Clinical characteristics and the long-term outcome of patients with atypical POEMS syndrome variant with undetectable monoclonal gammopathy
The diagnosis of polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) syndrome requires polyneuropathy and monoclonal plasma cell proliferation as two mandatory criteria. Our aim was to summarize clinical manifestations and treatment responses of POEMS variants with no evidence of monoclonal gammopathy. We queried all medical documentation of patients referred to Peking Union Medical College Hospital from August 2012 to July 2017, and reviewed the clinical and laboratory features of 13 patients with atypical POEMS syndrome with undetectable monoclonal gammopathy, and compared to prototypes published. The prevalence of polyneuropathy, organomegaly, skin changes, and extravascular fluid overload were 100%, 100%, 92%, and 100%, respectively. Other clinical manifestations, such as endocrinopathy, pulmonary hypertension, papilledema, thrombocytosis, and polycythemia affected similar percentages of patients as seen in prototypes. POEMS variants enrolled had a median serum vascular endothelial growth factor (VEGF) level of 4998 pg/ml (range 2155–11,029 pg/ml). Long-term follow-up found that all 12 patients received autologous stem cell transplant, melphalan-based therapy or lenalidomide/thalidomide-based therapy obtained clinical improvement, of which eight experienced decreased levels of VEGF by 50% or back to normal. The median progression-free survival was 101.5 months. Our findings raised a variant of POEMS syndrome variants with featured clinical manifestations, elevated VEGF levels, and good response to therapies targeting plasma cell.
KeywordsPOEMS syndrome Vascular endothelial growth factor Monoclonal gammopathy Plasma cell
We thank all patients and their families. We also thank Lijia Cui for technical support on statistical analysis, and Sarah Cui for polishing the written English language.
This study was funded by National Natural Science Foundation of China (Grant No. 81570195), Peking Union Medical College New Star (2011, to LJ), the CAMS Innovation Fund for Medical Sciences (Grant/Award Number: 2016-12M-1-002), and the National Key Research and Development Program of China (Grant/Award Number: 2016YFC0901503).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 3.D'Souza A, Hayman SR, Buadi F, Mauermann M, Lacy MQ, Gertz MA, Kyle RA, Kumar S, Greipp PR, Lust JA, Russell SJ, Zeldenrust S, Dingli D, Witzig TE, Rajkumar SV, Dispenzieri A (2011) The utility of plasma vascular endothelial growth factor levels in the diagnosis and follow-up of patients with POEMS syndrome. Blood 118(17):4663–4665. https://doi.org/10.1182/blood-2011-06-362392 CrossRefGoogle Scholar
- 4.Cao X, Wang C, Cai H, Duan M, Zhang W, Li T, Zhou D, Li J (2014) Diagnostic performance and clinical correlation of serum vascular endothelial growth factor levels in patients with newly diagnosed POEMS syndrome. Zhonghua Xue Ye Xue Za Zhi 35(12):1065–1068. https://doi.org/10.3760/cma.j.issn.0253-2727.2014.12.004 Google Scholar
- 8.Al-Mayoof O, Al Sughaiyer H, Abuomar W, Khan M (2017) POEMS syndrome: a rare cause of exudative ascites and chronic peripheral neuropathy. BMJ Case Rep. https://doi.org/10.1136/bcr-2016-219022
- 11.Huang X, Zhang C, Wang C, Cai Q, Cao X, Cai H, Zhang L, Feng J, Zhou D, Li J (2016) Measurement of beta-isomerized C-terminal telopeptide of type I collagen in patients with POEMS syndrome: diagnostic, prognostic, and follow-up utilities. Blood Cancer J 6(11):e495. https://doi.org/10.1038/bcj.2016.109 CrossRefGoogle Scholar
- 13.Dispenzieri A, Lacy MQ, Hayman SR, Kumar SK, Buadi F, Dingli D, Litzow MR, Gastineau DA, Inwards DJ, Elliott MA, Micallef IN, Ansell SM, Hogan WJ, Porrata LF, Johnston PA, Afessa B, Bryce A, Kyle RA, Gertz MA (2008) Peripheral blood stem cell transplant for POEMS syndrome is associated with high rates of engraftment syndrome. Eur J Haematol 80(5):397–406. https://doi.org/10.1111/j.1600-0609.2008.01037.x CrossRefGoogle Scholar
- 17.Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, Kumar S, Hillengass J, Kastritis E, Richardson P, Landgren O, Paiva B, Dispenzieri A, Weiss B, LeLeu X, Zweegman S, Lonial S, Rosinol L, Zamagni E, Jagannath S, Sezer O, Kristinsson SY, Caers J, Usmani SZ, Lahuerta JJ, Johnsen HE, Beksac M, Cavo M, Goldschmidt H, Terpos E, Kyle RA, Anderson KC, Durie BG, Miguel JF (2014) International myeloma working group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 15(12):e538–e548. https://doi.org/10.1016/S1470-2045(14)70442-5 CrossRefGoogle Scholar
- 22.Hineman VL, Phyliky RL, Banks PM (1982) Angiofollicular lymph node hyperplasia and peripheral neuropathy: association with monoclonal gammopathy. Mayo Clin Proc 57(6):379–382Google Scholar
- 24.Feigert JM, Sweet DL, Coleman M, Variakojis D, Wisch N, Schulman J, Markowitz MH (1990) Multicentric angiofollicular lymph node hyperplasia with peripheral neuropathy, pseudotumor cerebri, IgA dysproteinemia, and thrombocytosis in women. A distinct syndrome. Ann Intern Med 113(5):362–367CrossRefGoogle Scholar