POEMS syndrome: 2011 update on diagnosis, risk‐stratification, and management

Abstract

Disease overviewPOEMS 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 to 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. The benefit of anti‐VEGF antibodies is conflicting. 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. Prompt recognition and institution of both supportive care measures and therapy directed against the plasma cell result in the best outcomes. Am. J. Hematol. 86:592–601, 2011. © 2011 Wiley‐Liss, Inc.

PBSC mobilization in newly diagnosed patients with POEMS syndrome: outcomes and prognostic factors

“…It is reported that combination of CY and prednisone is an effective treatment regimen for patients with POEMS syndrome. 1 In addition, Jimenez-Zepeda et al 18 reported that short-term induction therapy of CY and prednisone before transplantation could significantly decrease the incidence of engraftment syndrome and reduce transplant-related mortality. Therefore, pretreatment with high dose of CY might decrease the level of pro-inflammatory cytokines, relieve disease activity and reduce G-CSF-related adverse effects, which might improve the efficacy and safety of mobilization.…”

“…Additional features include papilledema, extra-vascular volume overload, sclerotic bone lesions and Castleman's disease. 1,2 The pathogenesis of POEMS syndrome is not fully understood, but there is increasing evidence suggesting that high levels of serum vascular endothelial growth factor (VEGF) may contribute to certain features of POEMS syndrome such as extra-vascular volume overload, organomegaly and hemangioma. The course of POEMS syndrome is chronic and the median survival is usually 45 years.…”

“…The main causes of death are cardiopulmonary failure, renal failure and infection. 1,2 There is no standard treatment for POEMS syndrome. In the past decade, melphalan-based therapy has made significant progress in the treatment of POEMS syndrome, including chemotherapy of melphalan and dexamethasone, 3 and highdose melphalan followed by autologous PBSC transplantation.…”

“…8 There are limited data on the incidence of complications associated with mobilization, prognostic factors for successful mobilization and outcomes of subsequent transplantation. We retrospectively reviewed outcomes and prognostic factors of PBSC mobilization in newly diagnosed patients with POEMS syndrome from a single institute with two specific aims: (1) to explore the associations between successful mobilization and treatment regimen and various clinical factors and (2) to report incidence of complications associated with mobilization.…”

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

“…Two other patients using it as "salvage" improved, but relapsed and died despite continued therapy, normal VEGF at 3.5 and 5.5 years. Six other cases of use with or after other alkylator based therapy yielded one death and 4 patients with improvement [22][23][24][25][26][27]176] High-dose chemotherapy with peripheral blood stem cell transplant can also be quite effective, but selection basis may confound these reports. Case series suggest 100% of patients achieve at least some neurologic improvement [18,54,87,140,[149][150][151][152][153][154][155][156][181][182][183][184][185].…”