POEMS Syndrome Research Articles

Top 10 Clinical Pearls in Paraproteinemic Neuropathies.

Paraproteinemic neuropathies represent an important subset of peripheral neuropathies. Once identified, further evaluation into the paraproteinemic subtype, clinical exam pattern, and electrodiagnostic phenotype helps clarify if the paraproteinemia is coincidental or causal of the neuropathy, as not all paraproteinemias cause neuropathy. Of all paraproteinemias, immunoglobulin M (IgM)-associated peripheral neuropathy, or IgM neuropathy, is of particular importance as half of IgM neuropathies also harbor anti-myelin-associated glycoprotein antibodies, which produce a characteristic demyelinating pattern on nerve conduction testing. Immunoglobulin G and immunoglobulin A paraproteinemias are less strongly associated with peripheral neuropathy, except in the setting of multiple myeloma or osteosclerotic myeloma (POEMS syndrome), which have characteristic systemic features. In multiple myeloma, chemotherapy is more likely to result in neuropathy than the myeloma itself. Finally, the presence of systemic features (e.g., cardiomyopathy, nephropathy, recurrent carpal tunnel syndrome, and autonomic insufficiency) should raise concern for hereditary or acquired light (AL) chain amyloidosis. AL amyloidosis can occur in the setting of any light or heavy chain paraproteinemia. Central to the proper evaluation of paraproteinemic neuropathy is electrodiagnostic testing, which helps delineate axonal versus demyelinating paraproteinemic neuropathy, the latter often misdiagnosed as chronic inflammatory demyelinating polyradiculoneuropathy.

Efficacy of nebulized GM-CSF inhalation in preventing oral mucositis in patients undergoing hematopoietic stem cell transplantation: A retrospective study

ObjectiveTo study the efficacy of oxygen atomization inhalation of granulocyte-macrophage colony-stimulating factor (GM-CSF) for preventing oral mucositis in patients following hematopoietic stem cell transplantation. MethodsData from patients who received hematopoietic stem cell transplantation and were treated with GM-CSF for the prevention/treatment of oral mucositis in our hospital from June 2021 to June 2023 were collected. The enrolled patients were divided into an observation group and a control group according to the use of GM-CSF. The WHO Mucositis Scale Assessment Criteria were utilized to evaluate the characteristics of patients with oral mucositis (OM) from the beginning of the pretreatment period until they were discharged from the hospital. The general data, preconditioning protocol, transplantation method, overall grade and duration of oral mucositis, pain score, nutritional score and number of days of parenteral nutrition use, oral mucosal infection status and antibiotic use intensity, the granulocyte and megakaryocyte reconstruction time, and adverse reaction reports of the patients were collected and summarized through the medical records system. ResultsA total of 143 patients were included in this study, including 75 patients in the observation group. In the observation group, there were 36 males and 39 females aged 22–67 years. There were 45 patients who received autologous transplantation and 30 patients who received allogeneic transplantation. In terms of the disease distribution, there were 33 cases of leukemia, 24 cases of lymphoma, 11 cases of multiple myeloma, and 8 other cases (3 cases of aplastic anemia, 2 cases of myelodysplastic syndrome, 2 cases of myelofibrosis, 1 case of POEMS syndrome). There were 68 patients in the control group, including 33 males and 35 females; the control group patients were aged 25–74years. Forty-one patients received autologous transplantation, and 27 patients received allogeneic transplantation. The disease distribution included 29 cases of leukemia, 17 cases of lymphoma, 12 cases of multiple myeloma, and 7 other cases (3 cases of aplastic anemia, 2 cases of myelodysplastic syndrome, 1 case of myelofibrosis, 1 case of POEMS syndrome). There were no significant differences between the two groups concerning age, sex, disease distribution or the transplantation method (P > 0.05). In the observation group, 13 cases did not develop oral mucositis, and 32 cases developed oral mucositis (16 cases of Grade I, 14 cases of Grade II, 2 cases of Grade III, and 0 cases of Grade IV). In the control group, there were 5 cases without mucositis and 36 cases with oral mucositis (6 cases of Grade Ⅰ, 16 cases of Grade Ⅱ, 8 cases of Grade Ⅲ, and 6 cases of Grade Ⅳ), the difference was statistically significant (P < 0.05). The pain score and duration of mucositis in the observation group were significantly lower than those in the control group (P < 0.05). In addition, the oral infection rate, antibiotic use intensity, nutritional score, per capita number of days of parenteral nutrition use and hematopoietic reconstruction time in the observation group were significantly lower than those in the control group (P < 0.05). In the observation group, 8 patients did not develop oral mucositis, and 22 patients developed oral mucositis (13 cases of Grade I, 7 cases of Grade II, 1 case of Grade III, and 1 case of Grade IV). In the control group, 1 case did not develop mucositis, and 26 cases developed oral mucositis (3 cases of Grade Ⅰ, 10 cases of Grade Ⅱ, 9 cases of Grade Ⅲ, and 4 cases of Grade Ⅳ). The difference was statistically significant (P < 0.05). The pain score and duration of mucositis in the observation group were significantly lower than those in the control group (P < 0.05). In addition, the oral mucosal infection rate, antibiotic use intensity, nutritional score, per capita number of days of parenteral nutrition use and hematopoietic reconstruction time in the observation group were significantly lower than those in the control group (P < 0.05). No adverse reactions were reported in either group. ConclusionIn both autologous transplantation and allogeneic transplantation patients, GM-CSF atomized inhalation can improve the prevention and treatment of oral mucositis in stem cell transplantation patients, reduce the incidence of oral infection, reduce the intensity of antibiotic use and the number of days of parenteral nutrition use, and thus promote the process of hematopoietic reconstruction.

A case of paraprotein-negative POEMS syndrome: Case report and literature review.

POEMS syndrome is a rare monoclonal plasma cell disease. The diagnosis of POEMS requires polyradiculoneuropathy and monoclonal plasma proliferating as 2 mandatory criteria, at least 1 of the major criteria (Castleman disease, elevated vascular endothelial growth factor level, and sclerotic bone lesion), and at least 1 of the minor criteria (organomegaly, extravascular volume overload, endocrinopathy, skin changes, papilledema, and thrombocytosis/polycythemia). This multisystem disorder is of high heterogeneity, and few variants of POEMS with no evidence of monoclonal gammopathy have been described, which further complicates the diagnosis in clinical practice. Now, we report a case of paraprotein-negative POEMS syndrome. A 45-year-old woman complained of lower extremity edema, shortness of breath, abdominal distension, and lymphadenopathy for few years. Finally, she was diagnosed with paraprotein-negative POEMS syndrome. With the lenalidomide-based regimen, the symptoms were all relieved. Paraprotein-negative POEMS syndrome. Lenalidomide-based regimen and some supportive therapy. All symptoms were relieved after 1 year of treatment. Physicians should pay more attention to the POEMS syndrome, especially the POEMS syndrome variants, which are absence of paraprotein; probably, these variants are just "on the way" to classic POEMS syndrome antiplasma cell therapy, which remains the treatment of choice.

Kidney thrombotic microangiopathy with concurrent monoclonal gammopathy.

The concurrence of monoclonal gammopathy and TMA was suggested in a few studies. However, the complement activation was not fully studied in previous cases. In this study, we aimed to determine the complement activation in these group of patients and the association with clinical, laboratory and pathological features. Between 2007 to 2020, 20 patients with biopsy-proven renal TMA patients and monoclonal gammopathy in Peking University First Hospital were included in the study. Complement activation was tested by enzyme-linked immunosorbent assay. Associations with clinical features, pathological data, and laboratory findings were further investigated. Among renal TMA patients beyond 50 years of age, the prevalence of monoclonal gammopathy was 16.51% (18/109) which is almost 4-fold greater than the expected rate in population (4.2%). Eleven patients had acute kidney injury, and two patients required dialysis. Hematological diagnosis was consistent with monoclonal gammopathy of undetermined significance (n=10), unconfirmed MGUS (n=3), POEMS syndromes (n=4), Castleman's disease (n=2), and chronic lymphocytic leukemia (n=1). A majority of patients (84.2%) showed the activation of complement classical pathway. 15% (3/20) of patients received conservative therapy, 5% one patient received steroid only, 30% (6/20) received with immunosuppression, and 50% (10/20) received with clone-targeted chemotherapy. During 56 months Of median follow-up, ESRD developed in 2 patients, and 5 patients died mainly because of hematological progression. This study found the dysregulation of complement activation, especially the classical pathway, involved in the pathogenesis of biopsy-proven renal TMA and monoclonal gammopathy.

MM-250 Multicentric Castleman Disease in the Setting of POEMS Syndrome

MM-250 Multicentric Castleman Disease in the Setting of POEMS Syndrome

The Latin-American Experience in POEMS Syndrome: A Study of the GELAMM (Grupo de Estudio Latinoamericano de Mieloma Múltiple).

POEMS syndrome is a rare paraneoplastic syndrome caused by an underlying plasma cell disorder. The acronym refers to the following features: polyradiculoneuropathy, organomegaly, endocrinopathy, monoclonal paraproteinemia, and skin changes. The study was conducted at 24 hematological centers across 8 Latin-American countries. The study included a total of 46 patients {median age was 52 years (interquartile range [IQR]: 42-61.5), 30 males and 16 females} fulfilling the POEMS syndrome criteria diagnosed over a period of 12 years (January 1, 2011, through July 31, 2023). Epidemiological and clinical data were collected in an ad hoc database sent to the members of GELAMM, as well as the Kolmogorov-Smirnov test and Kaplan-Meier estimates. All patients had polyneuropathy and monoclonal gammopathy; 89% had bone marrow plasma cell infiltration, 33% had sclerotic bone lesions. Only 10 patients underwent vascular endothelial growth factor (VEGF) testing in plasma samples. The paraproteinemia was IgG λ in 32% and IgA λ in 30%. 59% patients presented with cutaneous changes, mainly hyperpigmentation, 54% had organomegaly, and 74% endocrinopathy. The median interval from symptom onset to diagnosis was 7.7 months (IQR: 4.0-12.6). 69% of patients received a single line of treatment. The median follow-up period was 25 months (IQR: 9.37-52.0) and the 2-year overall survival rate was 100%. All patients who underwent transplantation (43%) are alive, with a median follow-up of 45.62 months (IQR: 15.46-70). This study investigates POEMS syndrome in Latin America and presents an initial overview of the disease in the region. VEGF usage is recommended for accurate diagnosis, but only 7 hematology centers in the region used it. Survival rate in Latin America is comparable with those observed internationally.

Clinical applications of SPECT/CT in assessment of bone lesions in POEMS syndrome

PurposeRetrospectively analyse the 99mTc-MDP SPECT whole-body bone scan in POEMS syndrome to explore its clinical value.MethodsTwenty-four untreated patients with pathologically confirmed POEMS syndrome were included in the study. 24 of them underwent 99mTc-MDP SPECT whole-body bone scan, 24 underwent CT examination and 18 patients underwent X-ray examination in different parts. Features of bone lesions in 99mTc-MDP SPECT, and X-ray, CT were analysed. Three experienced radiologists read the images and gave diagnosed results for bone lesions.ResultsOf the 24 POEMS syndrome patients, three types of bone lesions were found: osteosclerotic lesions, osteolytic lesions and mixed lesions, of which the most common type was osteosclerotic. 54.16% (13/24) patients were found bone lesions by SPECT; 44.44% (8/18) patients underwent X-ray and 62.50% (15/24) patients underwent CT were detected bone lesions. We compared the difference of the X-ray, CT and SPECT scans of the bone lesions by chi-square and found that there was no difference (P = 0.51) in detection of bone lesions among the three methods.Conclusion99mTc-MDP SPECT wholebody bone scan also useful in evaluating patients with suspected POEMS syndrome. We can use it as a supplement examination of the CT in the confirmation of one minor diagnostic criterion for POEMS syndrome: bone lesions.

Ixazomib in POEMS syndrome: 'Ixa'ctly what we need?

The role of the proteasome inhibitor ixazomib in the treatment of POEMS syndrome continues to evolve. He and colleagues present the results of a study investigating ixazomib in combination with cyclophosphamide and dexamethasone in newly diagnosed POEMS patients. The triplet showed excellent efficacy and tolerability, and constitutes an effective treatment option for patients with POEMS. Commentary on: He etal. An open-label, prospective trial to evaluate the efficacy and safety of ixazomib in combination with cyclophosphamide and dexamethasone in patients with newly-diagnosed POEMS syndrome. Br J Haematol 2024;205:478-482.

An open-label, prospective trial to evaluate the efficacy and safety of ixazomib in combination with cyclophosphamide and dexamethasone in patients with newly diagnosed POEMS syndrome.

This open-label, prospective trial evaluated the combination of ixazomib, cyclophosphamide and dexamethasone (ICD) in 12 newly diagnosed POEMS syndrome patients. The study is registered with the Chinese Clinical Trials Registry (ChiCTR2000030072). The treatment protocol consisted of 12 cycles of the ICD regimen compromising ixazomib (4 mg on Days 1, 8 and 15), oral cyclophosphamide (300 mg on Days 1, 8 and 15) and dexamethasone (20 mg weekly). A total of 12 patients received a median of 10 (range: 3-23) cycles of the ICD regimen. The haematological response could be evaluated in 10 patients. The overall haematological response rate was 80% (8/10), with 30% (3/10) achieving complete haematological response, and the overall serum VEGF response rate and neurological response were 100% and 83.3% respectively. Two patients experienced grade 3/4 AEs, including diarrhoea (n = 1) and leukopenia (n = 1). The combination of ixazomib, cyclophosphamide and dexamethasone demonstrated both efficacy and safety in newly diagnosed POEMS syndrome, making it a viable treatment option.

A Rare Case of Castleman Variant of POEMS Syndrome

Abstract POEMS syndrome is a rare multisystemic disease, characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes. The presence of polyneuropathy and monoclonal plasma cell proliferation is mandatory for the diagnosis of typical POEMS syndrome. However, some patients lack one of the mandatory features and are classified as the variants of POEMS syndrome. A 61-year-old male presented with the clinical picture of progressive numbness in both lower extremities and weakness in all four extremities for a 6-month duration associated with bilateral axillary lymphadenopathies, pedal edema, clubbing, and unintentional weight loss of 15 kg in 6 months. A nerve conduction study showed severe sensorimotor polyneuropathy of demyelinating type in all four extremities. A lymph node biopsy showed Castleman disease, and the computed tomography scan was suggestive of multiple osteosclerotic lesions. A diagnosis of the Castleman variant of POEMS syndrome was made, and the patient was treated with Bortezomib-based therapy with improvement in his symptoms on follow-up at 1 year. Due to the lack of definite treatment guidelines for this disease, the information provided through case reports and case series becomes very important for the treatment of such patients leading to the resolution of polyneuropathy and the maintenance of functionality in patients.

Long-term outcomes of newly diagnosed POEMS syndrome patients who received first-line lenalidomide-based therapy.

Not available.

Elranatamab (Elrexfio)

CADTH recommends that Elrexfio should be reimbursed by public drug plans for the treatment of adult patients with relapsed or refractory multiple myeloma (MM) who have received at least 3 prior lines of therapy including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, and who have demonstrated disease progression on the last therapy if certain conditions are met. Elrexfio should only be covered to treat patients aged 18 years and older with relapsed or refractory MM who have received at least 3 prior treatments, have disease that has not responded to their last treatment, have not received prior B-cell maturation antigen (BCMA)–targeted treatment, and are in relatively good health. Elrexfio should not be reimbursed for the treatment of those patients whose MM is affecting their brain or spinal cord or those showing signs that the tissue layers protecting the brain and spinal cord are affected by MM. It also should not be reimbursed for the treatment of those with amyloidosis (a buildup of a protein, amyloid, in organs) that is not secondary to MM, those with POEMS (polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes) syndrome, and those with plasma cell leukemia. Elrexfio should only be reimbursed if it is prescribed and administered by health professionals at treatment centres with adequate medical resources and personnel, and if the price of Elrexfio is reduced.

Monoclonal gammopathy of clinical signifi cance with osteosclerotic lesions - a case report and a literature review.

Multiple myeloma is a common plasma cell neoplasia usually accompanied by the formation of osteolytic foci, whereas osteosclerotic myeloma is a very rare form of plasma cell dyscrasia. When osteosclerotic myeloma is detected, osteosclerotic foci are usually part of the POEMS syndrome. Osteosclerotic myeloma without other manifestations of the POEMS syndrome is an unusual finding. In a 46-year-old woman, osteosclerotic changes of the temporoparietal region caused soft tissue induration over this lesion, which initiated further investigation. Imaging studies subsequently showed multiple osteosclerotic foci in the skull. Examination of blood proteins revealed 8 g/L of IgG-lambda monoclonal immunoglobulin, subclass IgG1. In search of the cause of the osteosclerotic changes, FDG-PET/CT was performed, which revealed no FDG accumulation, i.e., no other tumor (breast or stomach cancer). Low-dose CT showed irregular bone structure, but not significant osteolytic or osteosclerotic foci. To map the extent of osteosclerotic changes, NaF-PET/CT imagination followed, which revealed multiple spots with high fluoride accumulation. A parietal bone biopsy showed osteosclerosis with minor clonal plasma cell infiltration. Trepanobioptic bone marrow sampling revealed an infiltration of bone marrow with atypical plasma cells in 8%. Flow-cytometric examination of bone marrow showed 0,37% of plasma cells, however predominantly (91%) clonal with lambda expression. MRI of the brain identified asymptomatic meningeal thickening. There was no evidence of POEMS syndrome in the patient; thus, we concluded the diagnosis as monoclonal gammopathy of clinical significance with osteosclerosis which was previously termed osteosclerotic multiple myeloma. Monoclonal gammopathy of clinical significance (MGCS) with osteosclerotic skeletal changes, documented on CT and multiple foci with intensive osteoneogenesis, documented on NaF-PET/CT without evidence of POEMS syndrome, is an extremely rare form of plasma cell dyscrasia. This publication documents the unique clinical manifestations of IgG-lambda type plasma cell proliferation without signs of POEMS syndrome and the role of NaF-PET/CT imaging. Classification of this disease as MGSC with osteosclerotic manifestations is more consistent with the indolent nature of the disease with a significantly better prognosis, compared with multiple myeloma.

Recent insights into haematology and peripheral nerve disease.

The association between clonal haematological disorders and peripheral nerve disease is recognized. Paraproteinaemic phenomena are the most common mechanism, but direct neural lymphomatous infiltration is seen and can be challenging to diagnose. Traditional and novel anticancer therapies have neuropathic side effects. Novel studies using sensitive techniques are refining the incidence of peripheral neuropathy in patients with a monoclonal gammopathy, and the pathogenesis of IgM Peripheral neuropathy (PN) and POEMS syndrome. Recent series give insight into the characteristics and diagnostic challenges of patients with neurolymphomatosis and amyloid light chain amyloidosis. There is an increasing repertoire of effective anticancer drugs in haematological oncology, but chemotherapy-related neuropathy remains a common side effect. This review of the current literature focuses on recent updates and developments for the paraproteinaemic neuropathies, and the evaluation, diagnosis and treatment of peripheral nerve disease due to high-grade and low-grade lymphomas and lymphoproliferative disorders.

POEMS syndrome with undetectable M-protein: a case report and literature review

BackgroundPolyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome is a rare plasma cell (PC) neoplasm with associated paraneoplastic syndrome. According to the current diagnostic criteria, peripheral polyneuropathy and monoclonal PC proliferative disorder represent two mandatory criteria.Case presentationWe report a 54-year-old male with peripheral neuropathy of bilateral lower limbs, sclerotic bone lesions, elevated vascular endothelial growth factor (VEGF) levels, splenomegaly, extravascular volume overload, endocrinopathy, and skin hemangiomas. Of note, serum and urine protein electrophoresis (PEP) and immunofixation electrophoresis (IFE) of this patient indicated undetectable M-protein and the normal ratio of free light chains κ and λ (FLC-R (κ/λ)). No monoclonal PCs were found in bone marrow examinations or biopsy of diseased bones. However, his clinical manifestations matched most of the diagnostic criteria. After excluding other diseases that are easily confused with POEMS syndrome, the diagnosis of variant POEMS syndrome with undetectable M-protein was proposed. The patient obtained clinically significant improvement and elevated VEGF returned to normal after 6 months of treatment with lenalidomide plus dexamethasone.ConclusionsMonoclonal PC dyscrasia (M-protein) while being a mandatory criterion for POEMS syndrome is undetectable in a considerable amount of patients that otherwise demonstrate typical symptoms. Here, we reported a case of variant POEMS syndrome with featured clinical manifestations, elevated VEGF levels, and good response to therapies targeting PCs but no evidence of M-protein. Therefore, negative results in M-protein and monoclonal PCs aren’t enough to reject the diagnosis of POEMS syndrome. It is imperative to recognize the variant form of POEMS syndrome.

The Preventive Effect of Levofloxacin Combined with G-CSF or Only G-CSF Supportive Therapy on Infection in Autologous Hematopoietic Stem Cell Transplantation

To investigate the role of levofloxacin combined with recombinant human granulocyte colony-stimulating factor (G-CSF) or only G-CSF supportive therapy in preventing infection in autologous hematopoietic stem cell transplantation(ASCT), and to analyze the length of hospital stay, hospitalization cost and post-transplant survival of the patients. A retrospective analysis was performed in the patients with hematological malignancies who accepted ASCT at our hospital from January 2012 to July 2022, the febrile neutropenia, the incidence of bacterial infection and the use rate of intravenous antibiotics in the levofloxacin+G-CSF group and only G-CSF support group during ASCT were observed. The length of hospital stay, total cost during hospitalization and survival after 90 days of transplantation between the two groups were compared. A total of 102 cases were included in this study, including 57 cases of multiple myeloma, 36 cases of acute leukaemia, 7 cases of lymphoma, 3 cases of myelodysplastic syndrome, 1 case of light chain amyloidosis, and 1 case of POEMS syndrome. 47 patients received levofloxacin+ G-CSF antibacterial prophylaxis, and 55 patients received G-CSF supportive therapy. In the levofloxacin+ G-CSF group, 40 cases (85.11%) developed febrile neutropenia, and 13 cases (27.66%) were confirmed as bacterial infection. In the G-CSF group, 44 cases (80.00%) developed febrile neutropenia, and 16 cases (29.09%) were bacterial infection. There was no statistically significant difference in the incidence of febrile neutropenia and bacterial infection between the two groups (χ2=0.46，P =0.50; χ2=0.03，P =0.87). The use rate of intravenous antibiotics in the levofloxacin+ G-CSF group was 85.11% (40/47), which was not statistically different from 85.45% (47/55) in the G-CSF group (χ2=0.04，P =0.84). The detection rates of levofloxacin-resistant bacteria in the levofloxacin+ G-CSF group and G-CSF group were 8.57% (3/35) and 21.43% (6/28), respectively, with no statistical difference (χ2=0.65, P >0.05). The median length and median cost of hospitalization in the levofloxacin+ G-CSF group and G-CSF group were 25 d vs 22 d and 78 216.24 yuan vs 80 724.38 yuan, with no statistically significant differences ( t =3.00，P =0.09; t =0.94，P =0.09). Within 90 days after transplantation, two cases (4.26%) died in the levofloxacin+ G-CSF group and one case (1.82%) died in the G-CSF group, with no statistically significant difference between the two groups (χ2=0.53，P =0.47). Application of levofloxacin+ G-CSF showed no significant benefit compared to G-CSF support for the prevention of bacterial infections during ASCT.

Paraproteinemic neuropathies

Paraproteinemic polyneuropathies (PPN) occur generally infrequently and arise from diseases, associated with formation and accumulation of a pathological protein, commonly known as paraprotein, which is typically an immunoglobulin or its free light chain. Such diseases include the following: monoclonal gammopathy of undetermined significance, multiple myeloma, Waldenström’s macroglobulinemia, AL amyloidosis, POEMS syndrome, etc. Diagnosis of PPN is challenging due to nonspecific, indistinct or atypical clinical manifestation, and it is necessary to apply specialized laboratory methods, including immunochemical analysis of blood and urine. Moreover, medications can cause symptoms of polyneuropathy themselves. Thus, it is important to suspect the first symptoms of the disease in time, determine the mechanism of damage to nerve fibers, carry out differential diagnosis and initiate therapy targeting the suppression of pathological protein synthesis.

#2699 Rare glomerular microangiopathy: clinicopathological characteristics and prognosis

Abstract Background and Aims Different from the typical histologic changes of thrombotic microangiopathy (TMA), we identified a group of patients whose pathology with glomerular involvement without blood vessel lesions, which was rare and known as glomerular microangiopathy (GMA). Method In Peking Union Medical College Hospital, a total of 33 patients were diagnosed as GMA with proliferation and swelling of glomerular endothelial cells, fragmented red blood cells, fibrin or platelet thrombi in the capillary lumen, thickening of the basement membrane, stenosis or occlusion of capillary lumen, but no abnormalities in the endothelium of renal small vessels. The pathology and clinical data were from the medical records and analyzed. Results The patients were 66.7% male with a mean of 45 years (14 to 74 years). The primary diseases were Castleman's disease (CD, 30.3%), POEMS syndrome (21.2%), cancer patients receiving agents targeting vascular endothelial growth factor (21.2%), and others. All the patients showed various degrees of proteinuria, with an average 24-hour urinary protein of 2.66 g/d, hematuria (63.6%), and acute kidney injury (AKI, 39.4%). The median serum creatinine (SCr) was 142 (107.5, 169) μmol/L. The AKI patients had lower Alb (P &amp;lt; 0.0001), PLT (P = 0.0192), higher high-sensitivity C-reactive protein (hs-CRP) (P = 0.0199), and reduction of IgA (P = 0.0021). There is no significant difference in SCr and proteinuria among patients with different etiologies. The CD patients exhibited higher hs-CRP and D-Dimer. Treatment included targeting therapy of underlying hematological disorders, glucocorticoid combination with or without immunosuppressant, and supportive treatment. After treatment, we observed proteinuria remission (66.7%), partial improvement (27.3%), or complete recovery (45.5%) of renal function. Conclusion In Castleman's disease, POEMS syndrome, and patients receiving agents targeting VEGF, initial attention to GMA might improve the prognosis and shed light on the study of the mechanisms.

Elevated serum levels of soluble B-cell maturation antigen as a prognostic biomarker for multiple myeloma.

Serum B-cell maturation antigen (sBCMA) levels can serve as a sensitive biomarker in multiple myeloma (MM). In the research setting, sBCMA levels can be accurately detected by enzyme-linked immunosorbent assay (ELISA), but the approach has not been approved for clinical use. Here, we used a novel chemiluminescence method to assess sBCMA levels in 759 serum samples from 17 healthy donors and 443 patients with plasma cell (PC) diseases including AL amyloidosis, POEMS syndrome, and MM. Serum BCMA levels were elevated 16.1-fold in patients with newly diagnosed MM compared to healthy donors and rare PC diseases patients. Specifically, the sBCMA levels in patients with progressive disease were 64.6-fold higher than those who showed partial response or above to treatment. The sBCMA level also correlated negatively with the response depth of MM patients. In newly diagnosed and relapsed MM patients, survival was significantly longer among those subjects whose sBCMA levels are below the median levels compared with those above the median value. We optimized the accuracy of the survival prediction further by integrating sBCMA level into the Second Revised International Staging System (R2-ISS). Our findings provide evidence that the novel chemiluminescence method is sensitive and practical for measuring sBCMA levels in clinical samples and confirm that sBCMA might serve as an independent prognostic biomarker for MM.

Detection of clonal plasma cells in POEMS syndrome using multiparameter flow cytometry

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein [M-protein], and skin changes) is a rare systemic disorder characterized by various symptoms caused by underlying plasma cell (PC) dyscrasia. Detection of monoclonal PCs is mandatory for the diagnosis of POEMS syndrome; however, the usefulness of EuroFlow-based next-generation flow cytometry (EuroFlow-NGF) in POEMS syndrome for detecting monoclonal PCs in bone marrow (BM) and the gating strategy suitable for flow cytometry study of POEMS syndrome remain unknown. We employed EuroFlow-NGF-based single-tube eight-color multiparameter flow cytometry (MM-flow) and established a new gating strategy (POEMS-flow) to detect the monoclonal PCs in POEMS syndrome, gating CD38 broadly from dim to bright and CD45 narrowly from negative to dim compared to MM-flow. MM-flow detected monoclonal PCs in 9/25 (36.0%) cases, including 2/2 immunofixation electrophoresis (IFE)-negative cases (100%). However, POEMS-flow detected monoclonal PCs in 18/25 cases (72.0%), including 2/2 IFE-negative cases (100%). POEMS-flow detected monoclonal PCs with immunophenotypes of CD19− in 17/18 (94.4%). In six cases where post-treatment samples were available, the size of the clones was significantly reduced after the treatment (P = 0.031). POEMS-flow can enhance the identification rate of monoclonal PCs in POEMS syndrome and become a valuable tool for the diagnosis of POEMS syndrome.