RESUMO
POEMS syndrome is a plasma cell neoplasm that presents with peripheral neuropathy, organomegaly, fluid retention, skin manifestations, osteosclerotic lesions, and λ-type M-proteinemia. The pathogenesis of POEMS syndrome is poorly understood, as the genetic profile of plasma cells in POEMS syndrome differs from that of myeloma. In most cases, POEMS syndrome is difficult to distinguish from chronic inflammatory demyelinating polyneuropathy (CIDP). Consequently, it is essential not to miss characteristic signs of POEMS syndrome such as M-protein, VEGF, pleural effusion, and osteosclerotic lesions. Novel agents for myeloma, such as thalidomide, lenalidomide, and bortezomib, are effective. For younger patients, these agents followed by autologous transplantation with high-dose melphalan is the standard of care. More relapses are now being reported in results of long-term observation, and treatment strategies for relapsed disease must be established.
Assuntos
Síndrome POEMS , Síndrome POEMS/diagnóstico , Síndrome POEMS/terapia , HumanosRESUMO
RATIONALE: POEMS syndrome is a rare monoclonal plasma cell disease. The diagnosis of POEMS requires polyradiculoneuropathy and monoclonal plasma proliferating as 2 mandatory criteria, at least 1 of the major criteria (Castleman disease, elevated vascular endothelial growth factor level, and sclerotic bone lesion), and at least 1 of the minor criteria (organomegaly, extravascular volume overload, endocrinopathy, skin changes, papilledema, and thrombocytosis/polycythemia). This multisystem disorder is of high heterogeneity, and few variants of POEMS with no evidence of monoclonal gammopathy have been described, which further complicates the diagnosis in clinical practice. Now, we report a case of paraprotein-negative POEMS syndrome. PATIENTS CONCERNS: A 45-year-old woman complained of lower extremity edema, shortness of breath, abdominal distension, and lymphadenopathy for few years. Finally, she was diagnosed with paraprotein-negative POEMS syndrome. With the lenalidomide-based regimen, the symptoms were all relieved. DIAGNOSIS: Paraprotein-negative POEMS syndrome. INTERVENTION: Lenalidomide-based regimen and some supportive therapy. OUTCOME: All symptoms were relieved after 1 year of treatment. LESSONS: Physicians should pay more attention to the POEMS syndrome, especially the POEMS syndrome variants, which are absence of paraprotein; probably, these variants are just "on the way" to classic POEMS syndrome antiplasma cell therapy, which remains the treatment of choice.
Assuntos
Síndrome POEMS , Humanos , Síndrome POEMS/diagnóstico , Feminino , Pessoa de Meia-Idade , Paraproteínas/análise , Lenalidomida/uso terapêutico , Lenalidomida/administração & dosagemRESUMO
POEMS syndrome is a rare plasma cell dysplasia. Its clinical manifestations include polyneuropathy, monoclonal protein, increased extravascular volume load, endocrinopathy, organomegaly and skin changes. The complex and atypical symptoms at presentation make early diagnosis challenging due to multiple system involvement. Peripheral neuropathy, limb numbness, is the most common initial symptom of this disease. However, case reports of increased extravascular volume load are rare. This article collected and analyzed the clinical data of two groups of patients with different initial symptoms (increased extravascular volume load and limb numbness). The clinical characteristics and treatment responses were summarized.
Assuntos
Síndrome POEMS , Humanos , Síndrome POEMS/diagnóstico , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , IdosoRESUMO
This open-label, prospective trial evaluated the combination of ixazomib, cyclophosphamide and dexamethasone (ICD) in 12 newly diagnosed POEMS syndrome patients. The study is registered with the Chinese Clinical Trials Registry (ChiCTR2000030072). The treatment protocol consisted of 12 cycles of the ICD regimen compromising ixazomib (4 mg on Days 1, 8 and 15), oral cyclophosphamide (300 mg on Days 1, 8 and 15) and dexamethasone (20 mg weekly). A total of 12 patients received a median of 10 (range: 3-23) cycles of the ICD regimen. The haematological response could be evaluated in 10 patients. The overall haematological response rate was 80% (8/10), with 30% (3/10) achieving complete haematological response, and the overall serum VEGF response rate and neurological response were 100% and 83.3% respectively. Two patients experienced grade 3/4 AEs, including diarrhoea (n = 1) and leukopenia (n = 1). The combination of ixazomib, cyclophosphamide and dexamethasone demonstrated both efficacy and safety in newly diagnosed POEMS syndrome, making it a viable treatment option.
Assuntos
Compostos de Boro , Ciclofosfamida , Dexametasona , Glicina , Síndrome POEMS , Humanos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Compostos de Boro/administração & dosagem , Compostos de Boro/efeitos adversos , Compostos de Boro/uso terapêutico , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Dexametasona/uso terapêutico , Glicina/análogos & derivados , Glicina/administração & dosagem , Glicina/efeitos adversos , Glicina/uso terapêutico , Síndrome POEMS/tratamento farmacológico , Síndrome POEMS/diagnóstico , Síndrome POEMS/sangue , Pessoa de Meia-Idade , Feminino , Masculino , Adulto , Estudos Prospectivos , Idoso , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagemRESUMO
The role of the proteasome inhibitor ixazomib in the treatment of POEMS syndrome continues to evolve. He and colleagues present the results of a study investigating ixazomib in combination with cyclophosphamide and dexamethasone in newly diagnosed POEMS patients. The triplet showed excellent efficacy and tolerability, and constitutes an effective treatment option for patients with POEMS. Commentary on: He et al. An open-label, prospective trial to evaluate the efficacy and safety of ixazomib in combination with cyclophosphamide and dexamethasone in patients with newly-diagnosed POEMS syndrome. Br J Haematol 2024;205:478-482.
Assuntos
Compostos de Boro , Dexametasona , Glicina , Síndrome POEMS , Compostos de Boro/uso terapêutico , Compostos de Boro/administração & dosagem , Compostos de Boro/efeitos adversos , Humanos , Síndrome POEMS/tratamento farmacológico , Síndrome POEMS/diagnóstico , Glicina/análogos & derivados , Glicina/uso terapêutico , Glicina/administração & dosagem , Glicina/efeitos adversos , Dexametasona/uso terapêutico , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Ciclofosfamida/uso terapêutico , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
Background - POEMS syndrome is a potentially well manageable disease with an ascendant therapeutic arsenal nowadays. The early recognition of the syndrome is key to prevent serious multiorgan damage, and that is still a big challenge for physicians. With the following two case reports the authors aimed to highlight the consequences of late recognition of the disease and summarize the potential therapeutic options for POEMS syndrome.
Results - We have presented two patients’ cases with a long history of examination and treatment because of uncleared polyneuropathy. Through these cases we could see how serious could be the consequences of late diagnosis and despite multiorgan impairment there are still therapeutic options which could improve the patient’s condition. Although the diagnosis of POEMS syndrome is not easy, it must raise our mind the thought and be prudent when we start a treatment in polyneuropathy.
.Assuntos
Síndrome POEMS , Humanos , Síndrome POEMS/diagnóstico , Síndrome POEMS/terapia , Pessoa de Meia-Idade , Masculino , Feminino , Diagnóstico TardioRESUMO
BACKGROUND: Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome is a rare plasma cell (PC) neoplasm with associated paraneoplastic syndrome. According to the current diagnostic criteria, peripheral polyneuropathy and monoclonal PC proliferative disorder represent two mandatory criteria. CASE PRESENTATION: We report a 54-year-old male with peripheral neuropathy of bilateral lower limbs, sclerotic bone lesions, elevated vascular endothelial growth factor (VEGF) levels, splenomegaly, extravascular volume overload, endocrinopathy, and skin hemangiomas. Of note, serum and urine protein electrophoresis (PEP) and immunofixation electrophoresis (IFE) of this patient indicated undetectable M-protein and the normal ratio of free light chains κ and λ (FLC-R (κ/λ)). No monoclonal PCs were found in bone marrow examinations or biopsy of diseased bones. However, his clinical manifestations matched most of the diagnostic criteria. After excluding other diseases that are easily confused with POEMS syndrome, the diagnosis of variant POEMS syndrome with undetectable M-protein was proposed. The patient obtained clinically significant improvement and elevated VEGF returned to normal after 6 months of treatment with lenalidomide plus dexamethasone. CONCLUSIONS: Monoclonal PC dyscrasia (M-protein) while being a mandatory criterion for POEMS syndrome is undetectable in a considerable amount of patients that otherwise demonstrate typical symptoms. Here, we reported a case of variant POEMS syndrome with featured clinical manifestations, elevated VEGF levels, and good response to therapies targeting PCs but no evidence of M-protein. Therefore, negative results in M-protein and monoclonal PCs aren't enough to reject the diagnosis of POEMS syndrome. It is imperative to recognize the variant form of POEMS syndrome.
Assuntos
Síndrome POEMS , Humanos , Síndrome POEMS/diagnóstico , Síndrome POEMS/patologia , Masculino , Pessoa de Meia-Idade , Lenalidomida/uso terapêutico , Talidomida/uso terapêutico , Talidomida/análogos & derivados , Fator A de Crescimento do Endotélio Vascular , Dexametasona/uso terapêutico , Resultado do Tratamento , Proteínas do Mieloma/análiseRESUMO
POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein [M-protein], and skin changes) is a rare systemic disorder characterized by various symptoms caused by underlying plasma cell (PC) dyscrasia. Detection of monoclonal PCs is mandatory for the diagnosis of POEMS syndrome; however, the usefulness of EuroFlow-based next-generation flow cytometry (EuroFlow-NGF) in POEMS syndrome for detecting monoclonal PCs in bone marrow (BM) and the gating strategy suitable for flow cytometry study of POEMS syndrome remain unknown. We employed EuroFlow-NGF-based single-tube eight-color multiparameter flow cytometry (MM-flow) and established a new gating strategy (POEMS-flow) to detect the monoclonal PCs in POEMS syndrome, gating CD38 broadly from dim to bright and CD45 narrowly from negative to dim compared to MM-flow. MM-flow detected monoclonal PCs in 9/25 (36.0%) cases, including 2/2 immunofixation electrophoresis (IFE)-negative cases (100%). However, POEMS-flow detected monoclonal PCs in 18/25 cases (72.0%), including 2/2 IFE-negative cases (100%). POEMS-flow detected monoclonal PCs with immunophenotypes of CD19- in 17/18 (94.4%). In six cases where post-treatment samples were available, the size of the clones was significantly reduced after the treatment (P = 0.031). POEMS-flow can enhance the identification rate of monoclonal PCs in POEMS syndrome and become a valuable tool for the diagnosis of POEMS syndrome.
Assuntos
Citometria de Fluxo , Síndrome POEMS , Plasmócitos , Síndrome POEMS/diagnóstico , Humanos , Citometria de Fluxo/métodos , Pessoa de Meia-Idade , Masculino , Feminino , Idoso , Plasmócitos/metabolismo , Plasmócitos/patologia , Adulto , Imunofenotipagem/métodos , Medula Óssea/patologiaRESUMO
POEMS syndrome is a multisystem disorder associated with monoclonal plasma cell proliferation and the overproduction of vascular endothelial growth factors. The prognosis of POEMS syndrome has significantly improved owing to anti-myeloma treatments such as thalidomide and autologous stem cell transplantation. Therefore, early diagnosis and appropriate treatment are becoming increasingly important. A thorough and comprehensive evaluation of both systemic symptoms and laboratory abnormalities associated with the disease is essential for early diagnosis. The collaboration between neurology and hematology is indispensable to ensure proper treatment.
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Síndrome POEMS , Síndrome POEMS/diagnóstico , Síndrome POEMS/terapia , Humanos , PrognósticoRESUMO
RATIONALE: This article presents the case of a patient with recurrent chronic diarrhea and cachexia who was misdiagnosed, followed by a literature review to summarize the reasons for misdiagnosis of POEMS syndrome and the treatment strategies. PATIENT CONCERNS: The diagnosis and treatment of this patient suggest that with the improvement of M-protein detection levels, the diagnosis of patients with low M-protein levels, such as those with POEMS syndrome, has been greatly aided. DIAGNOSES: POEMS syndrome requires polyneuropathy and monoclonal plasma cell proliferation as mandatory diagnostic criteria. Therefore, patients presenting with polyneuropathy should routinely undergo M-protein testing and consider the possibility of POEMS syndrome. INTERVENTIONS: The patient, in this case, was treated primarily with relatively conservative immunomodulatory agents. OUTCOMES: During follow-up after treatment, the patient's diarrhea and malnutrition showed significant improvement. LESSONS SUBSECTIONS: POEMS syndrome has low clinical specificity and a high rate of misdiagnosis. However, once a definitive diagnosis is made, the treatment outcome is favorable.
Assuntos
Síndrome POEMS , Humanos , Síndrome POEMS/complicações , Síndrome POEMS/diagnóstico , Resultado do Tratamento , Erros de Diagnóstico , Diarreia/complicaçõesRESUMO
BACKGROUND: To investigate the utility of regular serum VEGF (sVEGF) levels assessment in the monitoring of POEMS syndrome. METHODS: We retrospectively reviewed data of 30 patients with POEMS syndrome whose sVEGF was tested regularly every 6 months. sVEGF levels after treatment were measured and correlated with disability (Overall Neuropathy Limitations Scale, ONLS), clinical impairment (measured with the modified Clinical Response Evaluation Scale, mCRES), and relapse-free survival. The ability of sVEGF to predict disease flares during remission and refractory disease was also analysed. RESULTS: Patients with normalised serum VEGF levels (< 1000 pg/ml) at 6 months showed prolonged relapse-free survival (at 3-year 94% for complete VEGF response, 57% partial, 0% none, p < 0.001) and greater later clinical improvement (median ΔmCRES complete VEGF response -5 vs partial -4, p = 0.019, and vs no VEGF response -2, p = 0.006). After remission, the sensitivity of 6-month sVEGF monitoring in predicting clinical relapse was 58% with a specificity of 100%. In patients refractory to treatment, the sensitivity in predicting further clinical worsening was 15%. In addition, in 25% of the patients in remission and 16% of those refractory to therapy, sVEGF levels only increased at the time of relapse. CONCLUSIONS: Regular sVEGF assessment is a valid biomarker in the prediction of disease reactivation in POEMS syndrome and was particularly useful during the phase of remission.
Assuntos
Síndrome POEMS , Fator A de Crescimento do Endotélio Vascular , Humanos , Síndrome POEMS/diagnóstico , Estudos Retrospectivos , RecidivaRESUMO
Autologous peripheral blood stem cell transplantation (aPBSCT) provides optimal outcomes in POEMS syndrome but the definition of the best treatment before aPBSCT remains to be defined because of the rarity of the disease and the heterogeneity of published case series. We collected clinical and laboratory data of patients with POEMS syndrome undergoing aPBSCT from 1998 to 2020 in ten Italian centers. The primary endpoint of the study was to evaluate the impact of prior therapies and mobilization regimen on outcome. We divided the patients into three groups: patients who did not receive any treatment before transplant (15 patients, group A: front-line), patients pre-treated with other agents (14 patients, group B) and patients treated with cyclophosphamide as their mobilizing regimen (16 patients, group C). The three groups did not show differences in terms of demographic and clinical characteristics. All 45 patients underwent aPBSCT after a high-dose melphalan conditioning regimen, with a median follow-up of 77 months (range, 37-169 months). The responses were not statistically different between the three groups (P=0.38). Progression-free and overall survival rates at 6 years were: 70% (95% confidence interval: 55-85%) and 91% (95% confidence interval: 82-99) 65%, respectively, and did not differ between the three groups. The cumulative incidence of transplant-related mortality and relapse was 4% and 36%, respectively. In conclusion, in a relatively large number of patients with POEMS syndrome, undergoing an autologous transplant, pre-treatment and disease status at transplant did not appear to have an impact on major transplant outcomes.
Assuntos
Síndrome POEMS , Transplante de Células-Tronco de Sangue Periférico , Humanos , Síndrome POEMS/diagnóstico , Síndrome POEMS/terapia , Transplante Autólogo , Autoenxertos , Ciclofosfamida/uso terapêuticoRESUMO
RATIONALE: POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal paraproteinemia, and skin changes) syndrome is a rare clinical syndrome characterized by multiple peripheral neuropathies, hepatosplenomegaly, endocrine disorders, monoclonal paraproteinemia, and dermatosis. The main manifestations of POMES were nerve and skin changes, and bone disease was not reported. Here, we report a case of POEMS syndrome with the main manifestation of bone lesions. PATIENT CONCERNS: POMES is rare and its clinical manifestations are complex, making it difficult for patients to find the department they should visit. It is easy to miss diagnosis and misdiagnosis, delay the treatment time of patients, and affect the prognosis. DIAGNOSIS INTERVENTIONS: The patient was admitted to the gastroenterology department due to hepatic insufficiency. Multiple osteogenic changes were found by improved enhanced CT due to screening for causes of hepatic insufficiency, and spleen enlargement was indicated by abdominal ultrasound. Due to the involvement of multiple system problems, and follow-up of medical history, it was found that there was a history of discoloration of the distal limb in cold weather in the past 5 years. All things considered, it may be POMES. Further refinement of the bone marrow examination revealed active proliferation of granulocytes and erythrocytes. Bone marrow biopsy showed active hyperplasia, dominated by granulocytes. IFE showed IgA (type λ) and monoclonal myeloma (M) protein bands. To sum up, POMES diagnosis is considered. OUTCOMES: After the diagnosis is clear and the informed consent of the patient and his family is obtained, prednisone acetate is anti-inflammatory, lenalidomide is used to regulate immune function, liver and stomach protection treatment and bile secretion promotion are given. The patient reported improvement in liver function, significant improvement in overall and limb stiffness, and was discharged with improvement. LESSONS: Although bone lesions are not typically the main manifestation of POEMS syndrome, this diagnosis should be considered when this manifestation is combined with organ enlargement, skin changes, and peripheral neuropathy. In addition, the collection of medical history is crucial, when there is a clinical manifestation and auxiliary examination does not match, the idea should be expanded according to the relevant evidence, and finally make the corresponding diagnosis.
Assuntos
Doenças Ósseas , Doenças das Cartilagens , Doenças do Sistema Endócrino , Insuficiência Hepática , Síndrome POEMS , Paraproteinemias , Humanos , Síndrome POEMS/diagnóstico , Síndrome POEMS/patologiaRESUMO
BACKGROUND: Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome is a rare multisystemic clonal plasma cell disorder. Pulmonary involvement is frequently found in patients with POEMS syndrome, manifesting various clinical features. Therefore, to improve diagnostic accuracy and provide treatment strategies, a comprehensive analysis of pulmonary manifestations of POEMS syndrome is needed. METHODS: This retrospective study included patients with POEMS syndrome at Peking Union Medical College Hospital, a major referral medical center in China, between June 1, 2013, and June 1, 2023. Demographic data, laboratory findings, pulmonary function test results, echocardiograms, and chest imaging data were extracted. Continuous variables were compared using the t-test or Mann-Whitney method. Pearson's chi-square test or Fisher's exact test was conducted to compare categorical data. RESULTS: Overall, 282 individuals diagnosed with POEMS syndrome were included in this study, of which 56% were male with an average age of 48.7 years. Respiratory symptoms were found in 40.1% of the patients, with dyspnea as the most common symptom (34.4%). Chest computed tomography and echocardiography findings showed that 56.4% of patients exhibited pleural effusion, 62.8% displayed mediastinal or hilar lymphadenopathy, 46.5% presented pleural thickening, 27.3% demonstrated bone lesions of the ribs or thoracic vertebra, 7.8% showed lung interstitial abnormalities, and 35.5% had pulmonary hypertension. Decreased diffuse capacity and restrictive ventilatory patterns were identified in 85.2% (115 cases) and 47.4% (64 cases) of patients, respectively. Patients with respiratory symptoms exhibited higher declined lung function measures than those having no respiratory symptoms. High-risk patients with poor prognosis showed more pulmonary function abnormalities. CONCLUSION: Abnormalities in pulmonary manifestations constitute the significant features of POEMS syndrome. Several patients with POEMS syndrome presented with respiratory symptoms at the initial evaluation. These findings underscore the importance of early identification and accurate diagnosis of POEMS syndrome by clinicians, particularly in cases involving lung and multisystem.
Assuntos
Hipertensão Pulmonar , Pneumopatias , Síndrome POEMS , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Síndrome POEMS/complicações , Síndrome POEMS/diagnóstico , Estudos Retrospectivos , Pulmão/diagnóstico por imagemRESUMO
Several growth factors are expressed in distinct temporal and spatial patterns during fracture repair. Together, they lead to angiogenesis-osteogenesis coupling and hence bone healing by callus formation. Of these growth factors, vascular endothelial growth factor is of particular interest because of its ability to induce neovascularisation (angiogenesis) and osteoclast invasion in soft callus. Hyperplastic callus can be seen in metabolic bone disease, endocrine disease and in patients with traumatic brain injury, but has not been described so far in polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes (POEMS) syndrome. This report is a case of POEMS syndrome with unusual presentation in the form of exuberant callus formation at fracture sites.