Case Report
Acutely deteriorated extravascular volume overload during peripheral blood stem cell mobilization in POEMS syndrome: A case series with cytokine analysis

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Abstract

We describe two cases of polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS) syndrome patients with deteriorated extravascular volume overload without increased levels of vascular endothelial growth factor after the administration of cyclophosphamide + granulocyte colony-stimulating factor for stem cell mobilization. We then measured the serum levels of 27 cytokines from these cases using a multiplex suspension array system. The analysis revealed the changes of cytokine profiles before cyclophosphamide + granulocyte colony-stimulating factor and after the development of capillary leak symptoms in both cases. This may improve our current level of understanding of the pathogenesis of POEMS syndrome not driven by vascular endothelial growth factor.

Introduction

Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS) syndrome is a rare plasma cell disorder characterized by the constituent ailments that comprise its name. Signs of extravascular volume overload, which are frequently observed in POEMS syndrome, are among the most common preterminal events in POEMS syndrome [1]. It has been speculated that elevated levels of vascular endothelial growth factor (VEGF) play a crucial role in inducing extravascular volume overload via angiogenesis and microvascular hyperpermeability [1], [2]. However, discrepancies between disease activity and VEGF levels in POEMS syndrome patients have been reported [3]. Additionally, the efficacy of the anti-VEGF monoclonal antibody bevacizumab for POEMS syndrome patients has been a matter of controversy due to mixed study results [4], [5], [6]. Furthermore, several other cytokines, such as interleukin (IL)-6, IL-12, tumor necrosis factor-α, and hepatocyte growth factor, have been reported to be elevated in POEMS syndrome [7], [8], [9]. Therefore, VEGF may not be the driving force behind this disorder. Here we report two cases of patients with POEMS syndrome with acutely deteriorated extravascular volume overload without increased levels of VEGF after the administration of high dose cyclophosphamide (HD-CY) + granulocyte colony-stimulating factor (G-CSF) (CG) for peripheral blood stem cell (PBSC) mobilization. We then measured serum levels of 27 cytokines from these cases before and after CG using a multiplex suspension array system, and analyzed the changes in their cytokine profiles during their clinical courses.

Section snippets

Case 1

The first case (case 1) is a 61-year-old man who was diagnosed with POEMS syndrome and was referred to our institution in July 2008. His clinical course is shown in Fig. 1. The day of administration of G-CSF for PBSC collection is defined as day 0. The patient presented with monoclonal gammopathy (IgG-λ), a slight left pleural effusion, hepatosplenomegaly, and polyneuropathy with a performance status of 2. The level of serum VEGF was 8160 pg/mL on day minus 29. He was treated with high-dose

Case 2

The second case (case 2) is a 64-year-old woman who was diagnosed with POEMS syndrome with monoclonal gammopathy (IgG-λ), polyneuropathy, a left pleural effusion, and pericardial effusion at a different hospital in October 2005. She was suffering from refractory pleural effusion after receiving 2 courses of steroid-pulse therapy and melphalan (4 mg/day × 4 days) + prednisolone (20 mg/day × 4 days) therapy, and was referred to our hospital in September 2009. Her clinical course is shown in Fig. 2

Cytokine analysis

The serum concentrations of 27 cytokines and chemokines from these two cases were measured using a multiplex suspension array system (Table 1). The sera in case 1 were obtained 29 days before and 35 days after the administration of G-CSF for PBSC collection (Fig. 1). The sera in case 2 were obtained 163 days before and 33 days after the administration of G-CSF for second attempt of PBSC collection (Fig. 2). Sera from normal controls were obtained from people without malignancies at medical

Discussion

To our knowledge, this is the first analysis of cytokine profiles in POEMS syndrome patients who developed acutely deteriorated extravascular volume overload. The development of capillary leak symptoms without increased levels of VEGF prompted us to speculate that the cytokine profiles in our cases may be altered after the administration of CG. Although the cytokine profiles of two patients in this study were different, it is noteworthy that levels of IL-6 after CG were elevated in both cases.

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  • Cited by (3)

    • Safety and Efficacy of Granulocyte Colony–Stimulating Factor Monotherapy for Peripheral Blood Stem Cell Collection in POEMS Syndrome

      2017, Biology of Blood and Marrow Transplantation
      Citation Excerpt :

      Li et al. speculated that combining high-dose CY may reduce the G-CSF–related cytokine release [3]. However, we experienced 2 cases that developed severe capillary leak symptoms with increased levels of various proinflammatory cytokines during CG mobilization [2], suggesting that combining CY may not be enough to control cytokine levels. Kanai et al. reported that various proinflammatory cytokines were significantly increased in untreated POEMS patients [5]; therefore, induction chemotherapy is an effective strategy for reducing the hypercytokine status.

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