO KOMPENSASI
EKSTERNA ORGAN
INTERNA VITAL
LAIN2
TERAPI UTAMA : KOMPLIKASI
NUTRISI
ANTI STRES
IMUNITAS STABIL
SUPORTIV GAGAL
SIMPTOMATIK
REHABILITATIF
PALIATIF

KETENANGAN
KEBERSIHAN

NUTRISI ISTIRAHAT MENINGGAL

EXERSICE
 PATHOPHYSIOLOGY ASPECT
• ETIOLOGY : ( Polution, Nutrition, )
• RISK FACTOR
– INTERNAL : ( Stress, Immunity, Micronutrition,
Attitude
– EXTERNAL ( Polution, Environment,
• TRIGER FACTOR : Spiritual Attitude )
• DIAGNOSIS : ( Kriteria diagnostic )
• COMPENSATION : ( structur, function of organ,
system )
• COMPLICATION
ETILOGY OF ACUTE LEUKAEMIA
1. IONIZING RADIATION
2. BENZENE
3. GENETIC ( DOWN SYNDROME )
4. CHEMOTHERAPY
5. MOSTLY UNKNOWN
 PATHOLOGY PICTURES

• BONE MARROW (LEUCEMIC CELL ): Increase monoclonal,

Abnormal
• ABNORMAL STRUCTURES OF LEUCEMIC CELL :
– Chromosome
– Morphology
– histology
• BLOOD CELL FUNCTION
– Immunity, Regulator, Carrier
• BLOOD CIRCULATION SYSTEM
– Hypoxia, Hypercapmia
• ANOTHER BODY ORGAN AND SYSTEM : Compensation,
Decompensation, Failure
 DIAGNOSIS
• ANAMNESIS :
• PHYSICAL DIAGNOSIS :
• LABORATORIUM :
– Clinical Pathologic
– Anatomical Pathologic
• IMAGING :
– Plain Photo
– CT Scan, Pet Scan
– USG
• DIAGNOSIS CRITERIA :
 CLASSIFICATION OF
LEUCEMIA
• ACUTE LEUCEMIA
– ACUTE MYELOBLASTIC LEUCEMIA
– ACUTE LYMPHOBLASTIC LEUCEMIA
• CHRONIC LEUCEMIA
– CHRONIC MYELOCYTIC LEUCEMIA
– CHRONIC LYMPHOBLASTIC LEUCEMIA
 Laboratory Diagnosis 1
FAB classification of AML

• M0 Undifferentiated
• M1 Myeloid without differentiation
• M2 Myeloid with differentiation
• M3 Acute Promyelocytic Leukaemia
• M4 Myelomonocytic Leukaemia
• M5 Monoblastic Leukaemia
• M6 Acute Erythroleukaemia
• M7 Acute Megakaryoblastic leukaemia
 Lab findings 1
FAB classification L1 – L3
• L1 – Homogenous, small blasts, with scanty
cytoplasm. Regular nuclear shape.

• L2 – Heterogenous, large blasts. Variable

nucleus and cytoplasm

• L3 – Homogenous, large cells, basophilic

with cytoplasmic vacuolation.
 THERAPY STRATEGY ASPECT
• GOAL OF THERAPY
– CURATIVE
– PALLIATIVE CARE
• MODALITY OF THERAPY
– MEDICAMENTOSE
– NON MEDICAMENTOSE
– COMBINATION
• STRATEGY THERAPY
– MEDICAMENTOSE THERAPY
– NON MEDICAMENTOSE STRATEGY
• ROLE OF CURE AND CARE
 CURATIVE
• GOAL : Heal, Long Term Compensation
• MODALITY
– Medicamentose
– Non Medicamentose
– Combination
• MEDICAMENTOSE STRATEGY
– Induction and Remission
– Consolidation
– Maintenence
– Sanctuary
• BEST SUPPORTIVE CARE
– Nutrition
– Education
– exersice
 PALLIATIVE
• BEST SUPPORTIVE CARE
• HOLISTIC ASPECT OPTIMALIZATION
– Physic, Psychologic, Spiritual, Social, Cultural
• QUALITY OF LIFE
– Live with Leucemia and Happyness Togather
• QUALITY OF DEAD
– Increase Quolity Life with Leucemia till the end of Life
 MEDICAMENTOSE
• ANTI BIOTICA
• ANTI HISTAMINE
• CORTICO STEROID
• IMMUNO MODULATOR (SUPRESSOR,
STIMULATOR, STABILIZER )
• CYTOSTATICA
• VITAMINE
• MINERAL
 NON MEDICAMENTOSE
• NATURAL MANIPULATION
– NATURAL ENERGY
– WATER MEDIA, Natural Stone,
– HERBAL
• EDUCATION KNOWLEDGE
– PSYCHO THERAPY
– PRAYING TO THE TRUE SOURCE
• MASSAGE, ACCUPRESSURE, ACCUPUNCTURE
• BECAM
• MOLECULE TRANSFER FACTOR
 ACUTE LEUKAEMIAS

• Proliferation of maturation arrested

primitive cells
• Complex and heterogenous in nature
• Broadly divided into myeloid (AML) and
lymphoid(ALL)
• Subdivided into other classes by
morphology, cytogenetics, cellular markers
 GENERAL FEATURES OF ACUTE
LEUKAEMIA

• Symptoms usually of rapid onset

Petechiae, bruising, epistaxis
Fatigue and lethargy
Infection
Bone pain
Hepatosplenomegaly
Lymphadenopathy
ACUTE PROGRANULOCYTIC LEUKAEMIA

DIAGNOSIS

5-15% AML ARE APL

BLAST WITH ABUNDANT CYTOPL. GRANULES
CYTOPLS INTENSE MYELOPEROXIDASE
YOUNGER MEDIAN AGE
WITH DIC
MEDICAMENTOSE TREATMENT

ATRA ( All-trans-retinoic acid )

side effect : dryness, headache, abnormal liver
APL DIFFERENTIATION SYND.

ARSENIC TRIOXIDE ( ATO )

ANTHRACYCLINE
LAB DIAGNOSIS OF ACUTE LEUKAEMIA
• Normocytic, normochromic anaemia of
variable degree
• Platelets often low
• variable white count dependent on disease
• variable primitive cells in peripheral blood
• BM infiltrated with primitive clonal cells
CYTOCHEMISTRY

• Used to demonstrate
cellular components
which may be lineage
specific
eg myeloperoxidase
esterase
lipid
acid phosphatase
glycogen
 IMMUNOPHENOTYPING

Used to demonstrate lineage and maturation

specific cellular antigens
May be demonstrated using flow cytometry or
staining technique
Also useful to monitor for relapse in BM
 CYTOGENETICS

• Used to demonstrate presence of clonal abnormality

• May be disease specific
• May have prognostic significance
• Also used to monitor relapse, further mutation etc
 TREATMENT OF ACUTE
LEUKAEMIA
• Chemotherapy –induction, consolidation
and in ALL- maintenance
• Supportive Tx eg transfusion, platelets,
antibiotics
• Stem cell transplant
• Other methods in use
 ACUTE MYELOID LEUKAEMIA
• Comprise approximately 80% of adult and
20% of childhood acute leukaemia
• May occur as de novo event or secondary to
a ‘preleukaemic’ phase – myelodysplasia
• Linked to radiation exposure, chemicals
such as benzene and some
chemotherapeutic agents eg chlorambucil
• May be associated with specific
chromosomal abnormalities
 LABORATORY DIAGNOSIS 2

• Immunophenotyping – Shows lineage specific

markers
• Some specific cytogenetic abnormalities
eg t(15;17) in APML
• Cytochemistry shows myeloid specific features eg
myeloperoxidase, SBB and esterases
 PROGNOSIS
Good Bad
• Younger patients • Elderly patients
• Wbc <50 x 109/l at • Wbc >50 x 109/l at
presentation presentation
• Specific single • multiple cytogenetic
cytogenetic abnormality abnormalities
• < 20% blasts in BM after • > 20% blasts in BM after
1st induction 1st induction
• De novo AML • 2o AML
 OUTCOME

• Younger patients – approx 80-90% obtain

complete remission but only about 35% are
‘cured’
• Much lower rates in elderly patients
• Matched allograft – approx 50% ‘cure ‘
• Children approx 50% at 3 years.
 TREATMENT OF AML

• Treatment dependent on age of patient

• M3 patients receive a differentiating agent +
chemotherapy
• Chemotherapy typically a combination of
three drugs
 MYELODYSPLASIA
• Clonal proliferation of multipotent stem
cells, capable of differentiation
• Reduced marrow output of possibly
morphologically and functionally abnormal
cells
• Typically hypercellular BM with peripheral
pancytopenia
• FAB classification
• 1o and 2o MDS seen
 ACUTE LYMPHOBLASTIC
LEUKAEMIA

• Predominates in children
• Higher risk of CNS involvement
• Risk of testicular involvement
• Lymphadenopathy and moderate
hepatosplenomegaly common
• T-ALL associated with mediastinal mass
 LAB FINDINGS 2

• Immunological classification - B and T cell

lineage and level of maturity
• Cytochemistry PAS and acid phosphatase
• Cytogenetics – certain specific
abnormalities affecting prognosis
 PROGNOSIS

Good Bad
Children between 2 –10yrs Wbc > 100 x 109/l
Wbc < 20 x 109/l Poor response to treatment
Girls B-ALL and T-ALL
Caucasians boys
High hyperdiploidy (>50) Afro Caribbeans
L1 type Hypodiploidy (<46)
t(9;21), t(4;11), t(1;19)
L2 type
 TREATMENT
• Chemotherapy – Induction, consolidation
and then maintenance for 2 years
• CNS directed treatment
• Supportive treatment as before
• Stem cell transplant for poor risk groups
and relapses.
 OUTCOME
• Majority of children are ‘cured’ at 5 years
• Much lower in adults, especially the elderly
Best adults 15 –20 ish with good prognostic
features
 CHRONIC LEUKAEMIAS
• Much slower onset
• May be chance finding
• Proliferation of apparently mature cells
• Usually confined to adults
• May affect myeloid or lymphoid cell lines
CHRONIC LYMPHOID
LEUKAEMIAS
eg CLL

Disease of older age

Gradual advancement
Lymphadenopathy
Hepatosplenomegaly
Lymphocytosis
HAIRY CELL LEUKAEMIA

Disease of middle age

Splenomegaly
Pancytopenia
BM/Splenic infiltration
with hairy cells
Typical morphology,
cytochemistry and
immunophenotyping
 PROGNOSIS AND TREATMENT

CLL – often asymptomatic and requires no

treatment.
Progression may require treatment eg
chemotherapy, splenectomy, radiotherapy
and/or support
HCL – Very sensitive to chemotherapy,
giving excellent results.
CHRONIC MYELOID LEUKAEMIAS

Eg Chronic Granulocytic
Leukaemia
Incidence 1 in 100,000
Typical Ph chromosome
t(9;22)(q34;q11)
3 phase onset
Transformation to
myeloid or lymphoid
acute leukaemia
IMMUNOPROLIFERATIVE
DISORDERS
Eg Multiple myeloma

Clonal proliferation of Ig
secreting B cells
Monoclonal gammopathy
Bone pain, lytic lesions
Risk of renal failure
Hypercalcaemia
Primarily disease of elderly