Granulocyte‐macrophage colony‐stimulating factor as a cause of paraneoplastic leukaemoid reaction in advanced transitional cell carcinoma

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Abstract
Increasing evidence suggests that paraneoplastic syndromes may be mediated by tumour‐related cytokine release, although the specific factor(s) involved remain poorly defined. Colony‐stimulating factors (CSF) and interleukins (IL) promote colony growth in semi‐solid media and, when administered in recombinant form, increase blood counts in patients. However, normal serum CSF levels in individuals with physiologic blood counts and the relationship between specific serum CSF levels and paraneoplastic leukaemoid reaction are not well established. In this study, we found that normal serum levels of granulocyte‐macrophage CSF (GM‐CSF), as measured by ELISA, were generally < 55 pg ml−1; IL‐3, < 30 pg ml−1; and granulocyte CSF (G‐CSF), < 50 pg ml−1. In contrast, high levels of GM‐CSF (132 pg ml−1), but not G‐CSF or IL‐3, were found in a patient with a transitional cell carcinoma of the renal pelvis and increased leukocytosis correlating with the tumour burden. The GM‐CSF was biologically active, as demonstrated by its ability to stimulate colony growth in vitro. Based on these results it appears that autonomous production of GM‐CSF is one possible pathophysiologic mechanism underlying leukaemoid reaction in cancer patients.