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.

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

Extensive Bone Marrow Infiltration and Abnormal Free Light Chain Ratio Identifies Patients with Smoldering Myeloma At High Risk for Progression to Symptomatic Disease,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3926-3926
Author(s):  
Efstathios Kastritis ◽  
Lia A Moulopoulos ◽  
Maria Gkotzamanidou ◽  
Dimitra Gika ◽  
Maria Roussou ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Light Chain ◽  
Plasma Cells ◽  
Bone Lesions ◽  
Symptomatic Disease ◽  
Lytic Bone Lesions ◽  
Risk Of Progression ◽  
Bone Marrow Plasma ◽  
Substantial Risk

Abstract Abstract 3926 Asymptomatic/smoldering multiple myeloma (SMM) is a proliferative plasma cell disorder characterized by a substantial risk of progression to symptomatic myeloma. According to current recommendations, patients with SMM should be followed without treatment until they develop symptomatic disease. However, the risk of progression to symptomatic myeloma varies between different series and for individual patients; thus, significant effort is needed in order to identify factors that could discriminate those who are at high risk for progression. Such patients should be followed closer and should be considered candidates for clinical trials. In order to evaluate previously recognized risk factors and study patterns of progression we analyzed our series of patients with SMM, who have been diagnosed and followed in the Department of Clinical Therapeutics in Athens, Greece. SMM was defined as serum monoclonal (M) protein (IgG or IgA) level of ≥3 g/dL and/or bone marrow plasma cells ≥10%, absence of end-organ damage, such as lytic bone lesions, anemia, hypercalcemia, or renal failure, that can attributed to a plasma cell proliferative disorder (IMWG criteria, Br J Haematol 2003;121:749–57). Progression to symptomatic myeloma was defined as per the IMWG proposed criteria. We analyzed 95 patients with SMM, 53% of whom were females, 70% had IgG heavy chain, 22% had IgA, 5% had a biclonal SMM and 3% had light chain only SMM, while 65% had a kappa light chain and 35% a lambda light chain. Median infiltration by clonal plasma cells in BM trephine biopsy was 20% (range 10–90%), 10% of patients had ≥60% clonal plasma cells in BM biopsy. Fifty patients had MRI of the spine at the time of diagnosis of SMM and 19.5% had an abnormal pattern of BM infiltration (diffuse, focal or variegated pattern). In patients with available bone marrow immunohistochemistry data, 61% had clonal plasma positive for CD56, 17% for CD20 and 19% for cyclin D1. The median follow up of the cohort was 27 months (range 1–253 months) and 23 (24%) patients have progressed to symptomatic myeloma. The one-year, 2-year and 3-year cumulative probability of progression was 7%, 12% and 20% respectively. Nine patients (9.5%) progressed within the first two years from the diagnosis of SMM. All these patients had an M-protein of ≥1 g/dl (10 g/L), 67% had bone marrow plasma cells >60% and 80% had an abnormal MRI pattern of BM infiltration. The 3-year probability of progression to symptomatic myeloma was 4%, 18% and 87% for patients with <20%, 20–59% and ≥60% clonal plasma cells in bone marrow biopsy (P<0.001). The 2-year probability of progression to symptomatic myeloma was 0%, 13% and 60% for patients with <20%, 20–59% and ≥60% clonal plasma cells in BM biopsy (P<0.001). Patients with significantly abnormal free light chain ratio (either kappa/lambda ≥8 or kappa/lambda ≤0.125, according to Dispenzieri et al, Blood 2008;111:785–9) had a 3-year probability of progression to symptomatic MM of 41% vs. 15% (p=0.07). There was no significant difference in the risk of progression to symptomatic MM for patients with IgA vs. IgG myeloma. In multivariate analysis, abnormal FLC ratio less than 0.125 or more than 8 (HR: 6.4, 95% CI 1.3–34.5 p=0.032) and BM clonal plasma cells infiltration ≥60% (HR: 23, 95% CI 5–125, p<0.001) were independent risk factors for progression to symptomatic myeloma. Progression to symptomatic MM was manifested by the development of anemia in 52% of patients who progressed to symptomatic MM, development of lytic bone lesions or pathologic fracture in 48%, an increase of serum creatinine to ≥2 mg/dl in 13%, development of a soft tissue plasmacytoma in 4% and development of hypercalcemia in 4%. In conclusion, in our series of patients the 3-year probability of progression to symptomatic myeloma is about 20%, but there is a subgroup of patients with extensive bone marrow infiltration (≥60%) and highly abnormal FLC ratio, who have a substantial risk of progression to symptomatic disease within the first two years from the diagnosis of SMM. These high risk patients may also have other features such as abnormal MRI of the spine. Patients at high risk for progression should be considered for clinical trials evaluating the role of treatment before the development of symptomatic disease, which in most cases is manifested with anemia and/or lytic bone disease or pathologic fractures. Disclosures: No relevant conflicts of interest to declare.

Characteristics and Prognosis Of IgM Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1881-1881 ◽  
Author(s):  
Shebli Atrash ◽  
Qing Zhang ◽  
Xenofon Papanikolaou ◽  
Christoph Heuck ◽  
Aziz Bakhous ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Germinal Center ◽  
Clinical Characteristics ◽  
Plasma Cells ◽  
Initial Diagnosis ◽  
The Other ◽  
Bone Lesions ◽  
Disease Characteristics ◽  
Pet Ct ◽  
The Us

Abstract Introduction Multiple Myeloma (MM) is considered a malignancy of post germinal center long-lived plasma cells. Nevertheless T-cell independent antigen stimulation before the exposure of the B-cell to the germinal center can happen and results to IgM secreting short lived plasma cells and lymphoplasmacytes representing thus a potential alternative normal counterpart for IgM plasma cell dyscrasias. IgM myeloma is an infrequent subtytpe of MM with an estimated prevalence of 0.5%. Due to its rarity little is known about its characteristics and prognosis in comparison with Waldestrom’s macroglobulinemia (WM) and the other MM subtypes. Purpose To identify the characteristics and the prognosis of IgM MM, and compare it predominantly with WM and subsequently with the rest of the MM subtypes. Methods We interogatted our Multiple Myeloma Data Base for cases of IgM MM and their respective Overall Survival (OS), Progression Free Survival (PFS), bone disease as defined by x-Rays, PET-CT and MRI, Gene Expression Profile (GEP), and common disease characteristics (anemia,calcium, creatinine) and compare it to the prognosis of WM and non-IgM MM. Diagnosis was based on the morphological and immunophenotypical findings of pathologically examined biopsy specimens along with the presence or not of typical clinical characteristics of MM (lytic bone lesions, hypercalcemia, renal failure) or typical clinical characteristics of WM (organomegaly, lymphadenopathy). Results There were 22 confirmed IgM MM cases. 14 of them presented at MIRT at initial diagnosis while 8 had previously been treated elsewhere. Osteolytic bone lesions and/or pathological fractures by x-ray and CT examination were evident in 16 cases. For the remaining 6 cases active bone focal lesions by either MRI or PET were identified in three. There was no organomegaly evident in cases with an available PET/CT at baseline, while only one had evidence of hilar and mediastinal lymphadenopathy along with calcified lung nodules. Elevated creatinine levels (>2.0 mg/dl) were evident in 4 cases at initial diagnosis. Their disease characteristics are depicted in the table 1. Median OS for IgM MM was 4.9 years while PFS could not be accurately estimated due to lack of data on patients treated elsewhere. Median OS for a historical control of 158 WM cases in MIRT was 9.2 years (Clin Lymphoma Myeloma Leuk. 11(1):139-42). Median OS of the WM group remained largely unaffected, even when the subgroup of the WM cases requiring treatment was analyzed (9.0 years).To further clarify if the IgM MM differs in terms of OS from the other isotypes of MM, we compared the IgM group to a group of 61 non-IgM MM cases which were matched by important prognostic clinical factors (age, creatinine> 2mg/dl, LDH>190u/L, b-2M >5.5mg/dl and Albumin<3.5gr/dl). No statistical difference was found for OS (p=0.846). Out of 22 cases, 14 of them had available GEP data on initial diagnosis. In 6 of these cases the cyclin D1 gene expression was high enough to be consistent with a t(11;14) translocation at FISH analysis, one case was consistent with a t(14;16) translocation, one with a t(4;14) translocation and two more were classified as belonging to the hyperdiploid subgroup. A comparative genomic analysis was performed on the IgM MM, the non-IgM MM and WM cases with available GEP data at initial diagnosis (14, 61 and 42 cases respectively). 1155 probesets that had expression level significantly different between WM and non IgM MM (FDR<3E-06) were identified. Then, the expression values of these 1155 probesets in all GEP samples, including WM, non IgM MM, and IgM MM, were used to build a clustering tree. We found that IgM MM mainly clustered with non IgM MM, supporting the findings of the clinical data. Conclusion IgM MM is a discrete clinical entity that should be distinguished from WM. Bone disease is evident in the majority of the cases, especially when specialized radiological techniques are incorporated at the initial work up. It holds a distinct prognosis from WM, while when balanced for prognostic factors that hold importance in MM it does not differ from the other MM isotypes. Finally analysis of the genetic data further supports the resemblance between IgM MM and the non IgM MM, and the difference with WM. Disclosures: Zhang: University of Arkansas for Medical Sciences: Co-inventor of the DNA probes for FISH of IGHC/IGHV (14q32), MMSET/FGFR3 (4p16), CCND3 (6p21), CCND1 (11q13), MAF (16q23), and MAFB (20q12) loci, sub. to the US Patent & Trademark Office as Prov. App# 61/726,327: Methods of Detecting 14q32 Translocations, Co-inventor of the DNA probes for FISH of IGHC/IGHV (14q32), MMSET/FGFR3 (4p16), CCND3 (6p21), CCND1 (11q13), MAF (16q23), and MAFB (20q12) loci, sub. to the US Patent & Trademark Office as Prov. App# 61/726,327: Methods of Detecting 14q32 Translocations Patents & Royalties.

Restrictive usage of monoclonal immunoglobulin λ light chain germline in POEMS syndrome

Blood ◽  
2008 ◽  
Vol 112 (3) ◽  
pp. 836-839 ◽  
Author(s):  
Daijiro Abe ◽  
Chiaki Nakaseko ◽  
Masahiro Takeuchi ◽  
Hiroaki Tanaka ◽  
Chikako Ohwada ◽  
...  
Keyword(s):  
Light Chain ◽  
Plasma Cells ◽  
Poems Syndrome ◽  
Monoclonal Immunoglobulin ◽  
Variable Regions ◽  
Plasma Cell Disorder ◽  
Λ Light Chain ◽  
V Region ◽  
Restricted Use ◽  
Endothelial Growth Factor

Abstract POEMS syndrome is a rare plasma cell disorder characterized by peripheral neuropathy, monoclonal gammopathy, and high levels of serum vascular endothelial growth factor, the pathogenesis of which remains unclear. A unique feature of this syndrome is that the proliferating monoclonal plasma cells are essentially λ-restricted. Here we determined complete nucleotide sequences of monoclonal immunoglobulin λ light chain (IGL) variable regions in 11 patients with POEMS syndrome. The V-region of the Igλ gene of all 11 patients was restricted to the Vλ1 subfamily. Searching for homologies with IGL germlines revealed that 2 germlines, IGLV1-44*01 (9/11) and IGLV1-40*01 (2/10), were identified, with an average homology of 91.1%. The IGLJ3*02 gene was used in 11 of 11 re-arrangements with an average homology of 92.2%. These data suggest that the highly restricted use of IGL Vλ1 germlines plays an important role in the pathogenesis of POEMS syndrome.

Macrofocal Multple Myeloma Is a Particular Subgroup of Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1855-1855 ◽  
Author(s):  
Jianling Fan ◽  
Jian Hou ◽  
Juan Du ◽  
Lina Jin ◽  
Lihui Peng ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Plasma Cells ◽  
Progression Free Survival ◽  
Staging System ◽  
Tumor Burden ◽  
Bone Lesions ◽  
Serum Free Light Chain ◽  
Secretory Type ◽  
Stage 1

Abstract Some young multiple myeloma (MM) patients, coined macrofocal MM, have been reported to present with multiple lytic bone lesions and less than 10% bone marrow plasma cells (BMPCs). They usually have low tumor burden and favorable outcome. To further understand the clinical and laboratory features of macrofocal MM, we retrospectively analyzed about 1000 symptomatic MM patients of two centers and found that 49 (4.9%) patients fulfilled the criteria of macrofocal MM. Median age was 54 years; 39 (80%) were male. The immunoglobulin subtype included IgG (13), IgA (5), IgD (4), light chain only (4) and non-secretory type (23). International Staging System (ISS) stage 1 in 45 (92%), and no stage 3 patient. Durie-Salmon (DS) Staging System stage 3A in 48 (98%), and 2A in 1. Extramedullary plasmacytomas (EMPs) in 39 (80%) patients. The mean percentage of BMPCs was 2.1%, and 44 (90%) patients had less than 5% BMPCs. No patients had hypercalcemia and renal impairment. FISH cytogenetics, available in 11 patients, showed IgH translocation in 7, 13q del in 2, t(4;14) in 1, 1q21 amp in 6 and p53 del in 2 patients. Serum free light chain (sFLC), available in 14 patients, showed abnormal sFLC in 7 of 14 patients and 4 in 7 non-secretory type patients. Thirty eight (77.6%) patients received new drug-based induction therapies and 14 patients received autologous stem cell transplantation (ASCT) as consolidation therapy. After a median follow-up of 36 months,the estimated median progression-free survival (PFS) was 41 months and the median overall survival time (OS) had not been reached. Forty four macrofocal MM with ISS stage 1 and DS stage 3A were compared to all (93) typical symptomatic MM patients who were diagnosed at the same period with the same stages according to both ISS and DS Staging System. For macrofocal MM, there were significantly more male patients and EMPs, higher hemoglobin levels and lowerb2-microglobulin (b2M) levels than that of typical MM. There were no significant differences in the proportions of patients received novel agents-based chemotherapy and ASCT between two groups, however, the estimated median PFS of macrofocal MM was significant superior to typical MM (41 vs 23 months, respectively; P= 0.001) (Figure 1), and the estimated median OS was also better in macrofocal MM than typical MM (not reached vs 61 months; P= 0.004) (Figure 2). Multivariate analysis showed that only the type of disease was the independent prognostic factor of both PFS and OS. In summary, Macrofocal MM is a particular subgroup of MM with multiple bone lesions and lower tumor burden, higher frequency of EMPs, and better survival than typical symptomatic MM. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Fan: The National Natural Science Foundation of China: Research Funding. Hou:Novartis: Membership on an entity's Board of Directors or advisory committees.

A Highly Heterogeneous Mutational Pattern in POEMS Syndrome

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 19-19
Author(s):  
Jia Chen ◽  
Xue-min Gao ◽  
Hao Zhao ◽  
Hao Cai ◽  
Lu Zhang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Light Chain ◽  
Plasma Cells ◽  
Poems Syndrome ◽  
Newly Diagnosed ◽  
Driver Genes ◽  
Target Region ◽  
Whole Exome ◽  
Bone Marrow Plasma

Background: POEMS syndrome is a rare plasma cell dyscrasia. Despite the presence of monoclonal protein, POEMS syndrome patients commonly have less than 5% monoclonal plasma cells in the bone marrow. Only one study has reported the genetic and transcriptional features of bone marrow plasma cells, and the underlying role of aberrant plasma cells is not well understood. Herein, in the current study, we aimed to characterize the genetic profile of bone marrow CD138-positive cells from Chinese patients with newly diagnosed POEMS syndrome. Methods: Forty-two patients with newly diagnosed POEMS syndrome based on the International Myeloma Working Group criteria at our institute were included in our study. Twenty milliliters of bone marrow aspirates was obtained and sorted by magnetic microbeads conjugated to monoclonal human anti-CD138 antibodies. The mutational features of these bone marrow plasma cells were analyzed using a two-step strategy. DNA of the bone marrow plasma cells from ten patients was first sequenced by whole exome sequencing to find significantly mutated genes and mutated driver genes, with paired peripheral blood mononuclear cells as a control. Bone marrow plasma cells of an additional thirty-two patients were then analyzed by target region sequencing to validate the mutations. Results: Whole exome sequencing of 10 newly diagnosed patients showed a total of 170 somatic mutations in exonic regions and splicing sites. Three significantly mutated genes-LILRB1 (10%), HEATR9 (20%), and FMNL2 (10%)-and eight mutated known driver genes (MYD88, NFKB2, CHD4, SH2B3, POLE, STAT3, CHD3, CUX1) were identified in five patients. The mutation spectrum of WES revealed C &gt; T/G &gt; A as the most common mutation type, while the mutation signature was not the same as known signatures reported in various cancer types. For significant pathway and gene ontology analysis, 69 genes with possibly pathogenic nonsynonymous mutations were selected. Mutated genes were enriched in pathways including "chromatin organization", "chromatin modifying enzymes", and "apoptosis", and terms such as "cellular anatomical entity", "regulatory region nucleic acid binding" and "centrosome" that are used to describe cellular structure construction. To evaluate the mutation prevalence of genes identified in WES, we performed target region sequencing of 77 candidate genes in 32 other patients. The candidate gene list consisted of significantly mutated genes and known driver genes identified in WES, recurrently mutated genes previously detected in POEMS syndrome, the VEGF gene, and genes of light-chain amyloidosis, multiple myeloma, hematopoietic disease or lymphoid neoplasm in the public databases. As a result, a total of 32 mutated genes were identified in 28 of 32 patients. Genes recurrently mutated in more than three patients included CUX1 (19%), DNAH5 (16%), USH2A (16%), KMT2D (16%), and RYR1 (12%). Driver genes of multiple myeloma (BIRC3, LRP1B, KDM6A, ATM) and eleven genes reported in light-chain amyloidosis were also identified in target region sequencing. Notably, VEGFA mutations were detected in one patient. Conclusions: Heterogeneous genomic profiles of bone marrow plasma cells in POEMS syndrome were revealed in our study. The mutational landscape of POEMS syndrome might share some similarity to that of other plasma cell diseases. Disclosures No relevant conflicts of interest to declare.

Multiple Myeloma

2017 ◽  
Author(s):  
Mark P. Purdue ◽  
Jonathan N. Hofmann ◽  
Elizabeth E. Brown ◽  
Celine M. Vachon
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Plasma Cells ◽  
Organ Damage ◽  
The United States ◽  
Diagnostic Techniques ◽  
Bone Lesions ◽  
Newly Diagnosed ◽  
Chain Molecules ◽  
Common Malignancy

Multiple myeloma (MM) is the most common malignancy arising from plasma cells, fully differentiated B lymphocytes that produce the immunoglobulin (Ig) heavy- and light-chain molecules comprising antibodies. MM is characterized by an overproduction of clonal plasma cells in the bone marrow and, in most cases, monoclonal secretion of IgG, IgA, or light-chain Ig. Symptoms of end organ damage (hypercalcemia [C], renal failure [R], anemia [A], or bone lesions [B]), herein referred to as CRAB features, were traditionally a necessary criterion for diagnosing MM; however, improvements in treatment and diagnostic techniques have led to updated diagnostic criteria, enabling intervention among patients before the onset of organ damage. Multiple myeloma is an important cause of lymphoid malignancy (LM) mortality in Western populations. In the United States in 2015, MM was estimated to account for approximately one in every five newly diagnosed LMs, and one in every three LM-related deaths.

Immunoglobulin Variable Light Chain Restriction, Cytokine Expression and Plasma Cell-Stromal Cell Interactions in POEMS Syndrome Patients

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2744-2744 ◽  
Author(s):  
Bharathi Aravamudan ◽  
Caili Tong ◽  
Martha Q. Lacy ◽  
Suzanne R. Hayman ◽  
Francis Buadi ◽  
...  
Keyword(s):  
Cell Lines ◽  
Plasma Cell ◽  
Light Chain ◽  
Stromal Cell ◽  
Plasma Cells ◽  
Variable Region ◽  
Poems Syndrome ◽  
Light Chains ◽  
Gene Usage ◽  
Variable Gene

Abstract POEMS syndrome is defined by the presence of peripheral neuropathy (P), organomegaly (O), endocrinopathy (E), monoclonal protein expression (M), and skin changes (S). In addition, patients also have sclerotic bone lesions, papilledema, extravascular volume overload, thrombocytosis, and restrictive lung disease/pulmonary hypertension. A striking but inexplicable feature of the clonal plasma cells in patients with POEMS is that they are virtually always lambda restricted. More surprising is that of the 81 functional immunoglobulin light-chain variable-region genes (IgVL) available in the plasma cell/B cell repertoire, among the 13 cases in which variable gene light chain usage has been reported, all have been either IgVL1-40 or IgVL1-44. The molecular mechanisms triggering the initiation and the progression of POEMS syndrome or the clonal expansion of plasma cells marking this condition remain unclear. We have analyzed the immunoglobulin heavy and light chains sequences in the plasma cells of POEMS patients at the Mayo Clinic Rochester. We found that in 8 out of the 9 patients tested, we could document heavy chain clonality in any given patient; however, no restriction of gene usage among patients was observed in the variable regions of these chains. In the case of light chains, in 14 out of 17 patients we could document not only clonality but also restriction of light chain variable gene usage to IgVL1-40 or IgVL1-44. Our goal is to understand the relevance of this restricted expression of light chain variable region, and its effect on the communication between plasma cells and the neighboring stromal cells that might provide more insight into the disease pathology. To this end, we are generating viral vector constructs that will harbor the germline or mutant versions of IgVλ1-40 and IgVλ1-44 genes and introduced into pre-established malignant plasma cell lines (i.e. myeloma cell lines). We will assay the effects of this over expression in terms of alterations in the expression of cytokines such as VEGF and TNF, and on plasma cell-stromal cell interaction (in a co-culture system). Results from these assays will be discussed.

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.

Multiple Myeloma Is Exceptional in Paediatrics: Report of One Case From 1200 Patients in a Single Institution.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4957-4957
Author(s):  
Sophie Auger ◽  
Genevieve Margueritte ◽  
Renaud Tichit ◽  
Basheer Khalil ◽  
Philippe Quittet ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Light Chain ◽  
Plasma Cells ◽  
Complete Response ◽  
Cell Labelling ◽  
Bone Lesions ◽  
Lambda Light Chain ◽  
Allogenic Stem Cell Transplantation ◽  
Monoclonal Component

Abstract Abstract 4957 Multiple myeloma (MM), a disease usually observed in elderly patients, is extremely rare below 30 years of age. We present a case of a MM in a 10-year-old boy who has been admitted in September 2007 to the paediatric unit from the university hospital in Montpellier, with a fracture of his left femoral bone after a rugby match. In his history, he was known to present a juvenile myelomonocytic leukaemia (JMML) when he was 4-month-old in December 1998. For this diagnosis, he has been treated with aracytine and hydroxyurea for 4 years and he got a complete response (CR) since July 2005. At admission, surprisingly the radiography showed two lytic bone lesions. At MRI, it was found proximal and distal medullar metadiaphyseal spreading associated to a fracture, with no clinical symptom. The histology of the two tissue biopsies showed large dystrophic plasma cells, MI 15 positive with no clear evidence of a monoclonality by using light chain immunostaining. The bone marrow biopsy showed an interstitial infiltrate of dystrophic plasma cells, with only lambda light chain expression. Five percent of dystrophic plasma cells were observed on bone marrow smears. The monoclonal component IgG Lamda was 3.56 G/dL. Free kappa and lambda light chain dosages were respectively 5.65 mg/L and 766 mg/L, with a kappa lambda ratio under 0.01. Proteinuria was 0.64 g/day, haemoglobin was 106 G/L, and Beta2 microglobulin was 2.6mg/L. There was no hypercalcaemia and serum albumin and creatinin clearance were normal. Plasma cell labelling index (PCLI) was 1.16 % in the bone marrow and 6.6 circulating plasma cells/μL were counted in peripheral blood. Unfortunately, gene expression profiling analysis failed due to the low number of cells. PET scan found multiple uptakes in femoral, vertebral costal and sternal bones. So, this boy presented a multiple myeloma with stage IIIA according to Durie Salmon staging and ISS (International staging system) I. He underwent nine cycles of bortezomib (1.3 mg/m2 D1, D4, D8, D11) and dexamethazone (40mg/D, D1 to D4) to reach a complete response. A myeloablative allogenic stem cell transplantation was performed from his sister the 11th of September 2008, with a regimen based on cyclophosphamide (60mg/Kg, D1, D2) and TBI 12Gy. The immunosuppressive regimen associated methotrexate (D1, D3, D6) and cyclosporine. The graft contained 4.14 ×108 MNC/kg, 4.19 106 CD34/Kg and 6.16 107 CD3/Kg. At Day 120, a full donor chimerism was obtained, with no GVHd, but the monoclonal component reappeared. He received only a single cycle of bortezomib and dexamethazone because of severe peripheral neuropathy and gastro-intestinal intolerance. A second CR has been obtained in June 2009. Minimal residual disease by flow cytometry will be soon performed in order to discuss donor lymphocyte infusions. We report a case of MM during the childhood that is extremely rare. Very few cases have been reported in the literature. In this particular case, the patient has been also treated for a JMML that may have a relationship with the MM. Unfortunately, no cytogenetic or DNA profiling has been performed. To our knowledge, it is the first time that such feature is reported. The overall survival (OS) reported by the Mayo clinic in a series of 10 children was 87 months that may suggests a better OS as compared to adults (Blade J, Kyle RA, Greipp PR. Multiple myeloma in patients younger than 30 years - Report of 10 cases and review of the literature. Arch Intern Med. 1996;156:1463-8). Disclosures No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document