In their article, Hogan et al1 report the successful use of autologous bone marrow transplantation in treating a patient with POEMS syndrome who did not respond to conventional chemotherapy. We have used the same therapeutic approach in two patients with similar success.
A 43-year-old male was admitted to hospital in January 1989, with abdominal pain. The pain had begun in May 1988 and was followed by diarrhea and weight loss (7 kg in 2 months). On admission the patient reported paresthesiae in the lower limbs, and impotence. Neurologic examination revealed diffuse areflexia, without sensorimotor deficit, and papillary edema. Electromyography showed a demyelinating neuropathy. Cerebrospinal fluid analysis showed high protein levels (1.02 g/l) without cells. The sensorimotor deficit worsened. It was decided to perform plasmapheresis and to initiate corticosteroid therapy (1 mg/kg). The sensorimotor deficit subsquently regressed in the upper limbs. In December 1989, other lesions developed (sclerodactyly, thoraco-abdominal hypertrichosis and cutaneous angiomas), and the neuropathy again worsened. Electrophoresis was normal, and immuno- electrophoresis revealed IgAλ. These findings prompted the diagnosis of POEMS syndrome, and a plasma cell dyscrasia was sought. Bone marrow smears were normal. Skeletal survey revealed a band of osteosclerosis in the left ilium, which was confirmed by tomodensitometry. Bone scintigraphy showed no areas of increased uptake. The different classes of immunoglobulin were normal in value: IgG 8 g/l, IgM 1.9 g/l, IgA 2.3 g/l. Hemoglobin was normal at 15.3 g/l. Thrombocytosis was present at 511 000/mm3. Endocrinologic investigations showed low testosterone levels with normal FSH and LH values, hyperestrogenia and hyperprolactinemia. There was no hepatosplenomegaly or lymphoadenopathy. Radiotherapy – 45 Gy to the ilium – failed to improve his clinical condition, and monoclonal Ig was still present. Chemotherapy with cyclophosphamide and prednisone was initiated in early 1990. Four cycles of treatment produced no beneficial clinical effect. Examinations performed in November 1990 showed new osteosclerotic lesions in the left sacrum and ilium and the left ischiopubic ramus. Five further cycles of chemotherapy (adriamycin, melphalan and prednisone) were unsuccessful. Autologous transplantation was performed in June 1991 after collection of bone marrow stem cells and administration of melphalan (140 mg/m2). Gradual improvement was observed. Ten years later, the only sequellae of the neuropathy were sensorimotor deficit in both feet. There was no hepatosplenomegaly. Endocrine results were normal. There were no new bone lesions. Immuno-electrophoresis showed no monoclonal component. The serum vascular endothelial growth factor (VEGF), which was raised at onset (44604 pg/ml (N: 62–707)), had returned to normal levels (747 pg/ml).
A 59-year-old woman was admitted to hospital in 1999 with thoracic pain, diffuse erythroderma and an increased hematocrit. Examination revealed hepatosplenomegaly and bilateral subclavicular adenopathy. The patient complained of diffuse paresthesiae in the lower limbs, and deep tendon reflexes were absent. Endoscopy of the stomach showed erosive congestive gastritis. The hemoglobin was 170 g/l and platelets 560 × 109/l. Serum electrophoresis results were normal but immunofixation showed an IgG kappa M component. Measurement of red blood cell mass ruled out polycythemia. Serum erythropoietin was normal and bone marrow biopsy showed only a slight increase in reticulin without infiltration. Findings pointed toward the possibility of POEMS syndrome. Peripheral neuropathy was confirmed by electromyography. There was no papillary edema in the optic fundus. X-rays of the bone showed osteosclerosis in the right sacrum and the lower part of the right femoral metaphysis. MRI showed another spinal lesion at C3. Biopsy of the sacral tumor was performed at the beginning of 2000 and confirmed proliferation of malignant plasma cells. It was decided to give radiation therapy to the plasma cell areas and then to start chemotherapy. Radiotherapy lasted a month and a total dose of 40 Gy was delivered to three different sites. Peripheral stem cells were obtained by cytapheresis after three monthly cycles of treatment with cyclophosphamide and dexamethasone. The patient received melphalan 200 mg/m2 followed by hematopoietic stem cell transplantation. Evaluation of the procedure 6 months later (ie 2 years after the onset of the disease) showed complete remission both clinically and biologically. Plasma VEGF levels, which in the initial stages of the disease had been very high (4190 pg/ml (N: 0–115 pg/ml)), were now normal.
POEMS syndrome, with a 5-year survival of 60%,2 has a better prognosis than that of multiple myeloma. However, this high survival rate is largely due to cases where POEMS syndrome is secondary to plasmacytoma.3 In these patients, local treatment (surgery and/or radiotherapy) can cure the disease. Like Hogan et al, we think that POEMS syndrome is a paraneoplastic phenomenom mediated by a soluble agent produced by abnormal plasma cells. VEGF is thought to play an important role in the pathophysiology of this syndrome.4 Nakano et al5 reported VEGF production by plasmacytoma cells in a patient with a single plasmocytoma and a neuropathy. We agree with Hogan et al that a systemic approach is needed when the disease is not due to a localized tumor (ie osteosclerotic myeloma or MGUS). In our opinion, high-dose chemotherapy with stem cell rescue should be considered as first-line treatment. High-dose chemotherapy with stem cell rescue gives better results in the treatment of multiple myeloma than conventional chemotherapy, having a mortality risk of less than 2%.1 This therapeutic approach is similar to that proposed in the processing of amyloidosis, in which low-grade dysproteinemia is often observed.1
Hogan WJ, Lacy MQ, Wiseman GA et al. Successful treatment of POEMS syndrome with autologous hematopoietic progenitor cell transplantation Bone Marrow Transplant 2001 28: 305 309
Miralles DG, O'Fallon JR, Talley NJ . Plasma-cell dyscrasia with polyneuropathy. The spectrum of POEMS Syndrome N Engl J Med 1992 327: 1919 1923
Soubrier M, Dubost JJ, Sauvezie B The French Study Group on POEMS Syndrome. POEMS Syndrome: a study of 25 cases and a review of the literature Am J Med 1994 97: 543 552
Soubrier M, Dubost JJ, Serre AF et al. Growth factors in POEMS syndrome : evidence for a marked increase in circulating vascular endothelial growth factor Arthritis Rheum 1997 40: 786 787
Nakano A, Mitsui T, Endo I et al. Solitary plasmocytoma with VEGF overproduction: report of a patient with polyneuropathy Neurology 2001 56: 818 819
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Soubrier, M., Ruivard, M., Dubost, J. et al. Successful use of autologous bone marrow transplantation in treating a patient with POEMS syndrome. Bone Marrow Transplant 30, 61–62 (2002). https://doi.org/10.1038/sj.bmt.1703600