Transfusion medicine

Therapeutic apheresis


Last author update: 7 June 2023
Last staff update: 21 November 2023

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PubMed Search: Leukocytapheresis / therapeutic leukapheresis

Brian D. Adkins, M.D.
Garrett S. Booth, M.D., M.S.
Page views in 2023: 381
Page views in 2024 to date: 203
Cite this page: Adkins BD, Booth GS. Leukocytapheresis. website. Accessed May 19th, 2024.
Definition / general
  • Leukocytapheresis is the removal of white blood cells via apheresis
Essential features
  • Therapeutic leukocytapheresis is performed to acutely lower a patient's white blood cell (WBC) count due to symptoms associated with hyperleukocytosis or increased viscosity
  • Hyperleukocytosis (J Clin Apher 2019;34:171)
    • Generally defined as WBC count or blast count > 100,000/μL
    • Can be symptomatic with clinical manifestations or asymptomatic
    • Can lead to hyperviscosity / leukostasis syndrome
  • Hyperviscosity / leukostasis symptoms (J Clin Apher 2019;34:171)
    • Cerebrovascular insufficiency (altered mentation, transient ischemic attack, stroke)
    • Pulmonary complications (dyspnea, hypoxemia)
    • Disseminated intravascular coagulopathy (DIC)
    • More common in leukemia patients with monocytic or myeloid differentiation
  • Usually associated with (J Clin Apher 2019;34:171)
    • Acute myeloid leukemia (AML) with WBC > 100,000/μL
      • Incidence of AML with WBC > 100,000/μL is 12 - 18% in children and 5 - 18% in adults
      • Can occur with blast count > 50,000/μL especially with monocytic differentiation
      • Cells release cytokines which can lead to cellular adhesion (Blood 2015;125:3246)
    • Lymphoblastic leukemia / lymphoma (ALL) with WBC > 400,000/μL (> 3% of ALL patients)
Clinical features
  • Patients may present with DIC, tumor lysis syndrome or hypoxic ischemic type injury
  • Symptoms include vision changes, headache and shortness of breath
  • Neurologic symptoms may progress in the setting of intracranial hemorrhage
  • Hyperleukocytic symptoms manifest as hypoxic ischemic type injury associated with poor perfusion
  • A grading schema for hyperleukoctyic leukemia was described by Novotny, et al. (Eur J Haematol 2005;74:501)

Grading schema (adapted from Eur J Haematol 2005;74:501)
Group Probability of leukostasis syndrome Severity of symptoms Pulmonary symptoms Neurologic symptoms Other organ systems
0 Not present No limitations No symptoms and no limitations in ordinary activities No neurologic symptoms No symptoms
1 Possible Slight limitations Mild symptoms and slight limitation during ordinary activity, comfortable at rest Mild tinnitus, headache, dizziness Moderate fatigue
2 Probable Marked limitations Marked limitation in activity because of symptoms, even during less than ordinary activity, comfortable only at rest Slight visual disturbances, severe tinnitus, headache, dizziness Severe fatigue
3 Highly probable Severe limitations Dyspnea at rest, oxygen or respirator required Severe visual disturbances (acute inability to read), confusion, delirium, somnolence, intracranial hemorrhage Myocardial infarction, priapism, ischemic necrosis
Vascular access
  • Usually performed emergently using femoral apheresis or a dialysis catheter, which does not require radiographic confirmation
  • Central venous catheter, which requires radiographic confirmation, can be used in nonemergent situations
  • For therapeutic procedure, the American Society for Apheresis (ASFA) delineates leukapheresis based on the severity of the clinical presentation (J Clin Apher 2019;34:171)
    • Symptomatic leukostasis is ASFA category II
    • Prophylaxis is ASFA category III
      • ALL: WBC or blast count > 400,000/μL
      • AML: WBC or blast count > 100,000/μL
        • May be considered in monocytic subtypes of AML with WBC as low as 50,000/μL
    • Acute promyelocytic leukemia (APL) is a relative contraindication as studies have shown no improvement and one group showed increased mortality (J Clin Apher 2019;34:171)
      • APL has a strong association with DIC, and leukapheresis can induce a cytokine storm
      • All trans retinoic acid (ATRA) therapy is first line treatment for APL
  • Leukocytosis is now a category III indication regardless of symptoms (J Clin Apher 2023;38:77)
Volume exchanged and technical details
  • Generally limited to 1 procedure but number of treatments depends on WBC count decrease
  • 1.5 - 2 blood volume is usually performed for therapeutic leukapheresis procedure
  • This usually reduces the WBC count by 30 - 60%, although predicting the postprocedural WBC count is difficult due to mobilization of leukocytes from extramedullary sites
  • 6% hydroxyethyl starch (HES) is not necessary in leukemic patients
  • Red blood cell (RBC) units may be used with caution to prime the apheresis machine in patients with severe anemia but undiluted RBCs can increase the blood viscosity
  • Replacement fluid is recommended
  • Reference: J Clin Apher 2019;34:171
Adverse events
  • Leukapheresis is an apheresis procedure, with its typical complications
  • Also complications from the underlying leukemia, hypotension, citrate related toxicity, bleeding and infection
  • Elevated WBC
  • Elevated lactate dehydrogenase (LDH)
Case reports
  • 16 year old boy with hyperleukocytosis found to have T lymphoblastic leukemia / lymphoma (T ALL) was treated with leukocytapheresis and developed intracranial hemorrhage (J Pediatr Hematol Oncol 2021;43:e812)
  • 25 year old woman with chronic myeloid leukemia (CML) treated with leukocytapheresis (Cureus 2020;12:e12375)
  • 77 year old woman with chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL) was managed with leukocytapheresis (Am J Case Rep 2020;21:e924798)
  • Chemotherapy should be initiated as quickly as possible and should supersede leukocytapheresis if patients are asymptomatic
  • Therapeutic leukapheresis is not curative; WBC reduction is short lived and only a bridging therapy to definitive treatments such as chemotherapy
  • Studies show no improvement in early mortality with leukapheresis, though patients with symptomatic leukostasis are more likely to undergo the procedure (Transfusion 2020;60:2360)
  • Most studies are observational given the critically ill population investigated (Hematology 2022;27:141)
  • Symptomatic leukostasis treatment (J Clin Apher 2019;34:171)
    • Can be performed daily or as needed to treat leukemic patients with high WBC count with hyperviscosity syndrome
      • WBC count has a poor correlation with clinical symptoms; thus defining a WBC or blast goal is not optimal
      • Treatment should be continued until symptoms are resolved and WBC or blast count < 400,000/μL in ALL patients or < 50,000 - 100,000/μL in AML patients
    • Chemotherapy should be given concurrently with leukapheresis to prevent the rapid reaccumulation of WBC and blasts
    • Leukapheresis might decrease early death in leukemic patients with hyperviscosity but does not appear to increase overall survival
  • For prophylaxis (J Clin Apher 2019;34:171)
    • Leukapheresis is not superior to aggressive chemotherapy and supportive care
    • Might be useful in children with ALL and WBC > 400,000/μL (50% of these patients develop pulmonary complication from leukostasis)
    • Goal
      • ALL: WBC or blast count > 400,000/μL
      • AML: WBC or blast count > 100,000/μL
      • AML with monocytic differentiation: > 50,000/μL
Sample assessment & plan
  • Assessment: A 17 year old boy with T ALL underwent leukocytapheresis for hyperviscosity. 1.5 blood volumes were processed. Postprocedure WBC count is pending. The patient tolerated the procedure well.
  • Plan: Additional procedures will be performed as necessary to reduce WBC count > 400,000/μL but should not prevent initiation of chemotherapy.
Board review style question #1
A patient presents with the microgranular variant of acute promyelocytic leukemia (APL) with a white blood cell (WBC) count of 125,000/μL. What is the appropriate first step when a diagnosis is suspected?

  1. All trans retinoic acid (ATRA) therapy
  2. Induction chemotherapy
  3. Leukocytapheresis
  4. Stat PML::RARA t(15;17) fluorescence in situ hybridization (FISH)
Board review style answer #1
A. All trans retinoic acid (ATRA) therapy. Before a diagnosis is established, ATRA should be administered if APL is suspected or presumed as this can rapidly improve the risk of mortality. Newly diagnosed APL is a contraindication for leukocytapheresis due to risk of increased mortality. FISH analysis to confirm the diagnosis would be a good next step.

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Reference: Leukocytapheresis
Board review style question #2
What is the white blood cell (WBC) count suggested for prophylactic leukocytapheresis in B lymphoblastic leukemia / lymphoma (B ALL)?

  1. 20,000/μL
  2. 50,000/μL
  3. > 100,000/μL
  4. > 400,000/μL
Board review style answer #2
D. > 400,000/μL. For lymphoblastic leukemia / lymphoma, leukocytapheresis triggers are WBC or blast count > 400,000/μL. For acute myeloid leukemia (AML), WBC or blast count > 100,000/μL. For AML with monocytic differentiation, > 50,000/μL.

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Reference: Leukocytapheresis
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