The role of radiotherapy in the management of POEMS syndrome.

BACKGROUND: POEMS syndrome is a paraneoplastic syndrome caused by an underlying plasma cell proliferative disease. In this study, we examined the treatment outcomes and role of radiotherapy in the management of POEMS syndrome. METHODS: In total, 33 patients diagnosed with POEMS syndrome were analyzed. These patients presented with osteosclerotic myeloma (OSM, n = 13), Castleman's disease (CD, n = 4), OSM with CD (n = 10), and vascular endothelial growth factor elevation without gross lesions (VEGFe, n = 6), respectively. The patients were treated by radiotherapy alone (n = 4), chemotherapy alone (n = 16), or a combination thereof (n = 9). RESULTS: The clinical response rates of radiotherapy, chemotherapy, and radiotherapy plus chemotherapy were 75%, 69%, and 89%, respectively. In addition, the hematologic response rates were 50%, 69%, and 71%, respectively. Among the six patients with limited multiple lesions who underwent radiotherapy, the clinical symptoms were improved in five patients after radiotherapy. The median progression-free survival (PFS) was 51 months, and the median overall survival (OS) was 65 months. In univariate analysis, the administration of chemotherapy was significantly associated with better PFS (p = 0.007) and OS (p = 0.020). In contrast, underlying VEGFe was a significant factor worsening PFS (p = 0.035) and OS (p = 0.008). CONCLUSIONS: Radiotherapy produces a reliable clinical response and is effective in improving POEMS-associated symptoms that are refractory to chemotherapy in selected patients with clustered or limited multiple lesions that can be covered by single radiation field.

Muscle cramping over the diagnosis.

A 44-year-old man with hypogonadism and adrenal insufficiency presented with transient blurred vision and halos around lights. Visual acuity was 20/20 in both eyes, and he had mild bilateral optic disk edema. Brain imaging was unremarkable, and lumbar puncture showed an opening pressure of 28.5 cm H2O with elevated protein. He also complained of muscle cramping, and magnetic resonance imaging of the spine demonstrated a heterogenous bone marrow signal. Bone survey showed a mixed lytic and sclerotic lesion within the left femur that proved to be a plasmacytoma. Serum protein electrophoresis had a small IgA spike, and plasma vascular endothelial growth factor (VEGF) was elevated. He was diagnosed with POEMS syndrome and underwent radiation to the plasmacytoma. Two years later he had a stable neuro-ophthalmologic exam with no signs of multiple myeloma. POEMS syndrome is a rare paraneoplastic syndrome from a plasma cell dyscrasia that may cause optic disk edema.

Outcomes of patients with POEMS syndrome treated initially with radiation.

POEMS syndrome is a rare plasma cell dyscrasia presenting with polyneuropathy and other systemic findings. Patients with 1 to 3 bone lesions and negative bone marrows are often treated with involved field radiation therapy as the initial and potentially definitive therapy. Long-term outcomes of patients treated with this approach have not been systematically studied. Of the 146 patients with POEMS syndrome seen at the Mayo Clinic between January 1999 and September 2011, 38 (26%) were given targeted radiation as their initial primary therapy and are the ones studied here. The median number of bone lesions was 1 (range: 1-6). The median dose of radiation administered was 45 Gy (range: 35-54 Gy). Complete or partial hematologic, vascular endothelial growth factor, fluorodeoxyglucose-positron emission tomography, and clinical responses were documented in 31%, 14%, 22%, and 47%, respectively. With median follow-up of 43 months, the 4-year overall survival is 97% and event-free survival is 52%. Risk factors for needing salvage therapy included reduced pulmonary diffusing capacity of carbon monoxide and increased urinary total protein. The presence of 3 lesions compared with 1 or 2 did not increase risk for treatment failure. Among selected patients with POEMS syndrome, radiation produces durable, meaningful responses.

[New elements in the diagnosis and the treatment of primary AL amyloid polyneuropathy and neuropathy due to POEMS syndrome]. / Nouveautés dans le diagnostic et le traitement des neuropathies périphériques liées à l'amylose AL et au syndrome POEMS.

INTRODUCTION: 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. STATE OF THE ART: 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). PERSPECTIVES: 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. CONCLUSIONS: 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.

A case of POEMS syndrome with mixed hyaline vascular and plasma cell type Castleman's disease.

We report a 43-year-old man who developed progressive ascending sensorimotor polyneuropathy, a solitary bone plasmacytoma originating from a rib and an axillary lymph node with features of Castleman's disease, mixed hyaline vascular and plasma cell type. He was diagnosed of having non-Hodgkin's lymphoma seven years back and was treated. Examination revealed a smooth goitre, thickened skin, white nails, small testes and ankle oedema. Investigations revealed a monoclonal para-proteinaemia of 7.83 g/l and elevated levels of serum TSH and prolactin. In this case the Castleman's disease is localised and the lymphoma preceded the Castleman's disease.

POEMS syndrome.

POEMS syndrome is a rare paraneoplastic syndrome secondary to a plasma cell dyscrasia. Recognition of the complex of a combination of peripheral neuropathy, organomegaly, endocrinopathy, monoclonal plasmaproliferative disorder, skin changes, papilledema, extravascular volume overload (peripheral edema, pleural effusions, ascites), sclerotic bone lesions, thrombocytosis, Castleman disease is the first step in effectively managing the disease. A rise in the blood levels of vascular endothelial growth factor is usually confirmatory. More than 95% of patients will have monoclonal lambda sclerotic plasmacytoma(s) or bone marrow infiltration. In patients with a dominant sclerotic plasmacytoma, first line therapy should include radiation to the lesion. Retrospective analysis and personal experience would dictate that systemic therapy be considered for patients with diffuse sclerotic lesions or absence of any bone lesion and for those who have not demonstrated stabilization of their disease 3 to 6 months after completing radiation therapy. For those patients with diffuse disease, systemic therapy is indicated. Useful approaches include therapy with corticosteroids, low dose alkylator therapy, and high dose chemotherapy with peripheral blood stem cell transplant. Until the pathogenesis is fully understood, these are the mainstays of treatment for patients with POEMS syndrome. The role of anti-VEGF therapies, immune modulatory drugs, and proteasome inhibitors has not yet been defined, but drugs with known high rates of treatment related neuropathy should not be considered as first line therapy.

POEMS syndrome--a case for more aggressive treatment.

INTRODUCTION: Patients with POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal or M-protein and skin changes) syndrome exhibit a wide range of clinical manifestations and are often seen by a variety of specialists prior to diagnosis. CLINICAL PICTURE: We describe a case of POEMS syndrome that first presented with significant neuropathy but progressed to develop further manifestations of the condition, including marked gastrointestinal symptoms. TREATMENT: The patient was commenced on localised radiotherapy and chemotherapy in addition to immunomodulatory therapy for the neuropathy. CONCLUSION: We highlight several learning points that may benefit physicians from varied specialties. This case is also unique for its marked gastrointestinal manifestation. To our knowledge, this is the second reported case in the literature with this feature.

Strontium-89: a novel treatment for a case of osteosclerotic myeloma associated with life-threatening neuropathy.

Osteosclerotic myeloma is a rare disorder characterized by paraproteinaemia and osteosclerosis, and may be associated with a progressive peripheral neuropathy. Patients with widespread osteosclerotic lesions can succumb from neurological complications despite systemic chemotherapy. We present a case of disseminated osteosclerotic myeloma associated with POEMS (peripheral neuropathy, organomegaly, endocrinopathy, M band, skin changes) syndrome, which was complicated by a rapidly progressive, life-threatening neuropathy. The patient's symptoms remained unchanged in the face of combination chemotherapy. However, a substantial improvement was seen following outpatient treatment with the commonly available radioisotope strontium 89 in combination with steroids.

[Successful treatment of Crow-Fukase syndrome with radiation therapy].

A 73-year-old woman was referred to our hospital because of gait disturbance. She had peripheral polyneuropathy which was mainly of the demyelinating type, splenomegaly, a skin change and M protein (IgA-lambda). A bone scinti and a CT scan showed a mass lesion in the thoracic vertebra, and a biopsy revealed plasmacytoma. She was diagnosed as Crow-Fukase syndrome, and treated with local radiation therapy. After the treatment, M protein became undetectable, and gait disturbance was improved.

Marked improvement of severe polyneuropathy associated with multifocal osteosclerotic myeloma following surgery, radiation, and chemotherapy.

We describe a patient with a 3 year history of progressive polyneuropathy that rendered him severely quadriparetic and bedridden. Work up revealed an IgG lambda monoclonal spike and multifocal osteosclerotic myeloma. Remarkable improvement followed combined treatment with surgical excision, radiation therapy, and chemotherapy using chlorambucil, danazol, and hydrocortisone. Hence, we believe that aggressive local therapy associated with systemic chemotherapy should be considered in severely affected patients with multifocal osteosclerotic myeloma and peripheral neuropathy.

The POEMS syndrome.

The POEMS syndrome is an unusual disorder manifesting primarily as a peripheral sensorimotor neuropathy in association with a monoclonal gammopathy. The importance of its recognition is that significant clinical improvement may result from localization and treatment of the underlying plasma cell tumour.