POEMS Syndrome: A Report of 14 Cases and Review of the Literature

POEMS syndrome is a rare paraneoplastic disorder associated with an underlying plasma cell dyscrasia presenting polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes. This study reviewed the clinical characteristics of 14 POEMS patients in Zhongshan hospital. The ratio of male to female was 9 : 5, and the average age was 47.1 years. The clinical manifestations were various, including motorial symptoms (weakness), sensory symptoms (numbness), lymphadenopathy, edema, abdominal distention, and skin hyperpigmentation. Imaging studies and laboratory tests also exhibited hepatomegaly, splenomegaly, thrombocytosis, endocrinopathy, and positive serum immunofixation in most patients. In addition, increased plasma cells in bone marrow and Castleman Disease were found in bone marrow and lymph nodes biopsies. All the eight follow-up patients were treated with alkylator-based combination chemotherapy or corticosteroids and thalidomide, with or without autologous stem cell transplantation. Unfortunately, two patients died three or four years after diagnosis of POEMS syndrome. The others showed response to therapy to some extent, but not completely remission. Currently, treatments for POEMS include radiation to the plasmacytoma, and systemic therapy is indicated. Low-dose alkylators with or without corticosteroids are effective in some patients. However, high-dose chemotherapy with auto-SCT dramatically improved symptoms and outcomes for POEMS patients.

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POEMS Syndrome: A Patient with an IgA lambda Plasma Cell Disease. Expression Levels of VEGF and bFGF Correlates with Clinical Course.

Blood ◽

10.1182/blood.v106.11.5516.5516 ◽

2005 ◽

Vol 106 (11) ◽

pp. 5516-5516

Author(s):

Carsten Schrader ◽

Markus Tiemann ◽

Ute Zirrgiebel ◽

Andreas Guenther ◽

Dirk Janssen ◽

...

Keyword(s):

Bone Marrow ◽

Bone Marrow Transplantation ◽

Marrow Transplantation ◽

Plasma Cells ◽

Autologous Bone Marrow Transplantation ◽

Autologous Bone Marrow ◽

Poems Syndrome ◽

High Dose ◽

Autologous Bone ◽

High Dose Melphalan

Abstract Purpose: POEMS syndrome is a rare disease characterized by polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes. We present a severely ill woman with a four year history of polyneuropathy showing all signs of a POEMS syndrome. Response to chemotherapy including high-dose melphalan treatment and autologous bone marrow transplantation was monitored and vascular endothelial growth factor (VEGF) as well as basic fibroblast growth factor (bFGF) levels were measured. Methods: Blood investigation was done for serum electrophoresis analysis and analysis of VEGF, bFGF and IL-6 by ELISA. Bone marrow biopsy specimen was investigated immunohistochemically for kappa, lambda, alpha, gamma, CD20, CD56, Cyclin D1, VEGF. Results: Immunohistochemical investigation of the bone marrow biopsy showed a infiltration of lambda and alpha positive plasma cells (10%). Only few plasma cells expressed kappa. The tumor cell were negative for CD20, CD56 and Cyclin D1, but positive for VEGF in line with the high VEGF levels in the blood. Blood investigation revealed a discrete monoclonal gammopathy of IgA lambda type. Initially, high levels of VEGF (1468.7 pg/ml) and bFGF (112.9 pg/ml) were detected. However, treatment with high-dose melphalan and tandem autologous bone marrow transplantation proved extremely helpful in symptom control. Already after the first transplant the patient started to walk again and lost pulmonary hypertension. In parallel VEGF and bFGF levels decreased and the performance status of the patient improved dramatically. Conclusion: VEGF and bFGF measurement is a useful tool for monitoring disease activity in POEMS syndrome. Bone marrow transplantation is an important therapy also in severely ill patients.

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Full-length immunoglobulin high-throughput sequencing reveals specific novel mutational patterns in POEMS syndrome

10.1101/824722 ◽

2019 ◽

Cited By ~ 1

Author(s):

Sébastien Bender ◽

Vincent Javaugue ◽

Alexis Saintamand ◽

Maria Victoria Ayala ◽

Mehdi Alizadeh ◽

...

Keyword(s):

Bone Marrow ◽

Plasma Cell ◽

High Throughput ◽

High Throughput Sequencing ◽

Clinical Manifestations ◽

Diagnostic Value ◽

Poems Syndrome ◽

Full Length ◽

Plasma Cell Dyscrasia ◽

Multisystem Disease

AbstractPOEMS syndrome is a rare multisystem disease due to an underlying plasma cell (PC) dyscrasia. The pathophysiology of the disease remains unclear but the role of the monoclonal immunoglobulin (Ig) light chain (LC) is strongly suspected, due to the highly restrictive usage of two λ variable (V) domains (IGLV1-40 and IGLV1-44) and the general improvement of clinical manifestations following PC clone-targeted treatment. However, the diagnostic value of Ig LC sequencing, especially in case of incomplete forms of the disease, remains to be determined. Using a sensitive high-throughput Ig repertoire sequencing on RNA (RACE-RepSeq), we detected a λ LC monoclonal expansion in the bone marrow (BM) of 85% of patients with POEMS syndrome, including some in whom bone marrow tests routinely performed to diagnose plasma cell dyscrasia failed to detect λ+ monoclonal PCs. Twenty-four of the 30 LC clonal sequences found (80%) were derived from the IGLV1-40 and IGLV1-44 germline genes, two from the closely related IGLV1-36 gene, and all were associated with an IGLJ3*02 junction (J) gene, confirming the high restriction of VJ region usage in POEMS syndrome. RACE-RepSeq VJ full-length sequencing additionally revealed original mutational patterns, the strong specificity of which might crucially help establish or eliminate the diagnosis of POEMS syndrome in uncertain cases. Thus, RACE-RepSeq appears as a sensitive, rapid and specific tool to detect low-abundance PC clones in BM, and assign them to POEMS syndrome, with all the consequences for therapeutic options hereby.

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Type of Relapse in 91 Newly Diagnosed MM Patients Treated with High Dose Chemotherapy Followed by Autologous Stem Cell Transplantation.

Blood ◽

10.1182/blood.v108.11.5451.5451 ◽

2006 ◽

Vol 108 (11) ◽

pp. 5451-5451

Author(s):

Maria Teresa Petrucci ◽

Giuseppe Avvisati ◽

Ombretta Annibali ◽

Saveria Capria ◽

Maria S. De Propris ◽

...

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Plasma Cells ◽

High Dose Chemotherapy ◽

High Dose ◽

Newly Diagnosed ◽

Extramedullary Relapse

Abstract High dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) is now considered standard therapy in patients (pts) with Multiple Myeloma (MM) aged less than 65–70 years. Using this therapeutic approach, newly diagnosed MM pts may achieve a complete remission rate of 30–50% associated to prolonged disease-free and overall survival (OS) rates. Unfortunately, HDT followed by ASCT is not curative and only a small fraction of pts remains free of disease after a long follow-up. In this study we analysed the different patterns of relapse after HDT and ASCT in 91 previously untreated MM pts (M/F : 46/45; median age: 54 years, range 32 – 69). As for stage, according to Durie and Salmon criteria, 4 pts (4%) were stage IA, 26 (29%) IIA, 57 (63%) IIIA and 4 (4%) were stage IIIB. The monoclonal component (MC) was: IgG in 54 pts (60%), IgA in 23 pts (25%), IgD in 2 pts (2%); 11 pts (12%) had a micromolecular MM (k/l were 8/3). Only one patient had a non-secretory MM. Median bone marrow plasma cells were 43%. Of the 91 pts, 5 were not evaluable for response because had died early during the transplantation procedure. Causes of death were: hepatic toxicity (1 patient), cardiac complications (1 patient) and hemorrhagic complications (3 pts). Of the remaining 86 evaluable pts, 84 (98%) achieved an objective response and 2 (2%) showed a progressive extramedullary disease (cutaneous and thoracic). After a median follow-up of 49 months (range 6–169) from the HDT-ASCT, 45/84 (54%) responding pts have relapsed and 38/84 (46%) are still alive and responding, the remaining patient was lost to follow-up and considered as event in both OS and event free survival (EFS) curves. The relapse type was “classical” (bone marrow + increase in MC) in 34 (75%) pts, extramedullary in 8 (18%) pts and of both type in 3 (7%) pts. Extramedullary relapse was defined by the presence of normal bone marrow, no increase in MC and presence of plasma cell tumour masses outside the bone marrow demonstrated by clinical examination, imaging and histology. As of July 31 2006, the median OS was not yet reached with 66% of pts still alive. The median overall EFS and time to progression (TTP) were: 82 and 89 months, respectively. As for the 34 pts with “classical” relapse and the 8 pts with extramedullary relapse, median OS and EFS were 120 and 29 months versus not reached and 85 months, respectively. The median time from HDT-ASCT to extramedullary relapse was 85 months. Sites of extramedullary relapse included vertebral and para-vertebral localization (7 pts), humeral localization (2 pts) and thoracic localization (1 patient); one patient presented humeral and pancreatic localization. The 8 pts with isolated extramedullary relapses were treated by local radiotherapy (4 pts), radiotherapy combined to Melphalan-Prednisone (MP) (3 pts) and a combination of surgical treatment + MP (1 patient). In conclusion, HDT-ASCT has greatly improved the prognosis of MM pts, however about 10%–15% of transplanted pts experience an extramedullary relapse probably due to sub-clinical seeding of tumor cells suggestive of the presence of an extramedullary clone of plasma cells with a high degree of chemo resistance responding, however, to radiotherapy.

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Bone Morphogenic Protein 6: A Prognostic Factor Expressed by Normal Plasma Cells and Multiple Myeloma Cells Inhibiting Their Proliferation and Angiogenesis Induction

Blood ◽

10.1182/blood.v112.11.2701.2701 ◽

2008 ◽

Vol 112 (11) ◽

pp. 2701-2701

Author(s):

Anja Seckinger ◽

Tobias Meißner ◽

Jérôme Moreaux ◽

Hartmut Goldschmidt ◽

Axel Benner ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Overall Survival ◽

Cell Lines ◽

Plasma Cells ◽

Myeloma Cell ◽

High Dose Chemotherapy ◽

High Dose ◽

Myeloma Cells

Abstract BACKGROUND: Pathogenesis of multiple myeloma is partly attributed to an aberrant expression of proliferation-, pro-angiogenic and bone-metabolism modifying factors by malignant plasma-cells. AIM. Given the long and variable time-span from first diagnosis of early-stage plasma-cell dyscrasias to overt myeloma and the low proliferation rate of malignant plasma-cells, we hypothesize these to concomitantly express a novel class of anti-proliferative factors of potential prognostic relevance. Here, bone morphogenic proteins (BMPs) represent possible candidates, as they inhibit proliferation, stimulate bone formation, and have an impact on the survival of cancer patients. PATIENTS AND METHODS. We assessed expression of BMPs and its receptors by Affymetrix DNA-microarrays (n=434) including CD138-purified primary myeloma-cell-samples, normal bone-marrow plasma-cell-samples, polyclonal plasmoblasts-samples, human myeloma-cell-lines (HMCL), and whole bone-marrow. Presence and differential gene expression was determined by PANP-algorithm and empirical Bayes statistics. Event-free (EFS) and overall survival (OAS) were investigated for the 168 patients undergoing high-dose chemotherapy (HM-group) using Cox’s proportional hazard model. Findings were validated using the same strategy on an independent group of 345 patients from the Arkansas-group. For validation, quantitative real-time PCR and flow cytometry were performed. In vitro induction of angiogenesis was assessed using the AngioKit-assay. Effect of BMP6 on proliferation of HMCL was assessed by 3H-thymidine uptake. RESULTS. BMP6 is the only BMP expressed by normal- (13/14 samples) and malignant plasma-cells (228/233 samples). It is significantly lower expressed in proliferating non-malignant plasmablastic cells and human myeloma cell-lines. In vitro, BMP6 significantly inhibits proliferation of myeloma-cell-lines with an IC50 ranged from 0.08–2.15μg/ml, survival of primary myeloma-cells, and in vitro tubule formation down to the level of the negative control. High BMP6-expression in malignant plasma cells delineates significantly superior overall-survival for patients undergoing high-dose chemotherapy in both independent series of patients (n=168, P=.02 and n=345, P=.03, respectively, see below). CONCLUSION. With BMP6 we report for the first time the autocrine expression of a prognostically relevant anti-angiogenic and anti-proliferative factor and its receptors by normal and malignant plasma-cells. Figure Figure

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Lenalidomide Therapy in Nine Patients with POEMS Syndrome.

Blood ◽

10.1182/blood.v114.22.3872.3872 ◽

2009 ◽

Vol 114 (22) ◽

pp. 3872-3872 ◽

Cited By ~ 1

Author(s):

Arnaud Jaccard ◽

Julie Abraham ◽

Christian Recher ◽

Remy Dulery ◽

Isabelle Guichard ◽

...

Keyword(s):

Peripheral Neuropathy ◽

Board Of Directors ◽

Plasma Cells ◽

High Dose Chemotherapy ◽

Poems Syndrome ◽

Bone Lesions ◽

High Dose ◽

Advisory Committees ◽

Sclerotic Bone Lesions ◽

Vegf Level

Abstract Abstract 3872 Poster Board III-808 Introduction POEMS syndrome is a rare disease characterized by peripheral neuropathy, organomegaly, endocrinopathy, monoclonal plasma cells, skin changes, papilledema, volume overload, sclerotic bone lesions, thrombocytosis, and high serum VEGF level. Efficient treatments consist in irradiation for patients with localized solitary plasmocytoma and high-dose chemotherapy with autologous stem cell transplantation for appropriate candidates without a focal lesion. Conventional myeloma chemotherapy can only control the disease in a limited number of patients. Results of monoclonal anti-VEGF antibodies, which seem to be attractive due to the role of VEGF in this disease, are controversy with efficacy in 3 patients but treatment related deaths in 2 other patients. Thalidomide effectiveness has been reported in Japanese patients but enthusiasm for its use is tempered by the high incidence of thalidomide-induced peripheral neuropathy. Lenalidomide, which efficacy has been described in one observation (Dispenzieri, Blood 2007 110: 1075-1076), has the advantage of being anti-angiogenic, cytotoxic to malignant plasma cells and with a much lower risk of peripheral neuropathy. We reported here a multicentric French experience with this drug in POEMS syndrome. Patients and Methods There were 3 women and 6 men treated with Lenalidomide in 7 French centres. Median age was 60 (41-76). All patients had sensitive polyneuropathy with motor deficiency in 5 patients. A monoclonal component was present in all cases (IgA lambda in 7 patients, IgG lambda and lambda light chain only in 1 patient each). Other manifestations of POEMS syndrome included sclerotic bone lesions in 6 patients, endocrinopathies in 7 patients, skin changes in 8 patients, oedema in 7 patients, organomegaly in 5 patients, papilledema in 5 patients, thrombocytosis in 3 patients. VEGF serum level was elevated in 4 among 5 patients with a dosage. Previous treatments were high-dose chemotherapy with autologous stem cell transplantation in 3 patients, Melphalan-Prednisone in 3 patients because of advanced age, and prolonged steroid treatment in 2 patients. One patient received Lenalidomide as primary treatment before high-dose therapy. Lenalidomide was given during 21 days each month and sequentially associated with dexamethasone, 5 patients received 25 mg/day and 4 patients received 10 or 15 mg, for a median of 5 cycles (1 to 11). Results Serious side effects were noted in 3 patients with 2 hematologic toxicities (grade III and IV) and a cutaneous allergy. Six patients could be evaluated for hematologic response and all responded, complete response in 3 patients and partial in 3 (>25%). Clinical responses occurred early, before 3 months of treatment, in 6 cases among 8 (1 patient is not yet evaluable), with a marked improvement in performance and in neurological syndrome. Other manifestations of POEMS syndrome improved, especially oedema in 5 cases among 6. VEGF level (normal value < 500 pg/ml) could be serially measured in 4 patients with a normalization in 1 patient and a significant decrease in 3 patients, median 7100 pg/ml (2100-10100) before treatment to 887 pg/ml (304-3270). In 1 of these 3 patients VEGF level increased to initial value while he was still taking Lenalidomide. A second patient experimented a relapse 5 months after ending Lenalidomide, he is still in good response after Lenalidomide reintroduction. With a median follow-up of 12 months (1-26) all patients are alive. Conclusion Lenalidomide seems to be a very promising therapy in POEMS syndrome. It should be tested in larger studies in patients with a systemic disease, who are not able to receive high dose therapy, in relapsing patients and before high dose treatment to avoid transplant related morbidity, particularly engraftment syndrome. Disclosures: Jaccard: Celgene: Membership on an entity's Board of Directors or advisory committees. Facon:Celgene: Membership on an entity's Board of Directors or advisory committees and Speakers Bureau. Moreau:Celgene: Membership on an entity's Board of Directors or advisory committees. Fermand:Celgene: Speakers Bureau.

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