International Journal of Myeloma 9(3): 19–23, 2019
©Japanese Society of Myeloma

CASE REPORT

Successful autologous stem cell transplantation for POEMS­syndrome with an unusually large osteolytic lesion:
A case report and literature review
Tatsuzo MISHINA1,2, Nagisa OSHIMA-HASEGAWA1,2, Shokichi TSUKAMOTO1,2, Yurie NAGAI1,2,
Miki YAMAZAKI1,2, Arata ISHII1,2, Yutaro HINO1,2, Yusuke ISSHIKI1,2, Koji TAKAISHI1,2,
Kenji KIMURA1,2, Kensuke KAYAMORI1,2, Shintaro IZUMI1,2, Shio MITSUKAWA1-3,
Yusuke TAKEDA1,2, Naoya MIMURA1-3, Chikako OHWADA1,2, Masahiro TAKEUCHI1,2,
Sonoko MISAWA4, Tohru ISEKI1-3, Satoshi KUWABARA4, Chiaki NAKASEKO1,2,5 and Emiko SAKAIDA1,2
POEMS syndrome is a rare multisystemic disease related to monoclonal plasma cell proliferative disorder. Bonelesions in POEMS syndrome are usually sclerotic, and osteolytic lesions are uncommon. Although high-dose chemotherapy administration, followed by autologous stem cell transplantation (auto-SCT) is widely indicated for POEMS
syndrome, the pathogenesis and treatment strategy in patients with osteolytic lesions are still unclear. In this report,
we present the rare case of a patient with POEMS syndrome with a large osteolytic lesion who was successfully
treated with auto-SCT. A 36-year-old man presenting with edema and difficulty in walking was diagnosed withPOEMS syndrome based on peripheral polyneuropathy, hepatosplenomegaly, elevated levels of serum VEGF, andIgA-λ monoclonal protein gammopathy. FDG-PET/CT showed high FDG avidity on a large osteolytic lesion on theright pelvic bone, in addition to multiple osteosclerotic lesions. The patient was administered immunomodulatory
drugs and a proteasome inhibitor, and subsequently underwent high-dose chemotherapy, followed by auto-SCT.
Post transplantation, his symptoms improved gradually, and FDG avidity on the osteolytic lesion decreased. POEMS
syndrome with osteolytic lesions indicates a large tumor burden and could be a more progressive disease. For
long-term disease remission of POEMS syndrome with osteolytic lesions, an FDG-PET/CT-guided decision fortreatment is necessary.
Key words:

POEMS syndrome, osteolytic lesion, autologous stem cell transplantation, VEGF, FDG-PET/CT

Introduction

cell proliferative disorder, first described by Bardwick et al.
(1980) [1]. POEMS syndrome is also known as Takatsuki disease

The polyneuropathy, organomegaly, endocrinopathy, mono­[2], Crow–Fukase syndrome [3], or osteosclerotic myeloma.

clonal gammopathy, and skin changes (POEMS) syndrome

The diagnostic criteria are based on a composite of clinicalis a multisystemic disease related to monoclonal plasma

and laboratory features, including polyneuropathy, monoclonalReceived: July 15, 2019, accepted October 25, 20191
Department of Hematology, Chiba University Hospital, Chiba, Japan
2
Blood and Marrow Transplant Center, Chiba University Hospital,
Chiba, Japan3
Department of Transfusion Medicine and Cell Therapy, Chiba
University Hospital, Chiba, Japan
4
Department of Neurology, Chiba University Graduate School of
Medicine, Chiba, Japan
5
Department of Hematology, International University of Health andWelfare School of Medicine, Narita, Japan
Corresponding author: Emiko Sakaida, MD, PhD
Department of Hematology, Chiba University Hospital, 1-8-1
Inohana, Chuo-ku, Chiba 260-8670, Japan
E-mail: esakaida@faculty.chiba-u.jp

plasma cell proliferative disorder, and major (­Castlemandisease, osteosclerotic lesions, and vascular endothelial
growth factor [VEGF] elevation) or minor (organomegaly,
extravascular volume overload, endocrinopathy, skin changes,
papilledema, and thrombocytosis/polycythemia) criteria [4].
Although the POEMS syndrome pathogenesis is still unclear,aberrant monoclonal plasma cell proliferation is suspected to
be a basis of this disease. In addition, patients have high levelsof serum inflammatory cytokines, such as VEGF, interleukin-6,
and tumor necrosis factor-α, which indicate the presenceof various symptoms [5]. Therefore, POEMS syndrome is aparaneoplastic syndrome caused by monoclonal plasma cellproliferative disorder; however, its characteristics (younger

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MISHINA et al.

age and better survival) are different compared to multiple(IgA) (880 mg/dL; normal range = 110–410 mg/dL) levels.

myeloma (MM).

Serum immunofixation electrophoresis detected IgA-λ mono-

The incidence of bone abnormalities in patients with POEMS

clonal protein gammopathy (Fig. 1A), while the ratio of the

syndrome is reported to be up to 97% [6]. However, compared

serum free light chains was normal. There was no anemia,

to MM, bone lesions in POEMS syndrome are usually sclerotic,

hyper­
calcemia, or renal dysfunction. A hormonal study

and osteolytic lesions are uncommon [4]. Most bone lesions

found elevated adrenocorticotropic hormone (203.0 pg/mL;

are small (diameter < 1 cm [7]), and no cases with large

normal range < 46.0 pg/mL), thyroid-stimulating hormone­osteolytic lesions have been reported so far. In addition, few(7.043 μIU/mL; normal range = 0.350–4.940 μIU/mL), andstudies have reported the outcomes of osteolytic lesions after

estradiol (64 pg/mL; normal range = 11–44 pg/mL) levels,

the treatment of POEMS syndrome [7, 8], while the long-term

but free T3 and free T4 levels were within normal limit.

efficacy of treatment for osteolytic lesions is hardly known.

Bone marrow analysis showed 1.4% of plasma cells. Skeletal

In this report, we present the rare case of a patient with

X-ray and computed tomography (CT) scan revealed a 9-cm

POEMS syndrome who had a large osteolytic lesion and was

osteolytic lesion with a sclerotic rim on the patient’s righttreated successfully with high-dose chemotherapy (high-dose

pelvic bone and m­ ultiple osteosclerotic lesions on his spine

melphalan [HD-Mel]), followed by autologous stem cell trans-

and pelvis. Fluoro-2-deoxyglucose with positron emission

plantation (auto-SCT).

tomography/CT (FDG-PET/CT) showed markedly aberrant
FDG avidity on all bone lesions; in particular, the maximum

Case Presentation

standard uptake value (SUVmax) of the osteolytic lesion was
21.4 (Fig. 2, At diagnosis). A biopsy of the osteolytic lesion

A 36-year-old man with bilateral leg pain, difficulty in run-

was technically difficult and was not performed. Chest andning, walking up and down the stairs, and lower extremity

abdominal CT scans showed hepatosplenomegaly, but nonumbness and edema was referred to our institution for apleural effusion or ascites. Based on all these symptoms anddetailed examination. On admission, he was unable to walk for

examination results, the patient was diagnosed with POEMS

a long distance without the help of a walking stick. A physicalsyndrome with a large osteolytic lesion.

examination showed pitting edema in his lower extremities,

Radiation therapy was first recommended for the osteolytic

but there were no signs of skin change or bone pain. A neuro-

lesion. However, the patient did not agree for fear of delayed

logical examination revealed decreased strength of the proxi-

bone ossification due to radiation exposure. Instead, he agreed

mal and distal muscles of his lower extremities and hyper­

to receive thalidomide and dexamethasone (Td) therapy

algesia of his distal limbs, and a nerve conduction study (NCS)(Fig. 3). After one cycle of Td therapy, the patient’s serum VEGF

showed a demyelinating polyneuropathy pattern.

levels decreased to 2650 pg/mL, and the patient was sub­Laboratory studies revealed elevated serum VEGF (5700sequently administered bortezomib and dexamethasone (Bd)pg/mL; normal range < 680 pg/mL) and immunoglobulin A

therapy. However, four cycles of Bd therapy failed to control

Figure 1. Immunofixation electrophoresis at diagnosis and one month after auto-SCT. IgA, immunoglobulin A; auto-SCT, autologous stem celltransplantation.

20

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vol. 9 no. 3 (2019)

Osteolytic lesion in POEMS syndrome

Figure 2. Radiological surveys at diagnosis and one month after auto-SCT. (A) Frontal skeletal X-ray of the pelvis. (B, C, D) Axial CT of the pelvis
and fused PET/CT images. Arrows indicate osteolytic lesions, and dotted arrows indicate osteosclerotic lesions. CT, computed tomography;
PET, positron emission tomography; FDG, fluoro-2-deoxyglucose.

Figure 3. Clinical course of treatment and trend of serum VEGF and IgA levels after diagnosis. Td, thalidomide and dexamethasone; Bd,­bortezomib and dexamethasone; HD-CY, high-dose cyclophosphamide; PBSCH, peripheral blood stem cell harvesting; Rd, lenalidomide
and dexamethasone, HD-Mel, high-dose melphalan; VEGF, vascular endothelial growth factor; IgA, immunoglobulin A.

the symptoms, and the patient’s serum VEGF levels increased

cycles of lenalidomide and dexamethasone (Rd), the patient

to 5100 pg/mL. The patient underwent high-dose cyclophos-

received HD-Mel (200 mg/m2) followed by auto-SCT, eightphamide (2 g/m2) therapy, followed by peripheral blood stem

months after diagnosis.

cell harvesting, mobilized by the granulocyte-colony stimu­

The number of transplanted CD34-positive cells was 2.86

lating factor. Subsequently, his serum VEGF levels decreased

× 106/kg. The patient achieved neutrophil engraftment onmarkedly to 771 pg/mL. After additional treatment with three

day 18 post transplantation, without any symptoms of pre-International Journal of Myeloma

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MISHINA et al.

engraftment immune reactions. He suffered from diarrhea andtherefore, nearly 30% of bone lesions were reportedly over-febrile neutropenia, but both were manageable. One monthlooked in a skeletal X-ray survey [7]. A CT scan on the bone

post transplantation, the patient’s serum VEGF levels were

window level is effective in detecting bone lesions in POEMS

found to be within the upper normal limit, indicating the

syndrome. A large osteosclerotic lesion tends to have a lytic

achievement of a complete response in serum VEGF levels

site in its central part. An FDG-PET/CT scan is also helpful inaccording to Mayo Clinic response criteria [4]. However,detecting osseous sites because bone lesions in POEMS­immunofixation electrophoresis could still detect the IgA-λ­syndrome, especially osteolytic lesions, are FDG-avid [8, 11].

monoclonal protein (Fig. 1B). A CT scan showed no remark-

Neoplastic lesions, such as plasmacytomas and Castleman­

able changes in the osteosclerotic lesions. FDG-PET/CT­disease, can also be evaluated using FDG-PET/CT. The Mayoshowed that FDG avidity on the osteosclerotic lesions had

Clinic recommends treatment response criteria for POEMS­disappeared, but the osteolytic lesion could still be detected,

syndrome using an FDG-PET/CT parameter [4]. In this report,with the SUVmax decreasing to 6.32 (Fig. 2, After auto-SCT),

the FDG-PET/CT response one month post transplantation

indicating improvement according to Mayo Clinic response

indicated that the residual disease and response criteria of

criteria [4]. Therefore, the patient underwent consolidation

the Mayo Clinic are useful in assessing whether additional

therapy with Rd protocol post transplantation.

therapy is required.

Five months post transplantation, the patient’s leg strength

Although a standard therapy for POEMS syndrome has notshowed gradual improvement, and he was able to walk with-

yet been established, most patients are treated according toout a walking stick. Nine months post transplantation, thethe treatment strategy for other plasma cell neoplasms, suchpatient returned to his job under Rd therapy. Twelve months

as MM. In the case of a localized disease, when a patient has

post transplantation, FDG avidity on the osteolytic lesion still

only one or two bone lesions, radiotherapy is the most com-remained, and the patient continued Rd therapy. All the above

mon treatment option [12]. On the other hand, most patientstreatments were approved by the ethical committee of thehave a multifocal disease or bone marrow involvement, sug-

institutional review board, and written informed consent was

gesting the need for systemic chemotherapy. Conventionally,

obtained from the patient.

melphalan and dexamethasone [13] or single corticosteroid
therapy has been used, but recent studies have reported that

Discussion

novel agents, such as proteasome inhibitors (bortezomib[14]) and immunomodulatory drugs (thalidomide [15] andAn osteosclerotic lesion, so-called osteosclerotic myeloma,

lenalidomide [16]), are highly effective. It is still unclear

is one of the characteristics of POEMS syndrome, which iswhich proteasome inhibitors or immunomodulatory drugs

included in the diagnostic criteria and reportedly occurs inare better in the treatment of POEMS syndrome. Misawa S et

~54%–95% of patients with POEMS syndrome [6]. Differential

al. reported thalidomide was useful for auto-SCT ineligible

diagnoses for osteosclerotic lesions include a benign bone

POEMS syndrome patients [15]. Cai QQ et al. also reported

island and skeletal metastases of solid cancers. Why patientsthat lenalidomide was effective for relapsed or refractorywith POEMS syndrome develop osteosclerotic lesions is still

POEMS syndrome patients [16]. Therefore, immunomodu­

unclear, but VEGF affects bone repair and regeneration [9]latory drugs are useful for newly diagnosed and refractoryand is believed to play a key role in the pathogenesis of

POEMS syndrome patients as well as multiple myeloma. In

osteosclerotic lesions in POEMS syndrome.

our bortezomib-refractory case, immunomodulatory drugs

Most osteolytic lesions in POEMS syndrome exhibit mixed

are highly effective. High-dose chemotherapy, followed bysclerotic and lytic components, such as lytic central parts with

auto-SCT is expected to show a drastic improvement of poly-sclerotic rims or a “soap-bubble appearance,” and pure lytic

neuropathy in patients younger than 65–70 years. Jaccard

lesions are extremely rare [7]. Differential diagnoses include

et al. first reported five successful cases treated with auto-

aneurysmal bone cysts, non-ossifying fibroma, and fibrous

SCT [17], and subsequently, several studies have reported

dysplasia [4]. Unlike osteosclerotic sites, osteolytic sitesthat auto-SCT is effective for POEMS symptoms, especially poly­

reportedly have significantly increased plasma cells [10].

neuropathy [18–21]. A recent report from our institute, as well

Therefore, patients with POEMS syndrome with osteolytic

as another study, on long-term follow-up showed ~90% of

lesions are considered to carry a large tumor burden. However,

5-year overall survival and ~65% of 5-year progression-free

as in this report, determining the precise number of plasma

survival [22–25].

cells in an osteolytic lesion is often difficult. Instead, several

Bone lesions are also improved by treatment for POEMS

diagnostic imaging techniques are helpful. Osteosclerotic sites

syndrome. Glazebrook et al. reported that the treatment

in patients with POEMS syndrome are often smaller than 1 cm;

response shows, on the CT scan, a decrease in the size and22

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vol. 9 no. 3 (2019)

Osteolytic lesion in POEMS syndrome

number of osteosclerotic lesions or increased sclerosis inosteolytic lesions [7]. On the other hand, Pan et al. reported
that FDG-avid bone sites show a decreased SUVmax, but theappearance of bone lesions on CT scans does not change post
treatment [8]. Studies have reported that patients with POEMS
syndrome who do not achieve complete metabolic response
post transplantation have significantly poor prognosis andtend to have osteolytic sites [24]. In contrast, Wang et al.
reported that there is no correlation between serum marker
levels and bone lesion patterns [26]. In this report, auto-SCT
decreased the disease activity of bone lesions, as assessed by
an FDG-PET/CT scan, not by a CT scan; however, the remaining
FDG avidity post transplantation suggested the risk of­progression. Focal irradiation might have been a treatment
option, but because the patient refused radiation therapy, we
decided to administer additional consolidation chemotherapy,
which successfully controlled the patient’s disease activity.
In summary, we successfully treated the patient with POEMS
syndrome with a large osteolytic lesion using high-dose­chemotherapy, followed by auto-SCT. Treatment efficacy forthe osteolytic lesion was evaluated using an FDG-PET/CT scan.
POEMS syndrome with osteolytic lesions indicates a large
tumor burden and could be a more progressive disease. Therefore, an FDG-PET/CT-guided treatment decision is crucial
for long-term disease remission of POEMS syndrome withosteolytic lesions.

Disclosure of Conflicts of Interest
The authors declare no competing financial interests.

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