Light Chain Type Research Articles

Characterization of anti-EBNA-1 antibodies and exploration of their molecular mimicry potential in an EBV-infected Sjögren's syndrome patient

There is a potential link between autoimmune diseases and Epstein-Barr virus (EBV) infections, with EBV playing a substantial role in the onset of Sjögren's syndrome (SjS). Some EBV proteins could mimic host self-antigens post-infection, leading to molecular mimicry. This similarity may cause the immune system to attack its tissues mistakenly. Among the various proteins associated with EBV, nuclear antigen 1 (EBNA-1) is essential for the latent replication of infected cells and is prevalent in all EBV-related diseases. In the study, single-chain variable fragment (scFv) antibodies targeting EBNA-1 were isolated using phage display technology from a primary SjS patient who also had a chronic active EBV infection. The specific clones were enriched after panning, and the binding activity of selected scFvs targeting EBNA-1 was confirmed. Sequence analysis indicated that the scFvs exhibiting positive signals could be grouped into five clones, all of which used homologous heavy chain V regions derived from germline Vh4-39, and two types of light chain V regions stemming from germline Vλ1-44 and Vλ3-15. These scFvs were found to exhibit a high degree of somatic mutations, likely indicative of antigen selection. Of the scFvs, P1-3 demonstrated the strongest binding affinity to EBNA-1, exhibiting a determined value of 7.3 x 10-8 M, and showed cross-reactivity to the SjS associated La/SSB self-antigen. The experimental results combined with AlphaFold 3 predictions revealed a potential epitope for scFv P1-3 binding to EBNA-1. Additionally, scFv P1-3 could also cross-bind to the modeled structure of La/SSB. We inferred a possible structural correlation between EBNA-1 and La/SSB involving an X2AX6PG epitope motif. This research contributes to our understanding of the structural basis of the interactions between antibodies and EBNA-1, shedding light on the VH and VL gene usage of anti-EBNA-1 antibodies in EBV-infected SjS patients and the potential origins of autoantibodies.

Tandem mass tag-based quantitative proteomics analysis of modified atmosphere packaging in large yellow croaker (Pseudosciaena crocea) fillets during refrigerated storage

A tandem mass tagging-labeled proteomic approach was employed to explore the relationship between quality parameters and protein changes in large yellow croaker fillets refrigerated under carbon dioxide, oxygen, and nitrogen atmospheres. After 96 h, fillets stored in carbon dioxide and nitrogen showed improved texture, water-holding capacity, and color, compared to those stored in oxygen. Functional analysis respectively identified 117 and 65 differentially expressed proteins in carbon dioxide and nitrogen, including key proteins such as troponin, myosin light chain, actin, and collagen types IV and XIII, that were linked to extracellular adhesion, cytoskeleton integrity, energy metabolism, and membrane functions. Carbon dioxide and nitrogen were detrimental to the growth and reproduction of aerobic microorganisms. High concentrations of carbon dioxide can inhibit microbial activity, while nitrogen preserves freshness by regulating the pressure balance within the packaging. These findings provided a theoretical basis for the optimized gas-conditioned preservation of large yellow croaker fillets.

The association between joint Serum Neurofilament Light Chain and type 2 diabetes with all-cause and cardiovascular mortality in US adults: a longitudinal study of NHANES

BackgroundIn the past, there has been a clear conclusion regarding the sole impact of serum neurofilament light chain (sNfL) levels or type 2 diabetes mellitus (DM) on the risk of death. However, the combined effect of sNfL levels and type 2 DM on all-cause and cardiovascular mortality is still uncertain.MethodsThis study was a prospective cohort study based on data from the National Health and Nutrition Examination Survey (NHANES). The sNfL levels were measured through immunological methods using blood samples collected during the survey. The diagnosis of diabetes was based on rigorous criteria, and participants’ mortality data were followed up until December 31, 2019. Firstly, we separately examined the effects of sNfL and type 2 DM on all-cause and cardiovascular mortality, and finally studied the comprehensive impact of the combination of sNfL and type 2 DM on the risk of mortality. Cumulative Kaplan-Meier curves, multivariate logistic regression and sensitivity analysis were incorporated throughout the entire study.ResultsParticipants in the highest quartile of sNfL were observed. Multivariable COX regression model showed that increased sNfL levels and type 2 DM were respectively associated with an increased risk of all-cause and cardiovascular mortality. Furthermore, elevated sNfL levels were significantly associated with an increased risk of all-cause mortality and cardiovascular mortality after adjustment for confounding factors. When considering both elevated sNfL levels and type 2 DM, individuals had a significantly increased risk of mortality. Sensitivity analysis confirmed the robustness of the findings.ConclusionsThese results suggest that elevated levels of sNfL and type 2 DM are associated with an increased risk of all-cause and cardiovascular mortality, and that participants with increased sNfL levels associated with type 2 DM have higher all-cause mortality and cardiovascular mortality.

MultiBac System-based Purification and Biophysical Characterization of Human Myosin-7a.

Myosin-7a is an actin-based motor protein vital for auditory and visual processes. Mutations in myosin-7a lead to Usher syndrome type 1, the most common and severe form of deaf-blindness in humans. It is hypothesized that myosin-7a forms a transmembrane adhesion complex with other Usher proteins, essential for the structural-functional integrity of photoreceptor and cochlear hair cells. However, due to the challenges in obtaining pure, intact protein, the exact functional mechanisms of human myosin-7a remain elusive, with limited structural and biomechanical studies available. Recent studies have shown that mammalian myosin-7a is a multimeric motor complex consisting of a heavy chain and three types of light chains: regulatory light chain (RLC), calmodulin, and calmodulin-like protein 4 (CALML4). Unlike calmodulin, CALML4 does not bind to calcium ions. Both the calcium-sensitive, and insensitive calmodulins are critical for mammalian myosin-7a for proper fine-tuning of its mechanical properties. Here, we describe a detailed method to produce recombinant human myosin-7a holoenzyme using the MultiBac Baculovirus protein expression system. This yields milligram quantities of high-purity full-length protein, allowing for its biochemical and biophysical characterization. We further present a protocol for assessing its mechanical and motile properties using tailored in vitro motility assays and fluorescence microscopy. The availability of the intact human myosin-7a protein, along with the detailed functional characterization protocol described here, paves the way for further investigations into the molecular aspects of myosin-7a in vision and hearing.

Nasopharyngeal amyloidoma: report of three cases and review of the literature

BackgroundNasopharyngeal amyloidoma is a rare, locally aggressive tumor that has been reported in the English literature in only 38 cases to date, most of which were in the form of case reports. The present study was aimed to summarize the characteristics of this rare tumor, with the goal of providing new insights for diagnosis and treatment.Materials and methodsWe report three cases of nasopharyngeal amyloidoma diagnosed in our hospital following comprehensive medical examination and review the current literature on all cases of nasopharyngeal amyloidoma from PubMed. The journey of nasopharyngeal amyloidoma, including presentation, diagnostics, surgeries, and follow-up was outlined.ResultsNone of the three patients had systemic amyloidosis. CT and nasal endoscopy showed irregular masses obstructing the nasopharyngeal cavity. Congo red staining confirmed the deposition of amyloid, and immunohistochemical analysis showed that the amyloid deposition was the AL light chain type. Through literature review, we found that nasopharyngeal amyloidoma most commonly occurred in individuals over the age of 40, patients usually had a good prognosis after complete tumor resection; however, there were still cases of recurrence, and unresected patients were at risk of progression to systemic amyloidosis. The efficacy of radiotherapy and chemotherapy was currently uncertain.ConclusionEarly clinical and pathological diagnosis is crucial, and surgical intervention is the primary treatment option for this disease. Although patients usually have a favorable prognosis, long-term monitoring is necessary to detect potential relapses and initiate timely intervention.

Efficacy of a Daltuzumab-containing Regimen in Patients with mSMART High-Risk Multiple Myeloma

To investigate the efficacy and safety of a treatment regimen based on daratumumab in patients with high-risk relapsed refractory multiple myeloma(MM) with mSMART 3.0 score. Clinical data were collected from 16 patients with mSMART3.0 score high-risk relapsed refractory MM treated at the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from May 2020 to May 2023, all of whom received daltezumab-based regimen (regimen drugs including dexamethasone, isazomib, bortezomib, lenalidomide). The efficacy and safety of the treatment were retrospectively analyzed. The median age of 16 patients was 63.5 (47-70) years old, including 10 cases of IgG type, 2 cases of IgA type, and 4 cases of light chain type. The curative efficacy was judged in all 16 patients, with an overall response rate of 93.75% (15/16), including 4 cases of strict complete remission (sCR), 1 case of complete remission (CR), 2 case of very good partial remission (VGPR), partial remission (PR) in 5 cases, and minor remission (MR) in 3 cases. The median follow-up time was 11(2-30) months, and the median progression-free survival and median overall survival were not achieved in 16 patients at the median follow-up period. The hematologic adverse effects of the treatment regimen using daratumumab-based were mainly neutropenia, and the non-hematologic adverse effects were mainly infusion-related adverse reactions and infections. Daratumumab-based regimen for the treatment of relapsed refractory MM patients with high risk of mSMART3.0 score has better efficacy and safety.

Cardiac Amyloidosis: A Contemporary Review of Medical and Surgical Therapy.

Amyloidosis is a systemic disease initiated by deposition of misfolded proteins in the extracellular space, due to which multiple organs may be affected concomitantly. Cardiac amyloidosis, however, remains a major cause of morbidity and mortality in this population due to infiltrative /restrictive cardiomyopathy. This review attempts to focus on contemporary medical and surgical therapies for the different types of cardiac amyloidosis. Amyloidosis affecting the heart are predominantly of the transthyretin type (acquired in the older or genetic in the younger patients), and the monoclonal immunoglobulin light chain (AL) type which is solely acquired. A rare form of secondary amyloidosis AA type can also affect the heart due to excessive production and accumulation of the acute-phase protein called Serum Amyloid A" (SAA) in the setting of chronic inflammation, cancers or autoinflammatory disease. More commonly AA amyloidosis is seen in the liver and kidney. Other rare types are Apo A1 and Isolated Atrial Amyloidosis (AANF). Medical therapies have made important strides in the clinical management of the two common types of cardiac amyloidosis. Surgical therapies such as mechanical circulatory support and cardiac transplantation should be considered in appropriate patients. Future research using AI driven algorithms for early diagnosis and treatment as well as development of newer genetic engineering technologies will drive improvements in diagnosis, treatment and patient outcomes.

Clinical Significance of Serum Free Light Chain in Monoclonal Gammopathy

To investigate the expression and clinical significance of serum free light chain (sFLC) in patients with monoclonal gammopathy (MG). The peripheral blood of 98 patients with MG and 30 healthy volunteers were collected. The level of sFLC was detected by immunoturbidimetry, and the value of sFLC in diagnosis, disease severity, and efficacy evaluation was analyzed. Among 98 MG patients, there were 58 males and 40 females, 45 cases of monoclonal gammopathy of renal significance (MGRS), 33 cases of monoclonal gammopathy of undetermined significance (MGUS), 20 cases of hematological malignancy (HM), 58 cases of IgG type, 26 cases of IgA type, 7 cases of IgM type, 5 cases of light chain type, 2 cases of non-secreting type, 35 cases of κ type, 63 cases of λ type, 53 cases of renal insufficiency, 45 cases of normal renal function. The expression levels of sFLC-κ and sFLC-λ in MG patients were significantly higher than those of the control group (P <0.01). The expression levels of sFLC-κ and sFLC-λ in HM patients were significantly higher than MGRS and MGUS patients, and in MGRS patients were also significantly higher than MGUS patients (P <0.05). Patients with abnormal renal function had higher expression levels of sFLC-κ and sFLC-λ than patients with normal renal function (P <0.01). sFLC-κ and sFLC-λ were positively correlated with the expression level of globulin (r =0.392, r =0.435) and β2-MG (r =0.403, r =0.468) in MG patients, as well as serum creatinine in patients with abnormal renal function (r =0.586, r =0.631), while no significant correlation was found with age, sex, albumin, lactate dehydrogenase, and serum calcium. After treatment, the levels of sFLC-κ and sFLC-λ were significantly decreased (P <0.01). sFLC is significantly elevated in MG patients and can be quickly detected with high sensitivity, which is helpful for the diagnosis of disease type, judgment of disease severity, and evaluation of therapy.

The function of the inter-alpha-trypsin inhibitors in the development of disease.

Through the formation of covalent connections with hyaluronic acid (HA), the inter-α-trypsin inhibitor (IαI) family collaborates to preserve the stability of the extracellular matrix (ECM). The five distinct homologous heavy chains (ITIH) and one type of light chain make up the IαI family. ITIH alone or in combination with bikunin (BK) has been proven to have important impacts in a number of earlier investigations. This implies that BK and ITIH might be crucial to both physiological and pathological processes. The functions of BK and ITIH in various pathophysiological processes are discussed independently in this paper. In the meanwhile, this study offers suggestions for further research on the roles of BK and ITIH in the course of disease and summarizes the plausible mechanisms of the previous studies.

Smoldering Multiple Myeloma Progressing to Active Multiple Myeloma Vs De-Novo Active Multiple Myeloma - a Comparison of Disease Characteristics, Organ Involvement and Outcomes in a Real-Life Multicenter Retrospective Cohort Study

Background Smoldering Multiple Myeloma (SMM) is an intermediate precursor phase in Multiple Myeloma (MM) evolution. SMM patients are monitored for progression to active disease, supposing such surveillance will identify myeloma-defining events (MDEs) early and consequently hasten treatment, prevent complications and improve outcomes. To what extent this approach is successful is not well established. We aimed to compare disease characteristics, end organ involvement and outcomes between SMM patients who progressed to active MM vs newly diagnosed MM (NDMM) patients. Methods We performed a two-center real-world case-control retrospective cohort study. Consecutive patients receiving first line treatment for MM after progressing from SMM were identified; each was matched by age and year of diagnosis (±2 years) to a patient first presenting as NDMM. SMM, MM, MDEs and response were defined by the International Myeloma Working Group (IMWG) criteria (2014, 2016); progression-free survival (PFS) and overall survival (OS) were calculated from active MM diagnosis. Data was extracted in 07/2023. Results We identified two cohorts of newly diagnosed MM patients, presented between 09/2008and 02/2023: Post SMM (P-SMM, N=57) and De novo MM patients (D-MM, N=57). Median follow up time was 38.6 months (IQR 23.3 - 72.7). There were no differences in baseline demographics between gender (p=.19), and median age: 73.4 (range 42 - 88) in the P-SMM group and 72.9 (range 42 - 92) in the D-MM (p=.75). Comparing MDEs using SLiM-CRAB criteria between groups, more patients in the D-MM group presented with hypercalcemia (p=.02) and lytic lesions (p=.03). Other domains were similar between groups: anemia (p=.68), renal failure (p=.59), FLC ≥100 (p=.76), % bone marrow plasma cells (BMPC) ≥ 60 (p=.11). D-MM patients had higher ISS/R-ISS at presentation: ISS ≥ II (30 vs 11, p=.004) and R-ISS ≥ II (31 vs 13, p=.002). Additional disease characteristics were balanced at diagnosis of active MM: heavy chain (p=.53), light chain type (p=.69), M-Protein level (p=.23), extra medullary disease (p=.14), Al amyloidosis (p=.13), and high-risk cytogenetics (p=.65). Bone involvement was more frequent in D-MM vs P-SMM patients, with significantly more pathological fractures (p=.006), bone pain (p=.001), and a detrimental bone disease (p=.001) (defined as combination of pathological fracture and/or ≥ 3 lytic lesions) (Figure 1B). Significantly higher rates of hospital admissions for upfront therapy initiation were seen in the D-MM group compared with P-SMM, 18 vs 7 (p=.008), as well as more potentially irreversible MDEs (pathological fractures and/or renal injury): 43 (p=.009) vs 31 (41.9%) respectively. Treatment patterns were balanced excluding bortezomib used more often in the D-MM (p=.009) and daratumumab in the P-SMM group (p=.03). Best response rates to upfront therapy were comparable between groups, (p=.71) as well as ≥ very good partial response (VGPR) rates (p=.88), 52.4% vs 47.6% in P-SMM and D-MM respectively. Frequency of skeletal imaging tests up-to 2-year period prior to active MM diagnosis were associated with lower rates of detrimental bone disease (p=.006). Despite the similar ≥ VGPR rates between cohorts, PFS was longer in the P-SMM group vs D-MM group, 39.6 vs 21.6 months, respectively (log-rank 0.01). A superior PFS in P-SMM group vs D-MM remained after correction for % BMPC at diagnosis (46.2% vs 58.8%, p=.03). OS was also longer, not reached vs 93.7 months (log-rank=.047) (Figure 1A). Conclusions Patients who develop active MM post SMM clinic surveillance presented with a lower disease burden, as well as reduced rates of detrimental bone disease and potentially irreversible MDEs. P-SMM patients had favorable PFS and OS rates. This may reflect effectiveness of SMM monitoring resulting in lower disease burden at time of treatment onset; favorable long-term outcomes may also be affected by variability in treatment patterns between groups. Another possible explanation is that patients with more indolent MM biology may have extended periods of precursor condition, hence increasing their likelihood to be diagnosed by incidental laboratory tests during their SMM phase.

M-Protein Analysis Test: Effects of Combining Serum Protein Electrophoresis and Free Light Chain Assay Tests into One Order

Background: Approximately 10-15% of clonal plasma cell disorders (PCDs, such as monoclonal gammopathy of undetermined significance or MGUS, smoldering myeloma or SMM, and multiple myeloma, MM) secrete light chains only, which are often missed on a serum protein electrophoresis (SPEP) and only detected on a serum free light chain (sFLC) or 24 hour urine (UPEP) assay. For this reason, the IMWG has recommended that screening tests for PCDs should include both an SPEP and sFLC. In 2020, clinicians at our institution were instructed to order an sFLC analysis in addition to an SPEP (with reflex immunofixation electrophoresis) when assessing for PCDs. This did not, however, appear to improve adherence to IMWG guidelines or alter screening practice. In 2021 separate orders for SPEP and sFLC were removed from the EMR and a new, combined order, called an “M-protein analysis”, was implemented. We now evaluate the effect of this change in test order by comparing the data for the 12 months preceding to the 12 months after the change. Methods: All 1 st time SPEP and sFLC results were identified for two 12-month periods: Group A (7/1/2020- 6/30/2021) and Group B (7/1/2021-6/30/2022). Within each time frame, we also identified patients without an M-protein on SPEP but a positive sFLC which was defined as an elevated kappa or lambda free light chain and a ratio either &amp;gt;1.65 or &amp;lt;0.26 (Groups C and D, correlating with earlier and later time frames, respectively). Groups E (pre-order change) and F (post-order change) included the subsets of sFLC positive only pts from each time frame with an sFLC ratio &amp;gt;3.0 or &amp;lt;0.26 . These more restrictive groups were chosen to minimize those with polyclonal light chain findings which may be seen in renal disease. Results: Group A: 4192 SPEPs, 1876 sFLCs (45% of SPEPs); Group B: 3966 SPEPs, 3966 sFLCs (100% of SPEPs) Group C: those from A with a negative SPEP and a positive sFLC defined by an elevated kappa or lambda free light chain and a ratio either &amp;gt;1.65 or &amp;lt;0.26: 30 (1.6%) were identified. Group D: those from B with a negative SPEP but a positive sFLC defined by an elevated kappa or lambda free light chain and a ratio either &amp;gt;1.65 or &amp;lt;0.26: 102 (2.6%) were identified. Group E: those from A without an M-protein on SPEP but a positive sFLC defined by an elevated kappa or lambda free light chain and a ratio either &amp;gt;3 or &amp;lt;0.26: 17 (0.9%) were identified. Group F: those from B without an M-protein on SPEP but a positive sFLC defined by an elevated kappa or lambda free light chain and a ratio either &amp;gt;3 or &amp;lt;0.26: 28 (0.7%) were identified. For the total sFLC positive only groups (C and D): Average age= 74 (49-93); Race: 51% white, 42% AA, 7 % UK; sex: 93% male; light chain type: 91% kappa, 9% lambda; K:L ratio: med 4.5 (range 0.01-165). For Group E (pre-order change, ratio &amp;gt;3 or &amp;lt;0.26): of the 17 cases, most were diagnosed with MGUS (10), 1 SMM and 6 with MM (all of whom were symptomatic at time of testing). For Group F (post-order change, ratio &amp;gt;3 or &amp;lt;0.26): of the 28 cases, most were diagnosed with MGUS (23), 2 CLL, 2 SMM, 1 B-cell lymphoma and 1 with MM (who was asymptomatic at time of testing). Overall, in the 12 months post-order change there were 2090 more sFLCs performed which identified 72 additional sFLC positive only cases (an increase of 340%). Conclusions: Combining the SPEP and sFLC into one order test from two separate tests improved adherence to IMWG guidelines for getting both tests ordered (from 45% to 100%). This increased the number of sFLC tests being performed but also increased the number of PCDs diagnosed. Although most of these were MGUS, early detection of this diagnosis has been suggested in other studies to result in closer follow-up and better outcomes. In addition, in our series there was a case of asymptomatic MM which would have been missed and diagnosis delayed if just an SPEP had been ordered. M-protein analysis should be considered as a combined screening test order at other institutions.

Prevalence of Peripheral Neuropathy (PN) Among Patients with Asymptomatic Monoclonal Gammopathies: A Clinical & Electrophysiological Study

Introduction: Asymptomatic monoclonal gammopathies (MGUS, SMM or aWM) are common among adults &amp;gt;50y. Peripheral neuropathy (PN) refers to any disorder of the peripheral nervous system including mononeuropathies, and symmetrical or asymmetrical polyneuropathy. PN is also common among individuals &amp;gt;50y. Common risk factors include diabetes, vitamin deficiencies, alcohol, renal insufficiency, hypothyroidism, autoimmune diseases and exposure to neurotoxic medication. Epidemiological studies have shown an association between monoclonal gammopathies and PN but a mechanistic link has been established only for some (anti-MAG IgM-related PN, amyloidosis, POEMS syndrome etc). However, the true prevalence of PN among patients (pts) with monoclonal gammopathies is unknown and remains challenging to associate monoclonal gammopathy with PN. The aim of our study is to establish the prevalence of PN in a large cohort of pts with asymptomatic monoclonal gammopathy and identify potential determinants. Methods: This is an ongoing prospective, non-invasive study aiming to screen ~1500 pts with asymptomatic monoclonal gammopathies for PN. Pts under regular follow-up at the Department of Therapeutics, University of Athens, Greece are screened for neuropathic symptoms using the Michigan Neuropathy Screening Instrument (MNSI), a validated screening tool for the presence of PN that consists of 15 yes/no items. A cut off ≥ 4 has been proposed as a screening cut off in diabetic PN. All pts scoring ≥4 on MNSI and pts scoring &amp;lt;4 but without risk factors for PN were assessed clinically and electrophysiologically (EDX) with standard nerve conduction studies (NCS), sympathetic skin response (SSR) test and - if needed - electromyography (EMG) by a specialist. NCS protocol includes assessment of the median nerve (motor and sensory), superficial radial nerve (sensory), tibial nerve (motor) and sural nerve (sensory) conduction studies. Axonal PN was diagnosed when the sural to radial ratio (SRAR) is below 0.25 and/or the sural nerve action potential is below 6μV, demyelinating PN if the EAN/PNS criteria for demyelination are fulfilled and sympathetic dysfunction when the SSR amplitude was &amp;lt;500 uV. Results: As of to date, 320 pts (42.8% males, median 67y) with asymptomatic monoclonal gammopathy have been screened; 64.3% had a diagnosis of MGUS (72.3% IgG, 14.1% IgA, 6.3% IgM, 7.3% light chain only), 23.9% had SMM and 11.8% had aWM. Among enrolled pts, 217 (68%) had no common risk factors for PN and 82 pts (25.6%) had an MNSI score ≥4; the commonest symptoms were cramps (48.4%), weakness (26.9%) and pain when walking (26.3%). Among pts without risk factors for PN, 42 (19.4%) had an MNSI score ≥ 4 and the commonest symptoms were cramps (44.7%), pain when walking (22.1%) and weakness (21.7%) (Table 1). There was no difference in the prevalence of MNSI score ≥4 among pts with different paraprotein types. To date, 105 pts (41.9% males, median 66y) had EDX evaluation, of which 77 (73%) had no common risk factors for PN. Among the EDX evaluated pts, 23 (21.9%) had large fiber PN, 42 (40%) had sudomotor dysfunction and 53 (50.5%) had large fiber PN and/or sudomotor dysfunction. Among the cohort of pts without risk factors for PN, 13 (16.9%) had large fiber PN, 25 (32.5%) had sudomotor dysfunction and 34 (44.2%) had large fiber PN and/or sudomotor dysfunction. Nineteen pts that went through EDX were asymptomatic (MNSI=0), of those 4 (21.1%) had large fiber PN, 4 (21.1%) had sudomotor dysfunction and 7 (33.3%) had large fiber PN and/or sudomotor dysfunction. Only one patient, without other risk factors, had a demyelinating neuropathy while all other pts had a length-dependent axonal sensory or sensorimotor neuropathy. Pts with large fiber PN were older (73.7±11.4 vs 63±9.4, p&amp;lt;0.001) but no significant differences were found regarding sex, or paraprotein or light chain type. Pts with sudomotor dysfunction were more likely to have a non-IgM monoclonal gammopathy (90.2% vs 72.6 %, p=0.029). Conclusion: Peripheral neuropathy is common in pts with monocloncal gammopathies affecting ~20% of those without any other risk factors for PN. Although most pts with PN describe mild symptoms, both large fiber PN and sudomotor dysfunction may remain completely asymptomatic. This data provides a new insight into the prevalence of PN in pts with monoclonal gammopathies with implications for future research. The study is ongoing and updated results will be presented.

Immunophenotypic Profile of Chronic Lymphoproliferative Diseases in the State of Rio Grande Do Norte, Northeast, Brazil

INTRODUCTION: Chronic lymphoproliferative diseases (CLPD) are considered as a heterogeneous group of diseases characterized by monoclonal expansion and accumulation of apparently mature lymphocytes, which have a proliferative and/or survival advantage over normal lymphocytes in different organs such as bone marrow, peripheral blood and lymph nodes. This translates into the progressive accumulation of clonal cells and their products, causing peripheral blood and bone marrow lymphocytosis, in addition to lymphadenopathy, splenomegaly or other organomegaly. According to the World Health Organization, which reflects the international consensus and is based on pathological, genetic and clinical factors, lymphoproliferative neoplasms are classified according to the stage of maturation and the lineage where the neoplastic transformation occurs through flow cytometry (FC). OBJECTIVES: The aim of this study was to demonstrate the immunophenotypic diagnostic profiles of patients with CLPD in Rio Grande do Norte, Brazil by FC. METHODOLOGY: Were investigated 884 patients with CLPD of both sexes through CF with a panel of monoclonal antibodies directed to CLPD. In addition, other patient information, such as age, gender, and clinical and hematological data were also collected. RESULTS: The results showed that 89.7% of the cases were B Cell CLPD (B-CLPD) and 10.3% T and natural killer cells (T/NK-CLPD). The distribution of B-CLPD cases were as follows: 487 Chronic lymphocytic leukemia; 18 B-Cell Pro-lymphocytic leukemia; 25 Hairy cell leukemia; 6 variant Hairy cell leukemia; 6 Follicular lymphoma leukemized; 4 Splenic lymphoma with villous lymphocytes; 33 Mantle cell lymphoma; 4 Waldenstrom's macroglobulinemia; 69 Multiple myeloma; 14 Plasma cell leukemia; 11 Burkitt's lymphoma and 117 Leukemic Non-Hodgkin lymphoma (Table 1). The distribution of CLPD-T/NK was as follows: 12 Large granular lymphocytic leukemia; 14 T-Cell prolymphocytic leukemia; 18 Adult T-cell leukemia; 20 Sézary syndrome; and 24 Peripheral T-Cell lymphoma and 2 DLPC-NK (Table 1). DISCUSSION: The B-CLPD are the most commonly observed corresponding to more than 85% of all cases and are characterized by the presence of clonal B lymphocytes with expression of a single type of immunoglobulin light chain (kappa or lambda) in a proportion greater than 1/10, associated the strong positivity of Pam-B antigens such as CD19, CD22 and CD20 and the absence or low expression of Pam-T antigens. However, other antigens such as CD200, CD5, FMC7, CD79b and CD103, among others, may be present or absent, specifically characterizing these entities as Chronic lymphocytic leukemia (weak CD22+; CD200+, CD5+, FMC7-, CD79b-), Hairy cells leukemia (strong CD22+; FMC7+; CD79b+; CD5-; CD200-; CD103+; CD123+; CD11c+ and Follicular lymphoma (strongCD22+/CD20+, CD10+, CD200-, CD79B+, FMC7+). T/NK-CLPD are less frequent and are characterized by the expression of Pan-T antigens CD2, CD3, CD5, CD7, CD28 and TCL-1, with clonality evidenced by strong positivity of TCRα/β in most cases and increase of TCD4+ or TCD8+ lymphocytes in a ratio above 1:10 in most cases. In this group, large granular lymphocyte leukemia (LGLG) is a rare type of T/NK cell CLPD characterized by peripheral and medullary infiltration of large hypergranular lymphocytic cells, comprising about 2-5% of all cases, the most commonly seen being CD8+ T cells. CONCLUSION: The results presented demonstrate that immunophenotyping is a defining technique for clarifying the diagnosis of patients with CPLD, clonality was also successfully characterized in the investigated cases of CPLP of B ,T and NK lineages.

Insights into Presentation and Outcomes of Localized Immunoglobulin Light Chain Amyloidosis: A 12-Year Experience of a Large Academic Center

Introduction : Localized immunoglobulin light chain amyloidosis (Loc-AL) is an ultra-rare disease caused by the local deposition of misfolded AL fibrils. To date, limited data exists on reporting patterns of disease presentation and long-term outcomes. The primary aim of this study is to describe our institution's experience of patients with Loc-AL, including disease presentation, management, and risk for local and systemic progression. Methods: We retrospectively analyzed medical records of 3108 patients with amyloidosis and selected 141 (5%) patients with biopsy proven Loc-AL treated at our institution between 1/1/2010 and 7/1/2023. Patients with evidence of systemic AL disease involving the bone marrow and/or major organs, such as heart, kidney, liver, and nervous system on initial assessment were excluded. AL amyloid typing was available in all cases; mass spectrometry was performed in 85 (60%) cases. Chi-squared test and Kaplan-Meier method were used for statistical analysis. Results: Of the 141 patients with Loc-AL included in this analysis, 79 (56%) were female and 117 (83%) were White. The median age at diagnosis was 67 (range 18-92) years. The sites of involvement included: 22% lower respiratory system (16% lung/pleura, 4% tracheobronchial system, 2% multi-site), 18% gastrointestinal system (8% upper GI [esophagus, stomach, duodenum] tract, 9% lower GI [colon, rectum] tract, and 1% other), 18% head &amp; neck (eye [conjunctiva, lacrimal sac], auditory canal, oral cavity, pharynx/oropharynx), 9% urothelial system (prostate, bladder, ureteral, urethra), 9% soft tissue, 7% skin, 7% breast, 4% upper respiratory system (vocal cords, larynx, subglottic area), and 6% others (including two cases of central nervous system involvement) (Figure 1). At presentation, 75 (53%) patients were symptomatic, whereas in the remaining 65 (47%) patients Loc-AL was an incidental finding. Bone marrow biopsy, fat pad biopsy and cardiac imaging (echocardiogram and/or cardiac MRI) were obtained in 67 (48%), 20 (14%) and 105 (74%) patients, respectively. All bone marrow and pad biopsies were negative for AL amyloid; in addition, no bone marrow biopsy revealed monoclonal plasma cells. A serum monoclonal protein (sMP) was detected in only 29 (20%) patients, 12 of whom had serum light chain different from the localized light chain type. Of the 29 patients with positive sMP, 20 had IgG isotype, 6 had IgM, 2 IgA and 1 had light chains only. Abnormal free light chain ratio was reported in 17 (12%) patients, 6 of whom had a positive sMP. Twenty-four (17%) patients had coexistent autoimmune disease and 13 (9%) co-existent malignancy that was not plasma cell related. First line management approaches included: observation with or without supportive care (57%), surgical resection (38%), radiotherapy (2%), systemic therapy (3.5% chemotherapy, 3.5% steroids) and topical therapy (3.5%). Of the 5 patients who received chemotherapy, 4 had plasma cell-directed therapy; of them, 3 maintained stable disease based on follow-up imaging and 1 had no response. The fifth patient received rituximab for their underlying MALT lymphoma. Seventeen patients (12%) required repeated interventions (median 1 [range 1-4]) for local disease progression. The most common sites requiring repeated interventions were: genitourinary system (29%), respiratory system (24%) and breast (18%). No patient progressed to systemic AL. There were no deaths attributed to Loc-AL. The median follow-up time was 46.7 months. The 2- and 5-year local progression free survival rates were 93%, and 78%, respectively, and there was no difference with regard to site of disease. The estimated median overall survival (OS) was not reached; the 2- and 5-year OS rates were 99% and 92%, respectively (Figure 2). Conclusion: The results of our study suggest thatLoc-AL has an excellent prognosis, and does not progress to systemic AL disease. A significant number of patients have no symptoms at diagnosis. Observation and/or surgical removal are usually adequate initial approaches to manage Loc-AL, however, a small percentage of patients can relapse locally requiring repeated interventions for symptom control. Consultation with a hematologist is important to rule out systemic disease.

MiR-26 inhibits proliferation and promotes apoptosis of multiple myeloma cells by targeting BNIP3.

This study was carried out to investigate the molecular mechanism of microRNA-26 (miR-26) targeting BNIP3 to mediate proliferation and apoptosis of multiple myeloma (MM) cells. The expression of miR-26 and BNIP3 in MM and normal tissues was detected by qRT-PCR and Western blot. According to the average expression of miR-26 and BNIP3, the patients were divided into 12 cases with high miR-26 expression group, 18 cases with low miR-26 expression group, 20 cases with BNIP3 high expression group, and 10 cases with BNIP3 low expression group. The correlation between the expression of miR-26 and BNIP3 and the clinicopathological characteristics of MM patients was compared and analyzed. The effect of up-regulation of miR-26 expression and BNIP3 overexpression on the proliferation of multiple myeloma cells RPMI8226 was examined by MTT assay. Flow cytometry was used to detect the effect of miR-26 expression and BNIP3 overexpression on the apoptosis of RPMI8226 cells. The dual luciferase reporter assay validated the targeted regulation of miR-26 on BNIP3. The expression level of miR-26 in MM tissues was lower than that in normal tissues (P<0.05), and the expression level of BNIP3 in MM tissues was higher than that in normal tissues (P<0.05). miR-26 was closely related to clinical stage, M protein type and light chain type (P<0.05), while BNIP3 was closely related to M protein type and light chain type (P<0.05). After up-regulating miR-26 expression, cell viability was significantly decreased (P<0.05), apoptosis rate was significantly increased (P<0.05) Dual luciferase reporter experiments confirmed that miR-26 could target BNIP3 and negatively regulate the expression of BNIP3 (P<0.05). Overexpression of BNIP3 reversed the effect of up-regulation of miR-26 expression on proliferation and apoptosis of RPMI8226 cells. Up-regulation of miR-26 expression inhibits MM cell proliferation and promotes apoptosis by targeting BNIP3.

Hyposecretory Progression Pattern Indicates Inferior Survival of Multiple Myeloma

Introduction: The application of novel drugs has significantly enhanced the prognosis of patients with MM. However, most patients will inevitably experience disease progression and relapse. At progressive disease (PD), patients always exhibit distinct features characterized by varying levels of M protein and plasma cells in the bone marrow (BMPC), even in the presence of end-organ damage. Notably, a subgroup of patients initially diagnosed with secretory MM exhibits a higher proportion of BMPC but a lower level of M protein when PD, rendering identification of this subgroup challenging without conducting bone marrow evaluations, leading to many patients experiencing PD but without timely treatment. The identification and comprehension of the hyposecretion at progression remain unclear and require further investigation. Thus, in this study, we aimed to assess the impact of different patterns of disease progression according to M protein and BMPC percentage on the survival and describe the features of the subgroup. Methods: We retrospectively analyzed the baseline and progression clinical features of 268 patients in our hospital between January 1, 2013 to July 1, 2023. We classified the PD patterns into three categories based on the elevated level of M protein and clonal plasma cells in bone marrow at progression: a. hyposecretory progression (HypoP) means &amp;gt;10% increase of the absolute percentage of BMPCs but serum M-protein increase &amp;lt;5g/L (or urine M protein increase &amp;lt; 200 mg/24h) and patients with the non-secretory subtype at diagnosis were excluded.; b. extramedullary progression (EMP) means appearance of a new extramedullary lesion; c. classic progression (ClaP) means any one or more of the other PD criteria according to International Myeloma Working Group (IMWG) criteria. High burden refers to the percentage of BMPC &amp;gt; 50%. Time from the first relapse to death as overall survival (OS) after the first progression (pro-OS). Results: There were 268 patients included in the study, and according to their features of M protein and BMPC at progression, 206 (76.8%) patients were classified in the ClaP group, 39 (14.6%) patients in EMP group and 23 (8.6%) patients in HypoP group. The percentage of female in HypoP group was 52.2%, which was much higher than that in other two groups (36.5% in ClaP and 30.8% in EMP). In general, the patients with MM are predominantly of the IgG subtype. Interestingly, for patients featured by hyposecretion in progression, the M protein types were mainly IgA (47.9%) and light chain type (43.5%) ( P&amp;lt;0.001). Compared to the ClaP and EMP group, there were more patients in HypoP presenting t(11;14) (36.8% vs 16.7% vs 11.8%) and 1q21+ (70% vs 53.8% vs 53.8%) both at diagnosis and progression. And at disease progression, the proportion of patients with t(4;14) in the HypoP group was as high as 50%. Besides, in terms of clinical manifestations, HypoP patients were more likely to suffer from hypercalcemia, renal dysfunction, and lower serum M protein level and EMP experienced high level of lactate dehydrogenase (LDH) both at diagnosis and progression. The median follow-up was 67.0m (7.6-123.0m). Figure 1 demonstrates the progression-free survival (PFS), OS and pro-OS of patients with different progression patterns. Patients in ClaP and EMP groups experienced similar PFS whereas HypoP patients had significantly shorter median PFS ( P=0.003, 23.9m vs. 22.6m vs. 14.1m). We also found that patients with ClaP and HypoP feature had inferior median OS ( P=0.007, 71.4m vs. 48.0m vs. 53.9m for ClaP vs. EMP vs, HypoP) and pro-OS ( P=0.012, 34.2m vs. 17.3m vs. 23.4m for ClaP vs, EMP vs. HypoP). Then we refer to these two as non-ClaP. In the Cox-regression, multivariate analysis showed ISS-III, ASCT and non-ClaP were associated with shorter pro-OS and OS ( Figure 1). Conclusions: In conclusion, our results indicate that the hyposecretory progression pattern is a valuable indicator of inferior survival. In such cases, bone marrow testing plays a crucial role in identifying and detecting this special group. Patients presenting with EMP or HypoP features tend to have a poorer prognosis, representing unmet clinical need. Therefore, it is important to recognize these particular patients as early as possible and to intensify treatment strategies.

Role of EBUS-TBNA/EUS-FNA and mass spectrometry for diagnosis and typing of lymph node amyloidosis: 10-year experience in two tertiary care academic centers.

The objectives of this study were to investigate the utility of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA)/endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for the diagnosis of amyloidosis coupled with the feasibility of mass spectrometry (MS) for amyloid subtyping. All patients who had amyloid diagnosed by EBUS-TBNA/EUS-FNA at two tertiary care centers from 2011 to 2020 were retrieved along with the MS subtype, clinical findings, and outcomes. Eight patients were included: seven underwent EBUS-TBNA of mediastinal lymph nodes, and one underwent EUS-FNA of a periportal lymph node. Ages ranged from 37 to 79years (median, 69 years), with equal numbers of men and women. Presenting clinical history included one case each of follicular lymphoma, lymphoplasmacytic lymphoma, rheumatoid arthritis, possible sarcoid, cirrhosis, and chronic renal insufficiency, and one case each of suspected pulmonary and cardiac amyloidosis. All cases showed waxy, amorphous material on direct smears (n=5) or ThinPrep slides (n=3), which were confirmed as amyloid on Congo Red staining. Immunohistochemistry showed dominant lambda staining in two of three cases. MS was performed in all cases and identified five of the light-chain (AL) type, one of the heavy-chain/AL type, and two suggestive of AL amyloidosis. Bone marrow biopsy performed in seven patients demonstrated that three had monoclonal plasma cells and one had lymphoplasmacytic lymphoma. Two of four patients with systemic amyloidosis received chemotherapy and remained alive, whereas three with localized disease remained stable under observation. EBUS-TBNA/EUS-FNA is effective for amyloidosis diagnosis and provides adequate material for ancillary tests, including MS, which can identify the precursor amyloidogenic protein, leading to appropriate patient management.

Cardiac amyloidosis: pathological classification and clinical analysis of 48 cases

Objective: To investigate the histological features and clinical manifestations in different types of cardiac amyloidosis to improve diagnostic accuracy. Methods: The histopathological features and clinical manifestations of 48 patients diagnosed with cardiac amyloidosis by Congo red stain and electron microscopy through endomyocardial biopsy were collected in West China Hospital of Sichuan University from January 2018 to December 2021. Immunohistochemical stains for immunoglobulin light chains (κ and λ) and transthyretin protein were carried out, and a review of literature was made. Results: The patients age ranged from 42 to 79 years (mean 56 years) and the male to female ratio was 1.1 to 1.0. The positive rate of endomyocardial biopsy was 97.9% (47/48), which was significantly higher than that of the abdominal wall fat (7/17). Congo red staining and electron microscopy were positive in 97.9% (47/48) and 93.5% (43/46), respectively. Immunohistochemical stains showed 32 cases (68.1%) were light chain type (AL-CA), including 31 cases of AL-λ type and 1 case of AL-κ type; 9 cases (19.1%) were transthyretin protein type (ATTR-CA); and 6 cases (12.8%) were not classified. There was no significant difference in the deposition pattern of amyloid between different types (P>0.05). Clinical data showed that ATTR-CA patients had less involvement of 2 or more organs and lower N-terminal pro-B-type natriuretic peptide (NT-proBNP) than the other type patients (P<0.05). The left ventricular stroke volume and right ventricular ejection fraction of ATTR-CA patients were better than the other patients (P<0.05). Follow-up data of 45 patients was obtained, and the overall mean survival time was 15.6±2.0 months. Univariate survival analysis showed that ATTR-CA patients had a better prognosis, while cardiac amyloidosis patients with higher cardiac function grade, NT-proBNP >6 000 ng/L, and troponin T >70 ng/L had a worse prognosis (P<0.05). Multivariate survival analysis showed that NT-proBNP and cardiac function grade were independent prognostic factors for cardiac amyloidosis patients. Conclusions: AL-λ is the most common type of cardiac amyloidosis in this group. Congo red staining combined with electron microscopy can significantly improve the diagnosis of cardiac amyloidosis. The clinical manifestations and prognosis of each type are different and can be classified based on immunostaining profile. However, there are still a few cases that cannot be typed; hence mass spectrometry is recommended if feasible.

Efficacy and safety of VRD regimen of autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma

Objective: To explore the stem cell collection rate and efficacy and safety of patients aged 70 and below with newly diagnosed multiple myeloma (MM) treated with the VRD (bortezomib, lenalidomide and dexamethasone) regimen followed by autologous stem cell transplantation (ASCT). Methods: Retrospective case series study. The clinical data of 123 patients with newly diagnosed MM from August 1, 2018, to June 30, 2020, at the First Affiliated Hospital of Soochow University and Suzhou Hopes Hematology Hospital, who were eligible for VRD regimen sequential ASCT, were collected. The clinical characteristics, efficacy after induction therapy, mobilization regimen of autologous stem cells, autologous stem cell collection rate, and side effects and efficacy of ASCT were retrospectively analyzed. Results: Of the 123 patients, 67 were males. The median patient age was 56 (range: 31-70) years. Patients with IgG, IgA, IgD, and light-chain types accounted for 47.2% (58/123), 23.6% (29/123), 3.2% (4/123), and 26.0% (32/123) of patients, respectively. In addition, 25.2% (31/123) of patients had renal insufficiency (creatinine clearance rate<40 ml/min). Patients with Revised-International Staging System (R-ISS) Ⅲ accounted for 18.2% (22/121) of patients. After induction therapy, the rates of partial response and above, very-good partial response (VGPR) and above, and complete response (CR)+stringent CR were 82.1% (101/123), 75.6% (93/123), and 45.5% (56/123), respectively. Overall, 90.3% (84/93) of patients were mobilized with cyclophosphamide+granulocyte colony-stimulating factor (G-CSF) and 8 patients with G-CSF or G-CSF+plerixafor due to creatinine clearance rate<30 ml/min and one of them was mobilized with DECP (cisplatin, etoposide, cyclophosphamide and dexamethasone)+G-CSF for progressive disease. The rate of autologous stem cell collection (CD34+cells≥2×106/kg) after four courses of VRD regimen was 89.1% (82/92), and the rate of collection (CD34+cells≥5×106/kg) was 56.5% (52/92). Seventy-seven patients treated with the VRD regimen sequential ASCT. All patients had grade 4 neutropenia and thrombocytopenia. Among the nonhematologic adverse events during ASCT, the highest incidence was observed for gastrointestinal reactions (76.6%, 59/77), followed by oral mucositis (46.8%, 36/77), elevated aminotransferases (44.2%, 34/77), fever (37.7%, 29/77), infection (16.9%, 13/77) and heart-related adverse events (11.7%, 9/77). Among the adverse events, grade 3 adverse events included nausea (6.5%, 5/77), oral mucositis (5.2%, 4/77), vomiting (3.9%, 3/77), infection (2.6%, 2/77), elevated blood pressure after infusion (2.6%, 2/77), elevated alanine transaminase (1.3%, 1/77), and perianal mucositis (1.3%, 1/77); there were no grade 4 or above nonhematologic adverse events. The proportion of patients who achieved VGPR and above after VRD sequential ASCT was 100% (75/75), and the proportion of patients who were minimal residual disease-negative (<10-4 level) was 82.7% (62/75). Conclusion: In patients aged 70 and below with newly diagnosed MM treated with VRD induction therapy, the collection rate of autologous stem cells was good, and good efficacy and tolerability were noted after follow-up ASCT.

#6394 ACUTE KIDNEY INJURY IN MYELOMA WITH HIGH LIGHT CHAIN PRODUCTION: A 10-YEAR EXPERIENCE

Abstract Background and Aims In multiple myeloma (MM), a high serum light chain (LC) concentration significantly increases the probability of developing cast nephropathy. The use of high cut-off (HCO) hemodialysis (HD) membranes has not been clearly shown to be effective in 2 large European studies (MYRE and EuLITE) in terms of improved prognosis. Therefore, their use is currently controversial. We want to review our experience, in the last 10 years, of patients with Acute Kidney Injury (AKI) in the context of MM in progression with high circulating LC: whether or not any HD technique has been performed and what factors may have had an impact on kidney and patient survival. Method We reviewed all cases of MM flare or progression, with LC &amp;gt;1000 mg/L and AKI, evaluated by our service between May 2012 and May 2022 (N = 20). We collected data on baseline renal function, laboratory tests, type and amount of light chain and monoclonal component, whether or not HD was performed, type of technique, evolution of kidney function and mortality. Results We counted 60% males, median age of 76.5 years (69.5-83.0), and baseline creatinine of 1.30 (0.94-1.66) with an estimated glomerular filtration rate (eGFR) of 52 mL/min (35-58). At the time of AKI, the median obtained data were: peak creatinine 4.6 mg/dL (4.1-6.0), Hb 8.8 g/dL (8.3-11.6), albumin 3.6 mg/dL (3.1-4.1), calcemia 10.1 mg/dL (9.5-11.5), blood monoclonal component of 0.80 mg/dL (0.36-2.22) and serum LC of 5. 480 mg/L (2,143-11,825). In 9 cases the myeloma was CL kappa-producing and in 11 cases CL lambda-producing. In 9 of the 20 cases (45%) the patient died within 6 months. HD was performed in 11 cases: 7 with HCO membrane, 2 with polymethylmethacrylate (PMMA) and 2 with conventional technique. Of the 7 patients dialyzed with HCO, 3 died in &amp;lt;6 months (43%) and 2 of them (29%) were also HD-dependent at the time of death. The 2 patients dialyzed with PMMA had eGFR&amp;gt;30 mL/min at 6 months after the episode. In contrast, the 2 patients who underwent conventional HD died in &amp;lt;6 months without recovery of renal function. Of the 9 patients who did not undergo HD, 4 had optimal recovery of renal function (eGFR&amp;gt;45 mL/min) but 2 of them died in &amp;lt;6 months (50%). Of the remaining 5: 2 died in &amp;lt;6 months (40%), progression to end-stage CKD was observed in 2 cases (HD was not performed and one of them died in &amp;lt;1 year), and the remaining patient remains alive with eGFR&amp;gt;20 mL/min at 2 years of follow-up. Concerning chemotherapy (QT), 13 patients were treated with bortezomib (12 in 1st line), 4 with lenalidomide and only 1 case was not treated. Of 8 patients who achieved remission with chemotherapy (40% of the total), 7 remained alive at 2 years of follow-up (87.5% of them) and did not require HD, and only 1 of them died at 1 year after a new recurrence (despite HD being implemented). Although statistical significance was not reached due to the small sample size, we did observe a statistical trend towards a higher risk of death at 6 months in patients with peak creatinine &amp;gt;5 mg/dL (p = 0.078), albuminemia&amp;lt;3.5 mg/dL (p = 0.078) and lambda-type LC (p = 0.064). Conclusions The use of HCO membranes has not seemed to influence kidney and patient prognosis. In contrast, remission after chemotherapy appears to be the most important determinant of patient survival. Recovery of kidney function was not related in this review to increased patient survival. Analytical parameters such as peak creatinine, hypoalbuminemia and type and amount of circulating LC could be studied as prognostic factors in this entity.