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LEUKEMIA
8 Parameter Cell Counter
Hematocrit = 40 to 54 %
Hemoglobin = 13.5 to 18 g/dL
Red Cells = 4.6 to 6.3 x 106 cells / L
White Cells = 4.5 to 11 x 103 cells / L
Platelets = 150 to 450 x 103 cells / L
Acute Chronic
M0 -- Undifferentiated AML
M1 -- AML without maturation
M2 -- AML with maturation
M3 -- Acute Promyelocytic Leukemia
M4 -- Acute Meylomonocytic Leukemia
M5 -- Acute Monocytic Leukemia
M6 -- Erythroleukemia (DiGuglielmo’s)
M7 -- Megakaryoblastic Leukemia
M1 and M2
M4 M3
M5
Acute Leukemia
Presenting features:
Anemia
Fatigue, dyspnea, angina pectoris
Neutropenia - the leukocyte count may be high or
low, but neutropenia is characteristic
Unexplained fever, serious infections
Thrombocytopenia
Bruising, petechiae
Less common: lymphadenopathy, splenomegaly, skin
infiltration, chloromas (tumors composed of
malignant marrow cells)
Acute Leukemia
Myeloid Platelets
Hematopoetic
Stem Cell
B Cells
Lymphomas
Lymphoid
Hodgkins (30%)
T cells
Non Hodgkins (70%)
Haematopoiesis
B-lymphocytes
Plasma
Lymphoid cells
progenitor T-lymphocytes
AML
Hematopoietic Myeloid Neutrophils
stem cell progenitor
Eosinophils
Basophils
Monocytes
Platelets
Red cells
Where AML Originates
Genetic Associations
idiopathic (most)
underlying hematologic disorders
chemicals, drugs
ionizing radiation
viruses (HTLV I)
hereditary/genetic conditions
AML and its Impact on the
Immune System
AML affects the innate immune system
Secondary Immune System kicks in
The proliferation of immature neutrophils
and moncytes takes place
Unable to leave the bone marrow to go into
blood stream and tissues to fight off
infections
Main Types
Finger prick
Blood sample
Blood dye
Bone marrow sample
Spinal Tap/Lumbar Puncture
Lab Studies
Flow cytometry:
CD3 (T-lineage ALL)
CD19 (B-lineage ALL)
Cytogenetics:
t(22;9)
t(4;11)
t(2;8)
t(8;14))
Lab Studies
Coagulogramm:
elevated prothrombin time
decreased fibrinogen levels
presence of fibrin split products
Chemistry profile:
elevated lactic dehydrogenase level
elevated uric acid level
liver function tests
BUN/creatinine determinations
Cytogenetics
Technique
Needs dividing cells, so marrow usually better
Complemented and extended by FISH and
rtPCR
FISH: “Fluorescence In Situ Hybridization”
Typically in metaphase cells, peripheral blood works
fine- so ideal when marrow unavailable
rtPCR- for 15;17
rtPCR for BCR:ABL in ALL
Cytogenetics
Intermediate
Normal
One or two abnormalities
Cytogenetics
Bad…
Chromosome 7
Chromosome 5
Complex (3 or more)
11q23
Any trisomy?
Management:
A-Supportive measure:
-isolation in positive laminer flux room
-insertion of central line
-family and patient support by permanent social worker
-AlKaline diuresis to prevent tumor lysis syndrome
-oropharynx/GIT decontamination to prevent fungal
infection
-IV antibiotics for infection
-Blood transfusion if anemia and thrombocytopenia.
Therapeutic option
B-Curative intent:
only allogenic bone marrow transplant .
C_Classical approch(curative/palliative)
-induction chemotherapy
-consolidation of remission
-intensification
-maintenance chemotherapy
-CNS prophylaxis
Medical Care
Induction therapy:
4-drug regimen of vincristine, prednisone,
anthracycline, and cyclophosphamide or L-
asparaginase or a 5-drug regimen of vincristine,
prednisone, anthracycline, cyclophosphamide, and L-
asparaginase given over the course of 4-6 weeks.
Consolidation therapy:
a standard 4- to 5-drug induction usually include
consolidation therapy with Ara-C in combination with
an anthracycline or epipodophyllotoxin.
Maintenance
CNS prophylaxis
AML therapy
Cytarabine
Infusional or high-dose
Anthracycline
Any will do- dauno, ida, mitoxantrone
Other active agents
Etoposide
Cyclophosphamide
Hydroxyurea
6MP/TG
Topotecan
Supportive Care
Replacement of blood products: packed red blood
cells, platelets, fresh frozen plasma
Antibiotics: a third-generation cephalosporin (or
equivalent) with an aminoglycoside. Patients with
persistent fever after 3-5 days of antibacterial
antibiotics have amphotericin added to their regimen.
The use of prophylactic antibiotics in neutropenic
patients who are not febrile is controversial. A
commonly used regimen includes ciprofloxacin (500
mg orally twice daily, fluconazole (Diflucan) (200 mg
orally daily), and acyclovir (200 mg orally 5 times/d).
Supportive Care
Growth factors
Allopurinol 300 mg 1-3 times/d
Central venous catheter
Prognosis
Genetic abnormalities:
t(9;22) - poor outlook
t(4;11) - younger age, female predominance,
high white cell counts, and L1 morphology
t(8;14) - older age, male predominance, frequent
CNS involvement, and L3 morphology
Both are associated with a poor prognosis.
Prognosis in AML
Lymphoma.
Myelodysplastic syndrome.
Multiple myeloma.
Aplastic anemia
Sever megaloblastic anemia due to B12
defeciency.
Severe lymphocytosis due to infections.
Myeloid maturation
MATURATION
Smallest cells in
the blood.
Normal range
130,000-400,000.
Active role in
coagulation and
hemostasis.
Pictures Of Blood
Platelet Platelet
White Cell Red Cell Red Cell Blasts
White Cell
Mani, A, Lee, DA. Leukemic Gingival Infiltration. N Engl J Med 2008; 358(3): 274. Copyright ©2008 Massachusetts Medical Society
Chloromas
C
NEJM 1998
Effects On the Body
Chemotherapy
Immunotherapy
Radiation
Bone marrow transplant
Research
New drugs
Cord blood and planceta
Myeloblasts with auer rods
Lymphoblast
AML
Auer rods in AML
LEUKEMIA LIMFOBLASTIK AKUT
Kemoterapi
Radiasi CNS
ALL
ALL-L1
ALL-L2
LEUKEMIA LIMFOSITIK KRONIK
Hypogammaglobulinemia is common
Infection is the most common cause of death
Complications can include AIHA & ITP
May transform into an aggressive lymphoma
Cause unknown
Age: adults
Prognosis: 3-4 years without BMT, cures
possible with BMT
Treatment:
Imatinib (Gleevec)
Bone marrow transplant
Hydroxyurea +/- interferon;
Chronic Myelogenous Leukemia
PMN
Eosinophil
Early Myeloid
Cells
Basophil