Download - Final leukapheresis
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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The basic LRA Mechanics
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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
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Time Frame of WBC Reduction
WBC Count
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Date Day 1-Apheresis
Day 2-Apheresis
Day 3 Day 4-Apheresis
Day 5-InductionChemo
Day 6 Day 7 Day 8 Day 9
Hospital Day
WB
C
WBC count
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Waste Bags from LRA showing WBC/Blast layer
Day 1
Day 2