Review article
An update on the etiology and diagnostic evaluation of a leukemoid reaction

https://doi.org/10.1016/j.ejim.2006.04.004Get rights and content

Abstract

Persistent neutrophilic leukocytosis above 50,000 cells/μL when the cause is other than leukemia defines a leukemoid reaction. The diagnostic work-up consists of the exclusion of chronic myelogenous leukemia (CML) and chronic neutrophilic leukemia (CNL) and the detection of an underlying cause. The major causes of leukemoid reactions are severe infections, intoxications, malignancies, severe hemorrhage, or acute hemolysis. The present article points out the difficulties in the differential diagnosis of a leukemoid reaction and suggests an algorithm for a rational clinical and laboratory evaluation of this problematic entity.

Introduction

A leukemoid reaction (LR) is a hematological disorder, defined by a leukocyte count greater than 50,000 cells/μL, caused by reactive causes outside the bone marrow [1], [2]. It is characterized by a significant increase in mature neutrophils in the peripheral blood and a differential count showing marked left shift [2]. The diagnosis of LR is based on the exclusion of chronic myelogenous leukemia (CML) and chronic neutrophilic leukemia (CNL). The absence of immature cells, basophilia or monocytosis, increased leukocyte alkaline phosphatase (LAP), and the absence of the bcr/abl translocation distinguishes LR from CML. CNL is a rare, distinct myeloproliferative syndrome with a poor prognosis [3]. The differential diagnosis between LR and CNL may be difficult or even impossible because both conditions share identical morphological features, including a raised LAP score and the absence of the bcr/abl translocation [3].

The current review discusses the different causes of LR, pointing out the difficulties in the differential diagnosis. Moreover, a diagnostic approach to a rational clinical and laboratory evaluation that mainly refers to an isolated LR is proposed.

Section snippets

Etiology

The major causes of LRs are severe infections, intoxications, malignancies, severe hemorrhage, or acute hemolysis (Table 1). A variety of infections, such as colitis due to Clostridium difficile, disseminated tuberculosis [4], and severe shigellosis, have been associated with an LR. C. difficile colitis with an LR appears to be associated with a much higher mortality rate (∼ 50%) [5]. A study of 111 children with Shigella dysenteriae type 1 infection revealed 25 patients with LR. Its presence

Diagnostic evaluation

An LR is, by definition, diagnosed after the exclusion of a malignant hematological disorder. In the case of concomitant polycythemia vera or thrombocytosis,a diagnostic approach concerning general myeloproliferative diseases should be made. However, the underlying cause of an LR is usually obvious. The clinician should obtain a clear history which, together with a good physical examination and limited imaging procedures, may provide significant clues to a diagnosis, such as a neoplasm or an

Conclusions

A LR is a rare condition that can be challenging and that may require a careful diagnostic work-up. The diagnosis is verified by a combination of the following: (i) a complete blood count with a peripheral blood smear that shows marked mature neutrophilia with a left shift; (ii) a high leukocyte alkaline phosphatase (LAP) score; (iii) hypercellular bone marrow with intact maturation and morphology of all the elements; (iv) the absence of cytogenetic abnormalities by cytogenetic-molecular

References (24)

  • H.S. Nimieri et al.

    Leukemoid reaction response to chemotherapy and radiotherapy in a patient with cervical carcinoma

    Ann Hematol

    (2003)
  • J.T. Curnutte et al.

    Disorders of phagocyte function and number

  • J. Bohm et al.

    Evidence of clonality in chronic neutrophilic leukaemia

    J Clin Pathol

    (2003)
  • W.Y. Au et al.

    Disseminated hepatosplenic mycobacterial infection masking myeloproliferative diseases as leukemoid reaction: a diagnostic pitfall

    Leuk Lymphoma

    (2001)
  • M.A. Marinella et al.

    Leukemoid reactions complicating colitis due to Clostridium difficile

    South Med J

    (2004)
  • T. Azim et al.

    Lipopolysaccharide-specific antibodies in plasma and stools of children with Shigella-associated leukemoid reaction and hemolytic–uremic syndrome

    Clin Diagn Lab Immunol

    (1996)
  • A.K. Ganti et al.

    Uncommon syndromes and treatment manifestations of malignancy: case 2. Metastatic non-small-cell lung cancer presenting with leukocytosis

    J Clin Oncol

    (2003)
  • M.B. Mycyk et al.

    Leukemoid response in ethylene glycol toxication

    Vet Hum Toxicol

    (2002)
  • T. Kutluk et al.

    Mesenteric inflammatory pseudotumor: unusual presentation with leukemoid reaction and massive calcified mass

    J Pediatr Hematol Oncol

    (2002)
  • J.V. Juturi et al.

    Severe leukocytosis with neutrophilia (leukemoid reaction) in alcoholic steatohepatitis

    Am J Gastroenterol

    (1998)
  • C. Arguelles-Grande et al.

    Steroidal management and serum cytokine profile of a case of alcoholic hepatitis with leukemoid reaction

    Scand J Gastroenterol

    (2002)
  • M.A. Marinella

    Extreme leukemoid reaction associated with retroperitoneal hemorrhage

    Arch Intern Med

    (1998)
  • Cited by (82)

    • Jaundice with severe leucocytosis

      2024, Journal of Hepatology
    • Paraneoplastic leukemoid reaction: Case report and review of the literature

      2021, Pathology Research and Practice
      Citation Excerpt :

      Many cutoff points have been suggested; the most widely accepted are white blood cell (WBC) counts >40 or 50 K/μL [4]. The major causes of LRs are severe infection, intoxication, severe hemorrhage, acute hemolysis, and malignancy [5]. Paraneoplastic leukemoid reaction (PLR) is a hematologic abnormality in which a leukemoid reaction occurs in the presence of solid malignancy, excluding cases in which the bone marrow is infiltrated by tumor [6].

    View all citing articles on Scopus
    View full text