Conclusions
•LRA remains a useful tool in the acute setting of
hyperleukocytosis
•It will require more studies to establish definitive
LRA therapy guidelines
•The procedure is not without complications-
physicians should treat the patient not the
numbers
•New research on molecular interactions
between myeloblasts and endothelial cells might
lead to additional treatment options
Complications/Disadvantages
•Expense
•Technical skill required
•Personal time required
•Citrate toxicity-be wary in small children
•In infants, measure serum Ca every 30-45
minutes and possibly start a Ca Drip
Benefits of LRA in Leukemia
•Physical removal of blasts reduces burden
on patient as chemotherapy destroys the
blasts-LRA is an important pre-
chemotherapy treatment
•Removal of circulating blasts, draws extra-
vascular blasts into circulation
•Removal of blasts increases cells in S-
phase, this improves response to some
chemotherapy
Procedural Complications
•Vascular Access-always better to have a central
line, but large bore peripheral access can be
used in emergencies
•Large volume of blood needs to be processed
•Machine must be primed with 250-300 cc of
blood, important in small infants where is could
represent their entire blood volume
•6% hydroxyethyl starch (HES) is used as a red
cell sedimentation agent, to facilitate blast and
mature leukocyte removal
Disseminated Intravascular
Coagulation
•This is related to the release of
intracellular contents
•There are many interfering substances
described in hyperleukocytosis that may
cause DIC, but few studies have been
done
•More common presentation in ALL in
combination with tumor lysis syndrome
Tumor Lysis Syndrome
•Tumor lysis syndrome is the release of
intracellular chemicals
•Potassium, phosphate are important
electrolytes that are released
•Potassium should be corrected quickly as
fatal arrhythmia
•Purine and pyrimidine nucleotides are
degraded to uric acid-this can damage the
kidney
Hyperviscosity Syndrome
•Viscosity is the internal sheer force of a
liquid, it can be thought of as thickness
•Leukocrit between 12-15 mL/dL will cause
significant increases in viscosity, this is
dependent on blast size and morphology
•Increased viscosity reduces the proper
flow of blood in circulation
Leukostasis
•Clinically significant when pulmonary or
nervous system vascular blockage occurs
causing hypoxemia, respiratory distress,
and stroke
•Found at lower blast counts in AML (300-
450K) than ALL (600-800K), this is related
to blast size and expression of adhesion
markers
Complications of
Hyperleukocytosis
•Leukostasis
•Hyperviscosity syndrome
•Tumor Lysis syndrome
•Disseminated intravascular coagulation
(DIC)
•The goal of LRA is to reduce the incidence of
these complications by physically removing
blasts from the circulation
Indications for LRA
•Hyperleukocytosis
•Patients with significant
hyperleukocytosis are reported in cases
of:
•acute myelogenous leukemia (AML) 5%-25%
•acute lymphoid leukemia (ALL) 10%-30%
•chronic myelogenous leukemia (CML) ?%
•chronic lymphoid leukemia (CLL) ?%
•chronic monomyelocytic leukemia(CMML)
one reported case
The basic LRA Mechanics
Leukoreduction Apheresis
(LRA)
•The process of removing unwanted WBC
or blasts from the circulation
•The procedure is indicated for the rapid
correction of hyperleukocytosis, generally
defined as a WBC count over 30-50K
•One procedure generally removes
between 20-80% of WBC by processing 7-
10 liters of blood
Time Frame of WBC ReductionWBC Count
0
20
40
60
80
100
120
140
160
180
200
Date Day 1-
Apheresis
Day 2-
Apheresis
Day 3 Day 4-
Apheresis
Day 5-
Induction
Chemo
Day 6 Day 7 Day 8 Day 9
Hospital Day
WBC
WBC count
Waste Bags from LRA showing
WBC/Blast layer
Day 1
Day 2