Improvement in the Symptoms and VEGF Levels after Resection of an Extrame Dullary Spinal Tumor and Additional Chemotherapy in a Patient with Multiple Myeloma Complicated with POEMS Syndrome

The polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes (POEMS) syndrome is a rare multisystem disorder of obscure pathogenesis associated with osteosclerotic myeloma. Circulating levels of proinflammatory cytokines (tumor necrosis factor-alpha (TNF-alpha) interleukin-1 beta [IL-1 beta], IL-2, IL-6, and interferon-gamma [IFN- gamma]), anti-inflammatory cytokines (transforming growth factor beta 1 [TGF beta 1], IL-4, IL-10, and IL-13), the cytokine carrier protein alpha 2 macroglobulin, IL-1 receptor antagonist (IL-1ra), soluble TNF receptors (sTNFr) p55 and p75, and soluble IL-6 receptor (sIL-6r) were determined in 15 patients with POEMS syndrome and 15 with multiple myeloma. Patients with POEMS syndrome had higher serum levels of IL-1 beta, TNF-alpha, and IL-6 and lower serum levels of TGF beta 1 than did patients with multiple myeloma. Serum levels of IL-2, IL-4, IL-10, IL- 13, IFN-gamma, alpha 2 macroglobulin, and sIL-6r were similar in both groups. IL-1ra and sTNFrs were increased in POEMS syndrome, but out of proportion to the increase of IL-1 beta and TNF-alpha. Serial evaluations in 1 patient showed that proinflammatory cytokine serum levels paralleled disease activity assessed by platelet count and neurologic involvement. Our results suggest that the manifestations of POEMS syndrome might be regarded as the result of a marked activation of the proinflammatory cytokine network (IL-1 beta, IL-6, and TNF- alpha) associated with a weak or even decreased (TGF beta 1) antagonistic reaction insufficient to counteract the noxious effects of cytokines.

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Human Immunodeficiency Virus-Negative Castleman's Disease: Clinicopathological and Laboratory Characteristics and Outcomes in Patients Treated in a Single Institution

Blood ◽

10.1182/blood.v126.23.5027.5027 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5027-5027

Author(s):

Nalini Hasija ◽

Liliana Bustamante ◽

Michael V. Jaglal ◽

Lubomir Sokol

Keyword(s):

Multiple Myeloma ◽

Human Immunodeficiency Virus ◽

Retrospective Study ◽

Castleman’S Disease ◽

Surgical Excision ◽

Poems Syndrome ◽

Second Line ◽

Castleman's Disease ◽

Single Institution ◽

Immunodeficiency Virus

Background Human Immunodeficiency Virus (HIV)-negative Castleman's Disease (HIVnegCD) is a group of rare heterogeneous polyclonal lymphoproliferative disorders of poorly understood etiopathogenesis. Several histological subtypes were previously described including hyaline-vascular, plasma-cell, mixed and plasmablastic. Unicentric Castleman's disease (UCD) is usually treated with complete surgical excision of involved lymph node(s). Multicentric Castleman's Disease (MCD) frequently manifests with generalized lymphadenopathy and systemic B-symptoms due to inflammatory hypercytokinemia. An important role of inflammatory cytokine IL-6 was previously established in MCD in experimental and clinical studies. Patients with MCD usually require systemic therapy. Objectives Primary purpose of this study was to collect and analyze clinicopathological and laboratory characteristics and outcomes of patients with HIVnegCD treated in a single institution. Methods Institutional review board (IRB)-approved, Health Insurance Portability and Accountability Act (HIPAA) compliant, retrospective study was conducted at Moffitt Cancer Center. Clinical and laboratory characteristics were extracted from electronic medical records and analyzed using SPSS version 22.0 statistical software. Results We identified a total of 28 patients (pts) between 1993 and 2015. 14 pts had UCD and 14 MCD. Median age was 49 (35-87) years (UCD) and 47 (31 -79) years (MCD). Male: female ratio was 1:2.5 (UCD) and 1:1.33 (MCD). A majority of patients had a PS 0-1 in both groups (13/13 and 9/10 respectively). Only 2/13 (15.4%) pts with UCD presented with fatigue and 2 (15.4%) had CNS symptoms. 9 of 14 (64%) pts with MCD reported fatigue and 8/14 (57.1%) presented with night sweats and anorexia. 5 of 14 pts (36%) with MCD were concurrently diagnosed with POEMS syndrome, 2 pts with MGUS and 1 pt with smoldering IgA kappa light chain restricted multiple myeloma. HIV-1/2 ELISA test was negative in all tested pts (18/18). In the remaining 10 pts the test was not available, but a longitudinal follow-up revealed no evidence of immunodeficiency or history of opportunistic infections. HHV-8 test was negative in 9 of 9 tested pts. 2 of 18 pts showed polyclonal hypergammaglobulinemia. 10 of 18 pts had soluble IL-6 tested and only 1 pt with MCD had an elevated level. C-reactive protein (CRP) was elevated in only 1 of 10 pts. Confirmatory histology slide review in our institution revealed a hyaline-vascular subtype in 4 pts with UCD and 6 pts with MCD. 10 pts had plasma-cell subtype (6 with UCD and 4 with MCD) and 2 had mixed subtype (1 each in UCD and MCD). In 6 pts, pathological diagnosis was based only on outside report due to the absence of the original histology slides or insufficient tissue for confirmatory studies. 11 of 13 pts with UCD underwent surgical excision, 1 received radiation therapy and 1 chemotherapy in the frontline settings resulting in complete response. 1 patient with UCD received anti-IL-6 monoclonal antibody for the second line therapy followed by rituximab monotherapy. This patient was the only pt with UCD demonstrating progressive disease. Management of MCD included various systemic regimens listed in Table #1. Chemotherapy regimens included chloramubucil, thalidomide, cyclophosphamide, melphalan, DT-PACE, R-CHOP and lenalidomide. Only 3 pts died and all 3 had progressive refractory MCD. 2 of the pts who died also had POEMS syndrome. Median survival was not reached, as 25 of 28 pts were alive at the time of data collection. Conclusions This retrospective study indicated that HIVnegCD is a heterogeneous disorder with very good prognosis in patients with resectable UCD. Systemic therapy is usually required in patients with MCD. The increased frequency of malignancies associated with CD such as POEMS syndrome, multiple myeloma, and follicular dendritic cell sarcoma can have adverse impact on prognosis. Table 1. Treatment of MCD MCD First Line Surgery 1 12 8.3% Steroids 6 12 50% Rituximab 1 12 8.3% IL-6 2 12 16.7% Chemo1 2 12 16.7% Second Line Surgery 1 8 12.5% Rituximab 2 8 25% Chemo2 1 8 12.5% Combo chemo3 2 8 25% Surgery +XRT 1 8 12.5% Auto BMT 1 8 12.5% Third Line XRT 1 5 20% IL-6 1 5 20% Chemo4 2 5 40% Combo chemo5 1 5 20% 1 Chlorambucil/Pred, Thalidomide/Dex 2 Melphalan/Pred 3 Etoposide/Ritux, Lenalidomide/Ritux 4 DT-PACE, Cyclophosphamide/Pred 5 R-CHOP Disclosures Sokol: Janssen Research & Development, LLC: Consultancy.

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Paraproteinaemias

10.1093/med/9780199683307.003.0008_update_001 ◽

2018 ◽

Author(s):

Drew Provan ◽

Trevor Baglin ◽

Inderjeet Dokal ◽

Johannes de Vos ◽

Mammit Kaur

Keyword(s):

Multiple Myeloma ◽

Heavy Chain ◽

Monoclonal Gammopathy ◽

Poems Syndrome ◽

Systemic Amyloidosis ◽

Heavy Chain Disease ◽

Osteosclerotic Myeloma ◽

Undetermined Significance

Paraproteinaemias - Monoclonal gammopathy of undetermined significance (MGUS) - Asymptomatic multiple myeloma (‘smouldering’ myeloma) - Multiple myeloma - Variant forms of myeloma - Cryoglobulinaemia - POEMS syndrome (osteosclerotic myeloma) - Plasmacytoma - Waldenström macroglobulinaemia - Heavy chain disease - AL (1° systemic) amyloidosis

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Unmaintained remissions in multiple myeloma

Blood ◽

10.1182/blood.v51.6.1005.1005 ◽

1978 ◽

Vol 51 (6) ◽

pp. 1005-1011 ◽

Cited By ~ 66

Author(s):

R Alexanian ◽

E Gehan ◽

A Haut ◽

J Saiki ◽

J Weick

Keyword(s):

Multiple Myeloma ◽

Survival Time ◽

Median Survival ◽

Median Survival Time ◽

Plasma Cells ◽

Extensive Disease ◽

Abnormal Protein ◽

Additional Chemotherapy ◽

Term Evaluation

Abstract Twenty-eight patients with multiple myeloma responding to prior melphalan-prednisone combinations, but without additional chemotherapy, were followed until relapse. Patients receiving no further treatment had a median survival time similar to that of those receiving indefinite courses of melphalan-prednisone or carmustine-prednisone. Prolonged periods of unmaintained remission occurred primarily in patients without extensive disease at the time of diagnosis or in whom the abnormal protein disappeared from the electrophoresis strip. The initial relapse after an unmaintained remission was controlled in 80% of patients with the resumption of melphalan-prednisone, but second remissions were usually less marked in degree and shorter in duration. Results supported the long-term evaluation without chemotherapy of selected patients with low numbers of plasma cells after treatment who were likely to experience long durations of disease stability and respond again to retreatment with melphalan-prednisone.

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Paraproteinaemias

10.1093/med/9780199683307.003.0008 ◽

2015 ◽

Author(s):

Drew Provan ◽

Trevor Baglin ◽

Inderjeet Dokal ◽

Johannes de Vos

Keyword(s):

Multiple Myeloma ◽

Heavy Chain ◽

Monoclonal Gammopathy ◽

Poems Syndrome ◽

Systemic Amyloidosis ◽

Heavy Chain Disease ◽

Osteosclerotic Myeloma ◽

Undetermined Significance

Paraproteinaemias - Monoclonal gammopathy of undetermined significance (MGUS) - Asymptomatic multiple myeloma (‘smouldering’ myeloma) - Multiple myeloma - Variant forms of myeloma - Cryoglobulinaemia - POEMS syndrome (osteosclerotic myeloma) - Plasmacytoma - Waldenström macroglobulinaemia - Heavy chain disease - AL (1° systemic) amyloidosis

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