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-InductionChemo

Day 6 Day 7 Day 8 Day 9

Hospital Day

WB

C

WBC count

Waste Bags from LRA showing WBC/Blast layer

Day 1

Day 2