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-PDGFR
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
