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Leukemoid Reaction

A leukocyte count of 50 × 103/mm3 represents a leukemoid reaction and severe infections that lead to sepsis are the most common cause. Hematologic malignancies, prematurity and metastatic cancers can induce this reaction as well and the prognosis is poor if not recognized promptly. The diagnosis is made by through complete blood count and a detailed investigation to determine the underlying cause is necessary to treat this disorder.


Symptoms depend on the underlying cause, but because systemic infections and malignancies are probable culprits, most common signs are anemia, constitutional symptoms (malaise, fatigue, weakness) and high fever. Organ-related signs in various infections (cough in the setting of pneumonia, diarrhea and abdominal pain in gastrointestinal infections, etc.) can be readily observed, but LR can also occur as a paraneoplastic syndrome, which is why a thorough workup is paramount to determine the condition that triggered this phenomenon [5].

Larva Migrans
  • […] of dapsone Use of glucocorticoids Use of G-CSF or related growth factors All-trans retinoic acid (ATRA) Ethylene glycol intoxication Infections Clostridium difficile Tuberculosis Pertussis Infectious mononucleosis ( lymphocyte predominant) Visceral larva[en.wikipedia.org]


A complete blood count that confirms the presence of ≥ 50 × 103/mm3 or an absolute neutrophil count (ANC) of ≥ 30 103/mm3 is diagnostic for LR [1] [5]. Blood cultures, imaging studies such as computed tomography (CT) or magnetic resonance imaging (MRI), but also hematologic tests including peripheral smears and potentially bone marrow biopsy are necessary, in order to confirm the underlying cause.

  • Infection induced hemophagocytic lymphohistiocytosis with a leukemoid reaction was suspected because of fever, splenomegaly and bicytopenia in conjunction with elevated serum triglycerides and ferritin.[ncbi.nlm.nih.gov]


Treatment is aimed at the condition that induced LR. Aggressive antibiotics are used against infections and sepsis, whereas a combined approach to malignant diseases is used based on tumor staging and type. Symptomatic therapy in the form of fluid restoration, ensuring adequate tissue oxygenation and proper cardiovascular function is mandatory to preserve vital body functions and provide enough time to target the primary illness.


LR carries a grave prognosis in elderly patients and in those in whom sepsis is the underlying cause, whereas longer duration of LR is also a poor predictor of survival [5]. For these reasons, a prompt diagnosis and treatment of the underlying cause is vital.


The exact cause of LR remains unknown, as the condition appears in infections, hematologic malignancies, but also as a paraneoplastic disorder [2]. Abnormal activity of proinflammatory cytokines such as interleukins 1 and 6 (IL-1 and IL-6, respectively) and granulocyte-colony stimulating factor (G-CSF) is suggested as the cause, as it has been documented in some cases [6].


Data regarding the epidemiology of LR are scarce [5], but its occurrence is seen in 1.3-15% of neonates in the intensive care unit [2], whereas 1-4% of patients with malignant bone tumors develop this reaction [3]. Several conditions have shown to significantly increase the risk for LR, such as bronchopulmonary dysplasia, premature birth and exposure to antenatal steroids [1].

Sex distribution
Age distribution


The pathogenesis of leukemoid reaction remains unclear. Presumably, proinflammatory cytokines and G-CSF are produced in very high concentrations and cause overt leukocytic proliferation, and increased G-CSF was confirmed in paraneoplastic forms of LR [4].


Current preventive strategies are unknown.


A leukemoid reaction (LR) is defined as a leukocyte count of ≥ 50 × 103/mm3 and absolute neutrophil count (ANC) of ≥ 30 103/mm3, and it may occur in a variety of conditions [1] [2]. Infections, severe anemia, bronchopulmonary dysplasia, chromosomal abnormalities, but also prematurity have all known to induce profound proliferation of leukocytes [1] [2]. The pathogenesis, however, is yet to be determined, with most probable theories including genetic defects and aberrant activation of proinflammatory cytokines [3]. Abnormal activation of granulocyte-colony stimulating factor (G-CSF) has been described in a paraneoplastic-induced leukemoid reaction [4]. Infection is the most probable cause of this phenomenon and constitutional symptoms accompanied by fever and a range of manifestations depending on the type of infection (or malignancy) are usually present [5]. To make the diagnosis, it is necessary to perform a complete blood count (CBC) and try to find the underlying disease through blood cultures for infection, blood smears and potentially bone marrow biopsy for hematologic malignancies and imaging studies to exclude metastatic cancer [3]. Treatment aims to resolve the underlying cause, but prompt identification of the disorder and the condition that induced it is pivotal in reducing mortality rates, which have shown to be much higher if a leukemoid reaction is present for a prolonged period of time [5].

Patient Information

A leukemoid reaction (LR) is a clinical phenomenon characterized by abundant production and activation of white blood cells, most commonly as a result of infection and it is seen in patients of all ages, including newborn children. The exact cause remains unknown, but it is thought that trigger inflammation (infections and blood cancers) somehow cause overt stimulation of molecules that induce proliferation of white blood cells. LR carries a poor prognosis if not recognized on time and factors that further reduce the risk of survival are older age and a longer duration of LR, which emphasizes the importance of an early diagnosis. LR is confirmed by a complete blood count and observation of very high levels of leukocytes (and sometimes neutrophils), whereas additional studies should be performed to identify the underlying cause - cultures to detect infection and imaging studies such as computed tomography or magnetic resonance imaging to detect cancer. Treatment of LR necessitates treatment of the disorder that induced it.



  1. Hsiao R, Omar SA. Outcome of extremely low birth weight infants with leukemoid reaction. Pediatrics. 2005;116(1):e43-51.
  2. Duran R, Ozbek UV, Ciftdemir NA, Acunaş B, Süt N. The relationship between leukemoid reaction and perinatal morbidity, mortality, and chorioamnionitis in low birth weight infants. Int J Infect Dis. 2010;14(11):e998-1001.
  3. Ma X, Li G, Cai Z, Sun W, Liu J, Zhang F. Leukemoid reaction in malignant bone tumor patients - a retrospective, single-institution study. Eur Rev Med Pharmacol Sci. 2012;16(14):1895-1899.
  4. Kasi Loknath Kumar A, Satyan MT, Holzbeierlein J, Mirza M, Van Veldhuizen P. Leukemoid reaction and autocrine growth of bladder cancer induced by paraneoplastic production of granulocyte colony-stimulating factor – a potential neoplastic marker: a case report and review of the literature. Journal of Medical Case Reports. 2014;8:147.
  5. Potasman I, Grupper M. Leukemoid reaction: spectrum and prognosis of 173 adult patients. Clin Infect Dis. 2013;57(11):e177-181.
  6. Jardin F, Vasse M, Debled M, et al. Intense paraneoplastic neutrophilic leukemoid reaction related to a G-CSF-secreting lung sarcoma. Am J Hematol. 2005;80(3):243-245.

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Last updated: 2018-06-22 05:18