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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 Reduction
WBC 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

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Final leukapheresis

  • 1.
  • 2. 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
  • 3. 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
  • 4. 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
  • 5. 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
  • 6. 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
  • 7. 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
  • 8. 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
  • 9. 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
  • 10. 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
  • 11. 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
  • 12. The basic LRA Mechanics
  • 13. 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
  • 14. Time Frame of WBC Reduction WBC 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
  • 15. Waste Bags from LRA showing WBC/Blast layer Day 1 Day 2