Acute Leukemia

David Lee, MD, FRCPC

 Overview
• Concepts, biology
• Epidemiology
• Clinical and laboratory manifestations
• Diagnosis
• Management and prognosis
 Classification of leukemias

Acute Chronic

Myeloid Acute Myeloid Chronic Myeloid Leukemia

Leukemia (AML) (CML)
origin

Lymphoid Acute Lymphoblastic Chronic Lymphocytic Leukemia

Leukemia (ALL) (CLL)
origin
 ALL
naïve

B-lymphocytes

Plasma
Lymphoid cells
progenitor T-lymphocytes

AML
Hematopoietic Myeloid Neutrophils
stem cell progenitor

Eosinophils

Basophils

Monocytes

Platelets

Red cells
 Myeloid maturation

myeloblast promyelocyte myelocyte metamyelocyte band neutrophil

MATURATION
Adapted and modified from U Va website
 Acute Leukemia
• accumulation of blasts in the marrow
How to distinguish AML vs CML
from looking at peripheral blood
Myeloid cell CML AML normal
blasts  
promyelocytes 
myelocytes 
metamyelocytes 
bands 
neutrophils   
 Significance of adult acute
leukemia
• a hematologic urgency
• usually fatal within weeks to months
without chemotherapy
• with treatment, high mortality due to
disease or treatment-related complications
(unlike childhood acute leukemia)
• notify Hematologist promptly if acute
leukemia is suspected
 Classification of acute
leukemias
ALL AML
• mainly children • mainly adults
• M>F • M>F
• curable in 70% of
children
• curable in minority of • curable in minority of
adults adults
 Two-hit model of
leukemogenesis
Loss of function of Gain of function mutations of
transcription factors tyrosine kinases
needed for differentiation
eg. FLT3, c-KIT mutations
eg. AML1-ETO N- and K-RAS mutations
CBF-SMMHC BCR-ABL
PML-RAR TEL-PDGFR

differentiation enhanced Acute

block + proliferation Leukemia
 Causes of acute leukemias
• idiopathic (most)
• underlying hematologic disorders
• chemicals, drugs
• ionizing radiation
• viruses (HTLV I)
• hereditary/genetic conditions
 Clincal manifestations
• symptoms due to:
– marrow failure
– tissue infiltration
– leukostasis
– constitutional symptoms
– other (DIC)
• usually short duration of symptoms
 Marrow failure
• neutropenia: infections, sepsis
• anemia: fatigue, pallor
• thrombocytopenia: bleeding
 Infiltration of tissues/organs
• enlargement of liver, spleen, lymph nodes
• gum hypertrophy
• bone pain
• other organs: CNS, skin, testis, any organ
Gum hypertrophy
Chloromas

C
NEJM 1998
 Leukostasis
• accumulation of blasts in microcirculation
with impaired perfusion
• lungs: hypoxemia, pulmonary infiltrates
• CNS: stroke
• only seen with WBC >> 50 x 109/L
 Constitutional symptoms
• fever and sweats common
• weight loss less common
 Laboratory features
• WBC usually elevated, but can be normal
or low
• blasts in peripheral blood
• normocytic anemia
• thrombocytopenia
• neutropenia
• DIC
Bone marrow in acute leukemia
• necessary for diagnosis
• useful for determining type
• useful for prognosis
• Acute leukemias are defined by the
presence of > 20% blasts in bone marrow
(% of nucleated marrow cells)
 Distinguishing AML from ALL
• light microscopy
– AML: Auer rods, cytoplasmic granules
– ALL: no Auer rods or granules.
• flow cytometry
• special stains (cytochemistry)
AML
AML
Auer rods in AML
ALL
 Treatment of acute leukemias
Choice of Rx is influenced by:
• type (AML vs ALL)
• age
• curative vs palliative intent
 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
 Chemotherapy for acute
leukemias
• Phases of ALL treatment
– induction
– intensification
– CNS prophylaxis post-remission therapy

– maintenance
• Phases of AML treatment
– induction
– consolidation (post-remission therapy)
 Hematopoietic stem cell
transplantation
• permits “rescue” from otherwise
excessively toxic treatment
• additional advantage of graft-vs-leukemia
effect in allogeneic transplants
• trade-off for allogeneic transplantation:
greater anti-leukemic effect but more toxic
 Prognosis
Adult AML
Age CR DFS
< 60 75% ~ 30%
> 60 50% 5-15%
Adult ALL
similar to or worse than AML
 Overview
• Concepts, biology
• Epidemiology
• Clinical and laboratory manifestations
• Diagnosis
• Management and prognosis