melphalan and POEMS-Syndrome

POEMS syndrome is a clonal plasma cell disease characterized by polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes. Significant advances have been made in the diagnosis and treatment of POEMS syndrome over the last decade. Herein, the diagnostic criteria and characteristic features are reviewed, focusing the role of characteristic features in early diagnoses. Autologous peripheral blood stem cell transplantation has become the first-line treatment for younger patients with normal organ function. Autologous transplantation has resulted in a high response rate and durable remission. Moreover, transplantation-related morbidity and mortality has been significantly reduced over the past 5 years. Induction therapy before transplantation may improve the harvest of stem cells and decrease transplantation-related morbidity. Melphalan and dexamethasone is an effective and well-tolerated treatment for older patients or those with organ dysfunction. Novel agents may also offer benefits to patients with a poor performance status or renal dysfunction, and transform transplantation eligibility.

Topics: Antibodies, Monoclonal, Humanized; Bevacizumab; Boronic Acids; Bortezomib; Castleman Disease; Chromosome Aberrations; Combined Modality Therapy; Dexamethasone; Disease Management; Drug Therapy, Combination; Genes, Immunoglobulin; Humans; Hypertension, Pulmonary; Lenalidomide; Melphalan; Osteosclerosis; Peripheral Blood Stem Cell Transplantation; Plasma Cells; POEMS Syndrome; Prognosis; Pyrazines; Severity of Illness Index; Symptom Assessment; Thalidomide; Transplantation, Autologous; Vascular Endothelial Growth Factor A

POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) syndrome is a rare cause of demyelinating and axonal mixed neuropathy with monoclonal plasma cell proliferative disorder and multiorgan involvement. The pathogenesis of POEMS syndrome is not well understood, but overproduction of vascular endothelial growth factor (VEGF), probably secreted by plasmacytomas, is likely to be responsible for most of the characteristic symptoms. POEMS syndrome is a potentially fatal disease, and patients' quality of life deteriorates because of progressive neuropathy, massive pleural effusion or ascites, or thromboembolic events. There is a need for efficacious therapy to improve prognosis. This is the first update of a review first published in 2008.. To assess the effects of treatment for POEMS syndrome.. We searched the Cochrane Neuromuscular Disease Group Specialized Register (23 February 2012), CENTRAL (2012, Issue 2), MEDLINE (January 1966 to February 2012), EMBASE (January 1980 to February 2012) and CINAHL Plus (January 1937 to February 2012) for all papers on POEMS syndrome. We sought all randomized and quasi-randomized controlled trials, and non-randomized controlled studies. Since we discovered no such clinical trials, we assessed and summarized all retrospective case series including five or more patients in the 'Discussion' section.. Two review authors independently reviewed and extracted details of all potentially relevant trials with any treatment for POEMS syndrome. We then collated and summarized information on the outcome.. We found no randomized or non-randomized prospective controlled trials of treatment for POEMS syndrome. We summarized the results of retrospective case series containing five or more patients in the 'Discussion' section.. There are no randomized or quasi-randomized controlled clinical trials of treatment for POEMS syndrome on which to base practice.

Topics: Adrenal Cortex Hormones; Hematopoietic Stem Cell Transplantation; Humans; Melphalan; POEMS Syndrome; Retrospective Studies; Thalidomide

Primary AL amyloid polyneuropathy (AL-PN) and neuropathy due to POEMS syndrome (POEMS-N) are rare, associated with a monoclonal gammopathy (MG) IgGλ or IgAλ at a low rate and systemic manifestations. They are invalidating and life-threatening.. AL-PN usually mimics small fiber length-dependent axonal polyneuropathies, but also multifocal or painful neuropathies, POEMS-N corresponds to a rapid ascending CIDP with MG. To confirm the diagnosis of AL-PN, initial investigations should identify amyloidosis on nerve or accessory salivary glands, to establish the type of amyloid after serum free light-chain (FLC) measurements. For the diagnosis of N-POEMS, diagnosis is based on the presence of four criteria proposed by Dispenzieri. These neuropathies are associated with biomarkers, useful for diagnosis and treatment monitoring: elevated serum level of FLC monoclonal in (AL-PN) or VEGF (N-POEMS).. Early diagnosis of these neuropathies and early treatment using high-dose melphalan associated with an autologous hematopoietic stem cell graft or low monthly doses can improve the clinical manifestations and patient survival.. Systematic search for monoclonal gammopathy by immunofixation and serum free light chains is very useful for the management of progressive peripheral neuropathies of unknown origin.

Topics: Amyloid; Amyloid Neuropathies; Biomarkers; Biopsy; Castleman Disease; Combined Modality Therapy; Drug Therapy, Combination; Early Diagnosis; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin lambda-Chains; Melphalan; Paraproteinemias; Peripheral Nerves; POEMS Syndrome; Prednisone; Salivary Glands, Minor; Skin; Thalidomide; Vascular Endothelial Growth Factor A

Crow-Fukase syndrome is also called POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) syndrome and is a rare cause of demyelinating and axonal mixed neuropathy with multiorgan involvement. The pathogenesis of Crow-Fukase syndrome is not well understood, but overproduction of vascular endothelial growth factor (VEGF), probably mediated by monoclonal proliferation of plasma cells, is likely to be responsible for most of the characteristic symptoms. However, other cytokines are also upregulated and could contribute to the pathophysiology of this syndrome. The etiopathophysiology of peripheral neuropathy is unclear, but VEGF may affect the blood-nerve barrier and allow some neurotoxic substances in the serum to access the nerve parenchyma, resulting in nerve demyelination. Moreover, microangiopathy due to proliferative endothelial cells and hypercoagulability may contribute to the development of neuropathy. A recent molecular biological study has shown oligoclonal usage of V(lambda) subfamily in light chain of the M-protein, suggesting that particular patterns of V(lambda) gene are associated with the development of Crow-Fukase syndrome. There is no established treatment regimen for this syndrome. In appropriate candidates, high-dose chemotherapies with autologous peripheral blood stem cell transplantation is highly recommended, because this treatment can cause obvious improvement in neuropathy as well as other symptoms, with a significant decrease in serum VEGF levels. The indication for this treatment has not yet been established, and the long-term prognosis is unclear. Potential future therapies include the administration of thalidomide or lenalidomide, and anti-VEGF monoclonal antibody (bevacizumab).

Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Bevacizumab; Humans; Immunoglobulin lambda-Chains; Lenalidomide; Melphalan; Paraneoplastic Syndromes, Nervous System; Peripheral Blood Stem Cell Transplantation; POEMS Syndrome; Thalidomide; Transplantation, Autologous; Vascular Endothelial Growth Factor A

Crow-Fukase syndrome, also called POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) syndrome, is a rare cause of demyelinating and axonal mixed neuropathy with multiorgan involvement. The pathogenesis of Crow-Fukase syndrome is not well understood, but overproduction of vascular endothelial growth factor (VEGF), probably mediated by monoclonal proliferation of plasma cells, is likely to be responsible for most of the characteristic symptoms. There is no established treatment regimen. In appropriate candidates, high-dose chemotherapies with autologous peripheral blood stem cell transplantation is highly recommended, because this treatment could result in obvious improvement in neuropathy as well as other symptoms, with a significant decrease in serum VEGF levels. Indication of this treatment has not yet been established, and long-term prognosis is unclear at present. Thalidomide should be considered for patients who are not indicated for transplantation therapy. Treatments that should be considered as future therapy include lenalidomide, bortezomib, and anti-VEGF monoclonal antibody (bevacizumab).

Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Bevacizumab; Boronic Acids; Bortezomib; Combined Modality Therapy; Demyelinating Diseases; Humans; Lenalidomide; Melphalan; Peripheral Blood Stem Cell Transplantation; POEMS Syndrome; Pyrazines; Thalidomide; Transplantation, Autologous; Vascular Endothelial Growth Factor A

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) is a paraneoplastic disease associated with an underlying plasma cell dyscrasia. This syndrome usually progresses slowly and can be life-threatening. No large-scale controlled study providing convincing evidence for the treatment of this rare condition has thus for been conducted. However, several lines of evidence have shown the efficacy of conventional therapies such as radiation, alkylator-based treatment, and corticosteroid therapy. Recent studies have also proposed novel therapeutic strategies such as autologous peripheral blood stem cell transplantation (auto-PBSCT) and thalidomide, lenalidomide, and bevacizumab therapies. We reviewed the current treatment strategies for POEMS syndrome and summarized them as follows; 1) Radiotherapy or surgical resection is highly effective for isolated plasmacytoma. 2) Melphalan-predonisolone administration may be a treatment option for the patients with widespread bone lesions. 3) High dose chemotherapy with auto-PBSCT is a promising novel approach that can lead to dramatic improvement particularly in patients with good systemic condition. 4) Plasma exchange and immunoglobulin treatment are not recommended. 5) Administration of thalidomide and lenalidomide may ameliorate the clinical conditions of the patients who are unable to undergo auto-PBSCT; however, this needs further confirmation. Finally, we emphasized that the efficacy of these therapies largely depends on the appropriate early diagnosis of POEMS syndrome.

Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Bevacizumab; Combined Modality Therapy; Humans; Immunoglobulins; Melphalan; Peripheral Blood Stem Cell Transplantation; Plasma Exchange; POEMS Syndrome; Prednisolone; Prognosis; Radiotherapy; Surgical Procedures, Operative; Thalidomide; Transplantation, Autologous; Vascular Endothelial Growth Factor A

Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome is a rare multi-organ disease. Because the peripheral neuropathy is frequently the overriding symptom and because the characteristics of the neuropathy are similar to that chronic inflammatory demyelinating polyneuropathy(CIDP), patient are frequently misdiagnosed with CIDP or monoclonal gammopathy of undetermined significance (MGUS) -associated peripheral neuropathy. Production of vascular endothelial growth factor (VEGF), secreted by plasmacytoma, is considered responsible for these symptoms. For isolated plasmacytoma, radiotherapy is usually highly effective. Patients without isolated plasmacytoma require systemic chemotherapy, which is ineffective in many cases. In recent reports, high dose chemotherapy followed by autologous peripheral blood stem cell transplantation can dramatically improve clinical manifestations, particularly for polyneuropathy in such patients refractory for standard chemotherapy.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Bevacizumab; Biomarkers; Diagnosis, Differential; Drug Therapy, Combination; Hematopoietic Stem Cell Transplantation; Humans; Melphalan; POEMS Syndrome; Prednisolone; Thalidomide; Vascular Endothelial Growth Factor A

POEMS syndrome is a rare clonal plasma cell disorder without standard treatment. Based on the efficacy and low toxicity of a combination of melphalan and dexamethasone (MDex) for light chain amyloidosis, we conducted a prospective study of MDex treatment for patients with newly diagnosed POEMS syndrome. Thirty-one patients (19 men) were enrolled and the median age at the time of diagnosis was 44 years (range, 32-68 years). All patients received 12 cycles of MDex treatment. Twenty-five patients (80.6%) achieved hematologic response including 12 (38.7%) complete remission and 13 (41.9%) partial remission. Of all 31 patients, the neurologic response rate was 100%, assessed by overall neuropathy limitation scale (ONLS). The initial neurologic response was observed in 24 patients (77.4%) at 3 months after treatment and the median time to maximal neurologic response was 12 months (range, 3-15 months). Moreover, MDex substantially improved the level of serum vascular endothelial growth factor and relieved organomegaly, extravascular volume overload, and pulmonary hypertension. Only 6 patients (19.3%) suffered from grade 3 adverse events during treatment. All patients are alive and free of neurologic relapse after the median follow-up time of 21 months. Therefore, MDex is an effective and well-tolerated treatment option for patients with newly diagnosed POEMS syndrome.

Topics: Adult; Age of Onset; Aged; Anti-Inflammatory Agents; Dexamethasone; Drug Therapy, Combination; Female; Humans; Male; Melphalan; Middle Aged; Myeloablative Agonists; Neoadjuvant Therapy; POEMS Syndrome; Treatment Outcome

Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes syndrome is a rare multisystem disorder. Overproduction of vascular endothelial growth factor (VEGF) by plasmocytoma could be responsible for the symptoms. The authors treated four patients with high-dose chemotherapy and autologous peripheral blood stem cell transplantation. Within 6 months, symptoms associated with rapid normalization of serum VEGF levels improved.

Topics: Adult; Aged; Down-Regulation; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Myeloablative Agonists; Peripheral Nervous System Diseases; Plasmacytoma; POEMS Syndrome; Transplantation, Autologous; Treatment Outcome; Vascular Endothelial Growth Factor A

We treated 5 patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome and multifocal bone lesions or diffuse bone marrow plasmacytic infiltration with high-dose therapy (HDT) and autologous blood stem cell transplantation. In all cases, the treatment produced remission of plasma cell proliferation associated with marked improvement in the patients' performance status, neurologic symptoms, and other manifestations of the syndrome. HDT with stem cell support should be investigated further as a therapeutic option in patients with POEMS syndrome and disseminated plasma cell dyscrasia.

Topics: Adult; Antineoplastic Agents, Alkylating; Clone Cells; Combined Modality Therapy; Dose-Response Relationship, Drug; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulins; Male; Melphalan; Middle Aged; Nervous System Diseases; Plasma Cells; POEMS Syndrome; Remission Induction; Transplantation, Autologous; Treatment Outcome

Topics: Biomarkers; Humans; Lenalidomide; Melphalan; Outcome Assessment, Health Care; POEMS Syndrome; Thalidomide; Treatment Outcome; Vascular Endothelial Growth Factor A

POEMS syndrome is a rare plasma cell dyscrasia. This study compared the responses to and survival of 347 POEMS syndrome patients given three first-line treatment regimens: autologous stem cell transplantation (ASCT, N = 165) and melphalan + dexamethasone (MDex, N = 79), or lenalidomide + dexamethasone (LDex, N = 103). After a median 45-month follow-up, overall hematologic complete remission (CR

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Dexamethasone; Female; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Humans; Lenalidomide; Male; Melphalan; Middle Aged; POEMS Syndrome; Remission Induction; Retrospective Studies; Survival Rate; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome

Six patients with POEMS syndrome who received autologous peripheral blood stem cell transplantation (auto-PBSCT) were retrospectively analyzed. Conditioning regimen was high dose melphalan. Peripheral blood stem cells were collected after mobilization with cyclophosphamide (CTX) and growth factors. One patient presenting hydrothorax and ascites was treated with 3 cycles of lenalidomide and dexamethasone before mobilization. Auto-PBSCT was fairly tolerable. Hematopoietic reconstitution was successful in all patients without transplantation-related mortality. A decrease or normalization of serum vascular epithelial growth factor (VEGF) was observed in all patients at 3 months after transplantation. The neurological remission was seen in 5/6 patients.. 回顾性分析采用自体外周血造血干细胞移植（auto-PBSCT）治疗POEMS综合征的疗效及安全性。6例患者用大剂量马法兰预处理后进行auto-PBSCT治疗，干细胞动员采用环磷酰胺后注射粒细胞集落刺激因子，其中1例以胸腹水为首发表现的患者动员前予Rd方案（来那度胺+地塞米松）治疗。患者耐受性好，移植后均迅速造血重建，无移植相关死亡，3个月后血清血管内皮生长因子水平明显下降/恢复正常，神经系统缓解的比例为5/6。.

Topics: Antineoplastic Agents, Alkylating; Biomarkers; Cyclophosphamide; Dexamethasone; Humans; Lenalidomide; Melphalan; Peripheral Blood Stem Cell Transplantation; POEMS Syndrome; Retrospective Studies; Transplantation, Autologous; Treatment Outcome; Vascular Endothelial Growth Factor A

Topics: Adult; Aged; Autografts; Female; Hematopoietic Stem Cell Mobilization; Humans; Male; Melphalan; Middle Aged; POEMS Syndrome; Stem Cell Transplantation

Arterial and venous thromboses occur in almost one in five patients with POEMS syndrome and usually in macrocirculation.. We report a 67-year-old male with a POEMS syndrome who presented initially with a blue toe syndrome. He complained of Raynaud's syndrome and left foot paresthesia. Physical examination showed gynecomastia, lymphadenopathies and skin lesions. Cardiovascular investigations excluded atrial fibrillation, unstable atherosclerotic lesions and vascular calcifications. Imaging studies showed diffuse osteosclerotic lesions. Monoclonal protein with lambda light chain was discovered and serum level of VEGF was increased at 2900pg/ml.. This is to our knowledge the first case of thrombotic microangiopathy in POEMS syndrome without embolic cause or calciphylaxis.

Topics: Aged; Antineoplastic Agents, Alkylating; Blue Toe Syndrome; Dexamethasone; Glucocorticoids; Humans; Male; Melphalan; POEMS Syndrome; Positron-Emission Tomography; Tomography, X-Ray Computed; Vascular Endothelial Growth Factor A

To report the correlation between visual function and subfoveal choroidal thickness (SChT) in a case of POEMS syndrome.. A 53 year old man diagnosed with POEMS syndrome was referred due to blurred vision. Best corrected visual acuity (BCVA) was 0.5 in his right eye (RE) and 0.7 in his left eye (LE), with a mild perimetric defect in the RE. SChT was 356 and 263 µm in his RE and LE. After an autologous peripheral blood stem-cell transplantation, both visual and systemic symptoms improved. At the most recent visit, SChT was 284 and 222 µm in his RE and LE, BCVA was 1.2 in both eyes and the perimetric defects had improved.. SChT was inversely correlated with visual function in space and time. Due to the high sensitivity of choroidal tissue to vascular endothelial growth factor, SChT might be useful to monitor disease activity in POEMS.

Topics: Antineoplastic Agents, Alkylating; Choroid; Cord Blood Stem Cell Transplantation; Drug Combinations; Glucocorticoids; Humans; Immunoglobulins, Intravenous; Male; Melphalan; Middle Aged; Organ Size; POEMS Syndrome; Prednisone; Tomography, Optical Coherence; Vision Disorders; Visual Acuity; Visual Fields

POEMS (acronym for polyneuropathy, organomegaly, endocrinopathy, M protein myeloma and skin changes), is a rare disease which occurs in the setting of plasma cell dyscrasias. We describe a case of an adult lady who presented with gradual onset weakness of all four limbs and multisystem involvement characterized by pedal edema, ascites, hyperpigmentation and hypogonadism. Nerve conduction study showed severe sensorimotor polyneuropathy. Serum immunofixation showed lambda light chain restricted monoclonal gammopathy. Bone marrow biopsy consistent with plasma cell dyscrasia. Hormonal assay showed decreased FSH, LH and estradiol levels which led us to diagnosis of hypogonadotrophic hypogonadism. The patient responded well to combination therapy of thalidomide, melphalan and dexamethasone. Eight months after the therapy, she noted decreased paresthesias and increased strength. She had reduced edema and ascites.

Topics: Adult; Dexamethasone; Female; Humans; Hypogonadism; Melphalan; Paraproteinemias; POEMS Syndrome; Polyneuropathies; Thalidomide; Treatment Outcome

POEMS syndrome is the syndrome of Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein and typical Skin changes. A 65-year-old lady presented with the 2-day-history of inability to walk, 4-month-history of progressive worsening of muscle weakness of both lower limbs and 1-year-history of progressive worsening of bilateral numbness of lower limbs. Nerve conduction study revealed generalized sensorimotor demyelinating polyneuropathy. She was initially treated as chronic inflammatory demyelinating polyradiculoneuropathy with intravenous immunoglobulin (IVIG) and high-dose prednisolone. However, she had no significant neurological improvement despite getting standard therapy. In addition to peripheral neuropathy, the presence of hepatosplenomegaly, skin changes, polycythaemia and thrombocytosis prompted for further investigations. She was diagnosed as POEMS syndrome based on the presence of two mandatory major criteria [polyneuropathy, monoclonal plasma cell proliferative disorder (lambda)], one major criterion (sclerotic bone lesions) and three minor criteria (organomegaly, skin changes and thrombocytosis/polycythaemia). She received treatment with melphalan and prednisolone. She achieved clinical improvement and partial response (haematologic and radiological) after six cycles of therapy. We highlight the awareness of this rare syndrome, for patients presenting with peripheral neuropathy and not responding to its standard therapy, by recognizing other associated clinical manifestations and proceeding further diagnostic work-up.

Topics: Aged; Anti-Inflammatory Agents; Female; Humans; Melphalan; Myeloablative Agonists; POEMS Syndrome; Prednisolone

Polyneuropathy, Organomegaly, Endocrinopathy, M-protein and Skin changes syndrome is a rare paraneoplastic syndrome from a plasma cell dyscrasia, which most commonly presents with peripheral neuropathy. We report a 30-year-old female with blurred vision and vision loss as reasons for her initial treatment; the patient was diagnosed with bilateral opticneuritis. Five months later, the patient started to have lower extremity numbness and fatigue. Initial laboratory tests did not reveal positive monoclonal immunoglobulin. Therefore, simple peripheral neuropathy was considered for diagnosis, and the patient was treated in the Department of Neurology in our hospital; however, the symptom was not alleviated. Seven months later, the patient showed symptoms of cough, dyspnea, along with rough skin, pigmentation and drooping of both feet. Chest CT revealed bronchiectasis and infection of lungs, destruction of thoracic bones and ribs. Further examination indicated that the patient had splenomegaly, hypothyroidism and monoclonal IgA-λ chain zone, which led to a clear diagnosis of Polyneuropathy, Organomegaly, Endocrinopathy, M-protein and Skin changes syndrome.

Topics: Adult; Antineoplastic Agents, Alkylating; Diagnosis, Differential; Disease Progression; Dyspnea; Female; Humans; Melphalan; Optic Neuritis; Paresis; Peripheral Blood Stem Cell Transplantation; POEMS Syndrome; Treatment Outcome

Topics: Adult; Antigens, CD34; Disease-Free Survival; Female; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; POEMS Syndrome; Time Factors; Transplantation, Autologous; Treatment Outcome

We experienced the case of a 67-year-old man with refractory heart failure. He presented with dyspnea and progressive pitting edema of the lower limbs. Diuretics were insufficient to improve his symptoms. Cardiac catheterization demonstrated pulmonary hypertension. Additional examinations confirmed polyneuropathy, organomegaly, endocrinopathy and monoclonal gammopathy. The plasma vascular endothelial growth factor (VEGF) level was 1,340 pg/mL. The patient was diagnosed with Crow-Fukase (POEMS) syndrome. Echocardiography detected left ventricular hypertrophy and diastolic dysfunction. Polysomnography demonstrated severe sleep-disordered breathing. We herein describe a case of pulmonary hypertension with Crow-Fukase syndrome accompanied by left ventricular diastolic dysfunction and sleep-disordered breathing.

Topics: Aged; Dexamethasone; Diuretics; Drug Resistance; Edema; Furosemide; Heart Failure; Humans; Hypertension, Pulmonary; Hypertrophy, Left Ventricular; Male; Melphalan; POEMS Syndrome; Polysomnography; Prednisolone; Pulmonary Wedge Pressure; Sleep Apnea Syndromes; Thalidomide; Ultrasonography; Vascular Endothelial Growth Factor A; Ventricular Dysfunction, Left

Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome is a multisystem disorder associated with plasma cell dyscrasia. Elevated serum levels of vascular endothelial growth factor (VEGF), which strongly promotes neovascularization and vasopermeability, are considered to be responsible for the characteristic symptoms such as angiomata, pleural effusion/ascites, edema, and organomegaly in the disorder. To study whether other angiogenetic factors are upregulated in POEMS syndrome, we measured serum levels of basic fibroblast growth factor and hepatocyte growth factor (HGF), as well as VEGF, in 17 patients with POEMS syndrome. All these factors were significantly upregulated in the POEMS syndrome patients. After the treatment with anti-VEGF antibody, the levels of HGF did not change, suggesting that elevation of HGF levels is not secondary to VEGF overproduction. These results suggest that different angiogenetic factors might contribute to the pathogenesis of POEMS syndrome, and this fact might contribute to the insufficient clinical effects obtained by suppression of VEGF alone.

Topics: Adult; Aged; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Bevacizumab; Female; Fibroblast Growth Factor 2; Gene Expression Regulation; Hepatocyte Growth Factor; Humans; Male; Melphalan; Middle Aged; POEMS Syndrome; Thalidomide; Up-Regulation; Vascular Endothelial Growth Factor A

The acronym POEMS syndrome stands for a rare multi-system disorder, comprised of polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes. Here, we present a single-center report of a series of five POEMS patients treated with melphalan high-dose therapy (HDT) with subsequent autologous blood stem cell transplantation (ABSCT). After a median follow-up of 52 months from time of diagnosis (range, 15-192) and a median follow-up of 18 months after ABSCT (range, 11-120), all patients were alive. Overall, no severe transplantation-associated complications such as engraftment syndrome or peri- or post-transplant death were noted. In two cases, HDT followed by ABSCT resulted in a complete hematologic response; in the additional three cases, partial responses (PR) were achieved including one very good hematologic PR. Only one patient with initial PR developed progressive disease nearly 2.5 years after transplantation. Consequently, a second HDT with ABSCT was successfully applied resulting in clinical improvement and hematologic PR. In line with previous single-center reports, melphalan HDT followed by ABSCT proved to be a first-line treatment option with tolerable side effects in severely affected POEMS patients with progressing symptoms.

Topics: Adult; Anthracyclines; Combined Modality Therapy; Dexamethasone; Female; Humans; Male; Melphalan; Middle Aged; Myeloablative Agonists; Neurologic Examination; Peripheral Blood Stem Cell Transplantation; POEMS Syndrome; Transplantation, Autologous; Treatment Outcome; Vascular Endothelial Growth Factor A

We report a 48-year-old man, a farmer, presenting with chronic sensori-motor polyneuropathy. Electrophysiology revealed demyelinating type of neuropathy. Immunoelectrophoresis for monoclonal protein was negative; however, plasmacytoma was discovered on spine imaging. After receiving radiotherapy and chemotherapy over past 9 months there has been a considerable improvement in patient's disability. This case highlights the role of skeletal survey in evaluation of chronic demyelinating neuropathy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Humans; Male; Melphalan; Middle Aged; Plasmacytoma; POEMS Syndrome; Radiography; Spinal Neoplasms

POEMS syndrome is a rare plasma cell dyscrasia characterized by polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes. This study reviewed the clinical characteristics and long-term outcome of 99 consecutive Chinese patients with newly diagnosed POEMS syndrome in a single institute. The median age of 99 patients was 45 years, and the ratio of men/women was 1.4. The median time from onset of symptoms to diagnosis was 18 months. The typical five features of peripheral neuropathy, organomegaly, endocrinopathy, M protein, and skin change remained to be essential for patients with POEMS syndrome in China. The unusual features like pulmonary hypertension (36%) and renal impairment (37%) were not uncommon in China. Eighty-three percent patients were alive after follow-up time of 25 months, and 10% patients had survived more than 60 months. Melphalan-based therapy (OR, 0.076; 95% CI, 0.02-0.285) and normal renal function (OR, 0.246; 95% CI, 0.076-0.802) were independent prognostic factors for the survival of patients with POEMS syndrome. In conclusion, POEMS syndrome in Chinese patients was a multi-systemic disease with clinical features similar to non-Chinese ones. Active therapy can effectively improve the prognosis of patients with POEMS syndrome.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Castleman Disease; China; Female; Humans; Kidney; Male; Melphalan; Middle Aged; POEMS Syndrome; Prognosis; Retrospective Studies; Survival Rate; Treatment Outcome

Topics: Amyloidosis; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Hormonal; Biomarkers; Dexamethasone; Humans; Immunoglobulin Light Chains; Male; Melphalan; Middle Aged; Monitoring, Physiologic; POEMS Syndrome; Vascular Endothelial Growth Factor A

POEMS syndrome is defined by the presence of a peripheral neuropathy (P), a monoclonal plasma cell disorder (M), and other paraneoplastic features, the most common of which include organomegaly (O), endocrinopathy (E), skin changes (S). Not all features of the disease are required to make the diagnosis. We report a case of POEMS syndrome in a 50-year-old female who presented with weakness, abdominal swelling and history of red cell transfusions. Because of the hepatosplenomegaly (Schuffner VII) we diagnosed her as chronic myelocytic leukemia (CML) or myelofibrosis. Her peripheral blood smear did not show granulopoiesis maturation from myeloblast nor leukoerytroblastic feature which was characteristic of CML and myelofibrosis. We found also anemia, peripheral motoric neuropathy and hyperpigmentation at her legs. The protein electrophoresis showed monoclonal gammopathy on b2 globulin. Bone marrow examination showed normal plasma cells. There was no lytic or sclerotic lesion on Schedel and tibia x-ray. The echocardiography showed pulmonary hypertension, pulmonary regurgitation, right and left ventricle hypertrophy with normal ejection fraction (50%). She was treated with melphalan 10 mg/m2 (day 1-4) and prednisone 60 mg/m2 (day 1-4) every 6 weeks with packed red cells transfusion. After 3 cycles the monoclonal protein was reduced from 35.5% to 26.1% (normal 2-5%) without changes in her spleen size. Until then she continued on melphalan and prednisone treatment. Although POEMS syndrome is a rare disease, it should be considered in patient with hepatosplenomegaly, especially if accompanied by peripheral neuropathy.

Topics: beta 2-Microglobulin; Bone Marrow; Diagnosis, Differential; Drug Therapy, Combination; Electrophoresis; Female; Glucocorticoids; Humans; Melphalan; Middle Aged; Myeloablative Agonists; POEMS Syndrome; Prednisone

To evaluate the efficacy and safety of autologous peripheral blood stem cell transplantation (auto-PBSCT) after high dose melphalan in patients with POEMS syndrome.. Nine patients including 6 males and 3 females received 10 auto-PBSCT after high dose melphalan in our hospital from June 2005 to October 2009. The median age at transplantation was 44 (39 - 48) years. The median time from onset of disease to transplantation was 12 (5 - 60) months. Peripheral stem cells were mobilized by G-CSF alone in one patient and 8 patients by G-CSF plus chemotherapy. Two patients were conditioned by melphalan 140 mg/m(2) and 7 by melphalan 200 mg/m(2). The median number of MNC was 3.75 (1.05 - 8.33) × 10(8)/kg, and that of CD34(+) cell was 5.37 (1.32 - 10.90) × 10(6)/kg.. One patient received tandem auto-PBSCT and others received single one. Stem cell engrafted in all but 1 patient who died of severe infection and acute renal failure on day 9 after transplantation. Eight patients were evaluable for response. The median time to ANC ≥ 0.5 × 10(9)/L and platelet ≥ 20 × 10(9)/L was 10 (9 - 11) and 11.5 (9 - 14) days respectively. Two patient reached negative immunofixation electrophoresis (IFE) after stem cell mobilization and transplantation respectively, and the other 6 remained IFE postive after auto-PBSCT. Skin changes and edema of lower extremities were improved in 5 of 6 patients, lymphadenopathy relieved in 1 and papilledema improved in 2 of 3 patients. All but 1 patient achieved gradual neurologic improvement after transplantation.. PBSCT is an effective and safe therapy for POEMS syndrome patients with low treatment related mortality.

Topics: Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Humans; Melphalan; Peripheral Blood Stem Cell Transplantation; POEMS Syndrome

Topics: Adult; Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Cyclophosphamide; Cytarabine; Depression, Chemical; Dexamethasone; Doxorubicin; Drug Therapy, Combination; Humans; Male; Melphalan; Plasma Cells; POEMS Syndrome; Prednisone; Protease Inhibitors; Pyrazines; Remission Induction; Vascular Endothelial Growth Factor A; Vincristine

We present the case of a 54-year-old woman with papilledema associated to POEMS syndrome. The presence of intracranial hypertension was detected and treatment started with acetazolamide.. The most common ophthalmological pathology in POEMS syndrome is papilledema, the etiology of which could be infiltrative, intracranial hypertension, inflammation or an increase of the vascular permeability. The correct diagnosis and treatment of papilledema, depending on its etiology, should permit an acceptable visual outcome to be achieved.

Topics: Acetazolamide; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Drug Therapy, Combination; Female; Humans; Intracranial Hypertension; Melphalan; Middle Aged; Papilledema; POEMS Syndrome; Prednisone; Rituximab; Visual Fields

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Bevacizumab; Blood Transfusion, Autologous; Bone and Bones; Castleman Disease; Charcot-Marie-Tooth Disease; Demyelinating Diseases; Diagnosis, Differential; DNA Mutational Analysis; Genetic Testing; Genotype; Humans; Inheritance Patterns; Male; Melphalan; Middle Aged; Myeloablative Agonists; Pedigree; Peripheral Nerves; Peripheral Nervous System Diseases; POEMS Syndrome; Treatment Outcome; Vascular Endothelial Growth Factor A

Topics: Hematopoietic Stem Cell Transplantation; Humans; Melphalan; Myeloablative Agonists; POEMS Syndrome; Treatment Outcome; Vascular Endothelial Growth Factor A

POEMS syndrome is a rare plasma cell disorder, characterized by polyneuropathy, organomegaly, endocrinopathy, serum monoclonal protein, and skin lesions. Although not included in the acronym, renal lesions also are characteristic of this disease and sometimes require dialysis therapy. We treated a 61-year-old woman with POEMS syndrome with high-dose melphalan therapy (HDT) supported by autologous blood stem cell transplantation (SCT), and clinical remission was achieved. A repeated renal biopsy showed the striking effectiveness of this therapy on renal lesions. Pathological features of the renal lesions, such as membranoproliferative glomerulonephritis-like lesions, microangiopathic glomerulopathy, and mesangiolytic lesions with microcapillaries, almost completely disappeared. This treatment also markedly decreased serum levels of vascular endothelial growth factor (VEGF). These findings indicate that HDT with SCT is effective, even on renal lesions in patients with POEMS syndrome, and suggest that high serum VEGF concentrations are associated closely with the development of renal lesions in patients with this type of plasma cell disorder.

Topics: Combined Modality Therapy; Female; Humans; Kidney Diseases; Melphalan; Middle Aged; Peripheral Blood Stem Cell Transplantation; POEMS Syndrome; Remission Induction; Severity of Illness Index

A 36-year-old man was admitted because of numbness and muscle weakness in the lower extremities. He had gait disturbance, malaise, and body weight loss. Based on the existence of monoclonal gammopathy, the proliferation of abnormal plasma cells in the bone marrow, the presence of sclerotic bone lesion, polycythemia, mild splenomegaly, and an elevated level of serum vascular endothelial growth factor (VEGF) (14,900 pg/mL; normal, 62-707), he was diagnosed as having peripheral neuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. Following 2 courses of conventional chemotherapy with doxorubicin and dexamethasone, peripheral blood stem cells were mobilized by high-dose etoposide (500 mg/m(2) x 3 days) and granulocyte colony-stimulating factor. After purging by CD34+ selection using the CliniMACS device, the selected cells (12.4 x 10(6)/kg) were cryopreserved. He was then treated with tandem high-dose chemotherapy (HDC) (melphalan 100 mg/m(2) x 2 days) with autologous stem cell rescue. After the first course of HDC, the serum level of VEGF normalized and the minimal residual disease in the bone marrow was reduced below the detection limit of CDR3 analysis by polymerase chain reaction. The patient has been in remission for more than 20 months. He has gradually recovered from the neurological symptoms and now has no impairments of daily living. Our experience suggests that autologous purged stem cell transplantation should be considered as the treatment of choice for POEMS syndrome.

Topics: Adult; Antigens, CD34; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Purging; Dexamethasone; Doxorubicin; Etoposide; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Humans; Male; Melphalan; POEMS Syndrome; Remission Induction; Stem Cell Transplantation; Transplantation, Autologous

Topics: Adult; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Bone Marrow; Bone Marrow Examination; Dexamethasone; Diagnosis, Differential; Doxorubicin; Echocardiography, Transesophageal; Follow-Up Studies; Humans; Hypertension, Pulmonary; Male; Melphalan; Multiple Myeloma; Peripheral Blood Stem Cell Transplantation; POEMS Syndrome; Radiography, Thoracic; Time Factors; Treatment Outcome; Tricuspid Valve Insufficiency; Ultrasonography, Doppler, Color; Vincristine

A 39-year-old male presented with pedal edema, pleural effusion, splenomegaly, and generalized lymphadenopathy. Serum protein electrophoresis demonstrated the presence of a monoclonal protein. Histological examination of the spleen following splenectomy showed multifocal vascular proliferation and angiovascular lesions consistent with multicentric Castleman disease. He was treated with steroids and rituximab, but without improvement. The patient was found to have portal venous thrombosis and lower extremity arterial thrombosis. He then received combination chemotherapy with cyclophosphamide and mitoxantrone but developed a severe inflammatory polyneuropathy that left him disabled and wheelchair-bound. A diagnosis of multicentric Castleman disease with POEMS syndrome was made, and he then received high-dose chemotherapy with melphalan followed by autologous peripheral blood stem-cell transplantation. Following transplantation, his nerve conduction studies improved and his serum protein electrophoresis normalized. He is currently ambulatory and does not need wheelchair assistance. Hematopoietic stem-cell transplantation may be a treatment option for patients with multicentric Castleman disease and POEMS syndrome.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Castleman Disease; Guillain-Barre Syndrome; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Peripheral Blood Stem Cell Transplantation; POEMS Syndrome; Thrombosis; Transplantation, Autologous; Treatment Outcome

A 42-year-old woman presented with pericardial and pleural effusion, ascites and para-aortic lymphadenopathy of unknown etiology. Six months later she was admitted with fever, pain and motor disturbance of lower limbs, and exacerbation of the effusion, ascites and edema. Physical examination showed hepatosplenomegaly, skin pigmentation and hypertrichosis. Immunoelectophoresis revealed monoclonal IgA-lambda protein in the serum and Bence-Jones protein-lambda in the urine. Bone marrow aspiration showed a mild increase of atypical plasma cells. Vascular endothelial growth factor (VEGF) had markedly increased to 10,900 pg/ml. Electromyography showed changes suggestive of demyelination. These clinical features were consistent with the diagnosis of POEMS syndrome. VAD chemotherapy was not effective for the effusion and neuropathic deterioration. After control of the massive pleural effusion by chest tube drainage, peripheral blood stem cell (PBSC) collection was performed with cyclophosphamide and G-CSF. The patient received melphalan 100 mg/m2 on 2 consecutive days and the PBSC were infused 2 days later. The bone marrow recovered rapidly and the pericardial and pleural effusion disappeared completely. Her performance status markedly improved from a bedridden state. High-dose melphalan with auto-PBSCT should be investigated further as a recommended therapy for POEMS syndrome.

Topics: Adult; Antineoplastic Agents, Alkylating; Biomarkers; Combined Modality Therapy; Female; Humans; Melphalan; Peripheral Blood Stem Cell Transplantation; POEMS Syndrome; Transplantation, Autologous; Treatment Outcome; Vascular Endothelial Growth Factor A

In common with other plasma cell dyscrasias in which a small tumour burden is associated with severe clinical symptoms (notably systemic AL amyloidosis) the possible benefits of dose intensification are yet to be fully explored in POEMS syndrome. One important issue is whether the toxicity of the procedure is significantly increased in this group. We report two cases of POEMS syndrome with solitary asymptomatic bone lesions treated with high-dose melphalan (200 mg/m(2)) and peripheral blood stem cell (PBSC) rescue. In both cases there was minimal peri-transplant morbidity and a subsequent substantial and maintained improvement in the peripheral neuropathy.

Topics: Adult; Female; Humans; Male; Melphalan; Middle Aged; Peripheral Blood Stem Cell Transplantation; POEMS Syndrome; Tomography, X-Ray Computed; Treatment Outcome

Topics: Adult; Combined Modality Therapy; Drug Therapy, Combination; Humans; Ifosfamide; Melphalan; POEMS Syndrome; Prednisolone; Stem Cell Transplantation; Time Factors; Transplantation, Autologous; Treatment Outcome

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) is a plasma cell dyscrasia that differs substantially from classic multiple myeloma. It is often associated with disabling polyneuropathy in younger patients. Current therapeutic approaches are frequently inadequate and leave many patients wheelchair-bound with significant deterioration in quality and length of life. We present the case of a young man with progressive disease despite conventional therapeutic approaches. We describe a novel approach to treatment with a bone-seeking radiopharmaceutical, samarium-153 ethylene diamine tetramethylene phosphonate ((153)Sm-EDTMP), followed by myeloablative chemotherapy with autologous hematopoietic progenitor cell reconstitution. This approach resulted in regression of the organomegaly and skin changes and in neurologic improvement both clinically and electrophysiologically. The patient progressed from being wheelchair-bound to independent ambulation. An aggressive approach should be considered in patients with POEMS syndrome in whom standard therapeutic measures fail.

Topics: Adult; Antineoplastic Agents, Alkylating; Dose-Response Relationship, Radiation; Drug Therapy, Combination; Graft Survival; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Organometallic Compounds; Organophosphorus Compounds; POEMS Syndrome; Quality of Life; Radiopharmaceuticals; Transplantation, Autologous; Treatment Outcome

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, serum monoclonal protein and skin changes) is a rare plasma cell disorder of unknown pathogenesis and is diagnosed by the demonstration of a plasma cell proliferation at the biopsy of an osteoesclerotic lesion. When the lesions are in a limited area, radiation therapy is usually highly effective. Patients with disseminated disease require systemic chemotherapy, which is not effective in most cases. A patient with severe widespread POEMS syndrome resistant to melphalan who experienced a dramatic improvement after high-dose melphalan followed by autologous haematopoietic cell transplantation (AHCT) is reported. We believe that this is the first reported case of POEMS syndrome treated with AHCT, a procedure that could be considered in similarly affected patients.

Topics: Adult; Antineoplastic Agents, Alkylating; Combined Modality Therapy; Female; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Humans; Melphalan; POEMS Syndrome; Transplantation, Autologous; Treatment Outcome

The effects of long term melphalan-prednisolone (MP) therapy was studied on 12 patients with POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) syndrome. Six were treated with MP every six weeks for 16 to 52 months; three also with cyclophosphamide, and three with localised irradiation for osteoclastic lesions. Five of the six survived during the follow up period and showed various degrees of lessening of their neuropathy and other symptoms. There were no serious side effects. The other six patients received treatments that included corticosteroids, short term chemotherapy, or irradiation, but not long term chemotherapy. Five showed transient lessening of their non-neurological symptoms, and one, obvious neurological improvement. Five of these six patients died from nine to 70 months after POEMS onset. The findings suggest that long term MP therapy may be an effective treatment for the POEMS syndrome.

Topics: Adult; Aged; Anti-Inflammatory Agents; Antineoplastic Agents, Alkylating; Drug Therapy, Combination; Female; Humans; Male; Melphalan; Middle Aged; POEMS Syndrome; Prednisolone; Time Factors

A 42-year-old woman with Crow-Fukase syndrome developed acute myeloid leukemia (M6: FAB classification) following treatment with alkylating agents (a total of 2,500 mg of melphalan and 9,800 mg of cyclophosphamide). Chromosome analysis of the bone marrow showed 49,XX,der(1;7)(q10;p10), +8, +19, +21 in therapy-related myelodysplastic syndrome with additional chromosomes 8, and 12 and two additional chromosomes 21 in acute leukemia. Because of the risk of therapy-related leukemia, alkylating agents should be used with caution in the treatment of Crow-Fukase syndrome.

Topics: Adult; Alkylating Agents; Chromosome Aberrations; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 7; Cyclophosphamide; Female; Humans; Leukemia, Erythroblastic, Acute; Melphalan; Myelodysplastic Syndromes; POEMS Syndrome; Translocation, Genetic; Trisomy

A 67-year-old woman, who presented polyneuropathy, pleural effusion, ascites and sclerosing changes in the ribs, was admitted to our hospital on June 17, 1987. On admission, cerebrospinal examination showed a marked protein-cell dissociation and a delay in nerve conduction velocity. Bence-Jones protein was detected in urine, and the immunohistochemical study of biopsied bone marrow of the rib revealed lambda-chain positive plasmacytoma. Serum immunoelectrophoresis, however, showed no monoclonal gamma-globulinemia. From the findings described above, she was diagnosed as having Crow-Fukase syndrome associated with lambda-type light chain disease. Even with a therapy by prednisolone, platelet counts progressively declined to 10,000/ml3. Bone marrow aspiration showed normal number of megakaryocytes. Since platelet-associated IgG was increased to 452 ng/1.0 x 10(8) plt, a diagnosis of autoimmune thrombocytopenia was considered. Melphalan and cyclophosphamide to plasmacytoma resulted in a marked improvement of platelets. In addition, the level of platelet-associated IgG returned to normal range. Polyneuropathy, however, didn't respond to those therapies. It was suggested that both Crow-Fukase syndrome and thrombocytopenia were closely concerned with plasmacytoma but developed in a different manner.

Topics: Aged; Cyclophosphamide; Female; Humans; Hypergammaglobulinemia; Immunoglobulin G; Immunoglobulin lambda-Chains; Immunoglobulin Light Chains; Melphalan; Paraproteinemias; POEMS Syndrome; Thrombocytopenia