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Expert Opinion on Pharmacotherapy Jun 2010Treatment options for amyloidosis and polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) syndrome have rapidly increased in the past... (Review)
Review
IMPORTANCE OF THE FIELD
Treatment options for amyloidosis and polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) syndrome have rapidly increased in the past years, but many patients are diagnosed late in the disease course and do not receive state-of-the art therapy.
AREAS COVERED IN THIS REVIEW
Stem-cell transplantation and novel agents have widened the chemotherapy alternatives available in these disorders and combinations of novel agents with high-dose therapy further improve treatment options. This review covers the main areas of debate in the optimal treatment amyloidosis and POEMS patients, focusing on the implications for everyday clinical practice and management strategies published in the past 36 months.
WHAT THE READER WILL GAIN
Insights into treatment strategies are provided in the review. Keys to early recognition of the syndromes are reviewed.
TAKE-HOME MESSAGE
With early diagnosis most patients are therapy candidates. New agents and new application of stem-cell transplantation have dramatically improved outcomes for these previously uniformly poor prognosis disorders.
Topics: Alkylating Agents; Amyloidosis; Diagnosis, Differential; Humans; POEMS Syndrome; Prognosis; Stem Cell Transplantation
PubMed: 20426710
DOI: 10.1517/14656561003769874 -
Blood Advances Dec 2020Castleman disease (CD) includes a group of rare and heterogeneous disorders with characteristic lymph node histopathological abnormalities. CD can occur in a single...
Castleman disease (CD) includes a group of rare and heterogeneous disorders with characteristic lymph node histopathological abnormalities. CD can occur in a single lymph node station, which is referred to as unicentric CD (UCD). CD can also involve multicentric lymphadenopathy and inflammatory symptoms (multicentric CD [MCD]). MCD includes human herpesvirus-8 (HHV-8)-associated MCD, POEMS-associated MCD, and HHV-8-/idiopathic MCD (iMCD). The first-ever diagnostic and treatment guidelines were recently developed for iMCD by an international expert consortium convened by the Castleman Disease Collaborative Network (CDCN). The focus of this report is to establish similar guidelines for the management of UCD. To this purpose, an international working group of 42 experts from 10 countries was convened to establish consensus recommendations based on review of treatment in published cases of UCD, the CDCN ACCELERATE registry, and expert opinion. Complete surgical resection is often curative and is therefore the preferred first-line therapy, if possible. The management of unresectable UCD is more challenging. Existing evidence supports that asymptomatic unresectable UCD may be observed. The anti-interleukin-6 monoclonal antibody siltuximab should be considered for unresectable UCD patients with an inflammatory syndrome. Unresectable UCD that is symptomatic as a result of compression of vital neighboring structures may be rendered amenable to resection by medical therapy (eg, rituximab, steroids), radiotherapy, or embolization. Further research is needed in UCD patients with persisting constitutional symptoms despite complete excision and normal laboratory markers. We hope that these guidelines will improve outcomes in UCD and help treating physicians decide the best therapeutic approach for their patients.
Topics: Antineoplastic Agents; Castleman Disease; Consensus; Herpesvirus 8, Human; Humans; Rituximab
PubMed: 33284946
DOI: 10.1182/bloodadvances.2020003334 -
American Journal of Hematology Oct 2015POEMS syndrome is a paraneoplastic syndrome due to an underlying plasma cell neoplasm. The major criteria for the syndrome are polyradiculoneuropathy, clonal plasma cell... (Review)
Review
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.
Topics: Humans; Neoplasms, Plasma Cell; POEMS Syndrome; Risk Assessment
PubMed: 26331353
DOI: 10.1002/ajh.24171 -
Journal of Clinical Medicine Nov 2022POEMS is a rare clonal plasma cell disorder characterized by multi-systemic features that include demyelinating peripheral neuropathy, organomegaly, endocrinopathy,... (Review)
Review
POEMS is a rare clonal plasma cell disorder characterized by multi-systemic features that include demyelinating peripheral neuropathy, organomegaly, endocrinopathy, presence of monoclonal proteins (M-protein), and skin changes. Even though the pathophysiology is poorly understood, recent studies suggest that both clonal and polyclonal plasmacytosis leading to the production of pro-inflammatory cytokines and angiogenic mediators play the central role. These mediators including vascular endothelial growth factor (VEGF) are the driving forces of the syndrome. The diagnosis of POEMS is not always straight forward and often the diagnosis is delayed. It is based on fulfilling mandatory criteria of polyradiculoneuropathy and monoclonal protein and the presence of one major criterion (Castleman disease, sclerotic bone lesions, or elevated VEGF), and at least one minor criterion. Due to the presence of neuropathy, it can be confused with chronic inflammatory demyelinating polyradiculopathy (CIDP), and if thrombocytosis and splenomegaly are present, it can be confused with myeloproliferative neoplasms. Due to the rarity of the syndrome, clear guidelines for treatment are still lacking. Immediate treatment targeting the underlying plasma cell proliferation results in a dramatic response in most patients. The key is early diagnosis and immediate anti-plasma cell directed therapy for the best clinical outcomes. For patients with disseminated disease as defined by bone marrow involvement or more than three osteosclerotic bone lesions, high-dose chemotherapy with autologous hematopoietic stem cell transplant (ASCT) yields durable responses and is the preferred treatment in eligible patients. For patients with localized bony disease, radiotherapy has proven to be very effective. Lenalidomide and dexamethasone is a proven therapy in patients ineligible for ASCT. In this review article, we tackle the diagnostic approach and discuss the latest treatment modalities of this rare debilitating disease.
PubMed: 36498588
DOI: 10.3390/jcm11237011 -
American Journal of Hematology Aug 2017POEMS syndrome is a paraneoplastic syndrome due to an underlying plasma cell neoplasm. The major criteria for the syndrome are polyradiculoneuropathy, clonal plasma cell... (Review)
Review
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 3 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.
Topics: Algorithms; Bone Marrow; Castleman Disease; Combined Modality Therapy; Diagnosis, Differential; Disease Management; Humans; POEMS Syndrome; Phenotype; Severity of Illness Index
PubMed: 28699668
DOI: 10.1002/ajh.24802 -
American Journal of Hematology Feb 2014POEMS syndrome is a paraneoplastic syndrome due to an underlying plasma cell neoplasm. The major criteria for the syndrome are polyradiculoneuropathy, clonal plasma cell... (Review)
Review
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 PCD, 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 PCD 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. 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.
Topics: Bone Marrow; Castleman Disease; Diagnosis, Differential; Humans; POEMS Syndrome; Risk Factors; Treatment Outcome
PubMed: 24532337
DOI: 10.1002/ajh.23644 -
Mediterranean Journal of Hematology and... 2017POEMS syndrome is a rare, chronic and disabling condition. The causes of this condition remain unknown; however, chronic overproduction of proinflammatory cytokines... (Review)
Review
POEMS syndrome is a rare, chronic and disabling condition. The causes of this condition remain unknown; however, chronic overproduction of proinflammatory cytokines appears to be a major contributor. Early diagnosis is essential to start treatment before the clinical state of the patient becomes compromised. A complete evaluation of the disease at its onset is critical to the treatment decision. In localized disease, curative doses of radiation (50 Gy) is the recommended therapy. On the other hand, patients with disseminated disease should be given systemic therapy. Treatment-related morbidity can be minimized by an efficient induction therapy that modifies the cytokine status, improving clinical condition and control disease severity before mobilization and transplantation. Patients not suitable for hematopoietic stem cell transplantation (HSCT) are usually treated with alkylator-based therapy. Novel agents may also offer benefits to patients with a poor performance status or renal dysfunction, and induce transplantation eligibility. Given the biological characteristics of POEMS, immunomodulatory effects and the absence of neurotoxicity, lenalidomide appears to be an effective therapy for the treatment of POEMS, both as short induction therapy before PBSCT and in non-transplant eligible patients, as it showed high response rate and durable responses. At present, however, guidelines for the diagnosis and treatment of POEMS are not available and appear advocated.
PubMed: 28894560
DOI: 10.4084/MJHID.2017.051 -
Blood Cancer Journal May 2023
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; Multiple Myeloma; POEMS Syndrome; Thalidomide
PubMed: 37253713
DOI: 10.1038/s41408-023-00859-x -
Internal Medicine (Tokyo, Japan) Nov 2004
Topics: Humans; POEMS Syndrome; Platelet Aggregation Inhibitors; Ticlopidine; Vascular Endothelial Growth Factors
PubMed: 15609693
DOI: 10.2169/internalmedicine.43.1014 -
BMC Neurology Jun 2021This study aimed to investigate the frequency and risk factors for cerebral artery stenosis and occlusion in patients with polyneuropathy, organomegaly, endocrinopathy,...
BACKGROUND
This study aimed to investigate the frequency and risk factors for cerebral artery stenosis and occlusion in patients with polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome.
METHODS
We reviewed results of magnetic resonance angiography (MRA) or computed tomography angiography (CTA) in 61 patients with POEMS syndrome seen between 2010 and 2017. Stenosis or occlusion was assessed in the initial MRA/CTA. Multivariate analysis was used to identify risk factors for artery stenosis/occlusion. In an autopsy case, pathologic examination was conducted of the occluded middle cerebral arteries.
RESULTS
Stenosis (> 50 %) or occlusion of the major cerebral arteries was found in 29 (47.5 %) patients on the initial MRA/CTA. The internal carotid artery was involved most frequently (32.8 %), followed by the anterior (21.3 %) and middle (16.4 %) cerebral arteries. The basilar (1.3 %) and vertebral (3.6 %) arteries were rarely affected. Cerebral infarction developed in eight (13.1 %) patients. The serum vascular endothelial growth factor (VEGF) level was an independent predictor for stenosis/occlusion (odds ratio, 1.228; 95 % confidence interval, 1.042-1.447; P = 0.014). An autopsy study showed occluded middle cerebral arteries by fibrous and myxomatous thickening of intima with splitting of the internal elastic lamina. Follow-up MRA in 23 patients showed improved, worsened, and unchanged stenosis in 20.7 %, 8.7 %, and 69.6 %, respectively.
CONCLUSIONS
Cerebral large-vessel stenosis or occlusion is frequently seen in approximately half of patients with POEMS syndrome. Vasculopathy was related to serum VEGF levels and thereby disease activity. Assessment of cerebral vessels is recommended in these patients to improve management.
Topics: Cerebrovascular Disorders; Humans; Infarction, Middle Cerebral Artery; POEMS Syndrome
PubMed: 34167480
DOI: 10.1186/s12883-021-02260-2