The Significance of Leukocytosis in Malignancies: A Novel Paradigm Between Leukocytosis, G-CSF, Myeloid-Derived Suppressor Cells and Prognosis

• Published in: Blood 2018-11, Vol.132 (Supplement 1), p.4944-4944
• Main Authors: Tavakkoli, Montreh, Wilkins, Cy, Mones, Jodi V, Mauro, Michael J.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2018-99-117484

In clinical practice, leukocytosis is often overlooked after infectious and hematologic disease are ruled out, particularly in patients with solid tumors. This is unfortunate, as the mechanisms that mediate paraneoplastic leukocytosis may play a significant role in the underlying pathophysiology of cancer progression and prognosis. The relatively new discovery of neutrophilic and monocytic myeloid-derived suppressor cells (MDSCs) and their role in mediating tumor metastasis has particularly shed light into this process [Annu Rev Med, 66:97-110 (2015)]. Here, we present the case of a 58-year old gentleman with non-small cell lung cancer complicated by brain metastasis, status post resection who presented with sepsis and acute kidney injury (AKI) requiring ICU care for worsening AKI, hypoxic respiratory failure and leukocytosis. His peak WBC count, absolute neutrophilia and monocytosis were: 178.1, 172.7 and 4.2k/µL, respectively. His peripheral blood smear revealed mature neutrophils with left-shift and no blast forms. The underlying etiology of his leukocytosis was initially attributed to steroids administration and infection (Figure 1). His leukocytosis progressed, however, despite improvement in his sepsis and tapering of his steroids. Thus, we suspected either an evolving hematologic neoplasm or exogenous secretion of G-CSF by his tumor. Nonetheless, given his worsening clinical status, we initiated empiric hydroxyurea and leukapheresis. His FISH and PCR for BCR-ABL were negative in addition to the absence of leukemia-associated mutations and gene fusions and a normal phenotype by flow cytometry. However, we detected the highest documented level of G-CSF secreted by any tumor in the literature at 41,108.6pg/mL (normal