Leukocytapheresis for patients with acute myeloid leukemia presenting with hyperleukocytosis and leukostasis: a contemporary appraisal of outcomes and benefits

ABSTRACT

Introduction

Hyperleukocytosis, defined as a total white blood cell count (WBC) >50 or more commonly >100 × 10⁹ cells/L, is a presenting feature of acute myeloid leukemia (AML) in about 6–20% of cases and is associated with a higher risk of tumor lysis syndrome (TLS), disseminated intravascular coagulation (DIC), clinical leukostasis with end organ damage, and mortality.

Areas covered

In this review, authors discuss the implications of hyperleukocytosis in AML and the current understanding of cytoreductive strategies with a focus on the use of leukocytapheresis.

Expert commentary

Efforts to rapidly reduce peripheral myeloblasts have included the use of leukocytapheresis. Early studies demonstrated feasibility in reducing peripheral WBC and blast counts as well as clinically relevant patient outcomes which prompted its common use for many years. However, more recent data have directly challenged the previously touted reports of reduced TLS and DIC incidence as well as survival benefit, even in patients with clinical leukostasis. The use of leukocytapheresis remains highly controversial with wide practice variations among physicians, institutions, and countries given the lack of high-quality data, risks associated with leukocytapheresis itself, associated high costs, resource utilization, and lack of evidence-based clinical guidelines.

KEYWORDS:

• Acute myeloid leukemia
• AML
• hyperleukocytosis
• leukocytapheresis
• leukapheresis

Article highlights

• Hyperleukocytosis, commonly defined as a WBC >50 or >100 x 10⁹ cells/L, is a feature in up to 20% of all newly diagnosed AML and frequently co-associates with TLS, DIC, leukostasis, and early death.

• The majority of studies demonstrate no clear benefit with the use of leukapheresis and as a result its use appears to be declining.

• Timely and definitive leukemia-directed chemotherapy remains the gold standard treatment for AML patients with hyperleukocytosis.

• Novel therapies that inhibit the mediators of vascular endothelium-myeloblast adherence (e.g. selectins, vascular cell adhesion molecule-1, intracellular adhesion molecule-1), endothelial activation (e.g. tumor necrosis factor-α or interleukin-1β) and soft tissue infiltration (e.g. metalloproteinase) are needed.

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Declaration of interest

A.M. Zeidan received research funding (institutional) from Celgene, Acceleron, Abbvie, Otsuka, Pfizer, Medimmune/AstraZeneca, Boehringer-Ingelheim, Trovagene, Incyte, Takeda, and ADC Therapeutics. A.M.Z had a consultancy with and received honoraria from AbbVie, Otsuka, Pfizer, Celgene, Ariad, Incyte, Agios, Boehringer-Ingelheim, Novartis, Acceleron, Astellas, Daiichi Sankyo, Cardinal Health, Seattle Genetics, BeyondSpring, and Takeda. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.