Abstract
POEMS syndrome is a paraneoplastic disorder secondary to an underlying plasma cell dyscrasia. By definition, all patients with POEMS syndrome must display polyneuropathy and monoclonal plasma cell disorder. In addition, at least one major criterion (Castleman’s disease, sclerotic bone lesions, or vascular endothelial growth factor elevation) and one minor criterion (organomegaly, extravascular volume overload, endocrinopathy, skin changes, papilledema, thrombocytosis, or polycythemia) are required for diagnosis. Treatment is based on extent of the disease. Radiotherapy is used for localized disease. Systemic therapy is required for disseminated disease, with bone marrow involvement by clonal plasma cells, or in patients who progress shortly after radiation. Upfront autologous stem cell transplantation is the treatment of choice for transplant-eligible patients. Outcomes are typically superior to that of standard myeloma. Herein, using a case vignette, we outline the latest evidence regarding the prognostication and management of POEMS syndrome, with a focus on its relapsing-remitting course.
Similar content being viewed by others
References
Crow RS. Peripheral neuritis in myelomatosis. Br Med J. 1956;2(4996):802–4.
Takatsuki K, Sanada I. Plasma cell dyscrasia with polyneuropathy and endocrine disorder: clinical and laboratory features of 109 reported cases. Jpn J Clin Oncol. 1983;13(3):543–55.
Bardwick PA et al. Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes: the POEMS syndrome. Report on two cases and a review of the literature. Medicine (Baltimore). 1980;59(4):311–22.
Dispenzieri A. Castleman disease. Cancer Treat Res. 2008;142:293–330.
Nakanishi T et al. The Crow-Fukase syndrome: a study of 102 cases in Japan. Neurology. 1984;34(6):712–20.
Dispenzieri A et al. POEMS syndrome: definitions and long-term outcome. Blood. 2003;101(7):2496–506.
Soubrier MJ, Dubost JJ, Sauvezie BJ. POEMS syndrome: a study of 25 cases and a review of the literature. French Study Group on POEMS Syndrome. Am J Med. 1994;97(6):543–53.
Singh D et al. POEMS syndrome: experience with fourteen cases. Leuk Lymphoma. 2003;44(10):1749–52.
Li J et al. Clinical characteristics and long-term outcome of patients with POEMS syndrome in China. Ann Hematol. 2011;90(7):819–26.
Jaccard A, Magy L. Thalidomide and POEMS syndrome: a cautious step forward. Lancet Neurol. 2016;15(11):1104–5.
Fermand JP. From monoclonal gammopathy of undetermined significance (MGUS) to monoclonal gammopathy of clinical significance. In: World Congress on controversies in multiple myeloma. Paris, France; 2016.
Dispenzieri A. POEMS syndrome: update on diagnosis, risk-stratification, and management. Am J Hematol. 2015;90(10):951–62.
Straume O, Bergheim J, Ernst P. Bevacizumab therapy for POEMS syndrome. Blood. 2006;107(12):4972–3. author reply 4973-4.
Badros A, Porter N, Zimrin A. Bevacizumab therapy for POEMS syndrome. Blood. 2005;106(3):1135.
Kanai K et al. Markedly upregulated serum interleukin-12 as a novel biomarker in POEMS syndrome. Neurology. 2012;79(6):575–82.
Watanabe O et al. Greatly raised vascular endothelial growth factor (VEGF) in POEMS syndrome. Lancet. 1996;347(9002):702.
Abe D et al. Restrictive usage of monoclonal immunoglobulin lambda light chain germline in POEMS syndrome. Blood. 2008;112(3):836–9.
Mangalik A, Veliath AJ. Osteosclerotic myeloma with polyneuropathy. A case report. Cancer. 1971;28:1040–5.
Alberti MA et al. 18F-FDG PET/CT in the evaluation of POEMS syndrome. Eur J Radiol. 2010;76(2):180–2.
Shi X et al. CT characteristics in 24 patients with POEMS syndrome. Acta Radiol. 2016;57(1):51–7.
D’Souza A et al. Long-term outcomes after autologous stem cell transplantation for patients with POEMS syndrome (osteosclerotic myeloma): a single-center experience. Blood. 2012;120(1):56–62.
Nobile-Orazio E et al. Serum VEGF levels in POEMS syndrome and in immune-mediated neuropathies. Neurology. 2009;72(11):1024–6.
Dao LN et al. Bone marrow histopathology in POEMS syndrome: a distinctive combination of plasma cell, lymphoid, and myeloid findings in 87 patients. Blood. 2011;117(24):6438–44.
D’Souza A et al. The utility of plasma vascular endothelial growth factor levels in the diagnosis and follow-up of patients with POEMS syndrome. Blood. 2011;118(17):4663–5.
Dupont SA et al. Cerebral infarction in POEMS syndrome: incidence, risk factors, and imaging characteristics. Neurology. 2009;73(16):1308–12.
Wang C et al. Markedly elevated serum total N-terminal propeptide of type I collagen is a novel marker for the diagnosis and follow up of patients with POEMS syndrome. Haematologica. 2014;99(6):e78–80.
Belec L et al. Human herpesvirus 8 infection in patients with POEMS syndrome-associated multicentric Castleman’s disease. Blood. 1999;93(11):3643–53.
Bitter MA, Komaiko W, Franklin WA. Giant lymph node hyperplasia with osteoblastic bone lesions and the POEMS (Takatsuki’s) syndrome. Cancer. 1985;56(1):188–94.
Menke DM et al. Diagnosis of Castleman’s disease by identification of an immunophenotypically aberrant population of mantle zone B lymphocytes in paraffin-embedded lymph node biopsies. Am J Clin Pathol. 1996;105(3):268–76.
Menke DM, Camoriano JK, Banks PM. Angiofollicular lymph node hyperplasia: a comparison of unicentric, multicentric, hyaline vascular, and plasma cell types of disease by morphometric and clinical analysis. Mod Pathol. 1992;5(5):525–30.
Kulkarni GB et al. Clinicopathological profile of polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes (POEMS) syndrome. J Clin Neurosci. 2011;18(3):356–60.
Donaghy M et al. Peripheral neuropathy associated with Castleman’s disease. J Neurol Sci. 1989;89(2-3):253–67.
Scarlato M et al. Polyneuropathy in POEMS syndrome: role of angiogenic factors in the pathogenesis. Brain. 2005;128(Pt 8):1911–20.
Nasu S et al. Different neurological and physiological profiles in POEMS syndrome and chronic inflammatory demyelinating polyneuropathy. J Neurol Neurosurg Psychiatry. 2012;83(5):476–9.
Mauermann ML et al. Uniform demyelination and more severe axonal loss distinguish POEMS syndrome from CIDP. J Neurol Neurosurg Psychiatry. 2012;83(5):480–6.
Naddaf E et al. Thrombocytosis distinguishes POEMS syndrome from chronic inflammatory demyelinating polyneuropathy. Muscle Nerve. 2015;52(4):658–9.
Nobile-Orazio E, Casellato C, Di Troia A. Neuropathies associated with IgG and IgA monoclonal gammopathy. Rev Neurol (Paris). 2002;158(10 Pt 1):979–87.
Kapoor PAS, Fonseca R, et. al. Diagnosis and management of Waldenström macroglobulinemia: Mayo stratification of macroglobulinemia and risk-adapted therapy (mSMART) guidelines 2016. JAMA Oncology. 2017 Published online January 5, 2017. doi:10.1001/jamaoncol.2016.5763.
Dispenzieri A. Ushering in a new era for POEMS. Blood. 2011;117(24):6405–6.
Kourelis TV et al. Long-term outcome of patients with POEMS syndrome: an update of the Mayo Clinic experience. Am J Hematol. 2016;91(6):585–9.
Kourelis TV et al. Risk factors for and outcomes of patients with POEMS syndrome who experience progression after first-line treatment. Leukemia. 2016;30(5):1079–85.
Suh YG et al. The role of radiotherapy in the management of POEMS syndrome. Radiat Oncol. 2014;9:265.
Humeniuk MS et al. Outcomes of patients with POEMS syndrome treated initially with radiation. Blood. 2013;122(1):68–73.
Kuwabara S et al. Autologous peripheral blood stem cell transplantation for POEMS syndrome. Neurology. 2006;66(1):105–7.
Barete S et al. Skin manifestations and vascular endothelial growth factor levels in POEMS syndrome: impact of autologous hematopoietic stem cell transplantation. Arch Dermatol. 2010;146(6):615–23.
Soubrier M et al. Successful use of autologous bone marrow transplantation in treating a patient with POEMS syndrome. Bone Marrow Transplant. 2002;30(1):61–2.
Dispenzieri A et al. Peripheral blood stem cell transplant for POEMS syndrome is associated with high rates of engraftment syndrome. Eur J Haematol. 2008;80(5):397–406.
Li J et al. Combination of melphalan and dexamethasone for patients with newly diagnosed POEMS syndrome. Blood. 2011;117(24):6445–9.
Cai QQ et al. Efficacy and safety of low-dose lenalidomide plus dexamethasone in patients with relapsed or refractory POEMS syndrome. Eur J Haematol. 2015;95(4):325–30.
Misawa S et al. Safety and efficacy of thalidomide in patients with POEMS syndrome: a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2016;15(11):1129–37.
Vannata B et al. Efficacy of lenalidomide plus dexamethasone for POEMS syndrome relapsed after autologous peripheral stem-cell transplantation. Am J Hematol. 2012;87(6):641–2.
Dispenzieri A, Klein CJ, Mauermann ML. Lenalidomide therapy in a patient with POEMS syndrome. Blood. 2007;110(3):1075–6.
Jaccard A et al. A prospective phase II trial of lenalidomide and dexamethasone (LEN-DEX) in POEMS syndrome. Blood. 2014;124(21):36.
Royer B et al. Efficacy of lenalidomide in POEMS syndrome: a retrospective study of 20 patients. Am J Hematol. 2013;88(3):207–12.
Zagouri F et al. Lenalidomide in patients with POEMS syndrome: a systematic review and pooled analysis. Leuk Lymphoma. 2014;55(9):2018–23.
Sanada S et al. Marked recovery of severe renal lesions in POEMS syndrome with high-dose melphalan therapy supported by autologous blood stem cell transplantation. Am J Kidney Dis. 2006;47(4):672–9.
Ganti AK et al. Successful hematopoietic stem-cell transplantation in multicentric Castleman disease complicated by POEMS syndrome. Am J Hematol. 2005;79(3):206–10.
Peggs KS et al. Peripheral blood stem cell transplantation for POEMS syndrome. Bone Marrow Transplant. 2002;30(6):401–4.
Hogan WJ et al. Successful treatment of POEMS syndrome with autologous hematopoietic progenitor cell transplantation. Bone Marrow Transplant. 2001;28(3):305–9.
Dispenzieri A. How I treat POEMS syndrome. Blood. 2012;119(24):5650–8.
Kojima H et al. Successful treatment of a patient with POEMS syndrome by tandem high-dose chemotherapy with autologous CD34+ purged stem cell rescue. Int J Hematol. 2006;84(2):182–5.
Schmitz N et al. Randomised trial of filgrastim-mobilised peripheral blood progenitor cell transplantation versus autologous bone-marrow transplantation in lymphoma patients. Lancet. 1996;347(8998):353–7.
Imai N et al. Relapse of polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome without increased level of vascular endothelial growth factor following successful autologous peripheral blood stem cell transplantation. Neuromuscul Disord. 2009;19(5):363–5.
Kuwabara S et al. Treatment for POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) syndrome. Cochrane Database Syst Rev. 2012;6:CD006828.
Kuwabara S et al. Long term melphalan-prednisolone chemotherapy for POEMS syndrome. J Neurol Neurosurg Psychiatry. 1997;63(3):385–7.
Zhou JW et al. Clinical observation of thalidomide combined with VAD regimen for treatment of osteosclerotic myeloma (POEMS syndrome). Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2012;20(2):348–51.
Katayama K et al. Japanese POEMS syndrome with Thalidomide (J-POST) Trial: study protocol for a phase II/III multicentre, randomised, double-blind, placebo-controlled trial. BMJ Open. 2015;5(1):e007330.
Roccaro AM et al. Bortezomib mediates antiangiogenesis in multiple myeloma via direct and indirect effects on endothelial cells. Cancer Res. 2006;66(1):184–91.
Warsame R, Kohut IE, Dispenzieri A. Successful use of cyclophosphamide, bortezomib, and dexamethasone to treat a case of relapsed POEMS. Eur J Haematol. 2012;88(6):549–50.
Tang X et al. Successful bortezomib-based treatment in POEMS syndrome. Eur J Haematol. 2009;83(6):609–10.
Zeng K et al. Effective induction therapy with subcutaneous administration of bortezomib for newly diagnosed POEMS syndrome: a case report and a review of the literature. Acta Haematol. 2013;129(2):101–5.
Li J et al. Bortezomib and dexamethasone as first-line therapy for a patient with newly diagnosed polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes syndrome complicated by renal failure. Leuk Lymphoma. 2012;53(12):2527–9.
Ohguchi H et al. Successful treatment with bortezomib and thalidomide for POEMS syndrome. Ann Hematol. 2011;90(9):1113–4.
Kaygusuz I et al. Bortezomib: a new therapeutic option for POEMS syndrome. Eur J Haematol. 2010;84(2):175–7.
Wang X et al. Successful treatment with bortezomib and thalidomide for POEMS syndrome associated with multicentric mixed-type Castleman’s disease. Jpn J Clin Oncol. 2011;41(10):1221–4.
Kim do W et al. Intravitreal bevacizumab for the treatment of optic disc edema in a patient with POEMS syndrome. Korean J Ophthalmol. 2015;29(5):354–6.
Dietrich PY, Duchosal MA. Bevacizumab therapy before autologous stem-cell transplantation for POEMS syndrome. Ann Oncol. 2008;19(3):595.
Sekiguchi Y et al. Ambiguous effects of anti-VEGF monoclonal antibody (bevacizumab) for POEMS syndrome. J Neurol Neurosurg Psychiatry. 2013;84(12):1346–8.
Song HB, Yu HG. Optic disc edema responding to localized anti-vascular endothelial growth factor treatment in a patient with POEMS syndrome. Korean J Ophthalmol. 2015;29(5):357–8.
Terracciano C et al. Inverse correlation between VEGF and soluble VEGF receptor 2 in POEMS with AIDP responsive to intravenous immunoglobulin. Muscle Nerve. 2010;42(3):445–8.
Dispenzieri A. POEMS syndrome. Blood Rev. 2007;21(6):285–99.
Authier FJ et al. All-trans-retinoic acid in POEMS syndrome. Therapeutic effect associated with decreased circulating levels of proinflammatory cytokines. Arthritis Rheum. 1996;39(8):1423–6.
Ma L et al. Autologous cytokine-induced killer (CIK) cell immunotherapy combined with cyclophosphamide in five patients with POEMS syndrome. Clin Exp Immunol. 2016;184(1):83–9.
Guay DR. Update on gabapentin therapy of neuropathic pain. Consult Pharm. 2003;18(2):158–70. 173-8.
Zhang L et al. Prevalence and risk factors for depression in newly diagnosed patients with POEMS syndrome. Leuk Lymphoma. 2014;55(12):2835–41.
Wang C et al. Prognostic study for overall survival in patients with newly diagnosed POEMS syndrome. Leukemia. 2016;31(1):100–6.
Wang C et al. Prognostic value of serum heavy/light chain ratios in patients with POEMS syndrome. Eur J Haematol. 2016;97(1):48–54.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
Rahma Warsame and Uday Yanamandra each declare no potential conflicts of interest. Prashant Kapoor reports grants from Amgen, Takeda, and Celgene. Dr. Kapoor is a section editor for Current Hematologic Malignancy Reports.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Additional information
This article is part of the Topical Collection on Multiple Myeloma
Rights and permissions
About this article
Cite this article
Warsame, R., Yanamandra, U. & Kapoor, P. POEMS Syndrome: an Enigma. Curr Hematol Malig Rep 12, 85–95 (2017). https://doi.org/10.1007/s11899-017-0367-0
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11899-017-0367-0