Engraftment Syndrome Is Common in Patients with POEMS Syndrome Undergoing PBSCT.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2995-2995
Author(s):  
Angela Dispenzieri ◽  
Martha Q. Lacy ◽  
Suzanne R. Hayman ◽  
Shaji K. Kumar ◽  
Francis Buadi ◽  
...  
Keyword(s):  
Plasma Cells ◽  
Volume Overload ◽  
Poems Syndrome ◽  
Bone Lesions ◽  
Post Transplant ◽  
Gm Csf ◽  
Engraftment Syndrome ◽  
Sclerotic Bone Lesions ◽  
Definition Of ◽  
Discharge From Hospital

Abstract Background: POEMS syndrome is a devastating syndrome, characterized by peripheral neuropathy, organomegaly, endocrinopathy, monoclonal plasma cells, skin changes, papilledema, volume overload, sclerotic bone lesions, thrombocytosis, & high VEGF. We noted an unexpectedly high transplant related morbidity, which we have since postulated to be ES. Methods: 30 patients with POEMS were treated with PBSCT at Mayo Clinic Rochester. We retrospectively studied outcomes, with an emphasis on treatment related morbidity. Two definitions of ES were used: Spitzer (BMT 2001) and Maiolino (BMT 2003). Results: Two-thirds were male. Median age was 48, range 20–70. Time from first symptoms and diagnosis was 26 and 4 months, respectively. To mobilize stem cells, CTX/G-CSF was used in 5 & G-CSF in the remainder. Conditioning was Mel200 (n=19), Mel140 (n=10), and BEAM (n=1). Post-transplant 15 had GM-CSF begun day+6. Only 10% remained outpatient, and median time to discharge from hospital was transplant day 17 (range 0–175). Factors predicting for later dismissal included age (p=0.04), abnormal CXR 7 to 17 days post transplant (p<0.0001), & bolus corticosteroids (CS) beyond day 12 post-transplant (p=0.006). Ninety-three percent had fever, although only 9 had bacteremia. Eight satisfied criteria for ES according to Spitzer and 14 according to Maiolino. Another 3 patients received steroid bolus days 8, 12, and 11 for presumed ES but did not meet criteria because of delayed ANC recovery (days 16, 18, and 20, respectively). Of the 5 patients requiring endotracheal intubation, 3 satisfied Maiolino’s criteria for ES. Although these 3 received bolus CS during their course, administration was delayed at 18, 14, and 18 days. The patient whose CS bolus antedated intubation only received prednisone 30 mg/day. In toto, fourteen patients received bolus CS (daily doses between 20 and 1200 mg prednisone equivalents) commencing day 8 to 59. Those 7 patients who received CS before day 13 did better than the 7 who received them day 13 or later (Table). Conclusions: It is essential to recognize that nearly 50% of patients satisfied formal criteria for ES as defined by Maiolino. In these patients ES may run a self-limited course or lead to catastrophe. No Steroid (n=16) Steroid ≤ D12 (n=7) Steroid > D12 (n=7) P *Engraftment syndrome according to definition of Maiolino (M) or of Spitzer (S). ES M / S, n* 5 / 2 4 / 4 5 / 2 NA Wt change, % 0.6 (−.4.2–6.7) 6.7 (3.6–27.2) 11.2 (–2.1–23.2) 0.005 Rash, % 27 71 43 0.13 Diarrhea, % 73 86 86 0.71 Tmax, C 39 (37.8–41) 40.1 (39–41.1) 38.9 (38.7–40.8) 0.08 1st fever, day 10 (6–15) 8 (7–9) 12 (8–146) 0.007 Abn CXR1, % 13 71 71 0.03 Ventilator, % 0 14 71 0.004 First WBC, day 12 (8–21) 14 (12–14) 14 (12–17) 0.03 ANC500, day 15 (12–29) 16 (14–115) 18 (15–45) 0.08 PLT20, day 12 (8–41) 20 (11–115) 24 (9–170) 0.05 PLT50, day 15 (11–192) 32 (16–115) 56 (13–551) 0.03 RBCs, units 3 (2–8) 6 (4–31) 11 (6–64) 0.0008 PLTS, aph. units 2 (1–9) 9 (4–51) 18 (4–60) 0.0004 Hosp dsm, day 15 (13–36) 21 (15–69) 41 (16–175) 0.009

Lenalidomide Therapy in Nine Patients with POEMS Syndrome.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3872-3872 ◽  
Author(s):  
Arnaud Jaccard ◽  
Julie Abraham ◽  
Christian Recher ◽  
Remy Dulery ◽  
Isabelle Guichard ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Board Of Directors ◽  
Plasma Cells ◽  
High Dose Chemotherapy ◽  
Poems Syndrome ◽  
Bone Lesions ◽  
High Dose ◽  
Advisory Committees ◽  
Sclerotic Bone Lesions ◽  
Vegf Level

Abstract Abstract 3872 Poster Board III-808 Introduction POEMS syndrome is a rare disease characterized by peripheral neuropathy, organomegaly, endocrinopathy, monoclonal plasma cells, skin changes, papilledema, volume overload, sclerotic bone lesions, thrombocytosis, and high serum VEGF level. Efficient treatments consist in irradiation for patients with localized solitary plasmocytoma and high-dose chemotherapy with autologous stem cell transplantation for appropriate candidates without a focal lesion. Conventional myeloma chemotherapy can only control the disease in a limited number of patients. Results of monoclonal anti-VEGF antibodies, which seem to be attractive due to the role of VEGF in this disease, are controversy with efficacy in 3 patients but treatment related deaths in 2 other patients. Thalidomide effectiveness has been reported in Japanese patients but enthusiasm for its use is tempered by the high incidence of thalidomide-induced peripheral neuropathy. Lenalidomide, which efficacy has been described in one observation (Dispenzieri, Blood 2007 110: 1075-1076), has the advantage of being anti-angiogenic, cytotoxic to malignant plasma cells and with a much lower risk of peripheral neuropathy. We reported here a multicentric French experience with this drug in POEMS syndrome. Patients and Methods There were 3 women and 6 men treated with Lenalidomide in 7 French centres. Median age was 60 (41-76). All patients had sensitive polyneuropathy with motor deficiency in 5 patients. A monoclonal component was present in all cases (IgA lambda in 7 patients, IgG lambda and lambda light chain only in 1 patient each). Other manifestations of POEMS syndrome included sclerotic bone lesions in 6 patients, endocrinopathies in 7 patients, skin changes in 8 patients, oedema in 7 patients, organomegaly in 5 patients, papilledema in 5 patients, thrombocytosis in 3 patients. VEGF serum level was elevated in 4 among 5 patients with a dosage. Previous treatments were high-dose chemotherapy with autologous stem cell transplantation in 3 patients, Melphalan-Prednisone in 3 patients because of advanced age, and prolonged steroid treatment in 2 patients. One patient received Lenalidomide as primary treatment before high-dose therapy. Lenalidomide was given during 21 days each month and sequentially associated with dexamethasone, 5 patients received 25 mg/day and 4 patients received 10 or 15 mg, for a median of 5 cycles (1 to 11). Results Serious side effects were noted in 3 patients with 2 hematologic toxicities (grade III and IV) and a cutaneous allergy. Six patients could be evaluated for hematologic response and all responded, complete response in 3 patients and partial in 3 (>25%). Clinical responses occurred early, before 3 months of treatment, in 6 cases among 8 (1 patient is not yet evaluable), with a marked improvement in performance and in neurological syndrome. Other manifestations of POEMS syndrome improved, especially oedema in 5 cases among 6. VEGF level (normal value < 500 pg/ml) could be serially measured in 4 patients with a normalization in 1 patient and a significant decrease in 3 patients, median 7100 pg/ml (2100-10100) before treatment to 887 pg/ml (304-3270). In 1 of these 3 patients VEGF level increased to initial value while he was still taking Lenalidomide. A second patient experimented a relapse 5 months after ending Lenalidomide, he is still in good response after Lenalidomide reintroduction. With a median follow-up of 12 months (1-26) all patients are alive. Conclusion Lenalidomide seems to be a very promising therapy in POEMS syndrome. It should be tested in larger studies in patients with a systemic disease, who are not able to receive high dose therapy, in relapsing patients and before high dose treatment to avoid transplant related morbidity, particularly engraftment syndrome. Disclosures: Jaccard: Celgene: Membership on an entity's Board of Directors or advisory committees. Facon:Celgene: Membership on an entity's Board of Directors or advisory committees and Speakers Bureau. Moreau:Celgene: Membership on an entity's Board of Directors or advisory committees. Fermand:Celgene: Speakers Bureau.

POEMS syndrome: definitions and long-term outcome

Blood ◽  
2003 ◽  
Vol 101 (7) ◽  
pp. 2496-2506 ◽  
Author(s):  
Angela Dispenzieri ◽  
Robert A. Kyle ◽  
Martha Q. Lacy ◽  
S. Vincent Rajkumar ◽  
Terry M. Therneau ◽  
...  
Keyword(s):  
Median Survival ◽  
Plasma Cells ◽  
Bone Lesion ◽  
Volume Overload ◽  
Response To Therapy ◽  
Poems Syndrome ◽  
Bone Lesions ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Skin Changes

The POEMS syndrome (coined to refer to polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) remains poorly understood. Ambiguity exists over the features necessary to establish the diagnosis, treatment efficacy, and prognosis. We identified 99 patients with POEMS syndrome. Minimal criteria were a sensorimotor peripheral neuropathy and evidence of a monoclonal plasmaproliferative disorder. To distinguish POEMS from neuropathy associated with monoclonal gammopathy of undetermined significance, additional criteria were included: a bone lesion, Castleman disease, organomegaly (or lymphadenopathy), endocrinopathy, edema (peripheral edema, ascites, or effusions), and skin changes. The median age at presentation was 51 years; 63% were men. Median survival was 165 months. With the exception of fingernail clubbing (P = .03) and extravascular volume overload (P = .04), no presenting feature, including the number of presenting features, was predictive of survival. Response to therapy (P < .001) was predictive of survival. Pulmonary hypertension, renal failure, thrombotic events, and congestive heart failure were observed and appear to be part of the syndrome. In 18 patients (18%), new disease manifestations developed over time. More than 50% of patients had a response to radiation, and 22% to 50% had responses to prednisone and a combination of melphalan and prednisone, respectively. We conclude that the median survival of patients with POEMS syndrome is 165 months, independent of the number of syndrome features, bone lesions, or plasma cells at diagnosis. Additional features of the syndrome often develop, but the complications of classic multiple myeloma rarely develop.

THUR 215 Lessons in the diagnosis and management of poems syndrome

2018 ◽  
Vol 89 (10) ◽  
pp. A30.4-A31
Author(s):  
Adams-Carr Kerala ◽  
Keddie Stephen ◽  
Lunn Michael
Keyword(s):  
Light Chain ◽  
Plasma Cells ◽  
Selection Process ◽  
Position Sense ◽  
Joint Position Sense ◽  
Poems Syndrome ◽  
Ivig Treatment ◽  
Bone Lesions ◽  
Limb Weakness ◽  
Pet Ct

We present the case of a 46 year old man who developed a rapidly progressive sensorimotor neuropathy and skin changes. He was diagnosed with Guillain-Barré Syndrome, and subsequently CIDP, but his condition continued to progress despite IVIG treatment and plasma exchange. On transfer to the National Hospital of Neurology and Neurosurgery, six months after the onset of illness, he had profound lower limb weakness with power 0 distal to his knees, and upper limb involvement to the elbows. Deep tendon reflexes were absent, and vibration and joint position sense were reduced peripherally. Nerve conduction studies identified a length-dependent demyelinating polyneuropathy with secondary axonal loss, and blood tests demonstrated thrombocytosis, endocrine dysfunction, and a raised VEGF. Two FGD-avid mixed sclerotic and lytic bone lesions were identified on PET-CT. Biopsy of these lesions demonstrated plasmacytomas with lambda light-chain restriction, and bone marrow biopsy revealed 4% plasma cells, with polytypic light chain staining. A diagnosis of POEMS syndrome was made, and he was initiated on lenalidomide and dexamethasone treatment. With reference to this case we will discuss the challenges in the diagnosis of POEMS syndrome. Additionally, we will outline the therapeutic options available; providing an algorithm to simplify the treatment selection process.

Patients with POEMS Syndrome Have High Bone Turnover and Increased Circulating Angiogenic Cytokines; Should Angiopoietin-2 and Bone-Specific Alkaline Phosphatase Be Used As Minor Criteria for the Diagnosis of the Disease?

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 806-806 ◽  
Author(s):  
Evangelos Terpos ◽  
Meletios Athanasios Dimopoulos ◽  
Stephanie Harel ◽  
Francis K Buadi ◽  
Dimitrios Christoulas ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Markers ◽  
Poems Syndrome ◽  
Bone Lesions ◽  
Bone Specific Alkaline Phosphatase ◽  
High Bone ◽  
Sclerotic Bone Lesions ◽  
Angiopoietin 2 ◽  
Minor Criteria ◽  
Angiogenic Cytokines

Abstract Abstract 806FN2 POEMS syndrome is defined by the presence of peripheral neuropathy (P), monoclonal plasma cell disorder (M), organomegaly (O), endocrinopathy (E) and skin changes (S). The majority of patients have sclerotic bone lesions, although the underlying mechanisms are still unclear. Increased circulating vascular endothelial growth factor (VEGF) is another feature of the disease. However, there is almost no information on the role of other angiogenic molecules in POEMS biology. The aim of the study was to evaluate bone metabolism and angiogenic cytokines in POEMS and compare the results with multiple myeloma (MM) and osteosclerotic patients of other etiology. We retrospectively studied 61 POEMS patients (40M/21F, median age 52 years) who were diagnosed between 1996 and 2010 and were treated and followed in Mayo Clinic Rochester (MN, USA), Hôpital Saint-Louis, Paris (France) and in Alexandra Hospital, Athens (Greece). We evaluated the following indices of bone remodeling and angiogenesis in all patients at diagnosis and in 22 of them one month after front-line treatment: i) osteoclast regulators [sRANKL and osteoprotegerin (OPG)]; ii) osteoblast inhibitor dickkopf-1 (Dkk-1); iii) bone resorption marker CTX; iv) bone formation markers [bone-specific alkaline phosphatase (bALP) and osteocalcin]; and v) angiogenic cytokines [VEGF, angiogenin (ang), angiopoietin (angp)-1 and -2]. These molecules were also measured in 60 newly diagnosed, untreated MM patients (34M/26F, median age: 54 years) and 44 healthy controls. Bone markers were also evaluated in 24 patients with HbS/beta-thalassemia (10M/14F, median age: 43 years) who presented with osteosclerosis, defined as osteosclerotic bone lesions in plain radiography and high T-score of lumbar spine DXA (median: +3.6, range: +2 to +7.9). All POEMS patients presented with P and M, while 90% had E, 83% had S, 61% had O and 32% had papilloedema. One or more documented sclerotic bone lesions in plain X-rays were observed in 78% of patients (diffuse lesions in 44%), while 43% of patients had also an osteolytic component. Seven patients had Castleman disease. At diagnosis, compared to controls, POEMS patients had increased levels of bALP (mean ± SD: 48.3 ± 22.9 IU/L vs. 21.6 ± 8.2 IU/L; p<0.001), CTX (0.97 ± 0.94 ng/ml vs. 0.33 ± 0.24 ng/ml; p<0.001), Dkk-1 (p<0.001), sRANKL (p<0.001) and sRANKL/OPG ratio (p<0.001). Patients with diffuse osteosclerosis had increased levels of Dkk-1 compared to others (p = 0.05), suggesting a balance effect to increased formation activity. Patients with POEMS had increased levels of bALP and decreased levels of CTX compared to MM patients (p<0.001 and p = 0.03, respectively), while they had increased levels of CTX and sRANKL/OPG ratio compared to HbS/beta-thal patients (p = 0.001 for both comparisons). There were no other differences regarding bone markers among studied groups. Regarding angiogenic cytokines, at diagnosis, POEMS patients had elevated VEGF (1232 ± 565 pg/ml vs. 195 ± 211 pg/ml; p<0.001), ang (266 ± 82 ng/ml vs. 190 ± 45; p<0.001) and angp-2 (3.5 ± 2.2 ng/ml vs. 1.2 ± 0.6 ng/ml; p<0.001) and decreased angp-1 (p =0.05) and angp-1/angp-2 ratio (reflects increased angiogenic capacity; 9.1 ± 8.8 vs. 44.8 ± 76.1; p<0.001) compared to normal controls. We found no strong correlations between the levels of VEGF, ang and angps. When compared to MM patients, POEMS patients had increased circulating VEGF (p = 0.001) without any difference regarding the other angiogenic cytokines. Response to therapy was accompanied by a dramatic reduction of VEGF only (551 ± 541 pg/ml compared to baseline 1800 ± 1510 pg/ml; p = 0.003). Receiver-operating characteristic (ROC) curve analysis showed that high levels of angiopoietin-2 (≥ 2.3 ng/ml) and high bALP (≥ 38 IU/l) each have a 95% specificity for patients with POEMS syndrome. These results suggest that patients with POEMS syndrome have high bone turnover with increased bone formation as compared to healthy subjects, to MM patients, who have reduced bone formation, and to osteosclerotic HbS/beta-thal patients, who have diminished bone resorption. Importantly, our analysis supports the use of angp-2, bALP along with VEGF as minor criteria for the diagnosis of POEMS. Successful treatment reduced VEGF, which seems to be a suitable marker for the follow-up of POEMS patients. Furthermore the imbalance of angp-1/angp-2 pathway may indicate possible targets for the development of novel agents against POEMS. Disclosures: No relevant conflicts of interest to declare.

The Roel of High Dose Chemotherapy and Autologous Stem Cell Transplantation (ASCT) In PATIENTS with POEMS SYNDROME: A Retrospective study of the MM Subcommittee of the Chronic Leukemia Working Party of the EBMT,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4115-4115 ◽  
Author(s):  
Gordon Cook ◽  
Laurent Garderet ◽  
Anja van Biezen ◽  
Anja Henseler ◽  
Véronique Leblond ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Working Party ◽  
Poems Syndrome ◽  
Plasma Cell Dyscrasia ◽  
Bone Lesions ◽  
High Dose ◽  
Engraftment Syndrome ◽  
The Impact

Abstract Abstract 4115 Introduction: Polyneuropathy, organomegaly, endocrinopathy, skin changes associated with a paraproteinaemia (POEMS syndrome) is a rare paraneoplastic syndrome secondary to a plasma cell dyscrasia. Effective treatment, including ASCT, of the underlying plasma cell dyscrasia can control the disease and often dramatically control symptoms. Limited data is available for ASCT in POEMS. Specific Aim: The aim of this study was to describe the clinical outcome of ASCT for patients with POEMS syndrome, determining the impact of patient and disease-specific factors on prognosis. The incidence of engraftment syndrome and the presentation of relapse were examined. Methodology: Patient-, disease-, and transplant-related variables were collected according to the data entries in the EBMT database, including tracking incomplete data entries from participating centers. Results: 116 patients underwent an ASCT between 1997–2009 and satisfied the entry criteria. The median age was 50 yrs (range 26–69) with 56.8% of patients '50 year of age. 58.6% had peripheral neuropathy, 66.2% volume overload, 48.3% had organomegaly, 19.8% had papiloedema, 46.6% had dermopathies and 34.5% had sclerotic bone lesions at presentation. The median time from diagnosis to ASCT was 7.8 mns (range 1–346) with 34.5% of patients receiving an ASCT >12 months from diagnosis. The graft source was PBSC in 100% of patients. Disease status at ASCT was: 32% CR/PR, 30% SD/MR/untreated and 5 in PD. Missing information on stage in 33% of the cases. The conditioning regimen was Melphalan ≥200mg/m2 in 52.5%, Melphalan <200mg/m2 in 9.3% (38.1 of data on dose is missing) and TBI-containing only 1 patient. Engraftment was seen in 112 (96.6%) patients with failed engraftment reported in 3 patients (2.5%). Details of the occurrence of engraftment syndrome are currently under collection and analysis though peri-engraftment fever was reported in 23.4% and pulmonary infiltrates in 4.8%. Haematological response was characterized as CR in 31%, PR in 20.7%, <PR in 20.7% and currently unknown in 27.6%. Best disease response, in terms of end-organ response is under evaluation. With a median follow-up of 30.1 mns (range 0.1–161), 90.5 % of patients are alive and only 8.6% of patients have relapsed. The non-relapse mortality was 6.9%. Causes of death: 5 died of infection, 2 from graft failure, 1 from cardiac toxicity. The 3-year probabilities of PFS and OS are 82% and 94%, respectively. The 5-year probabilities of PFS and OS are 80% and 92%, respectively. The data analyzed in this study, to-date, demonstrates that ASCT can be an effective and safe therapeutic modality for patients with POEMS syndrome. The role of high dose therapy compared with more conventional dose therapies warrants further investigation. Disclosures: No relevant conflicts of interest to declare.

The Role Of High Dose Chemotherapy and Autologous Stem Cell Transplantation (ASCT) In Patients With POEMS Syndrome: A Retrospective study Of The Plasma Cell Disorders Subcommittee Of The Chronic Malignancy Working Party Of The EBMT

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 415-415
Author(s):  
Gordon Cook ◽  
Laurent Garderet ◽  
Simona Iacobelli ◽  
Curly Morris ◽  
Nikolaus Kroeger ◽  
...  
Keyword(s):  
Median Time ◽  
Plasma Cell ◽  
Poems Syndrome ◽  
Plasma Cell Dyscrasia ◽  
Bone Lesions ◽  
High Dose ◽  
Specific Response ◽  
Organ Specific ◽  
Engraftment Syndrome ◽  
The Impact

Abstract Introduction Polyneuropathy, organomegaly, endocrinopathy, dermopathy associated with a paraproteinaemia (POEMS syndrome) is a rare paraneoplastic syndrome secondary to a plasma cell dyscrasia. Effective treatment of the underlying plasma cell dyscrasia, including ASCT, can control the disease and often dramatically control symptoms though limited data is available for ASCT in POEMS. Specific Aim The aim of this study was to describe the clinical outcome of ASCT for patients with POEMS syndrome. We wish to determine the impact of patient and disease-specific factors on prognosis and effectively measure the extent of systemic disease involvement and organ-specific responsiveness of ASCT. Methodology Patient-, disease-, and transplant-related variables were collected according to the data entries in the EBMT database, including tracking incomplete data entries from participating centers. Systemic involvement and organ-specific response to ASCT was detailed utilizing an organ involvement tool pre- and post-ASCT. Results 127 patients underwent an ASCT between 1997-2010 and satisfied the entry criteria. The median age was 50 years (range 26-69) with 51.2% ≤50 years of age. The extent of systematic disease involvement was: peripheral neuropathy in 58.6%, volume overload in 66.2%, organomegaly in 48.3%, papilledema in 19.8%, dermopathy in 46.6% and 34.5% had sclerotic bone lesions at presentation. The median time from diagnosis to ASCT was 7.5 months (range 1-346) with 31.5% of patients receiving an ASCT >12 months from diagnosis. The graft source was PBSC in 100% of patients. Disease status at ASCT was: 47.5% CR/PR, 34% SD/MR/untreated and 18.4% in PD (missing information in 19% of patients). The conditioning regimen was Melphalan ≥200mg/m2 in 52.5%, Melphalan <200mg/m2 in 9.3% (38.1 of data on dose is missing) and TBI-containing in only 1 patient. The total rate of engraftment at 3 months was 96.8%, with 2 patients (1.6%) dying before engraftment. Engraftment syndrome was documented in 37% of ASCT recipients including peri-engraftment fever in 23.4% & pulmonary infiltrates in 4.8%. Haematological complete response (CHR) was characterized in 25.2% with 16.5% having progressive disease or died without attaining CHR. CHR was demonstrated in13.3% at 12 month, 20% at 36 months and 23% at 60 months (median time to CHR of 8.6 months) post-ASCT. Both organ-specific & overall systemic response data is currently under analysis, including time-to-maximum response. With a median follow-up of 47.7 months (95%CI 38.3, 58.6), the non-relapse mortality at 1, 2 & 5 years was 3.3% (95%CI 0.1-6.4%), 4.4% (95%CI 0.6-8.2%) & 7.7% (1.9-13.6%), respectively. The median progression-free survival (PFS) was 106 months (95% CI 87.8, NR) with a 5-year PFS of 73.5% (95%CI 63.2-83.7%). The 5-year overall survival (OS) was 88.6% (95% CI 81.5-95.8%). The data analyzed in this study, demonstrates that ASCT can be an effective & safe therapeutic modality for patients with POEMS syndrome. Due to the systemic inflammatory nature of the condition, due care should be taken to supporting these patients through this procedure, especially in relation to engraftment syndrome. Disclosures: Nagler: Teva: Honoraria, Travel grants, research grants Other.

scholarly journals An Atypical Case of POEMS Syndrome Associated with Autonomic Dysfunction

2019 ◽  
Vol 13 (1) ◽  
pp. 92-95
Author(s):  
Mariana B. Hämmerle ◽  
Karina L. Pires ◽  
Márcia B. Hammerle ◽  
Pedro de Mello Vianna P. Galvão ◽  
Lavinia L. Bergier ◽  
...  
Keyword(s):  
Chronic Inflammatory Demyelinating Polyneuropathy ◽  
Extended Period ◽  
Poems Syndrome ◽  
Bone Lesions ◽  
Vascular Endothelial ◽  
Sensorimotor Polyneuropathy ◽  
Protein Levels ◽  
Elevated Protein ◽  
Sclerotic Bone Lesions ◽  
Endothelial Growth Factor

A 52 year old patient showed, for two years, symptoms compatible with sensorimotor polyneuropathy preventing him from walking. An electroneuromyography found a demyelinating pattern suggesting Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). The patient did not respond to corticosteroid therapy and later suffered sexual Dysfunction, Swelling, Lymphadenopathy, Hypotension, astrointestinal dysmotility, urinary retention and neuropathic pain. Analysis of the Cerebrospinal Fluid (CSF) revealed elevated protein levels and Computed Tomography (CT) scan found sclerotic bone lesions. High Vascular Endothelial Growth Factor (VEGF) levels and the results of Lambda light-Chain monoclonal gammopathy in urine protein Electrophoresis Suggested a Diagnosis of POEMS syndrome. The most striking feature, in this case, was the patient’s heightened and atypical polyneuropathy without axonal injury even after an extended period of time, and significant and atypical dysautonomia.

Once Weekly Bortezomib (Velcade) Preserves Bone Health by a Direct Effect on Osteoclast Function Independent of Its Effect on the Malignant Plasma Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3458-3458
Author(s):  
Shachar Peles ◽  
Nicholas M. Fisher ◽  
Feng Gao ◽  
Steven M. Devine ◽  
Michael H. Tomasson ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Disease Progression ◽  
Patient Population ◽  
Plasma Cells ◽  
Bisphosphonate Therapy ◽  
Bone Lesions ◽  
Specific Marker ◽  
Serum Osteocalcin ◽  
Post Transplant ◽  
Osteoclast Function

Abstract Bone resorption is increased in multiple myeloma (MM) due to increased osteoclast activity leading to osteoporosis and osteolytic bone lesions. Assays of urinary excretion of N-telopeptide (NTX), a highly specific marker of bone resorption, decrease by 20–70% following treatment with bisphosphonates. Receptor activator of NF-kB (RANK) ligand increases osteoclast mediated bone resorption in part through activation of nuclear factor kappa-B(NF-kB). Preclinical studies have shown bortezomib to decrease osteoclast function through inhibition of NF-kB. However, no clinical data exists on the effect of bortezomib on markers of bone resorption. We designed a prospective clinical trial aimed at measuring the effect of bortezomib on urinary NTX excretion and serum osteocalcin levels in patients with MM. Patients received six cycles of consolidation bortezomib 1.3mg/m2 given once weekly (for ease of administration) for 4 of every 5 weeks, 90–120 days post transplant. Urinary NTX excretion and serum osteocalcin were measured on day 1 of cycles 1, 2 and 3 of therapy. Treatment with bisphosphonates was prohibited from 42 days prior to stem cell collection and until cycle 3 of post transplant bortezomib therapy. To date, 31 of 40 enrolled patients have proceeded to receive bortezomib consolidation therapy and are evaluable for markers of bone metabolism. Characteristics of the patient population and disease include (no. of patients): male (21), female (10), median age 56 years (range 39–70), Stage II (8), Stage III (23), IgG (20), IgA (9), free light chain (2). The median duration between discontinuation of prior bisphosphonate therapy and initiation of post transplantation weekly bortezomib was 158 days (Range 132–196). Of the 19 patients who have completed all 6 prescribed cycles of consolidation bortezomib, only one patient has had a 50% or greater reduction in paraprotein, 16 had stable disease and 2 had disease progression. Nevertheless, excretion of NTX decreased by a mean of 7.4 nmol/mmol creatinine over each 5 week treatment cycle (p=0.007) with a mean decline of 33% over baseline values after 2 cycles of consolidation, once weekly bortezomib therapy (see table). Only one patient displayed an increase in urinary NTX of greater than 30%. This was the only patient with evidence of disease progression during this period of consolidation. Contrary to preclinical and clinical reports of proteasome inhibition resulting in increased osteoblastic bone formation, a decrease was seen in serum osteocalcin. This data suggests that bortezomib, given just once weekly, has a substantial inhibitory effect on osteoclastic bone resorption in MM even in the absence of effects on the malignant plasma cells. The magnitude of effect appears comparable to that achieved with bisphosphonates. Given concerns regarding long term toxicities of bisphosphonate therapy, including nephrotoxicity and osteonecrosis of the jaw, bortezomib may represent an alternative agent effective in controlling both the myeloma and bone disease in this patient population. Cycle 1 Day 1 Cycle 2 Day 1 Cycle 3 Day 1 Mean Change p value Mean Osteocalcin (Range)(ng/ml) 28.16 (9.30 – 81.90) (n = 28) 26.69 (9.50 – 57.40) (n = 25) 26.12 (11.60 – 73.00) (n = 21) −4.6 (16%) 0.02 Mean NTX excretion (Range)(nmol/mmol Cr) 44.87 (10 – 121) (n = 23) 36.00 (7 – 65) (n = 24) 30.43 (9 – 87) (n = 21) −14.8 (33%) 0.007

scholarly journals A Prospective Phase II Trial of Lenalidomide and Dexamethasone ( LEN-DEX) in POEMS Syndrome

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 36-36 ◽  
Author(s):  
Arnaud Jaccard ◽  
Anne Lazareth ◽  
Lionel Karlin ◽  
Sylvain Choquet ◽  
Laurent Frenzel ◽  
...  
Keyword(s):  
Research Funding ◽  
Plasma Cells ◽  
Bone Marrow Involvement ◽  
Poems Syndrome ◽  
High Dose ◽  
Neurological Improvement ◽  
Engraftment Syndrome ◽  
Prospective Phase ◽  
Group 2 ◽  
Group 1

Abstract Background. POEMS syndrome is a rare form of B cell dyscrasia combining a proliferation usually of plasma cells, a polyneuropathy, osteocondensing bone lesions and multiple other clinical signs. The pathogenesis is not well understood but VEGF plays a major role. In patients with one or two sclerotic plasmacytoma and no bone marrow involvement, first line therapy should include radiation. For patients with diffuse sclerotic lesions, bone marrow involvement or absence of any bone lesion and for those who have not demonstrated stabilization of their disease 3 to 6 months after completing radiation systemic therapy is indicated, the most effective being high dose chemotherapy with autologous stem cell transplant (ASCT). Radiation of a single lesion is effective in about every other case and is accompanied by a fairly slow improvement of the neurological symptoms, often after initial worsening. ASCT seems to be accompanied by a number of important complications, in particular engraftment syndrome. Outside these 2 treatments there is no consensus therapy. Lenalidomide (LEN), a drug without serious neurological toxicity, has the advantage of being both anti-angiogenic and cytotoxic to malignant plasma cells (Richardson PG, Blood 2002;100(9):3063-7). We have recently reported a series of 20 French patients with POEMS syndrome treated by LEN with a good efficacy. We now report the first 27 patients of a prospective phase II trial using LEN + dexamethasone (LEN-DEX), 2 cycles preceding radiation or high dose treatment trying to obtain a rapid clinical response and to avoid engraftment syndrome or 9 cycles followed by 1 year LENalone in patients who cannot receive radiation or ASCT. Methods. Newly diagnosed or relapsing patients with POEMS syndrome who needed to be treated were eligible. Patients who can be treated by local radiation or intensive treatment with stem cell support receive two 28 day cycles of LEN 25 mg PO Days 1-21 and DEX 40 mg PO Days 1,8,15,22 before radiation or intensive treatment (Group 1), the other patients receive 9 cycles of the same LEN-DEX (Group 2) and then 12 cycles of continuous low dose LEN (10 mg). LEN dose was tapered to 10 mg for patients with a creatinine clearance between 30 and 50 ml/min and DEX to 20 mg for patients above 75 years of age and for those who were frail patients. Main eligibility criteria included a diagnosis of POEMS syndrome according to criteria by Dispenzieri et al (Am J Hematol 2012;87(8):804-14), an age of 18 or more, a creatinine clearance above 30 ml/min, no prior treatment with or contraindication to LEN and no uncontrolled thrombosis. Serum and plasma VEGF, serum electrophoresis, immunofixation and free light chain measurements were centrally monitored. Neurologic evaluations were performed using the Overall Neuropathy Limitations Scale (ONLS), the Neurological Impairment Scale (NIS) and the 10 meter walk test (10MWT). The primary endpoint was evaluation of the effectiveness of LEN-DEX combination using biological responses (decrease of monoclonal protein and serum VEGF level) and secondary endpoints were clinical and particularly neurological responses. Results. Twenty-seven patients have been included in 12 centres, median age was 61 (range 32-75), the median follow-up was 6.6 months (range 2-24). Eighteen patients were in group 1, with radiotherapy in 10 patients and ASCT in 8 patients; 9 patients were in group 2. Nineteen patients were in first line and 8 already treated. Only 2 patients experienced grade 3-4 adverse events due to LEN (cytopenia) and 2 patients had allergic rashes, no thrombotic event occurred. No engraftment syndrome was noted in the 5 patients already treated with ASCT. To date, no patient have died. Evolution of VEGF median values in serum and plasma, M-spike and dFLC levels and evolution of neurological measurements are reported in table 1. Neurological improvement was very rapid in some patients, using ONLS and 10MWT 11/18 evaluable patients had a neurological improvement after 2 cycles with an improvement of 1 or more of the ONLS score and/or change of 0.1 m/s or more in the 10MWT. Only one patient who progressed after nine cycles received another therapy. Conclusion. This is the first prospective trial of LEN-DEX in POEMS syndrome. This combination seems well tolerated in this disease with a good efficacy on VEGF measurements and rapid neurological improvement in the majority of patients. Updated data will be presented at the meeting. Figure 1 Figure 1. Disclosures Jaccard: Celgene: Drug supply to Trial Other. Tournilhac:mundipharma: Honoraria, Other, Research Funding; GSK: Honoraria, Other, Research Funding; Roche: Honoraria, Other, Research Funding. Moreau:celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.

High Bone Turnover and Increased Angiogenesis Cytokines in Patients with POEMS Syndrome.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3525-3525
Author(s):  
Evangelos Terpos ◽  
Meletios A. Dimopoulos ◽  
Ersi Voskaridou ◽  
Angela Dispenzieri
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Bone Turnover ◽  
Type I Collagen ◽  
Poems Syndrome ◽  
Bone Lesions ◽  
Type I ◽  
Tnf Α ◽  
Sclerotic Bone Lesions ◽  
Angiogenic Cytokines

Abstract POEMS syndrome is defined by the presence of peripheral neuropathy (P), monoclonal plasma cell disorder (M), organomegaly (O), endocrinopathy (E), and skin changes (S). Virtually all patients will have sclerotic bone lesions, although the mechanisms of their development have not been clarified to-date. Increased plasma level of VEGF is another characteristic of the disease. However, there is very little information for the role of other angiogenic molecules in POEMS pathogenesis. The aim of this study was to evaluate bone metabolism and angiogenic cytokines in POEMS and compare the results with multiple myeloma (MM) and osteosclerotic patients of other etiology. Seven patients with POEMS at diagnosis (6M/1F; median age: 49 years) were evaluated. A series of bone remodeling indices were measured: i) bone resorption markers [C- and N- telopeptide of type-I collagen (CTX and NTX), TRACP-5b], ii) bone formation markers [bone-alkaline phosphatase, osteocalcin (OC), and C-terminal propeptide of type-I collagen (CICP)], and iii) osteoclast regulators [soluble RANKL, osteoprotegerin (OPG), MIP-1α, and TNF-α]. Furthermore, the following angiogenic cytokines were measured in the plasma of POEMS patients: VEGF, VEGF-A, angiogenin, angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and bFGF. All above molecules were also measured in 25 newly diagnosed, untreated MM patients (14M/11F, median age: 64 years) and 20 healthy controls. Bone markers were also evaluated in 24 patients with HbS/beta-thalassemia (10M/14F, median age: 43 years) who presented with osteosclerosis, i.e. osteosclerotic bone lesions in plain radiography and a median T-score of lumbar spine Bone Mineral Density of +3.6 (range: +2 to +7.9). All POEMS patients had P, O, E, S, edema and thombocytosis; 6 had E and 2 Castleman’s disease. Six patients had sclerotic bone lesions, while 4 had also a lytic component in their bone lesions. POEMS patients had increased levels of sRANKL (p=0.003), OPG (p=0.008), TNF-α (p=0.001), NTX (p<0.001), CTX (p=0.001) and CICP (p=0.001) compared with controls. Interestingly, NTX levels were even higher in POEMS than in MM patients (p<0.01). NTX and CTX were elevated in POEMS compared with osteosclerotic HbS/β-thal patients (p<0.01), who had reduced bone resorption compared with controls. POEMS patients had increased levels of OC and CICP compared with MM (p=0.02 and p=0.003, respectively), and increased levels of OC compared with osteosclerotic HbS/β-thal patients (p<0.01). In terms of angiogenic cytokines, POEMS patients had increased levels of all studied cytokines compared with controls (p<0.01). All POEMS patients had at least 1.8-fold higher value of VEGF-A (the major angiogenic component of VEGF) compared with the higher value observed in controls. Furthermore, VEGF (p=0.03), VEGF-A (p<0.001), angiogenin (p<0.001), and bFGF (p=0.01) were higher in POEMS than in MM. The ratio of Ang-1/Ang-2 was very low in POEMS compared with both controls and MM. These results suggest that POEMS patients have increased bone turnover in contrast to MM patients who have reduced bone formation and osteosclerotic HbS/β-thal patients who have diminished bone resorption. Furthermore the imbalance of Ang-1/Ang-2 pathway and the increased levels of angiogenic cytokines, even compared with MM, may indicate possible targets for the development of novel agents against POEMS.

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