2013 articles about POEMS syndrome

Here are some things that jumped out at me when I looked at articles from 2013. Some are new; others reinforce what we already believed. I haven't read all the 2013 articles about POEMS—and not even all the articles in English! But I tried to read all the English-language articles whose abstracts seemed promising. (See PubMed to search for other articles.)

Full references are at the end of this page.

Many of these articles include Dispenzieri, Kuwabara, or Li as authors. They've all published enough good articles on POEMS to deserve a lot of trust. In particular, I trust them to have diagnosed POEMS correctly. The articles they weren't involved in (Kang, Royer, and Guo) do use Dispenzieri's criteria for diagnosis. (Unfortunately, that matters, since the name 'POEMS' misleads even some physicians, as far as I can tell from the literature.)

If I made any mistakes, missed anything, stated anything unclearly, or you have other questions about the articles, please let me know.

24 January 2014


  • Two English-language reviews of POEMS were published in 2013 (Li 2013a and Dispenzieri 2013).
  • (Kuwabara published a review also, in Japanese.)


  • Radiation therapy is a good option for treating someone with POEMS who has three or fewer bone lesions and a negative bone marrow—a quarter of the 146 POEMS patients in this study. About half (52%) of the 38 people treated with radiation had no disease progression after four years. Also, the four-year survival rate was 97%, which the authors reasonably say shows that even when people required other therapy (usually because the neuropathy either worsened or didn't improve), having had radiation didn't cause problems. (Those four-year rates are estimates; the median follow-up was 43 months.) (Humeniuk 2013)
  • Two factors predicted failure of radiation therapy: decreased DLCO (less than 75% of predicted) and increased total urine protein (>= 0.093 grams in 24 hours). (DLCO is a lung test—an optional part of pulmonary function tests (PFT).) Whether patients had three, rather than one or two, lesions did not predict failure of radiation therapy. (Humeniuk 2013)
  • Lenalidomide (Revlimid) is very effective at treating POEMS, helping nineteen of twenty patients (including eight patients who had relapsed one to five years after autos, and four newly diagnosed patients). Neuropathy improved in sixteen patients, and stabilized in the other four. During the follow-up period (a median of 22 months), four of the patients relapsed; three of them improved after other treatment. (Royer 2013)
  • Another article that was accepted in 2013, which I haven't read yet because it isn't actually published, collected previously published studies, finding 51 POEMS patients treated with lenalidomide, with good results. For example, overall, 92% of patients had improved neuropathy, and the neuropathy stabilized in the other 8%. The one-year progression-free survival estimate was 94%. (Zagouri 2014)
  • In three patients treated with bevacizumab (Avastin), a monoclonal antibody to VEGF), VEGF dropped dramatically, but two other angiogenic cytokines (hepatacyte growth factor (HGF) and basic fibroblast growth factor (bFGF)) didn't change. Since HGF increases vascular permeability (that is, makes blood vessels leaky), it may be responsible for the capillary leak syndrome some people treated with bevacizumab have experienced. (Yamada 2013) Further, four of six patients treated with bevacizumab did not improve; two of those four died. The improvement in the other two patients could have been caused by other treatments. (Sekiguchi 2013) (I hope this ends people's trying to treat POEMS with bevacizumab; the evidence was already strongly against using it, as far as I can see.)


  • 90% of 107 POEMS patients had skin symptoms—see the article for details and for interesting speculation about how high VEGF levels might cause POEMS skin symptoms. (>Miest 2013)
  • Patients with skin symptoms were more likely to have low DLCO (the lung test I mentioned above). And patients with IgG M-proteins were more likely to have hyperpigmentation (darker skin color) and hypertrichosis (excess or coarse hair). (Miest 2013)
  • 27% of 154 POEMS patients had pulmonary hypertension when they were diagnosed. (They used systolic pulmonary artery pressure on echo to diagnose pulmonary hypertension, which isn't as definitive as measuring the pressure during catheterization.) (Li 2013)
  • Pulmonary hypertension improved after treatment in 88% of patients (but only in half of patients who were treated only by steroids). (Li 2013)


  • 18-FDG-PET/CT (pet scan) 'misses very small and very sclerotic lesions'; '[t]he most densely sclerotic bone lesions in POEMS syndrome do not take up FDG, making that test unreliable in differentiating between a benign lesion and a lesion due to underlying plasma cells' (Humeniuk 2013 p.72). I don't remember seeing this mentioned before, and the fact that the article doesn't cite any other articles on this point suggests this may not have been published before.
  • In one patient, 18-FDG-PET/CT did not find a lesion that was visible on standard radiographs and CT. (Royer 2013 p.209)
  • One group used 18-FDG-PET/CT to monitor the results of treating POEMS with lenalidomide (Revlimid). They used radiation to treat two patients who had lesions still visible after the lenalidomide treatment, which improved their neuropathy. (But they didn't say whether those lesions could also be detected by CT or conventional radiographs.) (Royer 2013 page 211)


  • 22 of 38 patients treated with radiation had been incorrectly diagnosed with, and treated for, CIDP before being diagnosed with POEMS. (Humeniuk 2013)
  • One study of 20 POEMS patients and 36 CIDP patients found differences in the EMGs. They suggested that the differences could help distinguish POEMS from CIDP. That would be very useful! But they looked only at the groups, and not at whether the differences could help distinguish POEMS from CIDP in individual patients—and as far as I can see at least some of the differences couldn't. Perhaps I'm missing something I'd recognize if I knew more about EMGs. But in any event they didn't discuss how many of the individual diagnoses they could get right from the EMGs (unlike Mauermann 2012). (Guo 2013)


  • Seventeen POEMS patients all had elevated serum VEGF before treatment with lenalidomide, with serum VEGF of 1,196 to 10,100 (median 2,400) pg/ml. (Royer 2013 209)
  • Nine POEMS patients all had elevated plasma VEGF before treatment, with plasma VEGF of 146 to 1,036 (median 468, reference range 31 to 86) pg/mL. But just before transplant, the POEMS patients' VEGF wasn't very different from VEGF in patients with multiple myeloma or amyloidosis—so either previous treatment, or mobilization for the auto, dramatically reduced VEGF levels. (Keyzner 2013 p.1396)


  • In a small group of patients having autos, IL-12 was not elevated. This is interesting, since in a 2012 paper, Kanai and others (with Kuwabara as the senior author) found that IL-12 levels were high in a small group of POEMS patients. Since IL-12 is neurotoxic, Kanai et al. suggested that it might cause the neuropathy in POEMS (in conjunction with VEGF, which reduces the blood-nerve barrier). However, the new study didn't measure IL-12 before therapy and stem cell mobilization, which (as they note) may have affected the IL-12 levels (as it clearly affected VEGF levels). Further (as they recognize) the study was done on a very small number of patients. So this definitely does not rule out IL-12 as a cause of POEMS neuropathy. (Keyzner 2013)
  • We may be hearing more about IL-1 receptor antagonist (IL-1RA). In a small group of patients who received autos, patients who had lower levels of IL-1RA after the transplant was done were more likely to experience engraftment syndrome. IL-1RA is an anti-inflammatory acute-phase protein, and is involved in a number of diseases. Low levels can be caused by gene mutations. (Keyzner 2013; see especially p.1397)
  • Levels of thirty cytokines were measured in eighteen patients undergoing autos: nine for POEMS, four for multiple myeloma, and five for amyloidosis (derived from immunoglobulins). The POEMS patients had higher pre-transplant levels of IL-4 (proinflammatory), IL-10 (anti-inflammatory), IL-13 (anti-inflammatory), interferon-alpha, endothelial growth factor (EGF) (angiogenic), and lower levels of inducible protein 10 (IP-10) (proinflammatory). After transplant, the two groups seemed to have equal levels of IL-4, IP-10, IL-10, and interferon-alpha. IL-13 levels were correlated with—and may cause—delayed neutrophil engraftment in both the POEMS and the non-POEMS patients. (Keyzner 2013)
  • In seventeen POEMS patients, three factors that cause new blood vessels to form ('angiogenesis') were all elevated: VEGF, basic fibroblast growth factor (bFGF) and hepatocyte growth factor (HGF). Unlike VEGF, bFGF increases the blood-nerve barrier. Like VEGF, HGF increases vascular permeability. bFGF and VEGF were not correlated; HGF and VEGF were. (>Yamada 2013)


  • Thirteen of twenty patients with POEMS had cytogenetic changes often found in multiple myeloma—either 14q32 (IGH) translocations (which 'have long been recognized as primary genetic events in the pathogenesis of [plasma cell] dyscrasias'), 13q14 deletions, or 1q21 amplifications. (Kang 2013)


Guo 2013
Guo X, Qin X, Zhang Y, Huang C, Yu G. 'Electrophysiological features of POEMS syndrome and chronic inflammatory demyelinating polyneuropathy.' Journal of clinical neuroscience 15 Aug 2013.
Humeniuk 2013
Humeniuk MS, Gertz MA, Lacy MQ, Kyle RA, Witzig TE, Kumar SK, Kapoor P, Lust JA, Hayman SR, Buadi FK, Rajkumar SV, Zeldenrust SR, Russell SJ, Dingli D, Lin Y, Leung N, Dispenzieri A. 'Outcomes of patients with POEMS syndrome treated initially with radiation.' Blood 122 (4 July 2013) 68-73.
Kanai 2012
Kanai K, Sawai S, Sogawa K, Mori M, Misawa S, Shibuya K, Isose S, Fujimaki Y, Noto Y, Sekiguchi Y, Nasu S, Nakaseko C, Takano S, Yoshitomi H, Miyazaki M, Nomura F, Kuwabara S. 'Markedly upregulated serum interleukin-12 as a novel biomarker in POEMS syndrome.' Neurology 79 (7 Aug 2012) 575-582.
Kang 2013
Kang WY, Shen KN, Duan MH, Zhang W, Cao XX, Zhou DB, Li J. '14q32 translocations and 13q14 deletions are common cytogenetic abnormalities in POEMS syndrome.' European journal of haematology 91 (Dec 2013) 490-496.
Keyzner 2013
Keyzner A, D'Souza A, Lacy M, Gertz M, Hayman S, Buadi F, Kumar S, Dingli D, Engebretson A, Tong C, Dispenzieri A. 'Low levels of interleukin-1 receptor antagonist (IL-1RA) predict engraftment syndrome after autologous stem cell transplantation in POEMS syndrome and other plasma cell neoplasms.' Biology of blood and marrow transplantation 19 (Sep 2013) 1395-1398.
Li 2013
Li J, Zhou DB. 'New advances in the diagnosis and treatment of POEMS syndrome.' British journal of haematology 161 (May 2013) 303-315.
Li 2013a
Li J, Tian Z, Zheng HY, Zhang W, Duan MH, Liu YT, Cao XX, Zhou DB. 'Pulmonary hypertension in POEMS syndrome.' Haematologica 98 (Mar 2013) 393-398.
Miest 2013
Miest RY, Comfere NI, Dispenzieri A, Lohse CM, el-Azhary RA. 'Cutaneous manifestations in patients with POEMS syndrome.' International journal of dermatology 52 (Nov 2013) 1349-56.
Royer 2013
Royer B, Merlusca L, Abraham J, Musset L, Haroche J, Choquet S, Leleu X, Sebban C, Decaux O, Galicier L, Roussel M, Recher C, Banos A, Guichard I, Brisseau JM, Godmer P, Hermine O, Deplanque G, Facon T, Asli B, Leblond V, Fermand JP, Marolleau JP, Jaccard A. 'Efficacy of lenalidomide in POEMS syndrome: a retrospective study of 20 patients.' American journal of hematology 88 (Mar 2013) 207-212.
Sekiguchi 2013
Sekiguchi Y, Misawa S, Shibuya K, Nasu S, Mitsuma S, Iwai Y, Beppu M, Sawai S, Ito S, Hirano S, Nakaseko C, Kuwabara S. 'Ambiguous effects of anti-VEGF monoclonal antibody (bevacizumab) for POEMS syndrome.' Journal of neurology, neurosurgery, and psychiatry 84 (Dec 2013) 1346-1348.
Yamada 2013
Yamada Y, Sawai S, Misawa S, Kanai K, Shibuya K, Mori M, Moriya J, Sogawa K, Yamamoto H, Beppu M, Taniguchi J, Nakaseko C, Nomura F, Kuwabara S. 'Multiple angiogenetic factors are upregulated in POEMS syndrome.' Annals of hematology 92 (Jan 2013) 245-248.
Zagouri 2014
Zagouri F, Kastritis E, Gavriatopoulou M, Sergentanis TN, Psaltopoulou T, Terpos E, Dimopoulos MA. 'Lenalidomide in patients with POEMS syndrome: A systematic review and pooled analysis.' Leukemia and lymphoma 3 Dec 2013.

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