Primary Light Chain Amyloidosis Research Articles

A Comparative Study of Clinical Characteristics, Cytogenetic Abnormalities and Outcomes Among Multiple Myeloma, Primary Light-Chain Amyloidosis and Multiple Myeloma with Concurrent AL Amyloidosis

Introduction: Multiple myeloma (MM) and light-chain (AL) amyloidosis are both plasma cell dyscrasias and may coexist in the same patients, contributing to distinct clinical outcomes. Although they share a similar spectrum of cytogenetic abnormalities (CA), the distribution and prognostic value of these aberrations are varied. The use of fluorescence in situ hybridization (FISH) in predicting outcomes for MM is well established, while the prognostic value of CA in AL amyloidosis, notably in MM with concurrent AL amyloidosis, is still evolving. This study aimed to evaluate the outcomes of patients with MM, AL amyloidosis and coexistence of the two disorders, and address the landscape and prognostic implication of CA in patients with these 3 types of plasma cell dyscrasias. Methods: A total of 902 consecutive patients with newly diagnosed MM between January 2007 and October 2021 or AL amyloidosis between January 2007 and June 2023 were retrospectively included. Patients were classified as MM alone, MM with coexistent AL amyloidosis (MM-AL) or primary AL amyloidosis alone (pAL-alone). The presence of symptomatic MM was based on the International Myeloma Working Group (IMWG) criteria and the diagnosis of AL amyloidosis was confirmed by Congo-red-positive biopsy and immunoelectron microscopy study of the amyloid. Demographic and clinical characteristics, FISH results, along with real-world effectiveness outcomes including best hematologic response, overall survival (OS), and progression free survival (PFS) were assessed. Results: Of the 902 patients enrolled, 658 patients were in the MM-alone group, 99 in the MM-AL group and 145 in the pAL-alone group. The three groups share a similar incidence rate of CA, while the prevalence of t(11;14) was significantly higher in pAL-alone group than MM-AL and MM-alone group (41.0% vs. 24.5% vs. 16.6%, p<0.001), and the prevalence of del13q14, gain1q21 and IMWG high-risk cytogenetic abnormalities [HRCA, including t(4;14), t(14;16) and del17p] decrease in turn in MM-alone, MM-AL and pAL-alone group(del13q14, 46.4% vs. 38.1% vs. 29.7%, p=0.005; gain1q21, 52.6% vs. 46.4% vs. 27.8%, p<0.001; HRCA, 27.5 % vs. 17.2 vs. 7.6%, p<0.001) (Table). In patients with AL amyloidosis with or without coexisting MM, presence of del13q14 was associated with higher level of baseline bone marrow plasmacytosis and difference in involved and uninvolved free light chain (dFLC). Compared with the MM-alone group, a significantly lower proportion of the MM-AL group achieved hematologic response (90.4% vs. 67.7%, p<0.001) and very good partial remission (VGPR, 44.6% vs. 68.9%, p<0.001). The OS of patients with MM-AL was significantly inferior to patients with MM-alone (median, 25.2 months vs. 96.8 months, p<0.001) or pAL-alone (median, 25.2 months vs. not reached, p<0.001 )(Figure B), while patients with MM-alone has shorter PFS than AL amyloidosis irrespective of the presence or absence of MM (MM-alone vs. pAL-alone: median, 56.8 months vs. not reached, p=0.007; MM-alone vs. MM-AL: median, 56.8 months vs. not reached, p=0.515) (Figure A). Other than MM-alone group, no significant difference in PFS and OS was found between pAL patients with and without HRCA, as well as the MM-AL group, indicating the difference in prognostic implications of common HRCAs among the three groups. When stratified by the type of plasma cell disorders and status of t(11;14) (a CA that strongly related to poor outcome of pAL), patients with MM-AL and t(11;14) presented the worst OS (median, 8.2 months, p<0.001) (Figure C). Conclusion: This comparative study presented an apparent discrepancy in distribution and prognostic role of CA in different plasma cell dyscrasias. Comparing with patients with MM-alone and pAL-alone, MM-AL patients, notably with the presence of t(11;14), had the poorest survival.

Characteristics and outcomes of COVID-19 in patients with plasma cell dyscrasias during the first Omicron wave in Beijing since December 2022: a retrospective study at a National Clinical Research Center for Hematologic Disease.

The wave of coronavirus disease 2019 (COVID-19) with Omicron variant reached its first peak in Beijing, China in December 2022. We delineated characteristics and factors associated with adverse outcome of patients with plasma cell dyscrasias (PCDs) and COVID-19 during the first month of the wave. A total of 104 patients with a median age of 65 years were included in the study, with multiple myeloma (74%, n=77) and primary Immunoglobulin light chain amyloidosis (16.3%, n=17) being the two most common disease. Overall, severe or critical COVID-19 was developed in 18 (17.3%) patients, with a total all-cause mortality rate of 4.8% (n=5). The vaccination coverage was 41% and 48.1%, before and during the upsurge of Omicron, respectively, calling for the improvement of vaccination in PCD patients. Multivariable analysis revealed that age was the only independent risk factors (OR=1.14, 95% CI: 1.06-1.26, p = 0.002) associated with the development of severe or critical disease. Among patients with severe or critical group, low levels of albumin (HR=18.29; 95% CI: 1.82-183.44, p = 0.013) and high levels of lactic dehydrogenase (LDH) (HR=0.08; 95% CI: 0.01-0.65, p = 0.018) were associated with longer time to negative conversion of COVID-19.

#5339 TRANSTHYRETIN AMYLOIDOSIS WITH BIOPSY PROVEN RENAL INVOLVEMENT

Abstract Background and Aims Systemic amyloidosis is a cluster of disorders characterized by tissue deposition of amyloid (highly ordered fibrils composed of low molecular weight subunits of a variety of proteins). Transthyretin (TTR) amyloidosis (ATTR) is either an autosomal dominant inherited condition (ATTRv, where v stands for “variant”) or a non hereditary disease due to misfolding of wild-type TTR (ATTRwt). ATTR is likely underdiagnosed due to its clinical variability and lack of specific symptoms or biomarkers. The first aim of the study is to emphasise the importance of suspecting ATTR when facing certain clinical manifestations in association with renal impairment and urinary abnormalities. Furthermore, renal biopsy provides crucial information for a correct diagnosis and treatment approach. Method We report 5 cases of biopsy-proven renal ATTR deposition in patients presenting with mild to moderate renal impairment and mild urinary abnormalities. The TTR precursor has been confirmed in kidney specimens by immunohistochemistry. Genotyping was carried out in every patient. Results The presence of amyloid was found in all patients, with different distribution (#1-3 pericapsular and vascular; #2 vascular; #4 mesangial, vascular, in tubular basement membrane and in the interstitium of cortex and medulla; #5 pericapsular, vascular and interstitial). On genetic analysis three patients were wild-type (#1-2-5), one carried the c.424G>A (p.(Val142Ile)) mutation (#3) and the last one the Val30Met mutation (#4). Conclusion Suspicion of ATTR should be considered in patients with increase in serum creatinine, mild proteinuria and cardiac and peripheral nerve symptoms. This can be of utmost importance in elderly patients in whom a monoclonal gammopathy of undetermined significance can co-exist and drive a wrong diagnosis of primary light chain amyloidosis (AL), that could lead the clinician to undertake inappropriate treatments. Renal biopsy and genetic sequencing are both critical in diagnosing ATTR. Finally, we suggest distinguishing in the context of the ATTR deposition disease an ATTR nephropathy characterized by mesangial accumulation of amyloid, that impacts functional and urinary assessment, from isolated deposition in small vessels without specific clinical consequences, albeit critical for ATTR diagnosis.

Kidney and urinary tract involvement in systemic mastocytosis.

Systemic mastocytosis (SM) is a disorder of excessive mast cell accumulation in tissues due to a somatic gain-of-function mutation, commonly in the KIT gene, which prevents apoptosis of mast cells. Whereas bone marrow, skin, lymph nodes, spleen, and gastrointestinal tract are commonly involved, kidneys are rarely involved directly by SM. However, there are increasing reports of indirect kidney involvement in patients with SM. Novel anti-neoplastic agents to treat advanced forms of SM include non-specific tyrosine kinase inhibitors, which are reported to be associated with kidney dysfunction in some patients. SM is also associated with immune-mediated glomerulonephritis (GN) like mesangioproliferative GN, membranous nephropathy, and diffuse proliferative GN. Kidney injury, in the form of monoclonal deposition disease and primary light chain amyloidosis, is reported in SM associated with plasma cell dyscrasia. In this narrative review, we discuss the various ways kidneys (and the urinary tract) are involved in patients with SM.

Prognostic value of translocation t(11;14) in primary light-chain amyloidosis treated with bortezomib-based regimen

Objective: To investigate the prognostic value of translocation t(11;14) in newly-diagnosed primary light-chain (AL) amyloidosis patients treated with bortezomib-based regimen. Method: Clinical information of newly-diagnosed AL amyloidosis patients in Peking Union Medical College Hospital who had baseline t(11;14) data and accepted bortezomib-combined therapies from September, 2015 to September, 2021 was collected. The relationships between t(11;14) status and baseline characteristics, hematological response, organ response and prognosis were analyzed. Results: A total of 152 patients were included, aged (59.5±9.1) years and 93 cases were male (61.2%). Forty-six patients carried t(11;14) (30.3%). There was no statistical difference in the proportion of organ involved, distribution of Mayo 2004 and 2012 stages and laboratory indexes between patients with and without t(11;14) (all P>0.05). For hematological response, the difference in the rates of ≥very good partial response (VGPR) between those with t(11;14) and without after the first cycle [28.2%(11/39) vs 37.4%(34/91), P>0.05] was not statistically significant. After 3 cycles, the difference in the rates of ≥VGPR between two groups was not statistically significant [35.9%(14/39) vs 51.1%(46/90), P>0.05]. The difference in the ratio of the best hematological response reaching ≥VGPR between two groups during the first-line treatment was not statistically significant [52.2%(24/46) vs 64.2%(68/106), P>0.05]. But patients with t(11;14) had lower cardiac response rate at 3 months [15.2%(5/33) vs 34.6%(28/81), P=0.038] and 6 months [19.4%(6/31) vs 50.6%(42/83),P=0.003] than those without, but the difference in cardiac response rates at 12 months was not statistically significant [41.7%(10/24) vs 53.5%(38/71),P>0.05]. For survival, the differences in overall survival (not reached vs 50.1 months, P>0.05) and hematological event-free survival (36.2 months vs 39.9 months, P>0.05) between patients carrying t(11;14) and those without were not statistically significant. Conclusion: Patients with t(11;14) had lower cardiac response rate than those without, but their hematological response and survival are not significantly different from those free from t(11;14).

Prevalence, clinical characteristics and treatment outcome of factor X deficiency in a consecutive cohort of primary light-chain amyloidosis

Factor X (FX) deficiency is prevalent in light-chain (AL) amyloidosis but its clinical significance was not investigated deeply. We conducted a retrospective analysis of a consecutive cohort with 207 primary AL amyloidosis patients. FX deficiency was present in 129 patients (62.3%). Those with FX deficiency had higher dFLC (299.6 mg/L vs. 102.3 mg/L, P < 0.001), higher cardiac troponin I (0.05 μg/L vs. 0.02 μg/L, P < 0.001) and N-terminal pro-brain natriuretic peptide (3115 ng/L vs. 392 ng/L, P < 0.001), and more patients with bone marrow plasma cells > 10% (18.0% vs. 4.3%, P = 0.008). The prevalence of FX deficiency increased with the Mayo 2004 stage. FX-deficient patients exhibited inferior overall survival (P < 0.001) and progression-free survival (P < 0.001) than others. Fifty-five patients with FX deficiency received retesting of FX activity after anti-plasma cell therapy. The median variation in FX activity was + 6.8% (range, −24.5% ~ +73.4%). Better improvement of FX activity was observed in patients with complete hematologic response (+18.2% vs. +4.0%, P = 0.036) and at least one organ response (+14.4% vs. +3.4%, P = 0.024). FX deficiency is associated with a heavier disease burden and poorer survival in primary AL amyloidosis. Improvement of FX activity tends to appear in patients with better hematologic and organ responses after chemotherapy.

Value of (11)C-PiB PET/MRI in the evaluation of organ involvement in primary systemic light chain amyloidosis

目的分析11C标记的匹兹堡化合物B（11C-PiB）PET/MRI在原发性系统性轻链型淀粉样变（pAL）中评估器官受累的价值。方法回顾性分析2019年1月至2021年10月在华中科技大学同济医学院附属协和医院就诊的20例pAL患者及3名健康志愿者的临床资料，比较临床标准评估器官受累和PET/MRI评估的相关性，分析心脏相关生物学指标、疾病分期与心脏最大标准摄取值（SUVmax）之间的关系及24 h尿蛋白定量与肾脏SUVmax之间的关系。结果①纳入20例患者，初诊患者18例，非初诊患者2例。观察到11C-PiB摄取阳性的脏器分别为：心脏15例（75％），肺部8例（40％），骨髓10例（50％），肌肉10例（50％），舌肌7例（35％），甲状腺6例（30％），唾液腺4例（20％），脾脏2例（10％），胃壁1例（5％）。②11C-PiB在心脏及骨髓摄取的阳性率与临床评估标准具有很好的相关性。在肺组织、脾脏、腺体、肌肉和舌肌中，11C-PiB PET/MRI评估的阳性率明显高于临床标准。但对于神经系统受累和脂肪组织的评估11C-PiB PET/MRI具有局限性。③分析18例初诊患者心脏相关生物学指标与心脏SUVmax之间的关系。左心室射血分数（LVEF）<50％且室间隔厚度（ISV）≥1.2 cm的患者相较LVEF≥50％且ISV<1.2 cm的患者其心脏SUVmax更高（P<0.05）。心脏SUVmax值在Mayo2004分期、Mayo2012分期各期之间差异有统计学意义，分期越晚，SUVmax值越高（P<0.05）。心脏SUVmax与心肌肌钙蛋白酶Ⅰ、N 末端前体脑钠肽水平呈明显正相关（P<0.01），肾脏SUVmax与24 h尿蛋白定量无明显相关性（P>0.05）。结论全身11C-PiB PET/MRI作为一种淀粉样蛋白的可视化系统，若用于器官水平的定性评估，具有提高早期无创性诊断pAL水平的潜力；用于器官水平（尤其是心脏）的定量评估，有望更精准评估器官功能和预测疾病预后。

Awareness of Nuclear Medicine Physicians in Romania Regarding the Diagnostic of Cardiac Amyloidosis-A Survey-Based Study.

Amyloidosis is a heterogeneous group of diseases caused by the extracellular deposition of amyloid insoluble fibrils in multiple organs, resulting in various clinical manifestations. Cardiac amyloidosis (CA) occurs mainly in primary light-chain (AL) amyloidosis, hereditary transthyretin (ATTRv) amyloidosis and senile or wild-type transthyretin (ATTRwt) amyloidosis. Knowing that myocardial uptake at bone scintigraphy is an essential step in the ATTR-CA diagnostic algorithm, the level of awareness among nuclear medicine physicians (NMPs) using bone tracer scintigraphy is of great importance. The objective of the study was to evaluate NMPs’ awareness of scintigraphy with bisphosphonates for the detection of CA. We conducted an online survey among NMPs from Romania to assess their current awareness and state of knowledge of nuclear techniques used in CA. Among the total 65 Romanian NMPs, 35 (53%) responded to this questionnaire. Approximately three-quarters of participants (74%) found a diffuse accumulation of bisphosphonates in the heart on scintigraphy performed for bone pathology as an incidental discovery. Detection of myocardial uptake of 99mTc-labeled bisphosphonates on scintigraphy suggests CA-AL for 3% of participants and for 9% of respondents, the appearance is of uncertain cardiac amyloidosis, while 5% of participants observed cardiac uptake but did not report it as CA. Even if more than half of those who responded to this survey (54%) found abnormal cardiac uptake and interpreted it as CA-ATTR, only 14% contacted the referring physician to draw attention to the incidental discovery to refer the patient to a specialist in rare genetic cardiomyopathy. Regarding the knowledge about the categories of bisphosphonates recommended in the diagnosis of CA-ATTR, 54% answered inadequately that methylene diphosphonate (MDP) could be used. Romanian nuclear physicians are partially familiar with CA diagnosis by scintigraphy, but its diagnostic potential and standardization, recommended radiotracers and acquisition times and interpretation algorithms are known in varying proportions. Therefore, there is a need to enhance knowledge through continuing medical education programs in order to standardize the protocols for the acquisition, processing and interpretation of bisphosphonate scintigraphy for the detection of cardiac ATTR amyloidosis.

Reversing the poor prognosis of primary amyloid light‑chain amyloidosis with cardiac involvement.

Reversing the poor prognosis of primary amyloid light‑chain amyloidosis with cardiac involvement.

Daratumumab Monotherapy for Patients with Intermediate or High-Risk Smoldering Multiple Myeloma (SMM): Centaurus, a Randomized, Open-Label, Multicenter Phase 2 Study

Daratumumab Monotherapy for Patients with Intermediate or High-Risk Smoldering Multiple Myeloma (SMM): Centaurus, a Randomized, Open-Label, Multicenter Phase 2 Study

Clinical Analysis of Patients with MGUS, Primary Light Chain Amyloidosis, Multiple Myeloma or Multiple Myeloma with Concurrent Amyloidosis

To summarize and compare the clinical baseline characteristics of patients with monoclonal gammopathy of undetermined significance (MGUS), primary light chain amyloidosis (pAL), multiple myeloma (MM), or MM with concurrent amyloidosis, especially the differences in cytogenetic abnormalities. The clinical data of 15 cases of MGUS, 34 cases of pAL, 842 cases of MM and 23 cases of MM with concurrent amyloidosis were analyzed and compared retrospectively. Cytogenetic statistics showed that the incidence of t (11; 14) in the four groups (MGUS vs pAL vs MM vs MM with concurrent amyloidosis) was 0%, 33.3%, 16.4%, and 15.8%, respectively (P=0.037); that of 13q deletion was 20.0%, 14.7%, 45.8% and 56.5%, respectively (P<0.001); gain of 1q21 was 50.0%, 12.5%, 47.4% and 40.9%, respectively (P=0.001). Proportion of pAL patients with 0, 1 and≥2 cytogenetic abnormalities (including 13q deletion, 17p deletion, 1q21 amplification and IgH translocation) accounted for 41.9%, 41.9% and 16.1%, respectively; while the proportion of the same category in MM was 17.6%, 27.3%, and 55.2% respectively; this ratio of MM with concurrent amyloidosis was more similar to MM. Subgroup analysis showed that genetic abnormalities (including 13q deletion, 17p deletion and 1q21 amplification) were comparable within t (11; 14) negative and positive groups. Compared with positive cases, t(11; 14) negative patients with MM or MGUS were more likely to have 13q deletions and multiple genetic abnormalities. Clinical characteristics of pAL, especially cytogenetic abnormalities, are significantly different from MM with concurrent amyloidosis. It suggests that although the onset characteristics are similar, actually the two diseases belong to different disease subtypes which should be carefully predicted and identified.

A Case Report of Sick Sinus Syndrome as an Initial Presentation of Primary Amyloidosis

Primary light chain amyloidosis (AL amyloidosis) rarely presents as sick sinus syndrome (SSS), and only a few cases have been reported in the literature. A higher index of suspicion is needed to diagnose AL amyloidosis in patients presenting with SSS. Recognizing the electrocardiography (ECG) and transthoracic echocardiogram (TTE) findings for amyloidosis are crucial for early recognition, proper management, and to improve the patients' quality of life.A 79-year-old female initially presented with dyspnea and was diagnosed with SSS that required a pacemaker insertion. Ten days later, the patient had complained of dysphagia and difficulty swallowing. She underwent an esophagogastroduodenoscopy (EGD) to investigate further, and it revealed esophageal and duodenal ulcers, and biopsy was positive for amyloidosis. The patient was worked up for amyloidosis, including bone marrow biopsy, renal biopsy, frees light chains, and serum electrophoresis, which all confirmed the diagnosis of primary amyloidosis. Unfortunately, due to the terminal nature of her condition, the patient was discharged with comfort measures to hospice care.

S2935 Gastric Mass: A Case of Primary Amyloidosis

INTRODUCTION: We present a rare case of primary amyloidosis presenting as a bleeding gastric mass. Involvement of the gastrointestinal tract is very common in systemic amyloidosis (30-60%), but very rare in primary amyloidosis (8%). CASE DESCRIPTION/METHODS: An 81-year-old man presented to the hospital with anemia with a hemoglobin of 5.3 g/dL. Symptoms on presentation included severe generalized weakness and weight loss. Lab results showed MCV 94.3, Iron 26 ug/dl, Ferritin 15 ng/dl. Upper endoscopy revealed a large ill-defined mass in the gastric body with diffuse ulcerations, friable mucosa, and intramural hematoma (Figure 1). The mass was biopsied, and histology revealed Congo red positive amorphous proteinaceous material consistent with amyloid with apple-green birefringence under polarized light. (Figures 2A and 2B). Serum protein electrophoresis revealed a gamma monoclonal gammopathy. Serum immunofixation showed an IgG kappa and a free light chain lambda. A serum-free light chain assay was not obtained. A bone marrow biopsy revealed plasmacytosis, adjunct flow cytometry showed CD 38 + Plasma cell population with cytoplasmic kappa light chain excess/restriction. These findings where indictive of primary light chain amyloidosis (AL) and excluded the diagnosis of multiple myeloma or systemic amyloidosis (AA). DISCUSSION: Primary amyloidosis is a rare entity. The reported incidence in a population-based study was approximately 1 case per 100,000 population per year. Fatigue and weight loss are the most common clinical manifestations. Hemorrhagic manifestations, congestive heart failure, nephrotic syndrome, malabsorption, and constipation are all relatively common. The diagnosis is made by establishing the presence of amyloid in tissue. Amyloid is amorphous, waxy-appearing, and pink in H&E slides. The Congo red stain is the most used technique for confirming amyloid in a tissue biopsy. characteristic apple-green birefringence under polarized light is seen. Involvement of the gastrointestinal tract is very common in systemic amyloidosis (30–60%), but very rare in primary amyloidosis. The exact prevalence of primary amyloidosis involvement of the stomach is unknown, but the involvement of the upper gastrointestinal tract appears to be present in 8% of all cases. The mainstay treatment is chemotherapy. primary amyloidosis has a poor prognosis when compared to systemic amyloidosis with a predicted median survival of <2 years despite treatment.Figure 1.: Large ill-defined mass in the gastric body with diffuse ulcerations and friable mucosa.Figure 2A.: Congo red positive amorphous proteinaceous material.Figure 2B.: Apple green birefringence under polarized light.

Prognostic significance of the frontal QRS-T angle in patients with AL cardiac amyloidosis

IntroductionCardiac involvement is a leading cause of morbidity and mortality in primary light chain (AL) amyloidosis. The electrocardiographic spatial QRS-T angle reflects changes in the direction of the repolarization sequence and is a powerful predictor of outcome in patients with heart failure. We examined the significance of the frontal QRS-T angle in predicting the clinical outcome in patients with AL cardiac amyloidosis. MethodsForty-three consecutive patients with cardiac involvement of AL amyloidosis were studied. Patients were followed for survival. ResultsPatient median age was 62 years, 56% were males. After a median follow up of 56 months, 16 out of 43 patients had died (37%). The median QRS-T angle was 102° (interquartile range 35–148). QRS-T angle>102° was associated with increased prevalence of lambda free light chain disease and the presence of a pleural effusion. It was also associated with increased interventricular septum thickness, smaller left ventricle end-diastolic diameter, echocardiographic myocardial sparkling texture, pericardial effusion, elevated NT-Pro-BNP and increased restrictive physiology evident by increased E/A and E/e`. A QRS-T angle>102° was a significant predictor of increased mortality by Kaplan-Meier survival analysis (71.6 ± 11.1% vs. 45.7 ± 11.1%, P = .02). A QRS-T angle>102° was an independent predictor of mortality by Cox regression analysis (HR 3.00, 95% CI 1.01–8.89, P < .05). ConclusionsThe QRS-T angle is associated with indices of advanced amyloid disease and is an independent predictor of survival.

Home Treatment of Bortezomib: A Preliminary Exploration of a New Treatment Mode in China

Background:Bortezomib had been used as a standard treatment in plasma cell disorders patients for years. It has been proved that subcutaneous bortezomib was locally well tolerated, had non-inferiority effect andless peripheral neuropathy compared with intravenous administration. Few studies about home treatment of bortezomib had been reported to be feasible and of benefit to patients. But in these studies, bortezomib was adminstrated by special nurse visiting home regularly.In consideration of the shortage of medical resources in China and aiming to make it easier to receive bortezomib treatment for patients, we made a preliminary exploration of home treatment of bortezomib by patients or relatives themselves in China for the first time. Methods:234 patients provided written informed consent were enrolled in our study between March 2018 and April 2019.A clinical nurse specialist provided hands-on guidance on home-injection for patients in outpatient department. The following information including geographical and clinical data, adverse events in treatment, feedback from patients about cost and time saved than hospital injection, and difficulty degree and satisfaction with home treatment using a rating scale between 0 and 10 were collected. The higher the score, the easier the injection and more satisfied with the mode of home treatment. Results:The median age at diagnosis was 56 (27-83) years old. 75 (32.1%) patients were diagnosed with primary light chain amyloidosis, 70 (30.0%) POEMS syndrome, 62 (26.5%) multiple myeloma, 15 (6.4%) multi-center Castleman disease, 4 (1.7%) light chain deposition disease, 4 (1.7%) Waldenstrom's macroglobulinemia, 2 (0.9%) cryoglobulinemia, 1 (0.4%) mycosis fungoides and 1 (0.4%) monoclonal gammopathy-associated scleromyxedema.Patients lived within a 3,010 kilometer radius of the city of Beijing, 46 (19.7%) patients lived in Beijing and 67 (28.6%) patients lived more than 1,000 kilometers from our hospital (Figure 1. Geographical distribution of 234 patients. The dots represent number of patients in different provinces. The blue dot represents 46 patients lived in Beijing, the city our hospital located in). As so far, patients received a median number of 20 (4-36) injections and a total of 5068 injections of bortezomib. The most common injection-site reaction was redness (24.8%) and pigmentation (20.9%). In 5068 injections, 2 (0.04%) local hematomas at injection site, 7 (0.14%) injection dose errors and 5 (0.10%) needlestick injuries occurred, respectively. Medicine bottle was broken during drug dissolution for only once (0.02%). The median cost and time saved was RMB 200 (100-6000) and 4.5 (0.5-100) hours per injection per person for home treatment. The total saving of money was RMB 3927,804, and the total time saved was 15,617.5 hours. For the score of difficulty degree of injection and satisfaction with home treatment, 201 (85.9%) and 208 (88.9%) rated 8 and higher, respectively. Conclusion: Home treatment of bortezomib is feasible, and both cost-effective and time-saving in China, which should be promoted in other medical centers. Figure 1 Disclosures No relevant conflicts of interest to declare.

脾破裂と後腹膜血腫を契機に発見されたアミロイドーシスの1例(A case of amyloidosis diagnosed as spontaneous splenic rupture and retroperitoneal hemorrhage)

要旨 我々は，当初は外傷の可能性も考慮されたが，結果的にALアミロイドーシスと診断された体幹部多発出血の1例を経験し，適切な治療にて救命し得たので報告する。症例は高血圧の既往がある74歳の女性で，自宅で動けなくなっているところを発見・救急要請され，前医に搬送された。前医で行った腹部CT検査で後腹膜血腫を認め，骨盤骨折の疑いでドクターヘリが要請された。フライトドクターが現場でFAST（focused assessment with sonography for trauma）陽性と判断した。病院到着後，腹腔内液体貯留が増加，急速輸液に反応しないショック状態に対して，緊急開腹手術を行った。術中所見では，腫大脾の破裂がみられ，脾臓摘出術を行った。また，続いて行った血管造影検査にて，右腰動脈からのextravasationが確認され，コイル塞栓術を行って止血を完了した。摘出した脾臓組織の病理検査を行い，ALアミロイドーシスと診断された。その後，患者は退院し，外来通院中である。アミロイドーシスにおいて腫大脾が破裂・出血する症例はあるが，後腹膜出血を同時に併発した報告は検索する限り皆無であった。本症例のように外傷機転のない体幹多発出血の原因には，アミロイドーシスを鑑別に挙げるべきである。

Anti-CD38 human antibody Daratumumab in the treatment of relapsed or refractory primary light chain amyloidosis: 2 cases report and literatures review

Anti-CD38 human antibody Daratumumab in the treatment of relapsed or refractory primary light chain amyloidosis: 2 cases report and literatures review

Oral melphalan plus high-dose dexamethasone as first-line therapy for patients with primary light chain amyloidosis

目的探讨口服美法仑联合大剂量地塞米松（MDex）方案一线治疗原发性轻链型淀粉样变（pAL）的疗效。方法收集2009年1月至2017年7月接受MDex方案治疗的76例初治pAL患者临床资料，对其疗效及生存进行回顾性分析。结果①76例患者中，男47例，女29例，中位年龄为56（20~74）岁。66例患者可进行梅奥2004分期（1、2、3期者分别为21、32、13例），65例（85.53%）患者存在≥2个器官受累。中位疗程数为5（1~21）个。②在可评价疗效的60例患者中，总体血液学缓解率为48.33%（29/60），完全缓解率和非常好的部分缓解率均为20.00%（12/60），获得最佳血液学缓解的中位时间为5（1~15）个月；总体器官缓解率为36.67%（22/60）。③生存患者的中位随访时间为23（1~113）个月，中位无进展生存（PFS）及总生存（OS）时间及分别为34、43个月。治疗3个月后仍存活患者的中位PFS和OS时间分别为46、65个月。④梅奥2004分期3期和1~2期患者的中位OS时间分别为5、65个月，差异有统计学意义（P=0.001）。结论MDex方案是pAL早期患者一种有效的治疗手段，但不适用于心脏受累的晚期患者。

A rash with a heavy heart

Cardiac amyloidosis (CA) is relatively rare and frequently misdiagnosed. Other disorders presenting with increased left ventricular (LV) mass can mimic its diagnosis. This case illustrates unique findings of primary light chain (AL) amyloidosis in a patient with remarkable signs of CA. Here, we report a 49-year-old male with prior diagnosis of hypertrophic cardiomyopathy (HCM) based on an echocardiogram performed 1 year earlier, which presented with 8 weeks of periorbital rash. The patient had numbness in the past 3 years. More recently, the patient presented with shortness of breath. Physical examination was remarkable for periorbital purpura, macroglossia and orthostatic hypotension. Cardiac auscultation showed S3 and S4. Electrocardiography showed diffuse low-voltage QRS complexes. Echocardiography revealed severe diastolic impairment; granular ‘sparkling’ pattern of the myocardium with thickened walls, interatrial septum and valves; and pericardial effusion. Diastolic dysfunction and thick walls with low ECG voltage are compelling diagnostic findings. Laboratory workup showed increased free light chain-differential (FLC-diff), N-terminal fragment of brain natriuretic peptide (NT-BNP) and cardiac Troponin T (cTnT). Bone marrow biopsy confirmed AL amyloidosis. A diagnosis of AL amyloidosis with cardiac involvement mimicking HCM was made. The patient died during hospitalization due to sudden cardiac death. This case illustrates the importance of the combination of clinical, serological, and electro- and echocardiographic findings to establish the diagnosis of CA.

The diagnostic and prognostic values of serum free light chain in patients with primary light chain amyloidosis

目的研究血清游离轻链（sFLC）检测在原发性轻链型淀粉样变（pAL）中的诊断和预后价值。方法回顾性分析2009年1月至2015年6月确诊且有完整sFLC数据的126例pAL患者的临床资料，探讨sFLC的诊断价值，并采用Cox回归法分析sFLC差值（dFLC）的预后价值。结果126例患者中男女比例为1.57∶1，中位年龄为57 (37~81）岁，λ轻链型者80例（63.5%），肾脏受累者87例（69.0%），心脏受累者79例（62.7%）。126例患者的中位dFLC为99 (1~4 263）mg/L。血清蛋白电泳、血清免疫固定电泳、尿免疫固定电泳和sFLC比值异常法检测单克隆免疫球蛋白（M蛋白）的阳性检出率分别为34.9%（44/126）、63.5%（80/126）、77.0%（97/126）和81.0%（102/126）。联合上述四种方法可将M蛋白的检出率提高至98.4%（124/126）。中位随诊16个月后，37例患者死亡，所有患者的中位生存时间尚未达到。多因素分析发现dFLC ≥130 mg/L是影响pAL患者预后的独立危险因素（HR=3.272, 95% CI 1.384~7.739，P=0.007）。结论sFLC检测可显著提高pAL患者M蛋白的检出率；高水平dFLC是影响患者预后的独立危险因素。