Transfusion medicine
Therapeutic apheresis
Leukocytapheresis
Editorial Board Member: Mrigender Singh Virk, M.D.
Last staff update: 31 May 2023 (update in progress)
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PubMed Search: Leukocytapheresis / therapeutic leukapheresis
Table of Contents
Definition / general | Essential features | Terminology | Pathophysiology | Clinical features | Symptoms | Vascular access | Indications | Volume exchanged and technical details | Adverse events | Laboratory | Case reports | Treatment | Sample assessment & plan | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Adkins BD, Booth GS. Leukocytapheresis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/transfusionmedleukocytapheresis.html. Accessed June 2nd, 2023.
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
Terminology
- 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
- More common in leukemia patients with monocytic or myeloid differentiation
Pathophysiology
- 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 happen in patients with blast count > 50,000/μL if they have 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)
- Acute myeloid leukemia (AML) with WBC > 100,000/μL
Clinical features
- Patients may present with disseminated intravascular coagulation (DIC), tumor lysis syndrome or hypoxic ischemic type injury
- Symptoms include vision changes, headache and shortness of breath
- Neurologic symptoms may progress if severe or if patient develops intracranial hemorrhage
Symptoms
- Symptoms manifest as hypoxic ischemic type injury associated with poor perfusion
- A grading schema 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 do not require radiographic confirmation
- Central venous catheter, which requires radiographic confirmation, can be used in nonemergent situations
Indications
- 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)
- All trans retinoic acid (ATRA) therapy is first line treatment for APL
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
Laboratory
- 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)
Treatment
- 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
- Can be performed daily or as needed to treat leukemic patients with high WBC count with hyperviscosity syndrome
- 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.
Additional references
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?
- All trans retinoic acid (ATRA) therapy
- Induction chemotherapy
- Leukocytapheresis
- 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 provided if APL is suspected as this improves risk of mortality rapidly. Newly diagnosed APL is a contraindication for leukocytapheresis due to risk of increased mortality. FISH and induction chemotherapy would be good next steps.
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Board review style question #2
What is the white blood cell (WBC) count suggested for prophylactic leukocytapheresis in B lymphoblastic leukemia / lymphoma (B ALL)?
- 20,000/μL
- 50,000/μL
- > 100,000/μL
- > 400,000/μL
Board review style answer #2
D. > 400,000/μL. For lymphoblastic leukemia / lymphoma, leukocytapheresis goals 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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