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Leukoreduction Apheresis

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... FAB type M4 B) Acute Lymphocytic Leukemia (ALL) C) Chronic Lymphocytic Leukemia (CLL) D) Chronic Myelogenous Leukemia (CML), Blast Crisis E) ... – PowerPoint PPT presentation

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Title: Leukoreduction Apheresis


1
Leukoreduction Apheresis
  • MCG Transfusion Medicine On-line
  • James Fulcher, MD
  • jfulcher_at_mcg.edu

2
Case History
  • Patient is a 12 year old boy with a 2 week
    history of fatigue and easy bruising
  • ER physical exam shows widespread petechiae and
    several large bruises
  • WBC in the ER is 180,000/µL but pathologist
    review of smear estimates a WBC of 600,000/µL

3
Case History
  • Examination of peripheral smear shows 85 blasts
    with very high nucleus/cytoplasm ratios
  • Other important presentation data includes
    critically high serum uric acid, elevated lactate
    dehydrogenase, and increased liver enzymes

4
Presentation Labs
  • Test
    Patient Results Ref. Range
  • WBC count, x103/?L (x 109/L) 186
    (186) 3.7-9.4
    (3.7-9.4)
  • Hct
    24 37-49
  • Platelets x 103/?L (x109/L)
    27(27) 134-357(134-357)
  • Uric Acid mg/dL
    14.3
    4.5-8.5
  • LDH U/L
    2827
    100-200
  • AST U/L
    185
    lt40
  • ALT U/L
    107
    lt48
  • Alkaline Phosphatase IU/L
    223 20-130
  • Protime seconds
    14.2
    10-14

5
Presentation Blood Smear
40X
1000X
6
Diagnosis and Treatment
  • Patient has T-cell (by flow cytometric
    immunophenotype) ALL
  • Candidate for leukoreduction apheresis (LRA)
  • The patient received 3 apheresis procedures
    occurring on the evening of admission and
    hospital days 2 and 4

7
Leukoreduction History
  • Each pheresis procedure lasted several hours and
    removed between 589 cc and 465 cc of fluid of
    almost 100 leukemic blasts cells.
  • The serial leukoreduction apheresis procedures
    greatly reduced WBC and Chemotherapy was safely
    begun on day 5

8
Waste Bags from LRA showing WBC/Blast layer
Day 2
Day 1
9
Time Frame of WBC Reduction
10
Reduction of LDH and Uric Acid
11
Day 5 Blood Smear
40X
40X
12
Case Conclusion
  • Patient WBC counts were dropped to levels safe
    enough to begin chemotherapy on day 5
  • LDH and Uric acid level were also reduced (spike
    in LDH corresponded to start of chemotherapy
  • Case illustrates the usefulness of leukoreduction
    apheresis before treatment with chemotherapy

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
The basic LRA Mechanics
15
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

16
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

17
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

18
Myeloblast Interactions with Vessel Endothelial
Cells
  • Myeloblasts have been shown to induce their own
    adhesion by secreting inflammatory cytokines
  • Endothelial cells respond to the inflammation by
    releasing adhesion molecules-P/E -selectin,
    VCAM-1, ICAM-2
  • This composes a cycle of inflammation and
    adhesion

19
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

20
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

21
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

22
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

23
Procedural Issues
  • In cases of tumor lysis syndrome, pre-LRA
    treatment should include
  • aggressive hydration
  • urine alkalization
  • allopurinol
  • hydroxyurea

24
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

25
When is LRA Required in Hyperleukocytosis?
  • No agreed upon initiation criteria or therapeutic
    goals
  • Generally, LRA should be considered above
    peripheral blast counts above 50K
  • Reduction of blast count by 30 or below 100K is
    recommended
  • Patients should be considered on a case by case
    basis

26
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

27
Outcomes with LRA
  • Short term survival advantage has been described
    but recent data on treatment with hydration,
    allopurinol, and hydroxyurea show similar
    survival
  • No significant long-term survival advantage has
    been reported

28
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-physici
    ans should treat the patient not the numbers
  • New research on molecular interactions between
    myeloblasts and endothelial cells might lead to
    additional treatment options

29
Review Question 1
  • In which of the following has hyperleukocytosis
    not been described?
  • A) Acute Myelogenous Leukemia (AML) FAB type M4
  • B) Acute Lymphocytic Leukemia (ALL)
  • C) Chronic Lymphocytic Leukemia (CLL)
  • D) Chronic Myelogenous Leukemia (CML), Blast
    Crisis
  • E) Acute Megakaryocytic Leukemia

30
Review Question 2
  • 2. What is not a described complication of
    hyperleukocytosis?
  • A) Disseminated intravascular coagulation (DIC)
  • B) Leukostasis
  • C) Renal infract
  • D) Tumor lysis syndrome
  • E) Hypoxemia

31
Review Question 3
  • What best describes the role of Hydroxyethyl
    starch (HES) in leukoreduction apheresis (LRA)
    procedures?
  • A) Anticoagulant
  • B) Erythrocyte sedimentation agent
  • C) Alkalinization agent
  • D) Leukocyte sedimentation agent
  • E) Chelation agent

32
Review Question 4
  • What is the accepted therapeutic goal for LRA in
    cases of AML hyperleukocytosis?
  • A) Reduction of blasts by 30
  • B) Reduction of leukocrit to 12-15 ml/dL
  • C) Amelioration of leukostasis symptoms
  • D) No current consensus
  • E) Reduction of WBC count to less than 100,000
    ?/L

33
Review Question 5
  • What cellular adhesion marker is not known to
    have a role in myeloblast and endothelial cell
    binding?
  • A) ICAM-1
  • B) P-Selectin
  • C) VCAM-1
  • D) E-Selectin
  • E) E-cadherin

34
References available upon request
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