POEMS syndrome: Update on diagnosis, risk‐stratification, and management

Abstract

Disease overview: POEMS syndrome is a paraneoplastic syndrome due to an underlying plasma cell neoplasm. The major criteria for the syndrome are polyradiculoneuropathy, clonal plasma cell disorder (PCD), sclerotic bone lesions, elevated vascular endothelial growth factor, and the presence of Castleman disease. Minor features include organomegaly, endocrinopathy, characteristic skin changes, papilledema, extravascular volume overload, and thrombocytosis. Diagnoses are often delayed because the syndrome is rare and can be mistaken for other neurologic disorders, most commonly chronic inflammatory demyelinating polyradiculoneuropathy. POEMS syndrome should be distinguished from the Castleman disease variant of POEMS syndrome, which has no clonal PCD and typically little to no peripheral neuropathy but has several of the minor diagnostic criteria for POEMS syndrome.Diagnosis: The diagnosis of POEMS syndrome is made with three of the major criteria, two of which must include polyradiculoneuropathy and clonal plasma cell disorder, and at least one of the minor criteria.Risk stratification: Because the pathogenesis of the syndrome is not well understood, risk stratification is limited to clinical phenotype rather than specific molecular markers. The number of clinical criteria is not prognostic, but the extent of the plasma cell disorder is. Those patients with an iliac crest bone marrow biopsy that does not reveal a plasma cell clone are candidates for local radiation therapy; those with a more extensive or disseminated clone will be candidates for systemic therapy.Risk‐adapted therapy: For those patients with a dominant sclerotic plasmacytoma, first line therapy is irradiation. Patients with diffuse sclerotic lesions or disseminated bone marrow involvement and for those who have progression of their disease 3–6 months after completing radiation therapy should receive systemic therapy. Corticosteroids are temporizing, but alkylators are the mainstay of treatment, either in the form of low dose conventional therapy or high dose with stem cell transplantation. Lenalidomide shows promise with manageable toxicity. Thalidomide and bortezomib also have activity, but their benefit needs to be weighed against their risk of exacerbating the peripheral neuropathy. The benefit of anti‐VEGF antibodies is conflicting. Prompt recognition and institution of both supportive care measures and therapy directed against the plasma cell result in the best outcomes. Am. J. Hematol. 90:951–962, 2015. © 2015 Wiley Periodicals, Inc.

High-dose therapy and autologous stem cell transplantation in patients with POEMS syndrome: a retrospective study of the Plasma Cell Disorder sub-committee of the Chronic Malignancy Working Party of the European Society for Blood & Marrow Transplantation

“…Previously published data from the Mayo Clinic demonstrated a median OS of 13.8 years. 1 The therapeutic management has evolved over the years, much in parallel with new drug developments in myeloma. In patients with localized disease, irradiation remains the treatment of choice.…”

Chylothorax in POEMS Syndrome

“…Recently, anti-VEGF monoclonal antibodies have been used therapeutically (Sekiguchi et al 2013). During the course of the disease, 3%-43% of patients with POEMS syndrome developed pleural effusions (Dispenzieri 2012). However, there was no report of chylothorax associated with the disease.…”

“…In 2012, Dispenzieri published the major and minor diagnostic criteria of POEMS syndrome (Dispenzieri 2012). Plasma and serum levels of VEGF are markedly elevated in patients with POEMS syndrome, and the levels correlate with the activity of the disease.…”

“…Other signs are frequently observed in affected patients such as pleural effusion, sclerotic bone lesions, Castleman disease, papilledema, thrombocytosis, peripheral edema, ascites, polycythemia, fatigue, and clubbing. Not all features are required to make the diagnosis (Dispenzieri 2012).…”

The first case of POEMS syndrome with synchronous breast cancer: What are the associated diagnostic challenges?

“…Elevated VEGF levels are postulated to be involved in the pathogenesis of enhanced vascular permeability, increased endoneurial pressure, and the deposition of plasma cell‐derived material 14, 16, 17, which eventually cause a variety of symptoms, including extravascular volume overloading (edema, pleural effusion, and/or ascites), polyneuropathy (demyelination), sclerotic bone lesions, and skin changes 18, 19. However, the mixed results seen with anti‐VEGF therapy indicate that VEGF might not be the driver of the clinical manifestations of POEMS syndrome 20. Further studies of this issue are required.…”