Elevated Granulocyte Colony-Stimulating Factor, Non-Infectious Leukocytosis and Fevers in a Patient with Multiple Myeloma

Sebasky, Meghan M.; Gupta, Pankaj; Filice, Gregory

doi:10.1007/s11606-008-0789-4

Cited by 10 publications

(8 citation statements)

References 6 publications

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“…Truncating mutations of CSF3R can lead to both constitutive overexpression of the receptor and also to ligand hypersensitivity while proximal membrane mutations render cells ligand independent . We postulate that truncating and possibly other mutations of CSF3R can lead to toxic granulation and D€ ohle bodies in CNL whereas in neutrophilic leukaemoid reactions associated with plasma cell neoplasms similar cytological changes result from the synthesis of G-CSF by neoplastic plasma cells, which has been repeatedly demonstrated (Nagai et al, 1996;Saitoh & Shibata, 1996;Usuda et al, 1997;Kohmura et al, 2004;Kusaba et al, 2004;Sebasky et al, 2008;Rodr ıguez-Medina et al, 2013).…”

Section: Discussionmentioning

confidence: 76%

Chronic neutrophilic leukaemia and plasma cell‐related neutrophilic leukaemoid reactions

Bain

Ahmad

2015

Br J Haematol

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SummaryMany cases reported as 'chronic neutrophilic leukaemia' have had an associated plasma cell neoplasm. Recent evidence suggests that the great majority of such cases represent a neutrophilic leukaemoid reaction to the underlying multiple myeloma or monoclonal gammopathy of undetermined significance. We have analysed all accessible reported cases to clarify the likely diagnosis and to ascertain whether toxic granulation, D€ ohle bodies and an increased neutrophil alkaline phosphatase score were useful in making a distinction between chronic neutrophilic leukaemia and a neutrophilic leukaemoid reaction. We established that all these changes occur in both conditions. Toxic granulation and D€ ohle bodies are more consistently present in leukaemoid reactions but also occur quite frequently in chronic neutrophilic leukaemia. The neutrophil alkaline phosphatase score is increased in both conditions and is of no value in making a distinction.Keywords: monoclonal gammopathy of undetermined significance, multiple myeloma, chronic leukaemia, chronic neutrophilic leukaemia.As defined in the 2008 World Health Organization (WHO) classification (Bain et al, 2008), chronic neutrophilic leukaemia (CNL) is a Philadelphia-negative myeloproliferative neoplasm (MPN) characterized by a white cell count (WBC) of at least 25 9 10 9 /l with segmented neutrophils and band forms comprising more than 80% of leucocytes, circulating blast cells less than 1%, immature granulocytes (promyelocytes, myelocytes and metamyelocytes) less than 10% and monocytes less than 1Á0 9 10 9 /l. There is no evidence of another MPN or a myelodysplastic syndrome (MDS), no dysplasia in any lineage and no evidence of a myelodysplastic/myeloproliferative neoplasm (MDS/MPN). There should be no identifiable cause of physiological neutrophilia or, if such is present, there should be evidence of clonality. From the early 1900s onwards, more than 200 cases of CNL have been described but many of these would not meet current diagnostic criteria. The first known case meeting current criteria is that described by Tuohy in 1920 as 'A case of splenomegaly with polymorphonuclear neutrophil hyperleukocytosis' (Tuohy, 1920). However four other early cases had atypical features and appear more likely to have been primary myelofibrosis (Rathery, 1902;Hirschfeld, 1904;Emile-Weil & S ee, 1932). It is important to distinguish CNL from the neutrophilic leukaemoid reaction that can occur with multiple myeloma (plasma cell myeloma) and monoclonal gammopathy of undetermined significance (MGUS), which is attributable to cytokine release by neoplastic plasma cells. We were interested in reports of toxic granulation and D€ ohle bodies in patients considered to have CNL and we have also observed these phenomena in neutrophilic leukaemoid reactions. As toxic granulation is uncommon in myeloid neoplasms, this caused us to question whether some cases diagnosed as CNL might in fact have had a leukaemoid reaction to a plasma cell neoplasm. An increased neutrophil alkaline phosphatase (NAP) ...

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Section: Discussionmentioning

confidence: 76%

Chronic neutrophilic leukaemia and plasma cell‐related neutrophilic leukaemoid reactions

Bain

Ahmad

2015

Br J Haematol

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“…The presence of PL represented an ominous sign of poor prognosis (25). Prior studies have reported PL in hematopoietic malignancies, such as multiple myeloma and Hodgkin lymphoma (29–32). All of these patients presented with granulocytosis with predominant neutrophilia, elevated serum G‐CSF levels, and/or evidence of intratumor G‐CSF production (29–31).…”

Section: Discussionmentioning

confidence: 99%

“…Prior studies have reported PL in hematopoietic malignancies, such as multiple myeloma and Hodgkin lymphoma (29–32). All of these patients presented with granulocytosis with predominant neutrophilia, elevated serum G‐CSF levels, and/or evidence of intratumor G‐CSF production (29–31). Following initiation of chemotherapy, these patients showed signs of decreases in or normalization of leukocyte counts and/or of serum G‐CSF levels (29, 31, 32).…”

Section: Discussionmentioning

confidence: 99%

“…All of these patients presented with granulocytosis with predominant neutrophilia, elevated serum G‐CSF levels, and/or evidence of intratumor G‐CSF production (29–31). Following initiation of chemotherapy, these patients showed signs of decreases in or normalization of leukocyte counts and/or of serum G‐CSF levels (29, 31, 32). These reports attributed the presence of PL to G‐CSF‐producing tumors.…”

Section: Discussionmentioning

confidence: 99%

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Anaplastic large cell lymphoma with paraneoplastic leukocytosis: a clinicopathological analysis of five cases

Chang

Chen

et al. 2011

Apmis

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Anaplastic large cell lymphoma (ALCL) is a type of T-cell lymphoma with a relatively favorable prognosis. However, a certain group of ALCLs is highly aggressive, featuring paraneoplastic leukocytosis (PL) in clinical presentation. The present study evaluated five cases of ALCL presenting with PL, including four men and one woman, with a median age of 58 years. All cases revealed leukocytosis with a range from 15.3 to 112.9 × 10(3) /μL. Five (100%) and 4 (80%) cases demonstrated immunoreactivity for granulocyte-colony-stimulating factor (G-CSF) and tumor necrosis factor-alpha (TNF-α), respectively. There were significant differences in the expression of G-CSF and TNF-α between ALCL cases with or without PL (p < 0.05 for both). The prognosis of ALCL patients with PL was poor. Four of five patients (80%) died of the disease within a median survival time of 3.5 weeks. The release of G-CSF and TNF-α from lymphoma cells may associate with ALCL presenting with PL, leading to cytokine crisis and even poorer prognosis.

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“…It is currently not clear whether the CNL and plasma cell disorders are clonally related, or whether the neutrophilia occurs secondary to the underlying plasma cell neoplasm. Bain et al support the latter hypothesis with substantial additional data corroborating this, including studies demonstrating G‐CSF synthesis by neoplastic plasma cells, cases of spontaneous CNL remission, and improvements in neutrophil count following treatment of the underlying dysproteinemia . Furthermore, Pardanani et al did not identify a single CSF3R mutation in five cases of plasma cell neoplasm‐associated “CNL” .…”

Section: Disease Features and Diagnosismentioning

confidence: 99%

Chronic neutrophilic leukemia: 2020 update on diagnosis, molecular genetics, prognosis, and management

2019

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Disease overview: Chronic neutrophilic leukemia (CNL) is a rare, often aggressive myeloproliferative neoplasm (MPN) defined by persistent mature neutrophilic leukocytosis, bone marrow granulocyte hyperplasia, and frequent hepatosplenomegaly. The seminal discovery of oncogenic driver mutations in colony-stimulating factor 3 receptor (CSF3R) in the majority of patients with CNL in 2013 anchored a new scientific framework, deepening our understanding of its molecular pathogenesis, providing a diagnostic biomarker, and rationalizing the use of pharmacological targeting. Diagnostic criteria: In 2016, the World Health Organization (WHO) included the presence of activating CSF3R mutations as a central diagnostic feature of CNL. Other criteria include leukocytosis of ≥25 × 10 9 /L comprising >80% neutrophils with <10% circulating precursors and rare blasts, and absence of dysplasia or monocytosis, while not fulfilling criteria for other MPN.Disease updates: Increasingly comprehensive genetic profiling of CNL has disclosed a complex genomic landscape and additional prognostically relevant mutational combinations. Though prognostic determination and therapeutic decision-making remain challenging, emerging data on prognostic markers and the use of newer therapeutic agents, such as JAK inhibitors, are helping to define state-of-the-art management in CNL.

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Elevated Granulocyte Colony-Stimulating Factor, Non-Infectious Leukocytosis and Fevers in a Patient with Multiple Myeloma

Cited by 10 publications

References 6 publications

Chronic neutrophilic leukaemia and plasma cell‐related neutrophilic leukaemoid reactions

Chronic neutrophilic leukaemia and plasma cell‐related neutrophilic leukaemoid reactions

Anaplastic large cell lymphoma with paraneoplastic leukocytosis: a clinicopathological analysis of five cases

Chronic neutrophilic leukemia: 2020 update on diagnosis, molecular genetics, prognosis, and management

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