Plasma cell disorder

浆细胞疾病
  • 文章类型: Journal Article
    本评论强调需要针对癌症健康差异采取全面的结构性种族主义措施,特别是多发性骨髓瘤(MM)的黑白差异。最近的政治和社会呼吁以及量化结构性种族主义能力的进步导致对结构性种族主义的健康后果的研究迅速增加。然而,到目前为止,大多数研究都使用了结构种族主义的一维措施,这些措施不能捕获累积的影响,也不能识别造成差异的主要原因。此外,措施可能无法反映与潜在疾病过程和风险最相关的结构性种族主义方面。本研究提出了一种多方面的方法来衡量与MM相关的结构性种族主义,包括全面的、疾病和风险人群定制的社会和环境数据以及与结构性种族主义相关的潜在生物学变化相关的易感性和进展的生物标志物。这种新的结构性种族主义措施可能会提高评估结构性种族主义对癌症健康差异影响的能力,这可能会促进对疾病病因和种族群体观察到的差异的理解。
    This commentary highlights a need for comprehensive measures of structural racism tailored to cancer health disparities, in particular Black-White disparities in multiple myeloma (MM). Recent political and social calls and advances in the ability to quantitate structural racism have led to rapidly growing research on the health consequences of structural racism. However, to date, most studies have used unidimensional measures of structural racism that do not capture cumulative influences or enable the identification of factors most responsible for driving disparities. Furthermore, measures may not reflect aspects of structural racism most relevant to underlying disease processes and risks. This study proposes a multifaceted approach to measuring structural racism relevant to MM that includes comprehensive, disease- and at-risk population-tailored social and environmental data and biomarkers of susceptibility and progression related to underlying biological changes associated with structural racism. Such novel measures of structural racism may improve the ability to assess the influence of structural racism on cancer health disparities, which may advance understanding of disease etiology and differences observed by racialized groups.
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  • 文章类型: Case Reports
    意义不明的单克隆丙种球蛋白病(MGUS)是一种肿瘤前疾病,涉及浆细胞或淋巴浆细胞增殖-临床表现,从无症状到系统性器官受累的症状。它通常与轻链淀粉样变性有关,通常在诊断过程中增强。除贫血外,它通常与血小板减少症有关。该病例报告的重点是一名63岁的西班牙裔女性,该女性最初没有任何症状,但患有严重的血小板增多症。肾淀粉样变性的发现促进了MGUS的最终诊断。尽管血小板减少,但很少有患者最初出现严重的血小板增多症。这通常与浆细胞疾病有关。该病例强调需要考虑血液学表现异常的患者的浆细胞疾病。通过提供对临床表现和诊断评估的详细分析,强调了及时识别和干预以防止不可逆器官损害的重要性。
    Monoclonal gammopathy of undetermined significance (MGUS) is a pre-neoplastic condition involving plasma cells or lymphoplasmacytic proliferation-clinical presentations ranging from asymptomatic to symptoms of systematic organ involvement. It is commonly associated with light chain amyloidosis and usually strengthens during diagnosis. It is usually associated with thrombocytopenia in addition to anemia. This case report focuses on a 63-year-old Hispanic female who initially presented without any symptoms but with severe thrombocytosis. The finding of renal amyloidosis boosts the final diagnosis of MGUS. Rarely a patient is initially presented with severe thrombocytosis despite thrombocytopenia, which is commonly associated with plasma cell disorders. The case emphasizes the need for considering plasma cell disorders in patients with abnormal hematologic manifestations. It highlights the importance of timely identification and intervention to prevent irreversible organ damage by providing a detailed analysis of the clinical presentation and diagnostic evaluation.
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  • 文章类型: Case Reports
    POEMS综合征(多发性神经病,器官肿大,内分泌疾病,单克隆浆细胞疾病,皮肤变化)是指与浆细胞疾病有关的罕见副肿瘤实体,以多种全身表现为特征,必须一起研究以建立及时的诊断。我们报告了一个60岁的女性病例,最初被归类为格林巴利综合征1年零7个月,接受三个周期的免疫球蛋白,但无阳性反应。临床表现的特点是四肢疼痛性感觉异常和轻瘫,患者还发展为远端皮肤色素沉着过度和多发性腺病。神经传导研究显示,在脑脊液(CSF)研究中证明了慢性感觉运动轴索多发性神经病和白蛋白细胞学解离。在随后的评估中,发现了与Castleman病相容的Lambda轻链和淋巴结活检,因此确定患者符合POEMS综合征的标准。此病例报告强调了在遇到免疫起源的多发性神经病患者对常规疗法无反应时纳入其他诊断观点的重要性。
    POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal plasma cell disorder, Skin changes) refers to a rare paraneoplastic entity linked to a plasma cell disorder, characterized by multiple systemic manifestations that must be studied together to establish a timely diagnosis. We report a case of a 60-year-old female who had been initially classified to have Guillain Barré syndrome for one year and seven months, receiving three cycles of immunoglobulin without a positive response. The clinical picture was characterized by painful paresthesias in four limbs and paraparesis, with the patient also developing distal cutaneous hyperpigmentation and multiple adenopathies. Neuroconduction studies revealed chronic sensorimotor axonal polyneuropathy and albumin-cytological dissociation was evidenced in the study of cerebrospinal fluid (CSF). In the subsequent evaluation, Lambda light chains and a lymph node biopsy compatible with Castleman\'s disease were found, and hence it was determined that the patient met the criteria for POEMS syndrome. This case report highlights the importance of incorporating other diagnostic perspectives when encountering patients with polyneuropathy of immunological origin who fail to respond to conventional therapies.
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  • 文章类型: Journal Article
    背景:多发性神经病,器官肿大,内分泌病,单克隆丙种球蛋白病,皮肤改变(POEMS)综合征是一种罕见的多系统克隆浆细胞疾病。肺部受累常见于POEMS综合征患者,表现出各种临床特征。因此,为了提高诊断准确性并提供治疗策略,需要全面分析POEMS综合征的肺部表现.
    方法:这项回顾性研究包括北京协和医院POEMS综合征患者,中国主要的转诊医疗中心,2013年6月1日至2023年6月1日。人口统计数据,实验室发现,肺功能检查结果,超声心动图,并提取胸部影像学数据。使用t检验或Mann-Whitney方法比较连续变量。进行Pearson卡方检验或Fisher精确检验以比较分类数据。
    结果:总体而言,282名被诊断患有POEMS综合征的人被纳入这项研究,其中56%为男性,平均年龄48.7岁。40.1%的病人出现呼吸道症状,以呼吸困难为最常见症状(34.4%)。胸部计算机断层扫描和超声心动图检查结果显示,56.4%的患者出现胸腔积液,62.8%显示纵隔或肺门淋巴结病,46.5%的患者出现胸膜增厚,27.3%显示肋骨或胸椎的骨病变,7.8%显示肺间质异常,35.5%有肺动脉高压。在85.2%(115例)和47.4%(64例)的患者中,弥散能力和限制性通气模式降低。分别。有呼吸道症状的患者表现出比没有呼吸道症状的患者更高的肺功能下降指标。预后不良的高危患者表现出较多的肺功能异常。
    结论:肺部表现异常是POEMS综合征的重要特征。一些POEMS综合征患者在初步评估时出现呼吸道症状。这些发现强调了临床医生早期识别和准确诊断POEMS综合征的重要性,特别是在涉及肺和多系统的情况下。
    BACKGROUND: Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome is a rare multisystemic clonal plasma cell disorder. Pulmonary involvement is frequently found in patients with POEMS syndrome, manifesting various clinical features. Therefore, to improve diagnostic accuracy and provide treatment strategies, a comprehensive analysis of pulmonary manifestations of POEMS syndrome is needed.
    METHODS: This retrospective study included patients with POEMS syndrome at Peking Union Medical College Hospital, a major referral medical center in China, between June 1, 2013, and June 1, 2023. Demographic data, laboratory findings, pulmonary function test results, echocardiograms, and chest imaging data were extracted. Continuous variables were compared using the t-test or Mann-Whitney method. Pearson\'s chi-square test or Fisher\'s exact test was conducted to compare categorical data.
    RESULTS: Overall, 282 individuals diagnosed with POEMS syndrome were included in this study, of which 56% were male with an average age of 48.7 years. Respiratory symptoms were found in 40.1% of the patients, with dyspnea as the most common symptom (34.4%). Chest computed tomography and echocardiography findings showed that 56.4% of patients exhibited pleural effusion, 62.8% displayed mediastinal or hilar lymphadenopathy, 46.5% presented pleural thickening, 27.3% demonstrated bone lesions of the ribs or thoracic vertebra, 7.8% showed lung interstitial abnormalities, and 35.5% had pulmonary hypertension. Decreased diffuse capacity and restrictive ventilatory patterns were identified in 85.2% (115 cases) and 47.4% (64 cases) of patients, respectively. Patients with respiratory symptoms exhibited higher declined lung function measures than those having no respiratory symptoms. High-risk patients with poor prognosis showed more pulmonary function abnormalities.
    CONCLUSIONS: Abnormalities in pulmonary manifestations constitute the significant features of POEMS syndrome. Several patients with POEMS syndrome presented with respiratory symptoms at the initial evaluation. These findings underscore the importance of early identification and accurate diagnosis of POEMS syndrome by clinicians, particularly in cases involving lung and multisystem.
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  • 文章类型: Journal Article
    背景:淀粉样蛋白轻链淀粉样变性是一种罕见的疾病,其特征在于免疫球蛋白轻链的异常产生,其形状错误并形成淀粉样原纤维。随着时间的推移,这些淀粉样蛋白沉积物可以缓慢积累,导致器官和组织功能障碍。早期识别对于确保最佳治疗至关重要。我们的目标是确定一个更好的心脏淀粉样变性标志物,使用高级超声心动图,以改善诊断和可用治疗的时机。
    方法:108名连续的血液学患者(32,30%为女性,76,70%为男性)转诊到我们的心脏中心,接受了心电图检查,一级和二级超声心动图(斑点追踪)和完整的生化特征。ALCA的最佳预测因子(AUC≥0.8)包括在按AL评分分层的进一步分析中。
    结果:在ROC分析中,诊断ALCA的最佳生物体液预测因子为Nt-pro-BNP(AUC:0.97;p<0.01)和Hs-Tn(AUC:0.87;p<0.01)。关于超声心动图,最佳诊断预测因子是左心房的左心房僵硬度(LAS)(AUC:0.83;p<0.01);右心室的游离壁厚度(AUC:0.82;<0.01);左心室整体纵向应变(LVGLS)(AUC:0.92;p<0.01)和左心室的LVMi(AUC0.80;p<0.001);以及AL评分(AUC0.83p<0.01)。在AL-SCORE<1的患者中,LAS(AUC0.86vsAUC0.79),与AL评分较高(ALSCORE≥1)的患者相比,LVGLS(AUC0.92vsAUC0.86)和LV质量(AUC0.91vsAUC0.72)具有更好的诊断准确性。
    结论:LVGLS和LAS的多参数成像方法可能有助于检测AL淀粉样变性的早期心脏受累。
    BACKGROUND: Amyloid light-chain amyloidosis is a rare condition characterized by the abnormal production of immunoglobulin light chain that misshape and form amyloid fibrils. Over time, these amyloid deposits can accumulate slowly, causing dysfunction in organs and tissues. Early identification is crucial to ensure optimal treatment. We aim to identify a better marker of cardiac amyloidosis, using advanced echocardiography, to improve diagnosis and the timing of available treatments.
    METHODS: 108 consecutive hematological patients (32, 30% female and 76, 70% male) with a plasma cell disorder referred to our Cardiological center underwent ECG, first and second-level echocardiography (Speckle Tracking) and complete biochemical profile. The best predictors of ALCA (AUC ≥ 0.8) were included in a further analysis stratified by AL score.
    RESULTS: At ROC analysis, the best bio-humoral predictors for the diagnosis of ALCA were Nt-pro-BNP (AUC: 0.97; p < 0.01) and Hs-Tn (AUC: 0.87; p < 0.01). Regarding echocardiography, the best diagnostic predictors were left atrial stiffness (LAS) (AUC: 0.83; p < 0.01) for the left atrium; free wall thickness for the right ventricle (AUC: 0.82; <0.01); left ventricular global longitudinal strain (LVGLS) (AUC: 0.92; p < 0.01) and LVMi (AUC 0.80; p < 0.001) for the left ventricle; and AL-score (AUC 0.83 p < 0.01). In patients with AL-SCORE < 1, LAS (AUC 0.86 vs AUC 0.79), LVGLS (AUC 0.92 vs AUC 0.86) and LV mass (AUC 0.91 vs AUC 0.72) had better diagnostic accuracy than patients with higher AL-score (AL SCORE ≥ 1).
    CONCLUSIONS: Multi-parametric imaging approach with LVGLS and LAS may be helpful for detecting early cardiac involvement in AL amyloidosis.
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  • 文章类型: Journal Article
    背景:多发性骨髓瘤(MM)在45岁以下的青少年和年轻人(AYAs)中极为罕见。
    方法:使用来自ASCO的CancerLinQDiscovery®(CLQD)MM数据集和SEER的真实世界数据来表征现代治疗时代美国AYAMM患者的人口统计学和结果。SPM的频率,VTEs,并对感染进行了评估,OS和死因也是如此。
    结果:纳入了来自SEER的1946例AYAMM患者和来自CancerLinQ的1334例患者。就SPM而言,AYA更有可能发展为ALL(RR2.6,P=.003)和AML(RR1.7,P=.034),与≥45例的MM患者相比,非黑色素瘤皮肤癌(RR0.2,P=.001)和前列腺癌(RR0.1,P=.013)的可能性较小。AYAs的VTE风险较低(RR0.75,P=.002),感染风险略高(RR1.11,P=.002)。在两个数据集中,AYAMM患者的中位OS明显长于MM患者≥45。在SEER队列中,女性(HR0.74,P=0.003),非西班牙裔种族(HR0.73,P=0.005),家庭年收入≥$65,000/年(HR0.67,P=.001)与较低的死亡率风险相关.在CLQD队列中,OS受女性性别影响显著(HR0.6,P=.048)。种族在任何一个队列中都没有统计学上显著的OS影响。大多数AYAs死于MM(68.3%),其他原发性恶性肿瘤(7.5%,主要是白血病),和心血管事件(5.2%)。感染占死亡人数的3.2%。
    结论:该分析突出了现代美国AYAMM患者的一些独特特征。
    Multiple myeloma (MM) is exceedingly rare in adolescents and young adults (AYAs) < 45 years of age.
    Real-world data from ASCO\'s CancerLinQ DiscoveryⓇ (CLQD) MM dataset and SEER were utilized to characterize demographics and outcomes of AYA MM patients in the United States in the modern treatment era. Frequencies of SPMs, VTEs, and infections were assessed, as were OS and cause of death.
    A total of 1946 AYA MM patients from SEER and 1334 from CancerLinQ were included. In terms of SPMs, AYAs were more likely to develop ALL (RR 2.6, P = .003) and AML (RR 1.7, P = .034), and less likely to develop nonmelanoma skin cancer (RR 0.2, P = .001) and prostate cancer (RR 0.1, P = .013) than MM patients ≥ 45. AYAs were at lower risk of VTE (RR 0.75, P = .002) and slightly higher risk of infections (RR 1.11, P = .002). Median OS among AYA MM patients was significantly longer than MM patients ≥ 45 in both datasets. In the SEER cohort, female sex (HR 0.74, P = .003), non-Hispanic ethnicity (HR 0.73, P = .005), and annual household income ≥ $65,000 per year (HR 0.67, P = .001) were associated with lower hazards of mortality. In the CLQD cohort, OS was significantly influenced by female sex (HR 0.6, P = .048). Race did not have a statistically significant impact OS in either cohort. Most AYAs died of MM (68.3%), other primary malignancy (7.5%, mostly leukemia), and cardiovascular events (5.2%). Infections accounted for 3.2% of deaths.
    This analysis highlights some unique characteristics of AYA MM patients in the United States in the modern era.
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  • 文章类型: Case Reports
    多发性神经病,器官肿大,内分泌疾病,M-蛋白,皮肤变化(POEMS)综合征是一种罕见的疾病,具有多种表现和一系列症状。我们介绍了一名62岁的女性,她因急性呼吸困难而向急诊科就诊。胸部X光显示肋骨和胸椎硬化病变。计算机断层扫描(CT)和正电子发射断层扫描(PET)扫描的进一步成像研究暗示了良性过程。通过支持性管理看到了改善。几个月后,患者出现神经系统症状,运动耐量降低。肌电图诊断为混合性脱髓鞘和轴索多发性神经病。进一步的骨髓活检和免疫化学检测显示λ和κ浆细胞疾病,血管内皮生长因子(VEGF)升高。患者被诊断为POEMS并开始化疗。POEMS综合征由于其罕见且临床表现多样,通常被错过。VEGF在诊断中起着至关重要的作用。管理需要多学科方法。
    Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, Skin changes (POEMS) syndrome is a rare disorder with multiple presentations and a constellation of symptoms. We present a 62 year-old female who presented to the Emergency Department for acute dyspnea. Chest Xray showed sclerotic lesions in the ribs and thoracic spine. Further imaging studies with computed tomography (CT) and positron emission tomography (PET) scans were suggestive of a benign process. Improvement was seen with supportive management. A few months later, patient developed neurological symptoms with reduced exercise tolerance. Mixed demyelinating and axonal polyneuropathy was diagnosed by electromyography. Further work up with bone marrow biopsy and immunochemistry testing revealed lambda and kappa plasma cell disorder, with elevated vascular endothelial growth factor (VEGF). Patient was diagnosed with POEMS and initiated on chemotherapy. POEMS syndrome is commonly missed due to its rarity and varied clinical presentations. VEGF plays a crucial role in the diagnosis. Management requires a multidisciplinary approach.
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  • 文章类型: Journal Article
    免疫球蛋白轻链淀粉样变性可为全身性的或局部的。尽管这些条件具有相似的名称,他们截然不同。由于其较低的发病率和高度异质性的临床表现,局部轻链淀粉样变性已成为表征的挑战。这里,我们回顾了新兴的文献,强调最近关于局部淀粉样变性患者的大型队列的报道,并提供对这种情况的病理学和自然史的见解。我们发现,局部淀粉样变性患者的预后良好,总体生存率与普通人群相似。此外,进展为全身性疾病的风险较低,很可能代表最初错误描述为局部疾病.因此,我们主张在诊断时采用更敏感的技术来排除全身性疾病.尽管对这种情况的机械理解越来越多,关于细胞克隆进化和导致局部淀粉样蛋白形成的分子过程,还有很多有待发现。虽然有症状疾病的局部手术切除是典型的治疗选择,这种疾病在浆细胞性B细胞淋巴增殖性疾病中的表现,以及经常缺乏可识别的肿瘤克隆,在需要全身化疗的罕见情况下,可以使治疗选择成为挑战。
    Immunoglobulin light chain amyloidosis can be either systemic or localized. Although these conditions share a similar name, they are strikingly different. Localized light chain amyloidosis has been challenging to characterize due to its lower incidence and highly heterogeneous clinical presentation. Here, we review the emerging literature, emphasizing recent reports on large cohorts of patients with localized amyloidosis, and provide insights into this condition\'s pathology and natural history. We find that patients with localized amyloidosis have an excellent prognosis with overall survival similar to that of the general population. Furthermore, the risk of progression to systemic disease is low and likely represents initial mischaracterization as localized disease. Therefore, we argue for the incorporation of more sensitive techniques to rule out systemic disease at diagnosis. Despite increasing mechanistic understanding of this condition, much remains to be discovered regarding the cellular clonal evolution and the molecular processes that give rise to localized amyloid formation. While localized surgical resection of symptomatic disease is typically the treatment of choice, the presentation of this disease across the spectrum of plasmacytic B-cell lymphoproliferative disorders, and the frequent lack of an identifiable neoplastic clone, can make therapy selection a challenge in the uncommon situation that systemic chemotherapy is required.
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  • 文章类型: Journal Article
    电子显微镜是表征中心体超微结构的金标准。然而,大量形态测量数据的产生受到采集时间的高度限制。因此,我们开发了一种可推广的,半自动高通量电子层析成像策略研究纳米级稀疏患者来源癌细胞的中心体畸变.作为原则的证明,我们提供了1例复发/难治性多发性骨髓瘤患者的455个中心粒CD138pos浆细胞的电子断层扫描数据,以及3例健康供体的CD138neg骨髓单个核细胞作为对照。来自骨髓瘤患者的浆细胞显示122个过度延长的中心粒(48.8%)。特别是母亲中心粒也有严重的结构异常,包括破碎和扰动的微管圆柱体形成,而对照中心粒在表型上不显著。这些数据证明了我们可扩展的高通量电子断层扫描策略研究原发性肿瘤细胞中结构中心体畸变的可行性。此外,我们的电子层析成像工作流程和数据为表征中心体以外的细胞器提供了资源。
    Electron microscopy is the gold standard to characterize centrosomal ultrastructure. However, production of significant morphometrical data is highly limited by acquisition time. We therefore developed a generalizable, semi-automated high-throughput electron tomography strategy to study centrosome aberrations in sparse patient-derived cancer cells at nanoscale. As proof of principle, we present electron tomography data on 455 centrioles of CD138pos plasma cells from one patient with relapsed/refractory multiple myeloma and CD138neg bone marrow mononuclear cells from three healthy donors as a control. Plasma cells from the myeloma patient displayed 122 over-elongated centrioles (48.8%). Particularly mother centrioles also harbored gross structural abnormalities, including fragmentation and disturbed microtubule cylinder formation, while control centrioles were phenotypically unremarkable. These data demonstrate the feasibility of our scalable high-throughput electron tomography strategy to study structural centrosome aberrations in primary tumor cells. Moreover, our electron tomography workflow and data provide a resource for the characterization of cell organelles beyond centrosomes.
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  • 文章类型: Case Reports
    多发性骨髓瘤(MM)的白质脑病是一种罕见的脱髓鞘疾病,文献中报道的病例很少。Daratumumab是CD38靶向单克隆抗体,已广泛用于MM的管理。在没有中枢神经系统(CNS)疾病的情况下,许多药物诱发的白质脑病病例报告为MM,包括达雷妥单抗诱导的,与进行性多灶性白质脑病(PML)和约翰·坎宁安(JC)病毒有关。目前,在无中枢神经系统受累或PML的患者中,未报告达雷妥单抗诱导的白质脑病.我们讨论了2例患者在接受基于达雷妥单抗的治疗时发生白质脑病,但没有PML或CNS疾病的证据。在基于达雷妥单抗的治疗之前,两名患者的基线MRI均无明显的白质变化。患者在基于达雷妥单抗的治疗开始后约6至8个月开始出现神经功能缺损。一名患者在接受达雷妥单抗停药后症状改善评估之前去世。第二名患者在戒烟后症状有所稳定;然而,白质脑病仍然是不可逆的。随着抗CD38单克隆抗体类别在MM治疗中的扩展,我们强调了一个潜在的治疗并发症,以及在接受抗CD38治疗的患者中早期检测白质脑病的重要性.我们建议警惕监测任何新的或恶化的神经系统症状,以避免不可逆的白质脑病的严重并发症。
    Leukoencephalopathy in the setting of multiple myeloma (MM) is a rare demyelinating condition, with few reported cases in literature. Daratumumab is a CD38 targeted monoclonal antibody that has been widely used for the management of MM. In the absence of central nervous system (CNS) disease, many medication-induced leukoencephalopathy cases reported with MM, including daratumumab-induced, are associated with progressive multifocal leukoencephalopathy (PML) and John Cunningham (JC) virus. Currently, there are no reported cases of daratumumab-induced leukoencephalopathy among patients without CNS involvement or PML. We discuss 2 patients who developed leukoencephalopathy while receiving daratumumab-based therapy without evidence of PML or CNS disease. Both patients had baseline MRIs without significant white matter changes before daratumumab-based therapy. Patients began experiencing neurological deficits about 6 to 8 months after daratumumab-based therapy initiation. One patient passed away before being assessed for improvement of symptoms with daratumumab cessation. The second patient had some stabilization of symptoms after cessation; however, the leukoencephalopathy remained irreversible. As the class of anti-CD38 monoclonal antibodies expands in MM therapy, we highlight a potential treatment complication and the importance of detecting leukoencephalopathy early among patients receiving anti-CD38 therapy. We recommend vigilant monitoring of any new or worsening neurological symptoms to avoid serious complications of irreversible leukoencephalopathy.
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