Plasma Cell Proliferative Disorder Research Articles

P-100: Serum protein electrophoresis screening as a part of health-check program in Korea

<h3>Background</h3> Plasma cell myeloma and monoclonal gammopathy of undetermined significance (MGUS) have markedly increased in Korean population, especially in older age group. Serum protein electrophoresis (sPEP) with total protein level, can provide information about the overall distribution of serum protein and enables screening of plasma cell neoplasms. In this study, we analysed the results of sPEP screening in the hospital health-check program. <h3>Methods</h3> The sPEP was performed for 1405+2490 individuals, aged 23-83 years, who had visited in the health-check program of Pusan National University Yangsan Hospital for 10 years since 2010. The sPEP tests were performed using kit reagent (Protein 6 assay, Sebia, France) with automated multi-capillary electrophoresis system (Capillary 2, Sebia). According to the patterns of sPEP, we classified the whole data for 7 different groups. <h3>Results</h3> Among total of 3895 cases, 76.5% showed normal pattern including 164 cases which have only mildly decreased early alpha-2 fraction consisted with haptoglobin. Thirty cases (0.8%) showed acute inflammatory disease pattern with increase of alpha fractions. 11.0% of cases had mildly increased gamma fractions and 2.0% have more than 1.5 g/dL of the calculated quantity of gamma fraction. Three male patients were newly diagnosed as plasma cell myeloma and 36 cases were diagnosed as MGUS. The prevalence of plasma cell proliferative disorders in this study, 1.0% was lower than the previous report of Korea and similar that of large previous reports of large China population. <h3>Conclusion</h3> sPEP provides information about overall protein abnormalities in serum and is considered as the single most useful test for the detection of plasma cell neoplasm. As the prevalence of plasma cell proliferative disorders has been increasing, we suggest that sPEP may useful and cost-effective for screening in the health-check program.

Diffuse vertebral marrow changes at MRI: Multiple myeloma or normal?

Five MRI patterns of marrow involvement (diffuse, focal, combined diffuse and focal, variegated, and normal) are observed in patients with a marrow proliferative disorder including MM. The wide range of marrow involvement patterns in monoclonal plasma cell proliferative disorders mirrors that of their natural histories that can vary from indolent to rapidly lethal. MRI of the axial bone marrow contributes to stage these disorders, but it should not be obtained for disease detection and characterization because of its limited specificity and sensitivity. At MRI, diffuse benign hematopoietic marrow hyperplasia and marrow heterogeneities in elderly patients mimic the diffuse and variegated patterns observed in MM patients. Careful analysis of fat- and fluid-sensitive MR images and quantitative marrow assessment by using MRI and FDG-PET can contribute in differentiating these changes from those associated with neoplastic marrow infiltration, with some residual overlapping findings.

How to Recognize and Treat MGRS

AbstractMonoclonal gammopathy of renal significance (MGRS) represents a group of B-cell or plasma cell proliferative disorders that causes kidney injury via a monoclonal immunoglobulin they produce. The need for this new category of hematologic disorders came from a lack of renal definition in the current diagnostic criteria for plasma cell disorders, Waldenstrom macroglobulinemia and chronic lymphocytic leukemia (CLL). By definition, the hematologic conditions considered to be MGRS do not meet standard consensus criteria for malignancy or treatment, but they cannot be diagnosed as monoclonal gammopathy of undetermined significance (MGUS) because of the end-organ damage. Although generally not life threatening except in the cases of immunoglobulin (AIg) amyloidosis and monoclonal immunoglobulin deposition disease (MIDD) with extrarenal manifestations, the kidney diseases secondary to MGRS are progressive and are associated with significant morbidity. The MGUS designation is also problematic because treatment is not recommended for the MGUS stage of these hematologic disorders. The clone directed therapy required for preservation of kidney function would not be available when these conditions were classified as MGUS, IgM MGUS or low-grade CLL. MGRS clearly separates these conditions from MGUS and allows for the use of clone directed therapy without contradicting current diagnostic criteria and guidelines.

Poster: MM-359: Pattern-Based Identification of Normal and Aberrant Plasma Cell Compartment across a Spectrum of Plasma Cell Proliferative Disorders Using Multiparametric Flow Cytometry

Poster: MM-359: Pattern-Based Identification of Normal and Aberrant Plasma Cell Compartment across a Spectrum of Plasma Cell Proliferative Disorders Using Multiparametric Flow Cytometry

MM-359: Pattern-Based Identification of Normal and Aberrant Plasma Cell Compartment across a Spectrum of Plasma Cell Proliferative Disorders Using Multiparametric Flow Cytometry

Context The discriminative power of various antigens for delineating normal plasma cells (NPC) from aberrant plasma cells (APC) is variable; thus, understanding of the multiparametric flow cytometry (MFC)-based PC compartment is crucial for reliable PC characterization across various PC proliferative disorders (PCPD). Objective The expression profile and patterns of currently used immunophenotypic (IPT) markers were assessed for their ability to differentiate NPC from APC across the spectrum of PCPDs. Design This is a prospective analysis of patients diagnosed with PCPD (per standard IMWG criteria). Setting Tertiary care cancer center. Patients A total of 900 patients with diagnosis of PCPD were evaluated (MM: 724, PCL: 15, SMM: 12, MGUS: 42, Plasmacytoma: 54, Amyloidosis: 31, POEMS: 22). Interventions Bone marrow aspirate from cases (n=900) and controls (n=30) were processed per consensus guidelines from the Euro-flow protocol. An aberrant PC cluster was defined by >30 plasma cells with light chain expression beyond the range of control samples (0.26 to 3.08) and/or aberrant immunophenotypes (≥3). Main Outcomes Measures 1. Utility of cytoplasmic light chain restriction and 2. Most useful combination of markers to discriminate NPC from APC. Results All cases were segregated into three groups: cases with 1. only APC (n=181); 2. with both NPC and APC (n=574); or 3. only NPC (n=145). The PC compartment was solely characterized by light chain expression and IPT aberrancy in 36.22% (n=326) and 21.88% cases (n=197), respectively (p Conclusions Assessment of cytoplasmic light chain expression by MFC is essential for demonstrating clonality in cases with all normal or all aberrant PC. Pattern-based recognition is a useful parameter that identifies aberrant PC reliably in the majority of cases with co-existing NPC and APC, especially in setting of smaller clones of APC, which are likely to be missed by light chain assessment alone.

Extranodal Diffuse Gastrointestinal Mucosal Involvement in Castleman Variant of Poems Syndrome, Presenting as Chronic Diarrhea

POEMS syndrome is a rare paraneoplastic condition associated with polyneuropathy, organomegaly, monoclonal gammopathy, and endocrine and skin changes. It is a fatal disease and associated with compromised quality of life through volume overload, neuropathy, thromboembolic events, and weight loss. A diagnosis of POEMS syndrome is made with three of the major criteria, two of which must include polyneuropathy and monoclonal plasma cell proliferative disorder and at least one minor criterion Gastrointestinal (GI) involvement with initial predominant presentation as chronic diarrhea is extremely rare and rarely reported in the literature. Here, we highlight a case of Castleman disease variant of POEMS syndrome with predominant GI involvement and discuss plausible pathogenesis mechanism in relevance to the available literature.

Role of FDG PET in the staging of multiple myeloma.

18F-Fluorodeoxyglucose (FDG) PET has been used for staging of hematologic malignancies for years. In multiple myeloma, this imaging modality can be used in many different scenarios, including initial staging, evaluation of treatment response, and investigation of residual disease or early relapse. FDG PET-CT has excellent diagnostic performance, similar to other advanced imaging modalities such as whole-body CT and MRI, and it is particularly helpful for the assessment of extramedullary disease. It also offers important prognostic information on survival and risk of relapse, both at baseline and after therapy. This review will cover the main applications, advantages, and limitations of FDG PET-CT in multiple myeloma and related clonal plasma cell proliferative disorders, such as smoldering multiple myeloma and plasmacytoma.

POEMS SYNDROME WITH CASTLEMAN DISEASE - AN UNUSUAL PRESENTATION

Chronic Inflammatory Demyelinating Polyneuropathy(CIDP) is an acquired immune mediated disorder presenting as symmetric proximal and distal sensory motor polyneuropathy. It is treatable with immunosuppressant. CIDP may be associated with HIV-1 infection, SLE, para neoplastic disorders and Paraproteinemias. Paraproteinemias is abnormal monoclonal antibody or light chain in blood secondary to plasma cell disorder like multiple myeloma, Waldenstrom macroglobulinemia, monoclonal gammopathy of undetermined significance (MUGS), POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, monoclonal plasma cell proliferative disorder and Skin Changes) syndrome and Castleman disease with or without POEMS syndrome. These account for approximately 10% of CIDP. Diagnosing Paraproteinemic neuropathy is necessary to prevent delay in diagnosis, start appropriate treatment and estimate prognosis of the condition. POEMS syndrome is due to clonal proliferation of plasma cells. Castleman disease (CD), also known as angiofollicular or giant lymph node hyperplasia, is a rare non-neoplastic lymphoproliferative disorder . We present a Case report of relatively young male with right parotid swelling with chronic sensorimotor quadriparesis with wasting, with no predominant neuropathic pain and cranial nerve involvement. On Nerve Conduction Studies it was found to have severe sensori-motor neuropathy which was not associated with pain, an unlikely feature of either CIDP or Castleman disease; on further evaluation was found to have POEMS syndrome. Thus high index of suspicion is necessary to diagnose this condition. This case report emphasizes the fact that patients with Castleman disease-POEMS Syndrome may present at younger age than usual with short duration of illness, with severe sensorimotor neuropathy which may not be associated with pain. High index of suspicion and appropriate investigations may lead to early diagnosis and prompt treatment.

MM-081: Poems Syndrome: An Update from a Tertiary Care Institute in India from 1993-2020

Abstract: POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes) is a rare entity characterised predominantly by peripheral neuropathy and monoclonal plasmacytosis. Herein, we report a retrospective analysis of 72 patients with diagnosis of POEMS syndrome from 1993-2020 with primary objective of OS and secondary objective of haematological response rates. The median OS of the study cohort was 52.5 months. Eighteen patients had undergone ASCT. Introduction: POEMS is a plasma cell proliferative disorder characterised by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes. Lambda restriction is the predominant type. Literature provides insights through retrospective analysis of cohorts from across the globe; however, there is paucity of Indian data. Herein, we present retrospective data of 72 cases. Patients and methods: It was a retrospective study. Case files of all patients diagnosed with POEMS syndrome at a tertiary care centre from 1993-2020 were reviewed. The study included POEMS syndrome patients aged >18 years, who had received at least two cycles of therapy, and response evaluation had been done. The primary outcome of the study was overall survival (OS). Study cohort was characterized by descriptive statistics. Results: Seventy-two patients were included in the study. The median age of the study cohort was 45 years (range: 23-70years) with a male to female ratio of 3.8:1. Majority (68/72) of the patients reported peripheral neuropathy during initial presentation. Thirty patients (43%) had ECOG performance status of 4. The mean SPEP recorded was 0.7 gm/dl. There was a paradigm shift in treatment regimen: melphalan/prednisolone was the most commonly used regimen before 2012. However, bortezomib/dexamethasone and lenalidomide/dexamethasone are the commonly used regimens in the recent years. Hematologic response was recorded for 67 patients, of which 38 (56%) had complete response, 16 (23%) had partial response and 12 (17%) had stable disease. The median modified Rankin score improved from a baseline score of 4 to 2 (range: 1-5). Eighteen patients underwent ASCT. Mean melphalan dose used was 140 mg/m2. All 18 patients had a complete haematologic response along with clinical improvement. Conclusion: This retrospective study sheds light about the paradigm shift in management of POEMS syndrome in low-income countries like India. The outcomes have significantly improved with the usage of proteasome inhibitors and immunomodulators along with consolidation with ASCT.

Clinical and Pathological Characteristics of Related-Renal Damage in Patients with POEMS Syndrome

To investigated the clinical and pathological characteristics of related-renal damage in patients with POEMS syndrome. Five patients diagnosed as POEMS syndrome in our hospital were selected. Their clinical manifestation, pathological characteristics of kidney and laboratory examination were analyzed retrospectively. Among the 5 patients, three males and two females with a median age of 50 years old. The mean interval before diagnosis was 13.0±7.2 months. All the patients showed neuropathy, endocrinopathy, monoclonal plasma cell-proliferative disorder, skin changes and extravascular volume overload, in which 4 patients showed organomegaly. Proteinuria was found in 5 patients, and microhematuria was found in 4 patients. Moreover, 4 patients showed an elevated blood urea, while 2 patients showed creatinine elevation. 1 patient at chronic kidney disease (CKD)-G1 stage, 2 patients at CKD-G2 stage, and 1 patient at CKD-G3b stage, moreover, 1 patient at CKD-G5 stage. Endothelial injury and mesangial lesion were the main characteristics of renal pathology. 3 patients were pathologically diagnosed as thrombotic microangiopathy kidney damage, while 2 patients as light chain amyloidosis. POEMS syndrome is a multi-systemic disease with complex clinical manifestations. 5 patients had different degrees of renal insufficiency. Endothelial injury and mesangial lesion are the main features of renal pathology.

SAT-LB117 POEMS Syndrome: Rare Presentation of New Onset Diabetes Mellitus

Background: POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes) is characterized by the presence of a monoclonal plasma cell disorder, peripheral neuropathy, and one or more of the following features: osteosclerotic myeloma, Castleman disease, increased levels of serum vascular endothelial growth factor (VEGF), organomegaly, endocrinopathy, edema, typical skin changes, and papilledema. Clinical Case: 45 year old male with no chronic medical issues presented initially to the orthopedic clinic with right hip pain, pelvic MRI showed a right iliac crest lesion. CT Guided biopsy was done and showed plasmacytoma. SPEP showed elevated IgG lambda level in the gamma zone. In the meantime he was complaining of ascending numbness and weakness in hands and feet and he progressively became wheelchair bound. During his treatment and follow ups with Hematology/Oncology he was noted to have elevated blood sugars in the 500s. Hemoglobin A1C was elevated at 9.5 which confirmed the diagnosis of new onset diabetes. He was also noted to have splenomegaly which confirmed the diagnosis of POEMS syndrome. He was started on insulin and he managed to achieve good diabetes control with insulin and dietary changes. He is currently status post stem cell transplantation with a good response and the weakness and polyneuropathy improved with PT and OT. POEMS syndrome has major and minor criteria for diagnosis, mandatory major criteria includes polyneuropathy, monoclonal plasma cell proliferative disorder (almost always lambda). Additional major criteria are sclerotic bone disease, castleman disease, elevated VEGF. Minor criteria are organomegaly, extravascular volume load, endocrinopathy, and skin changes. In order to diagnose the syndrome, mandatory major criteria, and one major and one minor criteria need to be clinically present. Endocrinopathy includes the adrenal, pituitary, thyroid, gonadal, parathyroid, and pancreatic glands. Two-thirds of patients had at least one endocrine abnormality at presentation. Endocrine abnormalities can also develop later, during the course of the disease. Hypogonadism is the most common endocrine abnormality. Elevated levels of follicle stimulating hormone in the absence of primary hypogonadism levels have been reported, hence history and physical examination is crucial to detect the development of endocrinopathies in POEMS syndrome. There are no current guidelines or recommendations about the frequency of screening for endocrinopathies but it is suggested to obtain a baseline of thyroid function test, pituitary, gonadal, and adrenal axis. In addition to baseline parathyroid hormone level, close monitoring of calcium and blood glucose levels once the diagnosis is confirmed in patients with suggestive symptoms. Conclusion: POEMS syndrome is a rare condition that involves multiple endocrine organs, currently there are no guidelines or recommendations to obtain baseline endocrine labs once the diagnosis is confirmed, but it might be appropriate if there is a high clinical suspicion.

Limitations of Free Light Chain Assays caused by the Matrix Effect.

Serum free light chain (FLC) assays are used clinically to measure the concentration of κ and λ FLC in patients with suspected or diagnosed plasma cell proliferative disorders. Previous studies have demonstrated a loss of linearity in low concentration ranges of these assays. We hypothesized that this result could be caused by a matrix effect. Recovery studies were performed for κ and λ FLC in both serum and saline using the Freelite assay (Binding Site) on a Cobas c502 system (Roche). Samples were analyzed either at the recommended dilution or undiluted. Follow-up studies were performed in varying matrices ranging from 0% to 100% saline. Retrospective patient data were analyzed to assess the impact on reported κ FLC, λ FLC, and κ/λ ratio. FLC in a serum matrix demonstrated underrecovery relative to samples diluted in saline for both κ and λ FLC. Of 255 patient samples with λ FLC measured undiluted (λ FLC <6.0 mg/L), an unexpected gap was observed in patient results between 2.0 and 6.0 mg/L. In addition, 23 patients measured serially with λ FLC between 2.0 and 6.0 mg/L demonstrated dramatic changes in κ/λ ratio, with no changes in κ FLC, likely because of the matrix effect. The κ and λ Freelite assays exhibit a matrix effect when samples are tested undiluted, which has the potential to affect the κ/λ ratio. Consequently, our laboratory has stopped reporting λ FLC <6.0 mg/L.

Multiple Myeloma Bone Marrow Mesenchymal Stromal Cells Inhibit CD8+ T Cell Function in a Process that May Implicate Fibroblast Activation Protein α.

Multiple myeloma (MM) is a malignant plasma cell proliferative disorder with limited immunotherapy treatment because of T cell dysfunction. To investigate the immunomodulatory function of bone marrow mesenchymal stromal cells (MM-BMSCs) on CD8+ T cells. Proliferation and cytotoxicity were detected by cell counting kit-8 assay. Cell cycle was detected by flow cytometry, and p16 expression was detected by PCR. The expression of fibroblast activation protein α (FAPα) was evaluated by immunohistochemistry. Co-culture of CD8+ T cells with MM-BMSCs decreased the cell survival rate and increased the killing rate (p=0.03, p=0.001, respectively), the percentage of cells in G0/G1 phase and p16 expression (p<0.001). FAPα was mainly in the mesenchymal matrix of the MM microenvironment and elevated in MM derived bone marrow compared to healthy donors (p<0.001). The FAPα inhibitor PT-100, increased survival and the killing rate (p<0.001, p=0.043, respectively), and decreased the percentage of cells in G0/G1 phase and p16 expression (p=0.024, p=0.004, respectively). Therefore, MM-BMSCs inhibit the proliferation and cytotoxicity of CD8+ T cells, significantly block the cell cycle and increase p16 expression in co-cultured CD8+ T cells in a cell-cell contact-dependent manner.

The CCND1 870G Risk Allele Is Enriched in African Individuals with Plasma Cell Dyscrasias

Purpose: Multiple myeloma (MM) is a plasma cell (PC) malignancy with an increasing incidence in the US. Epidemiological studies demonstrate a 2-3 fold higher incidence of the pre-malignant monoclonal gammopathy of undetermined significance (MGUS) and MM with a ~4-year younger age of onset among African Americans (AA) compared to European Americans (EAs) (Fonseca, Leukemia, 2017). With equal access to care, AAs have better overall survival compared to EAs (Waxman, Blood, 2010). This disparity may be explained by ancestral-associated genetic predisposition of AAs to development of monoclonal gammopathies and to specific acquired, cytogenetically-defined subtypes. Using calculated genetic ancestry data, we have previously identified a higher prevalence of IgH translocations t(11;14), t(14;16) and t(14;20) in individuals with &gt;80% African ancestry (Baughn, BCJ, 2018). Since SNP rs9344 encoding the CCND1 870G&gt;A polymorphism has been reported in association with increased risk of t(11;14) (Weinhold, Nature Genetics, 2013), we investigated whether rs9344 correlates with African ancestry and with t(11;14) in our cohort of patients with plasma cell dyscrasias. Methods: We studied 898 patients with monoclonal gammopathies who had undergone uniform testing to identify MM-specific cytogenetic abnormalities. DNA from bone marrow samples was genotyped on the Precision Medicine Research Array and biogeographical ancestry was assessed using the Geographic Population Structure Origins tool (Elhaik, Nat Commun, 2014). Plasma cell proliferative disorder FISH of immunoglobulin (cIg)-stained positive plasma cells was performed as described (Baughn, BCJ, 2018). Individuals were divided into three ancestral groups: 1. EAs (&lt;0.1% African ancestry and &lt;30% Asian ancestry); 2. AAs (&gt; 80% African ancestry); and 3. Other. Chi-squared test was used to determine the overall comparison between the 3 ancestral groups and also between ancestral groups 1 vs 2, and 2 vs 3 using pairwise comparison. All tests were two-sided with alpha level set at 0.05 for overall statistical significance. Pairwise comparison was considered statistically significant when p&lt;0.025 based on Bonferroni method for multiple comparisons. Results: We identify increased risk of development of either a t(11;14), t(14;16) or t(14;20) in AAs (48.8%) compared to EAs (33.6%) (p-value=0.0051). To explore the genetic basis of increased t(11;14) specifically (37.4% AAs vs. 27.3% p-value=0.049), we evaluated the frequency of the G risk allele of rs9344 in relation to African ancestry. The frequency of the G risk allele was higher in AAs (0.81) compared to EAs (0.59) (p-value &lt;0.0001) and also higher in t(11;14) cases (0.73) compared to non-t(11;14) controls (0.58) (p-value &lt;0.0001). A multivariate model identified only rs9344 as significantly associated with t(11;14) after adjusting for age, gender and race group suggesting that it plays a role in the development of t(11;14) (p-value &lt;0.001 for GG, p-value=0.005 for AG). To test if these results are replicable, we studied the MMRF CoMMpass cohort. This cohort includes individuals with newly diagnosed MM along with self-report race information and translocation data from long insert whole genome sequencing. Although t(11;14) was not enriched in self-reported Black individuals from this cohort (17.5% Black vs. 20.4% White, p-value=0.47), there was association between the rs9344 and self-reported Black race (p-value &lt;0.0001) and with the presence of t(11;14) when the t(11;14) was analyzed by long insert whole genome sequencing (p-value=0.0001). Conclusions: To our knowledge, this study includes the largest group of African individuals with an abnormal plasma cell clone along with uniformly collected FISH, genotyping and ancestry data. We have identified in this diverse population the association of the CCND1 870G&gt;A polymorphism (rs9344) with African ancestry and with t(11;14) suggesting that it plays a role in the development of t(11;14) plasma cell dyscrasias. Disclosures Elhaik: DNA Diagnostics Center: Consultancy. Baird:DNA Diagnostics Center: Employment. Cerhan:Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; NanoString: Research Funding. Bergsagel:Celgene: Consultancy; Ionis Pharmaceuticals: Consultancy; Janssen Pharmaceuticals: Consultancy. Dispenzieri:Alnylam: Research Funding; Akcea: Consultancy; Intellia: Consultancy; Janssen: Consultancy; Pfizer: Research Funding; Takeda: Research Funding; Celgene: Research Funding. Kumar:Janssen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Takeda: Research Funding.

Treatment of Primary Plasma Cell Leukemia with Carfilzomib and Lenalidomide-Based Therapy: Results of the First Interim Analysis of the Phase 2 EMN12/HOVON129 Study

Treatment of Primary Plasma Cell Leukemia with Carfilzomib and Lenalidomide-Based Therapy: Results of the First Interim Analysis of the Phase 2 EMN12/HOVON129 Study

POEMS Syndrome: A Review of Our Patient Population

Introduction The "POEMS" Syndrome, defined by its hallmark features of polyneuropathy, organomagaly, endocrinopathy, monoclonal plasma cell proliferative disorder, and skin changes has long been an enigma in terms of diagnosis and treatment. In recent years, clinicians and researchers have attempted to clarify diagnostic criteria. It is known that "VEGF," vascular endothelial growth factor, plays a large role in the pathophysiology of this disease.1Most recently, Angela Dispenzieri proposed a set of diagnostic criteria, which were published in the American Journal of Hematology.2We applied this suggested diagnostic criteria retrospectively to patients in our institution who carried a diagnosis of POEMS Syndrome. Additionally, we recorded the VEGF of these patients and their outcomes. Methods The.medical record was queried for patients with POEMS diagnosed in the last 5 years. A total of 16 patients met criteria. The primary outcome was to determine the percentage of patients who met the criteria proposed by Dispenzieri. A secondary outcome was to determine, in those patients who did not meet the criteria, the reason that they were not met. Another secondary outcome was to determine the percentage of patients who were alive or deceased. The criteria proposed by Dispenzieri (Table 1) were applied to each patient to assess whether they were met. If the diagnostic criteria were not met, the reason as to why they were not was recorded. Each patient outcome of "alive," "deceased," or "unknown" was recorded. Results Of the 16 patients analyzed, 14 (88%) had enough information to be included. Of these 14 patients, nine (64%) met the criteria proposed by Dispenzieri. Of the five patients that did not meet the criteria, four (80%) did not meet them due to the lack of a presence of a major criteria. One patient of the five (20%) that did not meet the criteria did not have the mandatory finding of polyneuropathy. VEGF levels ranged from 26-9504pg/mL, with an average of 1190pg/mL. The range for the patients who met the diagnostic criteria proposed by Dispenzieri was 1755pg/mL. Of our total patient population analyzed, 10 out of 14 patients (72%) were alive at time of retrospective review, including six out of nine (66%) that met the diagnostic criteria. Two out of 14 patients (14%) were found on review to be deceased, including one out of the nine (11%) that met the diagnostic criteria. Two out of 14 patients (14%) were determined to be "unknown" if alive or deceased, both of whom met the diagnostic criteria. Discussion Patients with POEMS syndrome often experience a delay in diagnosis due to the rarity of the disease as well as a lack of high index of suspicion for the condition in many cases. Additionally, POEMS syndrome is often mislabeled as another neuropathic condition. Efforts have been made to establish a standard criteria for diagnosis. We applied the criteria proposed by Dispenzieri this year in the American Journal of Hematology. In our retrospective study, we found that that 64% of our patients who carried a diagnosis of POEMS syndrome met the criteria for POEMS diagnosis using these proposed criteria. We found that the most common reason for not meeting the criteria in our patient population was the lack of a major criterion. Major criteria (Table 1) include Castleman Disease, sclerotic bone lesions and VEGF elevation, one of which must be met to receive a diagnosis of POEMS syndrome. Additionally, one of our patients did not meet the criteria due to the lack of the mandatory finding of polyneuropathy. The average VEGF levels in our patients were 1190pg/mL, but were higher at 1755pg/mL in the cohort who met the diagnostic criteria. 72% of our total patients were alive at time of review, including 66% of the patients who met the diagnostic criteria. We conclude that the criteria proposed by Dispenzieri provide a concise guideline to identify patients with POEMS syndrome. These criteria are simple to apply, and would potentially help to increase the index of suspicion and earlier diagnosis of patients with POEMS syndrome. This would be expected to lead to earlier initiation of therapy. Additionally, this analysis supports previous studies that show that VEGF levels are correlated with disease activity and that overall prognosis for patients with POEMS syndrome is favorable. Disclosures No relevant conflicts of interest to declare.

Clinical heterogeneity and diagnostic challenges in poems syndrome and variant: A case series from Southeast Asia

POEMS syndrome is a rare paraneoplastic disorder associated with an underlying plasma cell dyscrasia presenting with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes. Diagnosis can be challenging especially among those with atypical presentation. The diagnosis of POEMS was based on published criteria. We reviewed the clinical, laboratory and imaging characteristics of 4 patients in Kuala Lumpur Hospital from year 2012-2018. Clinical spectrum and disease variant were determined. Three had POEMS syndrome and 1 had Castleman disease variant. Mean age of onset was 40 (SD 11.5), with male predominant (75%). All had refractory chronic demyelinating polyneuropathy to standard CIDP treatment as common presentation. Paraprotein IgA lambda from monoclonal plasma cell-proliferative disorder were found in 2 patients. Sclerotic bone lesion (100%) was the most common major criteria fulfilled. Organomegaly (75%) was the most common minor criteria fulfilled, followed by extravascular volume overload (oedema, 50%, pleural effusion 25%), papilledema (25%), thrombocytosis (25%) and acrocyanosis (25%). Finger clubbing was seen in 50% of the patients. The only surviving patient with Castleman variant had improvement of neuropathy following IV rituximab and was in remission following autologous bone marrow transplant. Rapidly progressive disease was observed in one patient, with clinical deterioration to completely bedbound within a year. In conclusion, POEMS syndrome is a rare disorder and should be suspected in atypical cases of CIDP particularly when there is treatment resistance. Extensive investigation is often needed to meet diagnostic criteria for POEMS and rapid referral to haematology team for definite treatment is warranted.

Whole-Body Imaging of Multiple Myeloma: Diagnostic Criteria.

Multiple myeloma (MM) is a clonal plasma cell proliferative disorder characterized by primary infiltration of bone marrow and excessive production of abnormal immunoglobulin. This disease is the second most common hematologic malignancy (after lymphoma), and its spectrum of characteristic features are widely known by the acronym CRAB (hypercalcemia, renal impairment, anemia, and bone lesions). Traditionally, the diagnosis and treatment of MM have been triggered by clear end-organ damage. However, owing to recently introduced treatment options that can extend patient survival and the increasing recognition of biomarkers that can be used to identify patients at high risk of progression to active disease, the diagnostic criteria have been revised. Bone disease is one of the most prominent features of MM, and imaging has an important role in diagnosis and follow-up, with each whole-body imaging modality having different indications in distinct disease situations. Skeletal survey has been the standard imaging procedure used during the past decade, but it should no longer be used unless it is the only option. Whole-body low-dose CT is a reasonable and cost-effective initial imaging approach. Whole-body MRI is the most sensitive technique for detecting bone involvement and assessing painful complications. PET/CT is the best tool for evaluating treatment response. The importance of radiologists has increased in this scenario. Therefore, to properly assist hematologists and improve the care of patients with MM, it is essential that radiologists know the updated diagnostic criteria for MM, indications for and limitations of each imaging option, and recommendations for follow-up. Online supplemental material is available for this article. ©RSNA, 2019.

PS1417 TREATMENT OUTCOMES OF PATIENTS WITH MONOCLONAL GAMMOPATHY OF CLINICAL SIGNIFICANCE

Background:Monoclonal gammopathy of clinical significance(MGCS) is defined by the relationship between a small dangerous B‐cell clone and severe organ damage due to the toxicity of the monoclonal immunoglobulin(MIg) or its fragment and their deposition in different organs. The kidney is one of the main targets of the MGCS which may occur in all B cell or plasma cell proliferative disorders that produce a nephrotoxic monoclonal immunoglobulin(MIg). The treatment strategy is based on chemotherapy adapted to the nature of the underlying clone. The rapid suppression of the secretion of nephrotoxic MIg has been shown to impact patient survival and increase the patients’ quality of life.Aims:In our study we evaluated the impact of kidney damage on patient's survival.Methods:Our cohort included 151 consecutive patients with MGCS‐associated organ damage since 2004 to 2019. The most common involved organs were kidney, heart, liver, nerves system and gastrointestinal tract. The diagnosis in most cases was established by organ biopsy, serum and urine protein immunofixation, analyses of serum free light chains, bone marrow aspiration and biopsy with flow cytometry. MGCS‐ associated renal lesions were: AL amyloidosis 88% (n = 126), monoclonal immunoglobulin deposition disease (MIDD) 5,6%(n = 8),proliferative glomerulonephritis with monoclonal Ig deposits and C3 glomerulopathy 4,2%(n = 6), trombotic microangiopathy 1,4 %(n = 2) and cryoglobulinemic glomerulonephritis type 1 0,7%(n = 1).Results:Median age of the patients was 62 years (38–79). Median follow‐up was 24,2 months (1–117,5 months). Renal involvement(RI) was noted in 92% of patients (n = 142). 21,8% (n = 31) of these patients required dialysis. The median time to dialysis was 2 months (1–70months).71,1% (101 patients) had nephrotic syndrome at the time of diagnosis. Prognostic criteria for RI were assessable in 117 patients. These criteria included a reduction in eGFR&lt;50 ml/min/1.73m2 and proteinuria (PU)&gt;5 g/24 hours. In our cohort, patients with stage I were 16,1% (n = 21), stage II – 46,4% (n = 66), stage III‐30,2%(n = 43). The 5‐years rate of progression to dialysis was significantly higher in patients with stage III (46,5% vs 9,1% vs 0 %, p &lt; 0,0001, for stage III, II, I,respectively) and in patients with nephrotic syndrome (23,8% vs 3,6%,p = 0,0026,for nephrotic syndrome and asymptomatic proteinuria). Stage III of RI was independent predictor of poor overall survival (OS), but did not impact on renal progression‐free survival (PFS). 5‐years overall survival was: 61,9%, 71,2 and 51,2% (p = 0.0052), 5‐years renal PFS was 90%, 67,7% and 60 % (p = 0,35) for I,II,III renal stage,respectively. Treatments included chemotherapy in 73% (n = 106) and stem cell transplantation 12,5% (n = 18). The median time from treatment initiation to first and best renal response was 7 month (1–68months) and 13,5month (1–69months) respectively. We assessed renal response in 61 patients. In our group of patients, the complete renal response (CR) was achieved in 4,9% cases (n = 3), very good partial response (VGPR) – 42,6% (n = 26), partial response – 32,7% (n = 20). 19,6% (n = 12) have not achieved renal response (NR). OS in patients with CR was 100%, VGPR–88,4%, PR–95%, NR–58,3% (p = 0,0031).5‐years renal PFS in patients who achieved renal response was 70,9%.Summary/Conclusion:Renal involvement and the depth of the response is a prognostically significant factor and a predictor of overall survival and renal survival of patients with MGCS. There is a need for early diagnosis of renal involvement, in order to identify and treat these patients before irreversible organ damage occurs.

A novel biomarkers score for the screening and management of patients with plasma cell proliferative disorders

To identify whether whole-tumour histogram analysis of pharmacokinetic parameters from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) could predict T-stage and regional lymph node metastasis (LNM) of resectable oesophageal squamous cell carcinoma (SCC).Forty-two consecutive patients with confirmed oesophageal SCC underwent thoracic DCE-MRI. Histogram metrics (median, mean, standard deviation [SD], skewness, kurtosis and entropy) of whole-tumour pharmacokinetic parameters including endothelial transfer constant (Ktrans), reflux rate (Kep) and fractional extravascular extracellular space volume (Ve) were generated by the Omni-Kinetics software. Histogram datasets were interpreted using the Mann-Whitney U test and receiver operating characteristic (ROC) statistical analyses.The Mann-Whitney U tests revealed that the median, mean and SD of Ktrans, the SD and entropy of Kep, and the median, mean and entropy of Ve of T1-2 stage oesophageal SCC were lower when compared with T3 stage (all Ps < 0.05); and the ROC analysis showed that the entropy of Ve could reliably distinguish T1-2 stage from T3 stage with an area under ROC (AUC) of 0.773. The Mann-Whitney U tests illustrated that the entropy of Ktrans, and the median, mean, SD and entropy of Kep were higher while the skewness of Kep was lower in tumours with LNM than without LNM (all Ps < 0.05); and the ROC analysis demonstrated that the SD of Kep could best identify tumours with LNM with an AUC of 0.702.Whole-tumour histogram analysis of pharmacokinetic parameters of oesophageal SCC on DCE-MRI could be used to predict T-stage and regional LNM.