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Leukemoid reaction in the pediatric population: etiologies, outcome, and implications

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Abstract

Leukemoid reaction (WBC > 30,000/μL) may indicate significant medical conditions, mostly infectious. Prompted by the lack of population-based data on the presentation, characteristics, and necessary workup in children with leukemoid reaction, we searched the database of a tertiary pediatric medical center for all children presented with at least one WBC count of ≥ 30,000/μL in 2009–2014. Demographic, clinical, and laboratory parameters were recorded. Children admitted with WBC < 30,000/μL served as controls. Pneumonia was the most common diagnosis in the leukemoid reaction group, with a 5.5-fold higher prevalence of pleuropneumonia than in the control group. The leukemoid group had a longer average hospital stay (7.5 vs. 5.5 days). Patients with WBC ≥ 50,000/μL had a sixfold higher rate of leukemia than patients with a lower count. There was a significant association of leukemia with low platelet count, low levels of C-reactive protein, and high levels of uric acid and lactate dehydrogenase.

Conclusion: Children presented with a leukemoid reaction are at high risk of pneumonia, especially pleuropneumonia, and a long hospital stay. Those with WBC ≥ 50,000/μL have a sixfold higher risk of leukemia. For prompt diagnosis, clinicians should be aware of the variables associated with leukemia.

What is Known:

• Leukemoid reaction has been associated with infectious diseases.

• Leukemoid reaction at presentation in adults is correlated with high morbidity and mortality.

What is New:

• Children with leukemoid reaction are at high risk of pleuropneumonia.

• We did not observe increased mortality in children with a leukemoid reaction.

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Abbreviations

ANC:

Absolute neutrophil count

ALC:

Absolute lymphocyte count

CRP:

C-reactive protein

DKA:

Diabetic ketoacidosis

ENT:

Ear, nose, and throat

ESR:

Erythrocyte sedimentation rate

OR:

Odds ratio

WBC:

White blood cells

References

  1. Au WY, Ma SK, Kwong YL (2001) Disseminated hepatosplenic mycobacterial infection masking myeloproliferative diseases as leukemoid reaction: a diagnostic pitfall. Leuk Lymphoma 42:805–808

    Article  PubMed  CAS  Google Scholar 

  2. Azim T, Qadri F, Ahmed S, Sarker MS, Halder RC, Hamadani J, Chowdhury A, Wahed MA, Salam MA, Albert MJ (1996) Lipopolysaccharide-specific antibodies in plasma and stools of children with Shigella-associated leukemoid reaction and hemolytic–uremic syndrome. Clin Diagn Lab Immunol 3:701–705

    PubMed  PubMed Central  CAS  Google Scholar 

  3. Beigelman A, Kapelushnik J, Shubinsky G, Haim A, Moser AM (2007) Leukemoid reaction in children: lymphocytes flow cytometry characterization and clinical etiologies. J Allergy Clin Immunol 119:S178

    Article  Google Scholar 

  4. Boggs DR, Joyce RA (1983) The hematopoietic effects of lithium. Semin Hematol 20:129–138

    PubMed  CAS  Google Scholar 

  5. Boxer LA, Stossel TP (1974) Effects of anti-human neutrophil antibodies in vitro. Quantitative studies. J Clin Invest 53:1534–1545

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Brauner M, Goldman M, Kozer E (2010) Extreme leucocytosis and the risk of serious bacterial infections in febrile children. Arch Dis Child 95:209–212

    Article  PubMed  Google Scholar 

  7. Butler T, Islam MR, Bardhan PK (1984) The leukemoid reaction in shigellosis. Am J Child 138:162–165

    CAS  Google Scholar 

  8. Dignan PS, Mauer AM, Franz CJ (1967) Phocomelia with congenital hypoplastic thrombocytopenia and myeloid leukemoid reactions. J Pediatr 70:561–573

    Article  PubMed  CAS  Google Scholar 

  9. Duran R, Ozbek UV, Ciftdemir NA, Acunaş B, Süt N (2010) The relationship between leukemoid reaction and perinatal morbidity, mortality, and chorioamnionitis in low birth weight infants. Int J Infect Dis 14:e998–e1001

    Article  PubMed  Google Scholar 

  10. Emery JL, Gordon RR, Rendleshort J, Varadi S, Warrack AJ (1957) Congenital amegakaryocytic thrombocytopenia with congenital deformities and a leukemoid blood picture in the newborn. Blood 12:567–576

    PubMed  CAS  Google Scholar 

  11. Etzioni A, Harlan JM (2007) Cell adhesion and leukocyte adhesion defects. In: Ochs HD, Smith CIE, Puck JM (eds) Primary immunodeficiency diseases, 2nd edn. Oxford University Press, New York, pp 550–564

    Google Scholar 

  12. Ganti AK, Potti A, Mehdi S (2003) Uncommon syndromes and treatment manifestations of malignancy: case 2. Metastatic non-small-cell lung cancer presenting with leukocytosis. J Clin Oncol 21:168–170

    Article  PubMed  Google Scholar 

  13. George TI (2012) Malignant or benign leukocytosis. Hematol Am Soc Hematol Educ Program 2012:475–484

    Google Scholar 

  14. Granger JM, Kontoyiannis DP (2009) Etiology and outcome of extreme leukocytosis in 758 nonhematologic cancer patients: a retrospective, single-institution study. Cancer 115:3919–3923

    Article  PubMed  Google Scholar 

  15. Hsiao R, Omar SA (2005) Outcome of extremely low birth weight infants with leukemoid reaction. Pediatrics 116:e43–e351

  16. Kasuga I, Makino S, Kiyokawa H, Katoh H, Ebihara Y, Ohyashiki K (2001) Tumor-related leukocytosis is linked with poor prognosis in patients with lung carcinoma. Cancer 92:2399–2405

    Article  PubMed  CAS  Google Scholar 

  17. Khan WA, Griffiths JK, Bennish ML (2013) Gastrointestinal and extra-intestinal manifestations of childhood shigellosis in a region where all four species of Shigella are endemic. PLoS One 8:e64097

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Krumbhaar EB (1926) Leukemoid blood pictures in various clinical conditions. Am J Med Sci 172:519–532

    Article  Google Scholar 

  19. Marinella MA, Burdette SD, Bedimo R, Markert RJ (2004) Leukemoid reactions complicating colitis due to Clostridium difficile. South Med J 97:959–963

    Article  PubMed  Google Scholar 

  20. McKee Jr LC (1985) Excess leukocytosis (leukemoid reactions) associated with malignant diseases. South Med J 78:1475–1482

    Article  CAS  Google Scholar 

  21. Mycyk MB, Drendel A, Sigg T, Leikin JB (2002) Leukemoid response in ethylene glycol toxication. Vet Hum Toxicol 44:304–306

    PubMed  Google Scholar 

  22. Naaraayan A, Aleta M, Basak P, Jesmajian S, Goldstein R (2015) Leukemoid reaction to Clostridium difficile infection. Anaerobe 34:158–160

    Article  PubMed  Google Scholar 

  23. Nimieri HS, Makoni SN, Madziwa FH, Nemiary DS (2003) Leukemoid reaction response to chemotherapy and radiotherapy in a patient with cervical carcinoma. Ann Hematol 82:316–317

    PubMed  CAS  Google Scholar 

  24. Potasman I, Grupper M (2013) Leukemoid reaction: spectrum and prognosis of 173 adult patients. Clin Infect Dis 57:e177–e181

    Article  PubMed  Google Scholar 

  25. Reding MT, Hibbs JR, Morrison VA, Swaim WR, Filice GA (1998) Diagnosis and outcome of 100 consecutive patients with extreme granulocytic leukocytosis. Am J Med 104:12–16

    Article  PubMed  CAS  Google Scholar 

  26. Sakka V, Tsiodras S, Giamarellos-Bourboulis EJ, Giamarellou H (2006) An update on the etiology and diagnostic evaluation of a leukemoid reaction. Eur J Intern Med 17:394–398

    Article  PubMed  CAS  Google Scholar 

  27. Wang YJ, Shian WJ, Chu HY, Chi CS (1994) Leukemoid reaction in a child with appendiceal abscess: a case report. Zhonghua Yi Xue Za Zhi (Taipei) 53:311–314

    CAS  Google Scholar 

  28. Weinstein HJ (1978) Congenital leukaemia and the neonatal myeloproliferative disorders associated with Down's syndrome. Clin Haematol 7:147–154

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics A and Unit of Pediatric Infectious Diseases, Schneider Children’s Medical Center of Israel, 14 Kaplan Street, 4920235, Petah Tikva, Israel

    Assaf Hoofien, Havatzelet Yarden-Bilavski, Shai Ashkenazi & Gilat Livni

  2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Havatzelet Yarden-Bilavski, Shai Ashkenazi, Gabriel Chodick & Gilat Livni

Authors
  1. Assaf Hoofien
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  2. Havatzelet Yarden-Bilavski
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  3. Shai Ashkenazi
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  4. Gabriel Chodick
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  5. Gilat Livni
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Contributions

Assaf Hoofien – initial data collection study design, writing and editing of drafts, writing and approval of final manuscript.

Havatzelet Yarden-Bilavski – study design, writing and approval of final manuscript.

Shai Ashkenazi – study design, writing and approval of final manuscript.

Gabriel Chodick – data analysis and statistics, writing and approval of final manuscript.

Gilat Livni – study design, writing and editing of drafts, writing and approval of final manuscript.

Corresponding author

Correspondence to Gilat Livni.

Ethics declarations

Ethical approval

This study was approved by the ethics committee of our medical center. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was waived by the ethics committee.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Communicated by Peter de Winter

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Cite this article

Hoofien, A., Yarden-Bilavski, H., Ashkenazi, S. et al. Leukemoid reaction in the pediatric population: etiologies, outcome, and implications. Eur J Pediatr 177, 1029–1036 (2018). https://doi.org/10.1007/s00431-018-3155-5

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  • DOI: https://doi.org/10.1007/s00431-018-3155-5

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