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LEUKEMOID REACTION: The Review: More Than Just Mimicry

An increase in the white cell count, which can be due to either an infection, inflammatory process, drug exposure or an underlying malignancy is known as leukocytosis. However, a leukemoid reaction is more than just leukocytosis. It is ‘leukemoid’ to show a similitude with leukaemia, one of the many haematological malignancies. Leukemoid reaction is a diagnosis of exclusion in many cases, but this is not the whole story about this quite perplexing entity. In today’s article, we shall review the definition, causes and diagnostic evaluation of this haematological disorder. It is more than just mimicry. Let’s get started.

By definition, a leukemoid reaction is having a leukocyte count greater than 50,000 cells/վL caused by factors/ diseases outside the bone marrow. There’s usually a persistent neutrophilia in the peripheral blood with a marked shift to the left on cell differential.

Both chronic myelogenous leukaemia (CML) and chronic neutrophilic leukaemia are landmarks. The basis of a leukemoid reaction rests on excluding them. Salient features that distinguish it from either CML or CNL exist. They are:- the absence of immature neutrophils, basophilia or monocytosis, increased leukocyte alkaline phosphatase (LAP), and absent cytogenetic abnormalities like bcr/abl translocation. 

Finding a leukemoid reaction in a patient with cancer is a sign of poor prognosis. However, this is a rare but well-recognized entity.

There are several causes of a leukemoid reaction. They are:- severe infections like Clostridium difficle colitis, disseminated or military tuberculosis, and severe shigellosis, malignancies like cancer of the lungs, oropharynx, gastrointestinal tract and genitourinary system, Hodgkin’s lymphoma, melanoma, and sarcoma, exposure to drugs like corticosteroids, minocycline, and recombinant haematopoietic growth factors, intoxication like ethylene glycol, retroperitoneal haemorrhage and other conditions like mesenteric inflammatory pseudotumor, and alcoholic steatohepatitis.

For the diagnostic evaluation of a leukemoid reaction, focused history, physical examination with a few noninvasive investigations should always obviate the diagnosis. As earlier said, it is a diagnosis of exclusion, due to the possibility of mimicry with either CML or CNL. 

Related article:

COMPLETE BLOOD COUNT: What You Need to Know.

After a thorough history and physical examination, several investigations can help the clinician delineate the possible aetiology. They are:- complete blood count with differential and peripheral blood smear, leukocyte alkaline phosphatase (LAP) score, serum Vitamin B12, and vitamin B12 binding capacity, bone marrow aspiration and biopsy, cytogenetic testing and molecular analysis of peripheral blood and bone marrow granulocytes, immunophenotyping of peripheral blood and bone marrow, serum levels of haematopoietic growth factors, cultures, imaging studies, and human androgen receptor gene assay (HUMARA).

With the investigations above, the following table can help differentiate a leukemoid reaction from either chronic myeloid leukaemia or chronic neutrophilic leukaemia.

Leukemoid reactionChronic myelogenous leukaemiaChronic neutrophilic leukaemia
Peripheral bloodMature neutrophils, marked "left shift"Immature cells, basophils, and eosinophilsMarked neutrophilia, no immature cells
LAP scoreHighLowHigh
Serum vitamin B12Variable?, highHighHigh
Bone marrowMyeloid hyperplasia, orderly maturation, normal morphologyBasophilia, eosinophilia, monocytosis, slight increase in blasts and reticulin fibrosisSimilar morphology with leukemoid reaction, packed bone marrow, slight increase in reticulin
Cytogenetic analysisNo cytogenetic abnormalitiesbcr/abl translocationCytogenetic abnormalities in 37% of cases
ImmunophenotypingCD13 (+++), CD15 (+++), CD34 (-), HLA-DR (-)CD13 (+++), CD15 (+++), CD34 (-), HLA-DR (+)CD13 (+++), CD15 (+++), CD34 (-), HLA-DR (+)
Serum G-CSFHigh (a)LowLow
Clonality studiesPolyclonalMonoclonalMonoclonal

In a nutshell, leukemoid reaction diagnosis can be challenging and requires a well thought out work-up such that clinicians promptly diagnose the offending disease entity and hence treated. The features that should confirm a leukemoid reaction but rule out CML or CNL include: a complete blood count with a peripheral smear showing marked neutrophilia with a left shift, a high LAP score, hypercellular bone marrow with normal cells, absence of cytogenetic abnormalities, mature granulocyte pattern, and a polyclonal pattern of blood neutrophils among others.

You can read more about leukemoid reaction through this article from here.

We dedicate this article is to these four brilliant doctors; Dr Bogere Naghib, Dr Naturinda Earnest, Dr Ssebambulidde Kenneth, and Dr Abiira Nathan.


MBChB (MUK), Graduate Fellow, Department of Physiology, Makerere University Founder and Content Creator Peer reviewer, Associate Editor

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